Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells

Purpose: Parkinson’s disease is a progressive neurodegenerative disease characterized by progressive and selective death of dopaminergic neurons. It has been reported that nicotine and morphine have protective roles during neuronal damage in Parkinson’s disease. In addition, the induction of cross-tolerance between their biological effects has been shown in numerous reports.

Methods: Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson’s disease. Cell damage was induced by 150?μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular reactive oxygen species, calcium level, and mitochondrial membrane potential were determined by fluorescence spectrophotometer method. Biochemical markers of apoptosis were also evaluated by immunoblotting.

Result: The data showed that morphine and nicotine prevent 6-OHDA- induced cell damage and apoptosis. However, the protective effects of nicotine were not observed in chronic morphine-pretreated cells. Morphine had no protective effects in chronic nicotine-incubated cells.

Conclusion: A cross-tolerance between protective effects of morphine and nicotine was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.     

French translation and validation of a fragile X syndrome screening checklist

Background: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability among men. This syndrome is frequently underdiagnosed in adults. The aim of this study was to develop and validate a French translation of the screening checklist Fragiele-X screeningslijst.

Method: The validation sample for the translated checklist included 22 pairs of men between the ages of 18 and 52, matched by age and degree of intellectual impairment.

Results: The translated checklist achieved coefficients of 0.92 for internal consistency, 0.90 for test-retest reliability and 0.65 for inter-rater reliability. These psychometric properties are commensurate with those of the original checklist.

Conclusion: Therefore, the translated checklist developed in this study can be considered a valid screening instrument for the detection of FXS in men with intellectual disabilities.

Abbreviations: FXS: fragile X syndrome; FMR1: fragile X mental retardation 1 (gene)     

Effect of activity-based mirror therapy on lower limb motor-recovery and gait in stroke: A randomised controlled trial

Objective: To determine the effect of activity-based mirror therapy (MT) on motor recovery and gait in chronic poststroke hemiparetic subjects.

Design: A randomised, controlled, assessor-blinded trial.

Setting: Rehabilitation institute.

Participants: Thirty-six chronic poststroke (15.89?±?9.01 months) hemiparetic subjects (age: 46.44?±?7.89 years, 30 men and functional ambulation classification of median level 3).

Interventions: Activity-based MT comprised movements such as ball-rolling, rocker-board, and pedalling. The activities were provided on the less-affected side in front of the mirror while hiding the affected limb. The movement of the less-affected lower limb was projected as over the affected limb. Conventional motor therapy based on neurophysiological approaches was also provided to the experimental group. The control group received only conventional management.

Main outcome measures: Brunnstrom recovery stages (BRS), Fugl-Meyer assessment lower extremity (FMA-LE), Rivermead visual gait assessment (RVGA), and 10-metre walk test (10-MWT).

Results: Postintervention, the experimental group exhibited significant and favourable changes for FMA-LE (mean difference?=?3.29, 95% CI?=?1.23–5.35, p?=?.003) and RVGA (mean difference?=?5.41, 95% CI?=?1.12–9.71, p?=?.015) in comparison to the control group. No considerable changes were observed on 10-MWT.

Conclusions: Activity-based MT facilitates motor recovery of the lower limb as well as reduces gait deviations among chronic poststroke hemiparetic subjects.     

A Note on the “One Case per Stagger Position” Character of Common Multiple-Baseline Intervention Designs

Purpose: To overcome the constraint of common multiple-baseline designs that only one case per stagger position is permitted.

Methods: Three alternative strategies for assigning more than one case to each stagger position are examined.

Results: The three recommended strategies achieve the objective while maintaining the study’s internal and statistical-conclusion validities.

Conclusions: ExPRT, a freely available Excel-based randomization-test package, can be used to assist in both the design and statistical analysis associated with each of the strategies.     

Exploring dimensions of social support and resilience when providing care at the end of life: a qualitative study

Background: Research shows that formal and informal social support can facilitate resilience in carers. There is a paucity of research exploring social support and resilience amongst recently bereaved informal carers.

Aim: To examine how the presence or absence of distinct dimensions of social support facilitate or hinder resilience in recently bereaved informal carers.

Participants: 44 bereaved carers, who had been identified by GP as ‘main carer’ of someone recently deceased (3–12 months), aged between 38 and 87 years old (mean= 67).

Methods: Thematic analysis then the Ecological Framework of Resilience as an organisational tool to develop overarching themes in the data. We used the Sherbourne and Stewart model to identify social support that was lacking as well as social support that was present.

Results: A range of social support types were identified. There was an emphasis on the importance of relationships with both health professionals and family members, including the care recipient. However, social support was not necessary for resilience if the participant had other resources.

Conclusions: Social support for carers providing end of life care is almost exclusively based around end of life care ‘work’. In comparison to other research our study suggests that relationships with family and health professionals are paramount. Multidimensional support is needed for carers to enhance their resilience.     

Estimation of skeletal muscle mass in patients with spinocerebellar ataxia type 3 and 10

Background: Neurodegenerative diseases may progress to a level in which patients present spontaneous weight loss, resulting in increased falls and functional disabilities when the disease is associated with muscle mass depletion.

Objective: Evaluate the muscle compartment in patients presenting spinocerebellar ataxia (SCA) type 3 and 10.

Methods: Forty-six patients presenting SCA type 3 and 10 were assessed and 76 volunteers were selected to the control group. In order to evaluate the muscle compartment, muscle mass anthropometric measurements were assessed and total skeletal muscle mass calculated through a predictive equation.

Results: Women with SCA3 presented greater weight loss and muscle mass reduction compared to those with SCA10 and the control group. Among the predictive measurements, calf muscle circumference showed a more significant correlation with total skeletal muscle mass (p = 0.718).

Conclusion: Patients presenting both types of ataxia did not show severe depletion in their nutritional status; however, those with SCA3 displayed greater weight loss and muscle mass reduction compared to the SCA10 group.     

A how-to guide to aphasia services: celebrating Professor Linda Worrall’s contribution to the field

Background: This article recognises Professor Linda Worrall’s contribution to aphasiology and discusses research themes which have grown from her work.

Aims: To review, summarise, and discuss literature relating to four themes which have emerged from the work of Professor Worrall: (1) Research capacity building; (2) Implementation of research evidence in clinical practice; (3) Meaningful outcome measurement; and (4) Improvement of psychological and emotional outcomes.

Main contribution: A review of the literature, with examples of practical applications.

Conclusions: The work of Professor Worrall has greatly influenced the field of aphasia; her legacy is the research capacity she has built in Australia and around the world.     

Screening Adherence for Depression Post Stroke: Evaluation of Outpatients,a London Experience (SAD PEOPLE)

Background: Post stroke depression (PSD) is common, and the transition home following discharge may be especially challenging for stroke survivors.

Objectives: This study aimed to determine how well specific Canadian Best Practice Recommendations for PSD screening were adopted within a stroke rehabilitation outpatient clinic before and after the utilization of a standardized clinical form.

Methods: Practices were evaluated through retrospective chart review before and after the implementation of the standardized form which cued physicians to administer the Patient Health Questionnaire 9 (PHQ-9) at the first outpatient visit. Participants included those aged ≥18 years with a primary diagnosis of stroke.

Results: One hundred thirty-five subjects’ charts were reviewed. Form implementation was associated with increased rates of PSD screening (93.8% versus 0%) and charting regarding mood (55.4% versus 15.7%).

Conclusion: This study highlights the frequency of depressive symptoms in an outpatient cohort and demonstrates how screening rates can be improved by using a standardized form. Routine PHQ-9 completion at the first outpatient visit was associated with more physician–patient discussion and documentation regarding mood.     

To what extent is subjective well-being in late adulthood related to subjective and objective memory functioning? Five-year cross-lagged panel analyses

Background: Population aging motivated a focus in contemporary research on factors, e.g. cognitive functioning, that contribute to ‘aging well.’ However, something that has been overlooked is relation between memory functioning, determined by objective tests as well as subjective memory ratings, and subjective well-being (SWB).

Objectives: The aim of the present study was to investigate cross-sectional and longitudinal (cross-lagged) relationships between episodic memory (both subjective and objective) and SWB.

Method: A total of 586 older individuals (60–90 years) were assessed on multiple measures of the targeted constructs at baseline (Time 1) as part of the Betula cohort study. Five years later (Time 2), 354 of the participants returned for follow-up measurements and were included in cross-lagged panel analyses.

Results: As expected, objective memory and subjective memory showed a pattern of cross-sectional age deficits and a mean level longitudinal decline was observed for objective memory. By contrast, SWB showed stable mean levels both across age and time. No cross-sectional or cross-lagged associations were observed between SWB and objective memory, whereas subjective memory and SWB showed a cross-sectional association.

Conclusion: The results underscore that successful aging is a multifaceted construct with no or only weak associations between the investigated components. However, SWB and rate of change at the individual level should be considered to define successful aging.     

Acute aseptic meningitis during isotretinoin treatment for nodular acne solely presenting with headache: case report and brief review of the literature

Purpose/aim: We describe, in detail, the first case of isotretinoin-induced aseptic meningitis. A brief summary of the literature on drug-induced aseptic meningitis (DIAM) is also presented.

Materials and methods: A 20-year old female patient with probable (Naranjo adverse reaction probability score of 7) DIAM during treatment with isotretinoin therapy for nodular acne solely, presenting with headache. Pseudotumor cerebri was appropriately ruled-out.

Results: Summary of data altogether lead us suggest that isotretinoin triggered DIAM, possible due to a delayed hypersensitivity mechanism type III or IV.

Conclusion: We highlight a quite uncommon cause of DIAM that may be increasing in frequency due to the current increasing use of isotretinoin against nodular acne.     

Choosing among second-generation antidepressant treatments for depressed patients with cardiac diseases

Objectives: The present paper aimed to assist physicians in the accurate choice among second-generation agents (SGAs) for patients with cardiovascular disease (CVD).

Methods: We reviewed the published pharmacokinetic (PK) and pharmacodynamic (PD) clinical data that report potential -or absence of- drug interactions between second-generation agents (SGAs) and CVD drugs most commonly used in cardiology, including antiplatelet drugs and anticoagulants, statins, beta-blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics and the antiarrhythmic drugs amiodarone and digoxin.

We also reviewed the cardiovascular safety profile that has been published for each class of SGAs and side effects reported by patients with CVD.

Results: Most relevant PK/PD data about SGAs and CVD drugs are based on small studies or detailed case reports. In many cases, the drug interactions are at most assessed in healthy volunteers so that the clinical relevance of findings needs further investigation in patients with CVD. Case reports of serious, sometimes fatal reactions due to concomitant administration of certain drugs require careful consideration.

The major cardiac side effects of SGAs include HR increase, postural hypotension and slight prolongation of the intraventricular conduction time and QT interval. On normal dosage of antidepressants, both advanced heart block and ventricular arrhythmias could occur in patients with severe heart disease, together with clinically important loss of myocardial contractile force.

Conclusions: Data reported in the present review should help physicians about their decision-making processes that govern SGAs use in CVD patients.     

A treatment comparison study of a photo activity schedule and Social Stories for teaching social skills to children with Autism Spectrum Disorder: brief report

Purpose: To compare the efficacy of two procedures, a photo activity schedule intervention and Social Stories, to teach social skills to four children diagnosed with Autism Spectrum Disorder (ASD).

Methods: An adapted alternating treatments design with an additional multiple baseline control was used, and two social skills were targeted for each of the four participants, one under each intervention condition.

Results: Results indicated that all four participants learned the target social behaviours with the photo activity schedule intervention, but did not learn target social behaviours with Social Stories.

Conclusions: Findings support the use of a photo activity intervention for teaching social skillsto children with ASD; we discuss the implications of inconsistent findings of effectiveness of Social Stories.     

Predictors of maternal stress in pre-school and school-aged children with autism

Background: Mothers of children with autism experience high levels of stress. However, little is known about whether maternal stressors differ across children of different ages.

Method: This study investigated stressors in mothers of 29 pre-school-aged and 27 school-aged children with autism. Correlation and regression analyses were used to determine if maternal stressors differed between the two age groups.

Results: Findings revealed no difference in maternal stress levels across the two age groups; however, stressors for each age group were different. Stressors in the school-aged group were related to repetitive behaviours, sensory sensitivities, and problematic behaviours, while stressors in the pre-school-aged group were mainly related to adaptive behaviours.

Conclusions: These findings are informative for practitioners and highlight the need for tailored supports and therapies for mothers of children with autism of different ages.     

An international survey of obesity and underweight in youth and adults with intellectual disabilities

Background: Increased levels of obesity have been reported for people with intellectual disability based on data mostly gathered in high income countries. Likewise few studies internationally have focussed on underweight in this population.

Method: Data on obesity and underweight were analysed from nearly 86,500 youth and adults with intellectual disabilities drawn from 178 countries attending Special Olympic events.

Results: Binary logistic regressions identified higher levels of obesity for athletes in high income countries – especially in North America – and for females and for adults aged 40 years and over; and for youth aged 8 to 10 years. Rates of underweight were higher for younger adults in low income countries of Asia-Pacific, and highest for males aged 11-13 from lower-middle income countries of Africa.

Conclusions: Contrasting intervention strategies are needed globally to enable people with intellectual disabilities to achieve healthy weight.     

Long-term cardiovascular safety of psychostimulants in children with attention deficit hyperactivity disorder

Objective: Side effects are a concern during psychostimulant treatment. Unfortunately, many previous studies only investigated short-term effects of psychostimulants in laboratory settings which lack clinical daily routines.

Methods: We examined 1042 patient records of patients with attention deficit hyperactivity disorder (ADHD) who were referred to a pediatric-psychiatry practice over 12?years. Data analysis was based on 466 children with ADHD who were newly treated with psychostimulants and who were not in treatment for elevated blood pressure. We analysed blood pressure percentiles, heart rate and BMI percentiles.

Results: There was a decrease in systolic and diastolic blood pressure percentiles. Heart rate was not affected. BMI slightly declined in girls.

Conclusions: In general psychostimulants were safe. To further elucidate negative effects of psychostimulants, long-term controlled and randomized studies in naturalistic settings are of interest.     

Pharmacogenetics and levodopa induced motor complications

Aim: L-dopa remains the most effective symptomatic therapy for Parkinson's disease (PD) but unfortunately, its chronic use is often associated with motor complications. This review highlights the importance of pharmacogenetics in an individualised PD therapeutic approach.

Material and Methods: review of the literature was done.

Results: PD patients show remarkable heterogeneity in their response to L-dopa and this profound interindividual heterogeneity suggests that there is a genetic predisposition.

Conclusions: The impact of the genetic makeup of every individual on PD treatment appears to be of great importance in order to achieve not only the optimum therapeutic effect, but also with minimal side effects.     

Smell your memories: Positive effect of odor exposure on recent and remote autobiographical memories in Alzheimer’s disease

Introduction: There is a burgeoning interest in the effects of odor exposure on autobiographical memory in Alzheimer’s disease (AD). We pursued this line of research by assessing the effect of odor exposure on the retrieval of recent and remote memories in AD.

Method: Twenty-six patients with mild AD and 28 controls were tested in two conditions: with and without odor exposure. In each condition, participants were invited to retrieve two childhood memories, two adulthood memories, and two recent memories.

Results: Analysis showed that AD patients produced a higher number of and more specific childhood memories, adulthood memories, and recent memories after odor exposure than without odor.

Discussion: These findings demonstrate how odor exposure may alleviate anterograde and retrograde amnesia, at least when considering the ability of patients with mild AD to retrieve few recent or remote memories.     

Therapeutic efficacy of the Ginkgo special extract EGb761® within the framework of the mitochondrial cascade hypothesis of Alzheimer’s disease

Objectives: The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction as an important common pathomechanism for the whole spectrum of age-associated memory disorders from cognitive symptoms in the elderly over mild cognitive impairment to Alzheimer’s dementia. Thus, a drug such as the Ginkgo special extract EGb 761^® which improves mitochondrial function should be able to ameliorate cognitive deficits over the whole aging spectrum.

Methods: We review the most relevant publications about effects of EGb 761^® on cognition and synaptic deficits in preclinical studies as well as on cognitive deficits in man from aging to dementia.

Results: EGb 761^® improves mitochondrial dysfunction and cognitive impairment over the whole spectrum of age-associated cognitive disorders in relevant animal models and in vitro experiments, and also shows clinical efficacy in improving cognition over the whole range from aging to Alzheimer’s or even vascular dementia.

Conclusions: EGb 761^® shows clinical efficacy in the treatment of cognitive deficits over the whole spectrum of age-associated memory disorders. Thus, EGb 761^® can serve as an important pharmacological argument for the mitochondrial cascade hypothesis of dementia.     

Do patients with severe poststroke communication difficulties have a higher incidence of falls during inpatient rehabilitation? A retrospective cohort study

Background: Falls in hospital are common and serious complications of stroke. Associations have been found between communication disorders and increased rates of falls, but have received relatively little consideration as a risk factor for falls among stroke survivors.

Objectives: To investigate whether there is an association between severe communication impairment and falls among patients receiving inpatient rehabilitation after stroke.

Methods: A retrospective audit of 149 records of consecutive patients admitted to an inpatient rehabilitation facility after stroke over a two-year period was conducted. The relationship between falls and severe communication impairment was explored using (1) direct comparison of falls in patients with and without functional communication for the inpatient ward environment and (2) multivariate logistic regression to examine factors that may predict falls, including presence or absence of functional communication. In each analysis, falls were examined both as a binary outcome (fall or no fall), and the rate of falls per day.

Results: The 32 patients in the sample (21.7%) who were unable to communicate their basic needs were almost twice as likely to fall in hospital as those with functional communication (RR 1.94, 95% CI 1.15 to 3.24). Several commonly assessed factors were not significant predictors of falls (including falls history, polypharmacy, and cognitive impairment) in this population. Lack of functional communication was the strongest independent predictor of falls rate.

Conclusions: Findings suggest that severe communication disorders may be under recognized as a falls risk factor after stroke.     

Effects of aging on the myelination of the optic nerve in rats

Aim of the study: Cognitive decline due to aging is most probably the result of changes in the white matter in the central nervous system (CNS) and/or demyelination.

Material and methods: We used electron microscopic analysis of the morphological changes in aging rats’ optic nerves as an easily accessible part of the CNS.

Results: Several age changes were observed in aging rats (36?months) vs. young adult rats (6?months), namely degeneration of axons, decreased packing density and morphological alterations of myelination, including the ballooning of some myelin sheaths, separation of myelin lamellae and degenerative changes in the oligodendrocytes population.

Conclusion: Cognitive decline related to aging may occur in part due to the disturbed myelination of axons in CNS white matter.