The poly lactate co-glycolic acid (PLGA) nanoparticles of tubercular drugs have been demonstrated to have sustained release profile over seven days. There is no information on the location or mode of release of these nanoparticles in living system. Therefore, we have planned the study to explore the pharmacokinetics and biodistribution of PLGA rifampicin nanoparticles in healthy human volunteers. Rifampicin was labeled with 99mTc by indirect method and nanoparticles were prepared by a single emulsion evaporation method. To investigate the pharmacokinetics and biodistribution of nanoparticles, a single dose of 450 mg of rifampicin was administered orally to healthy human volunteers divided into two different groups. Following a single oral dosage of the rifampicin nanoformulation, the PK parameters were significantly different between the nanoparticle and conventional groups AUC (113.8 vs 58.6), MRT (16.2 vs 5.8) and Ke (0.04 vs 0.10). Also SPECT/CT images revealed bio-distrubution of nanoparticles in the distal portions of the intestine, which is consistent with our dosimetry analysis Significant difference in PK parameters and bio-distribution of nanoparticles in spleen and lymph nodes with maximum deposition were observed in large intestine. Nanoparticle distribution pattern may be advantageous for the treatment of intestinal or lymph node TB and has the potential to result in a lower dose of rifampicin nanoformulation for the treatment of pulmonary TB.

Abstract Introduction NHS staff face mental health problems due factors including burnout, workload, exposure to trauma and lack of support. Healthcare professionals often face barriers to seeking help and are less likely to seek out professional help for their own mental health. Following staff suicides, this study aimed to identify the perceived barriers to seeking support faced by staff members across an NHS Trust. Methods Semi-structured interviews with 29 participants, each lasting approximately 90 minutes. A further 10 informal conversations were had with staff not wanting to be formally interviewed. Results Framework analysis was used to analyse the data, resulting in four themes being identified around perceived barriers to seeking support: stigma organisational culture privacy access to support Discussion Findings indicated that staff perceived significant barriers, including mental illness-related stigma, workplace trauma, organisational culture, confidentiality concerns and access to support. Many staff members who needed to help did not reach out for support within the workplace, despite knowing they needed it. Conclusion There are perceived barriers to seeking help affect both the individual and the culture of the organisation. Larger studies are needed to assess the perceived barriers experienced by staff nationwide, with the aim of tackling these to improve staff wellbeing.

Monitoring the condition of complex systems with implemented sensors in an online manner is of great importance to their safety and availability. Broad learning system (BLS), which expands the single-hidden-layer neural network by enriching the number of hidden-layer nodes, can greatly improve the model training efficiency. But, the randomly generated hidden-layer nodes make BLSs performing poorly in some high-dimensional data classification tasks. This paper focuses on providing some ideas to tackle this problem by optimizing the generation of initial nodes to compact the BLS hidden-layer structure. Specifically, logistic regression (LR) and structural causal model (SCM) are considered to obtain rough predictions of system fault state to replace the randomly generated hidden-layer nodes with no practical significance. Thus, the outputs of the initial node groups are more closely related to the system health status. The proposed methods are expected to improve the feature extraction effectiveness, to simplify the network structure, and to reduce the computational burden. Various simulation datasets are considered to prove the universality of the proposed method in complex system fault diagnosis. And, with real data from a high-speed train brake control system, the effectiveness of the proposed online monitoring framework is further verified. It is also shown that the proposed methods are convenient to migrate to new operation environments.

We study the ground state solutions for the following p\&q-Laplacain equation \[ \left\{ \begin{array}{ll} -\Delta_pu-\Delta_qu+V(x) (|u|^{p-2}u+|u|^{q-2}u)=\lambda K(x)f(u)+|u|^{q^*-2}u,~x\in\R^N, \\ u\in W^{1,p}(\R^N)\cap W^{1,q}(\R^N), \end{array} \right. \] where $\lambda>0$ is a parameter large enough, $\Delta_ru = \text{div}(|\nabla u|^{r-2}\nabla u)$ with $r\in\{p,q\}$ denotes the $r$ Laplacian operator, $1

From the author’s recent studies, it was found that, in low/medium/high cycle fatigue(LHCF) regime, the Wöhler Curve Method is well suitably employed to perform the fatigue life assessment of metals, in which the stress-based intensity parameter calculation is based on the linear-elastic analysis. In this study, an attempt is made through many fatigue test data of notch components of metals from the literature to illustrate that, in LHCF regime, the Notch S-N Curve Method is well suitable for fatigue life analysis of notch components of metals, in which the stress-based intensity parameter calculation is based on the linear-elastic analysis. By concepts of the critical stress and the critical distance by Taylor and by two calibration fatigue failure curves of a smooth specimen and notch specimen by Susmel and Taylor, further, a local approach for predicting the notch S-N curve is proposed based the linear elastic stress fields ahead of notches. Accuracy of the Notch S-N Curve Method is proven by many fatigue test data of notch components of metals from the literature in LHCF regime.

A method for accurately estimating the electron correlation energy as a 1 st order correction to the Hartree-Fock energy is presented. It succeeds by disallowing the representation of the electron repulsion operator to be more fine-grained than the corresponding representation of the two-particle density. To extract the electron correlation contribution to the molecular internal energy from the exact wavefunction, the short-range contribution to the electron repulsion operator is replaced by a corresponding correlation kinetic energy penalty. Utilizing the virial theorem, this self-interaction-free exact-exchange method becomes applicable on condition of stability of the Self-Consistent Field wave function. Laplace as well as Fourier transforms are resorted to as consistency checks. Atomic and small molecular ions are considered for validation. The latter require modelling of the screened Coulomb hole associated with 1s electrons owing to coupled short-range electron-nucleus and electron-electron interactions. For this purpose, Hooke's atom is analyzed (0.03 ≤ í µí¼” ≤ 1000) and consistency is demonstrated for 1s ! Helium-like ions (Z=1-36). While impacting core-valence interactions, the said screening is absent in the valence as confirmed by the Be-like ions (Z=3-36) 1í µí± ! 2í µí± ! systems, for LiH, BeH + , Li2 and for LiBe +. A chemistry associated exclusively with K-shell orbitals is briefly discussed based mainly on results for HeH + and H3 +. Fractional charges scaling the Coulomb hole is inferred to better represent the complex correlation hole in hydrogen clusters and high-pressure metallic hydrogen.

The Asian palm civet ( Paradoxurus hermaphroditus) is a wild mammal which is living in nature in Indonesia forest. Recently due to the highest demand of civet coffee, push the changes of the living environment of the Asian palm civet as the pet or captive breed. Changes in the environment from the wild to human intervention cause shift in their behaviour and feeding patterns. This is thought possibly to affect it’s anatomical structure and histology digestive organ and mainly the lingual papillae as an entrance of the food. This study aims to analyse the anatomical structure of the lingual papillae and the secretions of the lingual glands in Paradoxurus hermaphroditus due to the changes of the food behaviour by gross macroscopy, scanning electron microscopy (SEM) and light microscopy (LM) in the form of histochemical staining (hematoxyline eosin, Alcian Blue-Periodic Acid Schiff, and Masson’s Trichrome). The SEM results revealed that several type lingual papillae are found on the tongue of the Paradoxurus hermaphroditus they are: fungiform, arrowhead filiform, giant arrowhead filiform, scale-like filiform, conical, and circumvallate papillae. The histological results showed that on the radix of tongue of the civet are found Weber’s glands which produce the secretion of neutral and acid mucin. Collagen fibers were found scattered in all of the lamina propria and some of the tunica muscularis with higher collagen intensity at the apex. In conclusion, these results provide the new insight of the adaptation form of the lingual papillae of the Asian palm civet due to their changes of feeding behaviour based on the type, number, distribution of the papillae, as well as the type of lingual gland secret and the presence of the collagen fibre.

Isolated TAPVC is difficult to diagnose on a prenatal ultrasound as standard obstetric screening views are often normal. We present a case of isolated infra-cardiac TAPVC highlighting the utility of STIC imaging in the diagnosis ofTAPVC

A 69-year-old female presented to the emergency department with chest pain and EKG changes consistent with anterior STEMI. Left heart catheterization revealed multi-vessel CAD. She was referred for a CABG. Transthoracic echocardiography (TTE) with contrast raised concerns for apical pseudoaneurysm (Image 1). Cardiac computed tomography (CT) confirmed the presence of a multi-lobular dissecting pseudoaneurysm and extensive pericardial thickening (Images 3 and 4). This was confirmed at surgery, and she underwent partial pericardiectomy. Repair of the defects was deemed too high risk and adhesion prevented the insertion of any grafts. She subsequently underwent percutaneous revascularization.

Tracheal resection and end-to-end anastomosis has been the standard clinical approach for the treatment of most airway diseases, especially invading the lower trachea or carina. However, when long-length (exceeding 2 cm in children or 5 cm in adults) tracheal circular resection is performed, tracheal replacement therapy is often required. In this study, we aimed to utilize autologous tracheal epithelia and bone marrow mesenchymal stem cells (BMSCs) as the seeding cells, utilize polycaprolactone (PCL) coated with Silk Fibroin Methacryloyl (SilMA) as the scaffold to carry the cells and Kartogenin (KGN). Firstly, SilMA with the concentration of 10%, 15% and 20% was made, and the experiment of swelling and degradation was performed. With the increase of the concentration, the swelling ratio decreased, the degradation progress slowed down. Upon the result of CCK-8 test and HE staining of 3D co-culture, the 20% SilMA was selected. Next, SilMA and the cells attached to SilMA were characterized by scanning electron microscopy (SEM). Furthermore, in vitro cytotoxicity test shows that 20% SilMA has good cytocompatibility. The hybrid scaffold was then made by PCL coated with 20% SilMA. The mechanical test shows this hybrid scaffold has better biomechanical properties. In vivo tracheal defect repair assays were done to evaluate the effect of the hybrid substitution. H&E staining, immunohistochemical (IHC) and immunofluorescence (IF) staining showed that this hybrid substitution ensured the viability, proliferation and migration of epithelium. This study is expected to provide new strategies for the fields of tracheal replacement therapy needing mechanical properties and epithelization.

Objective: To assess the influence of vaccination on reproductive outcome treatment of in vitro fertilization (IVF) treatment. Design: A retrospective cohort study. Setting: A university-affiliated reproductive medical center. Population: The study included a total of 1105 couples who underwent 1269 IVF treatment cycles with fresh cycles from March.1.2021 to January.1.2022. 215 vaccinated couples, 677 unvaccinated couples, 101 couples with female vaccinated only, and 112 couples with male vaccinated only. Methods: 1105 couples were divided into four groups according to the inactivated COVID-19 vaccination status of both partners: Group A, both partners were vaccinated; Group B, only female partners were vaccinated; Group C, only male partners were vaccinated; Group D, neither of them was vaccinated. To compare the live birth and neonatal outcomes among different vaccinated couples or unvaccinated couples. Main Outcome Measure(s): The primary outcome was a live birth rate and secondary outcomes were a low birth rate and preterm birth rate. Result(s): The results showed that there are no significant differences in live birth rate and neonatal outcomes among different groups. The logistic regression model applied demonstrated that the different vaccination statuses of infertile couples had no effects on the live birth rates. Conclusion(s): The COVID-19 inactive vaccine did not affect the couples’ reproductive outcome in IVF treatment. To prevent serious complications related to COVID-19 infection during pregnancy and the perinatal period, active immunization with vaccines is available before pregnancy.

The contact fatigue of carbon steel gear tooth surfaces under different lubrication conditions has been investigated and a model of the effect of lubrication conditions on contact fatigue has been established. Electrochemical corrosion forms nonferrous oxide on the tooth surface, and the crack corrosion between the nonferrous oxide and the Fe matrix may become the initiation point for contact fatigue. High temperature generated by frictional heat can accelerate the plastic deformation. Micro damage less than Hertzian contact is more likely to expand into macro pitting. The pressure around the micro damage increases when the micro damage partially coincides with the contact width, so the tooth surface around the pit is more likely to produce new pits, and then form the superposition and aggregation. The larger the lubricating oil supply, the larger the contact width, and the larger the width of the micro damage can be activated, the improvement of lubrication can promote the propagation of micro damage.

The stability of residual stress plays an important role in the fatigue performance of materials. In this work, the stability of surface residual stress in carburized alloy steel with different carburized layers is studied by axial fatigue tests. Different stress amplitudes are applied to the specimens over several cycles, and the resulting residual stress on the surface is measured by X-ray diffraction. It is found that residual stress relaxation occurs on the specimens when the applied stress amplitude is large, and that the relaxation rate depends on the magnitude of the stress amplitude. The stress relaxation is most obvious in the first cycle, and changes slowly in the subsequent cycles. A model of surface residual stress evolution is established which can accurately describe the relaxation process. The residual stress on the surface of the specimen is found to be in a stable state, if the stress amplitude is less than 30% of the material yield strength.

Persistent high-risk human papilloma virus (HR-HPV) infection is the main risk factor for cervical cancer, threatening women’s health. Despite growing prophylactic vaccination, annual cervical cancer cases are still increasing and show a trend of younger onset age. However, therapeutic approaches towards HPV infection are still limited. 25-hydrocholesterol (25HC) has a wide-spectrum inhibitory effect on a variety of viruses. To explore efficient interventions to restrict HPV infection at an early time, we applied different pseudoviruses (PsV) to evaluate anti-HPV efficacy of 25HC. We tested PsV inhibition by 25HC in cervical epithelial-derived HeLa and C-33A cells, using high-risk (HPV16, HPV18, HPV59), possibly carcinogenic (HPV73), and low-risk (HPV6) HPV PsVs. Then we established murine genital HPV PsV infection models and applied IVIS to evaluate anti-HPV efficacy of 25HC in vivo. Next, with the help of confocal imaging, we targeted 25HC activity at filopodia upon HPV exposure. After that, we used RNA-seq and Western blotting to investigate 1) how 25HC disturbs actin cytoskeleton remodeling during HPV infection and 2) how prenylation regulates the cytoskeletal remodeling signaling pathway. Our findings suggest that 25HC perturbs F-actin rearrangement by reducing small GTPase prenylation. In this way, the phenomenon of HPV virion surfing was restricted, leading to failed infection.

Callicarpa subpubescens is endemic to the oceanic Ogasawara Islands, and multiple ecotypes have been suggested to exist within southern part of this group, the Hahajima Islands, each associated with unique localized habitats. We determined the habitat characteristics of each ecotype, the presence or absence of pre- and post-mating isolation, the amount of gene flow among ecotypes in adult trees and naturally pollinated seeds using EST-SSR markers, and discussed how ecotypes are maintained in this species. There were four ecotypes in the Hahajima Islands, one of which presumed to be derived from hybridization of the remaining two ecotypes. The spatial distribution and habitat of each ecotype showed distribution which have depended on the suitable environment for each ecotype, i.e. local adaptation. The leaf morphology and size distribution of each ecotype also indicated the appropriate forms for each habitat. Flowering times more or less overlap among the ecotypes, indicating that pre-mating isolation is not perfect. Artificial cross-pollination showed that no post-mating isolation exists between ecotypes. Hybridization rates in adult trees and naturally pollinated seeds were 37.2% and 26.4%, respectively, and most of the hybrids were backcrosses and few F1. The hybridization rates of each ecotype and paternal correlation indicated that the flowering synchrony and spatial distribution of ecotypes contributed to hybridization among ecotypes. The reversion to the original ecotype which adapted to the environment through backcrossing would contribute to the maintenance of the ecotypes.

Soft tissue sarcomas in neonates are rare and heterogeneous tumors. We report an aggressive neonatal undifferentiated round cell sarcoma with a YWHAE:NUTM2B fusion. The tumor was identified antenatally and the neonate underwent surgical resection at four days of age. Whole-genome and transcriptome sequencing of tumour and germline was undertaken to provide molecular characterization and elucidate possible novel therapies. In addition to molecular characterization of a YWHAE:NUTM2B fusion, RNA expression outliers were described. Targeted therapy was not pursued due to rapid clinical decline. Understanding the genomic profile of rare tumors remains important in the development of novel therapeutic strategies.

Cognitive Radios are the best available options for the increasing number of devices and users who need to access the limited physical spectrum for wireless network communications. They use the spectrum efficiently and allow the secondary users to be accommodated to use the network spectrum when the primary users are not actively transmitting. However, sensing the channel for primary users and their active transmissions is a challenge because there are numerous parameters in the transmission that are uncertain. The paper addresses this problem of channel sensing by proposing a parallel transmission and hence power control scheme has been developed for the transmission to analyze the power management and QoS parameters. The design has been simulated using the Qualnet simulation tool.

Introduction: There is an increased demand for well-validated PROMs in otology. This study will systematically assess the methodological quality of all published patient-reported outcome measures (PROMS) for patients with multiple ear complaints and to identify the best suitable PROM for use by clinicians treating patients with multiple ear complaints. Methods: An extensive systematic mapping review on all otology questionnaires was performed to identify questionnaires measuring multiple ear complaints. The ‘Consensus‐based standards for the selection of health measurement Instruments’ (COSMIN) checklists were used to evaluate the quality of the questionnaire by two researchers. The worst item score per aspect of the methodological assessment counted. Results: Twelve multiple complaint questionnaires were included in the study for quality assessment. Ten questionnaires were disease specific (COMQ-12, CES, ZCMEI-21, MD-POSI, PAN-QOL, ETDQ-7, MDOQ, GYSSCDQ, COMOT-15 and DEU-MDDS). Two questionnaires were ear domain specific (OQUA and COQOL). The majority of multiple complaint questionnaires lacked good design with concept elicitation and patient involvement. Conclusion: For the majority of questionnaires, the quality assessment was inadequate as only a few authors consulted with patients affected by the complaints in the development. Modifications of earlier versions of PROMS or combinations of multiple questionnaires lead to ongoing (cross-cultural) validation of these questionnaires albeit the mediocre design and validation. The two domain specific questionnaires are the COQOL and OQUA, both with adequate quality but different focus. COOQL to quantify the quality of life and OQUA to measure and evaluate severity and impact of ear complaints.

Commelina bicolor D. Q. Wang & M. E. Cheng is a late homonym of Commelina bicolor Poepp. ex Kunth, so it is renamed as Commelina anhuiensis R. Z. Huang & Han Xu.

In this paper, a coupling transmission epidemic model with mutualistic two-strain of virus in body and vitro of host is proposed, in which humoral immune response only works for strain 1 due to immunity evasion of mutation. For the within-host subsystem, the global stability of all feasible equilibria with and without environmental influence are discussed. For the between-host subsystem, the basic reproduction number R 0 is obtained. When R 0 < 1 , the disease-free equilibrium is local stable, while the endemic equilibrium is local stable and the disease is uniformly persistent if R 0 > 1 . Meanwhile, backward bifurcation would occur when there exists immune response within host. Finally, numerical examples are provided to illustrate obtained conclusions, by which we find that the mutualism between two strains during co-infection leads to a more persistent disease than single strain, even the basic reproduction number is small than 1 in each single strain.

The soil seed bank is one of the most important ecological indicators to evaluate and monitor the ecological restoration process of plant communities. We aimed to evaluate the influence of ecological restoration techniques on the plant community diversity and composition and functional group composition of the soil seed bank in two bauxite mining areas under compensatory restoration, Southeast Brazil. 30 soil samples were collected in each area (Area_A – Forest restoration by planting seedlings and nucleation techniques and Area_B – just restoration by planting seedlings). The samples were transported to a shade house and evaluated for six months, where germinated individuals were counted and identified weekly. The results indicated that the soil seed banks of the two areas are floristically similar (with a predominance of pioneer, herbaceous and native origin species), which show a higher natural regeneration potential. However, the higher species richness and abundance of zoochoric individuals in Area_A demonstrate that nucleation techniques, such as topsoil transposition and direct seeding were efficient to increase the recovery potential re-establishment. In the early successional stages, restoration techniques are more determinant in the functional group composition than in the floristic composition of the soil seed bank.

Editorial

Background – The incidence of pediatric asthma exacerbations during the COVID-19 pandemic has been evaluated; however, the incidence of severe acute asthma (SAA) requiring a Pediatric Intensive Care Unit (PICU) admission is unknown. Furthermore, we examined several factors which might influence this incidence, such as environmental triggers or changes in COVID-19 lockdown regulations. Methods – In this single-center, retrospective cohort study running from 2018 to 2021, all PICU admissions for SAA of children above two years of age at a tertiary hospital in the Netherlands were included. Information on potential asthma triggers during the pandemic, including viral infections, concentrations of ambient fine particulate matter (PM2.5) and pollen index were evaluated. Results – In total, 168 children were included in this study. While we observed a decrease in PICU admissions for SAA during lockdown periods, there was an increase in the admission rates in the periods without a lockdown, with the highest peak from August to November of 2021. This peak in the fall of 2021 did not align with pollen or ambient PM2.5 concentrations (r s=-0.04 for pollen and r s=0.23 for PM2.5). Discussion – COVID-19 lockdowns influenced the admission rates for SAA at the PICU both during and after the lockdowns in the Netherlands. We hypothesize that an increase in viral infections after lockdown periods was the reason for the altered incidence of SAA at the PICU in late 2021, rather than air pollution and pollen concentrations.

Corticosteroid resistance is the essential obstacle for effective treatment of chronic obstructive pulmonary disease (COPD). Oxidative stress and persistent chronic inflammation caused by cigarette smoke are likely to induce this corticosteroid insensitivity. Salidroside (Sal) is a main ingredient of traditional Chinese medicine rhodiola, which has the effects of anti-oxidation and anti-inflammatory. We aimed to investigate the role of Sal in the corticosteroid sensitivity of COPD. Collecting peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV) and patients with COPD, and human monocytic U937 cells stimulated by normal culture and cigarette smoke extract (CSE), corticosteroid sensitivity was determined as the dexamethasone concentration causing 30% inhibition of tumor necrosis factor alpha (TNF-α)-induced IL-8 production (Dex-IC 30) in these cells. Compared with PBMC from HV and normally cultured U937, in PBMC from COPD patients and U937 cells stimulated by CSE, the inhibitory effect of dexamethasone on IL-8 was weakened and the levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and histone deacetylase‐2 (HDAC2) was reduced. In conclusion, Sal restored dexamethasone inhibition of IL‐8 production, accompanied by raising the expression of Nrf2 and HDAC2 levels. Sal may upregulate HDAC2 expression by activating the Nrf2/HO-1 signaling pathway, and then restore corticosteroid sensitivity in COPD.