Waterloo Vision and Mobility Study: Normal gait characteristics during dark and light adaptation in individuals with age-related maculopathy

The purpose of this study was to evaluate the gait responses of individuals with low vision compared to those of normal-visioned individuals when their vision is challenged by extreme levels of light. Twenty subjects with age-related maculopathy (ARM) and 20 subjects with normal vision first walked along a flat, unobstructed path immediately after the ambient light level was changed from low (5 lux) to high (2500 lux). The procedure was repeated after the light was reduced from the high to the low level. Muscle activity, temporal and kinematic variables, and ground reaction forces were used to detect gait characteristics because of ambient light level changes. Data suggested that ARM subjects walked slower and with more caution than normal subjects but that these differences were not related to ambient light level. Head angle, an estimate of gaze direction, was lower for ARM subjects during high light, but the gaze direction for both groups was low during low light. Among these ARM subjects, extreme levels of ambient light did not affect gait; subjects made adaptations that were reasonable to encourage safe ambulation, despite the direction of light change. Normal-visioned individuals in this study experienced more difficulty in low light than high light situations.     

Effects of nicotine on bacterial toxins associated with cot death

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.     

Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration

First (DeltaE1/E3) and second (DeltaE1+DeltaE2/E3/E4) generation adenovirus (Ad) vectors have been shown previously to be of limited use in the treatment of human genetic diseases due to the induction of a host cytotoxic T-cell mediated immune response against virally expressed genes. In addition, a limited cloning capacity of approximately 8 kb does not cater for the incorporation of large upstream sequences essential for regulated tissue-specific expression or inclusion of multiple gene-expression cassettes. In this study we have exploited our recently developed Ad-based vector, the encapsidated adenovirus mini-chromosome (EAM) from which all of the viral genes have been deleted. EAMs contain only the inverted terminal repeats required for replication and five cis -acting Ad encapsidation signals necessary for packaging. We have shown previously that EAMs can efficiently transduce a variety of cell types in vitro. In this study we demonstrate that EAMs can transduce and rescue cells from the neurosensory retina in vivo. EAM-mediated delivery of the beta subunit of cyclic GMP phosphodiesterase (PDE) cDNA to mice affected with retinal degeneration (rd) allows prolonged transgene expression and rescue of rod photoreceptor cells. RT-PCR analysis from the injected retina indicates that transgene products are present for at least 18 weeks post-injection. Both the alpha and beta subunits of PDE could be detected up to 90 days postnatal in EAM-injected rd retina by western analysis. A maximal PDE activity of 150 nm/min/mg was detected at 33 days postnatal. Examination of outer nuclear thickness showed significant differences up to 12 weeks post-injection. These results demonstrate an improved level of rescue over first-generation adenoviral vectors and suggest the possibility of successful EAM- mediated treatment of some retinal diseases in humans.      

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

瞬时性受体电位通道香草酸受体5、6与骨代谢的关系

目的:探讨瞬时性受体电位通道香草酸受体5、6与骨代谢的关系。资料来源:应用计算机检索PubMed数据库1999-01/2006-07相关瞬时性受体电位通道方面的文献,检索词“TRPV”,限定文献语言种类为English。资料选择:对资料进行初审,选取包括瞬时性受体电位通道香草酸受体5、6的文献,开始查找全文。纳入标准:对两者及瞬时性受体电位通道家族进行研究的文章。排除标准:研究内容局限于瞬时性受体电位通道香草酸受体1～4的文章。资料提炼:共检索到106篇关于瞬时性受体电位通道香草酸受体的文献,最终纳入30篇符合标准的文献。资料综合:瞬时性受体电位通道香草酸受体5、6是瞬时性受体电位通道超家族中的成员,是专门的上皮样钙离子通道。目前研究已经证明它们在肠道和肾脏等组织中有表达,并对跨细胞钙离子转运起着关键性调控作用。但在骨组织中表达情况相关报道较少,在骨代谢机制上的研究更少,本文针对目前两者与骨代谢的关系进行综述。结论:深入研究瞬时性受体电位通道香草酸受体5、6钙离子通道在骨代谢中的作用,对于那些与骨代谢相关疾病的治疗将能从分子水平上找到解决的方法。