Expert’s comment concerning Grand Rounds case entitled “Slow correction of severe spastic hyperlordosis in an adult by means of magnetically expandable rods” by C. Birkenmaier et al. [Eur Spine J (2017): doi:10.1007/s00586-017-5366-2]

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A novel posterior approach preserving three muscles inserted at C2 in multilevel cervical posterior decompression and fusion using C2 pedicle screws

Abstract

Purpose

To present a novel posterior approach in multilevel cervical posterior decompression and fusion (PDF) using C2 pedicle screws that preserves the rectus capitis posterior major, oblique capitis inferior, and semispinalis cervicis.

Methods

We analyzed 30 consecutive patients who underwent C2–T1 PDF using an approach that preserved these three muscles without resecting. We assessed O-C2 range of motion (ROM), cross-sectional area of the cervical posterior muscles, rotational ROM, visual analog scale (VAS) for axial pain, neck disability index (NDI), and limitations of activities of daily living (ADL) involving neck movements.

Results

Mean preoperative O-C2 ROM (23.6°) was significantly increased postoperatively (33.0°). Mean atrophy rate of the cross-sectional area was 3.9%. Postoperatively, 69.8% of the preoperative rotational ROM (113.3°) was retained. The preoperative VAS for axial pain and the NDI did not increase postoperatively. The postoperative O-C2 ROM (33.9°) in 26 patients for whom extension ADL were possible was significantly larger than that in four patients for whom extension ADL were impossible (26.9°). The postoperative retained rate of rotational ROM (75.8%) in 18 patients for whom rotation ADL were possible was significantly larger than that in 12 patients for whom rotation ADL were impossible (62.3%).

Conclusions

This is potentially an effective approach for maintaining O-C2 ROM and rotational ROM, which enabled good levels of ADL after C2–T1 PDF. Axial pain and NDI were not worse after PDF.

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Regulation of cell proliferation in the retinal pigment epithelium: differential regulation of the death associated protein like-1 DAPL1 by alternative MITF splice forms

Summary

Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death associated protein like-1 DAPL1 cell-autonomously suppresses RPE proliferation in vivo and in vitro. Here we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (-) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (-) MITF stimulates the transcription of Musashi-homolog-2 (MSI2), which negatively regulates the processing of the anti-DAPL1 microRNA miR-7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation.

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Metastasis-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma

Summary

This study evaluated patterns of response as discerned by comprehensive metastasis-specific analysis in metastatic melanoma patients receiving anti-PD-1 antibodies. Bi-dimensional measurements of every metastasis in patients enrolled in the KEYNOTE-001 trial at a single institution were obtained at baseline and throughout treatment. Twenty-seven evaluable patients had 399 baseline metastases measurable on CT imaging. Complete response (CR) which occurred in 52.6% of metastases was smaller (mean 223mm² vs. 760mm², p < 0.01) and occurred more frequently in the lungs (65% vs 39.4%, p < 0.01). Response was heterogenous (new/progressing metastases alongside CR metastases) at first assessment in 4/14 patients with objective response (OR) as opposed to 7/13 patients with non-OR. CR of individual metastases is common and influenced by site and size. Most patients with OR demonstrate homogenous regression in all metastases at the first assessment. In contrast, patients with early heterogeneity had a poor outcome.

This article is protected by copyright. All rights reserved.

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Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg⁻¹ h⁻¹) in pregnant Sprague–Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult animals through a Nissl stain. Results showed a disinhibition and hyperactive behavior in pubertal animals exposed to ketamine, followed in adulthood with cognitive impairments, social withdrawal, anxiety, depression, and aggressive-like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was observed, without changes in cell density. These results strongly suggest a robust link between prenatal pharmacologic manipulation of NMDA receptors and schizophrenia.

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Children's anxiety symptoms and salivary immunoglobulin A: A mutual regulatory system?

Abstract

Anxiety can impact the immune system resulting in negative health outcomes. Salivary immunoglobulin A (sIgA) is a first line of defense against foreign antigens, with lowered levels indicative of weakened mucosal immunity. Little is known about how anxiety symptoms affect the diurnal rhythm of sIgA secretion, or the longitudinal transactional sequence between the two in children and adolescents. The goals of the two studies were to: (i) explore the concurrent associations between self-reported anxiety symptoms and diurnal variations of sIgA across the day using repeated daily samples of sIgA; and (ii) examine transactional relations between children's anxiety and aggregated total amount of sIgA levels across successive periods from middle childhood (Wave 1; ages 9–12) to early adolescence (Wave 2; ages 12–15), and from early to mid- adolescence (Wave 3; ages 15–18). Concurrent results showed a steeper (positive) rise in diurnal slope of sIgA from awakening to 5 hr post-awakening in children with higher anxiety. Longitudinally, higher levels of total anxiety, and specifically, worries at Wave 1 significantly predicted lower cumulative daily levels of sIgA 3 years later at Wave 2. Lowered sIgA levels at Wave 2 in turn predicted higher anxiety at Wave 3, illustrating a "vicious cycle" feedback loop. These findings broaden our understanding of the developmental links between anxiety symptoms, the immune system, and health.

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Cortisol profiles differentiated in adolescents and young adult males with fragile X syndrome versus autism spectrum disorder

Background

Fragile X syndrome (FXS) and non-syndromic autism spectrum disorder (ASD) are distinct disorders with overlapping behavioral features. Both disorders are also highly associated with anxiety with abnormal physiological regulation implied mechanistically. Some reports suggest atypical hypothalamus-pituitary-adrenal (HPA) axis function, indexed via aberrant cortisol reactivity, in both FXS and non-syndromic ASD. However, no study has compared cortisol reactivity across these two disorders, or its relationship to ASD symptom severity.

Methods

Cortisol reactivity (prior to and following a day of assessments) was measured in 54 adolescent/young adult males with FXS contrasted to 15 males with non-syndromic ASD who had low cognitive abilities.

Results

Greater ASD symptom severity was related to increased cortisol reactivity and higher levels at the end of the day, but only in the non-syndromic ASD group. Elevated anxiety was associated with increased HPA activation in the group with FXS alone.

Conclusions

Taken together, findings suggest a unique neuroendocrine profile that distinguishes adolescent/young adult males with FXS from those with non-syndromic ASD. Severity of ASD symptoms appears to be related to cortisol reactivity in the non-syndromic ASD sample, but not in FXS; while anxiety symptoms are associated with HPA activation in the FXS sample, but not in ASD despite a high prevalence of ASD, anxiety and physiological dysregulation characteristic in both populations.

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