Genetic insights on sleep schedules: this time, it's PERsonal.

The study of circadian rhythms is emerging as a fruitful opportunity for understanding cellular mechanisms that govern human physiology and behavior, fueled by evidence directly linking sleep disorders to genetic mutations affecting circadian molecular pathways. Familial advanced sleep-phase disorder (FASPD) is the first recognized Mendelian circadian rhythm trait, and affected individuals exhibit exceptionally early sleep-wake onset due to altered post-translational regulation of period homolog 2 (PER2). Behavioral and cellular circadian rhythms are analogously affected because the circadian period length of behavior is reduced in the absence of environmental time cues, and cycle duration of the molecular clock is likewise shortened. In light of these findings, we review the PER2 dynamics in the context of circadian regulation to reveal the mechanism of sleep-schedule modulation. Understanding PER2 regulation and functionality may shed new light on how our genetic composition can influence our sleep-wake behaviors

Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

Why do we need to sleep? What regulates when we sleep? And what dictates the number of hours we require? These are often viewed as three separate biological questions. Here, we propose they share molecular etiologies, whereby regulators of sleep schedules and sleep duration also govern the physiological purposes of sleep. To support our hypothesis, we review Mendelian human genetic variants sufficient to advance sleep-wake onset (PER2) and shorten sleep length (DEC2), and evaluate their emerging roles in immune responses that may rely on a sound night of slumber

Aldose reductase deficiency protects the retinal neurons in a mouse model of retinopathy of prematurity

Poster Presentation: P64PURPOSE: Retinopathy of prematurity (ROP) is a common retinal disease occurred in premature babies. It is found to be related to oxidative stress while dysfunction of the neural retina has also been documented. We previously showed that genetic deletion or pharmacological inhibition of aldose reductase (AR), a rate- limiting enzyme in the polyol pathway, prevented ischemia-induced retinal ganglion cell (RGC) loss and oxidative stress. Here, we assessed the effects of AR deletion on retinal neurons using a mouse model of ROP. METHODS: Seven-day-old mouse pups were exposed to 75% oxygen for five days and returned to room air. The pathological neuronal changes were examined and compared between wild-type (WT) and AR-deficient retinae on P14 and P17 (P, postnatal). Retinal thickness was measured and immunohistochemistry for calbindin, calretinin, PKCα, Tuj1, glial fibrillary acidic protein (GFAP), nitrotyrosine (NT), as well as poly(ADP-ribose) (PAR) was performed. RESULTS: After hyperoxia exposure, significantly reduced inner nuclear layer (INL) and inner plexiform layer (IPL) thickness were found in both genotypes. The intensity of calbindin staining for horizontal cells in INL was reduced in the WT retinae but not in AR-deficient retinae. In addition, significant reduction was found in calretinin-positive amacrine cell bodies in central INL especially in WT retinae. Serious distortion was also observed in the three calretinin-positive strata along IPL in the WT retinae but not AR-deficient retinae on P17. Moreover, increased GFAP intensity across IPL indicating Müller cell processes was observed in AR-deficient retinae on P14 and in WT retinae on P17. Furthermore, increased NT immunoreactivity in INL and nuclear or para-nuclear PAR staining along GCL were observed in WT retina while these changes were not apparent in AR-deficient retina. CONCLUSION: Our observations demonstrated morphological changes of retinal neurons in the mouse model of ROP and indicated that AR deficiency showed neuronal protection in the retina, possibly through modulating glial responses and reducing oxidative stress.postprin

Primary hyperaldosteronism among Chinese hypertensive patients: how are we doing in a local district in Hong Kong

OBJECTIVES: To estimate the point prevalence of primary hyperaldosteronism in a government out-patient setting and to compare associated patient characteristics with those having essential hypertension. DESIGN: Case series with external comparison. SETTING: A single public hospital (Caritas Medical Centre) and all five associated general out-patient clinics in Sham Shui Po district in Hong Kong. PATIENTS: All patients with confirmed primary hyperaldosteronism and randomly selected patients with essential hypertension from a medical specialist clinic and general out-patient clinics, retrieved from a computer database for the period January 2007 to December 2008. MAIN OUTCOME MEASURES: Estimated point prevalence of primary hyperaldosteronism among hypertensive patients treated in the public sector of Sham Shui Po district. Patient age when hypertension was diagnosed, number of antihypertensive drugs used for treatment, and the presence of target organ damage in the patients with primary hyperaldosteronism and those with essential hypertension were compared. RESULTS: Among the 46 012 patients receiving antihypertensive treatment, 49 were confirmed to have primary hyperaldosteronism. The estimated point prevalence of primary hyperaldosteronism among these hypertensive patients was 0.106% only, which was far smaller than figures from other countries. When compared with the 147 patients with essential hypertension by multivariate analysis, those with primary hyperaldosteronism were: (1) associated with longer durations of hypertension (odds ratio=1.14; 95% confidence interval, 1.06-1.24) despite being younger at the time of study, (2) likely to be taking three or more antihypertensive drugs (odds ratio=2.51; 95% confidence interval, 1.59-3.95), and (3) more likely to have left ventricular hypertrophy (odds ratio=5.01; 95% confidence interval, 1.83-13.69). All primary hyperaldosteronism patients studied presented with hypokalaemia. The need for antihypertensive drugs was markedly reduced after adrenalectomy for adrenal adenoma. CONCLUSIONS: Primary hyperaldosteronism, which is potentially a surgically curable cause of hypertension, appeared to be underdiagnosed in our locality. Screening by aldosterone-renin ratio of high-risk individuals may help improve patient outcomes.published_or_final_versio

The Effectiveness and Sustainability of a Universal School-Based Programme for Preventing Depression in Chinese Adolescents: A Follow-Up Study Using Quasi-Experimental Design

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The evaluation of the bone graft survival status in titanium cervical cages by radionuclide bone CT scan

To find a better way to evaluate the bone graft survival status in cervical cages, forty-one patients suffering from one-level cervical spondylosis were enrolled in this study. All underwent anterior cervical decompression and fusion with titanium cage and plate. When followed up, another 21 patients were confirmed as one-level cervical spondylosis without operation and were enrolled as control group. "Bolus" injection of radioactive 99mTc methylene diphosphonate (99mTc-MDP) with a dose of 25 ~ 30 mCi was performed through cubital vein, and radionuclide distribution images of cervical spine were obtained by single photon emission computed tomography/computed tomography (SPECT/CT). In sagittal view, bone graft was positioned accurately. By “region of interest” (ROI) technique, the same regions in bone graft and thoracic vertebra with the same level of suprasternal fossa were selected. Radioactive count ratio was then obtained. In the control group, “bone graft” was chosen on the inferior vertebra of the lesion segment, and the ratio was similarly gotten. Statistical difference was shown between bone graft group and control group by t test (t = 2.713, P < 0.05). The bone graft survival rate was 100% by SPECT/CT and bony fusion rate was 92.7% by CT scan. It indicated that in all bony fusion cases, bone graft survived; however, the bone survival was not surely together with bony fusion.Key words: Bone graft, titanium cervical cage, radionuclide bone CT

Anti-inflammatory effects of lutein in retinal ischemic injury: in vivo and in vitro studies

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The space group classification of topological band insulators

Topological band insulators (TBIs) are bulk insulating materials which feature topologically protected metallic states on their boundary. The existing classification departs from time-reversal symmetry, but the role of the crystal lattice symmetries in the physics of these topological states remained elusive. Here we provide the classification of TBIs protected not only by time-reversal, but also by crystalline symmetries. We find three broad classes of topological states: (a) Gamma-states robust against general time-reversal invariant perturbations; (b) Translationally-active states protected from elastic scattering, but susceptible to topological crystalline disorder; (c) Valley topological insulators sensitive to the effects of non-topological and crystalline disorder. These three classes give rise to 18 different two-dimensional, and, at least 70 three-dimensional TBIs, opening up a route for the systematic search for new types of TBIs.Comment: Accepted in Nature Physic

Tunneling magnetoresistance sensors with different coupled free layers

Large differences of magnetic coercivity (HC), exchange coupling field (HE), and tun- neling magnetoresistance ratio (TMR) in magnetic tunnel junctions with different coupled free layers are discussed. We demonstrate that the magnetization behavior of the free layer is not only dominated by the interfacial barrier layer but also affected largely by the magnetic or non-magnetic coupled free layers. All these parameters are sensitively controlled by the magnetic nanostructure, which can be tuned also by the magnetic annealing process. The optimized sensors exhibit a large field sensitivity of up to 261%/mT in the region of the reversal synthetic ferri- magnet at the pinned layers

Transitional care for a patient with chronic obstructive pulmonary disease

2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe