Equine hepacivirus (EqHV,
, hepacivirus) is a small, enveloped RNA virus generally causing sub-clinical hepatitis with occasional fatalities. EqHV is reported in equids worldwide, but for Italy data ...are limited. To address this, a survey study was set up to estimate prevalence at a national level and among different production categories (equestrian; competition; work and meat; reproduction) and national macro-regions (North, Central, South, and Islands). Data obtained testing 1801 horse serum samples by Real-Time RT PCR were compared within the categories and regions. The NS3 fragment of the PCR-positive samples was sequenced by Sanger protocol for phylogenetic and mutational analysis. The tertiary structure of the NS3 protein was also assessed. The estimated national prevalence was 4.27% 1.97-6.59, 95% CI and no statistical differences were detected among production categories and macro-regions. The phylogenesis confirmed the distribution in Italy of the three known EqHV subtypes, also suggesting a possible fourth sub-type that, however, requires further confirmation. Mutational profiles that could also affect the NS3 binding affinity to the viral RNA were detected. The present paper demonstrates that EqHV should be included in diagnostic protocols when investigating causes of hepatitis, and in quality control protocols for blood derived products due to its parental transmission.
Ultrasound-induced blood-brain barrier (BBB) opening using microbubbles is a promising technique for local delivery of therapeutic molecules into the brain. The real-time control of the ultrasound ...dose delivered through the skull is necessary as the range of pressure for efficient and safe BBB opening is very narrow. Passive cavitation detection (PCD) is a method proposed to monitor the microbubble activity during ultrasound exposure. However, there is still no consensus on a reliable safety indicator able to predict potential damage in the brain. Current approaches for the control of the beam intensity based on PCD employ a full-pulse analysis and may suffer from a lack of sensitivity and poor reaction time. To overcome these limitations, we propose an intra-pulse analysis to monitor the evolution of the frequency content during ultrasound bursts. We hypothesized that the destabilization of microbubbles exposed to a critical level of ultrasound would result in the instantaneous generation of subharmonic and ultra-harmonic components. This specific signature was exploited to define a new sensitive indicator of the safety of the ultrasound protocol. The approach was validated in vivo in rats and non-human primates using a retrospective analysis. Our results demonstrate that intra-pulse monitoring was able to exhibit a sudden appearance of ultra-harmonics during the ultrasound excitation pulse. The repeated detection of such a signature within the excitation pulse was highly correlated with the occurrence of side effects such as hemorrhage and edema. Keeping the acoustic pressure at levels where no such sign of microbubble destabilization occurred resulted in safe BBB openings, as shown by MR images and gross pathology. This new indicator should be more sensitive than conventional full-pulse analysis and can be used to distinguish between potentially harmful and safe ultrasound conditions in the brain with very short reaction time.
Spinal cord injury (SCI) is a neurological disorder that arises from a primary acute mechanical lesion, followed by a pathophysiological cascade of events that leads to further spinal cord tissue ...damage. Several preclinical and clinical studies have highlighted the ability of stem cell therapy to improve long‐term functional recovery in SCI. Previously, we demonstrated that moringin (MOR) treatment accelerates the differentiation process in mesenchymal stem cells inducing an early up‐regulation of neural development associated genes. In the present study, we investigated the anti‐inflammatory, anti‐apoptotic, and regenerative effects of gingival mesenchymal stem cells (GMSCs) pretreated with nanostructured liposomes enriched with MOR in an animal model of SCI. SCI was produced by extradural compression of the spinal cord at levels T6–T7 in ICR (CD‐1) mice. Animals were randomly assigned to the following groups: Sham, SCI, SCI + GMSCs (1 × 106 cell/i.v.), SCI + MOR‐GMSCs (1 × 106 cell/i.v.). Our data show that MOR‐treated GMSCs exert anti‐inflammatory and anti‐apoptotic activities. In particular, MOR‐treated GMSCs are able to reduce the spinal cord levels of COX‐2, GFAP, and inflammatory cytokines IL‐1β and IL‐6 and to restore spinal cord normal morphology. Also, MOR‐treated GMSCs influenced the apoptotic pathway, by reducing Bax, caspase 3, and caspase 9 expressions.
Este documento pretende ser una reflexión sobre el aporte de la Terapia Ocupacional y la Psicopedagogía en el armado de la autonomía en la infancia, desde una mirada holística del paciente, ...contemplando los contextos familiares en los que se encuentran inmersos y la responsabilidad de los mayores para contener, acompañar y provocar la independencia del niño.
The aim of this report is to be a reflection about the occupational therapy and Psychopedagogy support in the construction of the autonomy in childhood, from a holistic view of the patient, taking into account it familiar context and the adults responsabilities to contain, accompany and promote the child independence.
In the present study, human primary oral squamous carcinoma cells treated with cisplatin and 5-fluorouracil were analyzed, for the first time, by in vitro FTIR Microspectroscopy (FTIRM), to improve ...the knowledge on the biochemical pathways activated by these two chemotherapy drugs. To date, most of the studies regarding FTIRM cellular analysis have been executed on fixed cells from immortalized cell lines. FTIRM analysis performed on primary tumor cells under controlled hydrated conditions provides more reliable information on the biochemical processes occurring in in vivo tumor cells. This spectroscopic analysis allows to get on the same sample and at the same time an overview of the composition and structure of the most remarkable cellular components. In vitro FTIRM analysis of primary oral squamous carcinoma cells evidenced a time-dependent drug-specific cellular response, also including apoptosis triggering. Furthermore, the univariate and multivariate analyses of IR data evidenced meaningful spectroscopic differences ascribable to alterations affecting cellular proteins, lipids and nucleic acids. These findings suggest for the two drugs different pathways and extents of cellular damage, not provided by conventional cell-based assays (MTT assay and image-based cytometry).
Background
Monoallelic variants in the
KIF1A
gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum ...of central and peripheral nervous system involvement.
Methods
In a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in
KIF1A
. We conducted a literature systematic review with the aim to comparing our findings with previously reported
KIF1A
-related phenotypes.
Results
Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing
KIF1A.
Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit.
Conclusions
This study broadened our clinical, genetic, and neuroimaging knowledge of
KIF1A
-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate.
The short-term response of some soil physical, chemical and biological properties, and the growth of beet, to the application of vermicompost–compost mix and/or bone meal at different doses in an ...organic system was evaluated in the present work. Fractions of soil organic matter after amendment application were also evaluated. Though no differences were found in oxidizable carbon, the particulate organic carbon was incremented in treatments with the application of vermicompost–compost mix (VC) and the combination of compost and bone meal (VC–BM). When analyzing the fulvic, humic and humin fractions, the highest fulvic acids were found in vermi-compost and bone meal mix, at the higher dose (VC2–BM2). In general, the addition of compost and/or bone meal stimulated microbial respiration. The treatments produced a slight but significant increase in electrical conductivity, thought it was still far from limits that involve risk of salinization. An increment in extractable P was found in all the treatments with amendment application with the exception of bone meal applied at the lower dose (1
kg
m
−2). The cation exchange capacity showed a significant increment in VC2–BM2. A single application of VC at dose of 2
kg
m
−2 was enough to significantly reduce bulk density. An increment in kg dry matter m
−2 of beet was observed in all the treatments, but it only was significant in VC2–BM2. However, the highest N and P concentration was found in beet aerial tissues from the treatments with the higher dose of the compost–vermicompost mix (VC2 and VC2–BM2). Particulate organic carbon, fulvic acid fraction, C from respiration, and bulk density were the soil properties that showed a positive change after amendment application. Treatment combining vermicompost–compost and bone meal (VC2–BM2) seemed to be the best option to achieve an improvement both in soil and crop production and quality.
Fourier transform infrared imaging (FTIRI) is a powerful tool for analyzing biochemical changes in tumoral tissues. The head and neck region is characterized by a great variety of lesions, with ...different degrees of malignancy, which are often difficult to diagnose. Schneiderian papillomas are sinonasal benign neoplasms arising from the Schneiderian mucosa; they can evolve into malignant tumoral lesions (squamous cell carcinoma). In addition, they can sometimes be confused with the more common inflammatory polyps. Therefore, an early and definitive diagnosis of this pathology is mandatory. Progressing in our research on the study of oral cavity lesions, 15 sections consisting of inflammatory sinonasal polyps, benign Schneiderian papillomas, and sinonasal undifferentiated carcinomas were analyzed using FTIRI. To allow a rigorous description of these pathologies and to gain objective diagnosis, the epithelial layer and the adjacent connective tissue of each section were separately investigated by following a multivariate analysis approach. According to the nature of the lesion, interesting modifications were detected in the average spectra of the different tissue components, above all in the lipid and protein patterns. Specific band-area ratios acting as spectral markers of the different pathologies were also highlighted.
To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity.
The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was ...constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant.
A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease.
The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.
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