Disconnected optic axons persist in the visual pathway during regeneration of the retino-tectal projection in the frog

Summary In this study, we crushed one optic nerve in the frog Litoria (Hyla) moorei and at intervals thereafter anterogradely labelled optic axons with horseradish peroxidase (HRP). For one series, HRP was applied between the eye and the crush site and in a second series between the crush site and the chiasm. A tectal projection of regenerating axons was seen in both series but, in addition, up to 12 weeks post-crush, the second series displayed an additional projection. Its appearance matched that of the disconnected, but persisting, optic axon terminals which are found after enucleation or optic nerve ligation. We conclude that, in the frog, many disconnected optic axons persist throughout the period of optic nerve regeneration and of restoration of an orderly retino-tectal map.Abbreviation HRP horseradish peroxidase     

Bone width is correlated positively with the upper to the lower segment ratio in elderly men--the MINOS study

Before puberty, limbs grow more rapidly than the spine. During puberty, lengthening of the spine and increase in bone width accelerate. Correlation of parameters with lengths of the upper and lower segments and with the upper/lower segment ratio may indicate the period of growth critical for their determination. We assessed the association of bone mineral and width with the upper/lower segment ratio in 542 elderly men from the MINOS cohort. Areal bone mineral density (aBMD) was measured at the lumbar spine and right hip using pencil-beam dual-energy X-ray absorptiometry and at the distal forearm using single energy X-ray absorptiometry. Upper/lower segment ratio correlated positively with bone mineral content (BMC), aBMD and width of third lumbar vertebra (L3), femoral neck and distal radius. Men in the highest quartile of the upper/lower segment ratio had larger bones by 2.5 to 5.0% (0.3-0.4 SD, p<0.02-0.002) compared with the lowest quartile. Bone width correlated more strongly with the upper segment length than with that of the lower one. Volumetric BMD (vBMD) did not correlate with the upper/lower segment ratio nor with the lengths of the body segments. At the femoral neck and distal radius, men in the highest quartile of the upper/lower segment ratio had higher estimated cortical thickness (5.3%, 0.41 SD, p<0.01 and 4.0%, 0.31 SD, p<0.03), bigger cortical area (8.0%, 0.54 SD and 6.8%, 0.52 SD, p<0.0001) and higher estimated bending strength (9.3 to 13.3%, 0.46 to 0.54 SD, p<0.0001). Elderly men with the higher upper/lower segment ratio had higher BMC and bending strength because they had wider bones, not higher vBMD. The bone size correlated positively with the length of the upper segment, not negatively with that of the lower segment. Our data may suggest an important role of pubertal growth for both bone width and strength in men but do not establish the determinants of this association. Given methodological limitations, these results need to be confirmed in a younger and more representative group of men.     

Flexible real-time control of MagStim 200(2) units for use in transcranial magnetic stimulation studies

A method for two-way serial communication with MagStim 200(2) BiStim units using LabVIEW is described. A suite of LabVIEW 'virtual instruments' which give simple and reliable control of pulse parameters and delivery is described and made freely available online. The advantages of serial control include the ability to quickly and reliably change pulse parameters during an experiment, to randomly intersperse pulses with different parameters without manually resetting the unit, to deliver pulses with a reliable temporal relationship to other external events, and to control pulse parameters interactively. An application that uses the method for adaptive control of pulse intensity is reported.     

Enhanced recombinant adeno-associated virus-mediated vascular endothelial growth factor expression in the adult mouse retina: a potential model for diabetic retinopathy

Diabetic retinopathy, one of the most serious complications of long-term diabetes, could clinically be divided into two stages: 1) background retinopathy that does not cause visual impairment and 2) proliferative retinopathy, which is a potentially blinding condition. This study aims to investigate the correlation between enhancement of vascular endothelial growth factor (VEGF) expression and neovascular changes. A binary recombinant adeno-associated virus construct producing green fluorescent protein (GFP) and VEGF under the control of the human cytomegalovirus promoter, recombinant adeno-associated virus (rAAV).VEGF.GFP, was produced and injected into the subretinal space of C57BL mice. GFP expression was tracked by fluorescence fundus photography, and VEGF expression was confirmed by immunohistochemistry and enzyme-linked immunoassay. Neovascular changes were monitored by fluorescein angiography and histology and by quantifying the number of inner retinal vessels. GFP expression was found in 100% of injected eyes, and vascular changes were detected in 9 of 10 rAAV.VEGF.GFP-injected eyes. Of these, four demonstrated microaneurysms and five showed moderate to severe leakage. There was a statistically significant increase in blood vessel number in the inner nuclear layer (P < 0.03) and dilatation of retinal veins (P < or = 0.05). This work has demonstrated that the development of different stages of diabetic retinopathy is closely correlated with an increased VEGF level in the retina.     

The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women

Summary  Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70–85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. Introduction  Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70–85 years. Methods  Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. Results  The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (−2.8%) compared to the middle (−1.6%) and lowest tertiles (−1.2%) (P < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. Conclusion  In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.     

A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women

BACKGROUND: Airway remodelling is a characteristic feature of chronic asthma and there is evidence that an airway imbalance between levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) is associated with airway remodelling. On this basis, we hypothesised that polymorphisms in the MMP-9 and TIMP-1 genes were associated with the disease process. METHODS: A number of MMP-9 and TIMP-1 gene polymorphisms were examined in an adult white Australian population of mild (n = 259), moderate (n = 213) and severe (n = 71) asthmatics and non-asthmatic controls (n = 406) using PCR-RFLP and PCR-SSCP analyses. RESULTS: MMP-9 -1562C>T and 836G>A (Arg279Gln) were not associated with asthma (p> or =0.15) or asthma severity (p> or =0.13), and TIMP-1 434T>C (Phe124Phe) was not associated with asthma in women (p = 0.094) or men (p = 0.207). In this population, MMP-9 -861C>T and TIMP-1 323C>T (Pro87Pro) were not informative (with minor allele frequencies of <1%), and MMP-9 -1702T>A and TIMP-1 595C>T (Ser178Phe) were not detectable. However, a novel polymorphism was detected in the TIMP-1 gene 536C>T (Ile158Ile) which was significantly associated with asthma in women (p = 0.011; OR = 5.54, 95% CI 1.66 to 34.4) but not in men (p = 1.0). 536C>T was found to be in linkage disequilibrium with 434T>C, and haplotype analysis supported an association with asthma (p = 0.014). CONCLUSIONS: This is the first reported association between a polymorphism in the TIMP-1 gene and asthma, and supports the hypothesis that the protease/antiprotease balance has an important role in this common disease.     

Rapid slowing of maximal finger movement rate: fatigue of central motor control?

Exploring the limits of the motor system can provide insights into the mechanisms underlying performance deterioration, such as force loss during fatiguing isometric muscle contraction, which has been shown to be due to both peripheral and central factors. However, the role of central factors in performance deterioration during dynamic tasks has received little attention. We studied index finger flexion/extension movement performed at maximum voluntary rate (MVR) in ten healthy subjects, measuring movement rate and amplitude over time, and performed measures of peripheral fatigue. During 20 s finger movements at MVR, there was a decline in movement rate beginning at 7–9 s and continuing until the end of the task, reaching 73% of baseline (P < 0.001), while amplitude remained unchanged. Isometric maximum voluntary contraction force and speed of single ballistic flexion and extension finger movements remained unchanged after the task, indicating a lack of peripheral fatigue. The timing of finger flexor and extensor EMG burst activity changed during the task from an alternating flexion/extension pattern to a less effective co-contraction pattern. Overall, these findings suggest a breakdown of motor control rather than failure of muscle force generation during an MVR task, and therefore that the mechanisms underlying the early decline in movement rate are central in origin.     

Behavioral management of headache triggers: Avoidance of triggers is an inadequate strategy

The standard clinical advice for individuals who suffer from recurrent headaches is that the best way to prevent headaches is to avoid the triggers. This review challenges that advice from a number of perspectives, including: that the advice is given in a theoretical vacuum; it is associated with practical problems; and it is not evidence-based. The review considers cognate literatures on stress, negative affect, and chronic pain that advocate approach/confront strategies over avoidance strategies. It is suggested that advice to avoid triggers could result in maintenance of the capacity of the trigger to precipitate headaches or even a sensitization process whereby tolerance diminishes. As anxiety researchers have investigated extensively the issue of how stimuli acquire and lose their capacity to elicit fear, this literature is explored to draw inferences for headache triggers. The review concludes with suggestions concerning etiology of chronic headache and associated management implications, and directions for future research. It argues that the philosophy of ‘avoidance of triggers’ should be replaced with ‘coping with triggers,’ as the latter includes both avoidance and approach/confront strategies involving exposure to triggers.     

Longitudinal study of risk factors for habitual snoring in a general adult population: the Busselton Health Study

BACKGROUND: The aim of this longitudinal study was to identify body size, behavioral, and respiratory risk factors for the development of habitual snoring in a general adult population. METHODS: The sample for this study comprised 967 adults aged 25 to 74 years who reported not snoring in the 1981 Busselton Health Survey and who also attended the 1994-1995 follow-up survey. Logistic regression was used to identify and quantify the effect of baseline and change risk factors for the development of habitual snoring. RESULTS: A total of 13% had become habitual snorers by 1994-1995. Male gender (odds ratio [OR], 3.5) and baseline body mass index (OR, 1.4 per 3.4 kg/m(2)) were significant predictors of habitual snoring; after accounting for these variables, no other baseline body size, behavioral, or respiratory/allergy variables were significantly related to the development of habitual snoring. However, change in body mass index over the 14-year follow-up period (OR, 1.55 per 2.3 kg/m(2)), development of asthma (OR, 2.8), and commencement of smoking (OR, 2.2) were additional significant independent risk factors for development of habitual snoring. CONCLUSIONS: This study has confirmed male gender, obesity, and weight gain as key determinants of habitual snoring, and has indicated that development of asthma and taking up smoking also play a role. Maintaining a healthy weight and not smoking are recommended lifestyle preventive strategies to reduce the risk of sleep-disordered breathing and its sequelae.