Coding-Complete Genome Sequences of Emerging Rabbit Hemorrhagic Disease Virus Type 2 Isolates Detected in 2020 in the United States.

Five rabbit hemorrhagic disease virus type 2 (RHDV2) coding-complete genome sequences were obtained from the livers of domestic and wild rabbits during the 2020 outbreak in the United States. These represent the first available RHDV2 sequences from the United States.

Genome Sequences of Vesicular Stomatitis Indiana Viruses from the 2019 Outbreak in the Southwest United States.

We report the genomes of three vesicular stomatitis Indiana virus (VSIV) isolates collected from naturally infected bovines in Wyoming and Colorado during the 2019 outbreak in the United States. These genomes support molecular diagnostic efforts and provide data on the spread and ecology of VSIV in the United States.

Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity.

The anti-apoptotic function and tumor-associated expression of heat-shock protein 70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote tumorigenesis. However, its immunomodulatory activities to induce anti-tumor immunity predict the suppression of tumor growth. Using the Hsp70.1/3(-/-)(Hsp70(-/-)) mouse model, we observed that tumor-derived HSP70 was neither required for cellular transformation nor for in vivo tumor growth. Hsp70(-/-) murine embryonic fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison of Bcr-Abl-mediated transformation of WT and Hsp70(-/-) bone marrow and progression of B-cell leukemogenesis in vivo revealed no differences in disease onset or survival rates, and Eµ-Myc-driven lymphoma in Hsp70(-/-) mice was phenotypically indistinguishable from that in WT Eµ-Myc mice. However, Hsp70(-/-) E1A/Ras MEFs generated significantly larger tumors than their WT counterparts in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in intra-tumoral infiltration of innate and adaptive immune cells, including macrophages and CD8(+) T cells. Evaluation of several potential mechanisms revealed an HSP70-chemokine-like activity to promote cellular migration. These observations support a role for tumor-derived HSP70 in facilitating anti-tumor immunity to limit tumor growth and highlight the potential consequences of anti-HSP70 therapy as an efficacious anti-cancer strategy.

mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3.

Recent clinical trials using rapalogues in tuberous sclerosis complex show regression in volume of typically vascularised tumours including angiomyolipomas and subependymal giant cell astrocytomas. By blocking mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling, rapalogue efficacy is likely to occur, in part, through suppression of hypoxia-inducible factors (HIFs) and vascular endothelial growth factors (VEGFs). We show that rapamycin reduces HIF-1α protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma cells in a Tsc2+/- mouse model. We established that mTORC1 drives HIF-1α protein accumulation through enhanced transcription of HIF-1α mRNA, a process that is blocked by either inhibition or knockdown of signal transducer and activation of transcription 3 (STAT3). Furthermore, we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1α mRNA transcription. mTORC1 also regulates HIF-1α synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas HIF-1α degradation remains unaffected. We therefore proposed that mTORC1 drives HIF-1α synthesis in a multifaceted manner through 4E-BP1/eIF4E, S6K1 and STAT3. Interestingly, we observed a disconnect between HIF-1α protein levels and VEGF-A expression. Although both S6K1 and 4E-BP1 regulate HIF-1α translation, VEGF-A is primarily under the control of 4E-BP1/eIF4E. S6K1 inhibition reduces HIF-1α but not VEGF-A expression, suggesting that mTORC1 mediates VEGF-A expression via both HIF-1α-dependent and -independent mechanisms. Our work has important implications for the treatment of vascularised tumours, where mTORC1 acts as a central mediator of STAT3, HIF-1α, VEGF-A and angiogenesis via multiple signalling mechanisms.

Genomic analysis of filoviruses associated with four viral hemorrhagic fever outbreaks in Uganda and the Democratic Republic of the Congo in 2012.

In 2012, an unprecedented number of four distinct, partially overlapping filovirus-associated viral hemorrhagic fever outbreaks were detected in equatorial Africa. Analysis of complete virus genome sequences confirmed the reemergence of Sudan virus and Marburg virus in Uganda, and the first emergence of Bundibugyo virus in the Democratic Republic of the Congo.

Voluntary food fortification in the United States: potential for excessive intakes.

BACKGROUND: Historically, the voluntary addition of micronutrients to foods in the United States has been regarded as an important means to lessen problems of nutrient inadequacy. With expanding voluntary food fortification and widespread supplement use, it is important to understand how voluntary food fortification has an impact on the likelihood of excessive usual intakes. Our objective was to investigate whether individuals in the United States with greater frequency of exposure to micronutrients from voluntarily fortified foods (vFF) are more likely to have usual intakes approaching or exceeding the respective tolerable upper intake levels (UL). SUBJECTS/METHODS: The National Cancer Institute method was applied to data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) to estimate the joint distribution of usual intake from both vFF and non-vFF sources for 12 nutrients and determine the probability of consuming these nutrients from vFF on a given day. For each nutrient, we estimated the distribution of usual intake from all food sources by quintile of probability of consuming vFF and compared the distributions with ULs. RESULTS: An increased probability of consuming zinc, retinol, folic acid, selenium and copper from vFF was associated with a greater risk of intakes above the UL among children. Among adults, increased probability of consuming calcium and iron from vFF was associated with a greater risk of intakes above the UL among some age/sex groups. CONCLUSION: The high nutrient exposures associated with vFF consumption in some population subgroups suggest a need for more careful weighing of the risks and benefits of uncontrolled food fortification.

Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.

BACKGROUND: Few high-quality trials have examined the effects of progressive resistance training (PRT) on people with multiple sclerosis (MS). OBJECTIVE: To determine the effectiveness of PRT for people with MS, focusing on improving the gait deficits common in this population. METHODS: Using a single blind randomized controlled trial, people with relapsing-remitting MS were randomly allocated to either a PRT program targeting the lower limb muscles twice a week for 10 weeks (n = 36), or usual care plus an attention and social program conducted once a week for 10 weeks (n = 35). Outcomes were recorded at baseline, week 10 and week 22. RESULTS: Participants attended 92% of training sessions, with no serious adverse events. At 10 weeks, no differences were detected in walking performance. However, compared with the comparison group PRT demonstrated increased leg press strength (16.8%, SD 4.5), increased reverse leg press strength (29.8%, SD 12.7), and increased muscle endurance of the reverse leg press (38.7%, SD 32.8). Improvements in favor of PRT were also found for physical fatigue (Mean difference -3.9 units, 95%CI -6.6 to -1.3), and the physical health domain of quality of life (Mean difference 1.5 units, 95%CI 0.1 to 2.9). At week 22 almost no between-group differences remained. CONCLUSION: PRT is a relatively safe intervention that can have short-term effects on reducing physical fatigue, increasing muscle endurance and can lead to small improvements in muscle strength and quality of life in people with relapsing-remitting MS. However, no improvements in walking performance were observed and benefits do not appear to persist if training is completely stopped.

Association between isometric muscle strength and gait joint kinetics in adolescents and young adults with cerebral palsy.

The purpose of this study was to determine the association between isometric muscle strength of the lower limbs and gait joint kinetics in adolescents and young adults with cerebral palsy (CP). Twenty-five participants (11 males) with bilateral spastic CP, aged 14-22 years (mean: 18.9, sd: 2.0 yr) and Gross Motor Function Classification System (GMFCS) level II (n=19) and III (n=6) were tested. Hand held dynamometry was used to measure isometric strength (expressed in Nm/kg) of the hip, knee, and ankle muscles using standardized testing positions and procedures. 3D gait analysis was performed with a VICON system to calculate joint kinetics in the hip, knee and ankle during gait. Ankle peak moments exceeded by far the levels of isometric strength of the plantar flexors, while the knee and hip peak moments were just at or below maximal isometric strength of knee and hip muscles. Isometric muscle strength showed weak to moderate correlations with peak ankle and hip extension moment and power during walking. Despite considerable muscle weakness, joint moment curves were similar to norm values. Results suggest that passive stretch of the muscle-tendon complex of the triceps surae contributes to the ankle moment during walking and that muscle strength assessment may provide additional information to gait kinetics.

Identifying facilitators and barriers to physical activity for adults with Down syndrome.

BACKGROUND: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. METHOD: Semi-structured interviews were conducted to elicit the views of adults with Down syndrome and their support people about what factors facilitate physical activity and what factors are barriers to activity. A sample of 18 participants (3 men, 15 women) was recruited through two agencies providing services for adults with disabilities; six participants were adults with Down syndrome and 12 participants were support people (four were parents of adults with Down syndrome and eight participants were employed by day programmes attended by the adults with Down syndrome). The interviews were recorded, transcribed verbatim and independently coded by two researchers. RESULTS: Three themes around facilitators to physical activity were identified: (1) support from others; (2) that the physical activity was fun or had an interesting purpose; and (3) routine and familiarity. Three themes around barriers were also identified: (1) lack of support; (2) not wanting to engage in physical activity; and (3) medical and physiological factors. CONCLUSIONS: The results suggest that support people play a key role, both as facilitators and barriers, in the participation by adults with Down syndrome in physical activity. Many of the barriers and facilitators of activity for adults with Down syndrome indentified are similar to those reported for adults without impairment. Our findings are also consistent with established theories in the field of health behaviour change.

Regenerate: assessing the feasibility of a strength-training program to enhance the physical and mental health of chronic post stroke patients with depression.

OBJECTIVE: The Regenerate pilot study explored whether a 10-week, community-based progressive resistance training (PRT) program could reduce depressive symptoms in depressed chronic stroke survivors. METHODS: Participants were screened for depressive status using the PHQ-9 and confirmed by psychiatric assessment. Eligible people (n = 45) were randomised to PRT or a waiting-list comparison group. The PRT program included two high intensity sessions/week for 10 weeks at a community-based gymnasium. Depressive status, physical and mental health and quality of life were measured at baseline, 10 weeks and 6 months. Muscle strength was assessed using 1 repetition maximum (1-RM) for upper and lower limbs. RESULTS: The participants' median age was 69 years: 27 were male. The intervention group had lower depression scores than the comparison group at all time points. At 6-month follow-up, there was a trend for PRT participants to be more likely to be no longer depressed than the comparison group, but the difference was not significant after adjusting for baseline scores. There were modest improvements in health and wellbeing over time, but many scores were lower than reported in non-depressed people. Intervention participants demonstrated significant improvements in strength. Program adherence was good: on average 75% of the 10-week program was completed. CONCLUSIONS: The intervention appeared to be feasible within a community-based setting. To optimize stroke recovery and improve the quality of life of stroke survivors, health professionals should continue to focus on helping survivors' mental health recovery as well their physical rehabilitation.

US and France adult fruit and vegetable consumption patterns: an international comparison.

BACKGROUND/OBJECTIVES: To observe fruit and vegetable consumption as it relates to body mass index (BMI) and other variables, by analyzing the health surveys of two countries -- the United States and France -- with traditionally distinct diets, and identifying factors that may explain the differences. SUBJECTS/METHODS: Two nationally representative surveys that assess food intake via 24-h diet recalls. Respondents include 2126 women and 1911 men from the US National Health and Nutrition Examination Survey, and 1572 women and 1141 men from the French Nutrition Barometer Survey. Standard linear regression models and t-tests of both simple and predictive marginal means were run employing the software package SUDAAN. RESULTS: Americans appear to consume fruits and vegetables less often than their French counterparts (1.04 vs 1.33 times per day fruits; 1.98 vs 2.29 times per day vegetables). American men consume fruits and vegetables least often (0.98 times per day fruits; 1.88 times per day vegetables) than do American women or French men (1.10 vs 1.25 times per day fruits; 2.07 vs 2.18 times per day vegetables). French women consume fruits and vegetables most often (1.41 times per day fruits; 2.41 times per day vegetables). The French have lower mean BMI than Americans (23.34 vs 28.22 women; 25.20 vs 28.02 men). Regression analyses showed that age, BMI and educational attainment are strongly associated with frequency of consumption. CONCLUSIONS: These results support our hypothesis that the French tend to eat fruits and vegetables more often than Americans. This study proves to be an important first step in determining some of the influential factors that may affect various populations' consumption of fruits and vegetables.

A qualitative analysis of a progressive resistance exercise programme for people with Parkinson's disease.

PURPOSE: This qualitative study explored the perceptions of adults with Parkinson's disease (PD) about the positive and negative aspects and outcomes of a community-based progressive resistance strengthening programme (PRST), motivators to begin and continue with the PRST program, and factors that might facilitate or create barriers to participation in and completion of a PRST programme. METHODS: Three women and 10 men with PD participated in a 10-week community-based strengthening programme. Participants were interviewed at the end of the programme. A phenomenological theoretical framework and a grounded theory methodology were used to underpin the analysis of these data. RESULTS: Four themes emerged about the participants' experiences of the programme. These were: (i) Motivators for participation in the PRST programme were broader than physical outcomes, (ii) the outcomes were broader than just physical outcomes, (iii) the indicators of success for participants varied, and (iv) the participants' experience of a disease-specific exercise programme was positive. CONCLUSIONS: The outcomes of this study provide insights, not identified through the quantitative results, into the experiences of people with PD, which have implications for clinicians running future strength training programmes for people with PD.

Guideline implementation in allied health professions: a systematic review of the literature.

BACKGROUND: Clinical guidelines aim to improve the safety and quality of patient care by providing clinicians with graded recommendations based on evidence of best practice. OBJECTIVE: To evaluate the effects of the introduction of clinical guidelines for allied health professionals, and to estimate the effectiveness of the guideline dissemination and implementation strategies used. METHODS: A comprehensive search of six electronic databases to June 2006 and the Cochrane Effective Practice and Organisation of Care database was conducted. Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies were included if the intervention was aimed at implementing guidelines in the allied health professions. Articles were screened for eligibility and their methodological quality was assessed; data were extracted independently by two reviewers. RESULTS: Fourteen studies met the inclusion criteria. The methodological quality varied greatly, with the proportion of quality criteria met ranging from 0 to 6 out of seven. In most studies, the effects reported for patient and process outcomes were small and in favour of the intervention group. Of the 14 included studies, 10 focused on educational interventions. Six of the 14 studies used a single intervention strategy and seven used a multi-faceted implementation strategy. One study compared both single and multi-faceted strategies. Multi-faceted interventions were no more effective than single intervention strategies and effects of the same strategy varied across trials. CONCLUSIONS: There is no evidence to support a set guideline implementation strategy for allied health professionals. When implementing clinical guidelines it is important to first identify specific barriers to change using theoretical frameworks of behaviour change and then develop strategies that deal with these barriers. When measuring the effectiveness of these strategies, professionals should consider the use of both patient and process outcomes and choose outcomes that reflect their aims.

Progressive resistance exercise for people with multiple sclerosis.

PURPOSE: This study aimed to determine if participation in a progressive resistance exercise (PRE) programme can: (1) increase the ability to generate maximal muscle force, (2) increase muscle endurance, (3) increase functional activity, and (4) improve overall psychological function of people with multiple sclerosis (MS). METHODS: A pre-post single group research design with a 4-week baseline familiarisation phase was used. Nine people (mean age 45.6 years, SD 10.7) with MS attended a gymnasium three times over 4 weeks for familiarization. Participants then completed a twice-weekly 10-week PRE programme, with two sets of 10 - 12 repetitions of each exercise. Outcome measures of muscle strength (1RM for arms and legs), muscle endurance (repetitions at half 1RM), walking speed, the 2-min walk test (2MWT), a timed stairs test, and the impact of MS on physical and psychological function were taken at weeks 2, 4, and 14. RESULTS: Participants attended 94.3% (SD 8.2%) of the training sessions, with no adverse events. After accounting for baseline stability, significant improvements (P < 0.05) were found in arm strength (14.4%), leg endurance (170.9%), fast walking speed (6.1%), and there was a trend for increased distance in the 2MWT (P = 0.06). The perceived impact of MS on physical function was reduced (P = 0.02). CONCLUSIONS: Adults with MS benefited from a PRE programme by improving muscle performance and physical activities, without adverse events. These findings suggest that PRE may be a feasible and useful fitness alternative for people with mild to moderate disability due to MS.

A qualitative analysis of a progressive resistance exercise programme for people with multiple sclerosis.

PURPOSE: This qualitative study explored the perceptions of adults with multiple sclerosis about the positive and negative effects of a progressive resistance strengthening programme; and identified factors that might facilitate or create barriers to participation. METHODS: Seven women and two men (mean age 45.6 years, SD 10.7) with multiple sclerosis participated in a 10-week gymnasium based progressive resistance strengthening programme held twice a week. Participants were interviewed at the end of the programme. The recorded interviews were transcribed and then independently coded by three researchers. From these codes, the main themes emerged. RESULTS: Reports about the programme were very positive with physical, psychological and social benefits noted. Most participants said that they had less fatigue as a result of the programme. Few negative outcomes were reported and these were minor such as aches and pains. Key extrinsic factors for programme completion were the leaders' encouragement and knowledge of exercise; and the group aspect of the programme. Key intrinsic factors were enjoyment, determination, seeing the signs of progress, and a previously held positive attitude about the benefits of exercise. CONCLUSIONS: The results of this study suggest that progressive resistance strength training is a feasible fitness option for some people with multiple sclerosis. Factors perceived to be important for programme completion suggest that choosing encouraging leaders with knowledge of exercise, and exercising in a group may contribute to programme success.

Falls and injury prevention should be part of every stroke rehabilitation plan.

OBJECTIVE: To evaluate falls incidence, circumstances and consequences in people who return home after stroke rehabilitation, so that appropriate falls and injury prevention strategies can be developed. DESIGN: Prospective cohort study. SETTING: Community. SUBJECTS: Fifty-six subjects with stroke who were participating in a rehabilitation programme and returning to live in a community setting completed the study. MAIN MEASURES: Subjects completed a prospective falls diary for six months after discharge from rehabilitation, and were interviewed after falls. Physical function was measured by the Berg Balance Scale (BBS) and the Functional Independence Measure (FIM). RESULTS: Forty-six per cent of people (26/56) fell, with most falls (63/103 falls) occurring in the two months after discharge from rehabilitation. One subject had 37 similar falls and these falls were excluded from further analysis. Falls occurred more often indoors (50/66), during the day (46/66) and towards the paretic side (25/66). People required assistance to get up after 25 falls (38%) and 36 falls (55%) resulted in an injury. People sought professional health care after only 16 falls, and activity was restricted after 29 falls (44%). The Berg Balance Scale and Functional Independence Measure scores were lower in people who had longer lies after a fall, and who restricted their activity after a fall (p < 0.05). Lower physical function scores were also associated with falling in the morning, wearing multifocal glasses at the time of a fall, and injurious falls (p < 0.05). CONCLUSION: Falls are common when people return home after stroke. Of concern are the small number seeking health professionals' assistance after a fall, the high proportion restricting their activity as a result of a fall and the number of falls occurring towards the paretic side.

Expression of two membrane fusion proteins, synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein, in choroid plexus epithelium.

In addition to being the major site of cerebrospinal fluid formation, the choroid plexus epithelium emerges as an important source of polypeptides in the brain. Physiologically regulated release of some polypeptides synthesized by the choroid plexus has been shown. The molecular mechanisms underlying this polypeptide secretion have not been characterized, however. In the present study, synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein, two membrane fusion proteins playing a critical role in exocytosis in neurons and endocrine cells, were found to be expressed in the choroid plexus epithelium. It was also shown that in choroidal epithelium, synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein stably interact. Two members of the vesicle-associated membrane protein family, vesicle-associated membrane protein-1 and vesicle-associated membrane protein-2, were expressed in the rat choroid plexus at the messenger RNA and protein level. However, their newly discovered isoforms, vesicle-associated membrane protein-1b and vesicle-associated membrane protein-2b, produced by alternative RNA splicing, were not detected in choroidal tissue. Immunohistochemistry demonstrated that vesicle-associated membrane protein is confined to the cytoplasm of choroidal epithelium, whereas synaptosome-associated protein of 25 kDa is associated with plasma membranes, albeit with a varied cellular distribution among species studied. Specifically, in the rat choroid plexus, synaptosome-associated protein of 25 kDa was localized to the basolateral membrane domain of choroidal epithelium and was expressed in small groups of cells. In comparison, in ovine and human choroidal tissues, apical staining for synaptosome-associated protein of 25 kDa was found in the majority of epithelial cells. These species-related differences in cellular synaptosome-associated protein of 25 kDa distribution suggested that the synaptosome-associated protein of 25 kDa homologue, synaptosome-associated protein of 23 kDa, is also expressed in the rat choroid plexus, which was confirmed by reverse-transcriptase polymerase chain reaction. Our findings suggest that synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein are involved in secretion of polypeptides from the choroid plexus epithelium. The presence of synaptosome-associated protein of 25 kDa and its homologue as well as multiple isoforms of vesicle-associated membrane protein in choroidal epithelium may play a role in the apical versus basolateral targeting of secretory vesicles.

Changes in gait and fatigue from morning to afternoon in people with multiple sclerosis.

OBJECTIVES: The aim was to measure changes in walking patterns and self rated fatigue in people with multiple sclerosis (MS) compared with age matched control subjects, from the morning to the afternoon within a single day. METHODS: Fourteen patients with MS and the same number of matched control subjects performed four 10 m gait trials at their preferred walking speed at 10 00 am and then again at 3 00 pm on the same day. Gait speed, stride length, cadence, and the percentage of the gait cycle spent in double limb support were measured using a foot switch stride analyzer. Patients with MS also self rated their fatigue levels in the morning and afternoon using an 11 point scale. RESULTS: Compared with control subjects, patients walked very slowly, with reduced stride length and around twice as much variability in gait performance. Although self rated fatigue significantly increased from the morning to the afternoon, walking patterns remained consistent in both groups over the course of the day. CONCLUSIONS: These findings imply that mechanisms controlling locomotion are separate from those regulating perceived fatigue. Objective measures of performance, rather than self report, should be used to monitor change in patients with multiple sclerosis.

Association of awareness, intrapersonal and interpersonal factors, and stage of dietary change with fruit and vegetable consumption: a national survey.

PURPOSE: To examine associations of awareness, intrapersonal and interpersonal factors, and stage of change with consumption of fruits and vegetables. DESIGN: Nationally representative, random digit dial survey conducted in 1997 with a response rate of 44.5%. Psychosocial correlates of fruit and vegetable consumption were assessed using regression analyses. SETTING: United States. SUBJECTS: A total of 2605 adults who were 18 years and older. MEASURES: Awareness of the "5 A Day for Better Health" program and its message, along with stage of change; taste preferences; self-efficacy; and perceived benefits, barriers, threats, social support, and norms related to fruit and vegetable consumption. RESULTS: Awareness and intrapersonal and interpersonal factors explained 24% of the variance in fruit and vegetable consumption beyond the 9% explained by demographic characteristics. Knowledge of the 5 A Day message was associated with a 22% increase in fruit and vegetable consumption. Self-efficacy for eating fruits and vegetables and taste preferences (affect) were the factors most consistently and strongly associated with both higher consumption and higher likelihood of being in action or maintenance stages of change. Affect and perceived barriers were more strongly associated with increased vegetables and salad than fruit. CONCLUSIONS: Dietary intervention programs to increase fruit and vegetable consumption should emphasize the 5 A Day message, increased self-efficacy, and ways to make vegetables more palatable and easily accessible. Understanding the factors that influence dietary choices should be used when designing dietary interventions.

The biomechanics and motor control of gait in Parkinson disease.

Parkinson disease is a progressive neurological condition characterised by hypokinesia (reduced movement), akinesia (absent movement), tremor, rigidity and postural instability. These movement disorders are associated with a slow short-stepped, shuffling gait pattern. Analysis of the biomechanics of gait in response to medication, visual cues, attentional strategies and neurosurgery provides insight into the nature of the motor control deficit in Parkinson disease and the efficacy of current therapeutic interventions. In this article we supplement a critical evaluation of the Parkinson disease gait literature with two case examples. The first case describes the kinematic gait response of an individual with Parkinson disease to visual cues in the "off" phase of the levodopa medication cycle. The second case investigates the biomechanics and motor control of turning during walking in a patient with Parkinson disease compared with elderly and young control subjects. The results are interpreted in light of the need for gait analysis to investigate complex functional walking tasks rather than confining assessment to straight line walking, which has been the trend to date.