Background and Purpose: The promotion of hair regeneration and growth heavily depends on the activation of Wnt/β-catenin signaling in the hair follicle including dermal papilla (DP). KY19382, one of the newly synthesized analogs of indirubin-3’-monoxime (I3O) was identified as a Wnt/β-catenin signaling activator via inhibition of the interaction between CXXC-type zinc finger protein 5 (CXXC5) and Dishevelled (Dvl) interaction. Given the close relationship between the Wnt/β-catenin signaling and hair regeneration, we investigated the effect of KY19382 on hair re-growth and hair follicle neogenesis. Experimental Approach: In vitro hair induction effects of KY19382 was performed in human dermal papilla cells. The hair elongation effects of KY19382 was confirmed through the vibrissa culture system. In vivo hair regeneration abilities of KY19382 was identified in three models: hair regrowth, wound-induced hair follicle neogenesis (WIHN), and hair patch assays using C57BL/6 mice. The hair regeneration abilities were analyzed by immunoblotting, alkaline phosphatase (ALP) and immunohistochemical staining. Key results: KY19382 activated Wnt/β-catenin signaling and elevated the expression of ALP and proliferation marker PCNA in DP cells. KY19382 also increased hair length in ex vivo cultured mouse vibrissa follicles and induced hair regrowth in mice. Moreover, KY19382 significantly promoted the generation of de novo hair follicles as shown by WIHN and hair patch assays. Conclusion and Implications: These results indicate that KY19382 is a potential therapeutic drug that exhibits effective hair regeneration ability via activation of the Wnt/β-catenin signaling for alopecia treatments.

In this paper we consider an anomalous diffusion model in a planar polymeric matrix as a space-fractional diffusion problem with moving boundary conditions. An iterative implicit finite difference method with variable time-steps is established to solve the proposed problem. The stability and consistency of the numerical method are proved and the estimation of the numerical error is conducted. The numerical results are compared with the scale-invariant solutions when the diffusion coefficient is a constant and the agreement between the numerical results and the scale-invariant solutions is investigated. Furthermore the numerical results for a test case with time-dependent diffusion coefficient are reported.

In this paper, we study a class of Hamiltonian elliptic system and obtain the existence and multiplicity results under some suitable assumptions. Moreover, we get the existence of sign-changing solutions with a prescribed number of nodes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in China, is the cause of the global pandemic Coronavirus Disease 19 (Covid-19). To date, there is no widely available vaccine or treatment, hence containment strategies are currently centred around measures ameliorating human transmission via social distancing and quarantine. Due to the magnitude of the pandemic, elective operative work had ceased within cardiac surgery at our institution and strategies adapted to facilitate safe management of surgical candidates. Here, we present the case report of an asymptomatic inpatient with prolonged viral shedding on real-time polymerase chain reaction (RT-PCR) on oropharyngeal swabs who required urgent coronary artery revascularisation, and the lessons learnt from the adapted management strategy deployed for revascularisation during the COVID-19 pandemic.

A characterization of the symmetry algebra of the $N$th-order ordinary differential equations (ODEs) with maximal symmetry and all third-order linearizable ODEs is given. This is used to show that such an algebra $\mathfrak{g}$ determines – up to a point transformation – only one linear equation whose symmetry algebra is $\mathfrak{g}$ and an algorithmic procedure is given to find the linearizing coordinates. The procedure is illustrated by several examples from the literature.

Aims: Evogliptin is a newly developed oral glucose-lowering medication of dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. Combination of DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of present study was to evaluate pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone. Methods: A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence crossover study was conducted in healthy Korean male subjects. All subjects received evogliptin 5 mg once daily for 7 days (EVO), pioglitazone 30 mg once daily for 7 days (PIO) and co-administration of evogliptin 5 mg and pioglitazone 30 mg once daily for 7 days (EVO+PIO) according to the assigned sequence and period. Serial blood samples were collected for 24 hours for pharmacokinetic analysis and 3 hours after oral glucose tolerance test for pharmacodynamic analysis. Results: Thirty-four subjects completed the study. EVO+PIO and EVO showed similar maximum plasma concentration at steady state (Cmax,ss) and the area under the concentration-time curve during dosing interval at steady state (AUCτ,ss) of evogliptin, with geometric mean ratios (GMRs) (90% confidence interval (CI)) of 1.01 (0.97-1.05) and 1.01 (0.98-1.04), respectively. EVO+PIO and PIO showed similar Cmax,ss and AUCτ,ss of pioglitazone, with GMRs (90% CI) of 1.07 (0.99-1.17) and 1.08 (0.99-1.17), respectively. Reduction of glucose level after EVO+PIO was larger compared to PIO, and similar with EVO. Conclusion: Concomitant administration of evogliptin and pioglitazone showed similar glucose lowering effects with those of evogliptin alone without pharmacokinetic interactions when compared to intake of each drug alone.

1. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) frequently affect the ear, resulting in the development of external otitis, otitis media, sensorineural hearing loss, and facial paresis. 2. The lack of specific methods for detecting vasculitis of the ear occasionally hinders the early diagnosis of otologic involvement of GPA and EGPA. 3. Contrast-enhanced, 3D T1-weighted magnetic resonance imaging with gradient-echo sequences (CE-3D-GRE) demonstrate intense enhancement in the tympanic and mastoid segments of the Fallopian canal in spite of the absence of facial paresis. 4. Maximum intensity projection images clearly display an enhanced Fallopian canal, which was associated with adjacent inflammatory lesions. 5. Intense enhancement of the Fallopian canal on CE-3D-GRE can be used as a surrogate marker of otologic involvement of GPA and EGPA, which may enable early diagnosis, monitoring, and therapy optimisation in a less invasive manner.

Aims: Evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and glimepiride, a sulfonylurea, have been used to treat type 2 diabetes mellitus. This study aimed at evaluating the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride. Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or co-administration of the two (EVO+GLI). Serial blood and urine samples for PK and PD analyses were collected 168 and 24 hours post-dosing, respectively. Results: Thirty-four subjects completed the study. Co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUCτ,ss) of EVO+GLI to E were 1.02 (0.98 – 1.06) and 0.97 (0.95 – 1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01 – 1.17) and 1.08 (1.02 – 1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.80 – 1.25. Administration of EVO+GLI decreased the glucose excursion compared to evogliptin and glimepiride monotherapy, respectively. Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while combination therapy showed an additive glucose lowering effect compared to those of evogliptin or glimepiride monotherapy.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-19 (CoVID-19). The virus has exhibited unprecedented human to human transmission and progressed into a pandemic over a short duration. Aim To report the epidemiology; clinical, radiological, and laboratory characteristics; and outcome of SARS-CoV-2 infection in 19 patients in Germany. Methods Retrospective analysis of 19 patients contracting SARS-CoV-2 infection confirmed by PCR in Germany between March 1, 2020 and March 31, 2020. Results In 19 PCR-confirmed SARS-Cov-2 virus infection (median age 69 years; 12 (63%) males), the most common presentations were Fever (79%), cough (79%), fatigue (79%), and dyspnea (42%). The most common comorbidities were hypertension (47%), hypothyroidism (32%), and cardiac diseases (32%). According to chest X-ray, 15 (79%) of patients had abnormal chest X-rays; of these, 13 had bilateral chest infiltrates and two had unilateral infiltrates. Lactate dehydrogenase and C-reactive protein (CRP) were elevated in all patients at baseline investigations; 343 U/L (169-931 U/L) and 8 mg/dL (1-17 mg/dL), respectively. Of the 19 cases, 13 (68.4%) recovered and discharged, 9 (47.3%) needed ICU admission, and 4 (21.1%) cases died. Conclusion Among the 19 patients diagnosed with SARS-CoV-2, mild respiratory tract infections symptoms were frequently reported. Some patients required supplemental oxygen and had variable clinical outcomes following supportive and antibiotic treatments. These findings may contribute to the development of more effective strategies of infection control.

Objective The objective of this multicentre retrospective case review was to assess the natural clinical course, efficacy and safety of Mastoid Obliteration with S53P4 Bioactive Glass (bioactive glass). Study Design Retrospective case note review Setting Regional Tertiary Referral centre and District General Hospital Participants Patients undergoing mastoid cavity obliteration as part of primary or secondary procedure with bioactive Glass between 2012 – 2018. Outcome measures were assessed from a prospectively collated database and case note review. Main Outcome Measures Primary outcomes were the common morbidities of a mastoid cavity; dry or discharging ear (Merchant’s scale), vertigo in cold air and a water tight middle ear. Patients were also assessed for audiological outcomes and recidivism. Results 90 patients were included. During the follow up period, (mean = 22 months; range = 6 - 59 months) cholesteatoma recidivism was observed in 2% of ears, (2 patients). An acceptably dry (Merchant Grade 0 – 1) ear was achieved in 91% of all ears (95% Primary Cases, 80% Secondary Cases). Delayed healing of the graft in the external ear canal retaining the S53P4BAG Bioactive Glass (BonAlive,(BonAlive Biomaterials Ltd., Turku, Finland)) within the mastoid occurred in 13% (12 ears). However, in all cases conservative management resulted in complete healing. Conclusions Bioactive glass provides a safe and effective means of mastoid obliteration. Complications including overlay graft failure and slow epithelisation resulting in prolonged postoperative discharge (up to 2 months) and dehiscence into the external ear canal do not preclude full recovery and may be successfully managed conservatively.

The COVID-19 pandemic has been a serious health problem in most countries in the last few months, with every country adopting different preventive and therapeutic measures based on their specific circumstances. The epidemic began in Iran on February 19, 2020 and gradually spread across the country. The epidemic extent varies, and different preventive and therapeutic measures are taken in Iran. Shahroud and Miami Counties, covered by the Shahroud University of Medical Sciences, have experienced a highest incidence of COVID-19 in Iran. However, the epidemic is well controlled by integrating the activities of the health, treatment, and research sectors and using information technology and a proprietary software application. This model can be thus studied as a successful experience.

Background: Leukemia remains the leading cause of cancer-related death in Latin American (LA) children and adolescents. The aim is to evaluate leukemia mortality trends in children and adolescents (0-19y) from 13 LA countries in the last two decades and to predict mortality to 2032. Methods: We retrieved cancer mortality data through World Health Organization Mortality Database. Age-standardized (world standard population) rates were computed for 13 LA countries 2000–2017. Mortality trends were analyzed by Joinpoint regression, and Nordpred was utilized for the calculation of predictions. Results: Ecuador and Mexico had the highest mortality among LA countries. For boys, Ecuador continues to increase in 1.5% annually, while Mexico reported a decline by −0.3% annually. For both genders, Nicaragua showed a high rise, for boys (APC= +3.1) and for girls (APC= +2.3), while Puerto Rico experienced a large decrease, for boys (APC= −9.7), and girls ( APC= −6.0). The comparison between the last observed and projected period showed a greater increase in the risk of death from leukemia in Ecuador and Argentina for boys, and Nicaragua and Peru for girls. In Puerto Rico, there was a reduction in the percentage of cases associated with changes in size and population structure, despite the increased risk of death from leukemia. Conclusion: Ecuador and Mexico continue to report the highest mortality for leukemia among LA countries. However, in the last years, Mexico has shown favorable changes in mortality. Special attention should be given to Ecuador due to the significant increase in mortality rates.

The coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the outbreak has rapidly spread worldwide causing a global severe pneumonia pandemic. Several animals have been proven to be affected by the SARS-CoV-2, posing an enormous threat to humans. However, to confirm the intermediate hosts in the epidemic regions, it is unrealistic to detect its presence in each and every animal one by one. An active transmembrane serine protease 2 (TMPRSS2) which functions in priming of S-protein of SARS-CoV-2 is one of the most important prerequisites for an animal to be an intermediate host, but the utilizing capability of TMPRSS2 for non-human animals is largely unknown. Here, we systematically predicted the ability of TMPRSS2 to prime S-protein of SARS-CoV-2 in 164 vertebrates by analyzing the phylogenetic clustering and possible functional changes induced by amino acid variation in TMPRSS2. Mammals were predicted to be the most likely animals to effectively use the TMPRSS2 for priming S-protein of SARS-CoV-2. Especially, we predicted the possible effective utilizing ability of TMPRSS2 in rats and pigs, which are reported non-susceptible to SARS-CoV-2. Given the wide distribution and the close relationships among human, pig and rat, a periodic and careful monitoring is required for pigs and rats to prevent the possible SARS-CoV-2 transmission to human.

Every host is colonized by a variety of microbes, some of which can protect their hosts from pathogen infection. However, pathogen presence naturally varies over time in nature, such as in the case of seasonal epidemics. We experimentally coevolved populations of Caenorhabditis elegans worm hosts with bacteria possessing protective traits (Enterococcus faecalis), in treatments varying the infection frequency with pathogenic Staphylococcus aureus every host generation, alternating host generations, every fifth host generation or never. We additionally investigated the effect of initial pathogen presence at the formation of the defensive symbiosis. Our results show that enhanced microbe-mediated protection evolved during host-protective microbe coevolution when faced with rare infections by a pathogen. Initial pathogen presence had no effect on the evolutionary outcome of microbe-mediated protection. We also found that protection was only effective at preventing mortality during the time of pathogen infection. Overall, our results suggest that resident microbes can be a form of transgenerational immunity against rare pathogen infection.

The management of patients with dilated non-ischemic cardiomyopathy with a large anterior ventricular aneurysm presenting with ventricular tachycardia is not well described. We report a 45-year-old gentleman who presented with recurrent episodes of prolonged polymorphic ventricular tachycardia and previously failed medical management and endocardial and epicardial transcatheter ablation. We performed a Dor procedure to exclude the apical left ventricular aneurysm in conjunction with cryoablation to terminate his ventricular tachycardia. This surgical approach was found to be successful with conversion of the patient into normal sinus rhythm and restoration of the patient's left ventricular morphology and function.

Background: During this SARS-CoV-2 pandemic, there has been unprecedented stress on health care systems, resulting in a change to how services are carried out. The most prominent question for healthcare professionals specialising in cardiac surgery is, should we operate during this pandemic, and to what extent ? Methods: As one of the biggest, specialised cardiac surgery centres in the UK, we researched the available published evidence surrounding this question, to formulate an answer. During this process we considered the potential risks of cardiac surgery during a pandemic on the patients, staff, the healthcare system, and the community. We also considered the immunological aspect of cardiac surgery patients and the risk it entails on them. Results We have discussed the available evidence and consequences of our findings, and we found Patients are subjected to greater risk of catching Covid-19 whilst being in hospital. Patient’s immunity is disrupted for up to 3 months post CPB, which makes them more vulnerable to catch the Covid-19 infection during admission and after discharge. Plus the burden on the whole healthcare system, by using the precious resources and occupying the necessary staff and hospital beds needed during the pandemic surge. Conclusion: Try and minimise cardiac surgery operations down to emergencies or unstable patients who have no other options apart from surgery, particularly during the surge stage of the pandemic. Strictly following structured pathways and protocols, updating relevant protocols with emerging new evidence.

Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, these promising therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attributes (CQAs) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real-time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry (ESI-MS) and direct-from-culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (~3 weeks). Post hoc analysis of this real-time data reveals that DSP output is heavily dependent on spatial context. Importantly, these results demonstrate that an effective PAT must incorporate both spatial and temporal resolution to serve as an effective input f or feedback control in advanced therapy production.

With the aim of describing bound and continuum states for diatomic molecules, we develop and implement a spectral method that makes use of Generalized Sturmian Functions (GSF) in prolate spheroidal coordinates. In order to master all computational issues, we apply here the method to one-electron molecular ions and compare it with benchmark data for both ground and excited states. We actually propose two different computational schemes to solve the two coupled differential equations. The first one is an iterative 1d procedure in which one solves alternately the angular and the radial equations, the latter yielding the state energy. The second, named direct $2d$ method, consists in representing the Hamiltonian matrix in a two–dimensional GSF basis set, and its further diagonalization. Both spectral schemes are timewise computationally efficient since the basis elements are such that no derivatives have to be calculated numerically. Moreover, very accurate results are obtained with minimal basis sets. This is related on one side to the use of the natural coordinate system and, on the other, to the intrinsic good property of all GSF basis elements that are constructed as to obey appropriate physical boundary conditions. The present implementation for bound states paves the way for the study of continuum states involved in ionization of one or two-electron diatomic targets.

Current pagination concerns with exploration regarding thermal characteristics induced by Hybridization of  with MWCNT in a permeable tank filled with viscous fluid with magnetization. Roseland approximation is obliged to configure radiative heat flux aspects. Modeling and structuring of considered problem is established in partial differential setup. CVFEM is implemented to seek out solution of constructed differential layout. Data establishing properties of    with MWCNT’s is disclosed in tabular format. Impression of sundry variables in view of isotherm and stream pattern is divulged. Local convective thermal rate against involved variables in 3D snapshots is captured. Test about grid independence and comparison with conducted work to get assurance of present finding is explicated. It is deduced that heat transfer along walls enhances verses Rayleigh and Darcy parameters whereas delineates against mounting effect of magnetic field strength. 

In the present work, undoped and In-doped zinc oxide (ZnO) nanoparticles have been prepared by sol gel technique. The structural and morphological properties of the obtained nanoparticles have been studied using respectively X-ray diffraction (XRD), Raman spectroscopy and scanning electron microscopy (SEM). The electronic defects in the nanopowder band gap were investigated by photoluminescence (PL) spectroscopy. The antibacterial activities of the prepared nanopowders have been tested against Gram positive and Gram negative bacteria’s. Based on the inhibition zone determination. The In doping effect is explained in term of the electronic defect enhancement such as inertial defect Zni and vacancy defect Vzn with In doping, these two defects act as source of electrons and holes during the reactive oxygen species (ROS) production responsible for bacteria’s destruction. Due to the bonded hydrogen charge transfer crystal screening, the prepared ZnO nanoparticles exhibit a low antioxidant activity

Magnetic ferrite based nanoparticles (MFNPs) are becoming an interesting candidate for nanomedicine development and found application in drug delivery and diagnostics. In the present work, we have synthetized various spinel ferrite nanoparticles (NPs) by hydrothermal technique (a simple and cost effective technique). Different divalent metals, namely Ni, Zn, Cu and Co, were used for spinel ferrite preparation. Since these NPs are injected directly to the blood for therapeutic or diagnostic purpose their influence on the composition of human blood serum once in contact were investigated. The blood serum was analyzed by means of Fourier transform infrared (FTIR) and UV- Visible absorption spectroscopies. The results indicated the formation of protein-corona with all studied MFPN’s. Small amount of metal oxides were found to be released from the MFNP’s to the serum. Based on our study, ZnFe2O4 has been suggested as the most suitable spinel ferrite NPs for Nano medicine applications.

Monovalent cation permselective membranes (MCPMs) are highly desirable for the extraction of Li+ and Na+ ions from earth-abundant sources, such as salt lakes and seawater. Metal–organic frameworks (MOFs) are promising functional nanomaterials with excellent potential for ion separation technologies owing to their regular structure and tunable pore sizes. However, the successful use of MOFs in ion separation membranes is still challenging owing to the numerous difficulties in preparing ultrathin and defect-free MOF membranes. Here, we proposed a facile post-synthetic method for the preparation of UiO-66(Zr/Ti)-NH2 and subsequently immobilized UiO-66(Zr/Ti)-NH2 in an ultrathin polyamide layer (~100 nm). The resulting thin-film nanocomposite membranes presented high monovalent cation permeation and excellent selectivity for mono-/di-valent cations. The PNa+/Mg2+ and PLi+/Mg2+ permselectivities of the best-performing thin-film nanocomposite membrane were 13.44 and 11.38, respectively, which were 3.8 and 5.1 times higher, respectively, than those of the commercial state-of-art CSO membrane.

Suitable habitat fragment size, isolation, and distance from a source are important variables influencing community composition of plants and animals, but the role of these environmental factors in determining composition and variation of host-associated microbial communities is poorly known. In parasite-associated microbial communities, it is hypothesized that evolution and ecology of an arthropod parasite will influence its microbiome more than broader environmental factors, but this hypothesis has not been extensively tested. To examine the influence of the broader environment on the parasite microbiome, we applied high-throughput sequencing of the V4 region of 16S rRNA to characterize the microbiome of 222 obligate ectoparasitic bat flies (Streblidae and Nycteribiidae) collected from 155 bats (representing six species) from ten habitat fragments in the Atlantic Forest of Brazil. Parasite species identity is the strongest driver of microbiome composition. To a lesser extent, reduction in habitat fragment area, but not isolation, is associated with an increase in connectance and betweenness centrality of bacterial association networks driven by changes in the diversity of the parasite community. Controlling for the parasite community, bacterial network topology covaries with habitat patch area and exhibits parasite-species specific responses to environmental change. Taken together, habitat loss may have cascading consequences for communities of interacting macro- and microorgansims.  

The controllable mass transfer and reaction rate for phase transfer hydrogenation of acetophenone across a well-defined boundary were investigated. The effect of solvent was found important and 1-butanol exhibited the best performance among the five investigated homologous alcohol solvents, consistent with its higher solubility in water and greater dielectric constant. Initial reaction rates increased with increasing electric potential, consistent with enhanced mass transfer across the aqueous/organic boundary. At longer reaction times deactivation was apparent. It correlated with increasing voltage and is ascribed to lower equilibrium concentration of reactive species at the interface. External control over reaction rate was demonstrated by switching the applied electric potential over the course of the reaction. Effects of external electric field on enantioselectivity were also explored with reversal field direction. The changes correlate with catalyst decomposition.