TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients.

Diagnosis of ALS is based on clinical symptoms when motoneuron degeneration is significant. Therefore, new approaches for early diagnosis are needed. We aimed to assess if alterations in appearance and cellular localization of cutaneous TDP-43 may represent a biomarker for ALS.

Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study.

Introduction: Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.

Methods: Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board.

TGA-FTIR study of the pyrolysis of sodium citrate and its effect on the pyrolysis of tobacco and tobacco/SBA-15 mixtures under N and air atmospheres.

In this work, the effect of sodium citrate mixed with tobacco, in the presence and absence of SBA-15 material, was studied by thermogravimetric analysis coupled to Fourier-transform infrared spectrometry under N and air atmospheres. Depending on the atmosphere used, the decomposition of sodium citrate changes considerably at high temperatures, mainly due to the oxidation of the residue. The analysis of the experimental and calculated derivative thermogravimetric data of the sodium citrate/SBA-15 mixtures allows the observation of marked widening of the peaks appearing at lower temperatures, due to the presence of SBA-15, while the expected peak at high temperatures in air completely disappears.

Effect of castration at 10 months of age on growth physiology and behavior of male feral beef cattle.

This study compared the growth performance, plasma testosterone and cortisol levels around castration at 10 months of age, and plasma insulin-like growth factor (IGF)-I concentration and flight speed, in intact bulls and steers from 10 to 21 months of age in a feral Spanish breed. Fourteen bulls (366.5 ± 48.

Phase I pharmacokinetic/pharmacodynamic study of MLN8237, an investigational, oral, selective aurora a kinase inhibitor, in patients with advanced solid tumors.

Purpose: Aurora A kinase (AAK) is a key regulator of mitosis and a target for anticancer drug development. This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors.

Experimental Design: Patients received MLN8237 once daily or twice daily for 7, 14, or 21 consecutive days, followed by 14 days recovery, in 21-, 28-, or 35-day cycles.

Impact of moderate coronary atherosclerosis on long-term left ventricular remodeling after aortic valve replacemen.

Background: The role of coronary atherosclerosis (CA+) in ventricular remodeling after aortic valve replacement (AVR) for isolated aortic stenosis (AS) is not well defined. We sought to evaluate the impact of not revascularized moderate coronary atherosclerosis in long-term left ventricular (LV) remodeling after AVR.

Methods: We assessed by coronariography the coronary artery disease in 66 patients referred for AVR and evaluated morphological and functional LV data by echocardiography both preoperatively and postoperatively (3 ± 1.

Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics.

This phase I trial examined the safety, pharmacokinetics, and pharmacodynamics of MLN8054, an oral, selective, small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received increasing doses of MLN8054 in 28-day cycles until dose-limiting toxicity (DLT) was seen in ≥2 of 3-6 patients in a cohort. For the 10-mg and 20-mg cohorts, treatment was administered once daily on days 1 to 5 and 8 to 12.

Red blood cell depletion with a semiautomated system or hydroxyethyl starch sedimentation for routine cord blood banking: a comparative study.

Background: The major problem with long-term cord blood (CB) banking is the required storage space. In this sense, many studies have been performed to establish techniques for volume reduction of CB units.

Study Design And Methods: We compared two different methods for CB volume reduction in both development and routine phases: hydroxyethyl starch (HES) sedimentation and top-and-bottom fractionation with the Optipress II (Baxter Healthcare).

Utility of bag segment and cryovial samples for quality control and confirmatory HLA typing in umbilical cord blood banking.

Many cord blood (CB) banks have been established worldwide as a response to the increasing number of CB transplantations. In this study, we describe a quality control program in which the utility of an integral bag segment and cryovial containing aliquots of cryopreserved product as haematopoietic content control and HLA typing confirmation for CB units has been evaluated. For this purpose, every month one stored CB unit and its satellite cryovials were thawed and washed.

Optimizing donor selection in a cord blood bank.

Objectives: The main limitation factor for the wide use of umbilical cord blood (UCB) as a source of hematopoietic progenitor for transplantation is cell dose. One of the specific areas identified by some studies for improvement of UCB collection is donor selection.

Methods: Over a 3-mth period, 391 consecutive maternal-neonatal pairs were evaluated during the pre-partum period in the maternity ward at La Fe University Hospital (Valencia) by the Cord Blood Bank staff.

Quality analysis of blood components obtained by automated buffy-coat layer removal with a top & bottom system (Optipress (R)II).

Background And Objective: There are Council of Europe recommendations for the quality of blood components. We analyzed the quality of blood components processed by a top & bottom system (Optipress((R)) II), the routine method used in our blood bank, to test whether the components reached the recommended quality.

Design And Methods: Blood was collected in triple CPD-SAGM bags (Optipac((R)) Baxter).

[Analysis of the quality of hemoderivatives obtained using a buffy-coat extraction system with a top-and-bottom technique (Optipress II)].

Purpose: The aim of the present study is to know the results of the quality analysis of blood components processed with a Top & Bottom system (Optipress II) as a routine method in our blood bank, and compare it with the CE recommendations for quality of blood components.

Material And Methods: Blood was collected in triple CPD-SAGM bags (Optipac, Baxter) and whole blood (WB) were centrifuged at 4,158 g, 14 min. Blood separation was performed by an automated Top & Bottom system (Optipress II), in which parameters were individually configured in preliminary trials.

Speciation as an analytical aid in trace element research in infant nutrition.

The aim of this work was twofold: to study the binding pattern of trace elements in formulas as compared with breast milk and the relationship between trace elements in breast milk and in maternal dietary intake. To investigate the binding form of trace elements in these nutritive fluids, methods for protein separation were combined with methods for trace element determination in the eluted fractions. HPLC and ICP-AES or ICP-MS were coupled on-line for the simultaneous speciation of elements of nutritional interest, viz.

HLA-DQA, -DQB and -DRB allele contribution to narcolepsy susceptibility.

The association of narcolepsy with HLA class I antigens and HLA class II alleles was studies in a series of Spanish narcoleptic patients. The haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was found to be significantly associated with the disease, while the haplotype DRB1*0701-DRB4*01-DQA1*0201-DQB1*02 might confer a slight protective effect against narcolepsy. Gene dose-effect was not seen in any of the involved alleles, and linkage disequilibrium between the positively associated alleles was found to be stronger in patients than in controls.

Light and electron microscopic study of galanin-immunoreactive nerve fibers in the rat posterior thalamus.

Light and electron microscopic immunocytochemistry was used to study certain cell groups in the posteromedial thalamus which contain galanin-immunoreactive (GAL-IR) fibers. The nuclei subparafascicularis pars parvicellularis (SPFpc) and parafascicularis (PF) contain a dense network of GAL-IR fibers which form basketlike structures around unstained cells. The periventricular area also contains numerous GAL-IR fibers and these also occasionally form basketlike structures.

Immunocytochemical analysis of calcitonin gene-related peptide and vasoactive intestinal polypeptide in Merkel cells and cutaneous free nerve endings of cats.

Calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactivity were observed to coexist in Merkel cells of cats. No differences in peptide content were found between Merkel cells located in epithelia of the hard palate, in hairy and glabrous skin of the upper lip, and in vibrissae follicles. CGRP- and VIP-immunoreactive nerve fibres were also found near CGRP/VIP-immunoreactive Merkel cells.

C-PON containing neurons in the rat striatum are also positive for NADPH-diaphorase activity. A light microscopic study.

The indirect immunofluorescence technique to detect endogenous C-flanking peptide of neuropeptide Y (NPY), C-PON, in combination with NADPH-diaphorase (NADPH-d) histochemistry, were applied to the same sections to establish whether C-PON containing cell bodies in the rat striatum can be labelled by their content of NADPH-diaphorase activity. NADPH-diaphorase activity proved to be a reliable marker for these positive C-PON neurons. Our results suggest that, in the rat striatum, C-PON, SOM and NPY co-exist in the same cells.

Distribution of enkephalin-immunoreactive nerve fibres and terminals in the region of the nucleus basalis magnocellularis of the rat: a light and electron microscopic study.

This investigation was carried out on the distribution of enkephalin-containing nerve fibres and terminals in the region of the nucleus basalis magnocellularis (NBM) of the rat. At the light microscope (LM) level, enkephalin-immunoreactive sites and endogenous choline acetyltransferase (ChAT) were demonstrated by employing the two-colour immunoperoxidase staining technique, using highly specific monoclonal antibodies against enkephalin and ChAT. A pharmacohistochemical procedure to reveal acetylcholinesterase (AChE)-synthesizing neurons combined with the peroxidase-antiperoxidase (PAP) immunocytochemical technique to detect endogenous enkephalins, provided ultrastructural data on the relationships of neuronal elements containing AChE and enkephalins in the region of the NBM.

Presence of calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity in intraepidermal free nerve endings of cat skin.

Immunocytochemistry against neuropeptides contained within primary afferent neurons was used to study the morphology and distribution of intraepidermal free nerve endings in cat facial skin. Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity was found in similar intraepidermal nerve endings of cat glabrous and hairy skin epithelia. The greatest density of immunoreactive intraepidermal nerve endings was located in the nose epidermis.