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

Helmets for preventing injury in motorcycle riders

Background: Motorcycle crash victims form a high proportion of those killed or injured in road traffic accidents. Injuries to the head, following motorcycle crashes, are a common cause of severe morbidity and mortality. It seems intuitive that helmets should protect against head injuries but it has been argued that motorcycle helmet use decreases rider vision and increases neck injuries. This review will collate the \u27current available evidence on helmets and their impact on mortality, and head, face and neck injuries following motorcycle crashes.Objectives: To quantify the effectiveness of wearing a motorcycle helmet in reducing mortality and head and neck injury following motorcycle crashes.Search strategy: Databases including the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1,2003), MEDLINE (January 1966 to February 2003), EMBASE (January 1985 to February 2003), CINAHL (January 1982 to February 2003), IRRD (International Road Research Documentation), TRANSDOC, TRIS (Transport Research Information Service), ATRI (Australian Transport Index) (1976 to Feb 2003), Science Citation Index were searched for relevant articles. Web sites of traffic and road accident research bodies including government agencies were also searched. Reference lists from topic reviews, identified studies and bibliographies were examined for relevant articles.Selection criteria: We considered for inclusion studies that investigated a population of motorcycle riders who had crashed, examining helmet use as an intervention and with outcomes that included one or more of the following: death, head, neck or facial injury. Studies included any that compared an intervention and control group and, therefore, included any randomised controlled trials, non-randomised controlled trials, cohort, case-control and cross-sectional studies. Ecological and case series studies were excluded.Data collection and analysis: Two reviewers independently screened reference lists for eligible articles. Two reviewers independently assessed articles for inclusion criteria. Data were abstracted by two independent reviewers using a standard abstraction form.Main results: Fifty-three observational studies were identified of varying quality. Despite methodological differences there was a remarkable consistency in results, particularly for mortality and head injury outcomes. Motorcycle helmets appear to reduce the risk of mortality although, due to heterogeneity in study design, an overall estimate of effect was not calculated. There was some evidence that the effect of helmets on mortality is modified by speed. Motorcycle helmets were found to reduce the risk of head injury and from five well-conducted studies the risk reduction is estimated to be 72% (OR 0.28, 95%CI 0.23,0.35). Insufficient evidence was found to estimate the effect of motorcycle helmets compared with no helmet on facial or neck injuries. However, studies of poorer quality suggest that helmets have no effect on the risk of neck injuries and are protective for facial injury. There was insufficient evidence to demonstrate whether differences in helmet type confer more or less advantage in injury reduction.Conclusions: Motorcycle helmets reduce the risk of mortality and head injury in motorcycle riders who crash, although the former effect may be modified by other crash factors such as speed. Further well-conducted research is required to determine the effects of helmets and different helmet types on mortalIty, head, neck and facial injuries. However, the findings suggest that global efforts to reduce road traffic injuries may be facilitated by increasing helmet use by motorcyclists.<br /

Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was performed on Epac1-deficient (Epac1) mice, Epac2-deficient (Epac2) mice, and their wild type counterparts (Epac1+/+ and Epac2+/+). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2 ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2+/+. However, Epac1 ipsilateral retinae displayed similar pathology as those in Epac1+/+ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.published_or_final_versio

Selective over-expression of endothelin-1 in endothelial cells exacerbates inner retinal edema and neuronal death in ischemic retina

The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over-expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Müller cell bodies and processes, increased AQP-4 immunoreactivity in Müller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema. © 2011 Cheung et al.published_or_final_versio

Carriage niches and molecular epidemiology of Staphylococcus lugdunensis and methicillin-resistant S. lugdunensis among patients undergoing long-term renal replacement therapy

We collected nasal, axilla, and groin swabs from 252 adult patients from 2 nephrology centers in Hong Kong. Staphylococcus lugdunensis carriage was detected in 51.6% patients (groin, 39.3%; axilla, 19.8%; nose, 17.9%). The carriage rates of methicillin-sensitive S. lugdunensis and methicillin-resistant S. lugdunensis (MRSL) were 46.0% and 8.3%, respectively. Independent risk factors for S. lugdunensis carriage included male sex (odds ratio [OR], 4.4), hemodialysis (OR, 2.2), and aged 18–50 years (OR, 2.4). The isolates belonged to 10 pulsotype clusters (n = 129) and 8 singletons (n = 8). All MRSL and most gentamicin- and tetracycline-resistant strains were found in a predominating sequence type 3 clone, designated HKU1, which accounted for 51.8% of all colonizing S. lugdunensis strains. The 21 MRSL isolates had SCCmec type V (n = 18), type IV (n = 2), and type I (n = 1). The finding highlights the potential for dissemination of multidrug resistance through successful S. lugdunensis clones.postprin

The Relationship Between Family Dining Practices, Parenting Style And Family Functioning And Child Learning

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Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

A Mobile Web App to Improve Health Screening Uptake in Men (ScreenMen): Utility and Usability Evaluation Study.

BACKGROUND: Globally, the uptake of health screening is suboptimal, especially in men and those of younger age. In view of the increasing internet access and mobile phone ownership, ScreenMen, a mobile Web app, was developed to improve health screening uptake in men. OBJECTIVE: This study aimed to evaluate the utility and usability of ScreenMen. METHODS: This study used both qualitative and quantitative methods. Healthy men working in a banking institution were recruited to participate in this study. They were purposively sampled according to job position, age, education level, and screening status. Men were asked to use ScreenMen independently while the screen activities were being recorded. Once completed, retrospective think aloud with playback was conducted with men to obtain their feedback. They were asked to answer the System Usability Scale (SUS). Intention to undergo screening pre- and postintervention was also measured. Qualitative data were analyzed using a framework approach followed by thematic analysis. For quantitative data, the mean SUS score was calculated and change in intention to screening was analyzed using McNemar test. RESULTS: In total, 24 men participated in this study. On the basis of the qualitative data, men found ScreenMen useful as they could learn more about their health risks and screening. They found ScreenMen convenient to use, which might trigger men to undergo screening. In terms of usability, men thought that ScreenMen was user-friendly and easy to understand. The key revision done on utility was the addition of a reminder function, whereas for usability, the revisions done were in terms of attracting and gaining users' trust, improving learnability, and making ScreenMen usable to all types of users. To attract men to use it, ScreenMen was introduced to users in terms of improving health instead of going for screening. Another important revision made was emphasizing the screening tests the users do not need, instead of just informing them about the screening tests they need. A Quick Assessment Mode was also added for users with limited attention span. The quantitative data showed that 8 out of 23 men (35%) planned to attend screening earlier than intended after using the ScreenMen. Furthermore, 4 out of 12 (33%) men who were in the precontemplation stage changed to either contemplation or preparation stage after using ScreenMen with P=.13. In terms of usability, the mean SUS score of 76.4 (SD 7.72) indicated that ScreenMen had good usability. CONCLUSIONS: This study showed that ScreenMen was acceptable to men in terms of its utility and usability. The preliminary data suggested that ScreenMen might increase men's intention to undergo screening. This paper also presented key lessons learned from the beta testing, which is useful for public health experts and researchers when developing a user-centered mobile Web app

Human papillomavirus status in southern Chinese women

1. The overall and type-specific human papillomavirus (HPV) prevalence differed between Hong Kong and Guangzhou healthy women. The prevalence of HPV was significantly higher in Guangzhou than Hong Kong women. Younger women had significantly higher risk of HPV infection. 2. HPV16 remained the most common type detected in both regions; the frequency increased with increasing disease severity. The prevalence of HPV58 and HPV52 was relatively high in women with normal cervix and precancerous lesions.published_or_final_versio

Age-related changes in eye lens biomechanics, morphology, refractive index and transparency

Life-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency. We conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Lens capsule thickness and peripheral fiber cell widths increased between 2 to 4 months of age but not further, and thus, cannot account for significant age-dependent increases in lens stiffness after 4 months. In lenses from mice older than 12 months, we routinely observed cataracts due to changes in cell structure, with anterior cataracts due to incomplete suture closure and a cortical ring cataract corresponding to a zone of compaction in cortical lens fiber cells. Refractive index measurements showed a rapid growth in peak refractive index between 1 to 6 months of age, and the area of highest refractive index is correlated with increases in lens nucleus size with age. These data provide a comprehensive overview of age-related changes in murine lenses, including lens size, stiffness, nuclear fraction, refractive index, transparency, capsule thickness and cell structure. Our results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies