(1) Background: The RESILIEN-T system addresses the need for innovative solutions to support self-management in older people with Mild Cognitive Impairment (MCI). Despite the increasing prevalence of ...dementia and MCI, there is a lack of tailored solutions for these individuals. The RESILIEN-T system aims to empower and engage people with cognitive decline by providing a modular platform for self-management and coaching services. (2) Methods: Italian data collected for the RESILIEN-T project involved 62 older participants randomly assigned to the intervention or control group. Data were collected through questionnaires and user interactions with the system over a three-month period. (3) Results: Quantitative outcomes showed no significant differences between the intervention and control groups, except for an improvement in perceived memory capability in the intervention group. The usability assessment indicated a high level of acceptance of the RESILIEN-T system. (4) Discussions: Although no significant improvements were observed in most quantitative measures, the high user engagement and acceptance suggest the potential effectiveness of the RESILIEN-T system. Future improvements could involve integrating smart objects and interactive virtual agents. Overall, RESILIEN-T represents a promising step toward empowering individuals with cognitive impairment in their self-management and decision-making processes.
Reliable and valid assessment tools are needed to evaluate and predict physical function in older hospitalized patients. The aim of this study is to develop the Italian version of the Elderly ...Mobility Scale (I-EMS) and to evaluate its validity and inter-rater reliability for use with geriatric inpatients.
The study consists of two phases: (i) translation, where EMS version 2 was translated into Italian by two teams, each comprising 2 bilingual physiotherapists; translations were back translated by 2 native English speakers, and a committee of 2 physiotherapists and 1 physician refined the initial I-EMS version, which was pilot-tested for clarity in a group of ten experienced geriatric physiotherapists; (ii) an observational study assessed I-EMS metrics (reliability, validity) in older Italian inpatients at IRCCS INRCA (Ancona, Italy) between September 2022 and April 2023.
No statistically significant differences were found between the scores of individual items and the total score assigned by different raters. The ICC for total I-EMS was 0.951, SEM was 1.10 and MDC95 was 3.06. The absolute agreement and weighted kappa for individual items ranged 80.32-100% and 8.2-1, respectively. The validity of I-EMS was supported by a significant (
< 0.05) correlation with the Barthel Index (
= 0.827 and 0.834 for the I-EMS administered by rater A and rater B, respectively).
I-EMS showed good internal consistency and inter-rater reliability, and confirmed construct validity with respect to BI. Therefore, it can safely be used as an assessment tool for hospitalized Italian geriatric patients.
ClinicalTrials.gov, NCT05806242.
(1) Background: Parkinson's disease (PD) is one of the most frequent causes of disability among older people. Recently, virtual reality and exergaming have been emerged as promising tools for gait ...and balance rehabilitation in PD patients. Our purpose is to evaluate an innovative treatment for older patients with PD, based on non-immersive virtual reality exergames, improving gait and balance and reducing falling risk. (2) Methods: Thirty PD patients were recruited and randomly divided into two groups, to receive a traditional rehabilitation (CG) or a technological rehabilitation (TG). (3) Results: A statistical improvement of balance at the end of treatments was observed in both groups (CG: 12.4 ± 0.7 vs. 13.5 ± 0.8,
= 0.017; TG: 13.8 ± 0.5 vs. 14.7 ± 0.4,
= 0.004), while the overall risk of falling was significantly reduced only in the TG (POMA Total: 24.6 ± 0.9 vs. 25.9 ± 0.7,
= 0.010). The results between groups shows that all POMA scores differ in a statistically significant manner in the TG, emphasizing improvement not only in balance but also in gait characteristics (9.7 ± 0.8 vs. 11.4 ± 0.2,
= 0.003). Moreover, TG also improves the psychological sphere, measured thorough MSC-(17.1 ± 0.4 vs. 16.5 ± 0.4,
= 0.034). Although an improvement in FES-I and Gait Speed can be observed, this increase does not turn out to be significant. (4) Conclusions: Results suggest how non-immersive virtual reality exergaming technology offers the opportunity to effectively train cognitive and physical domains at the same time.
Amniotic membrane and amniotic fluid derived cells are regarded as a promising stem cell source for developing regenerative medicine techniques, although they have never been tested on male ...infertility diseases such as varicocele (VAR). The current study aimed to examine the effects of two distinct cell sources, human Amniotic Fluid Mesenchymal Stromal Cells (hAFMSCs) and amniotic epithelial cells (hAECs), on male fertility outcomes in a rat induced VAR model. To explain cell-dependent enhancement of reproductive outcomes in rats transplanted with hAECs and hAFMSCs, insights on testis morphology, endocannabinoid system (ECS) expression and inflammatory tissue response have been carried out alongside cell homing assessment. Both cell types survived 120 days post-transplantation by modulating the ECS main components, promoting proregenerative M2 macrophages (Mφ) recruitment and a favorable anti-inflammatory
expression pattern. Of note, hAECs resulted to be more effective in restoring rat fertility rate by enhancing both structural and immunoresponse mechanisms. Moreover, immunofluorescence analysis revealed that hAECs contributed to CYP11A1 expression after transplantation, whereas hAFMSCs moved towards the expression of Sertoli cell marker, SOX9, confirming a different contribution into the mechanisms leading to testis homeostasis. These findings highlight, for the first time, a distinct role of amniotic membrane and amniotic fluid derived cells in male reproduction, thus proposing innovative targeted stem-based regenerative medicine protocols for remedying high-prevalence male infertility conditions such as VAR.
Adequate management of postoperative pain after major spine surgery is often difficult to achieve. We investigated the efficacy of an antineuropathic pain drug, pregabalin (PG), on postoperative pain ...control and on improvement of quality of life (QoL).
Sixty patients scheduled for elective decompressive spine surgery were enrolled. One hour before surgery patients received 300 mg of either oral PG or placebo (PL) and 150 mg of PG or PL twice a day for 48 hours postoperatively. During the first 48 postoperative hours, a continuous infusion of morphine 0.01 mg/kg/h and ketorolac tromethamine 2.5 mg/h was administered. Intravenous morphine in 2-mg aliquots up to a maximum of 10 mg was used as rescue therapy. Pain was measured at rest and during movement using a visual analog scale (VAS score), and side effects were recorded in the first hour and at 4, 8, 12, 24, and 48 hours. Three months and 1 year after discharge, patients were contacted by telephone by 1 of the authors to obtain follow-up information using the EuroQoL questionnaire.
During the first 8 postoperative hours, VAS scores at rest were significantly lower in the PG group than in the PL group (P<0.05), whereas VAS scores on movement were significantly lower up to 12 hours after the operation in the PG group (P<0.05). The morphine consumption in the PG group was 3±2 mg, whereas in the PL group it was 9.5±2.5 mg (P<0.05). Postoperative incidence of constipation and nausea/vomiting was higher in the PL group than in the PG group. No significant differences between the 2 groups were observed with regard to other adverse effects. QoL measures revealed an improvement in outcome, especially in movement and in pain dimensions in both groups; however, at 3 months, subjective qualification of overall QoL was better in the PG group than in the PL group. There were no differences in QoL after the 1-year follow-up period.
Perioperative PG administration reduces early postsurgical pain at rest and particularly during movement after major spine surgery with less opioid consumption, and it seems to influence the improvement of overall QoL 3 months after surgery.
Abstract
Background
The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms ...responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background.
Methods
Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the “6Rs”, which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology.
Results
RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors.
Conclusions
These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This study aimed to set up a method for the long‐term management of Adriatic sturgeon, through the analysis of sex steroids and the genetic profiling of individuals in order to maximize the already ...reduced genetic variability of this species. Ten A. naccarii adults (nine of captive origin, one captured in the Ticino river and then moved into captivity) and eight subadults located in a semi‐natural land‐locked pond in Abbiategrasso (Milan, Italy) were analysed. Plasma testosterone differed significantly in the eight analysed subadults allowing their differentiation into two groups: the first group with an average testosterone concentration of 5.42 ± 1.31 ng/ml (probably female) and the second group with an average of 423.14 ± 75.97 ng/ml (probably male), as subsequently confirmed by artificial stripping. The plasma testosterone level was also significantly different between adult males and females (371.37 ± 43.58 vs. 95.34 ± 51.10 ng/ml), while the E2 levels showed no significant differences. Animals were genotyped on the basis of 10 microsatellite loci and their parental relationships were defined: four adults, two females and two males, generated the eight subadults. On the basis of pedigree analyses and genetic distances, 15 unrelated couples were identified for the future breeding seasons. Finally, the adult female captured in the Ticino River showed an interesting genetic profile, widely different from all of the other 17 specimens analysed, and represents a valuable source of genetic diversity.
•The mtDNA pathogenic variant m.3890G>A/MT-ND1 is now found in eight maternal lineages with independent mutational events.•This pathogenic variant is associated with a clinical spectrum that may ...range from “pure” LHON to Leigh-like syndrome.•The most severe and complex phenotypes are associated with very high heteroplasmy, or nearly homoplasmic m.3890G>A/MT-ND1 pathogenic variant.•Peculiar brain MRI lesions, within the spectrum of Leigh syndrome, are presented.
Isolated complex I deficiency causes several clinical syndromes, including Leigh syndrome (LS), Leber hereditary optic neuropathy (LHON) and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Here we reported two new patients carrying the rare m.3890G>A/MT-ND1 (p.Arg195Gln) mitochondrial DNA (mtDNA) pathogenic variant, revisited another two previously reported cases, and reviewed the remaining published cases, to refine the clinical and neuroimaging features. We also quantitatively assessed the mtDNA heteroplasmy in all available tissues.
The first patient was a 25-year-old male presenting with axonal polyneuropathy, optic atrophy consistent with LHON, gaze palsy and parkinsonism. MRI correlates included transient centromedullary T2 hyperintensity in the conus medullaris, transient signal intensity and increased lactate in the midbrain periaqueductal gray matter, and late atrophy of the optic nerves and chiasm, dorsal midbrain and conus medullaris.
The second patient was a 65-year-old woman with a classical LHON phenotype and a normal MRI.
Including the previously published cases, the clinical spectrum ranged from LHON to Leigh-like syndrome with peculiar CNS lesions and encephalopatic clinical symptoms. The most severe and complex cases were associated with very high heteroplasmy, or nearly homoplasmic m.3890G>A/MT-ND1 pathogenic variant in skeletal muscle, displaying neurological symptoms/signs consistent with Leigh-like lesions on brain MRI. Lower heteroplasmic mutational loads were instead associated with isolated LHON-like optic neuropathy of variable severity.
The m.3890G>A/MT-ND1 mtDNA pathogenic variant increasingly impairs complex I function dependent on heteroplasmic loads, leading to a spectrum of LHON and Leigh-like encephalopathy with distinguishing MRI features.
The relationship between varicocele and fertility has always been a matter of debate because of the absence of predictive clinical indicators or molecular markers able to define the severity of this ...disease. Even though accumulated evidence demonstrated that the endocannabinoid system (ECS) plays a central role in male reproductive biology, particularly in the testicular compartment, to date no data point to a role for ECS in the etiopathogenesis of varicocele. Therefore, the present research has been designed to investigate the relationship between testicular ECS gene expression and fertility, using a validated animal model of experimental varicocele (VAR), taking advantage of traditional statistical approaches and artificial neural network (ANN). Experimental induction of VAR led to a clear reduction of spermatogenesis in left testes ranging from a mild (Johnsen score 7: 21%) to a severe (Johnsen score 4: 58%) damage of the germinal epithelium. However, the mean number of new-borns recorded after two sequential matings was quite variable and independent of the Johnsen score. While the gene expression of biosynthetic and degrading enzymes of AEA (NAPE-PLD and FAAH, respectively) and of 2-AG (DAGLα and MAGL, respectively), as well as their binding cannabinoid receptors (CB1 and CB2), did not change between testes and among groups, a significant downregulation of vanilloid (TRPV1) expression was recorded in left testes of VAR rats and positively correlated with animal fertility. Interestingly, an ANN trained by inserting the left and right testicular ECS gene expression profiles (inputs) was able to predict varicocele impact on male fertility in terms of mean number of new-borns delivered (outputs), with a very high accuracy (average prediction error of 1%). The present study provides unprecedented information on testicular ECS gene expression patterns during varicocele, by developing a freely available predictive ANN model that may open new perspectives in the diagnosis of varicocele-associated infertility.
PDF
