Notes

Linear lucency in the brain container: Break or perhaps accessory skull suture.
A recently developed, open source toolbox was used for slow wave visualization and detection. BGB324 Slow waves were confirmed to be significantly smaller in FDRs compared to the control group. Additionally, several traveling parameters were analyzed. Traveled distances were found to be significantly reduced in FDRs, whereas origins showed a different topographical pattern of distribution from control subjects. In contrast, local speed did not differ between groups. Overall, these results suggest that slow wave traveling might be a viable method to study pathological conditions interfering with brain connectivity. BACKGROUND Posterior cingulate cortex (PCC) is a key aspect of the default mode network (DMN). Aberrant PCC functional connectivity (FC) is implicated in schizophrenia, but the potential for PCC related changes as biological classifier of schizophrenia has not yet been evaluated. METHODS We conducted a data-driven approach using resting-state functional MRI data to explore differences in PCC-based region- and voxel-wise FC patterns, to distinguish between patients with first-episode schizophrenia (FES) and demographically matched healthy controls (HC). Discriminative PCC FCs were selected via false discovery rate estimation. A gradient boosting classifier was trained and validated based on 100 FES vs. 93 HC. Subsequently, classification models were tested in an independent dataset of 87 FES patients and 80 HC using resting-state data acquired on a different MRI scanner. RESULTS Patients with FES had reduced connectivity between PCC and frontal areas, left parahippocampal regions, left anterior cingulate cortex, and right inferior parietal lobule, but hyperconnectivity with left lateral temporal regions. Predictive voxel-wise clusters were similar to region-wise selected brain areas functionally connected with PCC in relation to discriminating FES from HC subject categories. Region-wise analysis of FCs yielded a relatively high predictive level for schizophrenia, with an average accuracy of 72.28% in the independent samples, while selected voxel-wise connectivity yielded an accuracy of 68.72%. CONCLUSION FES exhibited a pattern of both increased and decreased PCC-based connectivity, but was related to predominant hypoconnectivity between PCC and brain areas associated with DMN, that may be a useful differential feature revealing underpinnings of neuropathophysiology for schizophrenia. INTRODUCTION Context processing deficiencies have been established in patients with schizophrenia and it has been proposed that these deficiencies are involved in the formation of positive symptoms. METHOD We administered a temporal context discrimination task to 60 schizophrenia patients and 60 healthy individuals. Pictures were presented in two sessions separated by half an hour and the participants were required to remember afterwards whether the pictures had been presented in the first or the second session. RESULTS The number of temporal context errors was significantly increased in the patient group. link2 More specifically, it was highly significantly increased in a subgroup of patients presenting hallucinations, while the patients without hallucinations were equivalent to the healthy individuals. Regression analyses revealed that, independently of memory of the pictures themselves, verbal and visual hallucinations, as well as thought disorganisation, were associated with more temporal context errors. In contrast, affective flattening and anhedonia were associated with fewer of these errors. CONCLUSION Inability to process or remember the temporal context of production of events might be a mechanism underlying both hallucinations and thought disorganisation. The categorical approach to defining schizophrenia spectrum disorders requires meeting established criteria. To advance early identification and intervention in young people, the field has progressed to studying help-seeking individuals who are at clinical high risk based on subthreshold psychosis spectrum symptoms, and criteria have been articulated for qualifying individuals as at risk. A broader dimensional examination of psychosis has been applied to population-based studies on non-help seekers. This review highlights the ascertainment and assessment approaches to such population-based studies. Most studies are cross-sectional and rely on questionnaires with limited overlap of tools. However, several consistent findings emerge on symptoms, neurocognitive deficits, and neuroimaging parameters and other biomarkers associated with emergence and persistence of psychotic features. The findings are consistent with the literature on abnormalities associated with schizophrenia, including the presence of neurocognitive deficits; abnormalities in brain structure, function, and connectivity that are related to distress; impairment; and functional outcome. These findings support the validity of studying psychosis experiences during development in a way that can chart the emergence of psychosis in the context of general psychopathology. Such studies are necessary for establishing developmental trajectories that characterize this emergence and for identifying risk and resilience biomarkers moderating or modulating the full range of schizophrenia-related manifestations. More community-based studies are needed, with better standardization and harmonization of measures and incorporating longitudinal follow-up, to establish mechanistic links between cellular-molecular aberrations and specific manifestations of psychosis as envisioned by the precision medicine agenda. BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed antihypertensive agents. Intriguingly, case reports and clinical trials have indicated that ACEIs, including captopril and lisinopril, may have a rapid mood-elevating effect in certain patients, but few experimental studies have investigated their value as fast-onset antidepressants. METHODS The present study consisted of a series of experiments using biochemical assays, immunohistochemistry, and behavioral techniques to examine the effect and mechanism of captopril on depressive-like behavior in 2 animal models, the chronic unpredictable stress model and the chronic social defeat stress model. RESULTS Captopril (19.5 or 39 mg/kg, intraperitoneal injection) exerted rapid antidepressant activity in mice treated under the chronic unpredictable stress model and mice treated under the chronic social defeat stress model. Pharmacokinetic analysis revealed that captopril crossed the blood-brain barrier and that lisinopril, another ACEI with better blood-brain barrier permeability, exerted a faster and longer-lasting effect at a same molar equivalent dose. This antidepressant effect seemed to be independent of the renin-angiotensin system, but dependent on the bradykinin (BK) system, since the decreased BK detected in the stressed mice could be reversed by captopril. The hypofunction of the downstream effector of BK, Cdc42 (cell division control protein 42) homolog, contributed to the stress-induced loss of dendritic spines, which was rapidly reversed by captopril via activating the mTORC1 (mammalian target of rapamycin complex 1) pathway. CONCLUSIONS Our findings indicate that the BK-dependent activation of mTORC1 may represent a promising mechanism underlying antidepressant pharmacology. Considering their affordability and availability, ACEIs may emerge as a novel fast-onset antidepressant, especially for patients with comorbid depression and hypertension. AIMS To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. RESULTS Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P less then 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P less then 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. CONCLUSIONS Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements. OBJECTIVE To develop a drug-eluting polymer film which can be easily personalized and rapidly made on the electrode array of a cochlear implant during surgery. METHODS A precursor solution was prepared with poly lactic-co-glycolic acid (PLGA) and trichloromethane. Using a dip-coating method, the silicone electrode array (HiFocus 1J, Advanced Bionics) was coated in polymer film produced from the precursor solution containing one of three drugs dexamethasone sodium phosphate (DSP), cytosine arabinoside hydrochloride (Ara-C), or nicotinamide adenine dinucleotide (NAD), and the release of these drugs from the polymer film was studied. The drug-eluting film on the electrode array was analyzed by environmental scanning electron microscopy (ESEM). link3 The water contact angle and the impedance of the electrode array were measured before and after coating. Drug release kinetics was evaluated in a quasi-stationary release model, using high performance liquid chromatography every 24 h for 15 days. RESULTS Five electrode arrcation for clinical use in cochlear implantation. The chemotherapeutic efficacy of paclitaxel against hypoxic tumors is usually unsatisfactory, which is partially due to the so-called hypoxia-induced drug resistance. The mechanism of hypoxia-induced resistance is primarily associated with hypoxia-inducible factor 1α (HIF-1α), which is an oxygen-sensitive transcriptional activator coordinating the cellular response to hypoxia. Apigenin is a natural occurring HIF-1α inhibitor that can suppress the expression of HIF-1α through multiple pathways and reverse the hypoxia-induced resistance found in cancer cells. Here we report that the use of apigenin can suppress the HIF-1α expression in hypoxic tumors through the simultaneous inhibition of the AKT/p-AKT pathway and HSP90, which is beneficial for enhancing the anticancer activity of the co-administered paclitaxel. The potential synergistic effect of apigenin and paclitaxel was further validated on HepG2 cell line and tumor-bearing mouse models.
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