Influence of successive heat waves on the thermoregulatory responses of pregnant and non-pregnant ewes.

The frequency of heat waves has increased over the last years, with an impact on animal production and health, including the death of animals. Therefore, the aim of this study was to evaluate the dynamics of thermoregulation and hormonal responses in non-pregnant and pregnant ewes exposed to successive heat waves. Twenty-four non-pregnant and 18 pregnant Santa Ines ewes with black coat color (live weight: 55 ± 9.03 kg; age: 60 months) were used. Weather variables such air temperature, relative humidity, and solar radiation were continuously recorded. The rectal and tympanic temperatures and respiratory rate were measured daily. Serum triiodothyronine (T3) and prolactin were evaluated during the heat wave and thermoneutral periods. The physiological variables were higher under the heat wave conditions and were related to the activation of the thermoregulatory system for maintaining homeothermy (P < 0.05). The core body temperature was higher during successive heat waves (P < 0.05), as was the tympanic temperature, which are both affected by changes in air temperature (P < 0.05). T3 and prolactin levels were not influenced by successive heat waves (P < 0.05) and rectal temperature and respiratory rate were highest in non-pregnant ewes (P < 0.05). Prolactin was not affected by temperature. The results indicate that the Santa Ines breed overcomes the thermal challenge during a heat wave without showing severe signs of thermal stress regardless of being pregnant or not.

Cardiac autonomic dysfunction in school age children with overweight and obesity.

BACKGROUND AND AIMS: We investigated cardiac autonomic function in overweight and obese school-age children. METHODS AND RESULTS: Quantitative cross-sectional study conducted with children (n = 110) of both genders. Children were divided by normal weight (NW; n = 54), overweight (OW; n = 24) and obese (OB; n = 32). Systolic (SBP) and diastolic (DBP) blood pressure and electrocardiograms were recorded and analyzed for heart rate and the heart rate variability (HRV) in time (SDRR, RMSSD, PRR50, SD1 and SD2) and frequency domains (HF, LF and LF/HF). The OB group presented higher SBP (p ≤ 0.01) and DBP (p ≤ 0.01). For HRV, the OB group had a lower PRR50 (p ≤ 0.01) and HF (p ≤ 0.01), associated with higher LF (p ≤ 0.01). Moderate negative correlations were found between the HF, BMI (r = -0.37; p ≤ 0.01) and WC (r = -0.38; p ≤ 0.01). Positive moderate correlation were found between LF, LF/HF and BMI (LF: r = 0.32; p ≤ 0.01; LF/HF: r = 0.31; p ≤ 0.01) and WC (LF: r = 0.34; p ≤ 0.01; LF/HF: = 0.34; p ≤ 0.01). Multiple linear regression showed a positive association between body fat and the SDRR (ß: 0.48; CI: 0.2-4.2; p = 0.02). No differences were observed in cardiac electrical activity. CONCLUSION: Children with obesity but not overweight presented higher blood pressure and cardiac autonomic dysfunction, with sympathetic predominance on the heart rate. This fact was positively correlated with BMI and may be considered an important marker for cardiovascular risk in children.

[Breast osteosarcoma originating in a phyllodes tumor. Report of one case]. / Tumor Phyllodes con transformación a osteosarcoma.

Phyllodes tumors account for less than 1% of tumors of the mammary gland, have both epithelial and stromal components and are classified as benign, borderline and malignant. The malignant tumors are highly heterogeneous: they can differentiate to liposarcomas, fibrosarcomas, rhabdomyosarcomas, chondrosarcomas or osteosarcomas. The differentiation to osteosarcoma is extremely rare, constitutes 1.3% of cases and is very aggressive. The standard treatment of these tumors is surgical. The role of radiotherapy and chemotherapy is not clear. However, in patients in whom wide surgical margins are not achieved, adjuvant radiotherapy can be of help. We report a 63 years old female with a right breast osteosarcoma with an osteoclastic component, originating in a phyllodes tumor. The tumor was excised surgically and afterwards she was treated with 10 sessions of 50 Gy of radiotherapy in 25 fractions. She has remained free of disease for the last 10 months.

[Initial surgical management of squamous carcinoma of the vulva]. / Manejo quirúrgico inicial del carcinoma epidermoide vulvar.

Vulvar cancer accounts for approximately 4% of gynecological malignancies. At the Instituto Nacional de Cancerologia in Mexico it occupies the fourth place. The purpose of this study is to assess the management of squamous carcinoma of the vulva with initial surgical treatment. It is a descriptive retrospective, observational study, from January 1, 2002 to December 31, 2012. Twenty-seven patients, clinical stages I, II, or III, initial surgical management, with at least one year of follow-up were included. In 51.85% a partial vulvectomy was performed and in 40.74% a wide excision; 66.66% underwent inguinofemoral dissection. Recurrence occurred in 25.91% of cases and the overall survival at 10 years was 63%. It is concluded that with invasion of up to 1 mm of lymph node, affection is 0%; with invasion of 1 mm and up to 5 mm this increases to 25%; an invasion of more than 5 mm implies up to 45%. Recurrence in our study was primarily distant, necessitating long-term monitoring with emphasis on symptoms to request imaging studies when suspected. Adjuvant therapy should be offered to patients with positive nodes, close or positive margins, and tumors larger than 4 cm.

Treatment of the acute sickle cell vaso-occlusive crisis in the Emergency Department: a Brazilian method of switching from intravenous to oral morphine.

OBJECTIVES: Describe the treatment of patients with vaso-occlusive crises (VOC) in a Brazilian emergency department (ED) and the successful switch from intravenous to oral morphine. PATIENTS AND METHODS: We analyzed records of 315 patients with sickle cell disease using two different protocols for pain: one in March 2010 prescribing intravenous morphine every 4 h throughout their stay, and another in March 2011 and 2012 prescribing one initial dose of intravenous morphine followed by equianalgesic doses of oral morphine every 4 h. Patients were triaged into three groups: mild, moderate, and severe VOC. The mild group was treated within 1 h after triage, the moderate within 30 min and the severe was treated immediately. Patients whose pain was not relieved within 6 h after the first dose of morphine were transferred into a different holding area of the ED where they continued to receive the same treatment for 48 h after which they were hospitalized if still in pain. RESULTS: The number of patients who stayed <24 h in the ED increased significantly from 63 in 2010 to 87 in 2012, and the number of admissions decreased from 26 in 2010 to 10 in 2012. The incidence of acute chest syndrome decreased from 8.5% in 2010 to 1.9% in 2012. CONCLUSION: Patients treated with oral morphine stayed a shorter time in the ED, had more pain relief, were admitted less frequently, and had less acute chest syndrome. These differences may be due to environmental, cultural, psychological, and pharmacogenetic factors.

Leg amputation for an extensive, severe and intractable sickle cell anemia ulcer in a Brazilian patient.

A 35-year-old African Brazilian patient had sickle cell anemia complicated with recurrent vasoocclusive (VOC) crises and refractory painful leg ulcers for 16 years. The ulcers started over both medial malleoli and expanded gradually. The ulcer on the left leg spread from the foot to the knee circumferentially and was refractory to all forms of therapy within the frame work of multi-disciplinary care. The patient agreed to a below the knee amputation of the left leg. He felt much better after the amputation but developed severe neuropathic phantom pain that was well controlled medically. He could differentiate the sickle cell anemia and ulcer pain from the neuropathic pain. About 6 months after the amputation he had dengue fever with fatal outcome. This is the first report of treatment of refractory sickle cell anemia leg ulcer with amputation and probably the first report of a Brazilian patient with sickle cell anemia and dengue fever.

Sustainable Polypropylene-Based Composites with Agro-Waste Fillers: Thermal, Morphological, Mechanical Properties and Dimensional Stability.

Natural fiber composites (NFC) are eco-friendly alternatives to synthetic polymers. However, some intrinsic natural fillers' properties hinder their widespread implementation as reinforcement in polymeric matrices and require further investigation. In the scope of this study, the thermal, rheologic, mechanical (tension and flexural modes), and morphological properties, as well as the water absorption and dimensional stability of the NF polypropylene (PP)-based injection molded composites reinforced with rice husk (rh) and olive pits (op) of 20 wt.% and 30% wt.%, respectively, were investigated. The results suggest that the higher content of the rice husk and olive pits led to a similar reduction in the melt flow index (MFI), independent of the additive type compared to virgin polypropylene (PPv). The melting and crystallization temperatures of the PPrh and PPop composites did not change with statistical significance. The composites are stiffer than the PP matrix by up to 49% and possess higher mechanical strength in the tension mode at the expense of decreased ductility. PPrh and PPop have a superior flexural modulus in the bending mode, while the flexural strength improvement was accomplished for the PP30%rh. The influence of the fibers' distribution in the bulk of the parts on their mechanical performance was confirmed based on a non-localized morphology evaluation, which constitutes a novelty of the presented research. The dimensional stability of the composites was improved as the linear shrinkage in the flow direction was decreased by 49% for PPrh and 30% for PPop, positively correlating with an increase in the filler content and stiffness. PPop was less susceptible to water sorption than PPrh due to fibers' composition and larger surface-to-area volume ratios.

Successful treatment of unilateral facial nerve palsy in a pediatric patient with syringobulbia and Chiari malformation type I: illustrative case.

BACKGROUND: Unlike syringomyelia, syringobulbia is not commonly observed in pediatric patients with Chiari malformation type I (CMI). Previous series have reported the incidence of syringobulbia as between 3% and 4% in these patients. Presentation is typically chronic, with the slow onset of neurological symptoms and cranial nerve (CN) palsies resulting from lower brainstem involvement. The authors report the first case of a pediatric patient with simultaneous CMI, syringobulbia, and unilateral CN VII palsy. OBSERVATIONS: A 7-year-old male presented with right facial weakness in addition to headaches, ataxia, urinary incontinence, and falls. Magnetic resonance imaging revealed CMI with a syrinx of the cervicothoracic spine and syringobulbia. Posterior fossa decompression with duraplasty was performed without complications, and the patient was discharged home on postoperation day 5. At the 3-week follow-up, the patient's neurological deficits had largely subsided. At the 3-month follow-up, his CN VII palsy and syringobulbia had completely resolved. LESSONS: Pediatric CMI patients with syringomyelia are at risk for developing syringobulbia and brainstem deficits, including unilateral facial palsy. However, craniocervical decompression can prove successful in treating such deficits.

Triple Stentriever "Bouquet" Deployment with Zoom 88 Large-Bore Aspiration and Walrus Balloon-Guide Catheter for the Definitive Thrombectomy of a Carotid Free-Floating Thrombus.

Formation of a carotid free-floating thrombus (CFFT) is a rare and life-threatening condition without an optimal management plan. A 78-year-old woman with a history of prior right internal carotid artery (ICA) mechanical thrombectomy and antiplatelet noncompliance presented with transient ischemic attacks secondary to a recurrent CFFT in the right ICA. Given her symptoms and recurrent CFFT, endovascular mechanical thrombectomy was performed. A balloon guide-catheter (BGC) and a Zoom 88 distal access catheter were brought into the right distal common carotid artery and proximal ICA bulb, respectively. Three 0.021-inch microcatheters, each loaded with a unique stentriever, were navigated beyond the thrombus into the upper cervical ICA and deployed in a bouquet fashion. The BGC was inflated to achieve flow arrest, and the Zoom 88 aspiration catheter was tracked over the three bouquet stentrievers to ingest the thrombus. Follow-up angiography demonstrated recanalization of the proximal cervical ICA without evidence of residual thrombus. Twenty-four-hour postoperative computed tomography imaging did not reveal any evidence of new infarction. The patient was discharged home with an intact neurological examination, compliant on aspirin and apixaban. We demonstrate a novel technique utilizing a large-bore catheter with a triple stentriever "bouquet" to thrombectomize a CFFT.

Association between Childhood Overweight and Altered Concentrations of Circulating Amino Acids.

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7-12 years with normal weight or overweight. Clinical and anthropometric parameters were measured. (3) Results: Overweight in children is associated with an altered AA profile, with increased branched-chain amino acids (BCAA) and decreased glycine levels, with no clinically manifested metabolic conditions. Moreover, z-BMI was positively and negatively correlated with BCAA and glycine levels, respectively, even after adjustment for age and gender. We also found a correlation between the AA profile and clinical parameters such as lipids profile and glycemia. (4) Conclusions: A pattern of low glycine, and increased BCAA is correlated to z-BMI, total cholesterol, and triglycerides in overweight but otherwise healthy children. Our data suggest that, in childhood overweight, AA disturbances may precede other clinical parameters, thus providing an early indicator for the later development of metabolic disease.

Immediate procedural safety of adjunctive proximal coil occlusion in middle meningeal artery embolization for chronic subdural hematomas: Experience in 137 cases.

BACKGROUND: Endovascular embolization of the middle meningeal artery (MMA) has emerged as an adjunctive and stand-alone modality for the management of chronic subdural hematomas (cSDH). We report our experience utilizing proximal MMA coil embolization to augment cSDH devascularization in MMA embolization. METHODS: MMA embolization cases with adjunctive proximal MMA coiling were retrospectively identified from a prospectively maintained IRB-approved database of the senior authors. RESULTS: Of the 137 cases, all patients (n = 89, 100%) were symptomatic and underwent an MMA embolization procedure for cSDH. 50 of the patients underwent bilateral embolizations, with 53% (n = 72) for left-sided and 47% (n = 65) for right-sided cSDH. The anterior MMA branch was embolized in 19 (14%), posterior in 16 (12%), and both in 102 (74.5%) cases. Penetration of the liquid embolic to the contralateral MMA or into the falx was present in 38 (28%) and 31 (23%) cases, respectively, and 46 (34%) cases had ophthalmic or petrous collateral (n = 41, 30%) branches. MMA branches coiled include the primary trunk (25.5%, n = 35), primary and anterior or posterior MMA trunks (20%, n = 28), or primary with the anterior and posterior trunks (54%, n = 74). A mild ipsilateral facial nerve palsy was reported, which remained stable at discharge and follow-up. Absence of anterograde flow in the MMA occurred in 137 (100%) cases, and no cases required periprocedural rescue surgery for cSDH evacuation. The average follow-up length was 170 ± 17.9 days, cSDH was reduced by 4.24 ± 0.5(mm) and the midline shift by 1.46 ± 0.27(mm). Complete resolution was achieved in 63 (46.0%) cases. CONCLUSION: Proximal MMA coil embolization is a safe technique for providing additional embolization/occlusion of the MMA in cSDH embolization procedures. Further studies are needed to evaluate the potential added efficacy of this technique.

Use of a large-bore 088 intracranial access support catheter for delivery of large intracranial devices: case series with the TracStar LDP in 125 cases.

BACKGROUND: The delivery of neuroendovascular devices requires a robust proximal access platform. This demand has previously been met with a 6Fr long sheath (8Fr guide) that is placed in the proximal internal carotid artery (ICA) or vertebral artery segments. We share our experience with the first 0.088 inch 8Fr guide catheter designed for direct intracranial access. METHODS: We retrospectively reviewed a prospectively maintained IRB-approved institutional database of the senior authors to identify all cases where the TracStar Large Distal Platform (LDP) was positioned within the intracranial vasculature, defined as within or distal to the petrous ICA, vertebral artery (V3) segments, or transverse sinus. Technical success was defined as safe placement of the TracStar LDP within or distal to the described distal vessel segments with subsequent complication-free device implantation. RESULTS: Over the 41-month study period from January 2020 to June 2023, 125 consecutive cases were identified in whom the TracStar LDP was navigated into the intracranial vasculature for triaxial delivery of large devices, 0.027 inch microcatheter and greater, for aneurysm treatment (n=108, 86%), intracranial angioplasty/stenting (n=15, 12%), and venous sinus stenting (n=2, 1.6%). All cases used a direct select catheter technique for initial guide placement (no exchange). Posterior circulation treatments occurred in 14.4% (n=18) of cases. Technical success was achieved in 100% of cases. No vessel dissections occurred in any cases. CONCLUSION: The TracStar LDP is an 0.088 inch 8Fr guide catheter that can establish direct intracranial access with an acceptable safety profile. This can be achieved in a wide range of neurointerventional cases with a high rate of technical success.

Feasibility of super-bore 0.088″ mechanical thrombectomy in M1 vessels smaller than 8 French: Experience in 20 consecutive cases.

INTRODUCTION: Superbore 0.088″ catheters provide a platform for optimizing aspiration efficiency and flow control during stroke mechanical thrombectomy procedures. New superbore catheters have the distal flexibility necessary to navigate complex neurovascular anatomy while providing the proximal support of traditional 8F catheters. The safety and feasibility of Zoom 88™ superbore angled-tip catheters in the middle cerebral artery (MCA) segments smaller than the catheter diameter have not been previously described. METHODS: Twenty consecutive cases of acute MCA mechanical thrombectomy were retrospectively identified from the senior authors' prospectively maintained Institutional Review Board-approved database, in which the Zoom 88 (Imperative Care, Campbell, CA) catheter was successfully navigated to at least the M1 segment. Patient demographics, procedural details, and periprocedural information were analyzed. Rates and averages (standard errors) are generally reported. RESULTS: The average National Institutes of Health Stroke Scale at presentation and age were 15 ± 2 and 73 ± 3 years, respectively. The M1 and M2 occlusions were evenly distributed. The average M1 measurements before thrombectomy ranged from 2.36 ± 0.07 mm proximally to 2.00 ± 0.11 mm distally, and after thrombectomy, they ranged from 2.34 ± 0.07 mm proximally to 1.97 ± 0.10 mm distally. First-pass modified thrombolysis in cerebral infarction (mTICI) 2C/3 recanalization was achieved in 40% of cases, and final mTICI 2C/3 recanalization was achieved in 90% of cases. A single case of mild vasospasm was managed with verapamil. No hemorrhagic or periprocedural complications were noted. CONCLUSION: Superbore 0.088″ catheters with flexible distal segments can be safely navigated to the MCA to augment mechanical thrombectomy even when the MCA segment is smaller than the catheter.

Exercise and Nutrition in the Mental Health of the Older Adult Population: A Randomized Controlled Clinical Trial.

(1) Background: Global population aging is changing demographic structures and presents significant challenges for health systems, which must adapt to an increasingly elderly population. (2) Methods: The study employed a randomized controlled trial design with a total of 116 older adults aged 65 or older, randomly assigned to an experimental group (n = 57) undergoing a combined resistance program and Mediterranean diet program and a control group (n = 59) who did not receive any intervention. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS), sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and perceived stress using the Perceived Stress Scale (PSS). (3) Results: Statistically significant improvements (p < 0.05) were observed both within and between groups in anxiety (Cohen's d = 0.38 and 0.78, respectively), depression (Cohen's d = 0.56 and 0.18, respectively), perceived stress (Cohen's d = 0.15 and 0.39, respectively), and in the PSQI domains: subjective sleep quality (Cohen's d = 1.01 and 0.53, respectively), sleep duration (Cohen's d = 0.112 and 0.53, respectively), sleep disturbances (Cohen's d = 1.92 and 0.95, respectively), use of medications (Cohen's d = 0.34 and 0.40, respectively), and the PSQI total score (Cohen's d = 0.68 and 0.49, respectively). No significant differences were observed in sleep latency or daytime dysfunction. (4) Conclusions: The results of the present study suggest that resistance intervention may be an effective therapeutic option to improve mental health and sleep quality in older adults aged 65 or older, offering a non-pharmacological approach to improving overall well-being in this demographic.

Structure-based identification of novel PPAR gamma ligands.

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor with an important role in the glucose metabolism and a target for type 2 diabetes mellitus therapy. The recent findings relating the use of the receptor full agonist rosiglitazone and the incidence of myocardial infarction raised concerns regarding whether receptor activation can actually be useful for diabetes management. The discovery of MRL-24 and GQ-16, ligands that can partially activate PPARγ and prevent weight gain and fluid retention, showed that a submaximal receptor activation can be a goal in the development of new ligands for PPARγ. Additionally, two previously described receptor antagonists, SR-202 and BADGE, were also shown to improve insulin sensitivity and decrease TNF-α level, revealing that receptor antagonism may also be an approach to pursue. Here, we used a structure-based approach to screen the subset 'Drugs-Now' of ZINC database. Fifteen ligands were selected after visual inspection and tested for their ability to bind to PPARγ. A benzoimidazol acetate, a bromobenzyl-thio-tetrazol benzoate and a [[2-[(1,3-dioxoinden-2-ylidene)methyl]phenoxy]methyl]benzoate were identified as PPARγ ligands, with IC50 values smaller than 10µM. Molecular dynamic simulations showed that the residues H323, H449, Y327, Y473, K367 and S289 are key structural elements for the molecular recognition of these ligands and the polar arm of PPARγ binding pocket.

Identification and evaluation of thermotolerance of yeasts from milk in natura exposed to high temperature and slow and fast pasteurization.

Milk is considered one of the basic raw materials of animal origin; it must present hygienic quality and physical-chemical properties suitable for processing and human consumption. Thus, the ingestion of milk in natura when not properly treated can be characterized as an opportunistic route of transmission of possible microbial pathogens, which can offer risks to public health. The present study aimed the yeast identification, to analyze the thermo-resistance of yeasts isolated from fresh milk, and to trace the susceptibility profile of the isolates to antifungal agents. For this, 23 samples of fresh milk type B, collected by manual or mechanical milking, were stored in collective refrigeration tanks of farms located in the Metropolitan Region of Natal and nearby, State of Rio Grande do Norte (RN), Brazil. Twenty samples of fresh milk commercially traded in the city of Ceará-Mirim RN were also analyzed. The yeasts were quantified by count of colony-forming units (CFU). All isolated species were treated by slow pasteurization (62-64 °C for 30 min) and fast (72-75 °C for 20 s), as well as by boiling (100 °C). Fifty yeast strains were obtained, and the species were identified as Candida tropicalis (28%), Candida parapsilosis (14%), Candida albicans (12%), Candida glabrata (10%), Candida krusei (10%), Kluyveromyces marxianus (10%), Candida guilliermondii (8%), Candida rugosa (2%), Candida orthopsilosis (2%), Pichia manshurica (2%), and Kodamaea ohmeri (2%). Five isolates showed resistance to the antifungal agents tested. Among all the isolates submitted to heat treatment, 80% were resistant to fast pasteurization and 60% to boiling, but none of them resisted the slow pasteurization. The milk collected through mechanical milking and stored in collective cooling tanks, presented higher rates of yeast contamination, compared to milk samples collected by manual milking and kept under the same storage conditions.

Trends in Dual Antiplatelet Therapy Use for Neurointerventional Procedures for the Management of Intracranial Aneurysms.

The use of periprocedural dual antiplatelet therapy (DAPT) has significantly evolved along with innovations in the endovascular management of intracranial aneurysms. Historically, aspirin and clopidogrel have been the most commonly employed regimen due to its safety and efficacy. However, recent studies highlight the importance of tailoring DAPT regimens to individual patient characteristics which may affect clopidogrel metabolism, such as genetic polymorphisms. In the present report, a systematic review of the literature was performed to determine optimal antiplatelet use with flow diverting stents, intracranial stents, intrasaccular devices, and stent-assisted coiling. Studies were analyzed for the number of aneurysms treated, DAPT regimen, and any thromboembolic complications. Based on inclusion criteria, 368 studies were selected, which revealed the increasing popularity of alternative DAPT regimens with the aforementioned devices. Thromboembolic or hemorrhagic complications associated with antiplatelet medications were similar across all medications. DAPT with ticagrelor, tirofiban, or prasugrel are effective and safe alternatives to clopidogrel and do not require enzymatic activation. Further clinical trials are needed to evaluate different antiplatelet regimens with various devices to establish highest-level evidence-based guidelines and recommendations.

Augmentation of flow diverter vessel wall apposition using the Comaneci device: case experience from a novel, off-label technique.

BACKGROUND: Flow diversion (FD) embolization of intracranial cerebral aneurysms is an increasingly common modality where treatment success depends on adequate vessel wall apposition of the device. This study aimed to investigate off-label use of the Comaneci device for augmenting vessel wall apposition in post-deployed flow diversion stents (FDS). METHODS: Over a 20- month period, all FD cases for the treatment of internal carotid artery (ICA) aneurysms were reviewed. Cases in which the Comaneci device was used to augment vessel wall apposition were analyzed. Data including patient demographics, case characteristics, and procedural outcomes were collected and analyzed as counts. RESULTS: From a total of 74 ICA FD cases, the Comaneci device was used to improve vessel wall apposition in 22 cases (29.7%) . Of these cases, 91% were female with a mean patient age of 64.9±11.3 years, and an average aneurysm size of 4.5±2.5 mm. Comaneci device deployment and retrieval was successful in all (100%) cases, with an average fluoroscopy time of 27.3±7.8 min, an average contrast usage of 25.8±13.2 mL, and an average radiation exposure of 915.1±320.8 mGy. Only two cases (9%) required subsequent balloon angioplasty after Comaneci deployment to improve vessel wall apposition throughout the FDS. CONCLUSION: Our experience with this technique demonstrates the feasibility of using the Comaneci device for augmentation of FDS vessel wall apposition with 100% success in the deployment and retrieval of the Comaneci device.

Mode of peroxisome proliferator-activated receptor γ activation by luteolin.

The peroxisome proliferator-activated receptor γ (PPARγ) is a target for treatment of type II diabetes and other conditions. PPARγ full agonists, such as thiazolidinediones (TZDs), are effective insulin sensitizers and anti-inflammatory agents, but their use is limited by adverse side effects. Luteolin is a flavonoid with anti-inflammatory actions that binds PPARγ but, unlike TZDs, does not promote adipocyte differentiation. However, previous reports suggested variously that luteolin is a PPARγ agonist or an antagonist. We show that luteolin exhibits weak partial agonist/antagonist activity in transfections, inhibits several PPARγ target genes in 3T3-L1 cells (LPL, ORL1, and CEBPα) and PPARγ-dependent adipogenesis, but activates GLUT4 to a similar degree as rosiglitazone, implying gene-specific partial agonism. The crystal structure of the PPARγ ligand-binding domain (LBD) reveals that luteolin occupies a buried ligand-binding pocket (LBP) but binds an inactive PPARγ LBD conformer and occupies a space near the ß-sheet region far from the activation helix (H12), consistent with partial agonist/antagonist actions. A single myristic acid molecule simultaneously binds the LBP, suggesting that luteolin may cooperate with other ligands to bind PPARγ, and molecular dynamics simulations show that luteolin and myristic acid cooperate to stabilize the Ω-loop among H2', H3, and the ß-sheet region. It is noteworthy that luteolin strongly suppresses hypertonicity-induced release of the pro-inflammatory interleukin-8 from human corneal epithelial cells and reverses reductions in transepithelial electrical resistance. This effect is PPARγ-dependent. We propose that activities of luteolin are related to its singular binding mode, that anti-inflammatory activity does not require H12 stabilization, and that our structure can be useful in developing safe selective PPARγ modulators.