Systemic administration of antisense p75(NTR) oligodeoxynucleotides rescues axotomised spinal motor neurons

The 75 kD low-affinity neurotrophin receptor (p75(NTR)) is expressed in developing and axotomised spinal motor neurons. There is now convincing evidence that p75NTR can, under some circumstances, become cytotoxic and promote neuronal cell death. We report here that a single application of antisense p75(NTR) oligodeoxynucleotides to the proximal nerve stumps of neonatal rats significantly reduces the loss of axotomised motor neurons compared to controls treated with nonsense oligodeoxynucleotides or phosphate-buffered saline. Our investigations also show that daily systemic intraperitoneal injections of antisense p75(NTR) oligodeoxynucleotides for 14 days significantly reduce the loss of axotomised motor neurons compared to controls. Furthermore, we found that systemic delivery over a similar period continues to be effective following axotomy when intraperitoneal injections were 1) administered after a delay of 24 hr, 2) limited to the first 7 days, or 3) administered every third day. In addition, p75(NTR) protein levels were reduced in spinal motor neurons following treatment with antisense p75(NTR) oligodeoxynucleotides. There were also no obvious side effects associated with antisense p75(NTR) oligodeoxynucleotide treatments as determined by behavioural observations and postnatal weight gain. Our findings indicate that antisense-based strategies could be a novel approach for the prevention of motor neuron degeneration associated with injuries or disease. (C) 2001 Wiley-Liss, Inc.

Vehicle and driver attributes affecting distance from the steering wheel in motor vehicles

The current study was designed to confirm that female drivers sit closer to the steering wheel than do male drivers and to investigate whether this expected difference in sitting position is attributable to differences in the physical dimensions of men and women. Driver body dimensions and multiple measures of sitting distance from the steering wheel were collected from a sample of 150 men and 150 women. The results confirmed that on average, women sit closer to the steering wheel than men do and that this difference is accounted for by variations in body dimensions, especially height. This result suggests that driver height may provide a good surrogate for sitting distance from the steering wheel when investigating the role of driver position in real-world crash outcomes. The potential applications of this research include change to vehicle design that allows independent adjustment of the relative distance among the driver's seat, the steering wheel, and the floor pedals.

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: The Health, Aging, and Body Composition Study

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm(2)) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both PM and muscle strength contributed to limb BMD. The following were the respective Beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-6.9 %; lower limb,.0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7 %; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa

User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 yea rs and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001)for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.

Challenges and approaches to estimating mortality attributable to the use of selected illicit drugs

A number of unique challenges are faced when attempting to estimate mortality attributable to illicit drugs. The hidden nature of illicit drug use creates difficulties in quantifying the prevalence of such use; identifying adverse health effects associated with exposure, and calculating the risk of these effects. The use of cohort studies of drug users allows the identification of causes of mortality associated with drug use and the determination of the risk of these causes. This risk estimate can then be used in conjunction with estimates of the prevalence of drug use to, extrapolate the burden of mortality. We identify a number of such studies and present some solutions to the major challenges faced when attempting to estimate the global burden of mortality attributable to illicit drug use. Copyright (C) 2001 S. Karger AG, Basel.

Motor imagery in Parkinson's disease: A PET study

We used positron emission tomography (PET) with O-15-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically off and after turning on as a result of dopaminergic stimulation. They were asked to imagine a Finger opposition movement performed with their right hand. externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal de-rees of activation of the SMA (proper) when both off and on. Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both off and when on) and ipsilateral premotor cortex (when off only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task on compared with their performance when off. PD patients when imagining movement and off showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when on. Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes a-re likely to contribute to the motor deficit in PD. (C) 2001 Movement Disorder Society.

Aspects of the biology of the yabby Trypea australiensis (Dana) (Decapoda : Thalassinidea) and the potential of burrow counts as an indirect measure of population density

The thalassinidean shrimp Trypea australiensis (the yabby) commonly occurs on intertidal sandflats and subtidal regions of sheltered embayments and estuaries along the east coast of Australia and is harvested commercially and recreationally for use as bait by anglers. The potential for counts of burrow openings to provide a reliable indirect estimate of the abundance of yabbies was examined on intertidal sandflats on North Stradbroke Island (Queensland, Australia). The relationship between the number of burrow openings and the abundance of yabbies was generally poor and also varied significantly through time, casting doubt on previous estimates of abundance for this species based on unvalidated hole counts. Spatial and temporal variation in population density, the size at maturity and the reproductive period of the yabby were also assessed. Except for an initial peak in abundance as a result of recruitment, the density of yabbies was constant throughout the study but considerably less than that estimated from a previous study in the same area. Ovigerous females were recorded at 3 mm carapace length (CL) which is smaller than previously recorded for this species and thalassinideans in general. Small ovigerous females were found throughout the study, including the summer months, which is unusual for thalassinideans in the intertidal zone. It was hypothesised that in the intertidal zone, small female yabbies may be able to balance the metabolic demands of reproduction and respiration at higher temperatures than can larger females allowing them to reproduce in the warmer months.

Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

We previously showed that 16-day-old rats exposed to a relatively high dose of ethanol at 10-15 postnatal days of age have fewer neurons in the hilus region of the hippocampus compared with controls. Dentate gyrus granule cell numbers, however, showed no statistically significant changes attributable to the ethanol treatment. It is possible that some of the changes in brain morphology, brought about as a result of the exposure to ethanol during early life, may not be manifested until later in life. This question has been further addressed in an extension to our previous study. Wistar rats were exposed to a relatively high daily dose of ethanol on postnatal days 10-15 by placement in a chamber containing ethanol vapour, for 3 h/day. The blood ethanol concentration was found to be similar to430 mg/dl at the end of the period of exposure. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anaesthetised and killed either at 16 or 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle and the physical disector methods were used to estimate, respectively, the regional volumes and neuron cell numerical densities in the hilus and granule cell regions of the dentate gyrus. The total numbers of neurons in the hilus region and granule cell layer were computed from these estimates. It was found that 16-day-old animals had 398,000-441,000 granule cells, irrespective of group. The numbers of granule cells increased such that by 30 days of age, rats had 487,000-525,500 granule cells. However, there were no significant differences between ethanol-treated rats and their age-matched controls in granule cell numbers. In contrast, ethanol-treated rats had slightly but significantly fewer neurons in the hilus region than did control animals at 16 days of age, but not at 30 days of age. Therefore, it appears that a short period of ethanol exposure during early life can have effects on neuron numbers of some hippocampal neurons, but not others. The effects on hilar neuron numbers, observed as a result of such short periods of ethanol treatment, appeared to be transitory. (C) 2003 Wiley-Liss, Inc.

Effects of age and alcohol exposure during early life on pyramidal cell numbers in the CA1-CA3 region of the rat hippocampus

We have previously shown that exposing rats to a relatively high dose of ethanol during early postnatal life can result in an alteration in spatial learning ability. The hippocampal formation is known to be involved in the control of this ability. The purpose of the present study was to determine whether exposure of rats to ethanol during early postnatal life had either immediate or delayed effects on the numbers of pyramidal cells in the CA1-CA3 subregion of the hippocampus. Wistar rats were exposed to a relatively high daily dose of ethanol at postnatal day 10-15 by placing them for 3 h/day in a chamber containing ethanol vapor. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anesthetized and killed at 16 and 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volumes of the CA1 and CA2+CA3 regions. The physical disector method was used to estimate the numerical density of neurons in each of the subdivisions. The total number of pyramidal cells was calculated by multiplying the appropriate estimates of the numerical density by the volume. There were significant age-related reductions in the total numbers of pyramidal cells at 16-30 days of age irrespective of the groups examined. Ethanol treated rats were found to have slightly but significantly fewer pyramidal cell neurons than either the MRC or SC groups. These observations indicate that pyramidal cells in the hippocampus may be vulnerable to a relatively high dose of ethanol exposure during this short period of early postnatal life. (C) 2003 Wiley-Liss, Inc.

Development Resource Planning: Complexity of Product Development and the Capacity to Launch New Products

Overcommitment of development capacity or development resource deficiencies are important problems in new product development (NPD). Existing approaches to development resource planning have largely neglected the issue of resource magnitude required for NPD. This research aims to fill the void by developing a simple higher-level aggregate model based on an intuitive idea: The number of new product families that a firm can effectively undertake is bound by the complexity of its products or systems and the total amount of resources allocated to NPD. This study examines three manufacturing companies to verify the proposed model. The empirical results confirm the study`s initial hypothesis: The more complex the product family, the smaller the number of product families that are launched per unit of revenue. Several suggestions and implications for managing NPD resources are discussed, such as how this study`s model can establish an upper limit for the capacity to develop and launch new product families.

Females of the weevil Zabrotes subfasciatus manipulate the size and number of eggs according to the host seed availability

In some insects, the finding of oviposition substrate triggers the uptake into oocytes of yolk proteins that are stored in the fat body during post-embryonic development. The main host of the bean weevil Zabrotes subfasciatus (Coleoptera; Chrysomelidae; Bruchinae; Amblycerini), in which larval resources are the sole source for future egg maturation, is Phaseolus vulgaris. Despite not feeding as adults, females of this species are able to lay eggs after encountering host seeds but it is not known how females react to changes in the availability of bean seeds. In the present study, the behaviour of Z. subfasciatus facing two very different environments for oviposition is investigated, as well as how this influences offspring fitness. The results obtained show that females of Z. subfasciatus react to variations in the availability of seeds belonging to the same host species by adjusting egg size and number. Females on low bean seed density lay larger and fewer eggs than those on high bean seed density, demonstrating a trade-off between these reproductive traits. Moreover, females can adjust egg size to changing levels of host availability during the first 4 days of their oviposition period. Although no difference in offspring weight is found, those from small eggs (low competition environment) result in larger adults. No response to selection on these traits after rearing beetles on the same host for 40 generations is observed. This unresponsiveness may indicate that beetle populations behave according to their reaction norm that already allows rapid adaptation to a varying amount of host-seed availability and better exploitation of the environments of this widespread stored-seed pest.

Reproductive strategy of the snapping shrimp Alpheus armillatus H. Milne-Edwards, 1837 in the South Atlantic: fecundity, egg features, and reproductive output

The family Alpheidae, composed by shrimps of relatively small size, popularly known as snapping shrimps, is the one of the most diverse decapod groups. These shrimps are found worldwide and Occur in tropical and subtropical waters, from the intertidal zone to great depths. We investigated reproductive aspects of Alpheus armillatus, in order to gather information on egg production, aiming to enhance knowledge of its reproductive strategies in a population in an intertidal area of the South Atlantic. Ovigerous females were collected under rocks, in May and July 2006 (dry season) and in November 2006 and March 2007 (rainy season). Egg production and reproductive output were analyzed and compared seasonally and during the period of embryonic development. Females measured on average 11.28 mm CL with a mean of 763 eggs and 0.11 mm(3) egg volume. The egg volume of this population was smaller than previous estimates for other species of snapping shrimps, but the mean egg number was higher. The volume of eggs doubled during the incubation period, but despite this increase, no significant loss of eggs was observed. Alpheus armillatus invests oil average about 12% of body weight in reproduction. The proportional investment in egg production IS Significantly higher in the rainy season when compared with the dry season (17.9% vs 4.8%), correlated with higher temperatures and increased food availability at this time. Our results corroborated the hypothesis of a pattern of egg production influenced by environmental conditions and intraspecific variability among the family Alpheidae, as a function of the biogeographic region.

Increase of gingival matured dendritic cells number in elderly patients with chronic periodontitis

Objective: The purpose of this study was to evaluate the inflammatory cell subset proportions in the upper gingival connective tissue, including mature dendritic cells (DC) in elderly and younger patients with generalized chronic periodontitis in order to further understand the effect of aging on gingival inflammatory phenomenon. Methods: Gingival tissue specimens presenting chronic periodontitis from 8 elderly patients aged >75 (test group, group T) and from 8 younger patients aged 50-60 (considered as controls, group C) were analysed by immunohistochemistry using monoclonal antibodies against CD45RB, CD4, CD8, CD19, CD68, DC-SIGN, DC-LAMP molecules. The number of each immunolabelled cells subset was counted using image analysis. Results: The difference in the number of CD45RB + leucocytes in the upper gingival connective tissue between groups was not significant permitting to use it as reference. As compared. to group C, the lymphocyte subsets/CD45RB + leucocytes ratios tended to decrease in group T but the decrease was significant only for CD4 + T lymphocytes/ CD45RB + cells ratio (p < 0.03). On the opposite, the ratios of antigen-presenting cells DC-SIGN + cells/CD45RB + cells and DC-LAMP + cells/CD45RB + cells were significantly increased;(p < 0.03 and <0.0001, respectively) in group T. Moreover, in group T the DC-LAMP + cells/DC-SIGN + cells ratio was significantly increased (p < 0.05) showing an increased number of matured dendritic cells. Conclusion: During chronic periodontitis in elderly patients, our results show a decrease in the ratio of gingival CD4 + lymphocyte subset associated with an increase in the ratios of antigen-presenting cells subsets and more particularly maturated DC-LAMP + dendritic cells. (C) 2008 Elsevier Ltd. All rights reserved.