Tailoring therapy for heart failure: the pharmacogenomics of adrenergic receptor signaling.

Heart failure is one of the leading causes of mortality in Western countries, and β-blockers are a cornerstone of its treatment. However, the response to these drugs is variable among individuals, which might be explained, at least in part, by genetic differences. Pharmacogenomics is the study of genetic contributions to drug response variability in order to provide evidence for a tailored therapy in an individual patient.

Cholinesterase inhibitors for Parkinson's disease: a systematic review and meta-analysis.

Background: Parkinson's disease (PD) is a progressive neurodegenerative movement disorder frequently associated with a wide variety of non-motor symptoms related to non-dopaminergic pathways. Although the depletion of dopamine is the key neurochemical impairment in PD and anticholinergic medications are used for symptomatic treatment, significant deficits in cholinergic transmission are also present and have been associated with cognitive decline and gait dysfunction. Therefore, use of a cholinesterase inhibitor (ChI) might improve cognitive function and reduce the risk of falls in patients with PD, although it could plausibly worsen motor features.

Closing-in is related to apathy in Alzheimer's disease patients.

Background: Apathy and depression are behavioral manifestations that may occur often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in (CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that apathetic symptoms are related to frontal dysfunctions in AD patients, whereas the cognitive bases of depressive symptoms in AD are still unclear.

Adrenal adrenoceptors in heart failure.

Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease.

Hypoglycemia is independently associated with multidimensional impairment in elderly diabetic patients.

Aim: To identify the characteristics associated with multidimensional impairment, evaluated through the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a standardized Comprehensive Geriatric Assessment (CGA), in a cohort of elderly diabetic patients treated with oral hypoglycemic drugs.

Methods And Results: The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers distributed throughout Italy, within the Metabolic Study. Inclusion criteria were diagnosis of type 2 diabetes mellitus (DM), 65 years old or over, and treatment with oral antidiabetic medications.

Hemostatic and fibrinolytic changes are related to inflammatory conditions in patients with psoriatic arthritis--effect of different treatments.

Objective: To prospectively evaluate the effect of tumor necrosis factor (TNF)-α inhibitors on hemostatic and fibrinolytic variables in subjects with psoriatic arthritis (PsA).

Methods: Among subjects with PsA who were taking traditional disease-modifying antirheumatic drugs (DMARD), 98 patients with active disease who switched to treatment with TNF-α inhibitors were enrolled in this study (Group 1). In parallel, 98 matched subjects with minimal disease activity (MDA) and treated with DMARD were enrolled (Group 2).

A study of the psychological distress in family caregivers of patients with prolonged disorders of consciousness during in-hospital rehabilitation.

Objectives: To study psychological distress in a sample of caregivers of patients affected by prolonged disorders of consciousness during hospital stay in the Neurorehabilitation Unit.

Materials And Methods: Twenty-four caregivers of 22 patients affected by prolonged disorders of consciousness admitted to postacute rehabilitation center, completed self-reported questionnaires for assessment of depressive symptoms, state and trait anxiety, psychophysiological disturbances, prolonged grief disorder, psychological coping strategies, quality of perceived needs, perceived social support, and caregiver burden; at admission, and after four and eight months.

Results: At admission depressive symptoms were found in 20/24 caregivers, high levels of anxiety in 16, and relevant psychophysiological disturbances in 10 participants; eight caregivers (32%) met criteria for prolonged grief disorder.

Sudden onset of coma in a 70-year-old woman with cryoglobulinemia.

Patient: Female, 70 FINAL DIAGNOSIS: Chronic Heaptitis C Symptoms: Coma Medication: - Clinical Procedure: Plamapheresis Specialty: Neurology.

Objective: Unusual clinical course.

Background: Hepatitis C Virus (HCV)-related chronic hepatitis can be associated with mixed cryoglobulinemia (MC).

β-adrenergic receptor responsiveness in aging heart and clinical implications.

Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called "β-adrenergic desensitization"). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis.

Neuro-hormonal effects of physical activity in the elderly.

Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer.

Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure.

Background: Short-term changes of neurohormones can give important prognostic information in heart failure (HF) patients. In this study, we evaluate whether changes in plasma Norepinephrine (NE) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) after exercise training predict cardiac mortality in HF patients.

Methods And Results: We enrolled 221 HF patients (mean age 72.

The role of embodied simulation in mental transformation of whole-body images: evidence from Parkinson's disease.

It has been repeatedly demonstrated that mentally performing an action and mentally transforming body-parts entail simulation of one's own body movements, consistent with predictions of embodied cognition theories. However, the involvement of embodied simulation in mental transformation of whole-body images is still disputed. Here, we assessed own body transformation in Parkinson's disease (PD) patients with symptoms most affecting the left or the right body side.

Clinical and neuropsychological long-term outcomes after late recovery of responsiveness: a case series.

Objective: To report clinical conditions and neuropsychological functioning of patients with late recovery of responsiveness at least 5 years after injury.

Design: Patient series.

Setting: Patients discharged from an inpatient rehabilitation unit.

Vascular endothelial growth factor blockade prevents the beneficial effects of β-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure.

Background: Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, β-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart.

β1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy.

Background: The sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G-protein-coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein-coupled receptor kinase-2, which triggers desensitization and downregulation processes.

Effectiveness of a rehabilitative programme in improving fatigue and function in rheumatoid arthritis patients treated with biologics: a pilot study.

Objectives: To evaluate the effectiveness of a personalised rehabilitative programme in improving fatigue and function in rheumatoid arthritis (RA) female patients treated with biologic DMARDs.

Methods: Thirty-eight consecutive female RA in-patients treated with biologics, entered this prospective pilot study. All subjects were in high disease activity (DAS-28>5.

Oral anticoagulation therapy in heart failure patients in sinus rhythm: a systematic review and meta-analysis.

Background: Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated.

Methodology And Principal Findings: We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm.

Instruments for geriatric assessment: new multidimensional assessment approaches.

During the last century the considerable increase in life expectancy has led to important demographic changes and, consequently, to new clinical scenarios. Nowadays, chronic conditions, comorbidities and socio-economic factors constitute a relevant health management issue. In particular, the definition of frail elderly individuals has proven to have a strong role in the identification of high-risk patients, their clinical management and prognosis.

Severe respiratory and skeletal muscles involvement in a carrier of dysferlinopathy with chronic obstructive pulmonary disease.

The natural course of progressive neuromuscular diseases can be complicated by respiratory muscle involvement. In muscular dystrophies such as Duchenne muscular dystrophy and myotonic dystrophy, respiratory muscle involvement is common. In others such as Becker, limb-girdle, and facioscapulo-humeral dystrophies, respiratory muscle involvement is infrequent and generally occurs in the more severe cases.

Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state.

Objectives: Late recovery of awareness in vegetative state (VS) is considered as an exceptional outcome, and has been reported prevalently after traumatic brain injury (TBI). The present prospective study aimed to verify frequency of late recovery (later than 1 year postonset in TBI and 3 months postonset in patients without TBI) of responsiveness and consciousness in traumatic and nontraumatic long-lasting (more than 6 months after onset) VS.

Methods: Fifty inpatients with long-lasting VS (36% TBI, 36% hemorrhagic, and 28% anoxic) were enrolled and followed up for a mean of 25.

Rehabilitation in psoriatic arthritis.

This article summarizes the state of the art of rehabilitation in psoriatic arthritis (PsA). Very little evidence was available to assess the efficacy of rehabilitation. Some data were borrowed from studies on ankylosing spondylitis.

Psoriatic arthritis spondylitis radiology index: a modified index for radiologic assessment of axial involvement in psoriatic arthritis.

Objective: To develop and validate a modified index for assessing the radiologic axial involvement in psoriatic arthritis (PsA) in a group of patients with established disease.

Methods: Patients were included on clinical and/or radiologic criteria. The modified index combined features of existing radiologic indices for ankylosing spondylitis (AS) with the addition of scores for the facet joints of the cervical and lumbar regions.

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms.

Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders. The pathogenesis of bronchiectasis is poorly understood.

Persistent airway inflammation and high exacerbation rate in asthma that starts at menopause.

Background And Aim: Asthma that begins around the time of menopause is frequently characterised by marked clinical severity and poor response to treatment. We sought to assess the clinical characteristics, bronchial responsiveness, perception of induced bronchoconstriction and airway inflammation in women with menopausal asthma, as compared to women of a similar age with pre-existing asthma.

Methods: Nine women with pre-existing asthma were selected for clinical severity (symptoms, lung function and medication requirements) similar to that in 11 women with menopausal asthma.

Effect of losartan in treatment of exercise-induced myocardial ischemia.

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind).