A Comparison of Frailty Assessment Instruments in Different Clinical and Social Care Settings: The Frailtools Project.

Objective: To determine which of 8 commonly employed frailty assessment tools demonstrate the most appropriate characteristics to be employed in different clinical and social settings.

Design: Cross-sectional multicenter European-based study.

Setting And Participants: 1440 patients aged ≥75 years evaluated in geriatric inpatient wards, geriatric outpatient clinics, primary care clinics, and nursing homes.

Optical coherence tomography confirms shunt malfunction and recurrence of raised intracranial pressure in optic atrophy.

Background: Investigating potential cerebrospinal fluid (CSF) shunt malfunction can be a challenge. Optical coherence tomography (OCT), a non-invasive imaging technique, is used to monitor changes at the optic nerve head in papilloedema. Conventional teaching suggests that in the presence of optic atrophy the optic nerve head may not re-swell in response to a relapse in raised intracranial pressure (ICP).

A Comparison of Patient-Reported Outcome Measures of Quality of Life By Dialysis Modality in the Treatment of Kidney Failure: A Systematic Review.

Background: There is an increasing demand to incorporate patient-reported outcome measures (PROMs) such as quality of life (QOL) in decision-making when selecting a chronic dialysis modality.

Objective: To compare the change in QOL over time among similar patients on different dialysis modalities to provide unique and novel insights on the impact of dialysis modality on PROMs.

Design: Systematic reviews, randomized controlled trials, and nonrandomized controlled trials were examined via a comprehensive search strategy incorporating multiple bibliographic databases.

11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension.

Background: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH).

Estrogens and development of the mouse and human external genitalia.

The Jost hypothesis states that androgens are necessary for normal development of the male external genitalia. In this review, we explore the complementary hypothesis that estrogens can elicit abnormal development of male external genitalia. Herein, we review available data in both humans and mice on the deleterious effects of estrogen on external genitalia development, especially during the "window of susceptibility" to exogenous estrogens.

Using Optical Coherence Tomography as a Surrogate of Measurements of Intracranial Pressure in Idiopathic Intracranial Hypertension.

Importance: There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging.

Objective: To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP.

Design, Setting, And Participants: This longitudinal cohort study used data collected from 3 randomized clinical trials that were conducted between April 1, 2014, and August 1, 2019.

Long-term surveys of age structure in 13 ungulate and one ostrich species in the Serengeti, 1926-2018.

The Serengeti ecosystem spans an extensive network of protected areas in Tanzania, eastern Africa, and a UNESCO Wold Heritage Site. It is home to some of the largest animal migrations on the planet. Here, we describe a dataset consisting of the sample counts of three age classes (infant, juvenile and adult) of 13 ungulate and one ostrich species.

Structure, Function, and Therapeutic Use of IgM Antibodies.

Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain.

New insights into the genetic basis of premature ovarian insufficiency: Novel causative variants and candidate genes revealed by genomic sequencing.

Ovarian deficiency, including premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR), represents one of the main causes of female infertility. POI is a genetically heterogeneous condition but current understanding of its genetic basis is far from complete, with the cause remaining unknown in the majority of patients. The genes that regulate DOR have been reported but the genetic basis of DOR has not been explored in depth.

Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension.

Background: Headache is the dominant factor for quality of life related disability in idiopathic intracranial hypertension (IIH) and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet clinical need.

Case Series: We report a series of seven patients in whom headaches were the presenting feature of IIH and the headaches had migraine-like characteristics, as is typical in many IIH patients.

Preserving Mobility in Older Adults with Physical Frailty and Sarcopenia: Opportunities, Challenges, and Recommendations for Physical Activity Interventions.

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade.

Characteristics of patients with diabetes hospitalised for COVID-19 infection-a brief case series report.

Objectives: Diabetes has been shown to be a risk factor for corona virus disease-2019 (COVID-19) infection. The characteristics of patients with diabetes vulnerable to this infection are less specified. We aim to present the characteristics of patients with diabetes admitted to hospital with COVID-19.

11β-Hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial.

Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension.

Diabetes in ageing: pathways for developing the evidence base for clinical guidance.

Older adults with diabetes are heterogeneous in their medical, functional, and cognitive status, and require careful individualisation of their treatment regimens. However, in the absence of detailed information from clinical trials involving older people with varying characteristics, there is little evidence-based guidance, which is a notable limitation of current approaches to care. It is important to recognise that older people with diabetes might vary in their profiles according to age category, functional health, presence of frailty, and comorbidity profiles.

Krill Oil Has Different Effects on the Plasma Lipidome Compared with Fish Oil Following 30 Days of Supplementation in Healthy Women: A Randomized Controlled and Crossover Study.

This is a follow-up of our previous postprandial study and it focused on the plasma lipidomic responses to 30 days of krill oil (KO) versus fish oil (FO) supplementations in healthy women. Eleven women (aged 18-50 years) consumed KO or FO for 30 days in a randomized, cross-over study, with at least a four-week washout period between supplementations. The daily supplements provided 1.

Blunted nutrient-response pathways in adipose tissue following high fat meals in men with metabolic syndrome: A randomized postprandial transcriptomic study.

Background: Excessive adipose tissue is central to disease burden posed by the Metabolic Syndrome (MetS). Whilst much is known of the altered transcriptomic regulation of adipose tissue under fasting conditions, little is known of the responses to high-fat meals.

Methods: Nineteen middle-aged males (mean ± SD 52.

New hypoglycaemic therapy in frail older people with diabetes mellitus-phenotypic status likely to be more important than functional status.

Frail older people are largely excluded from clinical trials and therefore glycaemic targets and optimum hypoglycaemic therapy in this group has not been fully investigated. Guidelines generally recommend tight glycaemic control in functionally fit individuals and relaxed targets in frail ones mainly due to the fear of hypoglycaemia. The newly introduced sodium glucose cotransporter-2 inhibitors and the glucagon like peptide-1 receptor agonists have shown benefit that is independent of glycaemic control and a minimal risk of hypoglycaemia.

Reviewing the Recent Developments in Idiopathic Intracranial Hypertension.

There is increasing evidence and appreciation of idiopathic intracranial hypertension (IIH) in medicine. The pathological processes underlying raised intracranial pressure are being studied, with new insights found in both hormonal dysregulation and the metabolic neuroendocrine axis. These will potentially lead to novel therapeutic targets for IIH.

Challenges and Strategies for Diabetes Management in Community-Living Older Adults.

The prevalence of diabetes is increasing, especially in older people, mainly because of an increase in life expectancy. The number of comorbidities also increases with increasing age, leading to a unique diabetes phenotype in old age that includes vascular disease, physical and neuropathic complications, and mental dysfunction. These three categories of complications appear to have a synergistic effect that can lead to a vicious cycle of deterioration into disability.

Cardiometabolic disease in the older person: prediction and prevention for the generalist physician.

Ageing is associated with chronic inflammation and oxidative stress that increase the risk of cardiovascular disease. Frailty and sarcopenia, which are associated with increased visceral obesity and muscle mass loss, are now emerging as new potential risk factors for cardiovascular disease. Increased muscle visceral fat leads to increased secretion of harmful proinflammatory adipokines and reduced muscle mass leads to reduced secretion of the protective myokines creating an abnormal cardiometabolic state increasing the risk of cardiovascular disease.

Synthesis and Initial Evaluation of a Novel Fluorophore for Selective FMDV 3C Protease Detection.

The development and evaluation of a Boc-AL(Boc)Q(Trt)-AMC fluorophore to detect 3C Protease, produced by Foot and Mouth Disease Virus (FMDV) is reported, with a view to a potential use as a rapid screen for FMDV infected livestock The peptide-linked conjugate fluorophore is evaluated in vitro for sensitivity, specificity, stability and rapidity and shows statistically significant increases in fluorescence when exposed to physiologically relevant concentrations of 3C Protease and selectivity when compared with other common proteases likely to be located, typically in the absence of FMDV. The stability of deprotected Boc-AL(Boc)Q(Trt)-AMC is reported as a limitation of this probe.

Closed-minded cognition: Right-wing authoritarianism is negatively related to belief updating following prediction error.

When confronted with information that challenges our beliefs, we must often learn from error in order to successfully navigate the world. Past studies in reinforcement learning and educational psychology have linked prediction error, a measure of surprise, to successful learning from feedback. However, there are substantial individual differences in belief-updating success, and the psychological factors that influence belief updating remain unclear.

Molecular determinants for dsDNA translocation by the transcription-repair coupling and evolvability factor Mfd.

Mfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongation is impeded. Depending on impediment severity, this action results in either transcription termination or elongation rescue, which rely on ATP-dependent Mfd translocation on DNA. Due to its role in antibiotic resistance, Mfd is also emerging as a prime target for developing anti-evolution drugs.

Emerging themes in idiopathic intracranial hypertension.

Purpose: Idiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets.