Oxygen–ozone therapy in the rehabilitation field: state of the art on mechanisms of action, safety and effectiveness in patients with musculoskeletal disorders

In recent years, the interest in oxygen–ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over‐activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state‐of‐the‐art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation

The analog signal processing board for the HEAT telescopes

Abstract The aim of the Pierre Auger Observatory is to measure with high statistics the flux, the arrival directions and the mass composition of cosmic rays at the highest energies. Since 2009, the Auger Collaboration has added three new High Elevation Auger Telescopes (HEAT) along with a new 25 km 2 infill array in the field of view of the new telescopes. These enhancements have lowered the energy threshold of the Observatory by about an order of magnitude. In combination with the existing telescopes in Coihueco the vertical field of view is extended to about 60°, allowing the measurement of nearby air showers arising from primaries with energies as low as 2×10 17 eV. In this paper we describe the new front-end analog board developed to process the signals generated by the photomultipliers of the HEAT telescopes. Eighty analog boards have been produced, fully characterized and tested. The main characteristics of the electronic circuits and the circuit parameters are illustrated

Efficacy of hyaluronate injections in rotator cuff disorders: a level-I meta-analysis

Background: Rotator cuff disease is the most common cause of shoulder pain and weakness. Conservative treatment is the first choice of shoulder pain management. Viscosupplementation of hyaluronic acid (HA) seems to be effective for management of tendon disorders. The objective of this study was to evaluate the scientific evidence reported in literature according to HA shoulder injection in rotator cuff disorders treatment. Methods: An English-language systematic literature search was performed by two independent researchers; data sources included the following databases: MEDLINE, Embase, CINAHL, Google scholar web, Ovid database, Physiotherapy Evidence Database (PEDro), and the Cochrane Library. We performed a broad research for relevant study up to February 2017. Articles were included if they reported data on clinical and functional outcomes in patients who had undergone HA injection for management of rotator cuff pathology compared to placebo, corticosteroid injection and/or physical therapies. Methodological quality was assessed with the PEDro rating scale. The outcomes were improvement of symptoms (assessed by VAS scale) and shoulder function (assessed through DASH and ASES Score). Results: 5 RCTs studies (990 patients) were pooled in the Meta-analysis. The PEDro rating scale ranged from 2 to 8. Two studies compared HA injection with corticosteroid injections, patients were injected once a week for three weeks. Four studies compared HA injection with placebo injection, of which two used 3 weekly injections and two used 5 weekly injections. Significant difference was found in pain reduction between HA and placebo group at 26 weeks follow-up (MD= -0.51, 95% CI -0.96 to -0.07), p=0.02. Conclusion: HA injections might be a valuable safe alternative to other conservative methods for the treatment of rotator cuff disorders. Nowadays, few and low quality randomized controlled trials have been published. Therefore, to reach an overall conclusion about the effect of HA injection in rotator cuff we need more high quality studies. Level of evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Study design: Meta-analys

SPARC (secreted protein acidic and cysteine-rich)

Review on SPARC, with data on DNA, on the protein encoded, and where the gene is implicate

Quantitative titanium imaging in fish tissues exposed to titanium dioxide nanoparticles by laser ablation-inductively coupled plasma-mass spectrometry

Imaging studies by laser ablation–inductively coupled plasma mass spectrometry have been successfully developed to obtain qualitative and quantitative information on the presence/distribution of titanium (ionic titanium and/or titanium dioxide nanoparticles) in sea bream tissues (kidney, liver, and muscle) after exposure assays with 45-nm citrate-coated titanium dioxide nanoparticles. Laboratory-produced gelatine standards containing ionic titanium were used as a calibration strategy for obtaining laser ablation–based images using quantitative (titanium concentrations) data. The best calibration strategy consisted of using gelatine-based titanium standards (from 0.1 to 2.0 μg g−1) by placing 5.0-μL drops of the liquid gelatine standards onto microscope glass sample holders. After air drying at room temperature good homogeneity of the placed drops was obtained, which led to good repeatability of measurements (calibration slope of 4.21 × 104 ± 0.39 × 104, n = 3) and good linearity (coefficient of determination higher than 0.990). Under the optimised conditions, a limit of detection of 0.087 μg g−1 titanium was assessed. This strategy allowed to locate prominent areas of titanium in the tissues as well as to quantify the bioaccumulated titanium and a better understanding of titanium dioxide nanoparticle spatial distribution in sea bream tissuesOpen Access funding provided thanks to the CRUE CSIC agreement with Springer Nature. Authors thank funding from European Union—Interreg POCTEP (ACUINANO, reference 07-12-ACUINANO_1_E); Ministerio de Economía y Competitividad (FOODNANORISK, reference PID2021-125276NB-I00); and Xunta de Galicia (Grupo de Referencia Competitiva, reference ED431C 2022/029)S

Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson’s disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson’s disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson’s disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson’s disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra’s morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson’s disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification

Straighten your back! Self-correction posture and postural balance in 'non rehabilitative instructed' multiple sclerosis patients

BACKGROUD: Patients with MS, regardless of the complexity of the activity or sensory conditions, commonly present a significant postural control deficit compared to healthy subjects. OBJECTIVE: To investigate which postural self-correction strategies are adopted by patients with Multiple Sclerosis versus a group of healthy-subjects and how self-correction can influence the control of postural balance. METHODS: A case-control prospective observational study was conducted. Person with Multiple Sclerosis and a group of healthy volunteers were enrolled. Patients included were instructed with vocal commands, to reach a self-correction posture, and they were compared to healthy subjects. Clinical assessments including Balance, Stabilometry and Postural evaluation of the spine were performed. RESULTS: Sixty patients (30: control-group; 30: treatment-group) were enrolled. In the treatment group, the analysis reported a significant statistical difference between path length and center of pressure speed in self-correction posture with closed-eyes (p=0,049; 0,047) and an improvement in C7 and L3 levels in self-correction posture (p<0,01-C7; p<0,01-L3). There are significant statistical differences about path length between the two groups in all examined conditions (p=0,0001). At sagittal plane evaluation, results show an increase of all measurements in both posture (C7-neutral posture p=0,0001; L3-neutral posture p=0,0001; C7-self-correction posture p=0,0001; L3-self-correction posture p=0,0001). CONCLUSION: Further study should investigate dynamic situations and different Multiple Sclerosis forms to complete balance analysis and to establish a correct rehabilitative program with self-correction exercise as powerful focus

Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers

While pralatrexate (PDX) has been successfully developed for the treatment of T-cell lymphoma, the mechanistic basis for its T-cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired PDX resistance, we generated resistant cells lines over a broad concentration range. PDX-resistant cell lines H9-12 and H9-200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells. Expression analysis of the proteins known to be important determinants of antifolate pharmacology revealed increase expression of dihydrofolate reductase (DHFR) due to gene amplification, and reduced folate carrier1 downregulation, as the putative mechanisms of resistance in H9-12 and H9-200 cells. Cross resistance was only seen with methotrexate but not with romidepsin, azacitidine (AZA), decitabine, gemcitabine, doxorubicin, or bortezomib. Resistance to PDX was reversed by pretreatment with hypomethylating agents in a concentration-dependent fashion. Comparison of gene expression profiles of parental and resistant cell lines confirmed markedly different patterns of gene expression, and identified the dual specificity phosphatase four (DUSP4) as one of the molecular target of PDX activity. Reduced STAT5 phosphorylation following exposure to PDX was observed in the H9 but not in the H9-12 and H9-200 cells. These data suggest that combination with hypomethylating agents could be potent, and that DUSP4 and STAT5 could represent putative biomarkers of PDX activity