Impact of Disease-Modifying Therapies on Gut–Brain Axis in Multiple Sclerosis

Multiple sclerosis is a chronic, autoimmune-mediated, demyelinating disease whose pathogenesis remains to be defined. In past years, in consideration of a constantly growing number of patients diagnosed with multiple sclerosis, the impacts of different environmental factors in the pathogenesis of the disease have been largely studied. Alterations in gut microbiome composition and intestinal barrier permeability have been suggested to play an essential role in the regulation of autoimmunity. Thus, increased efforts are being conducted to demonstrate the complex interplay between gut homeostasis and disease pathogenesis. Numerous results confirm that disease-modifying therapies (DMTs) used for the treatment of MS, in addition to their immunomodulatory effect, could exert an impact on the intestinal microbiota, contributing to the modulation of the immune response itself. However, to date, the direct influence of these treatments on the microbiota is still unclear. This review intends to underline the impact of DMTs on the complex system of the microbiota–gut–brain axis in patients with multiple sclerosis

CaregiverMatcher: Graph neural networks for connecting caregivers of rare disease patients

Rare diseases affect a growing number of individuals. One key problem for patients and their caregivers is the difficulty in reaching experts and associations competent on a particular disease. As a consequence, caregivers, often family members of the patient, learn much about the disease from their own experience. CaregiverMatcher is a proof of concept providing a smart solution to build a network of caregivers, linked by a matching mechanism based on graph neural networks. The caregivers and their experience with rare diseases are described by node features. Associations and care centers are invited to share their knowledge on the platform

Evaluation of basal ganglia haemodynamic changes with perfusion-weighted magnetic resonance imaging in patients with Parkinson's disease

The aim of our study was to assess the regional cerebral blood flow (rCBF) of basal ganglia and thalami in patients with Parkinson’s disease (PD) using perfusion–weighted magnetic resonance imaging (PW–MRI)

Differences in client and therapist views of the working alliance in drug treatment

Background - There is growing evidence that the therapeutic alliance is one of the most consistent predictors of retention and outcomes in drug treatment. Recent psychotherapy research has indicated that there is a lack of agreement between client, therapist and observer ratings of the therapeutic alliance; however, the clinical implications of this lack of consensus have not been explored. Aims - The aims of the study are to (1) explore the extent to which, in drug treatment, clients and counsellors agree in their perceptions of their alliance, and (2) investigate whether the degree of disagreement between clients and counsellors is related to retention in treatment. Methods - The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Client and counsellor ratings of the therapeutic alliance (using the WAI-S) were obtained during weeks 1-12. Retention was in this study defined as remaining in treatment for at least 12 weeks. Results - Client and counsellor ratings of the alliance were only weakly related (correlations ranging from r = 0.07 to 0.42) and tended to become more dissimilar over the first 12 weeks in treatment. However, whether or not clients and counsellors agreed on the quality of their relationship did not influence whether clients were retained in treatment. Conclusions - The low consensus between client and counsellor views of the alliance found in this and other studies highlights the need for drug counsellors to attend closely to their clients' perceptions of the alliance and to seek regular feedback from clients regarding their feelings about their therapeutic relationship

Decrease in n-acetylaspartate following concussion may be coupled to decrease in creatine

Objectives: To assess the time course changes in brain N-acetylaspartate (NAA) and creatine (Cr) in athletes who suffered a sport-related concussion. Participants: Eleven non-consecutive concussed athletes and 11 sex and age-matched control volunteers. Main outcome measures: At 3, 15, 30 and 45 days post-injury, athletes were examined by proton Magnetic Resonance Spectroscopy (1H-MRS) for the determination of NAA,(Cr) and choline (Cho). 1H-MRS data recorded in the control group were used for comparison. Results: Compared to controls (2.18 ± 0.19), athletes showed an NAA/Cr increase at 3 (2.71 ± 0.16; p < 0.01) and 15 days (2.54 ± 0.21; p < 0.01), followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, p < 0.05) and 45 days(2.17 ± 0.20; p <0.05) post-concussion. NAA/Cho decreased at 3, 15 and 30 days post-injury (p < 0.01 compared to controls), with no differences from controls at 45 days post-concussion. Significant increase in the Cho/Cr after 3 (+33%, p < 0.01) and 15 (+31.5%, p < 0.01) days post-injury was observed, whilst no differences compared to controls were recorded at 30 and 45 days post-impact. Conclusions: This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr. This occurrence provokes longer time of metabolism normalization, as well as longer resolution time of concussion-associated clinical symptoms

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are “disabling” or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0–5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0–1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS

Differences between Proximal versus Distal Intraorbital Optic Nerve Diffusion Tensor Magnetic Resonance Imaging Properties in Glaucoma Patients

Purpose. To analyze in vivo the diffusion tensor magnetic resonance imaging (DT-MRI) properties of the intraorbital optic nerve at two different levels: Proximal to the optic nerve head (ONH) and distal to the ONH at the level of the orbital apex in glaucoma patients. Methods. Twenty-four patients with primary open-angle glaucoma were examined. The categorization into early and severe glaucoma was performed by Hodapp's classification. Fifteen healthy individuals served as controls. DT-MRI was performed with a 3T-MR unit. Results. At early stage mean diffusivity (MD) values were higher at the proximal site with respect to the distal site. On the contrary, a decrease in fractional anisotropy (FA) was observed only relative to patient stage, independent of optic nerve site. Moreover, at early disease stage an increase in overall diffusivities, was evident at the proximal site, whereas at the distal site a decrease of the largest diffusivity and an increase in both the intermediate and smallest diffusivities were observed. FA and MD measured at the proximal site, had, respectively, the highest sensitivity and specificity in discriminating between healthy and glaucomatous eyes. Conclusions. Our study represents the first attempt to evaluate in vivo fiber integrity changes along the optic nerve with DT-MRI. Optic nerve degeneration appears to be a process that affects differently the proximal and the distal segments of the optic nerve. The complementary high sensitivity of FA with the high specificity of MD at the proximal site may provide reliable indexes for the identification of glaucomatous patients at early stages

Winnowing DNA for Rare Sequences: Highly Specific Sequence and Methylation Based Enrichment

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue

Ozone tertiary treatment for pharmaceuticals and personal care products removal from municipal wastewater

An ozone pilot plant was installed at a conventional WWTP to evaluate the removal rate of emerging contaminants, drugs, and fragrances, as tertiary treatment. The filtered secondary effluent flow rate ranged between 1.3÷1.9 m3/h with a retention time of 10÷30 minutes and the plant operated with an ozone dose of 2- 4 mgO3/l. The results evidenced a high removal rate of 80-100% for most of the organic targeted compounds: Amisulpride, Azithromycin, Carbamazepine, Diclofenac, Clarithromycin and Ofloxacin. Lower removal rates from 20% to 80%, were observed for some substances e.g. Gabapentin Lactam, Galaxolidone, Irbesartan, Lamotrigine, and Tonalide. Advanced Oxidation Process (AOP) treatment with O3/H2O2, (0.5–1.0–2 molH2O2/molO3) allowed improved results for almost all these latter. In addition, ozone determined up to 42% removal of the absorbance at 254 nm and 20% of COD, wastewater disinfection, a decrease of the GC-MS chromatographic area, and no acute toxicity effect nor estrogenic and mutagen effects have been detected