1H-NMR metabolomic profile of healthy and osteoarthritic canine synovial fluid before and after UC-II supplementation

The aim of the study was to compare the metabolomic synovial fluid (SF) profile of dogs affected by spontaneous osteoarthritis (OA) and supplemented with undenatured type II collagen (UC-II), with that of healthy control dogs. Client-owned dogs were enrolled in the study and randomized in two different groups, based on the presence/absence of OA (OA group and OA-free group). All dogs were clinically evaluated and underwent SF sampling for 1H-Nuclear Magnetic Resonance spectroscopy (1H-NMR) analysis at time of presentation. All dogs included in OA group were supplemented with UC-II orally administered for 30 days. After this period, they were reassessed (OA-T30). The differences in the 1H-NMR metabolic SFs profiles between groups (OA-free, OA-T0 and OA-T30) were studied. The multivariate statistical analysis performed on SFs under different conditions (OA-T0 vs OA-T30 SFs; OA-T0 vs OA-free SFs and OA-T30 vs OA-free SFs) gave models with excellent goodness of fit and predictive parameters, revealed by a marked separation between groups. β-Hydroxybutyrate was identified as a characteristic compound of osteoarthritic joints, showing the important role of fat metabolism during OA. The absence of β-hydroxybutyrate after UC-II supplementation suggests the supplement’s effectiveness in rebalancing the metabolism inside the joint. The unexpectedly high level of lactate in the OA-free group suggests that lactate could not be considered a good marker for OA. These results prove that 1H-NMR-based metabolomic analysis is a valid tool to study and monitor OA and that UC-II improves clinical symptoms and the SF metabolic profile in OA dog

Factors Affecting the Quality of Bacterial Genomes Assemblies by Canu after Nanopore Sequencing

Long-read sequencing (LRS), like Oxford Nanopore Technologies, is usually associated with higher error rates compared to previous generations. Factors affecting the assembly quality are the integrity of DNA, the flowcell efficiency, and, not least all, the raw data processing. Among LRS-intended de novo assemblers, Canu is highly flexible, with its dozens of adjustable parameters. Different Canu parameters were compared for assembling reads of Salmonellaenterica ser. Bovismorbificans (genome size of 4.8 Mbp) from three runs on MinION (N50 651, 805, and 5573). Two of them, with low quality and highly fragmented DNA, were not usable alone for assembly, while they were successfully assembled when combining the reads from all experiments. The best results were obtained by modifying Canu parameters related to the error correction, such as corErrorRate (exclusion of overlaps above a set error rate, set up at 0.40), corMhapSensitivity (the coarse sensitivity level, set to “high”), corMinCoverage (set to 0 to correct all reads, regardless the overlaps length), and corOutCoverage (corrects the longest reads up to the imposed coverage, set to 100). This setting produced two contigs corresponding to the complete sequences of the chromosome and a plasmid. The overall results highlight the importance of a tailored bioinformatic analysis

The use of silicon-germanium superlattices for thermoelectric devices and microfabricated generators

Low dimensional structures such as superlattices have the potential to improve the thermoelectric properties of materials by engineering the scattering of phonons to reduce the thermal conductivity and therefore improve the thermeoelectric performance. Here we demonstrate the reduction in thermal conductivity in Ge/SiGe superlattices using multiple barrier engineering to scatter acoustic phonons at the key wavelengths for thermal transport. The approach allows ZT to be increased in wide quantum well superlattices through the reduction of heterointerfaces which scatter both electrons and phonons

Physiological effects of lung protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

Background- Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. Methods- Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero=ZEEP, 4-8 cmH2O=PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure-PL,EE=PEEPTITRATED) were used for measurements. Results- Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [-7.6 – -2.3] cmH2O and lung elastance (EL) 44 [40 – 51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p=0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3 – 1.5] cmH2O and EL to 49 [43 – 59] (p=0.004 and p<0.001 compared to ZEEP and PEEPLOW, respectively). PL decreased at PEEPLOW (p=0.018) and increased at PEEPTITRATED (p=0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and PL. Conclusions- In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics

Molecular mechanisms and physiological changes behind benign tracheal and subglottic stenosis in adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different etiology. Although iatrogenic etiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent etiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS

Synthesis, computational and experimental pharmacological studies for (thio)ether-triazine 5-HT6R ligands with noticeable action on AChE/BChE and chalcogen-dependent intrinsic activity in search for new class of drugs against Alzheimer's disease

Alzheimer's disease is becoming a growing problem increasing at a tremendous rate. Serotonin 5-HT6 receptors appear to be a particularly attractive target from a therapeutic perspective, due to their involvement not only in cognitive processes, but also in depression and psychosis. In this work, we present the synthesis and broad biological characterization of a new series of 18 compounds with a unique 1,3,5-triazine backbone, as potent 5-HT6 receptor ligands. The main aim of this research is to compare the biological activity of the newly synthesized sulfur derivatives with their oxygen analogues and their N-demethylated O- and S-metabolites obtained for the first time. Most of the new triazines displayed high affinity (Ki < 200 nM) and selectivity towards 5-HT6R, with respect to 5-HT2AR, 5-HT7R, and D2R, in the radioligand binding assays. For selected, active compounds crystallographic studies, functional bioassays, and ADME-Tox profile in vitro were performed. The exciting novelty is that the sulfur derivatives exhibit an agonistic mode of action contrary to all other compounds obtained to date in this chemical class herein and previously reported. Advanced computational studies indicated that this intriguing functional shift might be caused by presence of chalcogen bonds formed only by the sulfur atom. In addition, the N-demethylated derivatives have emerged highly potent antioxidants and, moreover, show a significant improvement in metabolic stability compared to the parent structures. The cholinesterase study present micromolar inhibitory AChE and BChE activity for both 5-HT6 agonist 19 and potent antagonist 5. Finally, the behavioral experiments of compound 19 demonstrated its antidepressant-like properties and slight ability to improve cognitive deficits, without inducing memory impairments by itself. Described pharmacological properties of both compounds (5 and 19) allow to give a design clue for the development of multitarget compounds with 5-HT6 (both agonist and antagonist)/AChE and/or BChE mechanism in the group of 1,3,5-triazine derivatives

Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal

People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds

Understanding the rich physics of light propagation in slow photonic crystal waveguides

Selected papers. Held as part of SPIE Photonics West 2010.We study propagation losses in slow light photonic crystal waveguides and show that dispersion engineering can reduce the loss. We develop an improved understanding of why and how this occurs and develop an new approach to modeling these devices that provides new design insights.Postprin

Evaluation of clinical efficacy of undenatured type II collagen supplementation compared to cimicoxib and their association in dogs affected by natural occurring osteoarthritis

The aim of the study was to evaluate the clinical efficacy of 30 days treatment of undenatured type II collagen (UC-II (R)), compared to cimicoxib and to their combination, in osteoarthritic dogs. Client-owned dogs were enrolled in a clinical, randomized, controlled and prospective study. Posture, lameness, pain, range of motion and x-ray of affected joint(s) were evaluated and scored based on severity (CLINICAL score). The Liverpool Osteoarthritis in Dogs survey was used to score the owner evaluation of dog's mobility (LOAD score and MOBILITY score). Osteoarthritis (OA) stage was defined through the Canine Osteoarthritis Staging tool (COAST). After diagnosis (T0), all patients were randomly assigned to different treatment groups: C group = cimicoxib 2 mg/kg/day orally OS, F group = UC-II (R) 1 tablet per day OS; C + F group = cimicoxib-UC-II (R) at the same previous dosages; CTR group = dogs who didn't received any treatment. All treatments were administered for 30 days. Seventy-six dogs completed the study. LOAD score was recorded significant lower after treatment for each group, with a reduction in percentage of 29.5% for C, 31.4% for F, 21.1% for C + F. LOAD score was lower in C(P = 0.04), F(P = 0.001) and C + F(P = 0.009) group at T30 than CTR group. MOBILITY and CLINICAL scores were significantly lower in all groups at T30, when compared to T0. MOBILITY score was lower than CTR in C(P = 0.02) and F(P = 0.01); CLINICAL score was lower in C + F(P = 0.016). The present findings prove that the treatment with UC-II (R), cimicoxib and their combination provide significant reduction in clinical signs associated with OA