Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells.

Myelin basic protein (Mbp) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both Mbp protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role Mbp plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.

Early life social stress and resting state functional connectivity in postpartum rat anterior cingulate circuits.

INTRODUCTION: Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. METHODS: We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. RESULTS: ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. LIMITATIONS: The sample sizes for the fMRI groups were low, limiting statistical power. CONCLUSION: This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders.

Scrotal fixation in the management of low undescended testes.

AIMS: Scrotal fixation (SF) is a known technique for the management of low undescended testes (UDT). SF assumes that most low UDT have no patent processus vaginalis (PPV) and can be managed via scrotal mobilization alone. We report our experience of the role of SF in the management of low UDT. MATERIALS AND METHODS: A retrospective review of all palpable UDT operated on by the senior author between 1998 and 2008 was undertaken. Children diagnosed with palpable UDT were examined under general anesthesia; if the whole testis could be manipulated into the upper part of the scrotum, low UDT was assumed and SF was performed. Attempts to identify a PPV intraoperatively were made in all and, if found, the procedure was converted to standard inguinal incision orchidopexy. RESULTS: One hundred and thirteen children with 134 UDT were identified. SF was performed in 55 testes; inguinal orchidopexy (IO) in 75 and four testes were excised. The median (IQR) age at SF was 5.5 [4.7-6.3] years. Three SF were converted to an IO when a PPV was discovered. The complications in SF were scrotal hematoma (n = 1) and superficial wound infection (n = 1). No post-operative herniae or atrophied testis were seen and none required a redo operation. The mean (SD) operative times for SF and IO were 29.5 (18.1) and 42.7 (16.6) min, respectively (P = 0.04). CONCLUSION: In our study, 52 of 55 (94.5%) patients with low UDT lacked a hernial sac and were successfully fixed by SF. SF is a viable, simple, quick and safe alternative to IO in the management of low UDT.

Contralateral inguinal exploration in premature neonates: is it necessary?

PURPOSE: The purpose of this study was to review our management of neonatal inguinal hernias in premature infants over a 5-year period to ascertain any change in practice. METHODS: Premature infants who underwent inguinal herniotomy between 2002 and 2006 were identified. Case notes were analyzed recording patient demographics, primary side, complications, recurrence and how many re-presented with a metachronous hernia. RESULTS: 172 preterm infants were identified: 162 males (94.2%) and 10 females (5.8%). Median gestation was 31 weeks (25-36.7). Eighteen (10.4%) were incarcerated. Median age at surgery was 66.5 days (0-284). Thirty-two (18.6%) had bilateral hernias. Of the 63 who underwent unilateral herniotomy, 9 (14.3%) re-presented with a metachronous hernia. Median time to returning was 24 days. The number of contralateral explorations decreased over the study period. The complication rate was 6.4%. Median follow-up was 2.83 years (0.33-5.4). CONCLUSIONS: This is one of the largest series showing the current practice in managing preterm infants with inguinal hernia. There are limitations to this study and the follow-up period is short. The value of contralateral groin exploration in premature neonates remains doubtful and we have shown that the overall practice has changed.

Clinical management of children and young adults with heterozygous familial hypercholesterolaemia in the UK.

Life expectancy in familial hypercholesterolaemia (FH) has been greatly improved by the advent of statin therapy. In the UK, however, these agents are not licensed for use in children. We approached 169 physicians responsible for lipid clinics for information on their practice in young patients, and valid responses were received from 54%. A typical lipid clinic has only 3.5 patients aged under 16 with FH. In boys aged 10-15 years 65% of physicians were prepared to treat with bile acid sequestrants but only 23% with statins. There was greater reluctance to treat in girls of the same age, corresponding figures being 52% and 12%. Despite the efficacy of statins in reducing low-density-lipoprotein cholesterol, these agents are little used in children with FH. Their safety and clinical efficacy should be assessed by a randomized double-blind trial.