Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm

Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7-8 year old children born very preterm and age-matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age.     

Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.

Imipramine is the prototypic tricyclic antidepressant utilized in the treatment of major depression and exerts its therapeutic efficacy only after prolonged administration. We report a study of the effects of short-term (2 wk) and long-term (8 wk) administration of imipramine on the expression of central nervous system genes among those thought to be dysregulated in imipramine-responsive major depression. As assessed by in situ hybridization, 8 wk of daily imipramine treatment (5 mg/kg, i.p.) in rats decreased corticotropin-releasing hormone (CRH) mRNA levels by 37% in the paraventricular nucleus (PVN) of the hypothalamus and decreased tyrosine hydroxylase (TH) mRNA levels by 40% in the locus coeruleus (LC). These changes were associated with a 70% increase in mRNA levels of the hippocampal mineralocorticoid receptor (MR, type I) that is thought to play an important role in mediating the negative feedback effects of low levels of steroids on the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine also decreased proopiomelanocortin (POMC) mRNA levels by 38% and glucocorticoid receptor (GR, type II) mRNA levels by 51% in the anterior pituitary. With the exception of a 20% decrease in TH mRNA in the LC after 2 wk of imipramine administration, none of these changes in gene expression were evident as a consequence of short-term administration of the drug. In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression.     

Management of ductal carcinoma in situ according to Van Nuys Prognostic Index in Australia and New Zealand

Introduction: Clinicians often use the Van Nuys Prognostic Index (VNPI) to determine management of ductal carcinoma in situ (DCIS). The VNPI uses age, extent of DCIS, pathological grade and resection margins to stratify patients into three groups pertaining to risk of local recurrence: low-risk (where breast-conserving surgery - BCS - alone appears adequate), intermediate-risk (where BCS plus radiotherapy is recommended) and high-risk (where mastectomy may be the safest option). The purpose of this study was to determine patterns of management of DCIS in Australia and New Zealand according to the VNPI. Methods: Using the National Breast Cancer Audit for the period 2004-2009, 4578 cases of DCIS were identified where complete data were available. Patterns of management according to the VNPI were determined. The chi-squared test was used for statistical analysis. Results: In VNPI group 1, 77% of patients were treated with BCS compared with 63% in group 2 and 32% in group 3. Of patients in group 1 who underwent BCS, 58% also received adjuvant radiotherapy, compared with 80% in group 2. In group 3, 68% were treated with mastectomy, and of those who underwent BCS, 86% received radiotherapy. Overall, 23% of DCIS cases did not conform to best practice according to individual VNPI prognostic groupings. Conclusions: Significant differences in the management of DCIS according to VNPI groups were observed. The results suggest the possibility that some patients in the low-risk group were over-treated, while a proportion of patients in the intermediate- and high-risk groups were under-treated.     

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses

Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n = 99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited blood oxygen‐level dependent responses in the following circuitry: periaqueductal gray, hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO ‐ R OFC, R AMYG ‐ R OFC, and R AMYG ‐ R HIPP. Overall, our findings demonstrated sex‐dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex‐dependent lens in determining these biosignatures. Hum Brain Mapp 37:3733–3744, 2016. © 2016 Wiley Periodicals, Inc .     

Surgical Skills Beyond Scientific Management

During the Great War, the French surgeon Alexis Carrel, in collaboration with the English chemist Henry Dakin, devised an antiseptic treatment for infected wounds. This paper focuses on Carrel’s attempt to standardise knowledge of infected wounds and their treatment, and looks closely at the vision of surgical skill he espoused and its difference from those associated with the doctrines of scientific management. Examining contemporary claims that the Carrel–Dakin method increased rather than diminished demands on surgical work, this paper further shows how debates about antiseptic wound treatment opened up a critical space for considering the nature of skill as a vital dynamic in surgical innovation and practice.     

Antimicrobial prophylaxis in open reduction and internal fixation of compound mandibular fractures: a collaborative regional audit of outcome

We conducted a regional 2-stage prospective audit involving 5 different maxillofacial units in the Yorkshire region of the UK to evaluate the effectiveness of perioperative antimicrobial prophylaxis in the treatment of mandibular fractures. In the first stage (145 patients) we surveyed current practice concerning antimicrobial prophylaxis and found out the current infection rate after open reduction and internal fixation (ORIF) of mandibular fractures. In the second stage (157 patients) we implemented a common antimicrobial protocol in all units and recorded the infection rates using the new regimen. In the first stage a wide range of antimicrobial prophylaxis was used in different units. The agreed perioperative antimicrobial protocol in the second stage was to begin amoxicillin or clarithromycin and metronidazole intravenously on admission and include 2 postoperative doses. The infection rates were 10.3% and 8.9%, respectively, and the difference between the two groups was not significant (χ² = 0.051, df = 1, p = 0.83). The infection rate in the Yorkshire region was similar to results from other centres. We recommend short perioperative antimicrobial prophylaxis with a maximum of 2 postoperative doses after ORIF of mandibular fractures.