PIKE is essential for oligodendroglia development and CNS myelination

Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE^−/−) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE^−/− OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE^−/− mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE^−/− brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.Efficient propagation of action potentials depends on the presence of myelin sheath that spirals around the axon. As a membrane extension from oligodendrocytes (OLs), the myelin sheath has a unique lipid-rich composition that allows electrical insulation for high-speed conduction and fidelity of signal transfer (1). Generation of OLs is a developmentally regulated process, which involves the proliferation of oligodendrocyte progenitor cells (OPCs) at the germinal subventricular zones (SVZ), migration throughout the CNS, differentiation into mature OLs, and adhesion to the axon to form myelin (2). Although most OPCs first appear in early neonatal brain, maturation and myelination of OLs in rodents occur largely in postnatal life between P10 and P60 (1). The timing of s differentiation and myelin formation requires highly localized signaling mechanisms, which involves the coordinated activation/inactivation of Wnt/β-catenin, Hedgehog/Gli1, Jagged1/Notch, and PI3K/Akt/mTOR cascades (3). Disruption of these pathways via gene manipulation or modulation of their regulators results in defective OL development. For example, PI3K depletion causes reduced myelin expression in the cerebral cortex and striatum (4). On the other hand, mutation of PTEN, the negative regulator of PI3K/Akt cascade, causes thickening and unraveling of the myelin sheath surrounding hypertrophic axons in the corpus callosum (CC) (5).Phosphoinositide 3-kinase enhancer L (PIKE-L) is a CNS-specific GTPase that belongs to the centaurin family (6, 7). It participates in numerous cellular events to regulate neuronal activity and survival. Our previous studies show that PIKE-L interacts with both netrin receptor (UNC5H) and metabotropic glutamate receptor I (mGlu₁) to prevent apoptotic cell death (8, 9). In addition, PIKE-L controls cell-surface trafficking of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor and the formation of long-term potentiation in the postsynaptic neurons (10). Moreover, PIKE controls the neuronal dendritogenesis and survival through maintaining the integrity of the PI3K/Akt pathway (11). Indeed, PIKE is an important molecular switch to control the cellular PI3K/Akt activation as it links extracellular stimuli including netrin, glutamate, and neurotrophins to the intrinsic PI3K/Akt activities (12–14). Nevertheless, the functions of PIKE-L in nonneuronal cells such as OLs and astrocytes still remain unexplored. In this paper, we report that PIKE-L signals through the PI3K/Akt pathway to advance CNS myelinogenesis.     

The clinical landmark of infraorbital foramen in Chinese population: a prospective measurement study

Background

Infraorbital nerve block can only be administered effectively with good knowledge of the location of the infraorbital foramen (IOF). In this article, we will describe the clinical landmark of the IOF with references to the infraorbital rim (IOR), mid-pupillary line (MPL), and facial midline (FML).

Methods

In our division, maxillary swing approach was adopted for the access of the nasopharynx and skull base. Through a Weber-Ferguson-Longmire incision, the maxilla was freed from its bony connections and swung out to expose the skull base. With this approach, the infraorbital foramen and nerve were identified under direct vision. Prospective measurements were taken intraoperatively on a series of patients who underwent maxillary swing operation. The distances between the IOF and various reference points (IOR, MPL, and FML) were measured with caliper. Means, standard deviations, and ranges were determined.

Results

From April 2009 to October 2012, 30 patients were included in this study. The locations of 30 infraorbital foramina were analyzed. The distances between IOF and IOR, MPL, and FML ranged from 8 to 12 (mean 9.6?±?1.3) mm, 4 to 14 (mean 9.3?±?2.4) mm, and 24 to 38 (mean 32.7?±?3.4) mm, respectively.

Conclusions

To our knowledge, this is the first study in the literature demonstrating the clinical landmark of IOF on living persons and adopting MPL as a reference point. We believe that the IOR and MPL are convenient reference points for the accurate localization of IOF. Level of Evidence: Level IV, diagnostic study.     

Searching health information via the web: Hong Kong chinese older adults' experience

OBJECTIVE AND SAMPLE: This paper reports on the learning experience of 88 Chinese older adults who attended a health Web-navigating workshop. DESIGN: Through a 3-hr training workshop, participants were guided to browse through seven health Web sites that provide authoritative health information by the Hong Kong government, academic institutions, or professional bodies. METHODS: Upon completion of the workshop, an evaluation was made of the participants' confidence in navigating health Web sites by themselves at home and in utilizing the health information sources. RESULTS: The findings indicated that participants' confidence in seeking health information via the Internet was not associated with their age, educational level, or experience of using computers before the workshop but was significantly associated with their satisfaction with the workshop (p<.05). Significant change of source of health information was noted at follow-up, suggesting that the workshop was successful. CONCLUSIONS: Implications of the results for running health Web-navigating programs among Chinese older adults are discussed.     

Cyclooxygenase expression in splanchnic hyposensitivity to glypressin of bleeding portal hypertensive rats

BACKGROUND: Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL). METHODS: Fourteen days after the operation, the rats were divided into without- and with-bleeding groups. Three series of PVL rats were used to investigate (i). the haemodynamic effects of glypressin (0.07 mg x kg(-1) intravenously), (ii). COX-1/COX-2 mRNA expression over abdominal aorta and superior mesenteric artery and (iii). plasma levels of 6-keto-prostaglandin-F1alpha. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was re-infused before blood and vessel sampling or the administration of glypressin. RESULTS: Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage-transfused PVL rats with enhanced COX-1 expression of superior mesenteric artery and increased plasma levels of 6-keto-prostaglandin-F1alpha. There were no differences in the COX-2 expression of superior mesenteric artery and COX-1 and COX-2 expressions of abdominal aorta between without- and with-bleeding groups. CONCLUSION: In portal hypertensive rats with acute haemorrhage, COX-1 over-expression in the superior mesenteric artery plays a role in mediating the splanchnic hyposensitivity to glypressin.     

Measuring symptom prevalence, severity and distress of cancer survivors

The purpose of this paper is to describe patients’ self-reported symptom occurrence, symptom intensity and symptom distress at post-treatment of cancer therapy. A total of 243 outpatients with heterogeneous solid tumours within 12 months following the completion of initial cancer treatment (chemotherapy or radiotherapy) were assessed using the Chinese version of the Memorial Symptom Assessment Scale (MSAS). The mean age of the sample was 54.2 ± 12 and over half (57.6%) were women. The most common diagnoses were breast cancer (26.3%) and colon cancer (23.5%). The median number of symptoms per patient was 8 (range 0–23 symptoms) and the most prevalent were dry mouth (49.8%), lack of energy (46.9%), worry (39.1%), pain (35%) and feeling drowsy (33.7%). The mean symptom severity and distress scores measured on the MSAS were 1.92 ± 0.2 (range 1.7–2.3) and 1.37 ± 0.3 (.9–2), respectively. The prevalence of certain symptoms was influenced by the primary site of cancer. Pain, worrying and difficulty in swallowing were the most clinically important symptoms. In conclusion, intense physical and psychological symptoms were highly prevalent and distressing to cancer survivors. Comprehensive symptoms assessment is a requisite toward effective symptom control.     

Nonlinear characteristics of heart rate variability during unsupervised and steady physical activities

The heart rate (HR) exhibits various behavior patterns in different postures and during physical activities, whereas a conventional long-term analysis of HR variability has the confounding effect whether the subject was physically active or immobilized. A specially designed ambulatory recorder that simultaneously measures the electrocardiogram and body accelerations was used to study the short-term (< or =11 beats, alpha1) fractal correlation property and the approximate entropy (ApEn) of RR interval data during sleep, sitting and standing (passive standing or mild walking) levels and immediately after rising in the morning in 15 healthy subjects. The alpha1 exponent that increased from sleep to sitting to standing implies an increased correlation of HR dynamics, which is concomitant with an increased ratio of low-frequency power to high-frequency power (LF/HF) that is usually linked with an increased sympathetic activity. A lower ApEn value during standing and after rising implies a reduced complexity of HR dynamics. Compared to the HR measures during the standing level, the LF/HF ratio showed a quick autonomic shift and alpha1 showed a rapid recruitment of fractal HR behavior after rising, whereas the ApEn value had a slower recovery of HR complexity. In conclusion, both linear and nonlinear HR behaviors during different unsupervised physical activities can be better interpreted with the aid of the recorded movement data.     

Doppler blood flow velocity waveforms in alpha-thalassemia hydrops fetalis

Doppler shift blood flow velocity-time waveforms in the umbilical arteries (UA), aorta (A), and inferior vena cava (IVC) in eight fetuses with alpha-thalassemia (alpha-thal) hydrops fetalis were described. The UA waveforms in these fetuses with anemia in utero depicted a hyperdynamic circulatory state with a relative increase in acceleration slope, more linear decline from maximum systole to end diastole, and reduced spectral broadening. The aortic waveforms similarly displayed distorted systolic peaks, flow turbulence, and greatly elevated diastolic frequencies. Reversal of end diastolic flow in the IVC also indicated cardiac decompensation in these fetuses. Progressive changes in these waveforms were apparent in two fetuses that had serial evaluation. In another four fetuses in which alpha-thal major was diagnosed in the second trimester by DNA analysis and had Doppler evaluation before termination of pregnancy, consistent changes in the UA, A, and IVC waveforms were not observed. This study confirms the potential usefulness of Doppler spectral waveforms in depicting altered hemodynamic changes in the fetus and in the evaluation of hydrops fetalis. Doppler ultrasound examination can be included as part of the routine workup of hydrops fetalis.