Paediatric drug development: The impact of evolving regulations

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Subfractionation of human very low density lipoproteins by heparin-Sepharose affinity chromatography.

Very low density lipoproteins obtained from normolipidemic subjects were fractionated into subclasses by means of affinity chromatography on a heparin-Sepharose column in the presence of MnCl2. The four subfractions eluted at 0.05, 0.12, 0.20, and 0.38 M NaCl and they differed in chemical composition and apoprotein pattern. The relative amounts of apoB and apoE in subfractions increased with increasing concentrations of the NaCl eluant. Modification of the arginyl residues with 1-2 cyclohexadione demonstrated that arginine plays an important role in determining the elution pattern of VLDL. In vitro studies indicated that only fractions eluted at 0.2 and 0.5 M NaCl compete with LDL for cellular receptors. These data suggest that the various subfractions may represent VLDL at different stages of catabolism

Social contacts and loneliness in people with psychotic and mood disorders

Background Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions. Methods 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness. Results Patients had on average 1.7 (SD = 1.7) social contacts in the previous week (median = 1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n = 30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR = 2.246, p =.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR = 2.798; p <.05). Conclusions Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process

Evaluation of Load Distribution in a Mandibular Model with Four Implants Depending on the Number of Prosthetic Screws Used for OT-Bridge System: A Finite Element Analysis (FEA)

In full-arch implant rehabilitations, when the anterior screw abutment channel compromises the aesthetic of the patient, the OT-Bridge system used with its Seeger rings may provide the necessary retention of the prosthesis. However, no studies have evaluated the forces generated at the Seeger level during loading. This Finite Element Analysis aims to investigate the mechanical behavior of Seeger rings in a mandibular model with four implants and an OT-Bridge system, used without one or two anterior prosthetic screws. A 400 N unilateral load was virtually applied on a 7 mm distal cantilever. Two different variables were considered: the constraint conditions using two or three screws instead of four and the three different framework materials (fiberglass reinforced resin, cobalt-chrome, TiAl6V4). The FEA analysis exhibited tensile and compressive forces on the Seeger closest to the loading point. With the resin framework, a tension force on abutment 3.3 generates a displacement from 5 to 10 times greater than that respectively expressed in metal framework materials. In a full-arch rehabilitation with four implants, the case with three prosthetic screws seems to be a safer and more predictable configuration instead of two. Considering the stress value exhibited and the mechanical properties of the Seeger, the presence of only two prosthetic screws could lead to permanent deformation of the Seeger in the screwless abutment closest to the loading point

Qualitative evaluation of the effects of professional oral hygiene instruments on prosthetic ceramic surfaces

During professional hygiene procedures, different instruments used may cause various damage to dental prostheses. Deplaquing and scaling with curettes and ultrasonic instruments may inadvertently increase the surface roughness of the material and the risk of future bacterial adhesion and/or also compromise the marginal seal of the prosthesis. Hence, the aim of this study was to assess the qualitative effects of two types of curettes and one piezoelectric instrument with a stain-less-steel tip on three types of metal-free samples. After treating the samples with different instru-mentations, they were analyzed using the scanning electron microscope and then underwent a qualitative microanalysis by using a spectroscopy machine. All the materials tested in this study have undergone significant changes of their superficial structure after instrumentation both with mechanical and manual instruments. Plastic curettes appeared to be less aggressive than the other in-struments. Disilicate samples show a significantly lower degree of surface glazing erosion com-pared to the zirconia sample with all the instruments used

asociacion entre angioma cavernoso y glioma cerebral reporte de dos casos y revision de la literatura acerca de los llamados angiogliomas

La asociacion entre las malformaciones vasculares y los gliomas cerebrales es inusual. Mientras que la asociacion entre angioma cavernoso con lesiones gliomatosas es aun mas rara, es por esto considerado por algunos autores como una entidad patologica particular llamada angioglioma. Los autores reportan dos casos de asociacion de un angioma cavernoso con una ganglioglioma y un oligodendroglioma, respectivamente. Ademas se realizo una revision de la literatura sobre los llamados angiogliomas. En opinion de los autores, la entidad de los angiogliomas se presenta dentro de un espectro general de neoplasias angiomatosas, que incluyen tumores cerebrales, en su mayoria gliomas de bajo grado, asociados a su vez, con un componente vascular importante

Abnormal hyperventilation in patients with hepatic cirrhosis: Role of enhanced chemosensitivity to carbon dioxide

BACKGROUND: Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients. METHODS: We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54±8years, mean±SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55±7years). RESULTS: Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO(2)), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO(2) (PaCO(2)), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p<0.05). Rest ventilation was positively related to pH (R=0.41, p=0.023), chemosensitivity to hypercapnia (R=0.54, p=0.002), and progesterone (R=0.53, p=0.016) and negatively to PaCO(2) (R=0.61, p<0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO(2) (R=0.74, p<0.001), serum progesterone (R=0.50, p=0.016), and to plasma norepinephrine (R=0.57, p=0.004). CONCLUSIONS: Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the "unexplained" hyperventilation observed in such patients

Assessment of Preload Loss after Cyclic Loading in the OT Bridge System in an “All-on-Four” Rehabilitation Model in the Absence of One and Two Prosthesis Screws

The aim of this study was to evaluate the stability of prosthetic screws after applying cyclic loadings in an “all-on-four” rehabilitation model with the OT Bridge system. The model was tested both with and without anterior screws. Four implant analogues following the “all-on-four” concept were inserted in an edentulous mandibular resin model. An OT Bridge system with a Cr–Co prosthetic framework was fabricated. Depending on the presence or absence of one or two anterior screws on the implant analogues, three groups were created, i.e., Gr.1: three tightening screws, Gr.2: two tightening screws, Control Group: four tightening screws. Each single group underwent subsequent 400,000 cyclic loads, simulating approximately a year of chewing by using a dynamometer machine. This cycle was repeated five times for each group, and preload loss values were evaluated on each prosthetic screw after each cycle. All the data obtained were analyzed by one-way ANOVA and Student’s t-test. No statistically significant differences after intragroup analysis were found. A statistically significant difference within the Gr.1 between the screws in positions 33 and 36, equal to 15.2% (p-value = 0.0176), was found. The OT Bridge seems a useful system to maintain the retention of a prosthesis during mechanical stress conditions even in the absence of one screw in an “all-on-four” rehabilitation. This could represent a good solution to solve the esthetic problem of the screw buccal access hole for fixed solutions

Exosomes: From potential culprits to new therapeutic promise in the setting of cardiac fibrosis

Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents

4D flow imaging of the thoracic aorta: is there an added clinical value?

Four-dimensional (4D) flow MRI has emerged as a powerful non-invasive technique in cardiovascular imaging, enabling to analyse in vivo complex flow dynamics models by quantifying flow parameters and derived features. Deep knowledge of aortic flow dynamics is fundamental to better understand how abnormal flow patterns may promote or worsen vascular diseases. In the perspective of an increasingly personalized and preventive medicine, growing interest is focused on identifying those quantitative functional features which are early predictive markers of pathological evolution. The thoracic aorta and its spectrum of diseases, as the first area of application and development of 4D flow MRI and supported by an extensive experimental validation, represents the ideal model to introduce this technique into daily clinical practice. The purpose of this review is to describe the impact of 4D flow MRI in the assessment of the thoracic aorta and its most common affecting diseases, providing an overview of the actual clinical applications and describing the potential role of derived advanced hemodynamic measures in tailoring follow-up and treatment