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International Regulations for Bioequivalence Approval of Locally Acting Orally Inhale...
Dr. Vinod Gaikwad
Prajakta  Patil

Dr. Vinod Gaikwad

and 3 more

January 09, 2021
Bioequivalence (BE) is established between the brand drug and the generic drug to allow the linking of preclinical and clinical testing conducted on the reference listed drug. Regulatory agencies around the globe have come up with the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. The prime intent of the present article is to compare approaches of different international regulatory authorities such as Health Canada, European Medicines Agency and the US Food and Drug Administration that have published guidance related to locally acting OIDPs. Moreover, the Central Drugs Standard Control Organisation, India, has published guidelines for bioavailability and bioequivalence studies. BE recommendations from global regulatory agencies were based on comparison for different parameters, namely inhaler device, formulation, reference product’s selection, in-vitro as well as in-vivo studies (pharmacokinetics, pharmacodynamics, and clinical studies). In the case of in-vivo studies, details about study design, dose choices, inclusion/ exclusion criteria of the subject, study period, endpoint study, and equivalence acceptance criteria were discussed in the present review article.
Anesthesia during rigid bronchoscopy for tracheobronchial foreign body removal in chi...
Weiping wang
Shangyingying Li

Weiping wang

and 6 more

January 09, 2021
Background: There is no consensus regarding the optimal anesthetic approach to rigid bronchoscopy in children suffering from tracheobronchial FBA. We performed this meta-analysis to assess the efficacy and safety of the different anesthesia agents and ventilation modes for tracheobronchial foreign body removal via rigid bronchoscopy in young children. Methods: A systematic search of three major databases for all relevant articles. A meta-analysis was performed to analyze the data. Results: Four trials for evaluating different anesthetics and six trials for evaluating two kinds of ventilation modes were found. Compared with the sevoflurane-based volatile anesthesia group , the rate of perioperative complications included hypoxemia (OR, 2.07; 95% CI, 1.38–3.11; P=0.0004; I2 = 0%), apnea (OR, 2.74; 95% CI, 1.11–6.78; P = 0.03; I2 = 60%), laryngospasm (OR, 2.89; 95% CI, 1.67–4.98; P=0.0001; I2 = 0%), cough/bucking (OR, 2.93; 95% CI, 1.86–4.63; P<0.00001; I2 = 0%), and body movement (OR, 3.51; 95% CI, 2.03–6.09; P<0.00001; I2 = 0%) were significantly increased in the propofol-based total intravenous anesthesia and the duration of operation were longer in the Group Prop. Compared with the control ventilation group , the incidences of laryngospasm (OR, 0.16; 95% CI, 0.05–0.56; P=0.004; I2 = 54%), apnea (OR, 0.21; 95% CI, 0.09–0.50; P=0.0004; I2 = 0%), and cough/bucking (OR, 0.03; 95% CI, 0.01–0.10; P<0.00001; I2 = 41%) increased in the spontaneous ventilation group and the duration of operationand emergence from anesthesia significantly prolonged in the Group SV. Conclusions: Our meta-analysis suggests that sevoflurane-based volatile anesthesia was superior to propofol-based total intravenous anesthesia for the management of foreign body aspiration in children. There is still no strong evidence indicated that one ventilation technique was superio
Clinical and genetic analysis of multi-system pseudohypoaldosteronism type 1 caused b...
Sicui Hu
hongxiu yang

Sicui Hu

and 6 more

January 09, 2021
This article aims to provide a comprehensive review of the clinical features and genetics basis of multi-system pseudohypoaldosteronism type 1 caused by SCNN1B gene mutations.
Doege-Potter Syndrome In A Facial Solitary Fibrous Tumor: Diagnose And Clinical Manag...
Roser Fort-Culillas
Rebeca Barahona

Roser Fort-Culillas

and 8 more

January 09, 2021
Doege Potter syndrome is a rare paraneoplastic clinical entity. A 31-year-old woman consulted with a right indurated malar mass and hypoglycemia. Blood test showed a non-insulin-mediated hypoglycemia. CT scan revealed a solid tumor from the right temporal region with liver metastasis. The histopathological diagnosis revealed a solitary fibrous tumor.
An Enlarging Neck Mass with Dyspnea and Left Finger Pain in a 63-year-old Woman
Thanh Hoang
Andrea Snitchler

Thanh Hoang

and 2 more

January 09, 2021
We described an atypical presentation of papillary thyroid cancer metastasized to left finger. This case highlights the importance of an early and effective engagement of multidisciplinary team approach with family in order to optimize patient care.
Lateral Maxillary Sinus Floor Elevation in presence of a sinus osteoma : A case repor...
Mootaz MLOUKA
Mohamed Tlili

Mootaz MLOUKA

and 6 more

January 09, 2021
Maxillary sinus grafting is a well-know procedure with high predictability used to to correct vertical bone defects in the posterior region of the maxilla.The presence of a sinus osteoma adds to its difficulty and may recquire a more specific case management depending on the lesion's extent.
The Blue Man: Pediatric Diseases with Implications for Adulthood
Karuna Dewan
Charles MacDonald

Karuna Dewan

and 2 more

January 08, 2021
Blue discoloration of the skin and cartilage, or ochronosis, is a rare physical examination finding. Here are two cases of childhood onset ochronosis, one exogenous and one endogenous in etiology.
Opportunists in peritonitis in continuous ambulatory peritoneal dialysis: the example...
Christelle Fosso
Evelyne Maillart

Christelle Fosso

and 5 more

January 08, 2021
We report a case of P. yeei CAPD-peritonitis in a patient experiencing repeated episodes of peritonitis. P. yeei, an emerging opportunistic pathogen, takes advantage of specific virulence factors and peculiar circumstances. We discuss the exogenous or endogenous microbial source of the peritonitis and guidelines to decrease its occurrence.
Weekend effects of admission and surgery in acute aortic syndrome
Chao Song
YunLong Fan

Chao Song

and 3 more

January 08, 2021
Background: The weekend effect is a phenomenon characterized by increased early all-cause mortality among patients hospitalized or undergoing surgery over the weekend for emergencies. Objectives: With this meta-analysis we aimed to determine whether weekend hospitalization/surgery due to acute aortic syndromes (AAS) is associated with increased early all-cause mortality. Methods:Major electronic databases were searched for studies published up to October 2020 reporting early all-cause mortality rates for admissions/operations on weekends versus weekdays. Data were pooled using fixed- and random-effects models. The primary outcome of the study was early all-cause mortality after weekend versus weekday. Results: All the included studies were retrospective, comparative or cohort studies enrolling patients admitted or underwent surgery for AAS and reported early all-cause mortality after weekend (including holiday) versus weekday. A total of 18 studies including a total of 252807 patients were identified. This meta-analysis showed a significant increase in the early all-cause mortality for patients admitted/conducted surgery for AAS on weekends compare with weekdays (fixed-effect: OR 1.1;95% CI 1.06-1.14;P<0.00001). Conclusion: Weekend admission/surgery for AAS is associated with a increased risk of early all-cause mortality.
Implementation and evaluation of a nurse-driven noninvasive ventilation weaning proto...
Julie Cassibba
Marie Chevallier

Julie Cassibba

and 6 more

January 08, 2021
Rationale: Noninvasive ventilation (NIV) is the first-line therapy in infants with bronchiolitis-related acute respiratory failure. However, there is a lack of data regarding weaning from NIV in this setting. Working hypothesis: This study aims to evaluate a nurse-driven weaning protocol in this homogenous population. Study design: A retrospective single-center study with pre-versus-post comparative design in a tertiary center. Methodology: Data from all infants aged ≤ 6 months admitted to the PICU during 2 seasons with a clinical diagnosis of bronchiolitis and requiring any type of noninvasive ventilatory support on admission, were analyzed. Main results: In total, 187 infants (95 with standard and 92 with nurse-driven protocols) were included; the median age was 47 (IQR 24-75) and 31 days (19-58) in patients at baseline and after the protocol implementation, respectively. There was no difference in terms of weaning failure between the two periods (11 (12%) versus 14 (15%), p=0.46). At baseline, the ventilatory support duration was 70 hours (IQR 54-104) versus 56 hours (IQR 29-83) during the nurse-driven protocol period (p=0.29). The PICU and hospital lengths of stay did not differ between the two periods. No complication related to NIV occurred in the two periods. Conclusions: In patients with bronchiolitis supported by NIV, the nurse-driven weaning management - as opposed to physician-driven - was not associated with a significantly higher proportion of weaning failure cases.
Investigation on stress micro-cycles and mild wear mechanism in gear contact fatigue
Ye Zhou
Caichao Zhu

Ye Zhou

and 4 more

January 08, 2021
Gear contact fatigue is becoming a primary limitation for the growing demand of power density and service life in gear-driven equipment. The unchecked surface fatigue crack could further cause premature failure and put a serious risk to the safety and reliability of mechanical systems. In this work, an attempt is made to investigate the effects of rolling-sliding and mild wear on contact fatigue behavior. A comprehensive contact model is developed to capture the variation instantaneous pressure and stress field is calculated with the transient mixed EHL approach. Rolling-sliding contact is simulated with the time-varying roughness topography updated by Archard wear equation. The stress cycles are extracted and the relative contact fatigue life is obtained by using Zaretsky criterion. Results suggest that in rolling-sliding contact the contact fatigue life is obviously lower compared with pure rolling. The increases in the number and amplitude of stress micro-cycles is found to be the main contributors to the reduction of fatigue life. Mild wear tends to smooth the surface, subsequently mitigates the stress concentration and reduces stress cycles, then decrease the risk of surface contact fatigue.
When Starting a MICS Program, Don’t Assume Excellence: Prove It!
Rachel Eikelboom
Rashmi Nedadur

Rachel Eikelboom

and 3 more

January 08, 2021
Commentary:When Starting a MICS Program, Don’t Assume Excellence: Prove It!Rachel Eikelboom MD1,2, Rashmi Nedadur MD3,Roberto Vanin Pinto Ribeiro MD3, Bobby Yanagawa MD PhD31 Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada2 Division of Cardiac Surgery, McMaster University, Hamilton, Ontario, Canada3 Division of Cardiac Surgery, St Michael’s Hospital, University of Toronto, Toronto, Ontario, CanadaCorresponding author:Bobby Yanagawa MD, PhD, FRCSC Program Director, Division of Cardiac Surgery, University of Toronto Assistant Professor, Division of Cardiac Surgery, St. Michael’s Hospital  30 Bond Street, 8th Floor, Bond Wing Toronto, ON M5B 1W8 Canada Tel: 416 864 5706 Fax: 416 864 5031 Email: yanagawab@smh.caWord count: 430Conflict of interest: The authors have no conflict of interest and have not received any funding.Central Figure:
Incretin mimetics restore the ER-mitochondrial axis and switch neuronal fate towards...
Theodora Panagaki
Elisa B.  Randi

Theodora Panagaki

and 3 more

January 08, 2021
Background and Purpose: Amyotrophic lateral sclerosis with associated frontotemporal dementia, Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease are the major neurodegenerative disorders that afflict more than 7 million people worldwide. There are no disease-modifying or disease-retarding therapeutic agents currently available on the market. All four conditions feature several seemingly-disparate pathological and genetic lesions, which, however, converge into calcium dyshomeostasis and a disturbed function of the axis of the endoplasmic reticulum (ER) and mitochondria. Experimental Approach: Incretin mimetics – traditionally anti-diabetic therapeutic agents – have been repeatedly shown to exert neurotrophic effects in neuroblastoma cells, rodent primary neurones, and murine models of neurodegeneration. Herein, for the very first time, we assess the pharmacological effects of Liraglutide and the dual incretin DA-CH3 in terminally differentiated human neurones under conditions of calcium-dependent chronic ER stress and additionally assess their efficacy in one of the most critical regulatory point for neurones, the mitochondrial respiration and dynamics. Key Results: Liraglutide and DA-CH3 rescue the arrested oxidative phosphorylation and glycolysis. They mitigate the suppressed mitochondrial biogenesis and hyper-polarisation of the mitochondrial membrane, all, to re-establish normalcy of cellular bioenergetics under conditions of chronic ER stress. These effects correlate with a resolution of the unfolded protein response and the autophagic arrest to halt the excessive synaptic and neuronal death, with the dual incretin displaying a superior anti-apoptotic effect. Conclusions: Our findings pave the way for a therapeutic strategy for disorders with a considerable social-economic burden and deepen our understanding of the spectrum of the incretin-signalling functions.
REAL-WORLD CLINICAL OUTCOMES ASSOCIATED WITH CANAGLIFLOZIN IN PATIENTS AGED 65 YEARS...
MANUEL GARGALLO-FERNANDEZ
Alba Galdón Sanz-Pastor

MANUEL GARGALLO-FERNANDEZ

and 5 more

January 08, 2021
Abstract Objectives The observational REAL WECAN study showed that canagliflozin 100 mg (CANA100) as add-on therapy, and canagliflozin 300 mg (CANA300), switching from prior SGLT-2i therapy, significantly improved several cardiometabolic parameters in patients with T2DM. The aim of this sub-analysis was to assess the effectiveness and safety of canagliflozin in patients aged >65 years. The primary outcome of the study was the mean change in HbA1c over the follow-up time. Materials and Methods 583 patients met the inclusion criteria (39.5% > 65 years), 279 in the CANA100 cohort (36.9 % > 65 years, mean HbA1c 8.05%) and 304 in the CANA300 cohort (41.8 % > 65 years, mean HbA1c 7.51%). Results In the CANA100 cohort, older patients showed significant reductions in HbA1c (-0.78%) and weight (-4.5 kg). Patients aged >65 years switching to CANA300 experienced a significant decrease in HbA1c (-0.27%) and weight (-2.1 kg). There were no significant differences in HbA1c and weight reductions when the cohorts of patients <65 and >65 years were compared in a multiple linear regression model. The safety profile of canagliflozin was similar in both age groups. Conclusion These findings support canagliflozin as an effective therapeutic option for older adults with T2DM
Evaluation of fetal condition in uncomplicated pregnancies at 40 weeks and beyond by...
elvira semenova
Nikolai Rukhliada

elvira semenova

and 2 more

January 08, 2021
Objective. The aim of our data is to reveal the method of prognosis abnormal perinatal outcome, using combination US and Doppler results in uncomplicated pregnancies at 40 weeks and beyond. Design.1020 uncomplicated pregnant women at 40 weeks and beyond were examined 48 hours before delivery. We analyzed fetus’s condition during labor and just after. Setting. According these dates all women were divided into 3 groups after amniotic index(AI)and pulsatility indices(PI) in the middle cerebral artery(MCA). Population.260 women were included in the study because they met the inclusion criteria. Methods.All women were divided into 3 groups (group 1 - PI>0.835, any value of AI, group 2-AI >85, PI ≤ 0.835, group 3- AI ≤ 85 and PI ≤ 0.835).We analyzed fetus’s condition during labor and just after delivery (Apgar score <=7 and >7 on the 1st minute). Result. We’ve got trigger level for pulsatility index (PI) as 0.835, if we had PI less than that threshold cases of emergency cesarean section increases in 2,12 times, if PI less than 0,835 in combination with Amniotic Index(AI) 85 and less in 5,28 times. If PI =<0,835 risk of newborns having Apgar 7 and less increases in 1,18, but in combination with AI =<85 in 4,72 times. Conclusion. In results we found out the following data: low PI in the MCA may be parameter which cans prognoses fetus distress. Combination of PI reduce with low AI increases its specific and can use in practical ways to avoid hypoxic brain damage during labor.
An Association of the Arginase 1 Gene with Preschool Wheezing Phenotypes
Hartmut Grasemann
Fernando Holguin

Hartmut Grasemann

and 1 more

January 08, 2021
An Association of the Arginase 1 Gene with Preschool Wheezing PhenotypesHartmut Grasemann and Fernando HolguinArginases are enzymes that metabolize L-arginine to form urea and L-ornithine. The two arginase isoforms, arginase I and arginase II, which are encoded by two different genes (ARG1 and ARG 2), are expressed in various cell types throughout the human body, including the lungs and airways. Arginase competes with nitric oxide synthase (NOS) for L-arginine as substrate, and increased arginase expression and activity in asthma reduces nitric oxide (NO) bioavailability, causing airways obstruction and contributing to reactive oxygen species production (1). Arginase also plays a role in allergen-induced airway remodeling in chronic asthma, presumably due to increased formation of L-ornithine, the precursor of L-proline and the polyamines (2). Proline is further metabolized to collagen and the polyamines putrescine, spermidine and spermine, which among other functions, also inhibit NOS. Increased production of endogenous NOS inhibitors including the polyamines as well as asymmetric dimethylarginine (ADMA), further contribute to the imbalance of NOS and arginases in asthma (figure 1).Previous studies of genetic variations or single nucleotide polymorphisms (SNPs) in arginase genes had shown associations with atopy and asthma. For example, SNPs in both arginase genes were associated with atopy and asthma in children and with risk for asthma in adults (3,4,5). Interestingly, ARG1 and ARG2 were also found to be associated with bronchodilator response in children and adults with asthma, and ARG1 with long term outcome on inhaled corticosteroid (ICS) therapy in adult asthma (5,6,7,8,9).Preschool wheeze is a common phenomenon, usually benign and mostly self-limited (10,11). Different phenotypes of preschool wheeze have been described, including early transient wheeze, late onset wheeze and persistent wheeze (12). A more recent classifications distinguishes multiple trigger wheeze (MTW) from episodic wheeze (EW), which is mainly caused by viral respiratory tract infections. The clinical usefulness of phenotype driven classifications has been questioned for a number of reasons including the longitudinal instability of phenotypes. However, some evidence suggests that MTW may be linked to later onset allergic asthma and MTW may therefore be more likely to respond to asthma treatment as compared to EW (13,14,15,16,17,18). Interestingly, a more recent analysis of the natural history of MTW and EW in two large independent birth cohorts demonstrated that phenotypes may track over time (19), suggesting that the two indeed represent different disease entities and not just differences in severity of the same disease.In a study by Gokmirza Ozdemir et al., published in this issue of theJournal , the authors report an association between arginase 1 gene polymorphisms and preschool wheezing phenotypes (20). In a cohort of 83 well characterized preschool wheezers with either multi trigger wheeze (MTW) or episodic wheeze (EW) phenotype of Turkish origin and matched controls, there was a difference in homozygous frequency of the ARG1 rs2781667T>C SNP between wheezing phenotypes and between patients with vs without allergic rhinitis. The homozygous frequency of this SNP in ARG1 was significantly higher in MTW vs EW, and in allergic rhinitis vs no allergic rhinitis. There were no associations of other tested SNPs in either ARG1 or ARG2 with preschool wheezing, allergic rhinitis, presence of aeroallergen sensitivity or tobacco exposure. Further analyses also showed significant differences in a number of haplotype frequencies in ARG1 between all wheezers and controls, and also between wheezing phenotypes. No associations were found with ARG2 in this study (20). Thus, these results show that in the population studied, variants in ARG1 but not ARG2 were associated with wheezing phenotypes in pre-school age.This observation is exiting as the genotype-phenotype association implies that arginase I could be involved in the development of preschool wheeze and wheezing phenotypes, possibly through an effect on L-arginine availability for nitric oxide synthase (NOS) or by affecting airway remodelling. However, the population studied here was relatively small and the findings have not yet been confirmed by others. Therefore, the results need to be interpreted with caution and additional studies are needed for confirmation. Similarly, it is unclear at this point, whether the SNPs and haplotypes found to be different in frequency between groups, alter arginase expression or activity, and what the biological or molecular explanation could be for the observed associations. Nevertheless, these observations by Gokmirza Ozdemir et al. are promising, and once confirmed in larger and independent cohorts, also have the potential to help develop a genetic test for wheezing pre-schoolers that may predict future asthma risk and response to asthma therapies.References1) North ML, Grasemann H, Khanna N, Inman MD, Gauvreau GM, Scott JA. Increased ornithine-derived polyamines cause airway hyperresponsiveness in a mouse model of asthma. Am J Respir Cell Mol Biol. 2013 Jun;48(6):694-702.2) Maarsingh H, Dekkers BG, Zuidhof AB, Bos IS, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H. Increased arginase activity contributes to airway remodelling in chronic allergic asthma. Eur Respir J. 2011 Aug;38(2):318-28.3) Donthi S, Neela VSK, Gaddam S, Mohammed HH, Ansari SS, Valluri VL, Sivasai KSR. Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I. Indian J Med Res. 2018 Aug;148(2):159-168.4) Li H, Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Estela Del Rio-Navarro B, Kistner EO, Gjessing HK, Lara-Sanchez Idel C, Chiu GY, London SJ. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. J Allergy Clin Immunol. 2006 Jan;117(1):119-26.5) Vonk JM, Postma DS, Maarsingh H, Bruinenberg M, Koppelman GH, Meurs H. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta2 agonist and steroid response. Pharmacogenet Genomics. 2010 Mar;20(3):179-86.6) Duan QL, Gaume BR, Hawkins GA, Himes BE, Bleecker ER, Klanderman B, Irvin CG, Peters SP, Meyers DA, Hanrahan JP, Lima JJ, Litonjua AA, Tantisira KG, Liggett SB. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011 Feb 15;183(4):449-54.7) Litonjua AA, Lasky-Su J, Schneiter K, Tantisira KG, Lazarus R, Klanderman B, Lima JJ, Irvin CG, Peters SP, Hanrahan JP, Liggett SB, Hawkins GA, Meyers DA, Bleecker ER, Lange C, Weiss ST. ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts. Am J Respir Crit Care Med. 2008 Oct 1;178(7):688-94.8) Sy HY, Ko FW, Chu HY, Chan IH, Wong GW, Hui DS, Leung TF. Asthma and bronchodilator responsiveness are associated with polymorphic markers of ARG1, CRHR2 and chromosome 17q21. Pharmacogenet Genomics. 2012 Jul;22(7):517-24.9) Scaparrotta A, Franzago M, Marcovecchio ML, Di Pillo S, Chiarelli F, Mohn A, Stuppia L. Role of THRB, ARG1, and ADRB2 genetic variants on bronchodilators response in asthmatic children. J Aerosol Med Pulm Drug Deliv. 2019 Jun;32(3):164-173.10) Kurukulaaratchy RJ, Matthews S, Holgate ST, Arshad SH. Predicting persistent disease among children who wheeze during early life. Eur Respir J. 2003 Nov;22(5):767-71.11) Caudri D, Wijga A, A Schipper CM, Hoekstra M, Postma DS, Koppelman GH, Brunekreef B, Smit HA, de Jongste JC. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age. J Allergy Clin Immunol. 2009 Nov;124(5):903-10.e1-7.12) Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8.13) Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souëf PN, Brand PL. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr. 2010 Jan;99(1):56-60.14) Sonnappa S, Bastardo CM, Wade A, Saglani S, McKenzie SA, Bush A, Aurora P. Symptom-pattern phenotype and pulmonary function in preschool wheezers. J Allergy Clin Immunol. 2010 Sep;126(3):519-26.e1-7.15) Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, de Blic J, de Jongste JC, Eber E, Everard ML, Frey U, Gappa M, Garcia-Marcos L, Grigg J, Lenney W, Le Souëf P, McKenzie S, Merkus PJ, Midulla F, Paton JY, Piacentini G, Pohunek P, Rossi GA, Seddon P, Silverman M, Sly PD, Stick S, Valiulis A, van Aalderen WM, Wildhaber JH, Wennergren G, Wilson N, Zivkovic Z, Bush A. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008 Oct;32(4):1096-110.16) Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J, Kuehni CE, Merkus PJ, Pedersen S, Valiulis A, Wennergren G, Bush A. Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J. 2014 Apr;43(4):1172-7.17) Garcia-Marcos L, Martinez FD. Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity markers? J Allergy Clin Immunol. 2010 Sep;126(3):489-90.18) van Wonderen KE, Geskus RB, van Aalderen WM, Mohrs J, Bindels PJ, van der Mark LB, Ter Riet G.Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers. Clin Exp Allergy. 2016 Jun;46(6):837-47.19) Spycher BD, Cochrane C, Granell R, Sterne JAC, Silverman M, Pedersen E, Gaillard EA, Henderson J, Kuehni CE. Temporal stability of multitrigger and episodic viral wheeze in early childhood. Eur Respir J. 2017 Nov 2;50(5):1700014.20) Gokmirza Ozdemir, P, Eker D, Celik V, Beken B, Gurkan H, Yazicioglu M, Sut N. The relationship between arginase genes polymorphisms and preschool wheezing phenotypes. Pediatr Pulmonol. 2020 ….
Combining range and phenology shifts offers a winning strategy for boreal Lepidoptera
Maria Hällfors
Juha Pöyry

Maria Hällfors

and 8 more

January 08, 2021
Species can adapt to climate change by adjusting in situ or by dispersing to new areas, and these strategies may complement or enhance each other. Here, we investigate temporal shifts in phenology and spatial shifts in northern range boundaries for 289 Lepidoptera species by using long-term data sampled over two decades. While 40% of the species neither advanced phenology nor moved northward, nearly half (47%) -used one of the two strategies. The strongest positive population trends was observed for the minority of species (13%) that both advanced flight phenology and shifted their northern range boundaries northward. We show that, for Boreal Lepidoptera, a combination of phenology and range shifts is the most viable strategy under a changing climate. Effectively, this may divide species into winners and losers based on their propensity to capitalize on this combination, with potentially large consequences on future community composition.
Species diversity of freshwater shrimp in Henan Province, China, based on morphologic...
Chuanjiang Zhou
Mengxia Feng

Chuanjiang Zhou

and 5 more

January 08, 2021
Freshwater shrimp is an extremely rich species group with a long and problematic taxonomic history, attributed to its wide distribution, numerous species and similar morphology. Shrimp diversity and species identification is utmost important for fisheries management. However, identification based on morphological characteristics is difficult and complex for a non-specialist to perform. The water system of Henan Province is relatively abundant, but there are few investigations of freshwater shrimps and no description of molecular features. The aim of this study was to uncover the species diversity and phylogenetic of freshwater shrimp in Henan province by combining morphological identification and molecular species delimitation (barcoding gene: COI gene). About 1,200 freshwater shrimp samples from 46 sampling sites were collected for preliminary traditional morphological identification, 222 samples of these were been further microscopic examination and molecular delimitation. Here we used tree based method (NJ, ML) and distance based method (ABGD, bPTP) mainly to define species, detect the cryptic species and assess the validity of the barcoding in molecular. Comprehensive morphological identification and molecular delimitation results, there were 9 effective species and more than one cryptic species of freshwater shrimp in the province and moreover all of them can be identified by DNA barcoding. The results of morphological identification and molecular identification show high consistency, which proves the high efficiency in freshwater shrimp species identification of the DNA barcoding and the presence of cryptic species.
Anxiety And Depressive Effects Of Antiepileptics In Animal Models
Yasemin Karal
Mehmet Azizoğlu

Yasemin Karal

and 3 more

January 08, 2021
Aim: Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants Levetiracetam (60 mg/kg, p.o.), Vigabatrin (100 mg/kg, p.o.) and Sodyum Valproat (50 mg/kg, p.o.) on anxiety and depression on animal models of rats. Materials and methods: Elevated plus maze (EPM) and Forced swimming test- Porsolt tests (FST) were carried out after 12th weeks of the lifes of rats those that took the three anticonvülsion therapy administration. Results: The results of the present study indicate that none of the three antikonvülsan drugs taken in childhood period impairs anxiety and depression in adult hood. Conclusion: To conclude, long term administration of Levetiracetam, Vigabatrin and Sodyum Valproat have no effect on the anxiety and depression at adulthood time if epilepsy does not exist.
A guide for optimal iodine staining and high-throughput diceCT scanning in snakes
Jenna Margaret Crowe-Riddell
Sean Callahan

Jenna Margaret Crowe-Riddell

and 4 more

January 08, 2021
Diffusible iodine-based contrast-enhanced Computed-Tomography (diceCT) visualizes soft-tissue from microCT (µCT) scans of specimens to uncover internal features and natural history information without incurring physical damage via dissection. Unlike hard-tissue imaging, diceCT datasets are currently limited to a few individual specimens and taxonomically underrepresented. To initiate best practices for diceCT in a non-model group, we outline a guide for staining and high-throughput µCT scanning in snakes. We scanned the entire body and one region of interest (i.e., head) for 23 specimens representing 23 species from the clades Aniliidae, Dipsadinae, Colubrinae, Elapidae, Lamprophiidae and Viperidae. We generated 82 scans that include 1.25% Lugols iodine stained (soft tissue) and unstained (skeletal) data for each specimen. We found that duration of optimal staining time increased linearly with body size; head radius was the best indicator. Post-reconstruction of scans, optimal staining was evident by evenly distributed grayscale values and clear differentiation among soft-tissue anatomy. Under and over stained specimens produced poor contrast among soft-tissues, which was often exacerbated by user bias during “digital dissections” (i.e., segmentation). Regardless, all scans produced usable data from which we assessed a range of downstream analytical applications within ecology and evolution (e.g., predator-prey interactions, life history, and morphological evolution). Ethanol de-staining reversed the known effects of iodine on the exterior appearance of physical specimens, but required substantially more time than reported for other de-staining methods. We discuss the feasibility of implementing diceCT techniques for a new user, including approximate financial and temporal commitments, required facilities, and potential effects of staining on specimens. We present the first high-throughput workflow for full-body skeletal and diceCT scanning in snakes, which can be generalized to any elongate vertebrates, and increases publicly available diceCT scans for reptiles by an order of magnitude.
Plant community characteristics and degradation mechanisms of the desert riparian zon...
TJ Z
yaning Chen

TJ Z

and 3 more

January 08, 2021
The vegetation in the desert riparian zone represents a critical barrier in the maintenance of the ecosystem’s balance. However, in recent years, the vegetation degradation of the riparian zone have seriously hindered economic development and ecological environment conservation. Based on a field investigation and literature, the mechanisms of vegetation degradation in the lower reaches of the Ugan River are discussed in this study through the analysis of plant coverage, diversity, substitution rate, distribution pattern, grey correlation analysis, and the relationship with groundwater depth. The results showed that the vegetation coverage in this region is relatively low when the water depth exceeds 4 meters. Furthermore, the Shannon-Wiener index, the Simpson index and the Pielou index have all decreased with increases in water depth. Woody plants are the main species maintaining the ecological balance of the region with an aggregation distribution pattern. The degradation of vegetation is the result of the lack of water sources and intense water consumption caused by human activities(especially agricultural). To promote the ecological balance and vegetation restoration, the relative optimal water depth range can be maintained within 2 to 5 meters and proper control human activities.besides the degraded vegetation can gradually be restored using point and surface (i.e., flowering in the center and spreading to the surrounding areas).
Immune Responses in Mice Vaccinated with Virus-Like Particles of Western Equine Encep...
Jinzhu Ma
Hualei Wang

Jinzhu Ma

and 5 more

January 08, 2021
Western equine encephalitis virus (WEEV) can cause lethal encephalitis in humans and equines and represents a serious public health threat in many countries. Therefore, development of efficient vaccines against WEEV remains an important challenge in the field of disease control. This study described for the first time successful production of WEEV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is very suitable for production of WEEV VLPs. The immune experiment herein in mice showed that the VLPs formulated with 206-adjuvant were responsible for the stronger-VLP-specific cellular immune response, and were able to induce the secretion of IL-2, IL-4, IFN-γ and production of high titer antibodies that can effectively neutralize the WEEV pseudoviruses. The WEEV VLPs from insect cells could provide a new, safe, non-replicating and effective vaccine candidate against WEEV infections.
Breather-wave, multi-wave and interaction solutions for the (3+1)-dimensional general...
Jian-Guo Liu
abdul-majid wazwaz

Jian-Guo Liu

and 3 more

January 08, 2021
Under investigation is a (3+1)-dimensional generalized breaking soliton equation in nonlinear media. The interaction solution between lump wave and N-soliton (N = 2,3,4) are derived. The interaction solution between lump wave and periodic waves is also studied. Breather-wave and multi-wave solutions are obtained. The dynamical behavior is demonstrated by some 3D graphics and density plots. By means of mathematical induction, we also obtain the exact solution containing three arbitrary functions.
Evaluation of Flux-PIHM, a physically-based land surface hydrologic model in an agric...
Yuting He Smeglin
Yuning Shi

Yuting Smeglin

and 8 more

January 08, 2021
An agricultural watershed, Cole Farm, was established as the newest of the three subcatchments in the Susquehanna Shale Hills Critical Zone Observatory (SSHCZO) in 2017. The catchment contains mostly pasture and crops, with a small portion of deciduous forest. The observations in Cole Farm afford an opportunity to test the spatially distributed land surface hydrologic model, Flux-PIHM, in farmland for the first time. In this study, we calibrated the model to only discharge and groundwater level observations at Cole Farm, but it’s able to capture the variations and magnitudes of soil moisture, latent heat (LE) and sensible heat (H) fluxes. Modeled soil moisture on the ridge top matched the observations well, but modeled soil moisture in the mid-slope differed from observations likely due to the existence of fragipan in the soil column. Flux-PIHM reproduced the seasonality and diurnal variations of watershed-average evapotranspiration (ET), sensible heat flux (H), though modeled ET in summer is about 25% greater than tower ET. To study the impact of land cover on hydrology, we imposed two different LAI forcings to the model: spatially distributed versus uniform LAI. Spatially distributed LAI produced higher ET and lower soil moisture in the forested part of the watershed due to higher LAI of deciduous forest in comparison to crops and pasture. But the impact of different LAI forcings on discharge was small. We further compared the water budget simulated by Flux-PIHM in the agricultural watershed (Cole Farm) to a forested watershed (Shale Hills). Flux-PIHM simulated less discharge and higher transpiration and bare soil evaporation in the Cole Farm watershed relative to Shale Hills watershed. Our work shows that with a few key observations, Flux-PIHM can be calibrated to simulate agricultural watershed hydrology, but spatially distributed LAI and soils data are needed to capture the spatial variations in soil moisture and ET.
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