Utilizing an Ex Vivo Skin Penetration Analysis Model for Predicting Ocular Drug Penetration: A Feasibility Study with Curcumin Formulations.

Unlabelled: This study aimed to investigate the feasibility of using the digital image processing technique, developed to semi-quantitatively study dermal penetration, to study corneal penetration in an ex vivo porcine eye model. Here, we investigated various formulation strategies intended to enhance dermal and corneal bioavailability of the model hydrophobic drug, curcumin.

Methods: Several formulation principles were explored, including oily solutions, oily suspensions, aqueous nanosuspension, micelles, liposomes and cyclodextrins.

Development of transferosomes for topical ocular drug delivery of curcumin.

Background: Transferosomes (TFS) are ultra-deformable elastic bilayer vesicles that have previously been used to enhance gradient driven penetration through the skin. This study aimed to evaluate the potential of TFS for topical ocular drug delivery and to compare their penetration enhancing properties in different ocular tissues.

Methods: Curcumin-loaded TFS were prepared using Tween 80 as the edge activator.

A new predictive coding model for a more comprehensive account of delusions.

Attempts to understand psychosis-the experience of profoundly altered perceptions and beliefs-raise questions about how the brain models the world. Standard predictive coding approaches suggest that it does so by minimising mismatches between incoming sensory evidence and predictions. By adjusting predictions, we converge iteratively on a best guess of the nature of the reality.

The association between -methyl-d-aspartate receptor availability and glutamate levels: A multi-modal PET-MR brain imaging study in first-episode psychosis and healthy controls.

Background: Evidence from post-mortem studies and in vivo imaging studies suggests there may be reduced -methyl-d-aspartate receptor (NMDAR) levels in the hippocampus in patients with schizophrenia. Other studies have reported increased glutamate in striatum in schizophrenia patients. It has been hypothesised that NMDAR hypofunction leads to the disinhibition of glutamatergic signalling; however, this has not been tested in vivo.

Psychedelics and schizophrenia: Distinct alterations to Bayesian inference.

Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs.

A cross-sectional MR study of body fat volumes and distribution in chronic schizophrenia.

People with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using magnetic resonance imaging (MRI).

Could Reducing Body Fatness Reduce the Risk of Aggressive Prostate Cancer via the Insulin Signalling Pathway? A Systematic Review of the Mechanistic Pathway.

Excess body weight is thought to increase the risk of aggressive prostate cancer (PCa), although the biological mechanism is currently unclear. Body fatness is positively associated with a diminished cellular response to insulin and biomarkers of insulin signalling have been positively associated with PCa risk. We carried out a two-pronged systematic review of (a) the effect of reducing body fatness on insulin biomarker levels and (b) the effect of insulin biomarkers on PCa risk, to determine whether a reduction in body fatness could reduce PCa risk via effects on the insulin signalling pathway.

The magnitude and variability of brain structural alterations in bipolar disorder: A double meta-analysis of 5534 patients and 6651 healthy controls.

Background: Bipolar disorder is thought to be associated with structural brain alterations, but findings have been inconsistent. Our double meta-analysis investigated the variability and magnitude of differences in regional brain volumes in patients with bipolar disorder relative to healthy volunteers.

Methods: Databases were systematically searched for MRI studies reporting regional brain volumetric measures in patients with bipolar disorder and controls.

Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis.

Importance: Ketamine hydrochloride is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like or psychotomimetic symptoms. Despite this risk, the consistency and magnitude of symptoms induced by ketamine or what factors are associated with these symptoms remain unknown.

Objective: To conduct a meta-analysis of the psychopathological outcomes associated with ketamine in healthy volunteers and patients with schizophrenia and the experimental factors associated with these outcomes.

Associations of Serum Dickkopf-1 and Sclerostin With Cardiovascular Events: Results From the Prospective Bruneck Study.

Background Dickkopf-1 and sclerostin have been implicated in atherosclerosis and vascular calcification. We aimed to quantify the association of their serum levels with incident cardiovascular disease (CVD) in the general population. Methods and Results Among 706 participants of the prospective, population-based Bruneck Study, mean±SD of serum levels were 44.

Magnitude and heterogeneity of brain structural abnormalities in 22q11.2 deletion syndrome: a meta-analysis.

The 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder associated with a number of volumetric brain abnormalities.

Cardiac structure and function in schizophrenia: cardiac magnetic resonance imaging study.

Background: Heart disease is the leading cause of death in schizophrenia. However, there has been little research directly examining cardiac function in schizophrenia.

Aims: To investigate cardiac structure and function in individuals with schizophrenia using cardiac magnetic resonance imaging (CMR) after excluding medical and metabolic comorbidity.

Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis.

Two important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases.

Heterogeneity of Striatal Dopamine Function in Schizophrenia: Meta-analysis of Variance.

Background: It has been hypothesized that dopamine function in schizophrenia exhibits heterogeneity in excess of that seen in the general population. However, no previous study has systematically tested this hypothesis.

Methods: We employed meta-analysis of variance to investigate interindividual variability of striatal dopaminergic function in patients with schizophrenia and in healthy control subjects.

Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study.

Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls.

A Meta-analysis of Immune Parameters, Variability, and Assessment of Modal Distribution in Psychosis and Test of the Immune Subgroup Hypothesis.

Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naïve first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters.

Heterogeneity and Homogeneity of Regional Brain Structure in Schizophrenia: A Meta-analysis.

Importance: Schizophrenia is associated with alterations in mean regional brain volumes. However, it is not known whether the clinical heterogeneity seen in the disorder is reflected at the neurobiological level, for example, in differences in the interindividual variability of these brain volumes relative to control individuals.

Objective: To investigate whether patients with first-episode schizophrenia exhibit greater variability of regional brain volumes in addition to mean volume differences.

Low SpO2 With Normal SaO2 During General Anesthesia: A Case Report.

A 25-year-old Caucasian man with a history of spherocytosis, splenectomy, recurrent blood transfusion, and no cardiopulmonary disease presented for an emergent laparoscopic cholecystectomy with a baseline pulse oximetric saturation (SpO2) of 88% while breathing room air. The SpO2 increased to only 89% during preoxygenation with an FIO2 1.0.

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.

Background: The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

Methods: In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration.

Anterior cingulate glutamate levels related to clinical status following treatment in first-episode schizophrenia.

Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment.

Use of buprenorphine in children with chronic pseudoobstruction syndrome: case series and review of literature.

Objectives: Abdominal pain is the most challenging symptom in chronic intestinal pseudoobstruction (CIPO) syndrome, because of its severity and the limited availability of suitable opioid formulations, especially in pediatric patients with digestive problems. Most of the children with CIPO cannot tolerate oral formulations.

Case Reports: We present 4 cases of children with CIPO and severe intractable abdominal pain, and report on the use of a recently available form of opioid, transdermal buprenorphine in a dosage of 5 mcg/h.

Proton magnetic resonance spectroscopy and illness stage in schizophrenia--a systematic review and meta-analysis.

Background: It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to determine which brain regions show the most robust reductions in NAA first episode and chronic schizophrenia as measured by proton magnetic resonance spectroscopy and to determine whether these changes are present in individuals at high risk of developing schizophrenia.

Methods: We identified 131 articles, of which 97 met inclusion criteria.

Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo.

Background: gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. GABA(B) receptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABA(B) receptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABA(B) receptors is unclear.

Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain.

Pain is one of the most severe and debilitating symptoms associated with several forms of cancer. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves. Despite recent advances, the molecular mechanisms underlying the development and maintenance of cancer-evoked pain are not well understood.