Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. ...Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ₁₋₄₂ oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ₁₋₄₂ fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ₁₋₄₂ oligomers interact with PrPC, with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ₁₋₄₂ oligomers are responsible for cognitive impairment in AD and that PrPC is not required.
The head and neck district represents one of the most frequent sites of cancer, and the percentage of metastases is very high in both loco-regional and distant areas. Prognosis refers to several ...factors: a) stage of disease; b) loco-regional relapses; c) distant metastasis. At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases with an additional 20-30% developing metastases during the course of their disease. Diagnosis of distant metastases is associated with unfavorable prognosis, with a median survival of about 10 months. The aim of the present review is to provide an update on distant metastasis in head and neck oncology. Recent achievements in molecular profiling, interaction between neoplastic tissue and the tumor microenvironment, oligometastatic disease concepts, and the role of immunotherapy have all deeply changed the therapeutic approach and disease control. Firstly, we approach topics such as natural history, epidemiology of distant metastases and relevant pathological and radiological aspects. Focus is then placed on the most relevant clinical aspects; particular attention is reserved to tumours with distant metastasis and positive for EBV and HPV, and the oligometastatic concept. A substantial part of the review is dedicated to different therapeutic approaches. We highlight the role of immunotherapy and the potential effects of innovative technologies. Lastly, we present ethical and clinical perspectives related to frailty in oncological patients and emerging difficulties in sustainable socio-economical governance.
The Southern Copper Belt, Carajás Province, Brazil, hosts several iron oxide–copper–gold (IOCG) deposits, including Sossego, Cristalino, Alvo 118, Bacuri, Bacaba, Castanha, and Visconde. Mapping and ...U–Pb sensitive high-resolution ion microprobe (SHRIMP) IIe zircon geochronology allowed the characterization of the host rocks, situated within regional WNW–ESE shear zones. They encompass Mesoarchean (3.08–2.85 Ga) TTG orthogneiss, granites, and remains of greenstone belts, Neoarchean (ca. 2.74 Ga) granite, shallow-emplaced porphyries, and granophyric granite coeval with gabbro, and Paleoproterozoic (1.88 Ga) porphyry dykes. Extensive hydrothermal zones include albite–scapolite, biotite–scapolite–tourmaline–magnetite alteration, and proximal potassium feldspar, chlorite–epidote and chalcopyrite formation. U–Pb laser ablation multicollector inductively coupled mass spectrometry (LA-MC-ICP-MS) analysis of ore-related monazite and Re–Os NTIMS analysis of molybdenite suggest multiple Neoarchean (2.76 and 2.72–2.68 Ga) and Paleoproterozoic (2.06 Ga) hydrothermal events at the Bacaba and Bacuri deposits. These results, combined with available geochronological data from the literature, indicate recurrence of hydrothermal systems in the Southern Copper Belt, including 1.90–1.88-Ga ore formation in the Sossego–Curral ore bodies and the Alvo 118 deposit. Although early hydrothermal evolution at 2.76 Ga points to fluid migration coeval with the Carajás Basin formation, the main episode of IOCG genesis (2.72–2.68 Ga) is related to basin inversion coupled with Neoarchean (ca. 2.7 Ga) felsic magmatism. The data suggest that the IOCG deposits in the Southern Copper Belt and those in the Northern Copper Belt (2.57-Ga Salobo and Igarapé Bahia–Alemão deposits) do not share a common metallogenic evolution. Therefore, the association of all IOCG deposits of the Carajás Province with a single extensive hydrothermal system is precluded.
Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. ...Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.
Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by overgrowth, stemming from various genetic and epigenetic changes. This study delves into the role of
upregulation in BWS, ...focusing on insulin-like growth factor pathways, which are poorly known in this syndrome. We examined the IGF2R, the primary receptor of IGF2, WNT, and autophagy/lysosomal pathways in BWS patient-derived lymphoblastoid cell lines, showing different genetic and epigenetic defects. The findings reveal a decreased expression and mislocalization of IGF2R protein, suggesting receptor dysfunction. Additionally, our results point to a dysregulation in the AKT/GSK-3/mTOR pathway, along with imbalances in autophagy and the WNT pathway. In conclusion, BWS cells, regardless of the genetic/epigenetic profiles, are characterized by alteration of the IGF2R pathway that is associated with the perturbation of the autophagy and lysosome processes. These alterations seem to be a key point of the molecular pathogenesis of BWS and potentially contribute to BWS's characteristic overgrowth and cancer susceptibility. Our study also uncovers alterations in the WNT pathway across all BWS cell lines, consistent with its role in growth regulation and cancer development.
1. Though multistage axial turbines are being widely used since many decades for water steam expansion or in gas turbines, their use in ORCs has traditionally found limitations as a consequence of ...the choice of designing turbines with cantilever arrangements.
2. The choice of the cantilever arrangement is mainly related to the advantages of having simple shaft bearings design, only one rotating seal system in contact with the working fluid, a lighter and more compact turbine casing, only one side of the turbine casing occupied with the bearing and sealing systems (leaving the other side free to host the outlet duct for working fluid expanded vapour which often features very large volumetric flow rates), easiness of access for ordinary and extraordinary maintenance. Hence cantilever arrangement involves definitely lower turbine costs, both in terms of Capex and Opex and is practically the only solution adopted by the industrial suppliers of ORC turbines.
3. By adopting the cantilever arrangement the installation of several turbine discs hosting several expansion stages, traditionally installed one close to the other, would increase the overhang mass of the turbine rotor and decrease the natural frequencies of the system, yielding some mechanical problems and, at the end, limiting the possibility of installing, practically, more than 2-3 stages with this kind of arrangement.
4. On the other hand, however, modern ORC turbines require to increase number of stages to better exploit the expansion enthalpy drop, in order to increase turbine efficiency and/or to allow to adopt a low rotating speed (even 1,500 rpm) for a direct connection with synchronous generator.
5. The paper will describe an innovative solution that has allowed to increase the number of stages from the traditional 2-3 to at least 5 without leaving the effective cantilever arrangement, keeping the concept of ‘rigid’ rotor (i.e. operating below the first flexional natural frequency), with very low measured vibrations.
6. Operating data of a 9 MW 5 stage ORC turbine put in operation in 2016 will also be presented.
Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population.
In a ...multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020.
Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 95% CI 0.29-0.66;
= 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients;
= 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients;
= 0.0008) compared with patients receiving standard of care, respectively.
In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.
Substitution of the chlorido ligand of cyclometalated Pt (5-R-1,3-di(2-pyridyl) benzene)Cl (R = methyl, mesityl, 2-thienyl, or 4-diphenylamino-phenyl) by 4-phenylthiazole-2-thiolate leads to related ...thiolato complexes, which were fully characterized. Their photophysical properties were determined in degassed dichloromethane solution. The emission color of the novel complexes can be easily tuned by the nature of the substituents on the terdentate ligand, as is the case for the parent chlorido complexes. Their luminescence Quantum Yield is high, with that of the compounds with the 2-thienyl or 4-diphenylamino-phenyl substituents being much higher than that of the related chloride complexes. The platinum complex with the cyclometalated 5-(2-thienyl)-1,3-di(2-pyridyl) benzene was used as the emitter for the fabrication of a yellow solution-processable OLED.
COVID-19 survivors are at increased risk of persistent psychopathology after the infection. Despite long-term sequelae are an increasing concern, long-term neuropsychiatric consequences remain ...largely unclear. This cohort study aimed at investigating the psychopathological impact of COVID-19 in Italy one year after infection, outlining the trajectory of symptomatology at one, six-, and twelve-months follow-up.
We evaluated 402, 216, and 192 COVID-19 survivors respectively at one, six, and 12 months. A subgroup of 95 patients was evaluated longitudinally both at one, six, and 12 months. Validated self-report questionnaires were administered to assess depression, fatigue, anxiety, and post-traumatic distress. Socio-demographics and setting of care information were gathered for each participant.
At six and twelve months, respectively 94 (44%) and 86 (45%) patients self-rated in the clinical range in at least one psychopathological dimension. Pathological fatigue at twelve months was detected in 63 patients (33%). Considering the longitudinal cohort an interaction effect of sex and time was observed for depression (F = 8.63, p < 0.001) and anxiety (F = 5.42, p = 0.005) with males showing a significant increasing trend of symptoms, whereas an opposite course was observed in females.
High prevalence of psychiatric sequelae six and 12 months after COVID-19 was reported for the first time. These findings confirm the need to provide integrated multidisciplinary services to properly address long-lasting mental health sequelae of COVID-19 and to treat them with the aim of reducing the disease burden and related years of life lived with disability.
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