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Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression.
We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0–43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest.
Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF.
Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.
Mixing matrices quantify how people with similar or different characteristics make contact with each other, creating potential for disease transmission. Little empirical data on mixing patterns among persons who inject drugs (PWID) are available to inform models of blood-borne disease such as HIV and hepatitis C virus. Egocentric drug network data provided by PWID in Baltimore, Maryland between 2005 and 2007 were used to characterise drug equipment-sharing patterns according to age, race and gender. Black PWID and PWID who were single (i.e. no stable sexual partner) self-reported larger equipment-sharing networks than their white and non-single counterparts. We also found evidence of assortative mixing according to age, gender and race, though to a slightly lesser degree in the case of gender. Highly assortative mixing according to race and gender highlights the existence of demographically isolated clusters, for whom generalised treatment interventions may have limited benefits unless targeted directly. These findings provide novel insights into mixing patterns of PWID for which little empirical data are available. The age-specific assortativity we observed is also significant in light of its role as a key driver of transmission for other pathogens such as influenza and tuberculosis.
Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse.
Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions.
Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls.
The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.
Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions.
Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13–20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted.
For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA.
Childhood abuse is associated with widespread structural abnormalities in OFC–insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.
To report three cases illustrating that it is not unusual for a primary eyelid tumour to metastasise to the parotid gland and vice versa.
Two patients with malignant parotid tumours underwent radical parotidectomy and presented subsequently with eyelid lesions. Biopsy showed that both eyelid lesions were histologically similar to the primary parotid tumour. A third patient was noted to have ipsilateral upper eyelid and parotid gland tumours. Histology and immunocytochemistry were used to differentiate the primary tumour and the metastasis.
These cases illustrate that tumours involving eyelids and parotid glands can present simultaneously or sequentially, and either of these structures could be the focus of primary or metastatic tumour. The important message for oculoplastic and parotid surgeons is to routinely assess both the periocular and parotid area when patients present with a mass in either structure.
Background: Ciliary mutations cause multi-system disorders, often involving the CNS. We set to evaluate the prevalence of ciliary dysfunction in children with isolated neuroanatomical defects, by measuring nasal nitric oxide (nNO), a screening test for Primary Ciliary Dyskinesia (PCD). Study design: We measured nNO levels of 26 children with congenital midline CNS defects. We evaluated the effect of age, gender, and anomaly (brain, spinal cord, or combined) on measurements. We compared our results to the previously established normal range (153.6-509.9 nL/min), and to the cutoff for PCD (77 nL/min). Results: The range for nNO in our cohort was 56.5-334.7 nL/min, with age, gender, and anomaly not having a significant effect. The overall mean, 217.7 nL/min, was significantly lower than that of normal children, 314.51 nL/min (p<0.01). Four subjects (15.4%) had nNO levels below the lower end of normal, with two (7.7%) having values fitting the cutoff for PCD. Conclusions: We report an association between ciliary dysfunction and isolated midline neuroanatomical defects, not in context of any known syndrome. This suggests that genes causing isolated CNS defects, may be implied in the function of cilia. Longitudinal studies are required to investigate whether children with abnormal measurements suffer from any respiratory sequelae.
We describe appropriate wafer cleaning procedure and surface passivation characteristics of various passivants used for making measurement of minority carrier lifetime (τB ) of very high quality Si wafers. These passivants include: iodine ethanol (I-E), quinhydrone methanol (QH-M), SiO2, and Al2O3. The issues related to the passivation stability and the spatial uniformity for mapping τB are also discussed.
Iatrogenic and toxic movement disorders
Shyamal H. Mehta, Movement Disorders Program, Georgia’s Health Sciences University, Augusta, GA, USA,
Kapil D. Sethi, Movement Disorders Program, Georgia’s Health Sciences University, Augusta, GA, USA
Movement disorders attributable to prescribed medications and drugs of abuse are commonly encountered in the clinic. This chapter will review the wide variety of movement disorders due to dopamine-receptor blocking agents (DBAs), other medications, and the drugs of abuse.
Movement disorders due to DBAs
Antipsychotic agents, also termed neuroleptics or dopamine-receptor blocking agents (DBAs), are extensively utilized in the management of psychiatric disorders such as schizophrenia and bipolar disorders, and DBAs are employed in the treatment of neurological diseases such as Tourette’s syndrome, Huntington’s disease, psychosis in Parkinson’s disease, and dementias such as dementia with Lewy bodies. In addition, metoclopramide (MCP) is widely used to treat gastrointestinal motility disorders. The introduction of chlorpromazine in the early 1950s was nothing short of a miracle in the treatment of psychosis, but it was soon realized that there were significant neurological side effects associated with this class of drugs. Extrapyramidal side effects (EPS) was an umbrella term used to describe these side effects. Initially, it was thought that the induction of EPS was integral to the clinical antipsychotic efficacy of chlorpromazine and a dopamine depleter reserpine. More recently with the advent of clozapine, this tight linkage between EPS and antipsychotic efficacy has been shown to be fallacious. The evidence implicates the degree of D2 receptor antagonism and the speed of dissociation in the development of these EPS (DBAs with less D2 affinity and more rapid dissociation are less likely to produce EPS). In addition, the blockage of other neurotransmitter receptors such as 5-hydroxytryptamine (5-HT2) receptors may be important, allowing the development of drugs that are less likely to cause movement disorders.
To investigate whether inadequate dose to Point-A necessitates treatment plan changes in a time of computed tomography (CT)-image-guided brachytherapy treatment planning for cervix cancer.
Materials and methods
A total of 125 tandem and ovoid insertions from 25 cervix patients treated were reviewed. CT-image-based treatment planning was carried out for each insertion. Point-A is identified and the dose documented; however, dose optimisation in each plan was based on covering target while limiting critical organ doses (PlanTarget). No attempts were made to equate prescription and Point-A dose. For each insertion, a second hypothetical treatment plan was generated by prescribing dose to Point-A (PlanPoint-A). Plans were inter-compared using dose–volume histogram analyses.
A total of 250 treatment plans were analysed. For the study population, the median cumulative dose at Point-A was 80 Gy (range 70–95) for PlanTarget compared with 84·25 Gy for PlanPoint-A. Bladder and rectal doses were higher for PlanPoint-A compared with PlanTarget (p < 0·0001). Target D90 did not correlate with Point-A dose (p = 0·60).
Depending on applicator geometry, tumour size and patient anatomy, Point-A dose may vary in magnitude compared with prescription dose. Treatment plan modifications purely based on inadequate Point-A dose are unnecessary, as these may result in higher organ-at-risk doses and not necessarily improve target coverage.
Glassy samples of Se78−xTe20Sn2Pbx (0 ≤ x ≤ 6) system are prepared by melt quenching method. For non-isothermal study of crystallization kinetics, DSC scans have been taken at the heating rates 5, 10, 15 and 20 K/min in non-isothermal mode. Activation energy of crystallization (Ec) has been calculated using Kissinger method, Matusita-Sakka method and Augis-Bennett method. Various kinetic parameters of crystallization kinetics like peak crystallization temperature (Tc), Rate constants (K) and order parameter (n) are determined using these DSC scans. Thermodynamic parameters such as crystallization enthalpy (ΔHc) and entropy change during the crystallization (ΔS) are also evaluated. Results are discussed using chemical bond approach.
The success of central line-associated bloodstream infection (CLABSI) prevention programs in intensive care units (ICUs) has led to the expansion of surveillance at many hospitals. We sought to compare non-ICU CLABSI (nCLABSI) rates with national reports and describe methods of surveillance at several participating US institutions.
Design and Setting.
An electronic survey of several medical centers about infection surveillance practices and rate data for non-ICU Patients.
Ten tertiary care hospitals.
In March 2011, a survey was sent to 10 medical centers. The survey consisted of 12 questions regarding demographics and CLABSI surveillance methodology for non-ICU patients at each center. Participants were also asked to provide available rate and device utilization data.
Hospitals ranged in size from 238 to 1,400 total beds (median, 815). All hospitals reported using Centers for Disease Control and Prevention (CDC) definitions. Denominators were collected by different means: counting patients with central lines every day (5 hospitals), indirectly estimating on the basis of electronic orders (n = 4), or another automated method (n = 1). Rates of nCLABSI ranged from 0.2 to 4.2 infections per 1,000 catheter-days (median, 2.5). The national rate reported by the CDC using 2009 data from the National Healthcare Surveillance Network was 1.14 infections per 1,000 catheter-days.
Only 2 hospitals were below the pooled CLABSI rate for inpatient wards; all others exceeded this rate. Possible explanations include differences in average central line utilization or hospital size in the impact of certain clinical risk factors notably absent from the definition and in interpretation and reporting practices. Further investigation is necessary to determine whether the national benchmarks are low or whether the hospitals surveyed here represent a selection of outliers.