MRI Findings in Acute Tonsillar Infections.

BACKGROUND AND PURPOSE: Previous literature is vague on the prevalence and exact nature of abscesses in tonsillar infections, ranging from intratonsillar and peritonsillar collections to deep extension involving the parapharyngeal and retropharyngeal spaces. MR imaging has excellent diagnostic accuracy in detecting neck infections and can potentially clarify this issue. We sought to characterize the spectrum of MR imaging findings regarding tonsillar infections. MATERIALS AND METHODS: We conducted a retrospective cohort study of emergency neck MR imaging scans of patients with tonsillar infections. Imaging data were assessed in terms of signs of infection and the location of abscesses and were compared with clinical findings, final diagnoses, and surgical findings as reference standards. RESULTS: The study included 132 patients with tonsillar infection. Of these, 110 patients (83%) had ≥1 abscess (99 unilateral, 11 bilateral; average volume, 3.2 mL). Most abscesses were peritonsillar, and we found no evidence of intratonsillar abscess. Imaging showed evidence of parapharyngeal and retropharyngeal extension in 36% and 10% of patients, respectively. MR imaging had a high positive predictive value for both abscesses (0.98) and deep extension (0.86). Patients with large abscesses and widespread edema patterns had a more severe course of illness. CONCLUSIONS: Emergency neck MR imaging can accurately describe the extent and nature of abscess formation in tonsillar infections.

Long-range phase synchronization of high-frequency oscillations in human cortex.

Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100-400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se.

Influence of 2'-fucosyllactose and galacto-oligosaccharides on the growth and adhesion of Streptococcus mutans.

Human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), and galacto-oligosaccharides (GOS), a prebiotic carbohydrate mixture, are being increasingly added to infant formulas, necessitating the understanding of their impact on the oral microbiota. Here, for the first time, the effects of 2'-FL and GOS on the planktonic growth and adhesion characteristics of the caries-associated oral pathogen Streptococcus mutans were assessed, and the results were compared against the effects of xylitol, lactose and glucose. There were differences in S. mutans growth between 2'-FL and GOS. None of the three S. mutans strains grew with 2'-FL, while they all grew with GOS as well as lactose and glucose. Xylitol inhibited S. mutans growth. The adhesion of S. mutans CI 2366 to saliva-coated hydroxyapatite was reduced by 2'-FL and GOS. Exopolysaccharide-mediated adhesion of S. mutans DSM 20523 to a glass surface was decreased with 2'-FL, GOS and lactose, and the adhesion of strain CI 2366 strain was reduced only by GOS. Unlike GOS, 2'-FL did not support the growth of any S. mutans strain. Neither 2'-FL nor GOS enhanced the adhesive properties of the S. mutans strains, but they inhibited some of the tested strains. Thus, the cariogenic tendency may vary between infant formulas containing different types of oligosaccharides.

Implementation of a 23-h surgery model in a tertiary care hospital: a safe and feasible model with high patient satisfaction.

BACKGROUND: The 23-h surgery model consists of elective operative care with an overnight hospital stay for patients unsuitable for day case surgery. The aim of this study was to assess the success of the 23-h surgery model. METHODS: This was a prospective follow-up study of patients undergoing surgery with the planned 23-h model in a tertiary-care university hospital during a 12-month period 2 years after the model was implemented. Patients were interviewed 2 weeks after surgery, and the hospital operative database and patient records were searched. The primary outcome was the success of the process, defined as discharge before 10.00 hours on the first morning after surgery. Secondary outcomes were 30-day readmission and reoperation rates, adverse events, and patient satisfaction with the process. RESULTS: Between May 2017 and May 2018, 993 adult patients underwent surgery with the 23-h model, of whom 937 adhered to the model as planned (success rate 94·4 per cent). Gynaecological, gastrointestinal and orthopaedic surgery were the three most common surgical specialties. The surgical process was changed to an in-hospital model for 45 patients (4·5 per cent), and 11 (1·1 per cent) were discharged on the day of surgery. The readmission rate was 1·9 per cent (19 of 993), and five patients (0·5 per cent) had a reoperation within 30 days of surgery. Fifty-nine adverse events were noted in 53 patients (5·3 per cent), most commonly infection. Patient satisfaction was a median of 6-7 (maximum 7) points for various aspects of the model. CONCLUSION: The success rate and patient satisfaction for the 23-h surgery model was high.

ANTECEDENTES: El modelo de cirugía de 23 horas consiste en un procedimiento quirúrgico electivo con estancia en el hospital durante una noche en aquellos pacientes que no son adecuados para cirugía ambulatoria. MÉTODOS: Se puso en marcha un estudio prospectivo de seguimiento de pacientes sometidos a cirugía con un modelo planificado de 23 horas en un hospital universitario de tercer nivel durante un periodo de 12 meses a los dos años de la implementación del modelo. Los pacientes fueron entrevistados a las dos semanas tras la cirugía, y se realizaron búsquedas en las bases de datos operativas y en los informes de los pacientes. El resultado primario fue el éxito del proceso definido como el alta antes de las 10 horas en la primera mañana postoperatoria. Los resultados secundarios fueron el reingreso a los 30 días y la tasa de reoperaciones, eventos adversos, y satisfacción del paciente con el proceso. RESULTADOS: Entre mayo de 2017 y mayo de 2018, 993 pacientes adultos fueron sometidos a cirugía con un modelo planificado de 23 horas, de los cuales 937 pacientes siguieron el modelo tal como se planificó (tasa de éxito 94,4%). Las tres especialidades quirúrgicas más frecuentes fueron ginecología, aparato digestivo y ortopedia. El proceso quirúrgico se cambió a un modelo de hospitalización en 45 (4,5%) pacientes, y 11 (1,1%) pacientes fueron dados de alta en el día de la cirugía. La tasa de reingreso fue del 1,9% (n = 19) y 5 pacientes (0,5%) precisaron de una reoperación en los primeros 30 días tras la cirugía. Se observaron eventos adversos en 53 pacientes (5,3%), siendo una infección el más frecuente. La satisfacción del paciente tuvo una mediana de 6-7 (de un total de 7) puntos para varios aspectos del modelo. CONCLUSIÓN: La tasa de éxito y la satisfacción del paciente del modelo de cirugía de 23 horas son elevadas.

Comparison of liposomal drug formulations for transdermal iontophoretic drug delivery.

This study was aimed to evaluate the in vitro transdermal direct/pulsed current iontophoretic delivery of an amphiphilic model compound from various lipid vesicle-encapsulated formulations compared to free-drug formulation. Conventional, pegylated, ultradeformable liposomes (transfersomes) and ethosomes loaded with a negatively charged drug diclofenac sodium (DS) were prepared and characterized. All the liposomes possessed an average size of ≈100-150nm and negative zeta potential. No changes in colloidal stability were detected after 8h incubation of any vesicle formulation under constant or pulsed iontophoretic current. DS was released from all the liposome formulations with a similar, limited rate (≈50% in 24h), leading therefore to significantly lower transdermal fluxes across full-thickness porcine skin compared to the respective free drug formulation. From the tested lipid vesicle formulations, the transfersomes resulted in the highest passive flux and the ethosomes in the highest iontophoretic flux under direct constant current treatment. Higher negative surface charge of the vesicle led to better transport efficiency due to the higher mobility of the drug carrier under electric field. Pulsed current iontophoresis had no advantage over constant current treatment in combination with any type of lipid vesicular nanocarriers, in contrast to what has been described earlier with drug-loaded polymeric nanocarriers.

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and µ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and µ-receptor availabilities were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans. RESULTS: µ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS. SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli.

Comparison of Xpert Norovirus and RidaGene Norovirus assays for the detection of noroviruses in clinical fecal specimens.

The purpose of this study was to investigate the usability and performance of the Xpert Norovirus and RidaGene Norovirus assays for the detection of noroviruses in fecal specimens. Of the 186 stool specimens, 53 (28.5%) were considered true-positive for norovirus (NoV). Of the true-positive specimens, Xpert detected 53 and RidaGene detected 52. The respective sensitivity and specificity were 100% and 94.7% [95% confidence interval (CI), 91.0-98.5%] for the Xpert assay, and 98.1% (95% CI, 94.4-100%) and 97.0% (95% CI, 94.1-99.9%) for the RidaGene assay. Positive and negative predictive values (PPVs and NPVs) were 88.3% and 100% for the Xpert assay, and 92.9% and 99.2% for the RidaGene assay, respectively. Based on this study, it can be concluded that there were no significant differences (p-value > 0.5) between the results of the Xpert and RidaGene Norovirus assays. We found that both assays are useful for the detection of noroviruses in clinical stool samples.

Novel portable platform for molecular detection of toxigenic Clostridium difficile in faeces: a diagnostic accuracy study.

BACKGROUND: A novel portable platform for nucleic acid amplification enables rapid detection of diarrhoea causing toxigenic Clostridium difficile directly from faeces, even in resource-limited settings. We evaluated the accuracy and precision of the new commercial molecular test system. METHODS: One thousand one hundred and sixty faecal samples from patients suspected of having Clostridium difficile infection (CDI) were analysed using the Orion GenRead C. difficile test system (Orion Diagnostica Oy, Espoo, Finland) and comparative methods in three teaching hospital laboratories in Finland and France. The precision of the Orion GenRead C. difficile test system was evaluated in a reproducibility study with a set of blind-coded samples. The test system is based on a new isothermal amplification technology (Strand Invasion Based Amplification, SIBA®) and detection of the tcdB gene of C. difficile. We calculated the sensitivity, specificity, and the overall agreement according to Clinical and Laboratory Standards Institute recommendations. FINDINGS: The overall agreement of the Orion GenRead C. difficile test when compared to the comparative methods in routine use in the participating laboratories was between 96.7% and 98.8%. In the reproducibility study; the total percent agreement between three laboratories was 99.8%. INTERPRETATION: The identification of toxigenic C. difficile from faeces with the light-weight portable Orion GenRead test system was highly sensitive and specific, and the results were reproducible in the participating laboratories. This platform could enable fast and accurate molecular pathogen detection even in resource-limited or point-of-care settings.

Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.

The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations.

In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy.

Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo. Oral delivery of GLP-1 with nano- or micro-systems has been studied before, but the simultaneous nanodelivery of GLP-1 with iDPP4 is a novel strategy presented here. The type 2 diabetes mellitus (T2DM) rat model, induced through the combined administration of streptozotocin and nicotinamide, a non-obese model of T2DM, was used. The combination of both drugs resulted in an increase in the hypoglycemic effects in a sustained, but prolonged manner, where the iDPP4 improved the therapeutic efficacy of GLP-1. Four hours after the oral administration of the system, blood glucose levels were decreased by 44%, and were constant for another 4 h, representing half of the glucose area under the curve when compared to the control. An enhancement of the plasmatic insulin levels was also observed 6 h after the oral administration of the dual-drug composite system and, although no statistically significant differences existed, the amount of pancreatic insulin was also higher. These are promising results for the oral delivery of GLP-1 to be pursued further in a chronic diabetic model study.

Comprehensive real-time epidemiological data from respiratory infections in Finland between 2010 and 2014 obtained from an automated and multianalyte mariPOC® respiratory pathogen test.

Respiratory viruses cause seasonal epidemics every year. Several respiratory pathogens are circulating simultaneously and typical symptoms of different respiratory infections are alike, meaning it is challenging to identify and diagnose different respiratory pathogens based on symptoms alone. mariPOC® is an automated, multianalyte antigen test which allows the rapid detection of nine respiratory infection pathogens [influenza A and B viruses, respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, parainfluenza 1-3 viruses and pneumococci] from a single nasopharyngeal swab or aspirate samples, and, in addition, can be linked to laboratory information systems. During the study period from November 2010 to June 2014, a total of 22,485 multianalyte respi tests were performed in the 14 participating laboratories in Finland and, in total, 6897 positive analyte results were recorded. Of the tested samples, 25 % were positive for one respiratory pathogen, with RSV (9.8 %) and influenza A virus (7.2 %) being the most common findings, and 0.65 % of the samples were multivirus-positive. Only small geographical variations in seasonal epidemics occurred. Our results show that the mariPOC® multianalyte respi test allows simultaneous detection of several respiratory pathogens in real time. The results are reliable and give the clinician a picture of the current epidemiological situation, thus minimising guesswork.

Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity.

Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss. Here we measured brain µ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice-before and 6 months after bariatric surgery-using PET with [(11)C]carfentanil and [(11)C]raclopride. Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (P's<0.005). Weight loss did not influence D2R availability in any brain region. Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity. Because bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.

Method for 3D fibre reconstruction on a microrobotic platform.

Automated handling of a natural fibrous object requires a method for acquiring the three-dimensional geometry of the object, because its dimensions cannot be known beforehand. This paper presents a method for calculating the three-dimensional reconstruction of a paper fibre on a microrobotic platform that contains two microscope cameras. The method is based on detecting curvature changes in the fibre centreline, and using them as the corresponding points between the different views of the images. We test the developed method with four fibre samples and compare the results with the references measured with an X-ray microtomography device. We rotate the samples through 16 different orientations on the platform and calculate the three-dimensional reconstruction to test the repeatability of the algorithm and its sensitivity to the orientation of the sample. We also test the noise sensitivity of the algorithm, and record the mismatch rate of the correspondences provided. We use the iterative closest point algorithm to align the measured three-dimensional reconstructions with the references. The average point-to-point distances between the reconstructed fibre centrelines and the references are 20-30 µm, and the mismatch rate is low. Given the manipulation tolerance, this shows that the method is well suited to automated fibre grasping. This has also been demonstrated with actual grasping experiments.

In vivo imaging of the cannabinoid CB1 receptor with positron emission tomography.

Positron emission tomography (PET) can visualize and quantify receptors and other targets in the living human brain, and recent progress in radioligand development has enabled measurement of cannabinoid type-1 (CB1 ) receptors. Cannabinoid CB1 receptors have been implicated in multiple human diseases, such as obesity, mood disorders, and addiction. First in vivo human studies have shown distinctive spatial and temporal alterations in cannabinoid CB1 receptor binding in addictive disorders.

Comparison of BD Max Cdiff and GenomEra C. difficile molecular assays for detection of toxigenic Clostridium difficile from stools in conventional sample containers and in FecalSwabs.

In this study, the usability and performance of GenomEra™ C. difficile and BD Max™ Cdiff nucleic acid amplification tests (NAATs) for the detection of toxigenic Clostridium difficile were investigated in comparison with toxigenic culture and C. difficile toxin A- and toxin B-detecting immunochromatographic antigen (IA) test, the Tox A/B QuikChek®. In total, 302 faecal specimens were collected, 113 of which were in parallel to conventional sample containers and FecalSwab liquid-based microbiology (LBM) tubes. Seventy-nine specimens were considered true-positives for toxigenic C. difficile. The sensitivity and specificity were 97.5 % and 99.6 % and 93.7 % and 98.7 % for the GenomEra and BD Max assays respectively. Toxigenic culture and Tox A/B QuikChek had sensitivity and specificity of 91.1 % and 100 % and 34.2 % and 100 % respectively. Hands-on time for analysing 1 to 24 specimens using NAATs was 1 to 15 min. The rate of PCR inhibition was 0 % for both NAATs with faeces in LBM tubes, while with faeces in conventional sample containers the respective inhibition rates were 5.3 % and 4.4 % for the GenomEra and the BD Max assays. The NAATs demonstrated an excellent analytical performance, reducing significantly the overall workload of laboratory personnel compared with culture and IA test.

The prognostic significance of declining health-related quality of life scores at 6 months after coronary artery bypass surgery.

PURPOSE: Health-related quality of life (HRQoL) measured on the EQ-5D (European quality of life-5 dimensions)-questionnaire has been shown to improve after coronary artery bypass grafting (CABG), this study investigated whether changes in HRQoL predict later morbidity. METHODS: Included were 404 consecutive patients undergoing isolated CABG between 2008 and 2010 who filled the EQ-5D-questionnaire at baseline and 6 months postoperatively. Records were reviewed for later major adverse cardiac and cerebrovascular events (MACCE) after 6 months. Follow-up was 38.6 months (10-58). RESULTS: Patients who suffered later MACCE more often had suffered an in-hospital postoperative stroke, had a longer in-hospital stay, had lower HRQoL scores at 6 months and deteriorated on several EQ-5D-subscales. Logistic regression showed 6 months visual analogue scale scores and declining function scores to be independent predictors of later MACCE. CONCLUSION: Deteriorating function and HRQoL-scores at 6 months as compared to baseline postoperatively predict later adverse cardiovascular events after CABG.

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort.

BACKGROUND: The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an 'oversampling' study design. Method Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions. RESULTS: 5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'. CONCLUSIONS: This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high 'self-directedness' (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.

Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography.

Brain cannabinoid CB1 receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB1 receptors in alcohol dependent patients in early and protracted abstinence, and in comparison with control subjects without alcohol use disorders, using positron emission tomography and [(18)F]FMPEP-d2, a radioligand for CB1 receptors. We scanned 18 male in-patients with alcohol dependence twice, within 3-7 days of admission from ongoing drinking, and after 2-4 weeks of supervised abstinence. Imaging data were compared with those from 19 age-matched healthy male control subjects. Data were also analyzed for potential influence of a common functional variation (rs2023239) in the CB1 receptor gene (CNR1) that may moderate CB1 receptor density. On the first scan, CB1 receptor binding was 20-30% lower in patients with alcohol dependence than in control subjects in all brain regions and was negatively correlated with years of alcohol abuse. After 2-4 weeks of abstinence, CB1 receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB1 receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB1 receptor binding in the human brain and this reduction persists at least 2-4 weeks into abstinence. The correlation of reduced binding with years of alcohol abuse suggests an involvement of CB1 receptors in alcohol dependence in humans.

One-step sample preparation of positive blood cultures for the direct detection of methicillin-sensitive and -resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci within one hour using the automated GenomEra CDX™ PCR system.

A method for the rapid detection of methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) with a straightforward sample preparation protocol of blood cultures using an automated homogeneous polymerase chain reaction (PCR) assay, the GenomEra™ MRSA/SA (Abacus Diagnostica Oy, Turku, Finland), is presented. In total, 316 BacT/Alert (bioMérieux, Marcy l'Etoile, France) and 433 BACTEC (Becton Dickinson, Sparks, MD, USA) blood culture bottles were analyzed, including 725 positive cultures containing Gram-positive cocci in clusters (n = 419) and other Gram stain forms (n = 361), as well as 24 signal- and growth-negative bottles. Detection sensitivities for MSSA, MRSA, and MRCoNS were 99.4 % (158/159), 100.0 % (9/9), and 99.3 % (132/133), respectively. One false-positive MRSA result was detected from a non-staphylococci-containing bottle, yielding a specificity of 99.8 %. The lowest detectable amount of viable cells in the blood culture sample was 4 × 10(4) CFU/mL. The results were available within one hour after microbial growth detection and the two-step, time-resolved fluorometric (TRF) measurement mode employed by the GenomEra CDX™ instrument showed no interference from blood, charcoal, or culture media. The method described lacks all sample purification steps and allows reliable and simplified pathogen detection also in clinical microbiology laboratory settings without specialized molecular microbiology competence.