Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer's disease.

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer's disease (AD). In this study, we quantified the in vivo expression of the endoplasmic reticulum stress marker, sigma 1 receptor (S1R), using [C]SA4503 positron emission tomography (PET), the mitochondrial complex I (MC1) with [F]BCPP-EF, and the presynaptic vesicular protein SV2A with [C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and cerebral blood flow (CBF) measured with magnetic resonance imaging arterial spin labeling.

Out-of-Field Doses Produced by a Proton Scanning Beam Inside Pediatric Anthropomorphic Phantoms and Their Comparison With Different Photon Modalities.

Since 2010, EURADOS Working Group 9 (Radiation Dosimetry in Radiotherapy) has been involved in the investigation of secondary and scattered radiation doses in X-ray and proton therapy, especially in the case of pediatric patients. The main goal of this paper is to analyze and compare out-of-field neutron and non-neutron organ doses inside 5- and 10-year-old pediatric anthropomorphic phantoms for the treatment of a 5-cm-diameter brain tumor. Proton irradiations were carried out at the Cyclotron Centre Bronowice in IFJ PAN Krakow Poland using a pencil beam scanning technique (PBS) at a gantry with a dedicated scanning nozzle (IBA Proton Therapy System, Proteus 235).

Prevention of Orthopedic Prosthetic Infections Using Evidence-Based Surgical Site Infection Care Bundles: A Narrative Review.

The number of primary/revision total joint replacements (TJR) are expected to increase substantially with an aging population and increasing prevalence of comorbid conditions. The 30-day re-admission rate, in all orthopedic specialties, is 5.4% (range, 4.

Infection after ureteroscopy for ureteric stones: analysis of 71 305 cases in the Hospital Episode Statistics database.

Objectives: To investigate the burden of infectious complications following ureteroscopy (URS) for ureteric stones on a national level in England using data from the Hospital Episodes Statistics (HES) data warehouse.

Materials And Methods: A retrospective cohort was identified and followed up in HES during the period April 2013 to March 2020 for all procedure codes relating to ureteroscopic stone treatment (M27.1, M27.

Transcriptome profiling of kisspeptin neurons from the mouse arcuate nucleus reveals new mechanisms in estrogenic control of fertility.

Kisspeptin neurons in the mediobasal hypothalamus (MBH) are critical targets of ovarian estrogen feedback regulating mammalian fertility. To reveal molecular mechanisms underlying this signaling, we thoroughly characterized the estrogen-regulated transcriptome of kisspeptin cells from ovariectomized transgenic mice substituted with 17β-estradiol or vehicle. MBH kisspeptin neurons were harvested using laser-capture microdissection, pooled, and subjected to RNA sequencing.

Recovering staff, recovering services: massive-online support for recovering a paediatric service using Lean and compassionate communication.

The COVID-19 pandemic has infected tens of millions worldwide. Healthcare systems have been stretched caring for the most seriously ill and healthcare workers have struggled to maintain non-COVID services leading to backlogs.Strategies proposed to support the recovery of backlogs include additional administration support; waiting list data validation; enhanced patient communication; and use of systematic improvement methods to make rapid incremental improvements.

Research priorities for autosomal dominant polycystic kidney disease: a UK priority setting partnership.

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney condition, accounting for 7%-10% of patients with kidney failure. Fundamental basic science and clinical research on ADPKD is underway worldwide but no one has yet considered which areas should be prioritised to maximise returns from limited future funding. The Polycystic Kidney Disease Charity began a priority setting partnership with the James Lind Alliance (JLA) in the UK in 2019-2020 to identify areas of uncertainty in the ADPKD care pathway and allow patients, carers and healthcare professionals to rank the 10 most important questions for research.

Structural variants shape the genomic landscape and clinical outcome of multiple myeloma.

Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes.

Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project.

Purpose: Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+.

Spontaneous partial recovery of striatal dopaminergic uptake despite nigral cell loss in asymptomatic MPTP-lesioned female minipigs.

The Göttingen minipig is a large animal with a gyrencephalic brain that expresses -complex behavior, making it an attractive model for Parkinson's disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1-2 mg/kg of MPTP, and two with saline, three times a week over four weeks.

Investigating the veracity of a sample of divergent published trial data in spinal pain.

Evidence-based medicine is replete with studies assessing quality and bias, but few evaluating research integrity or trustworthiness. A recent Cochrane review of psychological interventions for chronic pain identified trials with a shared lead author with highly divergent results. We sought to systematically identify all similar trials from this author to explore their risk of bias, governance procedures, and trustworthiness.

A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk.

A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death.

In vivo vesicular acetylcholine transporter density in human peripheral organs: an [F]FEOBV PET/CT study.

Background: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects.

Coblation intracapsular tonsillectomy: A cohort study of NHS practice in England using Hospital Episode Statistics.

Objectives: To identify paediatric intracapsular Coblation tonsillectomy procedures from routine administrative data in England, and determine their safety.

Design: Retrospective observational cohort study of four ENT centres using routine data from Hospital Episode Statistics (HES).

Setting: Acute NHS trusts in England conducting exclusively intracapsular Coblation tonsillectomy.

Antimicrobial therapies for prevention of recurrent acute exacerbations of COPD (AECOPD): beyond the guidelines.

Background: Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators.

Factors determining development of researchers within a research network on cancer diagnosis in primary care (CanTest): an interview study.

Objectives: Developing connections with other researchers in a network, learning informally through these connections and using them to reach goals, is expected to increase research capacity and strengthen performance. So far, this has not been empirically demonstrated. We assessed what and how network collaboration adds to development of researchers.

Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension.

NT-proBNP (N-terminal pro-brain natriuretic peptide), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH.

Identifying the outcomes important to men with hypogonadism: A qualitative evidence synthesis.

Objective: Men with male hypogonadism (MH) experience sexual dysfunction, which improves with testosterone replacement therapy (TRT). However, randomised controlled trials provide little consensus on functional and behavioural symptoms in hypogonadal men; these are often better captured by qualitative information from individual patient experience.

Methods: We systematically searched major electronic databases to identify qualitative data from men with hypogonadism, with or without TRT.

Mid-regional proadrenomedullin (MR-proADM), C-reactive protein (CRP) and other biomarkers in the early identification of disease progression in patients with COVID-19 in the acute NHS setting.

Aims: There is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), procalcitonin, mid-regional proadrenomedullin (MR-proADM) and white cell count to support prediction of clinical outcomes.

Methods: 135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via reverse-transcription-qPCR were included.