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The discovery of new bioactivities is closely related to the generation of novel scaffolds, and in the past few years different strategies have been proposed to obtain unknown architectures from the manipulation of known compounds. In the present study, we exploited a vintage photochemical approach for the discovery of an unexpected pathway of reactivity related to Δ1-3-oxo-pentacyclic triterpenic acids gaining access to a new class of natural-unnatural 5(10â1)abeo-pentacyclic triterpenic acids.
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Triterpenos , Triterpenos Pentacíclicos/farmacología , Triterpenos/farmacología , Triterpenos/análisis , Cromatografía Líquida de Alta PresiónRESUMEN
Background and Objectives: In patients with multiple sclerosis (MS), a decrease in muscle strength can lead to limitations in pulmonary functions, potentially causing respiratory complications. To address these challenges, the lung volume recruitment (LVR) maneuver has emerged as a potential intervention. This study sought to evaluate the impact of a four-week LVR protocol on respiratory function in secondary progressive MS patients. Materials and Methods: In a quasi-randomized pre/post-controlled trial, 24 patients with secondary progressive MS were recruited. Participants aged 20-70 years with an EDSS score of 2 to 9 were alternately allocated to intervention (n = 12) or control groups (n = 12). The intervention group underwent a 4-week respiratory rehabilitation training focused on LVR, using a standardized cough machine treatment protocol twice daily. The control group received no respiratory intervention. Outcomes measured included forced vital capacity (FVC), maximal insufflation capacity (MIC), and peak cough flow (PCF), using turbine spirometry and other associated equipment. All measurements were taken at baseline (T0) and after 4 weeks (T1) by a blinded assessor. Results: For the intervention group, the mean difference pre/post-treatment in MIC (mL) was 0.45 (SD 1.13) (p = 0.02), and in MIC (%), it was 0.13 (SD 0.24) (p = 0.03). Compared to the control group (n = 10), the between-group mean difference for MIC (mL) was 0.54 (p = 0.02), and for MIC (%), it was 0.15 (p = 0.02). Conclusions: The short-term daily LVR protocol notably improved passive lung capacity, despite minimal changes in active lung capacity or cough force. The LVR maneuver offers promise for enhancing respiratory function, especially passive lung capacity, in secondary progressive MS patients. Further research should explore optimal treatment durations and frequencies for more extensive respiratory gains.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Humanos , Proyectos Piloto , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Tos , Mediciones del Volumen Pulmonar , Pulmón , Esclerosis Múltiple Crónica Progresiva/complicacionesRESUMEN
Targeted delivery of drugs into specific cancer cells is an effective way to enhance the efficacy and minimize the side effects of therapy. Prostate malignant cells overexpress the prostate-specific membrane antigen (PSMA), a membrane protein that may be a valid target for selective drug administration. To target prostate cancer cells, a ß-cyclodextrin perfunctionalised with dipeptide-like urea arms, a well-established mimic of a selective ligand against PSMA, is herein reported, to develop a multivalent drug delivery and targeting system. Firstly, fluorescein was used to validate the system on cells that express high levels of PSMA (prostate tumoral cells, LNCap) or very low levels of PSMA (non-tumoral cells, Hek293T). Then, the antineoplastic agent doxorubicin complexed with ß-cyclodextrin functionalized with PSMA-like ligand takes less time to induce cytotoxicity on LNCap cells compared to doxorubicin alone. This might represent a promising drug-delivery approach to selectively target prostate cancer cells.
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Neoplasias de la Próstata , beta-Ciclodextrinas , Antígenos de Superficie/metabolismo , Línea Celular Tumoral , Doxorrubicina/farmacología , Glutamato Carboxipeptidasa II/metabolismo , Células HEK293 , Humanos , Ligandos , Masculino , Neoplasias de la Próstata/patología , Urea/farmacología , Urea/uso terapéuticoRESUMEN
The synthesis of d-glucoheptose derivative containing a boronic moiety is described herein. Starting from benzyl 6,7-dideoxy-2,3,4-tri-O-benzyl-ß-d-gluco-ept-6-enopyranoside, the introduction of the boronic acid was performed through a metathesis reaction by using MIDA vinyl boronic acid and the 2nd generation Grubbs catalyst. Hydrogenation led to the final product in only two reaction steps. This new sugar-containing boronic acid in the skeleton could mimic carbohydrate behavior and follow the glucose uptake in living cells. The in vitro toxicity tests performed in fibroblasts and glioma tumor cell lines showed minimal toxicity. Boron uptake measured using ICP-MS was minimal in fibroblasts, while in glioma cells showed a value of 6 ng of total boron accumulation per mg of cells, implying that compound 1a is able to accumulate selectively in the tumor tissues compared to normal.
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Terapia por Captura de Neutrón de Boro , Glioma , Boro/farmacología , Compuestos de Boro/farmacología , Ácidos Borónicos/farmacología , Carbohidratos , Línea Celular Tumoral , Glioma/metabolismo , Glucosa , HumanosRESUMEN
BACKGROUND AND PURPOSE: Post-stroke dysphagia affects almost half of the survivors and severely influences quality of life, thus becoming swallowing rehabilitation of paramount importance. However, there is little adequate evidence on which the best rehabilitative strategy can be. Surface electromyography (sEMG) allows for recording swallowing muscles' activity and provides real time visual feedback, as a biofeedback adjunctive technique to improve treatment outcome. This study aimed to analyze the effectiveness of biofeedback rehabilitation of swallowing through sEMG compared to standard techniques, in post-stroke dysphagia. METHODS: A pilot-randomized controlled trial included 17 patients diagnosed with post-stroke dysphagia. Nine underwent sEMG-biofeedback rehabilitation; seven controls were submitted to control treatment, one dropout. The primary outcome was the functional oral intake scale (FOIS), secondary outcomes was pharyngeal clearance and safe swallowing, assessed through fiberoptic endoscopic evaluation of swallowing (FEES). RESULTS: FOIS improved in all patients, regardless of treatment. sEMG-biofeedback rehabilitation led to improvements of the pharyngeal clearance and swallowing safety. The rehabilitative effects appeared stable at 2-months follow-up. CONCLUSIONS: The application of biofeedback based on sEMG in post-stroke dysphagia patients resulted in an effective rehabilitative technique, in particular for pharyngeal clearance improvements and safe swallowing, thus reducing the risk of aspiration and malnutrition.
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Trastornos de Deglución , Accidente Cerebrovascular , Biorretroalimentación Psicológica/métodos , Deglución , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Humanos , Calidad de Vida , Accidente Cerebrovascular/complicaciones , Resultado del TratamientoRESUMEN
The preparation of anomeric tetrabutylammonium sulphates of glucose and galactose derivatives is reported and their role as donors in glycosylation reactions is studied. Metal triflates showed good performance in activating sulphate as a leaving group. Among them, ytterbium triflate in stoichiometric amounts gave the best results. Basic conditions using barium oxide in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) were also shown to give good results. Benzylated sulphates were much more reactive than benzoylated donors when activated either by ytterbium triflate or by BaO and TMSOTf. Different acceptors were tested, such as isopropanol, cholesterol, and other common sugar derivatives. High reaction rates and excellent glycosylation yields were obtained under mild reaction conditions. The α/ß anomeric ratio suggests a predominant SN2-like reaction mechanism.
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The rehabilitation of motor deficits following stroke relies on both sensorimotor and cognitive abilities, thereby involving large-scale brain networks. However, few studies have investigated the integration between motor and cognitive domains, as well as its neuroanatomical basis. In this retrospective study, upper limb motor responsiveness to technology-based rehabilitation was examined in a sample of 29 stroke patients (18 with right and 11 with left brain damage). Pretreatment sensorimotor and attentional abilities were found to influence motor recovery. Training responsiveness increased as a function of the severity of motor deficits, whereas spared attentional abilities, especially visuospatial attention, supported motor improvements. Neuroanatomical analysis of structural lesions and white matter disconnections showed that the poststroke motor performance was associated with putamen, insula, corticospinal tract, and frontoparietal connectivity. Motor rehabilitation outcome was mainly associated with the superior longitudinal fasciculus and partial involvement of the corpus callosum. The latter findings support the hypothesis that motor recovery engages large-scale brain networks that involve cognitive abilities and provides insight into stroke rehabilitation strategies.
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Trastornos del Movimiento/fisiopatología , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/fisiopatología , Extremidad Superior/fisiopatología , Anciano , Anciano de 80 o más Años , Cognición , Femenino , Lóbulo Frontal/fisiopatología , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Lóbulo Parietal/fisiopatología , Desempeño Psicomotor , Recuperación de la Función , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Resultado del TratamientoRESUMEN
In a patient suffering from tactile agnosia a comparison was made (using the ABABAB paradigm) between three blocks of neuropsychological rehabilitation sessions involving off-line anodal transcranial direct current stimulation (anodal-tDCS) and three blocks of rehabilitation sessions without tDCS. During the blocks with anodal-tDCS, the stimulation was administered in counterbalanced order to two sites: i) the perilesional parietal area (specific stimulation) and ii) an occipital area far from the lesion (nonspecific stimulation).Rehabilitation associated with anodal-tDCS (in particular in the perilesional areas) is more efficacious than without stimulation.
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Agnosia/fisiopatología , Agnosia/rehabilitación , Lóbulo Parietal/fisiopatología , Recuperación de la Función/fisiología , Percepción del Tacto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Parietal/patología , Estimulación Transcraneal de Corriente DirectaRESUMEN
After the development of accelerators as neutron source, the access to new suitable agents for boron neutron capture therapy (BNCT) became a major need. Among many others, sugar boronic acids have recently attracted attention as boron carriers. Herein we report the synthesis and preliminary biological studies of two new sugar analogues containing a boronic acid at the anomeric position. The analogues were obtained by hydroboration of proper open-chain terminal alkenes that, after quenching with water, spontaneously afforded cyclic boronic acids with hemiacetal-like structures.
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Somatoparaphrenic symptoms after left-hemisphere damage are rare. To verify the potential role of body-related sensory (proprioceptive, visual, and somatosensory) manipulation in patients experiencing sensations of hand disownership, the symptoms of a patient suffering from right-hand somatoparaphrenia were monitored and clinical and neuropsychological variables were controlled. Four types of manipulation were administered: changes in spatial position of the hand, multisensory stimulation, and self-observation using video or mirrors. Multisensory visuo-tactile stimulation was efficacious in terms of reducing somatoparaphrenia, and changes in the position of the hand produced some positive effects. Third-person perspective self-observation did not, however, result in any changes.
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Agnosia/etiología , Lesiones Encefálicas/complicaciones , Lateralidad Funcional/fisiología , Propiocepción/fisiología , Estimulación Acústica , Anciano , Agnosia/diagnóstico por imagen , Imagen Corporal , Lesiones Encefálicas/diagnóstico por imagen , Femenino , Humanos , Pruebas Neuropsicológicas , Estimulación Luminosa , Tomógrafos Computarizados por Rayos XRESUMEN
Asymmetric epoxidation represents a hot topic in organic synthesis. In recent years, organocatalysts based on sugar skeletons have been exploited in asymmetric epoxidation to achieve enantiomeric pure epoxides. In this work, two different endocyclic ketones derived from glucose and galactose protected with a 4,6-O-benzylidene group have been prepared and exploited for Shi-type epoxidation. The two carbohydrates show an opposite preferential stereoselective epoxidation on various olefins, affording the epoxides in high conversions and modest enantioselectivities. DFT calculations disclosed the reasons behind the inversion of selectivity achieved by the two catalysts, showing that a delicate balance between the catalyst conformation, its protecting groups, and the secondary interactions with the substrate govern the final observed results.
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The discovery of new glycosylation reactions is still a major challenge in carbohydrate chemistry. Traditional glycosylation reactions require the preparation of sugar donors with anomeric active or latent leaving groups. Dehydrative glycosylation is a fascinating alternative that enables the direct formation of the glycosidic bond from the hemiacetal, eliminating the need for (sometimes unstable) leaving groups, and allowing to reduce reaction, work-up, and purification times. Although some interesting methods of dehydrative glycosylation have been reported, in order to compete with conventional chemical glycosylation, a greater number of efficient and stereoselective methods need to be developed. Herein, a dehydrative procedure that uses a combination of iodine, triphenylphosphine, and a base (DMAP or imidazole) is described. This methodology allows for the preparation of sugar derivatives from commercially available 1-hydroxy glycosyl donors. The reaction takes place under mild conditions through the in situ-formation of an anomeric iodide intermediate, which, upon reaction with an alcohol, gives the corresponding glycosides up to quantitative yields and with high α-stereoselectivity.
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Yodo , Glicosilación , Compuestos Organofosforados , Química Orgánica , GlicósidosRESUMEN
PURPOSE: Acquired central dysgraphia is a heterogeneous neurological disorder that usually co-occurs with other language disorders. Written language training is relevant to improve everyday skills and as a compensatory strategy to support limited oral communication. A systematic evaluation of existing writing treatments is thus needed. METHOD: We performed a systematic review of speech and language therapies for acquired dysgraphia in studies of neurological diseases (PROSPERO: CRD42018084221), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist with a search on several databases for articles written in English and published until August 31, 2021. Only methodological well-designed studies were included. Further assessment of methodological quality was conducted by means of a modified version of the Downs and Black checklist. RESULTS: Eleven studies of 43 patients in total were included. For each study, we collected data on type of population, type of impairment, experimental design, type of treatment, and measured outcomes. The studies had a medium level of assessed methodological quality. An informative description of treatments and linkages to deficits is reported. CONCLUSIONS: Although there is a need for further experimental evidence, most treatments showed good applicability and improvement of written skills in patients with dysgraphia. Lexical treatments appear to be more frequently adopted and more flexible in improving dysgraphia and communication, especially when a multimodal approach is used. Finally, the reported description of treatment modalities for dysgraphia in relation to patients' deficits may be important for providing tailored therapies in clinical management.
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Agrafia , Trastornos del Lenguaje , Humanos , Agrafia/diagnóstico , Agrafia/etiología , Agrafia/terapia , Habla , Terapia del Lenguaje , Trastornos del Lenguaje/diagnóstico , Trastornos del Lenguaje/etiología , Trastornos del Lenguaje/terapia , LenguajeRESUMEN
OBJECTIVE: To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder. METHODS: A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021. RESULTS: Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was "object relations." Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with bipolar disorder - taking into account their analyzability and practical arrangements for conducting therapy - and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases. CONCLUSION: Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with bipolar disorder. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.
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Trastorno Bipolar , Psicoanálisis , Terapia Psicoanalítica , Humanos , Trastorno Bipolar/tratamiento farmacológico , Promoción de la Salud , Apego a ObjetosRESUMEN
Objective: In the dysphagic patient, pharyngeal residues (PR) are associated with aspiration and poor quality of life. The assessment of PR using validated scales during flexible endoscopic evaluation of swallowing (FEES) is crucial for rehabilitation. This study aims to validate and test the reliability of the Italian version of the Yale Pharyngeal Residue Severity Rating Scale (IT-YPRSRS). The effects of training and experience in FEES on the scale were also determined. Methods: The original YPRSRS was translated into Italian according to standardised guidelines. Thirty FEES images were selected after consensus and proposed to 22 naive raters who were asked to assess the severity of PR in each image. Raters were divided into two subgroups by years of experience at FEES, and randomly by training. Construct validity, inter-rater, and intra-rater reliability were assessed by kappa statistics. Results: IT-YPRSRS showed substantial to almost perfect agreement (kappa > 0.75) in validity and reliability for both the overall sample (660 ratings), and valleculae/pyriform sinus sites (330 ratings each). No significant differences emerged between groups considering years of experience, and variable differences were observed by training. Conclusions: The IT-YPRSRS demonstrated excellent validity and reliability in identifying location and severity of PR.
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Calidad de Vida , Traducciones , Humanos , Reproducibilidad de los Resultados , Deglución , Grupo SocialRESUMEN
It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.
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Agnosia , Síndrome de Gerstmann , Sustancia Blanca , Humanos , Sustancia Blanca/patología , Lóbulo Parietal , Encéfalo , Agnosia/complicacionesRESUMEN
Background: Stroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment's effect in a group of stroke survivors. Methods/design: A total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery. Discussion/summary: The integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions.
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Glycosylation is the key reaction by which our body can produce and modify carbohydrates and their conjugates which are molecules essential for life. The study of the diversity of their functions is a current and ever-expanding topic that requires the ability to provide pure saccharides quickly, efficiently and in a controlled way which can be achieved by chemical synthesis. Although the influence of the donor and the promoter on the outcome of a glycosylation reaction is well documented, the search for new methodologies and new promoters/activators is constantly expanding. In this review, after an introduction dealing with well-known glycosylation strategies, we describe the most recent advances in terms of the use of innovative approaches, focalizing the study on new promoters and leaving groups exploited in the last ten years.
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Carbohidratos , Carbohidratos/química , Glicosilación , EstereoisomerismoRESUMEN
Sugars are a versatile tool for targeting malignant cells and have been extensively used for drug delivery and imaging techniques. Their prototype, fluorodeoxyglucose ([18F]FDG), is currently used for positron emission tomography. Boron neutron capture therapy (BNCT) is a cancer treatment that relies on irradiation with thermal neutrons of cancer cells previously loaded with [10B]-containing compounds. The recent introduction of accelerators as a neutron source for clinical use prompts the planning of delivery compounds enriched with boron able to be traced in real time. This work describes the first synthesis of a new class of sugar derivatives conjugated to a trifluoroborate moiety as potential theranostic agents. Stability and cytotoxicity studies are reported for all compounds, together with [18F] radiolabeling optimization and in vivo preliminary positron emission tomography (PET) experiments on a selected compound.
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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy considered curable by modern clinical management. Nevertheless, the prognosis for T-ALL high-risk cases or patients with relapsed and refractory disease is still dismal. Therefore, there is a keen interest in developing more efficient and less toxic therapeutic approaches. T-ALL pathogenesis is associated with Notch signaling alterations, making this pathway a highly promising target in the fight against T-ALL. Here, by exploring the anti-leukemic capacity of the natural polyphenol curcumin and its derivatives, we found that curcumin exposure impacts T-ALL cell line viability and decreases Notch signaling in a dose- and time-dependent fashion. However, our findings indicated that curcumin-mediated cell outcomes did not depend exclusively on Notch signaling inhibition, but might be mainly related to compound-induced DNA-damage-associated cell death. Furthermore, we identified a novel curcumin-based compound named CD2066, endowed with potentiated anti-proliferative activity in T-ALL compared to the parent molecule curcumin. At nanomolar concentrations, CD2066 antagonized Notch signaling, favored DNA damage, and acted synergistically with the CDK1 inhibitor Ro3306 in T-ALL cells, thus representing a promising novel candidate for developing therapeutic agents against Notch-dependent T-ALL.