Microtechnologies in medicine: an overview.

Microsystems technology (MST) has become a significant enabler of novel medical devices and implants over the last years. Typical examples are MST units in cardiac rhythm management devices or in hearing implants. A classification of medical MST applications can be made according to their relationship with the anatomy that is based on the kind and duration of interaction with the human body: Class 1: Extra-corporeal devices such as telemetric health monitoring systems or point of care testing systems. Class 2: Intra-corporeal devices such as intelligent surgical instruments. Class 3: Temporarily incorporated or ingested devices, such as telemetric endoscopes. Class 4: Long-term implantable devices such as telemetric implants. Medical applications of MST are growing at double-digit compounded growth rates, leading to a forecasted global market volume of over USD 1 billion in 2006 or 2007, making MST devices a relevant segment of the medical technology market. The clinical foundation for promoting the use of MST in medicine is mainly based on the significant potential of MST to enable products that improve early disease detection and the monitoring of chronic illnesses. This refers to a number of the most important health problems such as cardiovascular disease, hypertension, diabetes and cancer, to name just a few. More recently microrobotics has become a relevant research area for enabling the atraumatic transport of MST-enhanced diagnostic and therapeutic devices inside the human body.     

Synapsin III is a key component of α‐synuclein fibrils in Lewy bodies of PD brains

Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α‐synuclein (α‐syn), are neuropathological hallmarks of Parkinson''s disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α‐syn and modulates α‐syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K‐resistant neuropathological inclusions that contained both α‐syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α‐syn‐positive fibrils in LB‐enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α‐syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α‐syn interactant and a key component of LB fibrils in the brain of patients affected by PD.     

Effect of Different Tube Feeding Methods on the Delivery of Docosahexaenoic and Arachidonic Acid: An In Vitro Pilot Study

Background: Arachidonic acid (AA) and docosahexaenoic acid (DHA) are crucial for neural and visual development after premature birth. Preterm infants usually require tube feeding (TF) until the achievement of adequate oral feeding skills; the impact of TF on DHA and AA delivery has not been investigated yet. This study aimed to evaluate the effect of different TF techniques on the delivery of AA and DHA contained in human milk (HM). Methods: HM samples (65 mL each) were collected and divided into three 20‐mL aliquots. The remaining 5 mL served as baseline. Three TF techniques were simulated (1 for each aliquot): gravity bolus feeding (BF), 3‐hour continuous feeding using a horizontal feeding pump, and 3‐hour continuous feeding with the feeding pump angled at 45°. For horizontal continuous feeding (HCF) and 45° angled continuous feeding (ACF), aliquots delivered between 0 and 90 minutes (T1) and 91 and 180 minutes (T2) were collected separately. AA and DHA concentration was analyzed by gas chromatography/mass spectrometry and compared among the TF methods. DHA and AA delivery at T1 and T2 was also evaluated. Results: Fifty‐one simulated feeds were performed. DHA and AA amounts after BF and ACF did not differ significantly compared with baseline, whereas HCF resulted in significantly lower DHA and AA concentration. During T2, ACF delivered almost twice the DHA and AA amounts compared with T1. Conclusion: The delivery of HM AA and DHA is significantly affected by TF, with potential clinical implications. When BF is not tolerated, ACF might represent a feasible alternative to reduce TF‐related DHA and AA loss.     

Effectiveness of community-based treatment on clinical outcome in children with autism spectrum disorders: An Italian prospective study

Objective: Little is known about outcomes of Autism Spectrum Disorders (ASDs) interventions in real-life settings. The main aim of this naturalistic study was to collect real-life data on the actual ASDs treatment practices in Italy.

Methods: A cohort of 48 children undergoing community-based interventions was observed in terms of personal and environmental characteristics, treatment typology and outcomes.

Results: An earlier start of treatment was associated with an improvement of autistic symptoms, independently from symptoms severity (p?<?0.05), but not with improvements in terms of intelligence quotient (p?=?0.8). Children belonging to lower socioeconomic status families began treatment later (48.0 months) than those belonging to middle (39.8 months) or upper (39.2 months) classes (p?<?0.05), and received less hours of treatment.

Conclusion: The study showed that ASDs interventions should be observed not only in experimental settings, but also in naturalistic environments, so to appraise the actual effectiveness of integrating different treatment methods in community settings.     

Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis

B cell chronic lymphocytic leukemia (B-CLL) is a neoplastic disorder characterized by accumulation of B lymphocytes due to uncontrolled growth and resistance to apoptosis. Analysis of B cells freshly isolated from 40 patients with chronic lymphocytic leukemia demonstrated that the Src kinase Lyn, the switch molecule that couples the B cell receptor to downstream signaling, displays anomalous properties. Lyn is remarkably overexpressed at the protein level in leukemic cells as compared with normal B lymphocytes, with a substantial aliquot of the kinase anomalously present in the cytosol. Whereas in normal B lymphocytes Lyn activation is dependent on B cell-receptor stimulation, in resting malignant cells, the constitutive activity of the kinase accounts for high basal protein tyrosine phosphorylation and low responsiveness to IgM ligation. Addition of the Lyn inhibitors PP2 and SU6656 to leukemic cell cultures restores cell apoptosis, and treatment of malignant cells with drugs that induce cell apoptosis decreases both activity and amount of the tyrosine kinase. These findings suggest a direct correlation between high basal Lyn activity and defects in the induction of apoptosis in leukemic cells. They also support a critical role for Lyn in B-CLL pathogenesis and identify this tyrosine kinase as a potential therapeutic target.     

Prognostic significance of personality profiles in patients with chronic migraine

BACKGROUND AND OBJECTIVE: The aim of this study was to assess whether the psychological profile may have prognostic significance in chronic migraine patients. METHODS: The Minnesota Multiphasic Personality Inventory-2 was used for the psychological assessment of patients with chronic migraine to explore personality traits. Patients with psychiatric disease and medication overuse were excluded. One hundred and two patients completed the study. Migraine-related disability was measured using the Migraine Disability Assessment questionnaire at baseline (T(0)) and again after 2 years (T(1)), during which patients received prophylactic treatment for migraine. At T(1) patients were classified into those exhibiting significant improvement (group 1: scores reduced by at least 50%) and those with unsatisfactory changes in headache-related disability (group 2: scores reduced by less than 50%). RESULTS: At T(1) 49 patients were in group 1 and 53 in group 2; at T(0), group 1 patients had significantly lower Minnesota Multiphasic Personality Inventory-2 scores in the neurotic (hypochondriasis: P < .01; depression: P < .001; hysteria: P < .01) and schizophrenia (P < .05) scales. None of the other variables studied, ie, age, sex, age at migraine onset, number of years from chronic migraine onset, T(0) Migraine Disability Assessment score, T(0) headache frequency, severity and temporal pattern (continuous vs intermittent) differed significantly between the groups. CONCLUSIONS: Findings suggest that psychological factors can influence the clinical course of chronic migraine and that psychological evaluation with Minnesota Multiphasic Personality Inventory-2 may be a reliable approach to obtain prognostic data and information for therapy planning in patients with chronic migraine.     

Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance

Neuropsychological status, as assessed by trailmaking test; plasma amino acids, and ammonia, were studied in 54 cirrhotics without clinical evidence of encephalopathy to determine the prevalence of subclinical mental dysfunction and its relationship to metabolic abnormalities. Control values for psychometric performance were established in 54 normal subjects matched for age, sex, educational level, and employment status. Of these subjects, 16 were also used as controls for fasting ammonia and plasma amino acids. Eighteen cirrhotics (33%) showed impaired performances of the psychometric test; free tryptophan and the ratio free tryptophan to neutral amino acids were increased in 37% and 62% of cases and correlated with the psychometric scores (r=0.45 andr=0.70, respectively). In eight cirrhotics with mild encephalopathy, psychometric and metabolic evaluations were repeated several times during the infusion of amino acid solutions rich in branched-chain amino acids. Again significant correlations were observed between the psychometric scores and plasma amino acids. We conclude that a considerable proportion of clinically normal cirrhotics have neuropsychological deficits. The severity of impairment may be related to the plasma amino acid imbalance, namely to an increased passage of tryptophan across the blood-brain barrier.     

A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-associated Virus Serotypes Upon Cerebrospinal Fluid Administration in Pigs

Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases.