Epigenomic control of gonadotrophin‐releasing hormone neurone development and hypogonadotrophic hypogonadism

Mammalian reproductive success depends on gonadotrophin‐releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival. Indeed, the GnRH neurone system was absent or abrogated in transgenic mice with reduced (ie, hypomorphic) Fgf8 and/or Fgf receptor (Fgfr) 1 expression, respectively. Moreover, we found that GnRH neurones were absent in the embryonic olfactory placode of Fgf8 hypomorphic mice, the putative birthplace of GnRH neurones. These observations, together with those made in human KS/CHH patients, indicate that the FGF8/FGFR1 signalling system is a requirement for the ontogenesis of the GnRH neuronal system and function. In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.     

Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention

The ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of “higher order” attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top‐down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention‐reorienting task to investigate top‐down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time–frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60–80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole‐brain voxel‐wise correlations between validity difference scores (i.e., attention reorienting trials—nonreorienting trials) in frontal theta activity and movement‐locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top‐down modulation of movement‐related gamma responses during attentional reorienting and movement execution.     

Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

BackgroundChildhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children.MethodsTypically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T₁-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site.ResultsWe found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampal regions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae.LimitationsWe assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma.ConclusionResults revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.     

Contralateral suppression of otoacoustic emissions in a clinical sample of children with auditory processing disorder

Objective: The suppression of evoked otoacoustic emissions (EOAE) may serve as a clinical tool to evaluate the medial olivocochlear (MOC) reflex, which is thought to aid speech discrimination (particularly in noise) by selectively inhibiting cochlear amplification. The present study aimed to determine if contralateral transient evoked otoacoustic emission (TEOAE) suppression was present in a clinical sample of children with listening difficulties with and without auditory processing disorder (APD).

Design: A three-group, repeated measure design was used.

Study sample: Forty three children aged 8–14?years underwent an auditory processing assessment and were divided into three groups: children with reported listening difficulties with APD, children with reported listening difficulties without APD, and children with normal hearing. APD was defined as per British Society of Audiology.

Results: TEOAE suppression was present in all three participant groups. No significant group, age or ear effects were observed for TEOAE suppression in dB or as a normalised index.

Conclusion: Contralateral TEOAE suppression method could not be used as a clinical tool to identify APD in this study’s participating children and did not support the hypothesised link between reduced MOC function and general listening difficulties in background noise in children with or without APD.     

Pancreatitis with arthropathy and subcutaneous fat necrosis

The occurrence of peripheral fat necrosis in exceptional cases of pancreatic disease is not well understood. We report studies on such a patient with arthropathy and subcutaneous nodules. Examination of serial serum samples demonstrated striking elevations of the pancreatic enzymes phospholipase A, 3–3.4 units/ml (normal 0.17–0.41); lipase, 7–39 Sigma-Tietz units/ml (normal < 1); immunoreactive trypsin, 912–3,207 ng/ml (normal 12–41). The distinguishing characteristic of the patient's synovial fluid was a marked elevation of hydrolized fatty acids (680 mg/dl versus 19 ± 19 in control inflammatory joint fluids). Synovial fluid fatty acid distribution was identical to values for tissue fat. In contrast, serum fatty acid levels and distribution were normal. No associated proteinase inhibitor or significant immunologic abnormality was detected. Certain properties of adipose cells and lipolytic enzymes may help explain the characteristically selective necrosis of fat cells observed in this syndrome.     

Consensus statement on networks for high-quality rural anesthesia,surgery, and obstetric care in Canada

ObjectiveTo describe the essential components of well-resourced and high-functioning multidisciplinary networks that support high-quality anesthesia, surgery, and maternity care for rural Canadians, delivered as close to home as possible.Composition of the committeeA volunteer Writers’ Group was drawn from the Society of Obstetricians and Gynaecologists of Canada, the Society of Rural Physicians of Canada, the Royal College of Physicians and Surgeons of Canada, the Canadian Association of General Surgeons, the College of Family Physicians of Canada, and the Association of Canadian University Departments of Anesthesia.MethodsA collaborative effort over the past several years among the professional stakeholders has culminated in this consensus statement on networked care designed to integrate and support a specialist and non-specialist, urban and rural, anesthesia, surgery, and maternity work force into high-functioning networks based on the best available evidence.ReportSurgical and maternity triage needs to be embedded within networks to address the tensions between sustainable regional programs and local access to care. Safety and quality must be demonstrated to be equivalent across similar patients and procedures, regardless of network site. Triage of patients across multiple sites is a quality outcome metric requiring continuous iterative scrutiny. Clinical coaching between rural and regional centres can be helpful in building and sustaining high-functioning networks. Maintenance of quality and the provision of continuing professional development in low-volume settings represent a mutual value proposition.ConclusionThe trusting relationships that are foundational to successful networks are built through clinical coaching, continuing professional development, and quality improvement. Currently, a collaborative effort in British Columbia is delivering a provincial program—Rural Surgical Obstetrical Networks—built on the principles and supporting evidence described in this consensus statement.