What about TSH and anti-thyroid antibodies in patients with autoimmune thyroiditis and celiac disease using a gluten-free diet? A systematic review

The prevalence of celiac disease (CD) in patients with chronic autoimmune thyroiditis (CAIT) is estimated to be between 2 and 7.8%. A gluten-free diet (GFD) in patients with CD is suggested to have a beneficial effect on CAIT. Thus, the present systematic review was undertaken to achieve more robust evidence about the change in thyroid stimulating hormone (TSH) and thyroid-specific antibodies (T-Ab) levels obtained in CD patients following a GFD. A specific search strategy was planned. The last search was performed on March 2022. The following data were mainly searched for in order to be extracted: sample size, mean and/or median with standard deviation (SD), and error (SE), individually, of thyroid hormones and T-Ab at baseline and after GFD, and the duration of the study. The initial search retrieved 297 records and 6 articles met the inclusion criteria. In total, 50 patients with both CD and CAIT and 45 controls were reported. The effects of a GFD on the thyroid hormonal and immunological profile could be extracted only in a part of the studies. Two studies were case reports. A low risk of bias was observed. These findings advise further studies, ideally randomized, in order to better investigate the potential relationship between GFD and thyroid homeostasis. The level of evidence is not still sufficient to recommend GFD to patients with CAIT

Italia-Germania, una comparazione dei livelli di competitivit\ue0 industriale

L\u2019indagine \ue8 stata realizzata dagli uffici dell\u2019area Lavoro e previdenza di Confindustria Bergamo e da ADAPT/Universit\ue0 degli Studi di Modena e Reggio Emilia, con il supporto scientifico ed operativo rispettivamente del Prof. Maurizio Del Conte dell\u2019Universit\ue0 Bocconi di Milano e del Prof. Michele Tiraboschi dell\u2019Universit\ue0 degli Studi di Modena e Reggio Emilia. La parte I, di carattere riassuntivo, esprime la valutazione di Confindustria Bergamo sugli esiti complessivi dell\u2019analisi normativa e della campionatura di esperienze aziendali realizzata. Le due note di approfondimento allegate sono state invece realizzate dai referenti scientifici Maurizio Del Conte e Michele Tiraboschi e riportano le opinioni degli AA. La parte II \ue8 stata redatta da Benedetto Fratello, avvocato giuslavorista e dottore di ricerca in diritto del lavoro presso l\u2019Universit\ue0 Bocconi di Milano (primo capitolo) e da Simone Caroli, Emmanuele Massagli, Davide Mosca e Paolo Tomassetti, ricercatori ADAPT (secondo capitolo). La parte III \ue8 stata redatta da Marina Mariani di Confindustria Bergamo, dottore di ricerca in formazione della persona e mercato del lavoro presso l\u2019Universit\ue0 degli Studi di Bergamo

The assessment of patient-reported outcomes for the authorisation of medicines in Europe: a review of European Public Assessment Reports from 2017 to 2022

Objectives: Health regulators have progressively increased their attention and focus on patient-reported outcomes (PROs), driven by the diffusion of a patient-centred approach to the drug development process. This study investigates the consideration of PROs and their measures (PROMs) in the authorisation of medicines in Europe. Methods: All medicines for human use authorised or refused by the European Medicines Agency (EMA) in the period 2017-2022 were identified, and corresponding European Public Assessment Reports (EPARs) were downloaded for review. Medicine and PROs/PROM characteristics were systematically recorded. A multivariate logistic regression was performed to identify variables associated with the use of patient-reported evidence in EPARs. Results: Overall, 497 EPARs of authorised medicines and 19 EPARs of refused medicines were analysed; of these, 240 (48.3%) and 10 (52.6%), respectively, reported any use of PROs/PROMs (p = 0.710). For authorised medicines, the likelihood of using PROs/PROMs was negatively affected by generic (OR = 0.01, p < 0.001) and biosimilar status (OR = 0.46, p = 0.013) and positively affected by orphan status (OR = 1.41, p = 0.177). The use of PROMs (50.6% in 2017 vs 47.9% in 2022) did not show a clear pattern over the 6-year period considered (p = 0.758) and was particularly uncommon in some therapeutic areas (e.g., 15.2% in infectious diseases). A total of 816 dyads of PROs/PROMs were identified. On average each EPAR considered 1.6 (range: 0-14) instruments. Patient-reported outcomes were typically secondary (53.3%) and exploratory endpoints (18.8%); in one-third of cases (32.5%), they assessed generic quality of life. Among the PROMs, 227 (27.8%) targeted general population; EQ-5D (11.0%), SF-36/SF-12 (5.9%) and EORTC QLQ-C30 (5.6%) were the instruments most frequently used. Conclusions: This study suggests PROs/PROMs are considered in less than half of total medicine assessments and even more rarely in some disease areas. The adoption of PROs is key in EMA strategy to 2025 and would be facilitated by consensus development on their measures and optimisation of data collection

Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the alpha II-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative alpha II-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes

Particle number and mass exposure concentrations by commuter transport modes in Milan, Italy

There is increasing awareness amongst the general public about exposure to atmospheric pollution while travelling in urban areas especially when taking active travelling modes such as walking and cycling. This study presents a comparative investigation of ultrafine particles (UFP), PM10, PM2.5, PM1 exposure levels associated with four transport modes (i.e., walking, cycling, car, and subway) in the city of Milan measured by means of portable instruments. Significant differences in particle exposure between transport modes were found. The subway mode was characterized by the highest PM mass concentrations: PM10, PM2.5, PM1 subway levels were respectively about 2-4-3 times higher than those of the car and open air active modes (i.e. cycling and walking). Conversely, these latter modes displayed the highest UFP levels about 2 to 3 times higher than the subway and car modes, highlighting the influence of direct traffic emissions. The car mode (closed windows, air conditioning and air recirculation on) reported the lowest PM and UFP concentration levels. In particular, the open-air/car average concentration ratio varied from about 2 for UFP up to 4 for PM1 and 6 for PM10 and PM2.5, showing differences that increase with increasing particle size. This work points out that active mode travelling in Milan city centre in summertime results in higher exposure levels than the car mode. Walkers’ and cyclists’ exposure levels is expected to be even higher during wintertime, due to the higher ambient PM and UFP concentration. Interventions intended to re-design the urban mobility should therefore include dedicated routes in order to limit their exposure to PM and UFP by increasing their distance from road traffic

EQ-5D-5L population norms for Italy

This study aimed to provide normative data obtained in response to the EQ-5D-5L questionnaire in Italy and compare this with data from other countries

Living and Dying: An Apposition Beteween the Ego and Superego

It`s a reflexion about the ego and superego role in decisions while the option between living and dying is urgent. Three historical characters will be analyzed by the psychoanalytical vertex in their cruciate moments of decision and correlated with a clinical case which reveals a fight between life preservation, ego`s primordial function and the preservation of moral and ethical values superego`s privilege. In order to do that three historical characters trial will be presented, such as: the philosopher Sócrates, the scientist Galileu Galilei and the farmer John Proctor, characters from “The Crucible”. We conclude that depending of the chosen vertex to reflect about the decisions, we can have a superegoic nature more idealized and cruel or an ego more flexible and vital

Morphologic study of the cornea by in vivo confocal microscopy and optical coherence tomography after bifocal refractive corneal inlay implantation

To evaluate the biocompatibility of the Flexivue Microlens intracorneal inlay based on healing of corneal wounds and analysis of corneal structural features using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT)

Visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Objectives: To evaluate visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Three subjects tone male and two females, mean age 55.3 +/- 2.9 years) belonging to an Italian family already diagnosed with CADASIL through clinicopathological and genetic studies and 14 control subjects (6 males and 8 females, mean age 52.7 +/- 3.6 years) were enrolled in the study. Flash electroretinogram (ERG), oscillatory potentials (OPs) and simultaneous recordings of pattern electroretinogram (PERG) and visual evoked potentials (VEPs) were assessed in all 3 subjects with CADASIL and age-matched controls. Results: Subjects with CADASIL showed: reduced ERG, OP and PERG (N35-P50, P50-N95) amplitudes with respect to our normal limits; delayed PERG (N35, P50) and VEP (P100) implicit times when compared with our normal limits; and VEP (N75-P100) amplitudes and retinocortical times within our normal limits. Conclusions: Subjects with CADASIL present a dysfunction in the outer, middle and innermost retinal layers when the index of neural conduction in the postretinal visual pathways is normal. The delay in visual cortical responses observed in subjects with CADASIL may be ascribable to retinal impairment with a possible functional sparing of the postretinal visual structures. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

Three-dimensional mapping of the orientation of collagen corneal lamellae in healthy and keratoconic human corneas using SHG microscopy

SHG image acquired with sagittal optical sectioning (A) of a healthy cornea and (B) of a keratoconic cornea. Scale bars: 30 μm. Keratoconus is an eye disorder that causes the cornea to take an abnormal conical shape, thus impairing its refractive functions and causing blindness. The late diagnosis of keratoconus is among the principal reasons for corneal surgical transplantation. This pathology is characterized by a reduced corneal stiffness in the region immediately below Bowman's membrane, probably due to a different lamellar organization, as suggested by previous studies. Here, the lamellar organization in this corneal region is characterized in three dimensions by means of second-harmonic generation (SHG) microscopy. In particular, a method based on a three-dimensional correlation analysis allows to probe the orientation of sutural lamellae close to the Bowman's membrane, finding statistical differences between healthy and keratoconic samples. This method is demonstrated also in combination with an epi-detection scheme, paving the way for a potential clinical ophthalmic application of SHG microscopy for the early diagnosis of keratoconus