Multi-marker approach for the evaluation of environmental impacts of APACS 50WG on aquatic ecosystems.

Neonicotinoids are the most widely used synthetic insecticides in the world. These insecticides are widely distributed in the ecosystem, indicating that more attention should be paid to the potential risks regarding their use in agriculture. Due their intensive use, non-target species in the environment are also exposed to their putative effects.

Aerodynamic properties and in silico deposition of isoniazid loaded chitosan/thiolated chitosan and hyaluronic acid hybrid nanoplex DPIs as a potential TB treatment.

Existing therapies yield low drug encapsulation or accumulation in the lungs, hence the site-specific drug delivery remains the challenge for tuberculosis. Lately, dry powder inhalers (DPIs) are showing promising drug deposition in the deeper lung tissues. Biocompatible polymers with the ability to naturally recognize and bind to the surface receptors of alveolar macrophages, the reservoir of the causative organism, were selected.

The Use and Concurrent Use of Side Effect Controlling Medications Among Women on Aromatase Inhibitors.

Women on aromatase inhibitors (AIs) as part of their breast cancer treatment often experience difficult to control side effects. Although there are several medications to manage the side effects of AI therapy, many of them are associated with their own risk, particularly sedation. The objective of this study was to describe the prescribing practices for side effect managing (SE) medications among women with breast cancer on AI therapy and to assess for combinations of medications that may present a clinical risk to patients.

Harnessing Natural Killer Cell Function for Genitourinary Cancers.

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.

Adsorption of Azobenzene on Hexagonal Boron Nitride Nanomesh Supported by Rh(111).

Adsorption properties of azobenzene, the prototypical molecular switch, were investigated on a hexagonal boron nitride (h-BN) monolayer ("nanomesh") prepared on Rh(111). The h-BN layer was produced by decomposing borazine (BNH) at 1000-1050 K. Temperature-programmed desorption (TPD) studies revealed that azobenzene molecules adsorbed on the "wire" and "pore" regions desorb at slightly different temperatures.

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer.

Importance: National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population.

Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.

Membrane protein biogenesis faces the challenge of chaperoning hydrophobic transmembrane helices for faithful membrane insertion. The guided entry of tail-anchored proteins (GET) pathway targets and inserts tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane with an insertase (yeast Get1/Get2 or mammalian WRB/CAML) that captures the TA from a cytoplasmic chaperone (Get3 or TRC40, respectively). Here, we present cryo-electron microscopy reconstructions, native mass spectrometry, and structure-based mutagenesis of human WRB/CAML/TRC40 and yeast Get1/Get2/Get3 complexes.

The effect of oral and nasal breathing on the deposition of inhaled particles in upper and tracheobronchial airways.

The inhalation route has a substantial influence on the fate of inhaled particles. An outbreak of infectious diseases such as COVID-19, influenza or tuberculosis depends on the site of deposition of the inhaled pathogens. But the knowledge of respiratory deposition is important also for occupational safety or targeted delivery of inhaled pharmaceuticals.

Simulation of the effect of mucociliary clearance on the bronchial distribution of inhaled radon progenies and related cellular damage using a new deposition and clearance model for the lung.

Most of the current dosimetry models of inhaled short-lived radon decay products assume uniform activity distributions along the bronchial airways. In reality, however, both deposition and clearance patterns of inhaled radon progenies are highly inhomogeneous. Consequently, a new deposition-clearance model has been developed that accounts for such inhomogeneities and applied together with biophysical models of cell death and cell transformation.

Numerical simulation of the effect of inhalation parameters, gender, age and disease severity on the lung deposition of dry powder aerosol drugs emitted by Turbuhaler®, Breezhaler® and Genuair® in COPD patients.

The effect of breathing parameters on the airway deposition of the inhaled aerosols with known size was intensively studied in the literature. However, in the case of dry powder aerosol drugs both the quantity and quality of the particles emitted by the inhaler and inhaled by the patients is a complex function of the patient's breathing parameters, which in turn depend also on the disease severity and current status of the patient. The aim of this study was to evaluate the impact of breathing parameters, gender, age, symptoms and exacerbation history related disease severity (GOLD groups) of chronic obstructive pulmonary disease (COPD) patients on the lung dose of four different drugs emitted by three DPIs (dry powder inhalers).

The Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen .

Small, cysteine-rich and cationic antimicrobial proteins (AMPs) from filamentous ascomycetes promise treatment alternatives to licensed antifungal drugs. In this study, we characterized the Q176 antifungal protein C (PAFC), which is phylogenetically distinct to the other two antifungal proteins, PAF and PAFB, that are expressed by this biotechnologically important ascomycete. PAFC is secreted into the culture broth and is co-expressed with PAF and PAFB in the exudates of surface cultures.

Novel combination of non-invasive morphological and solid-state characterisation of drug-loaded core-shell electrospun fibres.

In recent years, core-shell nanofibrous drug delivery systems have received increasing attention due to their ability to incorporate two or more active pharmaceutical ingredients (APIs) individually into the desired layer (either core or sheath) and thereby finely tune the release profiles of even incompatible drugs in one system. This study aims to perform formulation and solid-state characterisation of levofloxacin-loaded polylactic acid (PLA) - naproxen-sodium-loaded polyvinyl pyrrolidone (PVP) bicomponent core-shell fibrous sheets and examine the electro spinnability of the precursor combinations. The selected drugs have potential therapeutic relevance in similar systems intended for wound healing; however, in this study, they are used as model drugs to understand the physicochemical properties of a drug loaded system.

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study.

Purpose: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.

Methods: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2).

Sexual Harassment of Female Providers by Patients: a Qualitative Study.

Background: Sexual harassment of women is a pervasive problem. Prior studies found that sexual harassment of female providers by patients is common, but guidance on addressing this problem is limited.

Objective: To understand the experiences of female providers with sexual harassment by patients with a focus on how practicing providers address these events.

Raman-based dynamic feeding strategies using real-time glucose concentration monitoring system during adalimumab producing CHO cell cultivation.

The use of Process Analytical Technology tools coupled with chemometrics has been shown great potential for better understanding and control of mammalian cell cultivations through real-time process monitoring. In-line Raman spectroscopy was utilized to determine the glucose concentration of the complex bioreactor culture medium ensuring real-time information for our process control system. This work demonstrates a simple and fast method to achieve a robust partial least squares calibration model under laboratory conditions in an early phase of the development utilizing shake flask and bioreactor cultures.

TIM-3 and TIGIT are possible immune checkpoint targets in patients with bladder cancer.

The resurgence of immunotherapy as an effective anticancer strategy has been coupled with more mature understandings of the underlying immune pathways and the development of novel immune checkpoint targets. The clinical development of antibodies first directed against cytotoxic T-lymphocyte-associated antigen 4, and later against program death 1, achieved durable disease control in a subset of patients across a large number of tumor types. Previous work demonstrates that targeting the programmed death 1 pathway alone does not result in complete restoration of T cell function and in some cancers, targeting this axis does not restore T cell function at all, suggesting a need to identify other molecules and inhibitory pathways that are involved in T cell exhaustion.

A primer for pediatric radiologists on infection control in an era of COVID-19.

Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee.

Frequency and waveform dependence of alternating current electrospinning and their uses for drug dissolution enhancement.

The effect of different frequencies and waveforms was investigated for the first time on alternating current electrospinning (ACES). PVPVA64, a polyvinylpyrrolidone-vinyl acetate copolymer was selected for the experiments as an important matrix for amorphous solid dispersions but never processed with ACES. It has been proved that ACES could be operated in a wide range of frequencies (40-250 Hz) and using different waveforms (sinusoidal, square, triangle, saw tooth) without significant changes in fiber morphology.

Urothelial Papilloma of the Urinary Bladder in Children: Report of Two Cases.

Urothelial neoplasms of the bladder (UNB) are considerably rare throughout the pediatric population. UNB develops from the urothelial tissue in the form of a benign disease, generally favoring a successful prognosis in the majority of cases. The authors present the diagnosis and treatment regarding two medical case reports in which urothelial papilloma was diagnosed and effectively treated.

Evaluation of bladder shape using transabdominal ultrasound: Feasibility of a novel approach for the detection of involuntary detrusor contractions.

Conventional assessment of overactive bladder syndrome uses invasive pressure-measuring catheters to detect bladder contractions (urodynamics). We hypothesised that bladder shape changes detected and measured using transabdominal ultrasound scan could provide a non-invasive and clinically useful alternative investigation of bladder contractions. This feasibility study evaluated a novel transabdominal ultrasound scan bladder shape test during conventional urodynamics and physiological bladder filling.

Pericyte-secreted IGF2 promotes breast cancer brain metastasis formation.

Brain metastases are life-threatening complications of triple-negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease.

A solid doxycycline HP-β-CD formulation for reconstitution (i.v. bolus) prepared by scaled-up electrospinning.

In this study a new intravenous (i.v.) bolus dosage form of doxycycline was prepared by electrospinning.

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties.

Most of the marketed dry powder inhalation (DPI) products are traditional, carrier-based formulations with low drug concentrations deposited in the lung. However, due to their advantageous properties, their development has become justified. In our present work, we developed an innovative, carrier-based DPI system, which is an interactive physical blend of a surface-modified carrier and a spray-dried drug with suitable shape and size for pulmonary application.

Care of patients with non-small-cell lung cancer stage III - the Central European real-world experience.

Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements. Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally.