Bilateral choroidal effusions after taking acetazolamide for altitude sickness.

A fit and healthy 44-year-old woman took a single dose of oral acetazolamide (125 mg) in preparation for a hiking trip to Everest base camp. She awoke the next morning with profoundly blurred distance vision. She presented to eye casualty later that morning, approximately 18 hours postingestion: examination demonstrated myopia and bilateral choroidal effusions. Acetazolamide is used to minimise symptoms of altitude sickness. Rarely, its use can be linked with ophthalmic side effects, such as myopia. A handful of case reports also describe choroidal effusions secondary to its use as part of ophthalmic treatment (eg, postoperatively). This is the first reported case in which choroidal effusions have been demonstrated as a side effect of its prophylactic use against altitude sickness.

Lower eyelid involutional entropion following cataract surgery.

OBJECTIVES: To determine whether cataract surgery is associated with an increased risk of subsequent lower eyelid entropion and evaluate potential associated factors. METHODS: This retrospective cohort study included consecutive patients undergoing first eye cataract surgery over a 10-year period at a single institution (n = 14,574). The fellow phakic eye served as control. Patient records were evaluated up until either the time of second eye cataract surgery or any other intraocular or adnexal surgery. The primary outcome was the rate of entropion repair in both the pseudophakic (exposed) group and the phakic control group. Groups were compared using relative risk and Kaplan-Meier analysis. Multivariate logistic regression was used to compare pre-specified characteristics of those patients that underwent entropion repair in their pseudophakic eye with those that did not. RESULTS: A fourfold higher relative risk of undergoing entropion repair was observed in eyes that had undergone cataract surgery compared with the fellow unoperated eye (95% confidence interval 1.6-9.8; P < 0.001) with an increased risk at all timepoints between 1 and 12 years according to Kaplan-Meier analysis (P = 0.001). Median time to entropion repair after cataract surgery was 58 months (range 3-124). Documented intraoperative patient factors such as patient or eye movement, eyelid squeezing, pain or anxiety were an independent risk factor for subsequent entropion (P < 0.0001). CONCLUSIONS: Cataract surgery is associated with an increased risk of subsequent lower eyelid entropion. Surgeons should be aware of this risk in the pre- and post-operative assessment of patients undergoing cataract surgery.

Reactivation of herpes simplex keratitis following vaccination for COVID-19.

An 82-year-old man with a history of herpes simplex keratitis 40 years previously presented with recurrence, 1 day following vaccination for novel COVID-19. His condition worsened despite topical treatment with ganciclovir gel. A diagnosis of herpetic stromal keratitis was made, requiring systemic aciclovir, topical prednisolone, moxifloxacin and atropine, and oral doxycycline. He improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from 6/36 corrected at presentation, to 6/24 following treatment. Clearly, public and personal health benefits from vaccination are hugely important and we would not suggest avoiding vaccination in such patients. It is, however, important for ophthalmic providers to be aware of the rare potential for reactivation of herpetic eye disease following vaccination to enable prompt diagnosis and treatment.

Pseudophakic negative dysphotopsia and intraocular lens orientation: a prospective double-masked randomized controlled trial.

PURPOSE: To determine whether horizontal orientation of the intraocular lens optic-haptic junctions has an effect on the incidence of pseudophakic negative dysphotopsia. METHODS: Single-centre prospective double-masked randomized controlled trial. 220 eyes of 201 participants undergoing routine cataract surgery were randomized to receive their intraocular lens either orientated with the optic-haptic junctions at 180° ('horizontal') or without manipulation following implantation (control). Patients were excluded according to age (<19 and > 99 years), coexisting eye disease affecting visual function and insufficient cognitive function to complete the study. In the fourth postoperative week, a telephone interview was conducted to determine rates of negative dysphotopsia. The data were analysed to provide the relative risk of negative dysphotopsia with horizontal orientation of the intraocular lens (IOL) optic-haptic junctions compared with standard treatment. RESULTS: Orientating the IOL optic-haptic junctions horizontally halved the incidence of pseudophakic negative dysphotopsia in the fourth postoperative week (9/110 in the intervention group; 18/110 in the control group; RR: 0.50, 95% confidence interval: 0.235-1.064, p = 0.072). The overall incidence of negative dysphotopsia was 12.2% (27/220 participating eyes). No intraoperative adverse effects of intraocular lens rotation were reported. CONCLUSION: The simple intraoperative manoeuvre of rotating the intraocular lens to orientate the optic-haptic junctions at 180° may be a safe and effective measure to reduce the risk of developing postoperative pseudophakic negative dysphotopsia in the first postoperative month. This is the first report that demonstrates the benefit of horizontal optic-haptic junction positioning to be sustained beyond the first postoperative day.

Comparative performance reports in anaesthesia: impact on clinical outcomes and acceptability to clinicians.

In anaesthesia, the use of comparative performance reports, their impact on patient care and their acceptability is yet to be fully clarified. Since April 2010, postoperative data on theatre cases in our trust have been analysed and individual comparative performance reports distributed to anaesthetists. Our primary aim was to investigate whether this process was associated with improvement in overall patient care. A short survey was used to assess our secondary aim, the usefulness and acceptability of the process. There were significant improvements in the odds of all outcomes other than vomiting: 39% improvement in hypothermia (p<0.001); 9.9% improvement in severe pain (p<0.001%); 9.6% improvement in moderate pain (p<0.001); 5.3% improvement in percentage pain free (p=0.04); 9.7% improvement in nausea (p=0.02); 30% improvement in unexpected admissions (p=0.001). 100% of consultant respondents agreed that performance reports prompted reflective practice and that this process had the potential to improve patient care. The provision of comparative performance reports was thus associated with an improvement in outcomes while remaining acceptable to the anaesthetists involved.

Growing up with a father with PTSD: The family emotional climate of the children of Australian Vietnam veterans.

A non-clinical sample of male Australian Vietnam veterans, their wives, and adult offspring were interviewed in-person in a national epidemiological study to assess the relationship between the mental ill-health of veterans and the emotional climate of the family while the children were growing up. Veterans were assessed 17 years before their children using standardised psychiatric diagnostic interviews. Family emotional climate was assessed using offspring ratings of parental attachment, and codings of positive and negative family relationship styles based on five minute speech samples provided by the offspring. Sons and daughters had different views of their mothers and fathers, and were less positive towards their fathers particularly if he had posttraumatic stress disorder (PTSD). Veteran PTSD and depression significantly negatively impacted the family emotional climate, while mothers' mental health was not related. Veteran PTSD symptoms were lowest in secure attachment to the veteran and highest in inconsistent attachment for both sons and daughters, but were not related to attachment to the mother. Veteran PTSD was related to daughters' but not sons' perceptions of family emotional climate. The impact of veterans' PTSD on their families' emotional climate is more marked for daughters than sons.

Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance.

The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behavioral (anxiety and activity) outcomes with 94%-100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO), a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT), and behavior while reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity.

Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome.

Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD) feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J) and relative resistance (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.

Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia.

BACKGROUND: In the orbitofrontal cortex (OFC), reduced gray matter volume and reduced glutamic acid decarboxylase 67kDa isoform (GAD67) messenger (m)RNA are found in schizophrenia; however, how these alterations relate to developmental pathology of interneurons is unclear. The present study therefore aimed to determine if increased interstitial white matter neuron (IWMN) density exists in the OFC; whether gamma-aminobutyric acid (GABA)ergic neuron density in OFC white matter was altered; and how IWMN density may be related to an early-expressed inhibitory neuron marker, Dlx1, in OFC gray matter in schizophrenia. METHODS: IWMN densities were determined (38 schizophrenia and 38 control subjects) for neuronal nuclear antigen (NeuN+) and 65/67 kDa isoform of glutamic acid decarboxylase immunopositive (GAD65/67+) neurons. In situ hybridization was performed to determine Dlx1 and GAD67 mRNA expression in the OFC gray matter. RESULTS: NeuN and GAD65/67 immunopositive cell density was significantly increased in the superficial white matter in schizophrenia. Gray matter Dlx1 and GAD67 mRNA expression were reduced in schizophrenia. Dlx1 mRNA levels were negatively correlated with GAD65/67 IWMN density. CONCLUSIONS: Our study provides evidence that pathology of IWMNs in schizophrenia includes GABAergic interneurons and that increased IWMN density may be related to GABAergic deficits in the overlying gray matter. These findings provide evidence at the cellular level that the OFC is a site of pathology in schizophrenia and support the hypothesis that inappropriate migration of cortical inhibitory interneurons occurs in schizophrenia.

Increased interstitial white matter neuron density in the dorsolateral prefrontal cortex of people with schizophrenia.

BACKGROUND: Interstitial white matter neurons (IWMNs) may reflect immature neurons that migrate tangentially to the neocortex from the ganglionic eminence to form cortical interneurons. Alterations of interneuron markers have been detected in gray matter of dorsolateral prefrontal cortex in schizophrenia, and IWMNs are also reported to be altered in schizophrenia. In this study, we considered whether a potential link exists between these two pathological findings. METHODS: From a cohort of 29 schizophrenia subjects and 37 control subjects, IWMN densities were determined in the dorsolateral prefrontal cortex by counting neuronal nuclear antigen (NeuN) and somatostatin (SST)-positive cells. Double-label immunofluorescence was carried out to determine the overlap between SST+/NeuN+ and SST+/neuropeptide Y + neurons. RESULTS: We found that density of NeuN + IWMNs in superficial white matter is significantly increased in schizophrenia subjects compared with control subjects. There was a significant negative correlation between SST mRNA expression in gray matter and NeuN + IWMN density. In schizophrenic patients with increased NeuN IWMN density, the density of SST-expressing neurons in white matter was also higher compared with control subjects. A subpopulation of SST immunopositive cells also show coexpression of neuropeptide Y. CONCLUSIONS: Our study confirmed previous results indicating that the density of NeuN + IWMNs is increased in superficial white matter in schizophrenia. We provide the first evidence that increased IWMN density correlates with a gray matter interneuron deficit, suggesting that migration of interneurons from white matter to the cortex may be deficient in some patients with schizophrenia, consistent with an interneuron deficit in schizophrenia.

Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice.

Insulin resistance plays a central role in type 2 diabetes and obesity, which develop as a consequence of genetic and environmental factors. Dietary changes including high fat diet (HFD) feeding promotes insulin resistance in rodent models which present useful systems for studying interactions between genetic background and environmental influences contributing to disease susceptibility and progression. We applied a combination of classical physiological, biochemical and hormonal studies and plasma (1)H NMR spectroscopy-based metabonomics to characterize the phenotypic and metabotypic consequences of HFD (40%) feeding in inbred mouse strains (C57BL/6, 129S6, BALB/c, DBA/2, C3H) frequently used in genetic studies. We showed the wide range of phenotypic and metabonomic adaptations to HFD across the five strains and the increased nutrigenomic predisposition of 129S6 and C57BL/6 to insulin resistance and obesity relative to the other strains. In contrast mice of the BALB/c and DBA/2 strains showed relative resistance to HFD-induced glucose intolerance and obesity. Hierarchical metabonomic clustering derived from (1)H NMR spectral data of the strains provided a phylometabonomic classification of strain-specific metabolic features and differential responses to HFD which closely match SNP-based phylogenetic relationships between strains. Our results support the concept of genomic clustering of functionally related genes and provide important information for defining biological markers predicting spontaneous susceptibility to insulin resistance and pathological adaptations to fat feeding.

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice.

Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (129S6) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by (1)H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-N-oxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.