Demonstration of dual Shapiro steps in small Josephson junctions.

Bloch oscillations in small Josephson junctions were predicted theoretically as the quantum dual to Josephson oscillations. A significant consequence of this prediction is the emergence of quantized current steps, so-called dual Shapiro steps, when synchronizing Bloch oscillations to an external microwave signal. These steps potentially enable a fundamental standard of current I, defined via the frequency f of the external signal and the elementary charge e, I = ± n × 2ef, where n is a natural number.

Clinical outcome after surgical management of spontaneous spinal epidural hematoma.

Purpose: Spontaneous spinal epidural hematoma (SSEH) is a rare pathology characterized by a hemorrhage in the spinal epidural space without prior surgical or interventional procedure. Recent literature reported contradictory findings regarding the clinical, radiological and surgical factors determining the outcome, hence the objective of this retrospective analysis was to re-assess these outcome-determining factors.

Methods: Patients surgically treated for SSEH at our institution from 2010 - 2022 were screened and retrospectively assessed regarding management including the time-to-treatment, the pre-and post-treatment clinical status, the radiological findings as well as other patient-specific parameters.

Intraoperative Laser Speckle Contrast Imaging to Assess Vessel Flow in Neurosurgery: A Pilot Study.

Background And Objectives: Laser speckle contrast imaging (LSCI) has emerged as a promising tool for assessment of vessel flow during neurosurgery. We aimed to investigate the feasibility of visualizing vessel flow in the macrocirculation with a new fully microscope-integrated LSCI system and assess the validity and objectivity of findings compared with fluorescence angiography (FA).

Methods: This is a single-center prospective observational study enrolling adult patients requiring microsurgical treatment for brain vascular pathologies or brain tumors.

Resection of Low-Grade Gliomas in the Face Area of the Primary Motor Cortex and Neurological Outcome.

Objective: During surgery on low-grade gliomas (LGG), reliable data relevant to the primary motor cortex (M1) for the face area are lacking. We analyzed the impact of tumor removal within the M1 face area on neurological deficits.

Methods: We included LGG patients with resection within the M1 face area between May 2012 and November 2019.

Tumor Treating Fields - Behind and Beyond Inhibiting the Cancer Cell Cycle.

The unmet need for a safe treatment that significantly improves the overall survival, as well as the quality of life of patients with brain tumors, has urged researchers to work out new treatment modalities. About 15 years ago, it was shown that alternating electric fields significantly impair the growth of cancer cells. Recently, this potentially revolutionary approach called Tumor Treating Fields (TTFs) has been FDA-approved for the treatment of glioblastoma as well as mesothelioma.

Pharmacokinetic and pharmacodynamic evaluation of linagliptin in African American patients with type 2 diabetes mellitus.

Aim: This was an open label, multicentre phase I trial to study the pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin in African American patients with type 2 diabetes mellitus (T2DM).

Methods: Forty-one African American patients with T2DM were included in this study. Patients were admitted to a study clinic and administered 5 mg linagliptin once daily for 7 days, followed by 7 days of outpatient evaluation.

Adult attention deficit hyperactivity disorder and other psychiatric symptoms in recreational polydrug users.

Aims: Previous research has shown that recreational drug use is associated with more psychiatric symptoms and psychobiological distress. This study investigated whether symptoms of adult attention deficit hyperactivity disorder (ADHD) were also raised in polydrug users.

Methods: We assessed a non-clinical sample of 84 unpaid volunteers (mean age 27.

Digit ratio (2D:4D), salivary testosterone, and handedness.

The length of the index finger relative to that of the ring finger, the 2D:4D ratio, has been taken to be a marker of the amount of testosterone (T) that was present in the foetal environment (Manning, Scutt, Wilson, & Lewis-Jones, 1998). It has also been suggested (Geschwind & Galaburda, 1987) that elevated levels of foetal T are associated with left-handedness and that adult levels of circulating T might relate to foetal levels (Jamison, Meier, & Campbell, 1993). We used multiple regression analyses to investigate whether there is any relationship between either left or right hand 2D:4D ratio and handedness.

Dysbindin-1 genotype effects on emotional working memory.

We combined functional imaging and genetics to investigate the behavioral and neural effects of a dysbindin-1 (DTNBP1) genotype associated with the expression level of this important synaptic protein, which has been implicated in schizophrenia. On a working memory (WM) task for emotional faces, participants with the genotype related to increased expression showed higher WM capacity for happy faces compared with the genotype related to lower expression. Activity in several task-related brain areas with known DTNBP1 expression was increased, including hippocampal, temporal and frontal cortex.

Microdose pharmacokinetics of IDX899 and IDX989, candidate HIV-1 non-nucleoside reverse transcriptase inhibitors, following oral and intravenous administration in healthy male subjects.

IDX899 and IDX989 are new non-nucleoside reverse-transcriptase inhibitors (NNRTIs) that exhibit potent inhibition of HIV-1 replication, including NNRTI-resistant mutants. This microdose study investigates the pharmacokinetics and determined oral bioavailability. For each compound, 4 healthy male subjects are randomized to receive via a crossover design a single 100-microg oral and intravenous dose together with 100 nCi of [(14)C]-labeled drug.

The effects of GABA transporter inhibition on synaptophysin and synaptotagmin expression in diazepam tolerance.

Background: In light of the differential interactions seen between benzodiazepine, GABA transporter (GAT) inhibition and drug tolerance, the locomotor effects of a GAT1-specific inhibitor (SKF89976A) following diazepam tolerance were analysed and compared with the concomitant expression of synaptic vesicle proteins implicated in synaptic plasticity.

Methods: Male PVG/OlaHsd rats were chronically dosed with diazepam to produce tolerance, and the expression of mRNA for synaptophysin and synaptotagmin were analysed in the hippocampus by means of in situ hybridisation. The action of the GAT inhibitor SKF89976A on the expression of these mRNAs, and on open field behaviour was subsequently observed.

First administration to humans of a monoclonal antibody cocktail against rabies virus: safety, tolerability, and neutralizing activity.

Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies. The studies included healthy adult subjects in the USA and India and involved two parts.

Dance clubbing on MDMA and during abstinence from Ecstasy/MDMA: prospective neuroendocrine and psychobiological changes.

Background/aims: The present study is the first to prospectively compare a group of recreational Ecstasy users when dance clubbing on 3,4-methylenedioxymethamphetamine (MDMA) and when clubbing during abstinence from Ecstasy/MDMA.

Methods: Twelve normal healthy volunteers (mean age = 23.2 years) were assessed at a Saturday night dance club under self-administered MDMA.

Amygdala volume associated with alcohol abuse relapse and craving.

Objective: Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse.

Method: Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification.

Neurotrophic factor-related gene polymorphisms and adult attention deficit hyperactivity disorder (ADHD) score in a high-risk male population.

Adult attention deficit hyperactivity disorder (ADHD) is a widely under-reported but nevertheless common condition with a clear heritable component. Several genes have been proposed to play a role in the childhood onset of this neurodevelopmental disorder; however, association studies of persistence of ADHD into adulthood have rarely been performed. Neurotrophic factors (NTFs) are known to be involved in several aspects of neuronal development and neural plasticity in adults.

A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment.

Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, environmental conditions play an important role in its manifestation during childhood development. Here, we report the results of an investigation on the interaction of adverse childhood environment with a functional polymorphism of the serotonin transporter promoter gene (5-HTTLPR) and its impact on ADHD psychopathology in young adult delinquents. Standardized instruments were used to assess childhood and current ADHD and adverse childhood environment in 184 male delinquents.

Norepinephrine transporter and catecholamine-O-methyltransferase gene variants and attention-deficit/hyperactivity disorder symptoms in adults.

Attention deficit/hyperactivity disorder (ADHD) is a complex, highly heritable psychiatric condition. Neuropsychological and pharmacological studies suggest a dysregulation of central noradrenergic neurotransmission in addition to dopaminergic and serotonergic mechanisms. Only a few studies have focused on the association of noradrenergic susceptibility genes with ADHD.

A polymorphism at the 3'-untranslated region of the CLOCK gene is associated with adult attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is frequently found in childhood and persists in about 50% of cases into adulthood. Several studies demonstrate a relationship between ADHD, circadian rhythmicity and sleeping disturbances in unmedicated ADHD patients. Since ADHD is a very complex disease with a high genetic load involving multiple genes of moderate effect, we hypothesized a link between adult ADHD and genes involved in the circadian timekeeping system.

Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment.

Aggressive behavior is influenced by variation in genes of the serotonergic circuitry and early-life experience alike. The present study aimed at investigating the contribution of polymorphisms shown to moderate transcription of two genes involved in serotonergic neurotransmission (serotonin transporter, 5HTT, and monoamine oxidase A, MAOA) to the development of violence and to test for gene-environment interactions relating to adverse childhood environment. A cohort of 184 adult male volunteers referred for forensic assessment participated in the study.

Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation.

Objective: Niacin is an effective treatment for dyslipidemia due to its favorable effects on multiple lipid parameters. Clinical utility of niacin is sometimes limited, however, because of cutaneous flushing. A once-daily, extended-release (ER) niacin formulation has been shown to significantly reduce flushing compared to immediate-release niacin.

Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples.

To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the 'Mannheim Study of Risk Children' (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of > or =0.7% were identified.

Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts.

Background: Decreased sensitivity to and increased tolerance for the effects of alcohol is a phenotype, which was shown to be associated with an increased risk for alcoholism in humans and was observed in protein tyrosine kinase (PTK) fyn knockout mice.

Methods: We performed an association study of genetic variations of PTK fyn in 430 alcohol-dependent patients and 365 unrelated control subjects from two independent samples.

Results: In a combined analysis, we found an association of alcohol dependence with the single nucleotide polymorphism (SNP) T137346C in the 5' untranslated region (UTR) of the gene.

Using a UASB reactor for thickening and digestion of discharged sludge from submerged aerated biofilters.

Results from one year of experimental monitoring the wastewater treatment plant of UFES (Federal University of Espírito Santo) treating a residential urban area of city of Vitoria ES, Brazil, have shown a good performance by a UASB reactor as a part of domestic sewage treatment and also performing aerobic sludge thickening and digestion. The total solids concentration around 6% was obtained in main sludge blanket at bottom of reactor despite a high daily aerobic sludge load discharged from four aerobic submerged biofilters containing 0.4% TS and 80% of VS/TS.

Impaired bone metabolism following augmentation cystoplasties in growing rats.

Objective: The aim of this study was to evaluate the possible risk of impaired bone metabolism following augmentation cystoplasties with different gastrointestinal segments.

Method: 60 young rats underwent augmentation cystoplasties using gastric, ileal or sigma segments, or sham operations. An additional group undergoing sigma-cystoplasty received the bisphosphonate ibandronate to inhibit osteoclast-mediated bone resorption.