Preserving GABAergic interneurons in acute brain slices of mice using the N-methyl-<Emphasis Type="Italic">D</Emphasis>-glucamine-based artificial cerebrospinal fluid method

Defects in the function and development of GABAergic interneurons have been linked to psychiatric disorders, so preservation of these interneurons in brain slices is important for successful electrophysiological recording in various ex vivo methods. However, it is difficult to maintain the activity and morphology of neurons in slices from mice of >30 days old. Here we evaluated the N-methyl-D-glucamine(NMDG)-based artificial cerebrospinal fl uid(a CSF) method for the preservation of interneurons in slices from mice of up to ~6 months old and discussed the steps that may affect their quality during slicing. We found that the NMDG-a CSF method rescued more cells than sucrose-a CSF and successfully preserved different types of interneurons including parvalbumin- and somatostatin-positive interneurons. In addition, both the chemical and electrical synaptic signaling of interneurons were maintained. These results demonstrate that the NMDG-a CSF method is suitable for the preservation of interneurons, especially in studies of gap junctions.     

Using breast radiographers' reports as a second opinion for radiologists' readings of microcalcifications in digital mammography

Objective:

The aim of this study was to investigate a practical method for incorporating radiographers'' reports with radiologists'' readings of digital mammograms.

Methods:

This simulation study was conducted using data from a free-response receiver operating characteristic observer study obtained with 75 cases (25 malignant, 25 benign and 25 normal cases) of digital mammograms. Each of the rating scores obtained by six breast radiographers was utilized as a second opinion for four radiologists'' readings with the radiographers'' reports. A logical “OR” operation with various criteria settings was simulated for deciding an appropriate method to select a radiographer''s report in all combinations of radiologists and radiographers. The average figure of merit (FOM) of the radiologists'' performances was statistically analysed using a jackknife procedure (JAFROC) to verify the clinical utility of using radiographers'' reports.

Results:

Potential improvement of the average FOM of the radiologists'' performances for identifying malignant microcalcifications could be expected when using radiographers'' reports as a second opinion. When the threshold value of 2.6 in Breast Imaging-Reporting and Data System (BI-RADS®) assessment was applied to adopt/reject a radiographer''s report, FOMs of radiologists'' performances were further improved.

Conclusion:

When using breast radiographers'' reports as a second opinion, radiologists'' performances potentially improved when reading digital mammograms. It could be anticipated that radiologists'' performances were improved further by setting a threshold value on the BI-RADS assessment provided by the radiographers.

Advances in knowledge:

For the effective use of a radiographer''s report as a second opinion, radiographers'' rating scores and its criteria setting for adoption/rejection would be necessary.The number of mammography examinations has been increasing. In general, double reading by two radiologists is recommended in many countries, resulting in a shortage of radiologists. In order to solve this problem, the use of computer-aided detection (CADe) systems and/or reporting by radiographers as a second opinion for radiologists'' readings have been investigated. Since many research groups have demonstrated the clinical usefulness of various CADe systems,^1–6 CADe is accepted as the standard of care in the USA and is used in approximately 75% of screening examinations.^6,7 On the other hand, reporting by radiographers has been recommended as another approach to aid radiologists'' readings in several countries.^8–10 Although the use of CADe requires initial costs for introducing CADe systems, reporting by radiographers can be applied in almost all medical institutions without any additional facility costs. However, the practical utilization of radiographers'' reports has not been established because radiographers'' reading skills vary and owing to the insufficient evaluation of diagnostic accuracy provided by utilizing radiographers'' reports.The basic concept of “reporting by radiographers” was first developed by The College of Radiographers in 1997.⁸ Since the first practical guidance on reporting by radiographers was published, there have been a number of publications related to reporting by radiographers in the past decade, mainly in the UK.^10–14 To utilize radiographers'' reports more practically, a new reading protocol, double reading by two radiographers, was suggested. This reading protocol is a double reading using “non-discordant radiographer only (double) readings”, in which concordant cases are automatically recalled for assessment and discordant cases (where two readers disagree over an interpretation) are arbitrated by an experienced radiologist or breast clinician.¹⁵ Several studies confirmed the benefits of reporting by radiographers in screening mammograms, including cost effectiveness benefits.^16–20 Although a radiographer''s report is expected to be a substitute for one of the radiologists in a double-reading situation, questions remain, such as how to utilize a radiographer''s report in the most effective manner, as well as how to provide the best services to the patient without loss of quality.For reporting by radiographers to be effective, i.e., the highest cancer detection rate and the lowest recall rate, it is necessary to investigate the acceptance criteria to adopt or reject a radiographer''s report, as well as the acceptable performance level of a radiographer''s report. The aim of this study was to investigate a practical method on how a radiologist would adopt or reject a report provided by a single radiographer and to demonstrate the potential usefulness of radiologists reading digital mammograms utilizing radiographers'' reports. We used an existing free-response receiver operating characteristic (FROC) observer study^21,22 data set to simulate all possible combinations for evaluating radiologists'' performances with and without radiographers'' reports.     

Assessment of occult pancreatobiliary reflux in patients with pancreaticobiliary disease by ERCP

Background The aim of this study was to evaluate the degree of occult pancreatobiliary reflux by measuring the biliary amylase levels in the common bile duct (CBDA) and gallbladder (GBA) at endoscopic retrograde cholangiopancreatography (ERCP).Methods Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with pancreatobiliary maljunction (PBM) were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in 8 cases.Results Twenty-two cases (26%) revealed a CBDA level higher than serum amylase (high bile amylase level, HBA group) and 64 cases exhibited a CBDA level lower than serum (LBA group). The mean values of CBDA in the HBA and LBA groups were 5502IU/l and 29IU/l, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and those with choledocholithiasis (P < 0.05). Three cases (16%) showed a CBDA greater than twice the GBA. Eleven cases (58%) exhibited a GBA higher than the CBDA. The values of GBA obtained during ERCP and cholecystectomy were consistent.Conclusions These findings suggest that even non-PBM cases can exhibit occult pancreatobiliary reflux, which can thereby cause biliary disease.     

Comparison of three different approaches in the treatment of chronic low back pain

Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain, spinal mobility, disability, psychological state, and aerobic capacity. Sixty patients with chronic low back pain were randomized to three groups: group 1, aerobic exercise + home exercise; group 2, physical therapy (hot pack, ultrasound, TENS) + home exercise; group 3, home exercise only. Spinal mobility, pain severity, disability, and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up. Aerobic capacities of the patients were measured before and after treatment. All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up, and there was no significant difference between the groups. In group 2, a significant decrease in Beck Depression Inventory scores was observed with treatment. At 1-month follow-up, group 1 and 2 showed significant decreases in General Health Assessment Questionnaire scores. In group 2, there was also a significant improvement in Roland Morris Disability scores. There were similar improvements in exercise test duration and the MET levels in all the three groups. All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain. On the other hand, physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance.     

Secondary prevention of cryptogenic stroke in patients with patent foramen ovale: a systematic review and meta-analysis

The aim of our study is to compare patent foramen ovale (PFO) closure versus medical treatment and antiplatelet versus anticoagulant therapy in patients with cryptogenic stroke (CS) and PFO. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) of randomized trials. Primary outcomes are stroke or transient ischemic attack (TIA) and all-cause mortality. Secondary outcomes are peripheral embolism, bleeding, serious adverse events, myocardial infarction and atrial dysrhythmias. We performed an intention to treat meta-analysis with a random-effects model. We include six trials (3677 patients, mean age 47.3 years, 55.8% men). PFO closure is associated with a lower recurrence of stroke or TIA at a mean follow-up of 3.88 years compared to medical therapy [risk ratio (RR) 0.55, 95% CI 0.38–0.81; I²?=?40%]. The TSA confirms this result. No difference is found in mortality (RR 0.74, 95% CI 0.35–1.60; I²?=?0%), while PFO closure is associated with a higher incidence of atrial dysrhythmias (RR 4.55, 95% CI 2.16–9.60; I²?=?25%). The rate of the other outcomes is not different among the two groups. The comparison between anticoagulant and antiplatelet therapy shows no difference in terms of stroke recurrence, mortality and bleeding. There is conclusive evidence that PFO closure reduces the recurrence of stroke or TIA in patients younger than 60 years of age with CS. More data are warranted to assess the consequences of the increase in atrial dysrhythmias and the advantage of PFO closure over anticoagulants.     

Contrast agents for MRI

Molecular imaging is a rapidly growing field with the potential to revolutionize cardiovascular medicine by shifting diagnostic focus from functional abnormalities which occur late in a disease process to the biochemical events which precipitate the earliest stages of disease. MRI is a modality well suited to this task as it allows a variety of contrast mechanisms for detection of epitopes of interest, as well as high-resolution anatomical localization and functional information. In this review, we discuss the widerange of available molecular MRI contrast agents and their application to diseases such as atherosclerosis, thrombus imaging, and stem cell tracking, along with opportunities for molecularly targeted drug delivery.     

Serotonin mediates PGE<Subscript>2</Subscript> overexpression through 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in serum-free tissue culture of macrophage-like synovial cells

Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 muM serotonin and/or the antagonists ketanserin (5-HT(2A)), tropisetron (5-HT(3)) and parecoxib (COX-2). Prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT(2A) and 5-HT(3) receptors, and COX-2. PGE(2) in the supernatants increased by 261.2% +/- 56.7 (mean +/- SEM; P = 0.007) in response to serotonin. TNF-alpha, IL-1beta and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE(2). The serotonin-induced PGE(2) overexpression appeared thus to be mediated by 5-HT(2A) and 5-HT(3) receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT(3) antagonists.