Effect of brisk walking in 1 or 2 daily bouts and moderate resistance training on lower-extremity muscle strength, balance, and walking performance in women who recently went through menopause: a randomized, controlled trial

BACKGROUND AND PURPOSE: Menopause may induce a phase of rapid decreases in bone mineral density, aerobic fitness, muscle strength, and balance, especially in sedentary women. The purpose of this study was to examine the effects and feasibility of an exercise program of 1 or 2 bouts of walking and resistance training on lower-extremity muscle strength (the force-generating capacity of muscle), balance, and walking performance in women who recently went through menopause. SUBJECTS AND METHODS: The subjects were 134 women who recently went through menopause. The study was a 15-week, randomized, controlled trial with continuous and fractionated exercise groups. The outcomes assessed were lower-extremity muscle strength, balance, and walking time over 2 km. Feasibility was assessed by questionnaires, interviews, and training logs. RESULTS: One hundred twenty-eight women completed the study. Adherence to the study protocol was 92%. Both continuous and fractionated exercise groups improved equally in lower-extremity muscle strength and walking time but not in balance. Almost 70% of the subjects considered the program to be feasible. Two daily walking sessions caused fewer lower-extremity problems than did continuous walking. DISCUSSION AND CONCLUSION: Brisk walking combined with moderate resistance training is feasible and effective. Fractionating the walking into 2 daily sessions is more feasible than continuous walking.     

Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1

The proteins ClC-6 and ClC-7 are expressed in the endosomal-lysosomal system. Because Clcn6-deficient mice display some features of neuronal ceroid lipofuscinosis (NCL), CLCN6 may be a candidate gene for novel forms of NCL. Using landmarks of disease progression from NCL mouse models as a guide, we examined neuropathologic alterations in the central nervous system of Clcn6(-/-), Clcn7(-/-), andgl mice. gl mice bear a mutation in Ostm1, the β-subunit critical for Clcn7 function. Severely affected Clcn7(-/-) and gl mice have remarkably similar neuropathologic phenotypes, with pronounced reactive changes and neuron loss in the thalamocortical system, similar to findings in early-onset forms of NCL. In contrast, Clcn6(-/-) mice display slowly progressive, milder neuropathologic features with very little thalamic involvement or microglial activation. These findings detail for the first time the markedly different neuropathologic consequences of mutations in these two CLC genes. Clcn7(-/-) and gl mice bear a close resemblance to the progressive neuropathologic phenotypes of early onset forms of NCL, whereas the distinct phenotype of Clcn6-deficient mice suggests that this gene could be a candidate for a later-onset form of mild neurologic dysfunction with some NCL-like features.     

Measuring deterioration in international classification of functioning domains of people with multiple sclerosis who are ambulatory

BACKGROUND AND PURPOSE: Measures to detect important effects related to physical therapy interventions must be able to detect an important change. The purpose of this study was to select the most responsive physical functioning measures for multiple sclerosis (MS) using the International Classification of Functioning, Disability and Health (ICF) as a framework. SUBJECTS: The participants were 120 people with MS who were ambulatory from a population-based sample. METHODS: Physical functioning was assessed by quantitative clinical measures of activities (n=5) and body functions (n=7) and by self-reported performance in self-care, mobility, and domestic life domains in the activities and participation component of the ICF at baseline and 2 years later. A participant's perception of change and a change in Expanded Disability Status Scale (EDSS) scores were used as external criteria in the analysis of the receiver operating characteristic curve and the minimally important change score. The minimal detectable change was calculated as distribution-based responsiveness. RESULTS: According to the external criteria, 51% of the participants showed deterioration as measured by their own perceptions compared with the 26% of the participants who showed deterioration as rated by the clinician. Regardless of the external criterion applied, the measures most responsive to deterioration were self-reported scores in self-care, mobility, and domestic life; distance walked and change in heart rate during a 6-minute walk test; 10-m walk test speeds, stride length, and cadence; repetitive squatting; and Box and Block Test scores. DISCUSSION AND CONCLUSION: The results show the relative responsiveness of different measures in the subsample who deteriorated and provide data that can facilitate the interpretation of score changes in people with MS who are ambulatory for future studies and in clinical practice.     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.     

Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death

Background

Venous thromboembolism (VTE) and thromboembolic arterial diseases are usually considered to be distinct entities, but there is evidence to suggest that these disorders may be linked. The aim of this study was to determine whether a diagnosis of VTE increases the long-term risk of myocardial infarction (MI).

Methods

The incidence rate (IR) and relative risk (RR) of MI in a cohort of patients with a diagnosis of VTE (n = 4890) compared with that of a control cohort without prior VTE (n = 43 382) were evaluated in the UK General Practice Research Database (GPRD). Death during follow-up was also determined. Patients were followed for up to 8 years (mean of 3 years).

Results

The IR of MI per 1000 person-years was 4.1 (95% CI: 3.1–5.3) for the VTE cohort and 3.5 (95% CI: 3.2–3.8) for the control cohort. The IR of MI was highest in the first year after the VTE episode, but overall differences between the two cohorts were not significant (RR of MI associated with VTE: 1.2; 95% CI: 0.9–1.6). The risk of death was higher in the VTE cohort than the control cohort, even after adjustment for cancer, heart failure and ischaemic heart disease (RR: 2.4; 95% CI: 2.2–2.6), particularly during the first year after VTE (RR: 3.8; 95% CI: 3.4–4.3).

Conclusion

A VTE episode does not significantly increase the risk of MI, but does increase the risk of death, particularly in the first year following VTE diagnosis.     

Psychosocial functioning needs attention in adolescent eating disorders

We studied the differences in psychosocial functioning in the early stages of adolescent anorexia nervosa (AN) and bulimia nervosa (BN). The study group comprised 57 adolescent eating disorder (ED) outpatients (girls). Psychosocial functioning was evaluated by GAF (Global Assessment of Functioning), and by Morgan-Russell psychosocial subscales. GAF scores were very low in both AN and BN. On the Morgan-Russell subscales, bulimics reported more unsatisfactory relationships with family and impairment in work/school. Anorectics tended to have more difficulties in emancipation from family and in social contacts. Multivariate analysis showed associations of BN and high GSI with difficulties in relationships with family and of AN with difficulties in emancipation from family and with fewer social activities. Longer duration of illness predicted best impaired working ability. In adolescent EDs, psychosocial functioning is markedly impaired. We emphasize the importance of evaluating psychosocial functioning at the very onset of ED.     

Attitudes of general hospital emergency room personnel towards attempted suicide patients

The aim of this study was to compare the attitudes of emergency room staff towards patients who have attempted suicide between two general hospitals, one with psychiatric consultation available and the other without. The Understanding Suicidal Patients (USP) Questionnaire was given to all staff in the emergency rooms of Jorvi Hospital (in the city of Espoo, with routine psychiatric consultation) and Malmi Hospital (in the city of Helsinki, without routine psychiatric consultation) (n=115). There were clear differences in staff attitudes between the hospitals. Female gender, older age and working in Malmi Hospital without routine psychiatric consultation were associated with more positive attitudes towards attempted suicide patients. Surprisingly, only working in Jorvi Hospital was associated with more negative attitudes. Differences in attitudes towards suicide attempters between personnel working in the different hospitals were found. Further investigation is needed to find the ideal psychiatric consultation arrangement for suicide attempters in good cooperation with emergency room staff.