MiRNAs as novel adipokines : obesity-related circulating MiRNAs influence chemosensitivity in cancer patients

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes

A twin study of cilioretinal arteries, tilted discs and situs inversus

PURPOSE: To establish the prevalence and heritability of cilioretinal arteries (CRAs), tilted discs (TDs) and situs inversus (SI). METHODS: Fundus photos from the Twins UK Adult Twin registry twin database were analyzed: 1812 individuals, 526 complete monozygotic (MZ) twin pairs and 336 complete dizygotic (DZ) pairs. Images were assessed non-stereoscopically on a computer screen by the same ophthalmologist for presence of CRAs, TDs or SI. Prevalence figures, probandwise concordances and heritabilities were calculated. RESULTS: Prevalence of a CRA in subjects’ right eyes was 28.6% (26.5–30.8). Prevalence of subjects with a CRA in at least one eye was 45.0% (42.6–47.5), with a TD in at least one eye was 1.2% (0.8–1.9), and with SI at least one eye was 0.5% (0.3–1.0). There was no association between birth weight and presence of CRA. Concordance for CRA in at least one eye (MZ twins) was 60% (95% CI 55–64), and (DZ) was 45% (95% CI 39–51). Heritability for CRAs in at least one eye was 49.4% (95% CI 38.1–59.7) and for both eyes was 32.9% (95% CI 10.4–53.3). We were unable to calculate meaningful heritabilities or concordances for TDs and situs SI, due to insufficient numbers. CONCLUSIONS: The presence of CRAs appears to be moderately heritable, with greater variance explained by individual environmental factors or even stochastic events. They were not associated with low birth weight. Future genetic research and studies of birth/lifecourse cohorts may offer further insights into the etiology of congenital papillovascular abnormalities

Exploratory Study of the Association between the Severity of Idiopathic Intracranial Hypertension and Electroretinogram Photopic Negative Response Amplitude Obtained Using a Handheld Device

The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal electroretinography. This study explored the use of a handheld device (RETeval, LKC technologies, Gaithersburg, MD, USA) in 72 IIH patients of varying stages and severity (and seven controls) and investigated associations between PhNR parameters and disease severity. PhNR amplitudes at 72 ms (P72) and p-ratio (ratio to b-wave peak value) differed significantly across groups, with a trend towards smaller amplitudes in those with severe IIH, defined as papilloedema with Modified Frisén Scale (MFS) ≥ 3, retinal nerve fibre layer (RNFL) ≥ 150 μm or atrophic papilloedema (p = 0.0048 and p = 0.018 for P72 and p-ratio, respectively). PhNR parameters did not correlate with MFS, RNFL thickness, standard automated perimetry mean deviation or macular ganglion cell layer volume. This study suggests that PhNR measurement using a handheld device is feasible and could potentially augment the assessment of disease severity in IIH. The clinical utility of PhNR monitoring in IIH patients requires further investigation

Prevalence, Concordance, and Heritability of Vitreomacular Interface Abnormalities in a Twin Study

PURPOSE: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). METHODS: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. RESULTS: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40–89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4–16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0–22.7), and VMA was diagnosed in 11.8% (10.8–13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6–52.8) for ERM, 53.2% (95% CI = 41.8–63.2) for PVD, and 48.1% (95% CI = 33.6–58) for VMA. CONCLUSIONS: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis

The impact of urgency of umbilical hernia repair on adverse outcomes in patients with cirrhosis: a population-based cohort study from England

\ua9 2023, The Author(s). Introduction: Umbilical hernia is common in patients with cirrhosis; however, there is a paucity of dedicated studies on postoperative outcomes in this group of patients. This population-based cohort study aimed to determine the outcomes after emergency and elective umbilical hernia repair in patients with cirrhosis. Methods: Two linked electronic healthcare databases from England were used to identify all patients undergoing umbilical hernia repair between January 2000 and December 2017. Patients were grouped into those with and without cirrhosis and stratified by severity into compensated and decompensated cirrhosis. Length of stay, readmission, 90-day case fatality rate and the odds ratio of 90-day postoperative mortality were defined using logistic regression. Results: In total, 22,163 patients who underwent an umbilical hernia repair were included and 297 (1.34%) had cirrhosis. More patients without cirrhosis had an elective procedure, 86% compared with 51% of those with cirrhosis (P < 0.001). In both the elective and emergency settings, patients with cirrhosis had longer hospital length of stay (elective: 0 vs 1 day, emergency: 2 vs 4 days, P < 0.0001) and higher readmission rates (elective: 4.87% vs 11.33%, emergency:11.39% vs 29.25%, P < 0.0001) than those without cirrhosis. The 90-day case fatality rates were 2% and 0.16% in the elective setting, and 19% and 2.96% in the emergency setting in patients with and without cirrhosis respectively. Conclusion: Emergency umbilical hernia repair in patients with cirrhosis is associated with poorer outcomes in terms of length of stay, readmissions and mortality at 90 days

Effect of donepezil on transcranial magnetic stimulation parameters in Alzheimer's disease

INTRODUCTION: There is a need for a reliable, noninvasive biomarker for Alzheimer's disease (AD). We assessed whether short-latency afferent inhibition (SAI), a transcranial magnetic stimulation paradigm that assesses cholinergic circuits of the brain, could become such a biomarker. METHODS: Nineteen patients with AD underwent four SAI testing sessions. The timing of their usual donepezil dose was altered to create different cholinergic states for each session. This was compared to the SAI results from 20 healthy subjects. RESULTS: SAI was not able to distinguish the different cholinergic states assessed in our study. There appeared to be a diurnal variation in cholinergic function in the control group, which was not present in the AD cohort. DISCUSSION: SAI does not appear to have a role in diagnosis and assessment of AD patients. The loss of diurnal variation, however, warrants further investigation as it may provide further biochemical insights about AD

The Association of Ambient Air Pollution With Cataract Surgery in UK Biobank Participants: Prospective Cohort Study

Purpose: Air pollution is associated with chronic diseases of later life. Cataract is the most common cause of blindess globally. It is biologically plausible that cataract risk is increased by pollution exposure. Therefore, the relationship between air pollution and incident cataract surgery was examined. Methods: This was a prospective, observational study involving 433,727 UK Biobank participants. Ambient air pollution measures included particulates, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Outdoor air pollution was estimated based on land use regression models. Participants undergoing cataract surgery in either eye were ascertained via data linkage to the National Health Service procedure statistics. Those undergoing cataract surgery within 1 year of baseline assessment and those reporting cataract at baseline were excluded. Cox proportional hazards models were used to examine the associations between air pollutants and incident cataract surgery, adjusting for sociodemographic and lifestyle factors. Results: There were 16,307 incident cases of cataract surgery. Higher exposure to PM2.5 was associated with a 5% increased risk of incident cataract surgery (per interquartile range [IQR] increase). Compared to the lowest quartile, participants with exposures to PM2.5, NO2, and NOx in the highest quartile were 14%, 11%, and 9% more likely to undergo cataract surgery, respectively. A continuous exposure-response relationship was observed, with the likelihood of undergoing cataract surgery being progressively higher with greater levels of PM2.5, NO2, and NOx (P for trend P < 0.001). Conclusions: Although the results of our study showed a 5% increased risk of future cataract surgery following an exposure to PM2.5, NO2, and NOx, the effect estimates were relatively small. Further research is required to determine if the associations identified are causal

Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study

PURPOSE: To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK. METHODS: U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40-69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview. RESULTS: Fifty four percent of participants aged 40-69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40-44 years increasing to 46% at 65-69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White). CONCLUSIONS: Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study