Phosphoinositides in autophagy: current roles and future insights.

Today, the importance of autophagy in physiological processes and pathological conditions is undeniable. Initially, autophagy merely was described as an evolutionarily conserved mechanism to maintain metabolic homeostasis in times of starvation; however, in recent years it is now apparent that autophagy is a powerful regulator of many facets of cellular metabolism, that its deregulation contributes to various human pathologies, including cancer and neurodegeneration, and that its modulation has considerable potential as a therapeutic approach. Different lipid species, including sphingolipids, sterols, and phospholipids, play important roles in the various steps of autophagy.

MRI assisted focal boost integrated with HDR monotherapy study in low and intermediate risk prostate cancer (MARS): Results from a phase II clinical trial.

Purpose: There is growing concern that single-fraction HDR monotherapy to a dose of 19 Gy is suboptimal for the treatment of localized prostate cancer. We report the results of a phase II prospective trial of single-fraction 19 Gy HDR monotherapy with MRI-guided simultaneous focal boost.

Methods: Eligible patients had low or intermediate risk prostate cancer and an identified lesion on MRI.

Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients.

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses.

Probing Dark Matter Using Precision Measurements of Stellar Accelerations.

Dark matter comprises the bulk of the matter in the Universe, but its particle nature and cosmological origin remain mysterious. Knowledge of the dark matter density distribution in the Milky Way Galaxy is crucial both to our understanding of the standard cosmological model and for grounding direct and indirect searches for the particles comprising dark matter. Current measurements of Galactic dark matter content rely on model assumptions to infer the forces acting upon stars from the distribution of observed velocities.

Results of 15 Gy HDR-BT boost plus EBRT in intermediate-risk prostate cancer: Analysis of over 500 patients.

Purpose/objective: To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer.

Materials And Methods: A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured.

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management.

Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

Predictive Role of Computed Tomography Texture Analysis in Patients with Metastatic Urothelial Cancer Treated with Programmed Death-1 and Programmed Death-ligand 1 Inhibitors.

Background: Reliable biomarkers to predict the response of metastatic urothelial cancer (mUC) to programmed death-1 and programmed death-ligand 1 (PD-1/PD-L1) inhibitors are being investigated. Texture analysis represents tumor heterogeneity and may serve as a predictor of response in mUC.

Objective: To assess the predictive ability of computed tomography (CT) texture analysis for progression-free survival (PFS) in patients with mUC treated with PD-1/PD-L1 inhibitors.

Rhinovirus-16 induced temporal interferon responses in nasal epithelium links with viral clearance and symptoms.

Background: The temporal in vivo response of epithelial cells to a viral challenge and its association with viral clearance and clinical outcomes has been largely unexplored in asthma.

Objective: To determine gene expression profiles over time in nasal epithelial cells (NECs) challenged in vivo with rhinovirus-16 (RV16) and compare to nasal symptoms and viral clearance.

Methods: Patients with stable mild to moderate asthma (n = 20) were challenged intranasally with RV16.

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO).

Survey of isolation room equipment and resources in an academic hospital.

Purpose: The purpose of this paper, a point prevalence study, is to quantify the incidence of isolation and identify the type of communicable diseases in isolation. The paper evaluates isolation precaution communication, availability of personal protective equipment (PPE) as well as other equipment necessary for maintaining isolation precautions.

Design/methodology/approach: A standardised audit tool was developed in accordance with the National Standards for the Prevention and Control of Healthcare Associated Infections (May 2009).

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials.

Purpose: Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR.

Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota.

Background: There is currently a lack of experimental evidence for horizontal gene transfer (HGT) mechanisms in the human gut microbiota. The aim of this study was therefore to experimentally determine the HGT potential in the microbiota of a healthy preterm infant twin pair and to evaluate the global occurrence of the mobilized elements.

Methods: Stool samples were collected.

Anti-virulence potential of 2-hydroxy-4-methoxybenzaldehyde against methicillin-resistant Staphylococcus aureus and its clinical isolates.

Burgeoning antibiotic resistance among bacterial pathogens necessitates the alternative treatment options to control the multidrug-resistant bacterial infections. Plant secondary metabolites, a significant source of structurally diverse compounds, posses several biological activities. The present study was designed to investigate the anti-virulence potential of least explored phytocompound 2-hydroxy-4-methoxybenzaldehyde (HMB) against methicillin-resistant Staphylococcus aureus (MRSA) and its clinical isolates.

Potential applications of the quantitative susceptibility mapping (QSM) in MR-guided radiation therapy.

Magnetic resonance-guided radiation therapy (MR-GRT) offers great potential to improve radiation treatment outcomes by providing more accurate and patient-tailored therapy. Despite superior soft tissue contrast in MRI, one of the challenges towards MRI-only workflows is that the process often requires some sort of 'MR-invisible' metal-based devices. In this study, the feasibility of quantitative susceptibility mapping (QSM) for visualization of some MR-invisible radiation therapy devices was studied.

Effect of intracameral human cord blood-derived stem cells on lasered rabbit trabecular meshwork.

Background: This study aimed to investigate the effect of intracameral human cord blood stem cells on lasered rabbit trabecular meshwork.

Methods: Immediately following diode laser application to the trabecular meshwork, human cord blood stem cells were injected intracamerally, in one eye of 12 albino rabbits. The other eye of ten rabbits was lasered controls and two eyes were normal controls.

Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy.

Purpose: To explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.

Materials And Methods: Eligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials.

Aims: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored.

Neutrophilic inflammation in asthma and defective epithelial translational control.

Neutrophilic inflammation in asthma is associated with interleukin (IL)-17A, corticosteroid-insensitivity and bronchodilator-induced forced expiratory volume in 1 s (FEV) reversibility. IL-17A synergises with tumour necrosis factor (TNF)-α in the production of the neutrophil chemokine CXCL-8 by primary bronchial epithelial cells (PBECs).We hypothesised that local neutrophilic inflammation in asthma correlates with IL-17A and TNF-α-induced CXCL-8 production by PBECs from asthma patients.

A Convolutional Neural Network for the Detection of Asynchronous Steady State Motion Visual Evoked Potential.

A key issue in brain-computer interface (BCI) is the detection of intentional control (IC) states and non-intentional control (NC) states in an asynchronous manner. Furthermore, for steady-state visual evoked potential (SSVEP) BCI systems, multiple states (sub-states) exist within the IC state. Existing recognition methods rely on a threshold technique, which is difficult to realize high accuracy, i.

Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): Results from a prospective clinical trial.

Purpose: Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions.

Methods: Patients had low or intermediate risk prostate cancer.

Absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) appears predictive of disease control after high dose rate brachytherapy and external beam radiotherapy in intermediate risk prostate cancer.

Background And Purpose: To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome.

Materials And Methods: 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports.

The control of microbially induced corrosion by methyl eugenol - A dietary phytochemical with quorum sensing inhibitory potential.

The development of biofilms by microorganisms is conventionally attributed to microbially induced corrosion on stainless steel surfaces and leads to severe consequences in industrial and environmental settings. Since bacterial biofilm formation is regulated by the signal mediated quorum sensing (QS) system, targeting biofilms through QS inhibitors will possibly control biologically induced corrosion on the metal surface. In this study, biofilm formation on 316L stainless steel (SS 316L) immersed in a natural pond water system was effectively inhibited in the presence of the QS inhibitor methyl eugenol, as evidenced through epifluorescence microscopy, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) analyses.

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study.

Purpose: High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.