Reversal of the diabetic bone signature with anabolic therapies in mice

The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone architecture.Herein,we reveal the diabetic bone signature in mice at the tissue,cell,and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it.Diabetes decreased bone mineral density(BMD)and bone formation,damaged microarchitecture,increased porosity of cortical bone,and compromised bone strength.Teriparatide(PTH),abaloparatide(ABL),and romosozumab/anti-sclerostin antibody(Scl-Ab)all restored BMD and corrected the deteriorated bone architecture.Mechanistically,PTH and more potently ABL induced similar responses at the tissue and gene signature levels,increasing both formation and resorption with positive balance towards bone gain.In contrast,Scl-Ab increased formation but decreased resorption.All agents restored bone architecture,corrected cortical porosity,and improved mechanical properties of diabetic bone;and ABL and Scl-Ab increased toughness,a fracture resistance index.Remarkably,all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia.These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.

Anxiety,depression,and quality of life in Parkinson's disease:the implications of multidisciplinary treatment

Anxiety and depression in Parkinson's disease(PD)reduce well-being of the patients.Emotional alterations influence motor skills and cognitive performance;moreover,they contribute significantly and independently to worsen rehabilitative treatment response.We investigated anxiety,depression,and quality of life in PD patients subjected to multidisciplinary rehabilitative training.The self-controlled study included 100 PD patients(49 males and 51 females with the mean age of 64.66 years)admitted to 60 days hospitalization rehabilitative program,between January 2017 and December 2018.Motor,cognitive,linguistic abilities,and functional independence were evaluated at admission(T0 baseline visit)and 60 days after(T1)the multidisciplinary rehabilitation including motor exercises,speech therapies,and cognitive intervention.The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood,motor abilities,autonomy in the activities of daily life,perception of quality of life,cognitive performance and speech skills.Non-motor symptoms may worsen severe disability and reduce quality of life.They are often poorly recognized and inadequately treated.Nonetheless,multidisciplinary rehabilitative training represents an optimal strategy to improve disease management.The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico(IRCCS)Centro Neurolesi"Bonino-Pulejo"Ethical Committee(approval No.6/2016)in June 2016.

Health-related quality of life in Parkinson's disease patients in northeastern Sicily, Italy An ecological perspective

Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson＇s disease patients in nOrtheastern Sicily, Italy. Ninety Parkinson＇s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi ＂Bonino-Pulejo＂ （Messina）, were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale （UPDRS-Ⅲ） scores, the Parkinson Disease Questionnaire-39 Item scores （as a disease-specific measure of health-related quality of life）, scores on the Short Form （36） Health Survey Questionnaire （as a generic measure）, and answers to a brief checklist were recorded. A total of 85 Parkinson＇s disease patients （49% males and 51% females; mean age 70.8 ± 8.6 years mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years） completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.

Magnetic resonance imaging markers for early diagnosis of Parkinson's disease

Parkinson＇s disease （PD） is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called ＂prodromal＂, where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging （MRI） and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.

Deficit of pursuit ocular movements in early Alzheimer's disease

Previous studies have demonstrated that advanced Alzheimer＇s disease（AD）patients have deficiency of eye movements.However,there have been no reports on eye movement in the early stages of AD.The aim of this study was to evaluate pursuit ocular movements（POM）provided by a vision-based non-intrusive eye tracker in patients with early AD.POM values were significantly lower in AD patients than in normal controls（P 〈 0.01）.In AD patients,POM values were not closely correlated with the Mini-Mental State Examination scores（P = 0.3）.There was no significant difference in POM values among patients treated with or without anticholinesterase therapy.We used a vision-based method,for non-intrusive eye tracking,which can be proposed as a possible tool for supporting the diagnosis of early AD.

Diffusion-weighted imaging and fluid-attenuated inversion recovery sequence in sporadic Creutzfeldt-Jakob disease:One-case report

The diagnosis of sporadic Creutzfeldt-Jakob disease （sCJD） is extremely difficult. Diffusion-weighted imaging has been shown to be the most sensitive technique for the detection of signal alterations in sCJD patients. The present study analyzed the diagnostic value of diffusion-weighted imaging and fluid-attenuated inversion recovery sequence in the early stage of sCJD in one female patient and correlated the clinical symptoms during disease course and magnetic resonance manifestations. Thalamic and basal ganglia hyperintensities were observed on magnetic resonance images in a very early stage, i.e., when the clinical typical manifestations of the disease were not present. With the progression of the disease, cortical and basal ganglia hyperintensities were observed on magnetic resonance images, showing an obvious cerebral atrophy. These findings suggest that diffusion-weighted imaging and fluid-attenuated inversion recovery sequence are helpful in diagnosing sCJD.