Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury. Resistin treatment reduced cleaved protein level of Poly(ADP-ribose)polymerase-1 (PARP-1), a marker of cellular apoptosis, showing the anti-apoptotic activity of resistin. Resistin increased the level of phosphorylated Akt after ischemic brain injury. The neuroprotective effect of resistin was partially reversed by a PI3K inhibitor wortmannin, demonstrating that the PI3K/Akt signal pathway is involved in the anti-apoptotic mechanisms of resistin. Finally, we found that resistin treatment improved neurological function recovery at 14 days after treatment, including balance ability and muscle strength. Given these findings, resistin may have therapeutic potential for the treatment of stroke.

Purpose of Review: Patients with stable coronary artery disease (CAD) and a high risk of bleeding are not ideal candidates for a polymer-based drug-eluting stent (DES) because it requires 6–12 months of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI). The purpose of this review is to assess the angiographic and clinical outcomes of polymer-free drug-coated stents (PF-DCS) in stable CAD patients with a high bleeding risk. Recent Findings: Several randomized controlled trials (RCTs) have compared angiographic and clinical outcomes of PF-DCS with bare-metal stents (BMS), permanent polymer (PP)-DES, or biodegradable polymer (BP)-DES. However, none of these studies particularly recruited patients with stable CAD and a high risk of bleeding. Furthermore, there are limited data available on duration of DAPT following PF-DCS placement. Summary: PF-DCS has a better efficacy and similar safety as compared with BMS. PF-DCS with dual drug is noninferior to currently available PP-DES. Further RCTs are needed to assess the safety and efficacy of PF-DCS to BP-DES and PP-DES comparing shorter to standard durations of DAPT.

Objective:Iatrogenic acute limb ischaemia in paediatric patients is a well-recognised complication of vascular access. This retrospective review of a paediatric intensive care unit identified patients who developed iatrogenic acute limb ischaemia between January 2008 and July 2013. Methods: The medical records of inpatients diagnosed with acute limb ischaemia during the study period were reviewed. Patients with other causes of acute limb ischaemia were excluded. A descriptive analysis of demographics, primary diagnosis, type of vascular access used, affected anatomical region, clinical presentation, type of therapy, type of block, response to intervention used and outcomes was conducted. Results:A total of 28 patients presented with signs of acute limb ischaemia, of whom 28.6% were aged <30 days, 46.4 % were between one and 12 months and 25% were between one and five years old; 78.6% of the affected limbs were lower limbs. Four patients had resolution of ischaemia upon removal of the vascular access devices. 23 patients received various forms of pharmacological sympathectomy, in addition to conservative therapy. One patient had missing data on the type of sympathectomy that was done. The response to the sympathectomies was: 60.9% good, 8.7% moderate, 8.7% poor and in 21.7% no responses. Documented tissue loss related to the ischaemia occurred in six (21.4%) of the 28 patients. Conclusions: Iatrogenic acute limb ischaemia in children are usually managed without surgical intervention. Pharmacological sympathectomies lead to increased blood flow to the affected limb via vasodilatation of collateral vessels, with an added advantage of reducing ischemic pain. The improved blood flow is postulated to avoid and/or minimise the amount of tissue loss. Pharmacological sympathectomies may, thus, have a role to play in th e management of iatrogenic acute limb ischaemia in the paediatric population.

The educational medium GetWellNetWork (GWNW) in a large magnet teaching facility offered few educational videos specific to vascular patients with a focus on leg elevation after lower extremity bypass surgery. Supplying patient-specific education has the potential for providing cost-effective nursing care to vascular patients and improving hospital reimbursement. Guided by the interactive care model, a storyboard was developed using best-practice evidence for vascular postoperative patients that could lead to the development of a video to address the educational needs of vascular patients upon discharge. The practice focused question asked if a video addressing the importance of leg elevation would improve patients’ use of in-house educational videos and stakeholder satisfaction. A vascular physician (n = 1) and nursing staff (n = 9) provided feedback on the appropriateness of the evidence-based educational content for the storyboard by completing a 9-item, open-ended survey. Survey results supported development of the video and revealed positive feedback on storyboard content and that staff with 1–3 years’ experience or 15+ years’ experience had an increased understanding of the importance of evidence-based guidelines for leg elevation for vascular patients. The feedback will be used to develop a vascular-patient-specific educational video. Encouraging patients to view the video on leg elevation has the potential to improve cost effectiveness of patient care and hospital reimbursement, prevent hospital readmission that could lead to patient and caregiver hardships associated with readmission, and improve the health outcomes for postoperative vascular patients.

Introduction: The palate is a well-established donor site for obtaining graft tissue in periodontal plastic surgery procedures. However, proximity to the adjacent teeth on the lateral aspect and the greater palatine neurovascular bundle (GPB) on the medial aspect limit the amount of graft tissue that can be obtained from the palate. Previous studies have been concerned with the location of the greater palatine foramen as well as the greater palatine artery (GPA) and have established guidelines on how to estimate the distance between the teeth and the GPB. Traditionally, clinicians follow these guidelines and choose to avoid removing graft tissue in the area close to the GPB out of fear of possible complications such as hemorrhaging and paresthesias. Objectives: The purpose of the present investigation is to locate the position of the greater palatal artery (GPA) in relation to surrounding anatomical landmarks and determine if the tissue thickness covering the GPA is sufficient to permit gingival grafts to be obtained in the area close to the GPB. Materials and methods: Cadaver dissections were performed on a total of ten (n=10) cadaver hemifaces of which 7 were partially and 3 were completely edentulous. From the greater palatine foramen to the incisive foramen, the palatal tissues of the cadavers were dissected into vertical slices of 3 mm in width perpendicular to the median palatine raphe using a double bladed scalpel. On each tissue slice, the distance from the epithelial surface to the superior border of the vessel, the diameter of the vessel, the distance from the inferiorborder of the vessel to the palatal bone, the distance from median palatine raphe to the GPA and the distance from teeth or midline of the alveolar crest to the GPA were measured using both a periodontal probe and a digital caliper. The measurements were correlated to each other, the angle of the palatal vault, an estimate of the palatal depth and the head length of the cadavers. Results: The mean thickness of the tissue above the GPA was 4.30 ± 1.61 mm with a range of 1.92 – 8.72 mm. The tissue thickness decreased consistently from the 3rd molar to the canine area with the thickest mean tissue being in the 2nd molar region with 6.25 ± 1.09 mm and shallowest mean tissue thickness in the region of the lateral incisor with 2.92 ± 0.46 mm. The mean distance of the GPA from the median palatine raphe is 10.34 ± 3.41mm ranging from 13.77 ± 1.67 mm to 6.02 ± 0.83 mm with the greatest distance being from the 3rd molar region and smallest distance being from the lateral incisor area. No statistically significant correlations were found between the angel of the palatal vault, the estimate of the palatal depth and the head length. A significant correlation (R2=0.92) was found between the total palatal tissue thickness and tissue thickness above the GPA. Discussion: There was adequate gingival tissue above the GPA to harvest tissue for free gingival grafts of 1 - 1.5 mm in thickness in the entire palate. Donor tissue for 1.5 mm thick connective tissue grafts with a 1.5 mm epithelial flap could be obtained opposing the 1st molar and posterior to it staying above the GPA. Donor site for palatal grafts can be extended in a medial and posterior direction.A Formula (Tissue Thickness above the GPA = (Total Thickness of palatal tissue - 0.967) x 0.9) has been derived, which accurately locates the GPA based on the thickness of the palatal tissue. Unique to this study were measurements from the median palatine raphe, which will provide the clinician with a new landmark to more reliably locate the GPA at various locations on the palate. Conclusion: This descriptive pilot study on human cadavers provides a formula to locate the GPA within the palate using the total palatal tissue thickness and suggests that graft tissue can be harvested from the tissue above the GPA in the entire palate for FGGs and opposing to the 1st molar and posterior to it for CTGs not exceeding 3 mm in depth.

Indiana University-Purdue University Indianapolis (IUPUI) / Metabolic syndrome (MetS) affects 1/3 of all Americans and is the clustering of three or more of the following cardiometabolic risk factors: obesity, hypertension, dyslipidemia, glucose intolerance, and insulin resistance. MetS drastically increases the incidence of coronary artery disease (CAD), which is the leading cause of mortality globally. A cornerstone of CAD is arterial remodeling associated with coronary smooth muscle (CSM) cytodifferentiation from a contractile phenotype to proliferative and osteogenic phenotypes. This cytodifferentiation is tightly coupled to changes in intracellular Ca2+ handling that regulate several key cellular functions, including contraction, transcription, proliferation, and migration. Our group has recently elucidated the time course of Ca2+ dysregulation during MetS-induced CAD development. Ca2+ transport mechanisms, including voltage-gated calcium channels, sarcoplasmic reticulum (SR) Ca2+ store, and sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), are enhanced in early, mild disease and diminished in late, severe disease in the Ossabaw miniature swine. Using this well-characterized large animal model, I tested the hypothesis that this Ca2+ dysregulation pattern occurs in multiple etiologies of CAD, including diabetes and aging. The fluorescent intracellular Ca2+ ([Ca2+]i) indicator fura-2 was utilized to measure [Ca2+]i handling in CSM from lean and diseased swine. I found that [Ca2+]i handling is enhanced in mild disease with minimal CSM phenotypic switching and diminished in severe disease with greater phenotypic switching, regardless of CAD etiology. We are confident of the translatability of this research, as the Ca2+ influx, SR Ca2+ store, and SERCA functional changes in CSM of humans with CAD are similar to those found in Ossabaw swine with MetS. Single-cell RNA sequencing revealed that CSM cells from an organ culture model of CAD exhibited many different phenotypes, indicating that phenotypic modulation is not a discreet event, but a continuum. Transcriptomic analysis revealed differential expression of many genes that are involved in the osteogenic signaling pathway and in cellular inflammatory responses across phenotypes. These genes may be another regulatory mechanism common to the different CAD etiologies. This study is the first to show that CSM Ca2+ dysregulation is common among different CAD etiologies in a clinically relevant animal model.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18459号 / 医博第3914号 / 新制||医||1005(附属図書館) / 31337 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 坂田 隆造, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18882号 / 医博第3993号 / 新制||医||1009(附属図書館) / 31833 / 京都大学大学院医学研究科医学専攻 / (主査)教授 宮本 享, 教授 小泉 昭夫, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19549号 / 医博第4056号 / 新制||医||1012(附属図書館) / 32585 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 吉村 長久, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13207号 / 論医博第2161号 / 新制||医||1031(附属図書館) / (主査)教授 福原 俊一, 教授 湊谷 謙司, 教授 小池 薫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM