Parallelizable Microfluidic Resistive On-Line Detector of Micrometric Aggregates of Biopharmaceutical Antibodies

A microfluidic device based on the differential measurement of the ionic resistance of a micropore for detection of aggregates of antibodies in biopharmaceutical downstream process is presented. The main novelty of this contribution regards the experimental demonstration that, despite the poor solidness of proteins, their aggregates, in their standard production buffer, can be electrically detected down to 2.4 μm diameter with sub-ms transit time (flow rate of 5 μl/min). Thanks to the simple PDMS fluidic fabrication, compact DC readout circuit and convenient use of the same metallic silver tubing for both electrical and fluidic interconnection, the device can be straightforwardly parallelized in tens of units, thus combining single micrometric sensitivity with larger flow rates (>100 μl/min), suitable for in-line installation in pharmaceutical plants

Lipoprotein(a) Lowering-From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

It is well-known that elevated lipoprotein(a)-Lp(a)-levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)Lrx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents

Proteomics Profiling of Heterozygous and Homozygous Patients with ABCA1 Gene Mutation: A Tangier Disease Molecular Map

Tangier Disease (TD) is a rare inherited disorder with approximately 100 worldwide identified cases. Alpha-lipoprotein deficiency is the main characteristic of this disease, associated with a virtual absence of High Density Lipoproteins (HDL) in blood. Additional symptoms are mild hypertriglyceridemia, neuropathy and enlarged, orange-colored tonsils. Genetically TD is caused by mutations in the ABCA1 gene, which prevent the release of cholesterol and phospholipids from cells, leading to the accumulation of lipids within cells and body tissues. In this work a TD patient and his parental heterozygous were examined from a proteomics point of view. Plasma as well as proteome and secretome of circulating monocytes were analyzed. Plasma proteins underlined in TD the imbalance of lipid trafficking and metabolism, associated with the stimulation of pro-inflammatory pathways. Proteome and secretome of monocytes highlighted an extensive down regulation of mitochondrial enzymes and vesicular trafficking agents along with a substantial cytoskeletal rearrangement, suggesting a reduced activation state of monocytes from TD homozygous patient. This work is the first proteomics profiling of heterozygous and homozygous TD phenotypes and it suggests a TD case as a model to understand general mechanisms of lipid transport and metabolism and their linkage to inflammatory processes

Resectable IIIA-N2 non-small-cell lung cancer (NSCLC): In search for the proper treatment

Locally advanced non-small cell lung cancer accounts for one third of non-small cell lung cancer (NSCLC) at the time of initial diagnosis and presents with a wide range of clinical and pathological heterogeneity. To date, the combined multimodality approach involving both local and systemic control is the gold standard for these patients, since occult distant micrometastatic disease should always be suspected. With the rapid increase in treatment options, the need for an interdisciplinary discussion involving oncologists, surgeons, radiation oncologists and radiologists has become essential. Surgery should be recommended to patients with non-bulky, discrete, or single-level N2 involvement and be included in the multimodality treatment. Resectable stage IIIA patients have been the subject of a number of clinical trials and retrospective analysis, discussing the efficiency and survival benefits on patients treated with the available therapeutic approaches. However, most of them have some limitations due to their retrospective nature, lack of exact pretreatment staging, and the involvement of heterogeneous populations leading to the awareness that each patient should undergo a tailored therapy in light of the nature of his tumor, its extension and his performance status

Demodicosis felina por Demodex Gatoi

Demodex gatoi es responsable de una dermatosis felina rara que, hasta hace escasos años, solo se diagnosticaba en EEUU, pero que desde 2001 está emergiendo en Europa, habiéndose comunicado casos esporádicos (1). En esta presentación se describe el primer caso en España

Temperature and wavelength drift tolerant WDM transmission and routing in on-chip silicon photonic interconnects

We demonstrate a temperature and wavelength shift resilient silicon transmission and routing interconnect system suitable for multi-socket interconnects, utilizing a dual-strategy CLIPP feedback circuitry that safeguards the operating point of the constituent photonic building blocks along the entire on-chip transmission-multiplexing-routing chain. The control circuit leverages a novel control power-independent and calibration-free locking strategy that exploits the 2nd derivative of ring resonator modulators (RMs) transfer function to lock them close to the point of minimum transmission penalty. The system performance was evaluated on an integrated Silicon Photonics 2-socket demonstrator, enforcing control over a chain of RM-MUX-AWGR resonant structures and stressed against thermal and wavelength shift perturbations. The thermal and wavelength stress tests ranged from 27 degrees C to 36 degrees C and 1309.90 nm to 1310.85 nm and revealed average eye diagrams Q-factor values of 5.8 and 5.9 respectively, validating the system robustness to unstable environments and fabrication variations. (C) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreemen

Low-mass e+e- pair production in 158 A GeV Pb-Au collisions at the CERN SPS, its dependence on multiplicity and transverse momentum

We report a measurement of low-mass electron pairs observed in 158 GeV/nucleon Pb-Au collisions. The pair yield integrated over the range of invariant masses 0.2 < m < 2.0 GeV is enhanced by a factor of 3.5 +/- 0.4 (stat) +/- 0.9 (syst) over the expectation from neutral meson decays. As observed previously in S-Au collisions, the enhancement is most pronounced in the invariant-mass region 300-700 MeV. For Pb-Au we find evidence for a strong increase of the enhancement with centrality. In addition, we show that the enhancement covers a wide range in transverse momentum, but is largest at the lowest observed pt.Comment: 17 pages, 4 figures, submitted to Phys.Lett.

Consensus document on Lipoprotein(a) from the Italian Society for the Study of Atherosclerosis (SISA)

Aims: In view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided. Data synthesis: Lp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment. Conclusions: Awaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended

Otitis externa por Demodex cati

La demodicosis por Demodex cati es una enfermedad parasitaria poco común que se presenta bajo tres formas clínicas: generalizada, localizada y otitis externa ceruminosa u otodemodicosis. El objetivo de esta comunicación es presentar dos casos clínicos de otitis ceruminosa causada por D.cati sin la presencia de otros síntomas cutáneos

e+e--pair production in Pb-Au collisions at 158 GeV per nucleon

We present the combined results on electron-pair production in 158 GeV/n {Pb-Au} ($\sqrt{s}$= 17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996, and give a detailed account of the data analysis. The enhancement over the reference of neutral meson decays amounts to a factor of 2.31$\pm0.19 (stat.)\pm0.55 (syst.)\pm0.69 (decays)$ for semi-central collisions (28% $\sigma/\sigma_{geo}$) when yields are integrated over $m>$ 200 MeV/$c^2$ in invariant mass. The measured yield, its stronger-than-linear scaling with $N_{ch}$, and the dominance of low pair $p_t$ strongly suggest an interpretation as {\it thermal radiation} from pion annihilation in the hadronic fireball. The shape of the excess centring at $m\approx$ 500 MeV/$c^2$, however, cannot be described without strong medium modifications of the $\rho$ meson. The results are put into perspective by comparison to predictions from Brown-Rho scaling governed by chiral symmetry restoration, and from the spectral-function many-body treatment in which the approach to the phase boundary is less explicit.Comment: 39 pages, 40 figures, to appear in Eur.Phys.J.C. (2005