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Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC-MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrödinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC-MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 μg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski's rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Identification of upper airway (UA) obstruction based on pharyngeal factors is important for obstructive sleep apnea (OSA) evaluation. This study is to assess the association between UA collapse characteristics and Friedman tongue position (FTP) in patients with OSA through drug-induced sleep endoscopy (DISE)., Patients and Methods: Retrospective study in individuals with OSA who were intolerant to continuous positive airway pressure (CPAP) treatment, submitted to DISE between June 1, 2013, and July 31, 2017. All subjects were classified as having an FTP grade of I to IV, and the velum, oropharynx, tongue base, epiglottis (VOTE) classification was used to analyze the DISE findings. UA collapse characteristics by DISE and FTP grading were compared between groups. The associations between specific DISE findings and FTP were analyzed., Results: In total, 205 patients were assessed. A positive and significant correlation was identified between the presence of retropalatal complete concentric collapse (CCC) and FTP grade, according to the following distributions: I, 17.4%; II, 22.9%; III, 33.7%; and IV, 48.7% ( P = 0.014). A logistic regression model revealed that CCC was associated with FTP grade IV. After adjusting for age, sex, body mass index (BMI), and tonsil size (TS), the grade IV individuals had a 4.4-fold higher risk of having CCC than grade I individuals ( P = 0.026). Multiple collapse sites and palatopharyngeal or combined (palatopharyngeal and hypopharyngeal) collapse were more prevalent in grade IV individuals., Conclusion: OSA patients intolerant to CPAP have a strong positive correlation between the FTP grade and presence of retropalatal CCC. FTP grade IV is an independent risk factor for velum-CCC, controlling for sex, age, BMI, and TS grade., Competing Interests: Dr Robson Capasso reports personal fees from and served at the advisory board for Invicta Medical, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Zhao et al.)

Objective: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients., Study Design: Phase I was a case-control study and Phase II a transversal descriptive study., Subjects and Methods: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied., Results: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test., Conclusion: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

Cortical lesions represent a hallmark of multiple sclerosis and are proposed as a predictor of disease severity. microRNAs are suggested to be important players in the disease pathogenesis and the experimental autoimmune encephalomyelitis animal model. We implemented a mouse model recapitulating more closely the human pathology as it is characterized by both an autoimmune heterogeneity and the presence of cortical lesions, two parameters missing in experimental autoimmune encephalomyelitis. In our model, mice clustered in two groups displaying high or low clinical scores. Upon cortical cytokine injection, lesions appeared with a specific topography while cortical miRNA profiles were altered. These two features differed according to disease severity. We evidenced changes in miRNA regulators and targets suggesting that miRNA alteration had functional repercussions that could explain the differences in cortical lesions. This model represents a crucial tool for the study of both miRNA involvement and cortical lesion formation in disease pathogenesis., Competing Interests: NO, OG, RC, PB, PH, MC, GO, MA, GM No competing interests declared, (© 2020, Orefice et al.)

Cycas pectinata Buch.-Ham. is commonly used in folk medicine against various disorders. The present study investigated the antidepressant and cytotoxicity activity of methanol extract of C. pectinata (MECP) along with quantitative phytochemical analysis by GC-MS method. Here, the GC-MS study of MECP presented 41 compounds, among which most were fatty acids, esters, terpenoids and oximes. The antidepressant activity was assessed by the forced swimming test (FST) and tail suspension test (TST) models. In contrast, MECP (200 and 400 mg/kg) exhibited a significant and dose-dependent manner reduction in immobility comparable with fluoxetine (10 mg/kg) and phenelzine (20 mg/kg). MECP showed a weak toxicity level in the brine shrimp lethality bioassay (ED 50 : 358.65 µg/mL) comparable to the standard drug vincristine sulfate (ED 50 : 2.39 µg/mL). Three compounds from the GC-MS study were subjected to density functional theory (DFT) calculations, where only cyclopentadecanone oxime showed positive and negative active binding sites. Cyclopentadecanone oxime also showed a good binding interaction in suppressing depression disorders by blocking monoamine oxidase and serotonin receptors with better pharmacokinetic and toxicological properties. Overall, the MECP exhibited a significant antidepressant activity with moderate toxicity, which required further advance studies to identify the mechanism.

Ocular adnexal aterio-venous malformations (AVMs) are rare congenital disabling anomalies, which may enlarge causing disfiguring deformity and rarely severe hemorrhage. These lesions are generally treated by preliminary endovascular embolization to shrink the arterio-venous malformation, followed by surgical gross total resection. The authors report a case of eyelid arterio-venous malformation in a 12-year-old girl, which progressively increased in size in few months. The patient complained mild itching, blurring of the vision, and mild tenderness. Magnetic resonance imaging showed an expansive mass with multiple arterial vessels at the left superior eyelid and left forehead. The diagnosis of arterio-venous malformation was then confirmed by digital subtraction angiography. Primary surgical excision was excluded because of the high risk of intrasurgical bleeding. Embolization through superselective cannulation of the left external carotid feeder vessels was performed resulting in flow exclusion up to the 80% of the nidus. Subsequent surgical resection was not recommended due to clinical evidence of keloid-prone skin.

Caesalpinia ferrea C. Mart. , popularly known as "Jucá" or "Pau-ferro", belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea . The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea .

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC 50 = 461.05 μg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC 50 = 247.92 μg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.

Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins' defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.

Objective: A reduced transversal dimension of the maxilla leads to narrower nasal cavities, which may reduce airflow to the lungs. Maxillary expansion widens nasal floor. However, there is huge controversy regarding whether this increase does actually lead to increased airflow. In this systematic review and meta-analysis we aim to resolve this question by evaluating studies that have undertaken rhinomanometric measurements., Review Methods: Pubmed (Medline), the Cochrane Library, EMBASE and Trip Database were checked by two authors. Two authors extracted the data. Main outcome was expressed as the difference between resistance before and after treatment and the 95% confidence interval., Results: 30 studies were selected for full text reading. A total of 12 studies (301 patients) met the inclusion criteria. All selected articles found reduced resistance after palatal expansion. The data pooled in the meta-analysis reveals a statistically significant difference of 0.12 Pa s/cm 3 mean reduction after palatal expansion (CI 95% 0.06, 0.18) for nine uncontrolled studies. Regarding nasal airflow, the pooled data show a statistically significant difference of 29.9 cm 3 /s increase after palatal expansion (CI 95% 9.17, 50.64)., Conclusion: According to the available evidence, palatal expansion in pediatric patients decreases nasal resistance and increases nasal flow., Competing Interests: Declaration of competing interest The authors declare not to have any conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Inferior turbinates are the main structure related to impaired nasal breathing. When medical treatment fails, surgery is the next step, according to clinical guidelines. However, despite the widespread acceptance of this procedure, there is some controversy about performing it in children., Data Sources: Pubmed (Medline), the Cochrane Library, EMBASE, Scopus, Science direct, SciELO and Trip Database., Review Methods: We looked for articles in which the individual outcome of turbinate surgery in pediatric patients was investigated independently of whether it was the main objective of the study or not., Results: 13 papers (1111 patients) met the inclusion criteria. 6 authors performed diverse objective assessment and 11 authors used subjective scales. All of them found improvement after surgery. Due to the heterogeneity of the methods used, they could not be included in a metanalysis. Eleven out of the 13 authors reported 3.12% complication rates, being minor bleeding the most common (1.30%), followed by crust (0.49%) and pain (0.47%)., Conclusions: There is a lack of high quality studies in children. Turbinate surgery in children is a safe technique with low complication rates. The available evidence suggests improvement in subjective outcomes after turbinate surgery in children. We cannot make a formal recommendation of a surgical technique in children given the lack of high quality studies, and since comparison between available papers is not possible. Although the evidence at our disposal is weak, it suggests that the safest techniques are MAIT, radiofrequency, coblation and laser., Competing Interests: Declaration of competing interest This work is part of the research completed by Christian Calvo-Henriquez, MD, to obtain a PhD degree., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Amburana cearensis A.C. Smith is an endemic tree from Northeastern Brazil used in folk medicine as teas, decocts and syrups for the treatment of various respiratory and inflammatory diseases, since therapeutic properties have been attributed to compounds from its stem bark and seeds. Numerous pharmacological properties of semi-purified extracts and isolated compounds from A. cearensis have been described in several biological systems, ranging from antimicrobial to anti-inflammatory effects. Some of these activities are attributed to coumarins and phenolic compounds, the major compounds present in A. cearensis seed extracts. Multiple lines of research demonstrate these compounds reduce oxidative stress, inflammation and neuronal death induced by glutamate excitotoxicity, events central to most neuropathologies, including Alzheimer's disease (AD) and Parkinson's Disease (PD). This review focuses on the botanical aspects, folk medicine use, biological effects and pharmacological activities of A. cearensis compounds and their potential as novel non-toxic drugs for the treatment of neurodegenerative diseases.

Cancer is one of the most common causes of disease-related deaths worldwide. Despite the discovery of many chemotherapeutic drugs that inhibit uncontrolled cell division processes for the treatment of various cancers, serious side effects of these drugs are a crucial disadvantage. In addition, multi-drug resistance is another important problem in anticancer treatment. Due to problems such as cytotoxicity and drug resistance, many investigations are being conducted to discover and develop effective anticancer drugs. In recent years, researchers have focused on the anticancer activity coumarins, due to their high biological activity and low toxicity. Coumarins are commonly used in the treatment of prostate cancer, renal cell carcinoma and leukemia, and they also have the ability to counteract the side effects caused by radiotherapy. Both natural and synthetic coumarin derivatives draw attention due to their photochemotherapy and therapeutic applications in cancer. In this review, a compilation of various research reports on coumarins with anticancer activity and investigation and a review of structure-activity relationship studies on coumarin core are presented. Determination of important structural features around the coumarin core may help researchers to design and develop new analogues with a strong anticancer effect and reduce the potential side effects of existing therapeutics.

Caatinga flora which are found in a poor Brazilian region contain a substantial number of endemic taxa with biomedical and social importance for regional communities. This study examined the antioxidant and cytotoxic potential of 35 samples (extracts/fractions) from 12 Caatinga species and determined the antiproliferative and genotoxic action of dichloromethane fraction from Mimosa caesalpiniifolia stem bark (DC-Mca) on human and vegetal cells. Samples were assessed for chemopreventive ability, toxic effects on Artemia salina shrimp as well as cytotoxicity on tumor cell lines and erythrocytes. DC-Mca was also tested with respect to antiproliferative and genotoxic effects upon normal leukocytes and meristematic cells from A. cepa roots. Some extracts reduced free radical levels >95% and 7 samples exhibited a lethal concentration (LC) 50  < 100 µg/ml upon Artemia salina larvae. Eight samples displayed in vitro antitumor effects and three produced hemolysis. Data also demonstrated the pharmacological significance of bioactive extracts from Brazilian semi-arid region. There was no significant relationship between antioxidant, toxic, and antiproliferative activities, and that these properties were dependent upon the extractant. DC-Mca contained betulinic acid as main compound (approximately 70%), which showed higher (1) cytotoxic activity on cancer cell lines and dividing leukocytes, (2) reduced mitotic index of Allium cepa roots, and (3) induced cell cycle arrest and chromosomal bridges, thereby providing native promising sources for phytotherapy development., Abbreviations: ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); AcOH: ethyl acetate; ANOVA: analysis of variance; SUS: Brazilian Unified Health System; DC-Mca: dichloromethane fraction from Mimosa caesalpiniifolia stem bark; DMSO: dimethylsulfoxide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; EC 50 : effective concentration 50%; EtOAc: ethyl acetate; FDA: Food and Drug Administration; GC-Qms: gas chromatograph quadrupole mass spectrometer; GI: genotoxic index; HCT-116: colon carcinoma line; HL-60: promyelocytic leukemia line; HPLC: high-performance liquid chromatography; HRAPCIMS: high resolution atmospheric pressure chemical ionization mass spectrum; IC 50 : inhibitory concentration 50%; LC 50 : lethal concentration 50%; MeOH = methyl alcohol; MI: mitotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; MutI: mutagenic index; OVCAR-8 = ovarian carcinoma line; PBMC: peripheral blood mononuclear cells; RPMI-1640: Roswell Park Memorial Institute medium; SF-295: glioblastoma line; TEAC: trolox equivalent antioxidant capacity; TLC: thin-layer chromatography; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid.

Purpose: Myeloid sarcoma (MS) of the orbit is an uncommon condition in occurring in children, generally coupled to myeloproliferative neoplasms., Observations: We describe two rare cases of orbital MS in young boys with aggressive local symptoms but without evidence of acute myeloid leukemia (AML), both patients underwent orbitotomy for gross-tumor resection and biopsy. At follow up, there was no evidence of recurrence nor evolution of the myeloproliferative neoplasms clinically and by radiological and laboratory work-up. We also provide a detailed description of the magnetic resonance imaging presentation, with an extensive pathological analysis correlation., Conclusions and Importance: A comprehensive revision of the literature on isolated orbital MS was carried out with particular emphasis on clues for differential diagnosis and treatment options, stressing the need to consider MS even in the absence of sign and symptoms of an underlying myeloproliferative disorders., Competing Interests: The following authors have no financial disclosures (MP, MA, CR, HA, AM, SE, RM, MM, AE, LR, RC, DS)., (© 2020 The Authors.)

Since the outbreak of novel coronavirus disease (COVID-19) in December 2019, it has spread to various regions and countries, forming a global pandemic. Reducing nosocomial infection is a new issue and challenge for all healthcare systems. Otolaryngology is a high-risk specialty as it close contact with upper respiratory tract mucous, secretions, droplets and aerosols during procedures and surgery. Therefore, infection prevention and control measures for this specialty are essential. Literatures on the epidemiology, clinical characteristics and infection control measures of COVID-19 were reviewed, practical knowledge from first-line otolaryngologists in China, the United States, and Brazil were reviewed and collated. It was recommended that otolaryngology professionals should improve screening in suspected patients with relevant nasal and pharyngeal symptoms and signs, suspend non-emergency consultations and examinations in clinics, and rearrange the working procedures in operating rooms. The guidelines of personal protective equipment for swab sampling, endoscopy and surgery were listed. Indications for tracheotomy during the pandemic should be carefully considered to avoid unnecessary airway opening and aerosol-generation; precautions during surgery to reduce the risk of exposure and infection were illustrated. This review aimed to provide recommendations for otolaryngologists to enhance personal protection against COVID-19 and reduce the risk of nosocomial infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Friedman staging is a classic system to predict outcomes of obstructive sleep apnea (OSA) surgery. Increasing stage indicates more severe upper airway (UA) obstruction and worse surgical successful rate. In previous studies, the UA obstruction between stages were usually assessed based on awake examination. Drug-induced sleep endoscopy (DISE) is a new method that can evaluate airway collapse characteristics during sleep. Therefore, we planned to compare Friedman staging and DISE findings and fulfill the knowledge gap on the correlation between awake and sedated UA examination., Methods: Retrospective case series study that assessed patients with OSA who underwent DISE. Subjects were classified to stage II and stage III groups based on Friedman staging system. UA collapse characteristics based on velum, oropharynx, tongue base, epiglottis (VOTE) classification, including single/multiple obstruction sites, single/combined upper and lower obstruction levels, collapse degree and patterns in different sites, and surgical results among the groups were analyzed., Results: A total of 175 cases were analyzed. No significant differences were found in baseline measurements between groups. Stage III patients (n=102) had a higher proportion (74.5%) with 3 or 4 obstruction sites than stage II (57.5%, n=73). Velum (V) + oropharynx (O) + tongue base (T) was the most common multi-sites combined obstruction pattern with 33% in stage II and 37% in stage III, isolated lower level obstruction was the least with 6% and 4%, respectively. No significant differences were found in obstruction sites and levels. 106 patients underwent surgeries and 33 had post-surgical sleep study, 73.7% and 63.6% response rate were found in stage II and III with no significant difference., Conclusions: Upper and lower combined obstruction was the main pattern of collapse in both, Friedman stage II and III patients. Patients with OSA and Friedman stage III had more than 2 sites of obstruction than stage II patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1471). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.

Orexin-A (OX-A) protects the brain against oxidative stress-mediated ischemic injury. Since the endocannabinoid 2-arachidonoylglycerol (2-AG) and cannabinoid type-1 (CB1) receptors were previously shown to mediate some of the effects of OX-A exerted through the orexin-1 receptor (OX-1R), we investigated the involvement of 2-AG in OX-A-induced neuroprotection following oxygen and glucose deprivation (OGD) in mouse cortical neurons. OGD-induced reactive oxygen species (ROS) accumulation and neuronal death were prevented by both OX-A and arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1 receptor agonist, in a manner sensitive to OX-1R and CB1 receptor antagonists, SB334867 and AM251. OX-A stimulated 2-AG biosynthesis in cortical neurons. In neurons isolated from monoacylglycerol lipase (MAGL, a 2-AG hydrolyzing enzyme) null mice, 10-fold higher 2-AG concentrations were found and OGD failed to induce ROS production and cell death, whereas AM251 restored these noxious effects. OX-A-induced neuroprotection was mediated by the phosphoinositide-3-kinase/Akt (PI3K/Akt) survival pathway since both OX-A and ACEA induced phosphorylation of Akt and prevented OGD-induced cytochrome c release from the mitochondria, in a manner counteracted by SB334867 or AM251. Administration of OX-A reduced infarct volume and elevated brain 2-AG levels in a mouse model of transient ischemia. These results suggest that 2-AG and CB1 receptor mediate OX-A prevention of ischemia-induced neuronal apoptosis.

Laryngeal cancer (LCa), a neoplasm of the head and neck region, is a leading cause of death worldwide. Surgical intervention remains the mainstay of LCa treatment, but a crucial point is represented by the possible nodal involvement. Therefore, it is urgently needed to develop biomarkers and therapeutic tools able to drive treatment approaches for LCa. In this study, we investigated deregulated microRNAs (miRNAs) in tissues from LCa patients with either lymph node metastases (N+) or not (N-). miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. Results showed a significant decrease of miR-449a expression in N+ compared to N- patients, and miR-133b down-modulation in LCa tissues compared to paired normal ones. Receiver operating characteristic (ROC) curve analysis revealed the potential diagnostic power of miR-133b for LCa detection. According to the validation results, we selected miR-449a for further in vitro studies. Ectopic miR-449a expression in the LCa cell line Hep-2 inhibited invasion and motility in vitro, slowed cell proliferation, and induced the downregulation of Notch1 and Notch2 as direct targets of miR-449a. Collectively, this study provides new promising biomarkers for LCa diagnosis and a new opportunity to use miR-449a for the treatment of nodal metastases in LCa patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To review new devices and drugs relevant to otolaryngology-head and neck surgery that were approved by the US Food and Drug Administration (FDA) in 2019., Data Sources: Approval notifications for 2019 were extracted from the ENT (ear, nose, and throat) and general and plastic surgery sections of the FDA's medical devices and therapeutics listings., Review Methods: New therapeutics and medical devices identified from the query were analyzed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Technologies were assessed by 2 independent reviewers to ascertain relevance to otolaryngology, prioritized, and classified to subspecialty field with critical review based on extant scientific literature., Conclusions: Query of the FDA drug and device database returned 105 ENT devices (50 cleared, 55 with premarket approval, and 0 de novo), 543 general and plastic surgery devices (372 cleared, 170 with premarket approval, and 1 de novo), and 46 new otolaryngology-relevant drug approvals that occurred in 2019. Advances spanned all subspecialty areas with otology predominating, primarily due to hearing-related technologies. While scientific evidence was available for all new devices, there was significant heterogeneity in rigor of supporting scientific data., Implications for Practice: Technological and pharmaceutical innovation is an important catalyst for advances in the surgical specialties. Familiarity with new devices and therapeutics in otolaryngology-head and neck surgery ensures that clinicians keep abreast of developments with potential to improve prevailing standards of care., (© The Authors 2020.)

This article focuses on the role of skeletal surgery within the modified Stanford protocol with particular attention focused on the evolved role of MMA. First, surgery in patients presenting with congenital dentofacial deformity or characteristic drug-induced sleep endoscopy findings, then the growing role of maxillary expansion in a newly identified patient phenotype, and finally genioglossus advancement, are discussed. Less commonly used and validated techniques, such as isolated mandibular advancement and maxillomandibular expansion are not discussed in this article., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100-200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.

Chemically nickel oxide nanoparticles (NiONPs) involve the synthesis of toxic products, which restrict their biological applications. Hence, we developed a simple, eco-friendly, and cost-efficient green chemistry method for the fabrication of NiONPs using fresh leaf broth of Rhamnus triquetra (RT). The RT leaves broth was used as a strong reducing, capping, and stabilizing agent in the formation of RT-NiONPs. The color change in solution from brown to greenish black suggests the fabrication of RT-NiONPs which was further confirmed by absorption band at 333 nm. The synthesis and different physicochemical properties of RT-NiONPs were investigated using different analytical techniques such as UV-Vis (ultraviolet-visible spectroscopy), XRD (X-ray powder diffraction), FT-IR (Fourier-transform infrared spectroscopy), SEM (scanning electron microscopy), TEM (transmission electron microscopy), EDS (energy-dispersive X-ray spectroscopy), DLS (dynamic light scattering) and Raman. Further, RT-NiONPs were subjected to different in vitro biological activities and revealed distinctive biosafe and biocompatibility potentials using erythrocytes and macrophages. RT-NiONPs exhibited potential anticancer activity against liver cancer cell lines HUH7 (IC 50 : 11.3 µg/mL) and HepG2 (IC 50 : 20.73 µg/mL). Cytotoxicity potential was confirmed using Leishmanial parasites promastigotes (IC 50 : 27.32 µg/mL) and amastigotes (IC 50 : 37.4 µg/mL). RT-NiONPs are capable of rendering significant antimicrobial efficacy using various bacterial and fungal strains. NiONPs determined potent radical scavenging and moderate enzyme inhibition potencies. Overall, this study suggested that RT-NiONPs can be an attractive and eco-friendly candidate. In conclusion, current study showed potential in vitro biological activities and further necessitate different in vivo studies in various animal models to develop leads for new drugs to treat several chronic diseases., Competing Interests: The authors declare no conflict of interest.

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 2 3 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2- H -tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C)., Competing Interests: The authors declare no conflict of interest.

Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes. Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ 9 -tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol. The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions. Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions. Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract. With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.

Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound-Δ9-tetrahydrocannabinol (Δ9-THC)-as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa . However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

Over the last few years, the application of nanotechnology to nutraceuticals has been rapidly growing due to its ability to enhance the bioavailability of the loaded active ingredients, resulting in improved therapeutic/nutraceutical outcomes. The focus of this work is nanoprebiotics and nanoprobiotics, terms which stand for the loading of a set of compounds (e.g., prebiotics, probiotics, and synbiotics) in nanoparticles that work as absorption enhancers in the gastrointestinal tract. In this manuscript, the main features of prebiotics and probiotics are highlighted, together with the discussion of emerging applications of nanotechnologies in their formulation. Current research strategies are also discussed, in particular the promising use of nanofibers for the delivery of probiotics. Synbiotic-based nanoparticles represent an innovative trend within this area of interest. As only few experimental studies on nanoprebiotics and nanoprobiotics are available in the scientific literature, research on this prominent field is needed, covering effectiveness, bioavailability, and safety aspects.

The purpose of this study is to assess psychosocial risk across several pediatric medical conditions and test the hypothesis that different severe or chronic pediatric illnesses are characterized by disease specific enhanced psychosocial risk and that risk is driven by disease specific connectivity and interdependencies among various domains of psychosocial function using the Psychosocial Assessment Tool (PAT). In a multicenter prospective cohort study of 195 patients, aged 5-12, 90 diagnosed with acute lymphoblastic leukemia (ALL), 42 with epilepsy and 63 with asthma, parents completed the PAT2.0 or the PAT2.0 generic version. Multivariate analysis was performed with disease as factor and age as covariate. Graph theory and network analysis was employed to study the connectivity and interdependencies among subscales of the PAT while data-driven cluster analysis was used to test whether common patterns of risk exist among the various diseases. Using a network modelling approach analysis, we observed unique patterns of interconnected domains of psychosocial factors. Each pathology was characterized by different interdependencies among the most central and most connected domains. Furthermore, data-driven cluster analysis resulted in two clusters: patients with ALL (89%) mostly belonged to cluster 1, while patients with epilepsy and asthma belonged primarily to cluster 2 (83% and 82% respectively). In sum, implementing a network approach improves our comprehension concerning the character of the problems central to the development of psychosocial difficulties. Therapy directed at problems related to the most central domain(s) constitutes the more rational one because such an approach will inevitably carry over to other domains that depend on the more central function., Competing Interests: The authors have declared that no competing interests exist.

Objective: Mental health providers experience inappropriate sexual behavior from patients. It is unclear if training programs adequately prepare trainees to respond to such behaviors. Additionally, trainees may not seek support and guidance from supervisors after an incident. This is an exploratory study to document the prevalence of and assess the preparedness of trainees to deal with inappropriate sexual behavior., Methods: A survey was administered to 58 psychiatry residents and 14 psychology interns at the NYU School of Medicine. A total of 22 questions were asked regarding participants' experiences with inappropriate sexual behavior, including prevalence of, and preparedness during, and support received after the behavior., Results: Of those who completed the survey, 89% of respondents had experienced inappropriate sexual behavior. Seventy percent said they had no training in responding to inappropriate sexual behavior, and 95% wanted more training. A minority of respondents consistently sought support after these events, and of those who did, only 60% of trainees did so with a supervisor., Conclusion: Experiences involving inappropriate sexual behavior are prevalent among the mental health trainees surveyed, but most trainees did not feel that they received adequate training in preparation for or supervision after their experiences. Creating training or establishing protocols to respond to inappropriate sexual behavior may help trainees feel more capable and safer. Further studies are needed to understand inappropriate sexual behavior's impact on trainees and patient care, as well as to assess the efficacy of training and protocols developed to manage inappropriate sexual behavior.

Immune checkpoint blockade is an emerging anticancer strategy, and Nivolumab is a human mAb to PD-1 that is used in the treatment of a number of different malignancies, including non-small cell lung cancer (NSCLC), kidney cancer, urothelial carcinoma and melanoma. Although the use of Nivolumab prolongs survival in a number of patients, this treatment is hampered by high cost. Therefore, the identification of predictive markers of response to treatment in patients is required. In this context, PD-1/PDL1 blockade antitumor effects occur through the reactivation of a pre-existing immune response, and the efficacy of these effects is strictly associated with the presence of necrosis, hypoxia and inflammation at the tumour sites. It has been indicated that these events can be evaluated by specific assessments using a computed tomography (CT) texture analysis (TA) or radiomics. Therefore, a retrospective study was performed, which aimed to evaluate the potential use of this analysis in the identification of patients with NSCLC who may benefit from Nivolumab treatment. A retrospective analysis was performed of 59 patients with metastatic NSCLC who received Nivolumab treatment between January 2015 and July 2017 at Siena University Hospital (35 patients, training dataset), Catanzaro University Hospital and Reggio Calabria Grand Metropolitan Hospital, Italy (24 patients, validation dataset). Pre- and post-contrast CT sequences were used to contour the gross tumour volume (GTV) of the target lesions prior to Nivolumab treatment. The impact of variations on contouring was analysed using two delineations, which were performed on each patient, and the TA parameters were tested for reliability using the Intraclass Coefficient Correlation method (ICC). All analyses for the current study were performed using LifeX Software © . Imaging, clinical and pathological parameters were correlated with progression free survival and overall survival (OS) using Kaplan Meier analysis. An external validation testing was performed for the TA Score using the validation dataset. A total of 59 patients were included in the analysis of the present study. The reliability ICC analysis of 14 TA parameters indicated a highly reproducibility (ICC >0.70, single measure) in 12 (85%) pre- contrast and 13 (93%) post-contrast exams. A specific cut-off was detected for each of the following parameters: volume (score 1 >36 ml), histogram entropy (score 1 > 1.30), compacity (score 1 <3), gray level co-occurrence matrix (GLCM)-entropy (score 1 >1.80), GLCM-Dissimilarity (score 1 >5) and GLCM-Correlation (score 1<0.54). The global texture score allowed the classification of two subgroups of Low (Score 0-1; 36 patients; 61%) and High Risk patients (Score >1; 23 patients; 39%) that respectively, showed a median OS of 26 (mean +/- SD: 18 +/- 1.98 months; 95% CI 14-21 months) and 5 months (mean +/- SD: 6 +/- 0.99 months; 95% CI: 4-8 months; P=0.002). The current study indicated that TA parameters can identify patients that will benefit from PD-1 blockage by defining the radiological settings that are potentially suggestive of an active immune response. These results require further confirmation in prospective trials., (Copyright © 2020, Spandidos Publications.)

Convolvulus genus is a representative of the family of Convolvulaceae. Convolvulus plants are broadly distributed all over the world and has been used for many centuries as herbal medicine. Convolvulus genus contains various phytochemicals such as flavonoids, alkaloids, carbohydrates, phenolic compounds, mucilage, unsaturated sterols or terpenes, resin, tannins, lactones, and proteins. This review highlights the phytochemical composition, antimicrobial and antioxidant activities, application as food preservative, traditional medicine use, anticancer activities, and clinical effectiveness in human of Convolvulus plants. All the parts of Convolvulus plants possess therapeutic benefits; preliminary pharmacological data validated their use in traditional medicine. However, further preclinical and clinical experiments are warranted before any application in human health., (© 2019 John Wiley & Sons, Ltd.)

Nowadays, obesity is one of the most prevalent human health problems. Research from the last 30 years has clarified the role of the imbalance between energy intake and expenditure, unhealthy lifestyle, and genetic variability in the development of obesity. More recently, the composition and metabolic functions of gut microbiota have been proposed as being able to affect obesity development. Here, we will report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature, searching for the following keywords: metabolism, gut microbiota, dysbiosis, obesity. There is evidence for the association between gut bacteria and obesity both in infancy and in adults. There are several genetic, metabolic, and inflammatory pathophysiological mechanisms involved in the interplay between gut microbes and obesity. Microbial changes in the human gut can be considered a factor involved in obesity development in humans. The modulation of the bacterial strains in the digestive tract can help to reshape the metabolic profile in the human obese host as suggested by several data from animal and human studies. Thus, a deep revision of the evidence pertaining to the use probiotics, prebiotics, and antibiotics in obese patients is conceivable.

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds., Competing Interests: The authors declare no conflict of interest.

Background: To systematically review the literature for methods to localize the genial tubercle as a means for performing an advancement of the genioglossus muscle., Methods: PubMed, Google Scholar, CRISP, EMBASE, CINAHL, and Scopus were searched from inception through June 16, 2015., Results: One hundred fifty-two articles were screened, and the full text versions of 12 articles were reviewed in their entirety and 7 publications reporting their methodology for localizing the genial tubercle. Based upon these measurements and the results published from radiographic imaging and cadaveric dissections of all the papers included in this study, we identified the genial tubercle as being positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandibular border., Conclusion: Based upon the results of this review, the genial tubercles were positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandible border. It may serve as an additional reference for localizing the genial tubercle and the attachment of the genioglossus muscle to the mandible, although the preoperative radiological evaluation and the palpation of the GT are recommended to accurately isolate., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Euphorbia genus (Euphorbiaceae family), which is the third largest genus of angiosperm plants comprising ca. 2000 recognized species, is used all over the world in traditional medicine, especially in the traditional Chinese medicine. Members of this taxa are promptly recognizable by their specialized inflorescences and latex. In this review, an overview of Euphorbia -derived natural products such as essential oils, extracts, and pure compounds, active in a broad range of biological activities, and with potential usages in health maintenance, is described. The chemical composition of essential oils from Euphorbia species revealed the presence of more than 80 phytochemicals, mainly oxygenated sesquiterpenes and sesquiterpenes hydrocarbons, while Euphorbia extracts contain secondary metabolites such as sesquiterpenes, diterpenes, sterols, flavonoids, and other polyphenols. The extracts and secondary metabolites from Euphorbia plants may act as active principles of medicines for the treatment of many human ailments, mainly inflammation, cancer, and microbial infections. Besides, Euphorbia -derived products have great potential as a source of bioactive extracts and pure compounds, which can be used to promote longevity with more health., Competing Interests: The authors declare no conflict of interest.

Objectives/hypothesis: Examine US and international clinical trials in obstructive sleep apnea (OSA) to characterize researchers involved, interventions being studied, and opportunities for future investigation., Study Design: Retrospective database review., Methods: The information from ClinicalTrials.gov was used to assess OSA clinical trials between 1999 and 2017. Information was gathered on principle investigator (PI) demographics, interventions studied, study funding source, and regional distribution of research institutions., Results: There were 813 clinical trials studied. The majority of trials examined continuous positive airway pressure interventions (43.7%), with pharmacotherapies being the second most commonly investigated treatment (19.2%). Surgical interventions made up 10.7% (n = 87) of clinical trials for OSA. Most studies were based internationally (59.9%). PIs were predominantly male (72.0%); 72.7% had an MD and 28.6% had a PhD. There were no significant differences in funding source (National Institutes of Health vs. industry, P = .14) or institutional geography (international vs. US, P = .73) between surgical and nonsurgical studies. Surgical trials were significantly more likely to have a male PI and involve pediatric patients compared to nonsurgical trials (P < .001). Otolaryngologists represented 9.2% of all PIs and had similar rates of NIH funding compared to other medical specialists (P = .22)., Conclusions: This study provides a broad overview of past, current, and future treatment paradigms for OSA. Sleep surgery, specifically otolaryngology, is a small voice in the overall landscape of clinical trials for OSA. This information can help guide future research efforts and direct our specialty when setting priorities regarding research funding while encouraging a broad and interdisciplinary pursuit., Level of Evidence: NA Laryngoscope, 129:1940-1944, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Continuous positive airway pressure (CPAP) is the mainstay therapy for patients with obstructive sleep apnea (OSA) however compliance with CPAP is variable. Nasal ailments, such as nasal congestion are frequently mentioned as a cause for CPAP non-compliance, and potentially could be addressed prior to CPAP initiation, however, no specific criteria or recommendations for the evaluation and management of these patients exist. The aim of this retrospective study is to evaluate the effects of nasal anatomic features and disease on adherence to CPAP therapy for patients with OSA and determine the indications for pre-CPAP nasal treatment by using data obtained at clinical examination., Methods: In total, 711 adult patients with initial diagnosis of OSA and an apnea-hypopnea index of ≥20 who were amenable to CPAP were included. We analyzed nasal parameters, past history of nasal disease, subjective symptoms, and disease severity in addition to whether CPAP therapy had been initiated, rate of CPAP therapy use (initial and 1year), treatment continuation rate at 2 months and 1year, and nasal treatments for all patients., Results: CPAP therapy was initiated in 543 of 711 patients. Nasal resistance was significantly higher in patients who discontinued therapy soon after CPAP initiation. Nasal disease and nasal parameters were not found to be predictors of treatment adherence at 1year. Allergic rhinitis, moderate to severe nasal congestion at bedtime, slight or extensive sinus opacification, and a high nasal septum deviation score were found to be independent predictors of nasal treatment, while strong awareness of nasal congestion, a past history of sinusitis, and a total nasal resistance (supine position) of ≥0.35Pa/cm 3 /s were independent predictors of surgical treatment., Conclusion: Long-term CPAP therapy adherence in patients with OSA can be predicted from initial CPAP adherence. Nasal disease and nasal parameters are important factors for early CPAP therapy discontinuation and should be adequately treated before therapy initiation to ensure long-term adherence. Indications for pre-CPAP nasal treatment and nasal surgery for patients with OSA can be predicted from the data obtained at the first examination, and these patients should be treated differently from those without OSA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Intramedullary spinal cord metastases are rarely encountered in patients suffering from extra - central nervous system primary cancer, with only 2 described cases reported in the literature deriving from esophageal cancer. Intramedullary spinal cord metastases may occur at any level of the spinal cord but cervical location is the most frequent. We report the first case of intramedullary metastasis affecting the thoracic spinal cord from esophageal squamous cell carcinoma in a 35-year-old patient.

There is a growing interest in a potential use of essential oils (EOs) as a replacement for traditional pesticides and herbicides. The aims of this study were to: (i) Identify the chemical composition of the two EOs derived from Origanum heracleoticum L. and O. majorana L., (ii) evaluate the in vitro antifungal activity of the EOs against some postharvest phytopathogens ( Botrytis cinerea , Penicillium expansum , Aspergillus niger and Monilinia fructicola ), (iii) evaluate the in vitro antibacterial activity against Bacillus megaterium , Clavibacter michiganensis , Xanthomonas campestris , Pseudomonas fluorescens and P. syringae pv. phaseolicola , (iv) evaluate the effect of both studied EOs on the spore germination percentage and their minimum inhibitory concentration (MIC) against M. fructicola , and (v) study the possible phytotoxicity of the two EOs and their major constituents, carvacrol for O. heracleoticum and terpinen-4-ol for O. majorana , against tha germination and initial radicle growth of radish, lettuce, garden cress and tomato. The two EOs demonstrated promising in vitro antimicrobial and antifungal activities against all tested microorganisms. EOs showed high inhibition of spore germination percentage at the minimal inhibitory concentration of 500 and 2000 µg/mL, respectively. Moreover, both germination and radical elongation of selected plant species were sensitive to the oils.

This work is an updated snapshot of Lamium plants and their biological activities. The main features of the plant are described and the components of its essential oils are summarized. The traditional medicinal uses of Lamium plants has been reported. The presence of these chemicals i.e., hydroxycinnamic acids, iridoids, secoiridoids, flavonoids, anthocyanins, phenylpropanoids, phytoecdysteroids, benzoxazinoids, betaine can provide biological activities. After the discussion of antioxidant properties documented for Lamium plants, the biological activities, studied using in vitro models, antimicrobial, antiviral, anti-inflammatory, anti-nociceptive activity, and pain therapy and cytotoxicity and cytoprotective activity are here described and discussed. Finally, targeted examples of in vivo studies are reported.

Cucurbita genus has received a renowned interest in the last years. This plant species, native to the Americas, has served worldwide folk medicine for treating gastrointestinal diseases and intestinal parasites, among other clinical conditions. These pharmacological effects have been increasingly correlated with their nutritional and phytochemical composition. Among those chemical constituents, carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, and functional carbohydrates and polysaccharides are those occurring in higher abundance. However, more recently, a huge interest in a class of triterpenoids, cucurbitacins, has been stated, given its renowned biological attributes. In this sense, the present review aims to provide a detailed overview to the folk medicinal uses of Cucurbita plants, and even an in-depth insight on the latest advances with regards to its antimicrobial, antioxidant and anticancer effects. A special emphasis was also given to its clinical effectiveness in humans, specifically in blood glucose levels control in diabetic patients and pharmacotherapeutic effects in low urinary tract diseases.

(1) The beneficial effects of hydrogen sulfide (H 2 S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H 2 S biosynthesis, previously used as a marker for H 2 S production, is dramatically increased in circulation in uremia, while H 2 S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H 2 S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H 2 S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine-β-synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca 2+ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid.

Background and Purpose: Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, results in chronic inflammation and irreversible skeletal muscle degeneration. Moreover, the associated impairment of autophagy greatly contributes to the aggravation of muscle damage. We explored the possibility of using non-euphoric compounds present in Cannabis sativa, cannabidiol (CBD), cannabidivarin (CBDV) and tetrahydrocannabidivarin (THCV), to reduce inflammation, restore functional autophagy and positively enhance muscle function in vivo., Experimental Approach: Using quantitative PCR, western blots and [Ca 2+ ] i measurements, we explored the effects of CBD and CBDV on the differentiation of both murine and human skeletal muscle cells as well as their potential interaction with TRP channels. Male dystrophic mdx mice were injected i.p. with CBD or CBDV at different stages of the disease. After treatment, locomotor tests and biochemical analyses were used to evaluate their effects on inflammation and autophagy., Key Results: CBD and CBDV promoted the differentiation of murine C2C12 myoblast cells into myotubes by increasing [Ca 2+ ] i mostly via TRPV1 activation, an effect that undergoes rapid desensitization. In primary satellite cells and myoblasts isolated from healthy and/or DMD donors, not only CBD and CBDV but also THCV promoted myotube formation, in this case, mostly via TRPA1 activation. In mdx mice, CBD (60 mg·kg -1 ) and CBDV (60 mg·kg -1 ) prevented the loss of locomotor activity, reduced inflammation and restored autophagy., Conclusion and Implications: We provide new insights into plant cannabinoid interactions with TRP channels in skeletal muscle, highlighting a potential opportunity for novel co-adjuvant therapies to prevent muscle degeneration in DMD patients., Linked Articles: This article is part of a themed section on 8 th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc., (© 2018 The British Pharmacological Society.)

In states of intestinal dysbiosis, a perturbation of the normal microbiome composition, the intestinal epithelial barrier (IEB) permeability is increased as a result of the disruption of the epithelial tight junction protein network, in which occludin is mostly affected. The loss of IEB integrity promotes endotoxemia, that is, bacterial lipopolysaccharide (LPS) translocation from the intestinal lumen to the circulatory system. This condition induces an enhancement of pro-inflammatory cytokines, which leads to neuroinflammation through the gut-brain axis. Orexin-A (OX-A), a neuropeptide implicated in many physiological functions and produced mainly in the brain lateral hypothalamic area, is expressed also in several peripheral tissues. Orexin-producing neurons have been found in the myenteric plexus to project to orexin receptor 1 (OX-1R)-expressing enterocytes of the intestinal villi. In the present study we investigated the protective role of OX-A against LPS-induced increase of IEB permeability and microglia activation in both an in vivo and in vitro model of the gut-brain axis. By exploiting biochemical, immunocytochemical, immunohistochemical, and functional approaches, we demonstrate that OX-A preserves the IEB and occludin expression, thus preventing endotoxemia and subsequent neuroinflammation.