Immune predictors of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.

Background: Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) can derive great benefit from immune checkpoint inhibitors (ICI). However not all responses and predictors of primary resistance are lacking.

Methods: We compared the immune tumor microenvironment of MMRd EC ICI-responders (Rs) and ICI non-responders (NRs), using spatial multiplexed immune profiling and unsupervised hierarchical clustering analysis.

The cortical neurophysiological signature of amyotrophic lateral sclerosis.

The progressive loss of motor function characteristic of amyotrophic lateral sclerosis is associated with widespread cortical pathology extending beyond primary motor regions. Increasing muscle weakness reflects a dynamic, variably compensated brain network disorder. In the quest for biomarkers to accelerate therapeutic assessment, the high temporal resolution of magnetoencephalography is uniquely able to non-invasively capture micro-magnetic fields generated by neuronal activity across the entire cortex simultaneously.

Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy.

Purpose: This study investigates changes in CD8+ cells, CD8+/Foxp3 ratio, HLA I expression, and immune coregulator density at diagnosis and upon neoadjuvant chemotherapy (NACT), correlating changes with clinical outcomes.

Experimental Design: Multiplexed immune profiling and cell clustering analysis were performed on paired matched ovarian cancer samples to characterize the immune tumor microenvironment (iTME) at diagnosis and under NACT in patients enrolled in the CHIVA trial (NCT01583322).

Results: Several immune cell (IC) subsets and immune coregulators were quantified pre/post-NACT.

The septate junction component bark beetle is required for intestinal barrier function and homeostasis.

Age-related loss of intestinal barrier function has been documented across species, but the causes remain unknown. The intestinal barrier is maintained by tight junctions (TJs) in mammals and septate junctions (SJs) in insects. Specialized TJs/SJs, called tricellular junctions (TCJs), are located at the nexus of three adjacent cells, and we have shown that aging results in changes to TCJs in intestines of adult .

Limited value of serum neurofilament light chain in diagnosing amyotrophic lateral sclerosis.

A biomarker specific for the diagnosis of amyotrophic lateral sclerosis must be sensitive across a spectrum of clinical heterogeneity. Neurofilament light chain levels in amyotrophic lateral sclerosis correlate with the rate of disability progression. Previous attempts to establish a diagnostic role for neurofilament light chain have been limited to comparison with healthy individuals or controls with alternative diagnoses unlikely to be confused with amyotrophic lateral sclerosis in real-world clinical practice.

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times.

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand.

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.

The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis ( = 258), other neurological diseases ( = 80) and healthy control participants ( = 101), were recruited and followed at intervals of 3-6 months for up to 30 months.

Genetic testing in motor neurone disease.

A minority (10%-15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance.

A nudge towards better lumbar puncture practice.

Background: Despite a body of evidence demonstrating reduced incidence of post-lumbar puncture headache associated with pencil-point (vs bevelled-edge) needles, their use remains variable in the UK.

Methods: A multimodal longitudinal intervention was performed over a 12-month period at a tertiary neurology referral centre. In addition to simulation training using pencil-point needles and an electronic documentation pro forma, a change in the default needles presented in clinical environments was performed.

Therapeutic non-invasive brain stimulation in amyotrophic lateral sclerosis: rationale, methods and experience.

The neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) is characterised by increased cortical excitability, thought to reflect pathological changes in the balance of local excitatory and inhibitory neuronal influences. Non-invasive brain stimulation (NIBS) has been shown to modulate cortical activity, with some protocols showing effects that outlast the stimulation by months. NIBS has been suggested as a potential therapeutic approach for disorders associated with changes in cortical neurophysiology, including ALS.

The relationship of perivascular adipose tissue and atherosclerosis in the aorta and carotid arteries, determined by magnetic resonance imaging.

Background And Aims: Imaging studies have relied on the 'overall' volumetric quantification of perivascular adipose tissue. We sought to assess the relationship of circumferential distribution between perivascular adipose tissue and adjacent wall thickness of carotid and aortic arteries using dedicated magnetic resonance imaging sequences.

Methods: Vessel wall and perivascular adipose tissue were acquired using magnetic resonance imaging (1.

Methods for detecting Gemmata spp. bacteremia in the microbiology laboratory.

Objective: Gemmata bacteria are fastidious, Gram-negative and aerobic. The only representatives are Gemmata obscuriglobus and Gemmata massiliana. These Planctomycetes appear to be a part of human digestive tract microbiome, and G.

INJURIES IN QUIDDITCH: A DESCRIPTIVE EPIDEMIOLOGICAL STUDY.

Background: Quidditch is a fast growing, physically intense, mixed-gender full-contact sport. Originally adapted from Harry Potter novels, quidditch was first played in 2005 in the USA but is now played worldwide. It is essential to elucidate patterns of injury for the safety and growth of the sport of quidditch.

Vascular tortuosity in relationship with hypertension and posterior fossa volume in hemifacial spasm.

Background: Hemifacial spasm (HFS) is a disabling neurological condition. Vascular tortuosity in HFS patients has not been quantified objectively and its relationship with hypertension and posterior fossa volume (PF) is unknown. In a case control magnetic resonance imaging and angiographic (MRI/A) study, we quantified and compared the vascular tortuosity in HFS and controls, and evaluated its relationship with hypertension and PF.

A church-based diet and physical activity intervention for rural, lower Mississippi Delta African American adults: Delta Body and Soul effectiveness study, 2010-2011.

Introduction: Obesity, diabetes, and hypertension have reached epidemic levels in the largely rural Lower Mississippi Delta (LMD) region. We assessed the effectiveness of a 6-month, church-based diet and physical activity intervention, conducted during 2010 through 2011, for improving diet quality (measured by the Healthy Eating Index-2005) and increasing physical activity of African American adults in the LMD region.

Methods: We used a quasi-experimental design in which 8 self-selected eligible churches were assigned to intervention or control.

Detection of cytomegalovirus antigens in phagocytosed serum complexes from a patient with rheumatoid arthritis, vasculitis, peripheral neuropathy, cutaneous ulceration, and digital gangrene.

A patient with rheumatoid arthritis, vasculitis, peripheral neuropathy, cutaneous ulceration, and digital gangrene was studied. Circulating immune complexes were detected by C1q binding although serum complement levels were within the normal range. Immunofluorescent staining of buffy coat cells with specific antisera showed the presence of IgG and IgM in phagocytosed inclusions but complement C3 was not detected.

The burden of chronic illness in local authority residential homes for the elderly.

A survey of all Part III residential homes in the Central and Southern area of Liverpool Health District examined the diagnoses and medication of 331 residents. A heavy burden of chronic illness was observed with cardio-vascular, psychiatric and orthopaedic problems being the most prevalent. Of the top 10 diagnoses, accounting for over half of all conditions, all disease instances required monitoring of their response to treatment.

Do polyclonal rheumatoid factors carry an 'internal image' of cytomegalovirus, Epstein-Barr virus and nuclear antigens?

Rabbit antisera have been prepared against isolated rheumatoid factors (RF's). It was considered that RFs are anti-idiotype antibodies and that the anti-RF antisera had anti-anti-idiotype specificity. Furthermore, it was considered that the RF's carry an "internal image" of the putative "antigen X" and that the rabbit antisera would have specificity for this "antigen-X".

Determining drug-drug interactions and related effects on microcomputers.

Algorithms for determining drug-drug interactions are described. They handle all the generic drugs in the British National Formulary (BNF) (Number 5, British Medical Association and Pharmaceutical Society of Great Britain, 1984) and allow these drugs to be identified by generic or trade name. They also accept and identify interactions for compound drugs prescribed by a single trade name.

A comparison of the reactivity and immunogenicity of RA 27/3 strain rubella vaccine prepared in WI-38 or MRC5 human diploid cells.

The immunogenicity and clinical reactivity of rubella vaccine derived from WI-38 or MRC5 human diploid cells was compared in 125 seronegative adolescent females. Seroconversion rates, assessed by single radial haemolysis testing of paired pre- and post-vaccination samples exceeded 98% (56/57 and 68/68 vaccinees, respectively) for both vaccines. Quantitative assessment of rubella-specific antibodies in 53 post-vaccination sera by an ELISA technique also failed to reveal any difference in immunogenicity between the vaccines.

The impact of a rubella prevention policy on the outcome of rubella in pregnancy.

Surveillance of rubella vaccination in schoolgirls has continued intensively in Edinburgh since 1970. Screening for rubella antibody of all women attending antenatal clinics has been available since 1974. The analysis of cases of rubella occurring in pregnancy during an outbreak in 1979 confirmed the efficacy of schoolgirl vaccination in the city but indicated poor implementation of postnatal vaccination.