Population size is a central parameter for conservation, however monitoring abundance is often problematic for threatened marine species. Despite substantial investment in research, many marine species remain data-poor resulting in uncertain population forecasts and restricting the evaluation of past and present conservation actions. Such is the case for the white shark (Carcharodon carcharias), a highly mobile apex predator for whom population monitoring is a conservation priority following substantial declines recorded through the 20th century. Here, we estimate the effective number of breeders that successfully contribute offspring in one reproductive cycle (Nb) providing a snapshot of recent reproductive effort in an east-Australian New Zealand population of white shark. Nb was estimated over four consecutive age cohorts (2010, 2011, 2012, 2013) using two genetic estimators (linkage-disequilibrium; LD and sibship assignment; SA) based on genetic data derived from two types of genetic markers (single-nucleotide-polymorphisms; SNPs and microsatellite loci). While estimates of Nb using different marker types produced comparable estimates, microsatellite loci were the least precise. The LD and SA estimates of Nb within cohorts using SNPs were comparable, for example the 2013 age-cohort Nb(SA) was 289 (95%CI 200-461) and Nb(LD) was 208.5 (95%CI 116.4-712.7). We show that over the time period studied Nb was stable and ranged between 206.1(±45.9) and 252.0(±46.7) per year using a combined estimate of Nb(SA+LD) from SNP loci, and a simulation approach showed that in this population effective population size (Ne) per generation can be expected to be larger than Nb per reproductive cycle. This study demonstrates how breeding population size can be monitored over time to provide insight into the effectiveness of recovery and conservation measures for the white shark, where the methods described here may be applicable to other data-poor species of conservation concern.

1. Toxin resistance in all taxa is important for their survival. Resistance to bufadienolide toxin is mediated by molecular changes to the sodium-potassium-pump. As for toads themselves, the parotid is consisted of extremely high concentration of bufadienolide toxin, it indicates toads need stronger resistance for self-protection than any other species involved in toad predation. Thus, besides the widespread convergence of Na+/K+-ATPase, toads may develop a unique self-resistance way for their accumulated bufadienolide toxin. 2. Our studies on invasive cane toads from Australia and common asiatic toads from China showed that toads store defensive venom in parotid as a combinatorial library composed of low-toxic protoxin (conjugated bufadienolides), which is characterized by two building blocks, i.e. high-toxic toxin (free bufadienolide) and the argininyl side chain contributed to toxin absorption promotion. This protoxin could be hydrolyzed to high-toxic toxin for defense immediately as it is discharged from parotid at the time when toad is attacked or stimulated by predators. 3. Our results revealed that toads indeed develop a unique protoxin self-resistance way to their own extremely high concentration of bufadienolide toxin for self-protection besides the widespread convergence of Na+/K+-ATPase. The revelation of this protoxin self-resistance way highlights the importance and ecological multifunctionality of the sophisticated combinatorial chemistry of nature and may partly account for the strong adaptability of toad as infamous ailing invaders. It completes the picture of self-resistance mechanism to their own bufadienolide toxin for toad or may even for many other venomous animals.

This paper is devoted to the study of a nonlinear pseudoparabolic equation in an annular with Robin-Dirichlet conditions. At first, by applying the standard Faedo-Galerkin method, we prove existence and uniqueness results. Next, using concavity method, we prove blow-up results for solutions when the initial energy is nonnegative or negative, then we also establish the lifespan for the equation via finding the upper bound and the lower bound for the blow-up times. Finally, we give a sufficient condition for the global existence and decay of weak solutions.

This paper is concerned a novel spreading dynamical model for Echinococcosis with stochastic parameter perturbation. we show that there exist a unique positive solution of the stochastic model. Sufficient conditions for the stationary distribution which is ergodic is established by appropriate Lyapunov functions. Furthermore, we obtain the conditions on which the system will extinct. Finally, we illustrate our results by numerical simulation.

We evaluated filtration behavior and virus removal capability for a mAb and plasma IgG under constant flow rate directly following flow-through column chromatography in an integrated process. For mAb solution with quantified host cell protein (HCP) content processed in flow-through mode on in-series mixed-mode AEX and modified CEX columns connected to the Planova BioEX filter (pool-less), HCP logarithmic reduction value (LRV) of 2.3 and 93.9% protein recovery were achieved for the process. Filtration behavior for 5 to 15 mg/mL plasma IgG run at flux of 10 to 100 LMH to 100 L/m2 throughput on Planova BioEX filters showed similar behavior across the protein concentrations tested although filtration pressure increased with throughput at 50 LMH and above, indicating the suitability of lower flux processes for continuous processing. Comparing both plasma IgG and mAb filtration behavior to four clogging models showed little difference in fit among the models, but with slightly better fit to the cake filtration model. Viral clearance tested by in-line spiking X-MuLV or MVM into purified plasma IgG showed robust removal at low flux. Integrating the Planova BioEX filter into continuous processes with column chromatography can achieve efficient downstream processing with reduced footprint and process time.

Abstract: Background. Doxorubicin chemotherapy drug , use is limited by it’s potential to cause cardiotoxicity. In resource poor settings, like Malawi, monitoring of doxorubicin cardiotoxicity is not routinely conducted in cancer patients and the incidence of doxorubicin cardiotoxicity is not known. Methods. Children aged 3 months to 18 years with cancer were prospectively enrolled from the paediatric oncology ward and followed up from January 2016 to June 2019. Transthoracic echocardiographic monitoring of left ventricular ejection fraction (LVEF) was done at baseline, one month, six months and a year after completion of therapy. Cardiotoxicity was defined as a decline in LVEF of ≥10% to a final value of <50%, and an overall incidence risk of developing cardiotoxicity was estimated. A one-way analysis of variance was conducted to compare baseline LVEF with that measured during follow up intervals. Findings. A total of 91 children were enrolled into the study, 74% (68/91) were male, and 67% (62/91) were aged 5 months to 14 years. Burkitt lymphoma was diagnosed in 41% (38/91) of the children. No one experienced cardiotoxicity during the study period. However, of 77 children who had at least one follow up, five children 6·54% (95% CI: 2.1-14.5) experienced a reduction in LVEF of >10%, though not to a final value of <50%. No deterioration of systolic function was found among 20 children who had completed follow up. (F= 2·43, p-value=0·07). Interpretation. In this cohort, there were no observed cardiotoxic events associated with doxorubicin administration as per pre-defined criterion

Introduction: The aim of this study was to assess the impact of the COVID-19 pandemic on the activity of private medical practices in Morocco. Methods: An online survey was carried out in June 2020. The study population consisted of physicians (General practitioners and specialists) who run private practices in different regions of Morocco. The questionnaire comprised 3 sections: demographic and professional data, the impact noticed by the doctors and the strategies adopted to tackle this impact. Results: We analyzed 225 responses. Specialists represented 71.6% of the respondents. The majority (94.2%) of the private practices were located in urban areas. Almost all respondents have noticed a change in the demand for medical services, mainly a decrease (96,44%). There was an increase in urgent consultations (30.7%) and consultations for acute motives (39.1%). Respondents also reported less (69,3%) or no (23,1%) regular follow-up visits for patients with chronic diseases. Decreased incomes concerned 97,33% of the practices. Doctors reacted by working less hours (87,55%), delaying some procedures (78,22%), and applying recommended safety measures (100%). Telemedicine was used in an informal way to facilitate the communication with patients. Discussion and conclusion: During this pandemic, private practices were challenged to contribute to the continuity of healthcare services while ensuring the safety of the staff and the patients. Several strategies were adopted to cope with the new situation and to survive its many challenges.

An 88-year-old male patient with no significant medical history presented with nausea, vomiting and hypothermia. He was admitted for further testing which revealed elevated CK-MB and Troponin with no significant electrocardiogram changes.He denied cardiac symptoms or any previous cardiac history.We share this rare case of hypothermia induced elevation of CK-MB.

A novel approach towards developing a micro-bubble detection technology based on using a PZT transducer to induce an acoustic resonance state within the system under investigation is here presented. The concept, originally proof-of-concept tested in a cylindrical acoustic resonant chamber, has proven to be able to detect single microbubbles with diameters in the range of 390 to 600 µm in a swine thigh, with either saline solution or sheep blood as the medium in the bubble guide. It has shown to be extremely adaptable, capable of accommodating industrial pipes as well as biological specimens, resilient and extremely energy efficient, able to detect micro-bubbles with as little as 0.8 mW and potentially less.

Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclosporine and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase the mortality and morbidity, as a weakened immune system can lead to longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and its associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organisation), U.S FDA (Food and Drug Administration) and other accredited global health organisations. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications and drug-drug interactions. Our study will help government partners and international health organisations to better understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised and organ transplant patients will help lower the mortality and morbidity associated with the disease amid COVID-19 pandemic.

Salicylic acid (SA) plays pivotal roles in plant defense against biotrophic and hemibiotrophic pathogens. Tremendous progress has been made in the field of the SA biosynthesis pathways and SA-mediated plant defense signaling networks in the past three decades. As one of the SA receptors, NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) functions as a master regulator of SA-mediated plant defense. The function of NPR1 is tightly regulated by transcriptional and post-translational regulation. This review discusses recent advances in SA and NPR1 biology, including SA perception, SA signaling, the function of SA and NPR1 in plant immunity, and the transcriptional and post-translational regulation of NPR1.

Molecular simulations from small molecules to large bio-macromolecules and polymer systems are routinely used to simulate thermodynamics properties of interests by molecular mechanics-based potentials. In a recent paper, via three different semi-empirical methods, we reported quantum singularities in dihedral energies as signature of chemical bond break-up process revealed under experimental X-ray as broken chemical moieties. In this present work, applying first principle methods of Hartree-Fock, Density Functional as well as MollerPlesset techniques we have reconfirmed the previous general predictions of singularities in in dihedral energies for the case of water dimer that connects two water monomers by weak hydrogen bond. Due to quantum nature of chemical bond breaking process leading to break-point conditions in otherwise connected molecular topology, the singularities in dihedral energies are also suggestive of large forces as onset in the bond-breaking process. We have presented the details of these novel interesting findings in this paper. These results of quantum singularities can have significant impacts to improve current force fields and can open up new areas we define as “Fracture Molecular Mechanics” or “Fracture Force Field” in overlap regions of molecular and quantum mechanics based approaches to explore and account for chemical bond-breaking mechanisms in molecular simulation techniques.

The use of deadly force to counter the threat of a knife attack is a constitutionally permissible means of ensuring police and public safety.  This paper reviews the constitutional standard for use-of-force by police, relevant case law, academic literature, statistical tables, and current police methodologies before evaluates the options available to police officers and suggesting a number of measures for minimizing the use of deadly force when encountering a person armed with a knife.

Thrombus formation inside the left ventricle (LV) is a dreaded complication following myocardial infarction. Depending on their anatomical characteristics, they pose significant risk of embolism, specifically stroke. Cardiac surgery in a patient with acute cerebral infarct is a tough predicament for the treating surgeon. Mobile clots carry higher risk than mural clots and need urgent thrombectomy. We present a case of massive LV clot in a young man leading to multiple acute embolic infarcts who was successfully treated by LV thrombectomy.

Hemolytic anaemia often challenges congenital heart surgery. Hereditary spherocytosis is a rare familial hemolytic anaemia. When associated with congenital heart disease, the safe performance of cardiopulmonary bypass becomes a priority. The increased risk of hemolysis during cardiopulmonary bypass could potentially lead to significant secondary organ damage. Till now, only very few reports of successful repair of a congenital heart defect in patients with hereditary spherocytosis have been reported. We report the only case of successful repair of a congenital heart defect in an infant with hereditary spherocytosis.

A water-soluble polymer stabilizer (VIB-co-VI-co-Py, Figure 1) assisted liquid-phase exfoliation (LPE), implemented by high-shear mixing rather than currently more often used bath/probe sonication, was developed as a new method for efficient production of few-layer graphene (FLG) in aqueous liquid. With help of VIB-co-VI-co-Py, stable aqueous dispersion of FLG forms in-situ with 90% of dispersed flakes of fewer than five layers and production rate up to 0.86 g h-1 by 5.0 L of aqueous liquid, representing the highest production rate per volume (0.17 g L-1 h-1) reported hitherto for LPE with the liquid volume no less than 5.0 L. The scale-up shear-exfoliated FLG exhibits high quality and excellent redispersibility in water, thus paving the way for a wide range of applications. As typical application demonstrations, the FLG-based flexible conductive films and polymer composite hydrogels were prepared and evaluated. The results show that the VIB-co-VI-co-Py exfoliated FLG performs well therein.

Background: Soft tissue sarcomas are a highly heterogenous group of tumors that are classified by differentiation. Their invasive or destructive growth pattern, recurrence and distant metastatic capacity are variable according to their subtype and also their localization. Aim: The aim of this study is to evaluate clinical characteristics, histopathologic subgroups, therapeutic modalities and clinical course of head and neck sarcomas. Study Design: Retrospective study and review of literature Materials and Methods: Patients with head and neck sarcomas who underwent surgery at XXXX University, Faculty of Medicine, Department of Otorhinolaryngology between 2007 to 2016 were retrospectively evaluated. Demographic features of the patients, histopathologic subtypes, immunohistochemical markers, locations of the tumor, type of surgery, margins of the specimens, type of reconstructive surgery and type of adjuvant treatment were reviewed. Results: The histopathologic subtypes were rhabdomyosarcoma, primitive neuroectodermal tumor, osteosarcoma, chondrosarcoma, leiomyosarcoma, Ewing’s sarcoma and synovyal sarcoma. The most frequent site was nasal cavity and was detected in 7 cases. Local recurrence developed in three patients. Conclusion: Sarcomas of the head and neck region are relatively rare tumors. Radical resection of the tumors is essential for these cases.

Title: Congenital Insensitivity to Pain, with Impaired Pulmonary Functions, and Diminished Cough Reflex.

Background: Depression and anxiety symptoms in patients with cystic fibrosis (CF) and their caregivers are 2-3 times higher than in the normal population. This study aims to evaluate the frequency and severity of depression and anxiety symptoms and to determine possible risk factors in CF patients and their mother and/or fathers at Marmara University CF center. Methods: The study included 132 CF patients who were followed up at our CF center. Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Questionnaire (GAD-7) were used to screen depression and anxiety. The questionnaires were completed by 50 CF patients (aged 12 - 17 years) and 132 parents of patients (aged 0-17 years). Results: While moderate to severe depression were seen in 25.5% of patients, 33.7% of mothers and 14.6% of fathers; moderate to severe anxiety were present in 17.6%, 21.8% and 8.5%, respectively. None of the demographic characteristics was identified as a predictor of depression or anxiety. GAD-7 scores have shown a higher incidence of anxiety in mothers of patients with chronic methicillin-resistant Staphylococcus Aureus (p = 0.034). Additionally, hospitalization in the last 12 months was statistically significantly higher in PHQ-9 scores of fathers (p = 0.043). Analysis of patients’ adherence to medical treatment and airway clearance showed higher depression and anxiety in mothers of the non-adherent group (p = 0.002). Conclusion: Depression and anxiety were common in CF patients and their parents. These results illustrate the importance of depression/anxiety screening and psychosocial support for the CF patient and their parents.

Article Type: News and Views: Groundbreaking Discoveries in ImmunologyTitle: Emollients for the prevention of atopic dermatitisAuthors: Akash Kothari1(https://orcid.org/0000-0003-1980-161X), Arielle Locke2,Thomas Eiwegger1,3,4(https://orcid.org/0000-0002-2914-7829)1Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada2Department of Medicine, National University of Ireland, Galway, Ireland3Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada4Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, CanadaCorrespondence to: Thomas Eiwegger, MD, Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Department of Paediatrics, Hospital for Sick Children, 555 University Ave, Toronto, Canada, E-mail: thomas.eiwegger@sickkids.ca, Tel.: +1 416-813-7654 ext. 1862Conflicts of Interest: AK and AL have nothing to disclose. TE reports to act as local PI for company sponsored trials by DBV and sub-investigator for Regeneron, holds grants from Innovation Fund Denmark, CIHR outside the submitted work. He is Co-Investigator or scientific lead in three investigator initiated oral immunotherapy trials supported by the Food Allergy and Anaphylaxis Program SickKids and serves as associate editor for Allergy. He/his lab received unconditional/in-kind contributions from Macro Array Diagnostics and an unrestricted grant from ALK. He holds advisory board roles for ALK.Financial support: This work was supported by The Hospital for Sick Children, The Food Allergy and Anaphylaxis Program at The Hospital for Sick Children, and The Dr Lorus J And Dr Margery J Milne Scholarship from Victoria University at the University of Toronto.Statement of Author Contribution: All authors critically reviewed the original articles (references 6 and 7) and wrote the News & Views: Groundbreaking discoveries in Immunology article. All authors contributed, revised, edited, and approved the final version of the manuscript as submitted and agreed to be accountable for all aspects of the work.Keywords: emollient, atopic eczema, infancyAbbreviations : food allergy, FA; filaggrin gene, FLG; atopic dermatitis, AD; transepidermal water loss, TEWL; Barrier Enhancement for Eczema Prevention, BEEP; Preventing Atopic Dermatitis and Allergies, PreventADALL

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation (CCAM), is a rare developmental lung abnormality with the potential for malignant transformation. Bronchioloalveolar carcinoma (BAC), pleuropulmonary blastoma (PPB), rhabdomyomatous dysplasia/rhabdomyosarcoma (RMS) have been associated with CPAM. We report an unusual case of a 1-day-old male newborn who underwent lobectomy for a cystic lung lesion, which was found to be a mucinous BAC with K-ras mutation in a type 1 CPAM. The case supports the relationship between type 1 CPAM and BAC/KRAS mutant, and highlights that the malignant transformation can occur in very early stage of the infancy.

We used the lung ultrasound score (LUSS) to analyze the ultrasound images and assess the lesions and aeration loss in 12 lung regions of 11 COVID-19 neonates born to mother with COVID-19 and 11 age- and gender-matched controls. In the COVID-19 group, 132 regions were reviewed and 83 regions (62.8%) detected abnormalities. Compared with controls, COVID-19 neonates showed more increased B-lines (83 regions), abnormal A-lines (83 regions), abnormal pleural line (29 regions) and subpleural consolidation (5 regions). among which 49 regions (37%) were normal, 73 regions (55%) scored 1, and 10 regions (8%) scored 2. The LUSS was significantly higher in COVID-19 group. All the lesions were bilateral, multiple regions involved, and mainly located in bilateral lower lobes and right middle lobe. The intra-observer and inter-observer reproducibility of LUSS were excellent. Lung ultrasound is a noninvasive and convenient method for the assessment of neonatal COVID-19 pneumonia and presents typical signs. LUSS provides valuable semi-quantitative information about the lesion distribution and severity.

Background: To date, no disease-specific tool is available to assess the impact of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) on Health Related Quality of Life (HRQoL). Therefore, the purpose of this study was to develop and validate a questionnaire specifically designed to this aim: the Nasal Polyposis Quality of Life questionnaire –NPQ. Methods: According to the current guidelines, the development and validation of the NPQ occurred in two separate steps involving different groups of patients. Results: In the development process of NPQ an initial list of items of 40 items was given to 60 patients with CRSwNP; the 27 most significant items were selected and converted into questions. The validation procedure involved 107 patients (mean age 52.9±12.4). NPQ revealed a five-dimensional structure and high levels of internal consistency (Cronbach’s alpha 0.95). Convergent validity (Spearman’ coefficient r=0.75; p< 0.01), discriminant validity (sensitivity to VAS score), reliability in a sample of patients with a stable health status (Interclass Coefficient 0.882) were satisfactory. Responsiveness to clinical changes was accomplished. The minimal important difference was 7. Conclusion: NPQ is the first questionnaire for the assessment of HRQoL in CRSwNP. Our results provide that the new tool is valid, reliable, and sensitive to individual changes.

ABSTRACT Background Exposed to house dust mite (HDM) is known to be associated with allergic asthma. Endoplasmic reticulum (ER) stress is involved in the regulation of mucus hyper secretion. However, the mechanism remains unclear. Our main goal was to investigate the relationship of TBK1 pathway regulates the expression of MUC5AC under the HDM induced ER stress promote allergic asthma. Methods Using HDM induced allergic mice and stimulated over expression of MUC5AC in human airway epithelial cells. We examined the mucus and the expression of ER stress markers both in vivo and in vitro. Additionally, we investigated whether TBK1, NF-κB, STAT6 play an important role in the HDM induced ER stress promote airway mucus hyper secretion. Results Mice exposed to HDM were identified ER stress, hyper secretion of mucus, and activated TBK1-NF-κB/STAT6 signaling pathway in airway epithelial cells of asthmatic mice. Similarly results had also been observed in the human airway epithelial cells after exposed to HDM. Both in vivo and in vitro study not only revealed that an anti-allergy drug, Amlexanox, reduced super response of mucus and weaken TBK1-NF-κB/STAT6 signal of induced asthma. But also indicated HDM induced ER stress result in over production of MUC5AC, which can be decreased by the inhibition of TBK1, NF-κB, STAT6, or even by using ER stress inhibitor 4-PBA, respectively. Conclusions Our results show that TBK1-NF-κB/STAT6 plays a pivotal role in the HDM induced ER stress result in over production of mucus protein MUC5AC in the asthmatic airway.