Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role?

Secondary adrenal insufficiency (SAI) is a potentially life-threatening endocrine disorder due to an impairment of corticotropin (ACTH) secretion from any process affecting the hypothalamus or pituitary gland. ACTH deficit can be isolated or associated with other pituitary failures (hypopituitarism). An increased mortality due to cardiovascular, metabolic, and infectious diseases has been described in both primary and secondary adrenal insufficiency. However, few studies have provided compelling evidences on the underlying mechanism in SAI, because of the heterogeneity of the condition. Recently, some studies suggested that inappropriate glucocorticoid (GCs) replacement therapy, as for dose and/or timing of administration, may play a role. Hypertension, insulin resistance, weight gain, visceral obesity, increased body mass index, metabolic syndrome, impaired glucose tolerance, diabetes mellitus, dyslipidemia have all been associated with GC excess. These conditions are particularly significant when SAI coexists with other pituitary alterations, such as growth hormone deficiency, hypogonadism, and residual tumor. Novel regimen schemes and GC preparations have been introduced to improve compliance and better mimick endogenous cortisol rhythm. The controlled trials on the improved replacement therapies, albeit in the short-term, show some beneficial effects on cardiovascular risk, glucose metabolism, and quality of life. This review examines the current evidence from the available clinical trials investigating the association between different glucocorticoid replacement therapies (type, dose, frequency, and timing of treatment) and glycometabolic alterations in SAI

Le sopravvenienze: dall’equilibrio contrattuale alla nullità sopravvenuta

La nozione civilistica e la nozione contabile di sopravvenienza a confronto. Introduzione e genesi del principio di equilibrio contrattuale. Equilibrio giuridico ed equilibrio economico come criteri di qualificazione della causa in concreto del contratto: la rilevanza delle sopravvenienze sull’equilibrio contrattuale. La nullità sopravvenuta del contratto in relazione al principio di equilibrio contrattuale.La nozione civilistica e la nozione contabile di sopravvenienza a confronto. Introduzione e genesi del principio di equilibrio contrattuale. Equilibrio giuridico ed equilibrio economico come criteri di qualificazione della causa in concreto del contratto: la rilevanza delle sopravvenienze sull’equilibrio contrattuale. La nullità sopravvenuta del contratto in relazione al principio di equilibrio contrattuale.LUISS PhD Thesi

Exploring Novel Anticancer Approaches: Design, Synthesis and Biological Evaluation of Small Molecules and NGR Tumor-Homing Peptides

In anticancer drug discovery DNA secondary structures, called G-quadruplexes (G4s), emerged as targets of interest, owing to their localization in crucial positions of the genome, such as in telomers and oncogene promoter regions. It has been widely accepted that G4 stabilization by small molecules at these levels, may represent a realistic anticancer strategy. Since a diimidazo[1,2-a:1,2-c]pyrimidine bis-guanylhydrazone derivative was found to be a potent stabiliser of several quadruplex DNAs over duplex DNA, a library of analogues was designed and synthesized to shed light on the structural requirements for G4 binding. The newly synthesized hydrazones were evaluated for their ability to stabilize several G4 with different topology and also for their antiproliferative activity. In particular the most promising compound of the series showed the capability to selectively stabilize a specific G4 structure and to inhibit cancer cell growth in the nanomolar range. Tumor-homing peptides have been considered promising tools for imaging and therapy of tumors over-expressing their target ligand. In this context, the cyclic CNGRC peptide has been extensively used as tumor-homing carrier for its ability to specifically recognise aminopeptidase N (APN/CD13), a zinc-dependent ectoenzyme, upregulated in tumor blood vessels undergoing angiogenesis and in the majority of cancer cells. Considering the potential of APN-directed tumour homing strategies and taking into account the recently reported crystal structure of porcine APN complexed with cCNGRCG, a library of C-terminus and N-terminus functionalized cCNGRC peptides was designed and synthesized with the aim to confirm the importance of N-terminal amine group of the cCNGRC in the APN binding. The synthesized peptides were assayed for their ability to inhibit APN in vitro. The C-terminus was identified as the right conjugation site of the cCNGRC peptide, which was consequently conjugated with a fluorescent probe for APN imaging studies in cancer cells

Greater intermanual transfer in the elderly suggests age-related bilateral motor cortex activation is compensatory

ABSTRACT. Hemispheric lateralization of movement control diminishes with age; whether this is compensatory or maladaptive is debated. The authors hypothesized that if compensatory, bilateral activation would lead to greater intermanual transfer in older subjects learning tasks that activate the cortex unilaterally in young adults. They studied 10 young and 14 older subjects, learning a unimanual visuomotor task comprising a feedforward phase, where there is unilateral cortical activation in young adults, and a feedback phase, which activates the cortex bilaterally in both age groups. Increased intermanual transfer was demonstrated in older subjects during feedforward learning, with no difference between groups during feedback learning. This finding is consistent with bilateral cortical activation being compensatory to maintain performance despite declining computational efficiency in neural networks

Clinical signs, telemedicine and online consultations in head and neck diseases during the SARS CoV-2 pandemic: an Italian experience

SUMMARY Objective. The aim of this paper is to describe the application of a telemedicine (TM) syn-chronous model designed to deliver care during the Coronavirus Disease 2019 (COVID-19) pandemic to patients with head and neck disease. Methods. The first step was to identify the classes of patients eligible for tele-examination. Mild, flu-like symptomatology represents the characteristics of the typical patient who is a candidate for tele-examination. The standard requirements for TM include a computer associated with a digital camera, alternatively a smartphone or tablet. The TM platform is based on the Lifesize™ software, which can be freely downloaded. Results. The overall number of teleconsultations was 178, of which 163 (91.5%) were man-aged at home, while 15 (8.5%) were invited for in-presence examination. The number of patients coming from general practitioners was 98 (55.1%), from spoke units 52 (29.2%), patients needing prompt stabilisation and transfer to the hub centre were 20 (11.2%,) while 8 (4.5%) were immediately fast-tracked in the spoke unit after multi-professional tele-con-sultation. Conclusions. Telemedicine improves organisational models, and provides a scalable solu-tion to overcome problems of overcrowding, resources and time. Should these develop-ments continue, we could face to a gradual transition to a more digital and efficient health-care system

Thyroglossal Duct Lipoma: A Case Report and a Systematic Review of the Literature for Its Management

Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk’s procedure). For other pathologies associated with the TGD tract, the latter operation might be not necessary. In the present report, a case of a TGD lipoma is presented and a systematic review of the pertinent literature was performed. We present the case of a 57-year-old woman with a pathologically confirmed TGD lipoma who underwent transcervical excision without resecting the hyoid bone. Recurrence was not observed after six months of follow-up. The literature search revealed only one other case of TGD lipoma and controversies are addressed. TGD lipoma is an exceedingly rare entity whose management might avoid hyoid bone excision

NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.Peer reviewedPublisher PD

Hearing characterization in oculoauriculovertebral spectrum : a prospective study with 10 patients

Oculoauriculovertebral spectrum (OAVS), also known as Goldenhar syndrome, is considered a condition associated to failing of embryogenesis involving the first and second branchial arches, leading to structural abnormalities arising from it. The aim of this study is to verify the hearing features presented by patients with OAVS and provide additional information that may contribute to improvement of speech therapy. The sample consisted of 10 individuals diagnosed with OAVS and cared for by the Clinical Genetics Service. All patients underwent objective assessment of auditory function through tonal and vocal audiometry. This evaluation was completed using TOAE and BERA. The patient’s age ranged from 1 year and 9 months to 27 years and 4 months. At physical examination it was found that 10 had microtia, 7 preauricular tags, 6 low-set ears, 6 ear canal atresia, and 2 preauricular pits. Among the patients, five presented with abnormal hearing. Three patients had conductive hearing loss ranging from mild to moderate, and two patients had sensorineural hearing loss from mild to profound. Three patients had hearing loss in both ears. Speech-language disorders are common in children with OAVS. Thus, the referral to the audiologist and speech pathologist is indicated as soon as possible. Early recognition and detailed understanding of aspects related to the etiology, clinical features, and outcome of patients with OAVS are essential for their proper management

Association of the chronotype score with circulating trimethylamine n‐oxide (Tmao) concentrations

Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference (p < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet (p < 0.001) and the lowest circulating TMAO concentrations (p < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = −0.627, p < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = −0.479, t = −12.08, and p < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 (p < 0.001, R2 = −0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD