Fluoxetine-induced toxicity results in human placental glutathione S-transferase-π (GST-π) dysfunction

Context: The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase-π (GST-π) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations. Objective: To elucidate the interaction of placental GST-π with FLU. Materials and methods: First, concentration-dependent inhibition of human placental GST-π was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5?mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows. Results: The V_m, at variable [CDNB] (142?±?16?U/mg protein) was 3 times higher than the V_m obtained at variable [GSH] (49?±?4?U/mg protein). On the other hand, the K_m for CDNB was ～10 times higher than the K_m for GSH (1.99?±?0.36?mM versus 0.21?±?0.06?mM). The IC₅₀ value for FLU was 8.6?mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the K_i values of 5.62?±?4.37 and 8.09?±?1.27?mM, respectively. Conclusion: Although the K_i values obtained for FLU in vitro are high, due to their uneven distribution, long elimination time and inhibitory behavior on detoxification systems, it may cause defects in adults but these effects may be much more severe in fetus and result in congenital malformations.     

Microbiological diagnostics of bloodstream infections in Europe—an ESGBIES survey

ObjectivesHigh-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories.MethodsWe performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries.ResultsResponses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC.ConclusionsLaboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.     

Migraine and associated comorbidities are three times more frequent in children with ADHD and their mothers

Objective

Attention deficit and hyperactivity disorder (ADHD) is a neuro-developmental disorder related to internalizing and externalizing disorders as well as somatic complaints and disorders. This study was conducted to evaluate the prevalence of headache subtypes, epilepsy, atopic disorders, motion sickness and recurrent abdominal pain among children and adolescents with ADHD and their parents.

Modification of local anesthetic-induced antinociception by fentanyl in rats

In clinical practice, using the lowest doses of drugs for anesthesia or analgesia is the main goal. Opioid combinations with local anesthetics can be preferable for achieving adequate anesthesia or analgesia. The primary purpose of this study was to examine possible thermal antinociceptive effects of the opioid -fentanyl and the amide local anesthetics levobupivacaine and lidocaine when locally administered alone or in combination. The paw withdrawal latencies to noxious thermal stimuli in rats were measured to assess the antinociceptive actions of drugs after subcutaneous intraplantar injection into the hind paw. All drugs examined in this study produced dose- and time-dependent increases in the paw withdrawal latencies. Fentanyl is approximately 125 and 500 times more potent than levobupivacaine and lidocaine, respectively. At the same dose, the antinociceptive potency of levobupivacaine was 3.6-fold higher than that of lidocaine. Co-injection of the lowest doses of levobupivacaine and lidocaine dramatically increased the paw withdrawal latency. However, in the presence of fentanyl, the effects of levobupivacaine and lidocaine were different. Although co-injection of levobupivacaine with fentanyl both enhanced and prolonged antinociceptive action, the lidocaine-fentanyl combination did not significantly change the paw withdrawal latency. These results suggest that intraplantar co-administration of fentanyl with levobupivacaine, but not lidocaine, may provide more effective antinociception without increasing the dose requirements.     

Biomechanical comparison of a new technique of mandibular angle fractures: biplanar and bicortical superior proximal 3 holes and bicortical inferior plate fixation

Miniplates have been used for mandibular angle fractures during the past 2 decades. The technique of placing single miniplate at the upper border based on the tension lines of the fracture was proposed by Michelet and Champy. The need for a second miniplate to be applied to the lower mandible has been discussed recently. Biomechanical comparison of biplanar and monoplanar dual-miniplate fixation techniques was investigated by Haug. Our hypothesis is in dual-miniplate fixation; the proximal 3 holes of superior border miniplate could be fixated by bicortical screws. The first 2 are at the proximal bone segment and are not related to the tooth and also superior to the alveolar nerve. Generally, the third molar tooth is extracted because it is at the fracture site. Hence, the proximal third hole could also be fixated by bicortical screws. We define a biplanar dual-miniplate technique in which the lower plate and the proximal 3 holes of the upper plate are fixated by bicortical screws. We have designed a study for biomechanical comparison of our method and popular types of mandibular fixation methods.     

The frequency of the celiac disease among children with familial Mediterranean fever

We aimed to assess the frequency of celiac disease (CD) in patients with Familial Mediterranean Fever (FMF). This prospective study was carried out from October 2015 to March 2016 and included 303 patients with FMF. We used 98 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastro-duodenoscopy and intestinal biopsy for a definite diagnosis of CD. Only 9 of 303 patients (2.9%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA and only one of them (0.3%) had a positive result. This patient underwent gastro-duodenoscopy. The pathological report was compatible with Marsh 0 classification score for the diagnosis of CD. Two subjects from the control group were positive for tTG IgA but none of them had positive EMA antibodies. We did not find CD in the large cohort of childhood FMF patients. The prevalence of CD did not show association with presence of childhood FMF in this study and CD would not be a considerable complication of childhood FMF.     

Association of Reactive–Proactive Aggression and Anxiety Sensitivity with Internalizing and Externalizing Symptoms in Children with Attention-Deficit/Hyperactivity Disorder

This study evaluates the associations among the symptoms of anxiety, depression, and disruptive behavioral disorders (DBD) in the context of their relationships with reactive–proactive aggression and anxiety sensitivity in children with attention-deficit/hyperactivity disorder (ADHD). The sample consisted of 342 treatment-naive children with ADHD. The severity of ADHD and DBD symptoms were assessed via parent- and teacher-rated inventories. Anxiety sensitivity, reactive–proactive aggression and severity of anxiety and depression symptoms of children were evaluated by self-report inventories. According to structural equation modeling, depression and anxiety scores had a relation with the DBD scores through reactive–proactive aggression. Results also showed a negative relation of the total scores of anxiety sensitivity on DBD scores, while conduct disorder scores had a positive relation with anxiety scores. This study suggests that examining the relations of reactive–proactive aggression and anxiety sensitivity with internalizing and externalizing disorders could be useful for understanding the link among these disorders in ADHD.     

Automatic detection of bubbles in the subclavian vein using Doppler ultrasound signals

INTRODUCTION: It is possible to detect venous gas bubbles by listening to the Doppler audio signals. However, a serious disadvantage of the audio evaluation is the inability of continuous monitoring and the inter-rater agreement. Several researchers have worked on the automated detection of emboli, but no current system has the required sensitivity and specificity for clinical use. METHOD: We developed software that integrated frequency filtering, processing, and detection phases of microemboli into a graphical user interface. The detection algorithm consists of a rule-based criterion with a user-defined threshold sliding in-time axis that estimates the duration of the embolic event. Subclavian Doppler audio recordings obtained from a high altitude diving expedition were analyzed using digital filtering and non-linear operator combinations of the software. The data set includes 43 embolic events in 9 recordings from 4 different subjects. RESULTS: It was determined that embolic signals are best differentiated from the background signal at the 4500-8000-Hz frequency band. By using the non-linear "Teager Energy Operator", embolic signals were amplified against their background and a high level of sensitivity and specificity was obtained (83.7% and 97.3%, respectively). The duration of the detected emboli was estimated as 12.17 +/- 4.36 ms (mean +/- SD). DISCUSSION: The optimal frequency band for the detection of subclavian emboli is significantly higher than previous findings for the transcranial site. The duration output of the software can be used to estimate the size and the composition of emboli. Successful integration of the software into an ambulatory detection system may provide important site-specific bubble size distribution data for decompression modeling.