Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia), cognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia composite) and three complementary magnetic resonance imaging measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared with placebo, l-methylfolate increased plasma methylfolate levels (d=1.00, P=0.0009) and improved PANSS Total (d=0.61, P=0.03) as well as PANSS Negative and General Psychopathology subscales. Although PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving l-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity and increased cortical thickness. In conclusion, l-methylfolate supplementation was associated with salutary physiological changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials. ClinicalTrials.gov, NCT01091506.

Disgust as an emotional driver of vaccine attitudes and uptake? A mediation analysis.

Research on the drivers of vaccine acceptance has expanded but most interventions fall short of coverage targets. We explored whether vaccine uptake is driven directly or indirectly by disgust with attitudes towards vaccines acting as a possible mediator. An online cross-sectional study of 1007 adults of the USA via Amazon's Mechanical Turk was conducted in January 2017. The questionnaire consisted of four sections: (1) items assessing attitudes towards vaccines and vaccine uptake, (2) revised Disgust Scale (DS-R) to measure Disgust Sensitivity, (3) Perceived Vulnerability to Disease scale (PVD) to measure Germ Aversion and Perceived Susceptibility, and (4) socio-demographic information. Using mediation analysis, we assess the direct, the indirect (through Vaccine Attitudes) and the total effect of Disgust Sensitivity, Germ Aversion and Perceived Susceptibility on 2016 self-reported flu vaccine uptake. Mediation analysis showed the effect of Disgust Sensitivity and Germ Aversion on vaccine uptake to be twofold: a direct positive effect on vaccine uptake and an indirect negative effect through Vaccine Attitudes. In contrast, Perceived Susceptibility was found to have only a direct positive effect on vaccine uptake. Nonetheless, these effects were attenuated and small compared to economic, logistic and psychological determinants of vaccine uptake.

Supplementing a yeast probiotic to pre-weaning Holstein calves: Feed intake, growth and fecal biomarkers of gut health.

Diarrhea, resulting from gastrointestinal infection by pathogens, is a common cause of the high mortality and morbidity of neonatal calves. The objective of this study was to evaluate the effects of supplementing a yeast product in milk replacer (MR) on growth and health of calves, and on fecal populations of some targeted microorganisms related to calf health and growth (i.e., total bacteria, Escherichia coli, Clostridium cluster XIVa, Faecalibacterium prausnitzii and Bifidobacterium spp.). We hypothesized that feeding a Saccharomyces cerevisiae var boulardii (SCB) product would improve gastrointestinal health and growth performance of calves. Forty-two Holstein bull calves (42.6 ± 0.77 kg at birth) were randomly assigned on day 2 of age to either a control or SCB treatment. The SCB was supplemented in MR and fed at 5 g/d per head to supply 10 billion colony-forming units per day. All calves received high quality colostrum (>50 mg/mL of immunoglobulin G) during the first 24 h of life, and were fed with 8 L MR (150 g/L mixed with 40 °C water) daily from day 2-35, and 4 L daily from day 35-42. Calves were also fed calf starter ad libitum from day 7-56. Daily MR and starter offered and refused, daily fecal scores, nasal scores, ear scores, and weekly body weight of calves were recorded. Fecal samples were collected on day 7, 35 and 56 after the first feeding of that day for microbial targets analysis. Overall, there is no serious disease challenge for all the calves during the entire experimental period. No differences were observed in MR intake, starter intake, metabolizable energy (ME) intake, average daily gain, ME intake to gain ratio, fecal score, nasal score, eye score or any targeted microorganisms between treatments throughout the experiment. These results suggest that supplementing SCB in MR has no additive effects on animal growth or fecal biomarkers of gut health when calves do not show deteriorated health status.

Validation of a calf-side ß-hydroxybutyrate test and its utility for estimation of starter intake in dairy calves around weaning.

Recent research suggests that circulating ß-hydroxybutyrate (BHB) levels may be a meaningful indicator of grain intake and rumen development in pre-ruminant calves. As such, BHB levels may be a surrogate measure of rumen function to contribute to minimal weaning stress during the transition from liquid to solid feed. The primary objective of this study was to determine the optimal cut-point of circulating BHB levels that would be predictive of sufficient grain intake and rumen development for a successful transition from liquid to solid feed at the time of weaning. An additional objective was to validate the Precision Xtra (Abbott Diabetes Care, Abingdon, UK) calf-side test for determination of BHB in whole blood in calves around weaning, as compared with the gold standard laboratory method. A total of 20 Holstein female calves were randomly assigned at birth to be weaned at 6 wk (n=10) or 8 wk (n=10) of age. Milk replacer (mixed at 150 g/L) was offered at 1.2kg/calf per d in 2 meals until a 1-wk step down, when milk meals were reduced by 50% 1 wk before weaning. Daily measurements included the intakes of starter grain, chopped straw, and water. Weekly measurements included body weight and blood BHB, until 70 d of life. To assess digestive tract development, rumen fluid samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids. Whole blood was collected by jugular venipuncture, and BHB was determined by the Precision Xtra test at calf-side. In addition, serum was separated from a clotted sample, frozen, and stored until laboratory analysis was performed. Laboratory BHB results were correlated with both the Precision Xtra test (r=0.95) and starter intake over 1 d (r=0.89), a 3-d average (r=0.90), and a 7-d average (r=0.90). Additionally, laboratory BHB results were associated with total ruminal volatile fatty acids (r=0.82), ruminal butyrate (r=0.77), and body weight (r=0.69). A receiver operating characteristic curve was created to plot the true positive rate against the false positive rate at 10µmol/L BHB intervals to determine the optimal cut-point of circulating BHB that is predictive of an average starter intake of 1,000 g/d over a 3-d period. The optimal combination of sensitivity (95.7%) and specificity (96.1%) was at 100µmol of BHB/L of blood. A value of 0.2 mmol/L on the Precision Xtra test yielded a sensitivity and specificity of 84.0 and 97.2%, respectively, over the 3-d average period of starter intake. These results show considerable promise for use of the Precision Xtra whole blood BHB test in the decision-making process of determining sufficient starter grain intake and rumen development for a successful transition from liquid to solid feed, and indicate that this test conducted at calf-side is highly accurate.

Weaning age affects growth, feed intake, gastrointestinal development, and behavior in Holstein calves fed an elevated plane of nutrition during the preweaning stage.

Recent research has revealed potential advantages of feeding an elevated plane of nutrition to calves during the preweaning period. However, calves fed more nutrients preweaning may be more susceptible to depressed growth and weaning stress during the transition from liquid to solid feed. The objective of this study was to investigate the relationship between the age of weaning and feed intake, and its influence on growth, gastrointestinal development, and behavioral indicators in dairy calves fed an elevated plane of nutrition during the preweaning period. To meet this objective, 20 female Holstein calves were randomly assigned at birth to be weaned at 6 or 8 wk. Milk replacer (mixed at 150 g/L) was offered at 1.2 kg/calf per day in 2 meals until a 1-wk step-down, when meals were reduced by 50% 1 wk before weaning. Daily starter, chopped oat straw, water intake, and weekly body weights were measured until d 70 of life. To assess digestive tract development, rumen fluid, fecal, and blood samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, respectively. Behavioral indicators of weaning stress, including vocalizing and non-nutritive oral behavior, were measured by visual observation for 1 h, 3 times per week, before the second feeding of the day during the period from 2 wk before weaning to 2 wk after weaning. The calves weaned at 8 wk compared with 6 wk had higher average daily gain for the week preweaning (0.79±0.09 vs. 0.34±0.10 kg/d) and postweaning (1.05±0.09 vs. 0.35±0.11 kg/d), and were heavier at d 70 (99.9±1.81 vs. 91.0±2.26 kg). From 5 to 8 wk of age, starter and water intakes were lower in calves weaned at 8 wk of age. However, overall starter intake did not differ during the last week of the experiment. Furthermore, calves weaned at 8 wk compared with 6 wk had higher starter intake for 1 wk preweaning (1.36±0.13 vs. 0.40±0.08 kg/d) and postweaning (2.51±0.20 vs. 1.16±0.15 kg/d). In both treatments, weaning increased ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, yet the differences between the week before and after weaning were greater for calves weaned at 6 wk compared with those weaned at 8 wk. Treatment × week relative to weaning interactions indicated that several behaviors varied between early- and later-weaned calves during the week before weaning; calves weaned at 6 wk tended to exhibit 75% more non-nutritive oral behavior and spent 55% less time ruminating, and 36% less time lying compared with calves weaned at 8 wk. Under the conditions of this study, the results suggest that calves fed an elevated plane of nutrition preweaning have higher starter intakes and average daily gain during the weaning period when weaning is extended from 6 to 8 wk of age.

A 70% Reduction in Mosquito Populations Does Not Require Removal of 70% of Mosquitoes.

We added a vector control component to our existing abundance model to simulate intensive vector control in Puerto Rico. Removing 20-30% of gravid females in the model matches observed 60-80% reductions. The model's capacity to reproduce vector control increases its utility for planning and evaluation strategies.

Interventions to increase physical activity in children 0-5 years old: a systematic review, meta-analysis and realist synthesis.

OBJECTIVE: The objective of the study is to evaluate the effectiveness of interventions to increase physical activity (PA) in 0-5 year olds and to determine what works, for whom, in what circumstances. DESIGN: Systematic review, meta-analysis and realist synthesis. DATA SOURCES: Embase and EBSCOhost (Academic Search Complete, CINAHL Complete, Global Health, MEDLINE Complete, PsycINFO, SPORTDiscus with full text), up to and including April 2017. ELIGIBILITY CRITERIA: Published in a peer-reviewed English language journal; randomized or controlled trial design; aimed to increase children's PA levels; reported on objectively assessed PA in children between 0 and 5.9 years at baseline and post-intervention. RESULTS: Thirty-four studies were included in the review, mostly conducted in the preschool/childcare setting. Meta-analyses showed an overall non-significant (Z = 0.04, p = 0.97) mean difference of 0.03 (95% CI = -1.57, 1.63) minutes/day for light-intensity PA (n = 11). The overall mean difference for moderate-intensity to vigorous-intensity PA (n = 21) was 2.88 (95% CI = 1.54, 4.23) minutes/day, indicating a small but significant overall positive effect (Z = 4.20, p < 0.001). The realist synthesis provided insights into the key contexts and mechanisms that appeared to be effective at changing children's PA. CONCLUSION: Based on a quantitative and qualitative examination of the evidence, this review provides specific recommendations for effective early childhood PA interventions for practitioners and policymakers.

Invasion of bluetongue and other orbivirus infections into Europe: the role of biological and climatic processes.

The invasion of multiple strains of the midge-borne bluetongue virus into southern Europe since the late 1990s provides a rare example of a clear impact of climate change on a vector-borne disease. However, the subsequent dramatic continent-wide spread and burden of this disease has depended largely on altered biotic interactions with vector and host communities in newly invaded areas. Transmission by Palearctic vectors has facilitated the establishment of the disease in cooler and wetter areas of both northern and southern Europe. This paper discusses the important biological and climatic processes involved in these invasions, and the lessons that must be drawn for effective risk management of bluetongue and other midge-borne viruses in Europe.

A systematic review of methods to measure family co-participation in physical activity.

The family environment is key in influencing children's health behaviours. Encouraging family co-participation in physical activity may therefore be an effective approach to increasing children's physical activity levels. Yet, little is known about how to best assess family co-participation in physical activity. This review summarizes methods to measure family co-participation in physical activity, which was defined as joint physical activities including at least one healthy child (0-18 years) and one other family member. Methods were identified through a systematic literature search, cross-referencing pre-selected reviews and contacting research groups. Thirty-seven measurement methods were included. Questionnaires were the most common method used, with the majority assessing frequency of co-participation and few also assessing duration and type. Reliability and internal consistency of scales were often reported, but rarely specified for the item(s) relevant to co-participation. Other methods of measuring co-participation included diaries, event history calendars, direct observations and accelerometry combined with diary, ecological momentary assessment or global positioning systems (GPS). Whilst a large number of measurement methods of family co-participation in physical activity exist, few are comprehensive and/or report acceptable psychometric properties. Future work should focus on reaching consensus in defining family co-participation in physical activity, and subsequently developing reliable and valid measures.

Family-based interventions to increase physical activity in children: a systematic review, meta-analysis and realist synthesis.

OBJECTIVE: Family-based interventions represent a potentially valuable route to increasing child physical activity (PA) in children. A dual meta-analysis and realist synthesis approach examined existing interventions to assist those developing programmes to encourage uptake and maintenance of PA in children. DESIGN: Studies were screened for inclusion based on including participants aged 5-12 years, having a substantive aim of increasing PA by engaging the family and reporting on PA outcome. Duplicate data extraction and quality assessment were conducted. Meta-analysis was conducted in STATA. Realist synthesis included theory development and evidence mapping. RESULTS: Forty-seven studies were included, of which three received a 'strong' quality rating, 21 'moderate' and 23 'weak'. The meta-analysis (19 studies) demonstrated a significant small effect in favour of the experimental group (standardized mean difference: 0.41; 95%CI 0.15-0.67). Sensitivity analysis, removing one outlier, reduced this to 0.29 (95%CI 0.14-0.45). Realist synthesis (28 studies) provided insight into intervention context (particularly, family constraints, ethnicity and parental motivation), and strategies to change PA (notably, goal-setting and reinforcement combined). CONCLUSION: This review provides key recommendations to inform policy makers and other practitioners in developing evidence-based interventions aimed at engaging the family to increase PA in children, and identifies avenues for future research.

Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy.

OBJECTIVE: Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene. METHODS: Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively. RESULTS: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9 years. CONCLUSION: This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.

Anesthesia during hormone administration abolishes the estrogen induction of preproenkephalin mRNA in ventromedial hypothalamus of female rats.

Estrogen treatment increases preproenkephalin (PPE) mRNA levels in the ventromedial nucleus of the hypothalamus (VMH). Roy et al. (Brain Res., 337 (1985) 163-166) discovered that anesthesia during estrogen priming could reduce female rat sexual receptivity. In the present study we tested whether the action of estrogen to induce PPE gene expression in the VMH could be similarly affected by anesthesia. By quantitative in situ hybridization and slot-blot analysis techniques we found a 1.8-fold increase in PPE mRNA levels in the VMH after 1 hour of estrogen treatment in ovariectomized (OVX) Sprague-Dawley female rats. Anesthetizing the rats with pentobarbital for 1 h during the exposure to estrogen blocked the estrogen induction of PPE mRNA in the VMH. By way of contrast no changes in the PPE mRNA levels were observed in the caudate putamen. A similar trend was seen using chloral hydrate. It appears that neuronal activity is required for the early phase of estrogen induction of PPE mRNA levels in the VMH. This in turn could be correlated with changes in female sociosexual behaviors.

Cellular uptake of intracerebrally administered oligodeoxynucleotides in mouse brain.

Intracerebral diffusion, cellular uptake and intracellular localization of oligodeoxynucleotides (ODN) after their microinjection in mouse brains were examined. Using either tetramethylrhodamine-5-(and -6)-isothiocyanate (TRITC)- or gamma-33P ATP-labeled ODNs, it was found that both phosphodiester ODNs (D-ODN) and phosphorothioate ODNs (S-ODN) quickly diffused (up to about 500 microns) and were taken up by many cells around the injection site as early as 15 min after administration. Fluorescence labeling intensity and silver grain accumulation of D-ODNs were greatly reduced by 4 h after injection, whereas those of S-ODNs were stable beyond at least 8 h after injection. Most of labeled ODNs were found in neuronal cells as identified by immunocytochemistry for neurofilament, NF 200, and to a much lesser extent in astrocytic cells as identified by immunocytochemistry for glial fibrillary acidic protein.

ABO blood group in relation to hypernephroma.

The correlation of blood groups in adenocarcinoma of the kidney is attempted in 125 cases. It appears that there is an inherited element in the susceptibility or protection against the hypernephroma according to blood groups.

Activation of protein kinase C in the hypothalamic ventromedial nucleus or the midbrain central gray facilitates lordosis.

Many neurotransmitters and neuropeptides can act through the hypothalamic ventromedial nucleus (VMN) or midbrain central gray (MCG) to facilitate lordosis. Since these lordosis-facilitating agents can also stimulate the phosphoinositide (PI) second-messenger pathway, it was hypothesized that direct activation of this pathway can also potentiate the behavior. To evaluate this possibility, a phorbol ester, TPA (12-O-tetradecanoyl phorbol 13-acetate), was used to activate a key enzyme, protein kinase C (PKC), of the PI pathway in ovariectomized (OVX) rats either primed or not primed with estrogen. These female rats were paired with males for mating tests before and after an intracerebral infusion of TPA, and both the lordosis quotient (LQ) and the lordosis strength (LS) were measured. Bilateral infusion of TPA (5 micrograms/0.5 microliter or 0.2 microgram/0.2 microliter, but not 0.1 microgram/0.2 microliter/side) into the VMN or MCG of estrogen-primed subjects facilitated both LQ and LS in 30 min, peaked at 60-90 min, and the facilitation lasted for more than 180 min. This facilitatory effect of TPA was: (1) not observed in OVX rats not primed with estrogen; (2) not observed if the infused TPA did not reach both sides of the VMN or MCG; (3) not mimicked by 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC; (4) blocked by PKC inhibitors (H7 10 mM or staurosporine 1 microM, 0.2 microliter/side), which by themselves did not facilitate lordosis; and (5) was not affected by pretreatment of the progestin antagonist RU486.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in immediate-early gene proteins in the rat forebrain induced by acute morphine injection.

Injection of morphine (10 mg/kg) induced a complex immediate-early gene response in the rat forebrain, as detected with immunocytochemistry. The c-Fos protein was induced consistently in the dorsomedial caudate-putamen, the nucleus accumbens, and in midline and intralaminar nuclei of the thalamus. In some rats induction was also seen in the parietal and insular cortex and in lateral regions of the caudate-putamen. Induction was detectable, although weak, at 30 min, was maximal at 2 h, and was undetectable 3 h after injection. JunB was induced in the same regions of the caudate-putamen as found for c-Fos, but was not induced in the nucleus accumbens or thalamus. In the caudate-putamen, JunB induction was still present 3 h after injection. A considerably smaller induction of c-Jun was noted in the dorsomedial caudate-putamen and in deep neocortex. Expression of JunD was inhibited in intralaminar and midline thalamic nuclei. Increases in numbers of cells immunoreactive for a Jun-related antigen (Jra) were found in the caudate-putamen and nucleus accumbens. These results indicate a complex immediate-early gene response to acute morphine, suggesting that morphine activates or inhibits specific neurons and circuits in the forebrain.

Androgenic-anabolic steroids blunt morphine-induced c-fos expression in the rat striatum: possible role of beta-endorphin.

Self-administration of large doses of androgenic-anabolic steroids (AAS) in a significant portion of the population suggests that these agents are drugs of abuse. However, acute administration of AAS did not induce striatal immediate-early genes (IEG) expression in male rats, indicating that AAS do not share a common mechanism of action with other drugs of abuse. Surveys have indicated that people who abuse AAS are more likely to self-administer other drugs of abuse than do people who do not take AAS. In the present study, chronic administration of AAS blunted the striatal c-fos response to morphine, indicating that AAS can alter the molecular responses to at least one drug of abuse. Chronic administration of AAS also increased the content of beta-endorphin in the midline thalamus, suggesting a possible mechanism by which AAS may modulate the response to morphine through regulation of thalamo-striatal neurons.

A two focal plane method for digital quantification of nuclear immunoreactivity in large brain areas using NIH-image software.

In principle, digital acquisition of cell-count data from serially-sectioned immunocytochemical material is a straightforward enterprise. First, a serial brain section is magnified by use of a microscope interfaced to a computer. Then, using appropriate hardware and software, a digital image is captured, and cellular profiles of interest are segmented from background objects according to mean grayscale intensity and pixel area. Ideally, the cells of interest would be uniformly distinguishable from other objects or areas of the image, with respect to grayscale intensity and size. However, due to non-uniformity in background staining of neuropil, immunocytochemical material often departs markedly from this ideal situation. As a consequence, determining grayscale intensity and cell size cutoff values which separate cells of interest from background becomes laborious and arbitrary. This problem can be diminished by increasing the magnification of the digitized image, which increases the figure-ground resolution of the image. However, high-magnification images make tissue navigation difficult and require that multiple images be captured. This paper describes a two focal plane procedure for obtaining cell counts from nuclear-stained immunocytochemistry material. This procedure allows the capturing and cell counting of relatively low-magnification images with high digital figure-ground resolution.

Effect of ewe and lamb genotype on gestation length, lambing ease and neonatal behaviour of lambs.

To distinguish between ewe and lamb breed effects on prenatal growth, ease of parturition and early lamb behaviour, an embryo-transfer study was carried out using a hill breed (Scottish Blackface; liveweight: 54.25 +/- 1.03 kg, mean +/- s.e.m.) and a lowland breed (Suffolk; 80.33 +/- 1.52 kg) to obtain the four possible combinations of ewe and lamb. Data were collected from 38 Blackface ewes (18 with Blackface lambs and 20 with Suffolk lambs) and 41 Suffolk ewes (20 with Blackface lambs and 21 with Suffolk lambs); all ewes were given single embryos. Suffolk lambs had a significantly longer gestation than Blackface lambs (1.5 days, P < 0.01), regardless of ewe breed. Suffolk lambs also had a longer labour (20 min, P < 0.05) and were significantly more likely to require birth assistance (17/21, 81% of all assisted deliveries; P < 0.001), as were male lambs (19/21, 90%; P < 0.01). These variables were independent of ewe breed. Blackface lambs were significantly more active than Suffolk lambs in the first 2 h after birth; ewe breed had little effect on lamb behaviour. Blackface lambs stood twice as quickly as Suffolk lambs after birth (13 min v. 24 min; P < 0.001), and were significantly more likely to suckle within the first 2 h after birth (92% v. 66%; P < 0.05). The behavioural retardation of Suffolk lambs may be a consequence of their birth difficulty which increases their likelihood of suffering birth trauma and hypoxia at parturition. Together, these factors may increase the probability of neonatal death in these lambs.

A "step-to" gait decreases pressures on the forefoot.

Physical therapists use various gait training strategies to reduce stress on the lower extremities, but we could find no description or evaluation of the step-to gait using a cane. The purpose of this study was to evaluate the effect of a step-to gait pattern and a cane on peak plantar pressures on the forefoot and the heel. Ten healthy subjects were evaluated (five females, five males, mean age = 24.6 +/- 4.9 years). In addition, one subject with peripheral neuropathy was tested to determine if a patient could be trained to use the step-to walking pattern and show similar results. All subjects were instructed in four walking conditions; step-to with and without a cane and step-through with and without a cane. Walking speed during the step-through pattern (normal walking) was matched to the speed of the step-to pattern. For the 10 healthy subjects, peak plantar pressures and walking speed of each of the four conditions were compared using a 2 x 2 repeated measures analysis of variance. One factor was gait pattern and one factor was use of a cane. Peak plantar pressures decreased an average of 53% on the forefoot but increased an average of 14% on the heel when subjects walked using step-to gait compared with a step-through gait. There was no effect due to use of a cane or walking speed between the conditions. The patient with peripheral neuropathy demonstrated a similar pattern but greater magnitude of changes compared with the healthy subjects. The foot initiating the step-to pattern showed a reduction in peak plantar pressures on the forefoot, probably because the foot remained flat during stance phase and a large push-off was not required. The step-to pattern, however, results in a slower and less symmetrical gait. The use of a step-to gait may be beneficial for patient populations that need to reduce plantar pressures on the forefoot.