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.

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.

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.

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.

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: [email protected] count: 430Conflict of interest: The authors have no conflict of interest and have not received any funding.Central Figure:

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 ….

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.

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.

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.

Aim: The aim of this study was to assess the efficacy of pre-operative axillary ultrasonography (AUS) and pre-operative axillary fine-needle aspiration biopsy (FNAB) from suspicious lymph nodes in clinically node-negative breast cancer to compare with radiologically positive and sentinel lymph node biopsy (SLNB) positive involvement. Method: Clinically node-negative early-stage breast cancer patients were included in the study. These patients under went pre-operative AUS examination, suspicious lymph nodes were evaluated with FNAB. AUS-FNAB results were compared with those of SLNB or of axillary dissection. Results: Of 181 patients undergoing AUS, 32 were reported to have axillary metastasis, 25 suspicious and 124 benign nodes. The suspicious group underwent FNAB examination and metastasis was found in 9 of them. The sensitivity of AUS-FNAB was found to be 64.06%, specificity 100%, positive predictive value 100% and negative predictive value (NPV) 83.5%. False negativity rate (FN) of this method was 16,4%. Lymphovascular invasion and tumor size were found statistically significant factors for false negativity. Conclusion:It was concluded that axillary AUS-FNAB with its high NPV, low FN rate, may be a clinical alternative to SLNB for early stage breast cancer patients.

Aim The aim of this study is to model the past, current and future distribution of J. phoenicea s.s., J. turbinata and J. canariensis, based on bioclimatic variables using a maximum entropy model (MaxEnt) in the Mediterranean and Macaronesian regions. Location Mediterranean and Macaronesian Taxon Cupressaceae, Juniperus Methods Data on the occurrence of the J. phoenicea complex was obtained from the GBIF, the literature, herbaria, and the authors’ field notes. The bioclimatic variables were obtained from the WorldClim database (http://worldclim.org/) and Paleoclim (http://www.paleoclim.org/). The climate data related to species localities were used for predictions of niches by implementation of MaxEnt and we evaluated the model with ENMeval. Results The potential niches of Juniperus phoenicea during the LIG, LGM and MH covered 30%, 10% and almost 100%, respectively, of the current potential niche. Climate warming could reduce potential niches by 30% and 90% in scenarios RCP2.6 and RCP8.5, respectively. The potential niches of Juniperus turbinata had a broad circum-Mediterranean and Canarian distribution during the LIG and the MH, extending its distribution during the LGM when it was found in more areas than at present; the predicted warming in scenario RCP2.6 and RCP8.5 could reduce the current potential niche by 30% and 50%, respectively. The model did not find suitable niches for J. canariensis during the LIG and the LGM, but during the MH its potential niche was 30% larger than at present. The climate warming scenario RCP2.6 indicates a reduction of the potential niche by 30%, while RCP8.5 does so by almost 60%. Main conclusions This research can provide information to increase the protection of the juniper forest and to try to counteract the phenomenon of local extinctions caused by anthropic pressure and climate changes.

Aneurysms of the sinus of Valsalva are rare, with dissecting aneurysms of the sinus of Valsalva that extend into the interventricular septum being even more rare. This report describes a young patient with syphilis and a quadricuspid aortic valve who experienced a spontaneously dissecting aneurysm of the sinus of Valsalva and the basal interventricular septum.

Introduction: Several homeostatic changes like an increase in sympathoadrenal response and oxidative stress occur in hypoglycemia. As a result of these findings, an increase in inflammation and pre-atherogenic factors is observed and these changes may lead to endothelial dysfunction. Aim: Our study aims to reveal possible cardiac risks (systolic-diastolic functions and endothelial dysfunctions) in patients who have applied to the emergency department with hypoglycemia. Methods: This cross-sectional, case-control study included 46 hypoglycemia patients who admitted to the emergency with symptoms compatible with hypoglycemia and diagnosed with hypoglycemia and 30 healthy volunteers. All patients were evaluated with baseline echocardiography, tissue-doppler imaging(carotid and brachial artery). Also, the fasting blood tests of the patients referred to the internal medicine department were examined. Results: There were no differences between the groups regarding age, weight, body mass index, and systolic blood pressure. Total cholesterol, LDL, HDL, Vitamin B12, TSH, and fasting blood glucose levels were similar in the groups’ blood tests (all p values>0.05). We observed a statistically significant decrease in diastolic dysfunction parameters: E/A and E/e’ ratios (respectively, p=0.020 and 0.026). It was shown that insulin resistance was influential in forming these considerable differences. The patient group observed that the carotid intima-media thickness was more remarkable(p=0.001), and the brachial flow-mediated dilatation value was smaller(p=0.003), giving an idea about endothelial functions.

Described is an atypical presentation of a rare condition. It highlights the importance of thorough algorithm of medical and family history, physical examination, appropriate investigations and perioperative workup and for surgery. This case raises the awareness that a lateral neck mass (or lateral ectopic thyroid mass) can be benign.

This report describes the case of a 53-year-old man with SARS-CoV-2 infection and occurrence of complete unilateral sensorineural hearing loss, adding new evidence to the association between COVID-19 and hearing loss. Whether this is the result of endothelial cell dysfunction in the cochlea or central auditory pathways remains unclear.

Adoptive immunotherapy using Epstein-Barr Virus (EBV)-specific T cells is a potentially curative treatment for patients with EBV-related malignancies where other clinical options have proved ineffective. We describe improved GMP-compliant culture and analysis processes for conventional lymphoblastoid cell line (LCL)-driven EBV-specific T cell manufacture, and describe an improved phenotyping approach for analyzing T cell products. We optimized the current LCL-mediated clinical manufacture of EBV-specific T cells to establish an improved process using xenoprotein-free GMP-compliant reagents throughout, and compared resulting products with our previous banked T cell clinical therapy. We assessed effects of changes to LCL: T cell ratio in T cell expansion, and developed a robust flow cytometric marker panel covering T cell memory, activation, differentiation and intracellular cytokine release to characterize T cells more effectively. These data were analyzed using t-Stochastic Neighbour Embedding (t-SNE) algorithm. The optimized GMP-compliant process resulted in reduced cell processing time and improved retention and expansion of central memory T cells. Multi-parameter flow cytometry determined the optimal protocol for LCL stimulation and expansion of T cells and demonstrated that cytokine profiling using IL-2, TNF-α and IFN-γ was able to determine the differentiation status of T cells throughout culture and in the final product. We show that fully GMP-compliant closed-process culture of LCL-mediated EBV-specific T cells is feasible and profiling of T cells through cytokine expression gives improved characterization of start material, in-process culture conditions and final product. Visualization of the complex multi-parameter flow cytometric data can be simplified using t-SNE analysis.

We aimed to test the hypothesis that a lung ultrasound severity score (LUS) and assessment of left ventricular eccentricity index of the interventricular septum (LVEI) by focused heart ultrasound can predict extubation success in mechanically ventilated infants. We conducted a prospective study on premature infants <34 weeks’ of gestation. LUS was performed on postnatal days 3 and 7 by an investigator who was masked to infants’ ventilator parameters. LVEI and pulmonary artery pressure (PAP) were measured at postnatal day 3. A receiver operator curve was constructed to assess the ability to predict extubation success. Spearman correlation was performed between LVEI and PAP. A total of 104 studies were performed to 66 infants; of them 39 had mild and 65 had moderate-severe lung disease. LUS predicted extubation success with a sensitivity and a specificity of 91% and 69%, respectively. Area under the curve was 0.83 (CI: 0.75-0.91). LVEI did not differ between infants that succeeded and failed extubation. It correlated with PAP during systole (r=0.66). We conclude that LUS predicts extubation success in mechanically ventilated preterm infants whereas LVEI correlates with high PAP.

As the clinical course of COVID-19 infection in SCD patients is not clear, close monitoring is essential. We emphasize that RBC exchange should be offered early to avoid possible deterioration. We present a case of COVID-19 infection in a SCD patient causing severe hemolysis, that improved after RBC exchange.