Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

Neurological Sciences - Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient...     

Estimation of optical properties of neuroendocrine pancreas tumor with double-integrating-sphere system and inverse Monte Carlo model

The investigation of laser-tissue interaction is crucial for diagnostics and therapeutics. In particular, the estimation of tissue optical properties allows developing predictive models for defining organ-specific treatment planning tool. With regard to laser ablation (LA), optical properties are among the main responsible for the therapy efficacy, as they globally affect the heating process of the tissue, due to its capability to absorb and scatter laser energy. The recent introduction of LA for pancreatic tumor treatment in clinical studies has fostered the need to assess the laser-pancreas interaction and hence to find its optical properties in the wavelength of interest. This work aims at estimating optical properties (i.e., absorption, μ _a , scattering, μ _s , anisotropy, g, coefficients) of neuroendocrine pancreas tumor at 1064 nm. Experiments were performed using two popular sample storage methods; the optical properties of frozen and paraffin-embedded neuroendocrine tumor of the pancreas are estimated by employing a double-integrating-sphere system and inverse Monte Carlo algorithm. Results show that paraffin-embedded tissue is characterized by absorption and scattering coefficients significantly higher than frozen samples (μ _a of 56 cm^?1 vs 0.9 cm^?1, μ _s of 539 cm^?1 vs 130 cm^?1, respectively). Simulations show that such different optical features strongly influence the pancreas temperature distribution during LA. This result may affect the prediction of therapeutic outcome. Therefore, the choice of the appropriate preparation technique of samples for optical property estimation is crucial for the performances of the mathematical models which predict LA thermal outcome on the tissue and lead the selection of optimal LA settings.     

Ischaemia-induced sympathoexcitation in spinalyzed rats

Systemic ischaemia increases sympathetic activity via both reflex and direct effects on the nervous system, which include the hypothalamus and brainstem structures that provide excitatory drive to sympathetic pre-ganglionic motoneurones. Using an arterially perfused working heart-brainstem preparation (WHBP), we evaluated the sympathoexcitatory response recorded from the thoracic sympathetic chain (tSC) in response to systemic ischaemia (produced by arresting perfusion for 30 s) before and after transecting consecutively at both the ponto-medullary and medullary-spinal cord junctions. Ischaemia produced a striking increase in tSC activity that persisted after transecting at both the ponto-medullary and medullary-spinal cord levels (intact: 70+/-3%; ponto-medullary: 77+/-7%; medullary-spinal cord: 61+/-6%; n=9). In sino-aortic denervated (SAD) rats (n=4), sympathoexcitatory responses were smaller in both intact and ponto-medullary, but not in medullary-spinal cord transected versus intact rats. Following administration of a ganglionic blocker [hexamethonium (hex), 25 mg/kg] after medullary-spinal cord transection the ischaemia-induced sympathoexcitatory response was reduced (12+/-6% increase relative to control, n=4). In medullary-spinal cord transected preparations, intrathecal injection of N2-saturated saline increased tSC discharge (22+/-3%, n=4), which was attenuated by hex (5+/-1%). We propose that neural mechanisms within the cervical-thoracic segments can make a substantial contribution to the sympathoexcitatory response during systemic ischaemia.     

In vitro and in vivo behaviour of biodegradable and injectable PLA/PGA copolymers related to different matrices

This study comparatively investigates the in vitro and in vivo behavior of injectable polymeric materials for the treatment of bone defects. The tested materials were three injectable and biodegradable PLA/PGA 50/50 copolymers dispersed in different matrices: Fisograft-gel (GEL) was dispersed in an aqueous matrix of poly-ethyl-glycole (PEG); Slurry2 (SL2) was dispersed in an aqueous matrix of PEG and dextran; and Slurry6 (SL6) was dispersed in a 3% agarose matrix. The biological characterization of these materials was studied by in vitro and in vivo tests: the in vitro test assessed the cellular response in terms of viability, differentiation and synthetic activity, while the in vivo test evaluated the healing capacity of bone defects treated with these biomaterials. GEL and SL2 induced a similar response for viability and differentiation of MG63 osteoblast-like cells after a 7-day culture, while SL6 caused a higher production of both interleukin-6 and type I collagen. Since the results showed that the materials were biocompatible and not cytotoxic in vitro, the in vivo study was carried out: materials were implanted, under general anesthesia, in critical size defects of rabbit femoral condyles; after 4 and 12 weeks, the healing rates and the quality of the regenerated bone were histomorphometrically calculated. The SL2-treated defects healed better at 12 weeks with a more similar microarchitecture of the newly formed bone to normal bone in comparison with other materials, as demonstrated by bone volume fraction and trabecular thickness values.     

Anti-hyperalgesic effects of two sphingosine derivatives in different acute and chronic models of hyperalgesia in mice

Background

The study evaluated the effects of two sphingosine derivatives N-(2-tert-butoxycarbamylhexadecyl)glutaramide (AA) and N-(1-benzyloxyhexadec-2-yl)glutaramide (OA) in different models of hypersensitivity in mice.

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N_females = 130; N_males = 81) and 567 age-matched controls (N_females = 317; N_males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020     

Semen analysis of Golden Retriever healthy dogs and those affected by muscular dystrophy

This study aimed to characterise canine flow cytometry semen analysis, as well as seminal reactive oxygen species dosage using the Golden Retriever breed as model of study. Moreover, we searched for the influence of muscular dystrophy in Golden Retriever dogs on semen parameters. Thirty‐seven semen samples were obtained from healthy Golden Retrievers (n = 15) and from muscular dystrophy affected dogs (n = 22). Sperm‐rich fractions were analysed by standardised breeding soundness examination in addition to the assay of fluorescence assisted cell sorting for acrosome integrity, mitochondrial activity and DNA fragmentation. Volume of ejaculate, per cent of motile spermatozoa and vigour were similar between groups; there were no differences in the per cent of minor and major defects. Integrity of acrosomal membrane, mitochondrial potential and sperm DNA fragmentation had no significant differences between groups either. Animals from control group had higher concentration of spontaneous seminal oxidative species in comparison with affected animals. Dogs affected by dystrophy had seminal parameters similar to those observed in healthy dogs except for the lower concentration of oxidative species. Future studies aiming to establish reference values for canine seminal parameters should be considered preferably with distinction of breeds.