Role of high dose octreotide LAR for the treatment of GEP-NETs

Neuroendocrine Tumours (NETs) are a heterogeneous group of rare neoplasms that account for 0,5% of all malignancies. The increased incidence observed in the last few decades may be accounted for by increased awareness, improved diagnostic tools and a revision in the definition. The main primary sites are the gastro-entero-pancreatic (GEP) tract (62-67%), and the lung (22-27%). In patients with GEP-NETs, the strongest predictor of 5-years survival is the staging. An adequate clinical management of GEP-NETs should be multidisciplinary and should aim at assuring a good quality of life. Somatostatin (sst) analogues are widely used in these tumours, which often express sst receptors, since they are demonstrated to reduce clinical symptoms and tumour growth. Herein we explore the usefulness of doubling octreotide LAR dose in selected patients after escaping from symptoms control and/or tumour stabilization in course of treatment with standard dose

Light-Induced Access to Carbazole-1,3-dicarbonitrile: A Thermally Activated Delayed Fluorescent (TADF) Photocatalyst for Cobalt-Mediated Allylations

The stability of a photocatalyst under irradiation is important in photoredox applications. In this work, we investigated the stability of a thermally activated delayed fluorescence (TADF) photocatalyst {3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]}, recently employed in photoredox-mediated processes, discovering that in the absence of quenchers the chromophore is unstable and is efficiently converted by irradiation with visible light into another species based on the carbazole-1,3-dicarbonitrile moiety. The new species obtained is itself a TADF emitter and finds useful applications in photoredox transformations. At the excited state, it is a strong reductant and was efficiently applied to cobalt-mediated allylation of aldehydes, whereas other TADFs (4CzIPN and 3DPAFIPN) failed to promote efficient photocatalytic cycles

Effects of IGF-1 isoforms on muscle growth and sarcopenia.

The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin-like growth factor-1 (IGF-1) has been implicated in many anabolic pathways in skeletal muscle. IGF-1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF-1Ea and IGF-1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF-1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF-1Ea or IGF-1Eb transgenes was protective against age-related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1-α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF-1Ea and MLC/IGF-1Eb mice during aging. These data suggest that IGF-1 is a promising therapeutic agent in staving off advancing muscle weakness

Effects of IGF-1 isoforms on muscle growth and sarcopenia.

The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin-like growth factor-1 (IGF-1) has been implicated in many anabolic pathways in skeletal muscle. IGF-1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF-1Ea and IGF-1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF-1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF-1Ea or IGF-1Eb transgenes was protective against age-related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1-α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF-1Ea and MLC/IGF-1Eb mice during aging. These data suggest that IGF-1 is a promising therapeutic agent in staving off advancing muscle weakness

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach

Background: To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. Methods: 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity. Results: Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with >= 60 Gy (n = 58) and those irradiated with 3 cm (p 3 toxicity. Conclusions: SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments

KIT is dispensable for physiological organ vascularisation in the embryo

Blood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Additionally, KIT has been reported to be expressed in endothelial cells during embryonic brain vascularisation and has been implicated in pathological angiogenesis. However, it is neither known whether KIT expression is widespread in normal organ endothelium nor whether it promotes blood vessel growth in developing organs. Here, we have used single-cell analyses to show that KIT is expressed in endothelial cell subsets of several organs, both in the adult and in the developing embryo. Knockout mouse analyses revealed that KIT is dispensable for vascularisation of growing organs in the midgestation embryo, including the lung, liver and brain. By contrast, vascular changes emerged during late-stage embryogenesis in these organs from KIT-deficient embryos, concurrent with severe erythrocyte deficiency and growth retardation. These findings suggest that KIT is not required for developmental tissue vascularisation in physiological conditions, but that KIT deficiency causes foetal anaemia at late gestation and thereby pathological vascular remodelling

Performances Analysis of Titanium Prostheses Manufactured by Superplastic Forming and Incremental Forming

Abstract Titanium and its alloys are widely used in cranioplasty because they are biocompatible with excellent mechanical properties and favor the osseointegration with the bone. However, when Titanium alloys have to be worked several problems occurred from a manufacturing point of view: the standard procedure for obtaining Titanium prostheses is represented by the machining processes, which result time and cost consuming. The aim of this research consist to introduce alternative flexible sheet forming processes, i.e. Super Plastic Forming (SPF) and Single Point Incremental Forming (SPIF), for the manufacturing of patient-oriented titanium prostheses. The research activities have already highlighted the potentiality of the investigated forming processes that can be alternatively used taking into account both the damage morphology and the need of urgency operation. In the present work, the way of manufacturing the Ti prostheses by SPF and SPIF is described. A comparative analysis has been performed, thus highlighting the peculiarities of the investigated processes and the prostheses feasibility

Exon-trapping assay improves clinical interpretation of COL11A1 and COL11A2 intronic variants in stickler syndrome type 2 and otospondylomegaepiphyseal dysplasia

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report our previously unpublished intronic variants in COL11A1 (c.2241 + 5G>T, c.2809 − 2A>G, c.3168 + 5G>C) and COL11A2 (c.4392 + 1G>A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorder

Efficacy of transcranial magnetic stimulation treatment in reducing neuropsychiatric symptomatology after traumatic brain injury

BackgroundNeuropsychiatric disorders are highly disabling in traumatic brain injury (TBI) patients, and psychopharmacological treatments often fail to adequately mitigate their detrimental effects. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment in neurology and psychiatry, showing potential in treating psychiatric disorders.ObjectiveThis study investigates the efficacy of a novel, dual-site sequential rTMS protocol designed to treat neuropsychiatric symptoms in a TBI patient who was refractory to conventional treatments.MethodsA 34-year-old woman with severe head trauma and complex psychopathology underwent 20 daily sessions of focal-coil rTMS, combining inhibitory stimulation (1 Hz) on the right dorsolateral prefrontal cortex (DLPFC) and excitatory (10 Hz) on the left DLPFC, guided by a neuronavigation system. Psychiatric and neurocognitive assessments were conducted at baseline and at 2, 4, and 8 weeks following the beginning of rTMS treatment.ResultsAfter 2 weeks of treatment, the patient showed decreased impulsivity and obsessive-compulsive symptoms, along with improvements in attention and processing speed. After 4 weeks, impulsivity further declined, though no other significant changes were noted. At 8 weeks, a persistent positive effect was observed, including enhanced positive emotions.DiscussionThese findings suggest that guided, alternating neurostimulation of the DLPFC may modulate activity within cortico-striato-thalamo-cortical circuits, providing a promising alternative for managing neuropsychiatric symptoms in TBI patients who are resistant to traditional treatments

Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19

Background The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. Methods This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. Results Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5–10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. Conclusion Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus