Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model.

Taurine, as a free amino acid, is found at high levels in many tissues including brain, heart and skeletal muscle and is known to demonstrate neuroprotective effects in a range of disease conditions including stroke and neurodegenerative disease. Using in vitro culture systems we have demonstrated that taurine can elicit protection against endoplasmic reticulum stress (ER stress) from glutamate excitotoxicity or from excessive reactive oxygen species in PC12 cells or rat neuronal cultures. In our current investigation we hypothesized that taurine treatment after stroke in the rat middle cerebral artery occlusion (MCAO) model would render protection against ER stress processes as reflected in decreased levels of expression of ER stress pathway components. We demonstrated that taurine elicited high level protection and inhibited both ATF-6 and IRE-1 ER stress pathway components. As ischemic stroke has a complex pathology it is likely that certain combination treatment approaches targeting multiple disease mechanisms may have excellent potential for efficacy. We have previously employed the partial NMDA antagonist DETC-MeSO to render protection against in vivo ischemic stroke using a rat cerebral ischemia model. Here we tested administration of subcutaneous administration of 0.56 mg/kg DETC-MeSO or 40 mg/kg of taurine separately or as combined treatment after a 120 min cerebral ischemia in the rat MCAO model. Neither drug alone demonstrated protection at the low doses employed. Remarkably however the combination of low dose DETC-MeSO plus low dose taurine conferred a diminished infarct size and an enhanced Neuroscore (reflecting decreased neurological deficit). Analysis of ER stress markers pPERK, peIF-2-alpha and cleaved ATF-6 all showed decreased expression demonstrating that all 3 ER stress pathways were inhibited concurrent with a synergistic protective effect by the post-stroke administration of this DETC-MeSO-taurine combination treatment.

Venous Thromboembolism Prophylaxis in Plastic Surgery.

Background: In 2011, the American Society of Plastic Surgery (ASPS) formed the Venous Thromboembolism Task Force Report, which encouraged the use of the 2005 Caprini score and was amended in 2013. Still, there have been several studies that have questioned the validity of the Caprini score. As a result, the goal of this study is to present our experience with chemoprophylaxis in cosmetic patients compared with the current recommendations for venous thromboembolism (VTE) chemoprophylaxis endorsed by the ASPS. Methods: A retrospective analysis was conducted in all patients operated on by a single surgeon from 2006 to 2016. Exclusion criteria were surgery length >6 hours, patients with known hypercoagulable states, or a personal history of deep vein thrombosis (DVT)/pulmonary embolism (PE). Demographic data were collected and analyzed. Results: There were 1272 patients from a single institution who met the inclusion criteria. We determined that 71% of patient VTE scores were in the high to highest risk categories (n = 657), median age was 46 years, 79% of the population was Caucasian, 35% of patients had a body mass index of overweight or obese, and the average length of stay was 1 day. The rate of VTE in our patient population was found to be 0.08% (1 patient), which was uncomplicated and resolved with conservative therapy. Conclusions: This retrospective study found no significant difference in the incidence of VTE by providing chemophrophylaxis to patients without utilizing a scoring system. Our study suggests that the Caprini Scoring system might not be optimal in predicting VTE in patients undergoing aesthetic surgery.

Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis.

Intradermal injection of autologous platelet-rich plasma (PRP) is a non-surgical cosmetic therapy to rejuvenate the periorbital area pathologies of wrinkles, periorbital hyperpigmentation (POH), and photoaging. The past decade has seen the adoption of this novel therapy around the world. This is the first systematic review and meta-analysis evaluating PRP treatment of periorbital pathologies. This is a PRISMA compliant review that includes a comprehensive search of the databases Cochrane Library, Ovid Medline, Ovid Embase, and clinicaltrials.gov. The search was performed in June 2019 to obtain all peer-reviewed articles published in English that describe the application of PRP to periorbital pathologies. A meta-analysis of patient satisfaction was performed for randomized controlled trials. Nineteen studies treating 455 patients (95% female, age range 28-60) were included. Studies were categorized based on reported outcomes: wrinkles (11 studies), POH (7 studies), and photoaging (6 studies). Patients were treated a mean of 3 times (range 1-8) in mean intervals of 23 days (range 14-56 days). Follow-up averaged 3 months (range 1-6 months). Meta-analysis of 3 randomized controlled clinical trials (RCTs) shows that patients treated with PRP have increased satisfaction above controls of saline, platelet-poor plasma, mesotherapy, and as an adjunct to laser therapy (overall effect p = 0.001, heterogeneity I2 = 64%). PRP treatment of periorbital area pathologies results in histologic improvements of photoaging, subjective satisfaction score increases, and blind evaluator assessments of rejuvenated skin appearance. Future studies are needed to address limitations of the current literature and should include long-term follow-up, delineation of the POH etiology that is treated, RCTs with low risk of bias, and be absent conflicts of interest or industry sponsors.Trial registration: Prospero Systematic Review Registration ID: CRD42019135968.

Outcome Study after Nasal Alar/Peri-alar Subunit Reconstruction: Comparing Paramedian Forehead Flap to Nasolabial Flap.

OBJECTIVE: Contours of the lower nasal third are unique and present challenges in surgical reconstruction. The nasal alar intricate curved anatomy makes the area easily compromised after Mohs surgery. Managing patient and surgeon expectations with regard to aesthetics and functionality remains the reconstructive goal. The purpose of the study was to compare patients' perspective on aesthetics and functional outcomes of nasal alar reconstruction post Mohs ablative surgery using nasolabial or forehead flaps. METHODS: A single surgeon's results of 23 patients, who underwent nasal alar reconstruction post Mohs surgery, were included for analysis (15 forehead and 8 nasolabial flaps). Initially, 103 consecutive patients undergoing nasal reconstruction were reviewed, with 67 excluded due to nonalar subunit involvement and an additional 13 excluded for other discussed reasons. Mean follow-up period was 2.3 years. Evaluation of a patient satisfaction questionnaire assessed aesthetics and functionality and also surgical scar noticeability. Additionally, 3 board-certified plastic surgeons assessed postoperative images. RESULTS: Twenty-three patients completed the survey. There was no statistically significant difference in gender ratio, follow-up time, or scar noticeability among groups. A difference was noted in both aesthetics and functionality score (P < 0.03) for both variables favoring forehead flaps. Results from the surgeon's questionnaire also confirmed the superiority of forehead flaps concerning scar, alar contour/symmetry, and nostril opening symmetry. CONCLUSIONS: The forehead flap has a better functional and aesthetic outcome and an overall superior level of satisfaction post Mohs ablative surgery.

Palatal Protective Stents Prevent Oro-Nasal Fistulas after Surgery for Velopharyngeal Insufficiency: A Preliminary Report.

BACKGROUND: One of the potential complications of surgery for velopharyngeal insufficiency (VPI) is postoperative oral-nasal fistula (ONF). Reported rates vary from 0 to 60%. Several factors are on account of these disproportionate rates. OBJECTIVE: The purpose of this study was to describe the use of a palatal protective stent (PPS) to preserve the VPI repair surgical site and to study its effectiveness for decreasing the incidence of postoperative ONF. MATERIALS AND METHODS: A retrospective study was carried out. All patients undergoing surgery for VPI with complete preoperative and postoperative evaluations including at least one year follow up after surgery from 2012 to 2016 were studied. Some of the patients were operated on using a pre-molded palatal protective stent (PPS). Twenty-seven patients were included in the study group. Most of the patients underwent a customized pharyngeal flap according to findings of imaging procedures. The remaining cases underwent a Furlow palatoplasty. Twelve patients were operated on using PPS. RESULTS: There were no surgical complications during the procedures. ONF was detected in four of the patients operated on without PPS. None of the patients undergoing surgery using PPS demonstrated ONF. All fistulas were located at the soft/hard palate junction. VPI was corrected in 92% of the cases. CONCLUSION: Although only a reduced number of cases were studied, these preliminary results suggest that using PPS during surgical procedures for correcting VPI is a safe and reliable tool for preventing ONF.

Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a novel therapy for stroke in a rat model.

One approach for protecting neurons from excitotoxic damage in stroke is to attenuate receptor activity with specific antagonists. S-Methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO), the active metabolite of disulfiram, has been shown to be a partial antagonist of glutamate receptors and effective in reducing seizure. First, we investigated neuroprotective effect of DETC-MeSO on primary cortical neuronal culture under hypoxia/reoxygenation condition in vitro. Then, DETC-MeSO was administered subcutaneously for 4 and 8 days with the first injection occurring 1 h before or 24 h after reperfusion in the rat middle cerebral artery occlusion stroke model. Rats were subjected to the neuroscore test, and the brain was analyzed for infarct size. Monitoring neurotransmitter release was carried out by microdialysis. Heat shock proteins, key proteins involved in apoptosis and endoplasmic reticulum (ER) stress, were analyzed by immunoblotting. DETC-MeSO greatly reduced both cell death following hypoxia/reoxygenation and brain infarct size. It improved performance on the neuroscore test and attenuated proteolysis of αII-spectrin. The level of pro-apoptotic proteins declined, and anti-apoptotic and HSP27 protein expressions were markedly increased. Levels of the ER stress protein markers p-PERK, p-eIF2α, ATF4, JNK, XBP-1, GADD34, and CHOP significantly declined after DETC-MeSO administration. Microdialysis data showed that DETC-MeSO increased high potassium-induced striatal dopamine release indicating that more neurons were protected and survived under ischemic insult in the presence of DETC-MeSO. We also showed that DETC-MeSO can prevent gliosis. DETC-MeSO elicits neuroprotection through the preservation of ER resulting in reduction of apoptosis by increase of anti-apoptotic proteins and decrease of pro-apoptotic proteins.