Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study.

Diagnostic laboratories are currently required to provide routine testing of asymptomatic staff and patients as a part of their clinical screening for SARS-CoV-2 infection. However, these cohorts display very different disease prevalence from symptomatic individuals and testing capacity for asymptomatic screening is often limited. Group testing is frequently proposed as a possible solution to address this; however, proposals neglect the technical and operational feasibility of implementation in a front-line diagnostic laboratory.

Refeeding syndrome as described in 1507 by Antonio Benivieni in Florence.

In 1981, Weinsier and Krumdieck described death resulting from overzealous total parenteral nutrition in two chronically malnourished, but stable, patients given aggressive total parenteral nutrition. This was the birth of what is now called the refeeding syndrome, a nutrition-related disorder associated with severe electrolyte disturbances. The purpose of this work is to demonstrate that refeeding syndrome was first described medically in Florence by Antonio Benivieni in 1507 in his book On Some Hidden and Remarkable Causes of Diseases and Cures.

Carmelo Giordano (1930-2016): a giant in Nephrology.

Carmelo Giordano (Carmine, Louis, Joseph Giordano) was born in Naples on August 23, 1930 in the house of Rafael and Anna Tirone He received the MD cum laude in 1954. He was Fellow and assistant to Professor Flaviano Magrassi and studied nephrology at the Peter Bent Brigham Hospital, University of Harvard in Boston, under the guidance of John P. Merrill (1958-1960).

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD.

Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.

Background: Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC detection system called CTCscope. This method detects a multitude of tumour-specific markers at single-cell level in blood.

Dasatinib and chronic myeloid leukemia: two-year follow-up in eight clinical trials.

Imatinib is currently regarded as the best initial treatment for patients with chronic myeloid leukemia (CML). However, a significant proportion of patients who relapse, fail to respond, or develop intolerance might benefit from the use of second-generation tyrosine kinase inhibitors. In this review, we report the 2-year results in 8 clinical trials involving more than 2000 patients treated with dasatinib (phases I-III).

Homocysteine-induced endoplasmic reticulum protein (herp) is up-regulated in parkinsonian substantia nigra and present in the core of Lewy bodies.

Background: Recent studies highlight the role of endoplasmic reticulum (ER) stress and aberrant protein degradation in the pathogenesis of neurodegenerative disorders. Herp which is encoded by the HERPUD 1 (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1) gene is a stress-response protein localized in the ER membrane of neurons and other cell types. Herp has been suggested to improve ER-folding, decrease ER protein load, and participate in ER-associated degradation (ERAD) of proteins.

Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)--a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen.

Background: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen.

Patients And Methods: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment.

Does a rise in the BCR-ABL1 transcript level identify chronic phase CML patients responding to imatinib who have a high risk of cytogenetic relapse?

BCR-ABL1 transcript numbers were monitored in 161 patients who started treatment with imatinib early after diagnosis of chronic myeloid leukaemia in chronic phase and achieved complete cytogenetic responses (CCyR). A confirmed doubling in BCR-ABL1/ABL1 transcript levels was found to be a significant factor for predicting loss of CCyR [relative risk (RR) 8.3, P < 0.

European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor.

The majority of patients with chronic myeloid leukemia in chronic phase gain substantial benefit from imatinib but some fail to respond or lose their initial response. In 2006, the European LeukemiaNet published recommendations designed to help identify patients responding poorly to imatinib. Patients were evaluated at 3, 6, 12, and 18 months and some were classified as "failure" or "suboptimal responders.

DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in parkinsonian astrocytes.

DnaJ/Hsp40 chaperones determine the activity of Hsp70s by stabilizing their interaction with substrate proteins. We have predicted, based on the in silico analysis of a brain-derived whole-genome transcriptome data set, an increased expression of DnaJ/Hsp40 homologue, subfamily B, member 6 (DnaJB6) in Parkinson's disease (PD; Moran et al. [2006] Neurogenetics 7:1-11).

Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression.

Purpose: Kinase domain (KD) mutations in the BCR-ABL gene are associated with resistance to imatinib in chronic myeloid leukemia (CML) but their incidence and prognostic significance in chronic phase (CP) patients without resistance are unclear.

Patients And Methods: We analyzed outcome for 319 patients with CML-CP who were treated with imatinib; 171 were in early CP (ECP) and 148 were in late CP (LCP). Patients were screened routinely for mutations using direct sequencing regardless of response status.

Striatal beta-amyloid deposition in Parkinson disease with dementia.

Dementia is common in Parkinson disease (PD), although its anatomic and pathologic substrates remain undefined. Recently, striatal abnormalities in Lewy body diseases have been described, but their clinical relevance is not clear. Thirty PD cases from the United Kingdom Parkinson's Disease Society Tissue Bank were grouped as demented (PDD; n = 16) and nondemented (PD; n = 14) based on a review of clinical records.

Towards a pathway definition of Parkinson's disease: a complex disorder with links to cancer, diabetes and inflammation.

We have previously established a first whole genome transcriptomic profile of sporadic Parkinson's disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature.

The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease: a critical analysis of alpha-synuclein staging.

Aims: It has been proposed that alpha-synuclein (alpha Syn) pathology in Parkinson's disease (PD) spreads in a predictable caudo-rostral way with the earliest changes seen in the dorsal motor nucleus of the vagus nerve (DMV). However, the reliability of this stereotypical spread of alpha Syn pathology has been questioned. In addition, the comparative occurrence of alpha Syn pathology in the spinal cord and brain has not been closely studied.

Neuronal pentraxin II is highly upregulated in Parkinson's disease and a novel component of Lewy bodies.

Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in the Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson's disease (PD). NPTX2 is also known as the neuronal activity-regulated protein (Narp), which is secreted and involved in long-term neuronal plasticity.

In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib.

We sought kinase domain (KD) mutations at the start of treatment with dasatinib in 46 chronic myeloid leukemia (CML) patients resistant to or intolerant of imatinib. We identified BCR-ABL mutant subclones in 12 (26%) cases and used pyrosequencing to estimate subsequent changes in their relative size after starting dasatinib. Four patients lost their mutations, which remained undetectable, 3 patients retained the original mutation or lost it only transiently, 3 lost their original mutations but acquired a new mutation (F317L), and 2 developed another mutation (T315I) in addition to the original mutation within the same subclone.

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

Background: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival.

Methods: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period.

Microglia in gemistocytic astrocytomas.

Objective: Although gemistocytic astrocytomas are graded as World Health Organization II astrocytomas, they behave more aggressively than other astrocytomas. Their proliferative potential is low, and it remains an intriguing question why these tumors are so biologically "successful." They show a high mutation rate of the P53 gene, cytological abnormalities, and frequent perivascular mononuclear infiltrates.

The medial and lateral substantia nigra in Parkinson's disease: mRNA profiles associated with higher brain tissue vulnerability.

Sporadic Parkinson's disease (PD) is characterized by progressive death of dopaminergic neurons within the substantia nigra. However, pathological cell death within this nucleus is not uniform. In PD, the lateral tier of the substantia nigra (SNl) degenerates earlier and more severely than the more medial nigral component (SNm).

Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra.

The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN).

The microglial gene regulatory network activated by interferon-gamma.

We have analysed the microglial pathway stimulated by interferon-gamma (IFN-gamma) using an in silico approach employing a database of eukaryotic molecular interactions and a microarray dataset validated by quantitative real-time PCR (qRT-PCR). Following IFN-gamma stimulation, production of neuroprotective factors by microglia was found to be reduced while caspase 1 and serping1 which are involved in cell death cascades are up-regulated suggesting a safeguarding mechanism. Extracellular matrix interactions and intracellular protein degradation are altered in concert with these changes.

Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration.

The concept of gliodegenerative diseases has not been widely established although there is accumulating evidence that glial cells may represent a primary target of degenerative disease processes. In the central nervous system (CNS), examples that provide a "proof of concept" include at least one alpha-synucleinopathy, multiple system atrophy (MSA), but this disease is conventionally discussed under the heading of "neurodegeneration". Additional evidence in support of primary glial affection has been reported in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and transmissible spongiform encephalopathies.

Vulnerable patients with a fractured neck of femur: nutritional status and support in hospital.

Background And Aim: Malnutrition has serious consequences for recovery and increases the risk of complications in hospital patients. Fractured neck of femur (NOF) patients may be particularly at risk because of their old age and frail state of health. We conducted an observational study to evaluate the nutritional state and the nutritional support, which was provided to this group during their stay in hospital.