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To investigate serotonin (SERT) and dopamine (DAT) transporter availabilities in depressed patients under treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram.
27 patients (10m, 42±16y) underwent [123I]β-CIT SPECT to assess SERT and DAT availabilities at baseline and after four weeks of treatment with escitalopram. Hamilton Rating Scale for Depression (HAMD) and Beck Depression Inventory (BDI) were used for clinical ratings. Parametric maps with specific to nonspecific ratios (BPND) were calculated for each voxel using cerebellum as reference region. VOI-based BPND were calculated in striatum (DAT) and midbrain/pons (SERT).
At baseline, mean DAT-BPND was 6.06±0.81 in striatum and SERT-BPND 1.94±0.18 in thalamus. There were negative correlations with age of DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under treatment there was a 20% occupancy of SERT in thalamus (p < 0.0001), whereas DAT availability increased by 17% in striatum (p<0.001), notably in the younger patients; higher SERT occupancy was associated with lesser DAT increase (R=0.55, p<0.05). There was a negative correlation of baseline HAM-D and DAT availability in putamen (R=- 0.45, p<0.05).
DAT and SERT availabilities decreased age-dependently comparable to studies in healthy volunteers. The SSRI-induced increase in DAT was less pronounced in elderly patients, even though occupancy of SERT was higher. These findings might have implications on dosage and side effect profile of SSRI medication in older patients.
At baseline, mean DAT-was 6.06±0.81 in striatum and SERT-1.94±0.18 in thalamus. There were negative correlations with age of DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under treatment there was a 20% occupancy of SERT in thalamus (p < 0.0001), whereas DAT availability increased by 17% in striatum (p<0.001), notably in the younger patients; higher SERT occupancy was associated with lesser DAT increase (R=0.55, p<0.05). There was a negative correlation of baseline HAM-D and DAT availability in putamen (R=- 0.45, p<0.05).
27 patients (10m, 42±16y) underwent [123I]β-CIT SPECT to assess SERT and DAT availabilities at baseline and after four weeks of treatment with escitalopram. Hamilton Rating Scale for Depression (HAMD) and Beck Depression Inventory (BDI) were used for clinical ratings. Parametric maps with specific to nonspecific ratios (BPND) were calculated for each voxel using cerebellum as reference region. VOI-based BPND were calculated in striatum (DAT) and midbrain/pons (SERT). Results At baseline, mean DAT-was 6.06±0.81 in striatum and SERT-1.94±0.18 in thalamus. There were negative correlations with age of DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under treatment there was a 20% occupancy of SERT in thalamus (p < 0.0001), whereas DAT availability increased by 17% in striatum (p<0.001), notably in the younger patients; higher SERT occupancy was associated with lesser DAT increase (R=0.55, p<0.05). There was a negative correlation of baseline HAM-D and DAT availability in putamen (R=-0.45, p<0.05).
Several lines of evidence suggest that cognitive deficits represent a core feature of schizophrenia.
The concept of “cognitive dysmetria” has been introduced to characterize disintegration at the system level of frontal-thalamic-cerebellar circuitry which has been regarded as a key network for a wide range of neuropsychological symptoms in schizophrenia.
The present multimodal study aimed at investigating effective and structural connectivity of the frontal-thalamic circuitry in schizophrenia.
Univariate fMRI data analysis and effective connectivity analysis using dynamic causal modeling (DCM) were combined to examine cognitive control processes in 40 patients with schizophrenia and 40 matched healthy controls. BOLD signal and parameters of effective connectivity were related to parameters of corresponding white matter integrity assessed with diffusion tensor imaging (DTI).
In the DTI analysis, significantly decreased fractional anisotropy (FA) was detected in patients in the right anterior limb of the internal capsule (ALIC), the right thalamus and the right corpus callosum. During Stroop task performance patients demonstrated significantly lower activation relative to healthy controls in a predominantly right lateralized frontal-thalamic-cerebellar network. An abnormal effective connectivity was observed in the right lateralized connections between thalamus, anterior cingulate and dorsolateral prefrontal cortex. FA in the right ALIC was significantly correlated with the fronto-thalamic BOLD signal, effective connectivity and cognitive performance in patients.
Present data provide evidence for the notion of a structural and functional defect in the prefrontal-thalamic-cerebellar circuitry, which seems to be the basis of the cognitive control deficits in schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Although contraception allows women to delay childbirth, stop unwanted childbearing, and postpone childbirth, not all contraception is equally effective, equally easy to access, or equally easy to use. Due to heterogeneity in women’s contraception opportunities and choices, in the effectiveness of the contraception used and even in luck, women differ in both their birth intervals and their age at first childbirth. We explore this heterogeneity, theoretically, incorporating contraception effectiveness and uncertainty (along with potential earnings, contraception costs, and net child benefits) into a potential mother’s childbearing decisions. Empirically, these factors are incorporated into a first hit time duration model, focusing on time to first birth, estimated with data from the Democratic Republic of Congo. The results provide nuanced insights into the income-fertility puzzle. Our evidence suggests that educated women start childbearing later, and are better able to use contraception, even less effective contraception. Thus, there are education-related heterogeneities in contraceptive effectiveness. Further, we find that women using more effective contraception start childbearing at a later age, as do women with better access to contraception. Both improved female education and improved access to modern contraception have the potential to hasten the fertility transition in the Democratic Republic of Congo.
Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to ‘test and treat’ those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.
High-fidelity simulators (HFSs) have been shown to prompt critical actions at a level equal to that of trained human actors (HAs) and increase perceived realism in intrahospital mass-casualty incident (MCI) exercises. For unannounced prehospital MCI exercises, however, no data are available about the feasibility of incorporating HFSs. This case report describes the integration of HFSs in such an unannounced prehospital MCI drill with HAs and provides data about the differences concerning triage, treatment, and transport of HFSs and HAs with identical injury patterns. For this purpose, 75 actors and four high-fidelity simulators were subdivided into nine groups defined by a specific injury pattern. Four HFSs and six HAs comprised a group suffering from traumatic brain injury and blunt abdominal trauma. Triage results, times for transport, and number of diagnostic and therapeutic tasks were recorded. Means were compared by t test or one-way ANOVA.
Triage times and results did not differ between actors and simulators. The number of diagnostic (1.25, SD = 0.5 in simulators vs 3.5, SD = 1.05 in HAs; P = .010) and therapeutic tasks (2.0, SD = 1.6 in simulators vs 4.8, SD = 0.4 in HAs; P = .019) were significantly lower in simulators. Due to difficulties in treating and evacuating the casualties from the site of the accident in a timely manner, all simulators died. Possible causal factors and strategies are discussed, with the aim of increasing the utility of simulators in emergency medicine training.
SchulzCM, SkrzypczakM, RaithS, HinzmannD, KrautheimV, HeuserF, MayerV, KreuzerC, HimslM, HollM, LippC, KochsEF, WagnerKJ. High-fidelity Human Patient Simulators Compared with Human Actors in an Unannounced Mass-Casualty Exercise. Prehosp Disaster Med. 2014;29(2):1-7.
Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.
Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).
In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.
This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.
The crystal structure of Fe2SiO4 spinel at room temperature was investigated at seven different pressures by X-ray diffraction, using a diamond anvil cell to examine the influence of Fe substitution on ringwoodite behaviour at high pressure. The results compared with those of a pure Mg endmember show that the substitution of Fe into the spinel structure causes only small changes in the compression rate of coordination polyhedra and the distortion of the octahedron. The data show that the compression rate for the octahedron and tetrahedron in (Mg,Fe)2SiO4 can be considered statistically equal for FeO6 and MgO6, as well as for SiO4 in both the endmembers. This shows why almost identical bulk moduli are reported along the solid solution in recent literature.
Performance metrics of every class of semiconductor amplifier or laser system depend critically on semiconductor QW optical properties such as photoluminescence (PL), gain and recombination losses (radiative and nonradiative). Current practice in amplifier or laser design assumes phenomenological parameterized models for these critical optical properties and has to rely on experimental measurement to extract model fit parameters. In this tutorial, I will present an overview of a powerful and sophisticated first-principles quantum design approach that allows one to extract these critical optical properties without relying on prior experimental measurement. It will be shown that an end device L-I characteristic can be predicted with the only input being intrinsic background losses, extracted from cut-back experiments. We will show that textbook and literature models of semiconductor amplifiers and lasers are seriously flawed.
We demonstrate a highly strained InGaAs/GaAs VECSEL operating at 1173 nm with more than 8.5 W output power and tunable over 40 nm. High-efficiency yellow-orange emission is then achieved by intra-cavity frequency doubling. Over 5 W of CW output power in the 585-589 nm spectral regions is achieved. This compact low-cost high-power yellow-orange laser provides an innovative alternative for sodium guidestar lasers or other medical / communication applications.
Background: The local anaesthetic prilocaine has a low systemic toxicity mainly because of a high absorption in the lung and a large volume of distribution and thus is associated with a lower risk of neurological or cardiac side-effects. However, the major disadvantage is the formation of methaemoglobin by its metabolite o-toluidine. This prospective observational study was performed to identify factors that are associated with increased prilocaine-induced methaemoglobinaemia. Patients and methods: One Hundred and sixty two patients undergoing major knee surgery under general anaesthesia combined with peripheral nerve blocks (femoral nerve block, combined femoral/sciatic nerve block or lumbar plexus block) received a single bolus injection of 300 or 400 mg prilocaine about 30 min before surgery via a catheter. The proper placement was verified using nerve stimulation via a stimulating catheter. Three hours after prilocaine injection, venous blood samples were drawn and methaemoglobin levels were measured by standard photometric technique. Data was subjected to a stepwise multiple regression analysis. Results: The mean methaemoglobin for all patients was 2.7% (range: 0.9–15.4%). A higher dose of prilocaine and younger age were the most important predictive factors for higher methaemoglobin formation. Female sex and to a lesser extent the use of high-concentration/low-volume prilocaine also increased methaemoglobin levels. These four factors of the model explain 36% of the total variance. Other investigated factors, including the patient’s height, weight, body mass index, the site of catheter insertion, the anaesthetist’s judgement concerning the difficulty of catheter placement, duration of catheter placement or an inadvertent puncture of a venous or arterial vessel, had no significant impact on the concentration of methaemoglobin. Conclusion: The use of prilocaine for regional block is safe, since the older patients who might be more susceptible to suffer from clinical symptoms of methaemoglobinaemia usually form less methaemoglobin. However, since prediction of high methaemoglobin levels is difficult, anaesthesiologists performing regional blocks in patients who might be jeopardized by a decreased oxygen transport capacity should avoid high doses of prilocaine.
A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East Germany, starting in April 2004. While only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by June 2005. To determine the reservoir responsible for the infections, a total of 43 rodents were trapped in Lower Bavaria. Serological and genetic investigations revealed that Puumala virus (PUUV) is dominant in the local population of bank voles. Partial PUUV S segment nucleotide sequences originating from bank voles at four different trapping sites in Lower Bavaria showed a low divergence (up to 3·1%). This is contrasted by a nucleotide sequence divergence of 14–16% to PUUV strains detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be responsible for the observed increase of human hantavirus infections in 2004–2005.