Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Overuse-related musculoskeletal injuries mostly affect athletes, especially if involved in preseason conditioning, and military populations; they may also occur, however, when pathological or biological conditions render the musculoskeletal system inadequate to cope with a mechanical load, even if moderate. Within the MOVIDA (Motor function and Vitamin D: toolkit for risk Assessment and prediction) Project, funded by the Italian Ministry of Defence, a systematic review of the literature was conducted to support the development of a transportable toolkit (instrumentation, protocols and reference/risk thresholds) to help characterize the risk of overuse-related musculoskeletal injury. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach was used to analyze Review papers indexed in PubMed and published in the period 2010 to 2020. The search focused on stress (overuse) fracture or injuries, and muscle fatigue in the lower limbs in association with functional (biomechanical) or biological biomarkers. A total of 225 Review papers were retrieved: 115 were found eligible for full text analysis and led to another 141 research papers derived from a second-level search. A total of 183 papers were finally chosen for analysis: 74 were classified as introductory to the topics, 109 were analyzed in depth. Qualitative and, wherever possible, quantitative syntheses were carried out with respect to the literature review process and quality, injury epidemiology (type and location of injuries, and investigated populations), risk factors, assessment techniques and assessment protocols.

Objectives:The aim of the study is to make an international comparison of Health Technology Assessment (HTA) Agencies, to show their similarities and differences.Methods:An e-mail questionnaire was sent to thirty HTA agencies internationally. Questions related to the structure of the agency, the relationship with health-related institutions, the prescriptiveness of the decisions taken, the main core and the modalities to spread the assessment, and the type of funding.Results:Twenty-four HTA Agencies answered the questionnaire: 25 percent in America, 4.2 percent in Australia, and 70.8 percent in Europe. Fifty-four percent of HTA Agencies are governmental institutions (83.3 percent have central government funding), while 62.5 percent have relationships with health-related governmental institutions. Of the agencies, 87 percent reported that their decisions are not prescriptive, while for 20.8 percent and 8.3 percent of them stated that this was the case totally or partially, respectively, especially for the governmental and American Agencies. Seventeen agencies (70.8 percent) declared their work on multiannual programs (77 percent of the governmental HTA Agencies and 100 percent of the American ones). The assessments mainly addressed diagnostic procedures (85.7 percent) and pharmaceuticals (25 percent). The most common way to disseminate results is by means of paper report (91.7 percent), followed by the Internet (16.7 percent), and seminars to expert audiences (12.5 percent).Conclusions:The comparative analysis of HTA Agencies showed that governmental and American Agencies have a profound impact on the prescriptiveness of their assessment, and this could be linked to the fact that these types of Agencies work on multiannual programs. European and American HTA Agencies have many similarities in terms of type of assessment, funding, and dissemination of results.

3D-printed insoles are increasingly used for the management of foot pathologies, and the recent literature reports on various experimental studies dealing with either whole foot orthoses or pads fabricated through 3D-printing processes. In the case of diabetic foot disease, the main aim is to deliver more effective solutions with respect to the consolidated processes to reduce compressive risk forces at specific plantar foot sites. Clinical studies are, however, still limited, at least in peer-review journals. Additionally, in Italy, the manufacturing process of these medical devices has not been formally integrated yet into the list of care processes approved for reimbursement by the public healthcare service. Within the Italian DIAPASON project (DIAbetic PAtients Safe ambulatiON), a feasibility pilot study has been conducted in the territory on 21 patients with diabetic foot complications to assess the pros and cons of an innovative process. The process, which relies on in-shoe pressure measurements and on a patented 3D modeling and printing procedure, includes the prescription, design, manufacturing and testing of 3D-printed personalized insoles. The process has been tested in an ambulatory setting and showed the potential to be also implemented in community settings. In this paper, we report a case study on a single volunteer, and we describe and comment on how the whole process has been proven safe and suitable for the purpose.

A growing body of research in retinal imaging is recently considering vascular tortuosity measures or indexes, with definitions and methods mostly derived from cardiovascular research. However, retinal microvasculature has its own peculiarities that must be considered in order to produce reliable measurements. This study analyzed and compared various derived metrics (e.g., TI, TI_avg, TI*CV) across four existing computational workflows. Specifically, the implementation of the models on two critical OCT images highlighted main pitfalls of the methods, which may fail in reliably differentiating a highly tortuous image from a normal one. A tentative, encouraging approach to mitigate the issue on the same OCT exemplificative images is described in the paper, based on the suggested index TI*CV.

Background and Aim: Food quality control techniques based on process control methods are increasingly adopted in livestock production systems to fulfill increasing market's expectations toward competitiveness and issues linked to One Health pillars (environment, animal, and human health). Control Charts allow monitoring and systematic investigation of sources of variability in dairy production parameters. These parameters, however, may be affected by seasonal variations that render impractical, biased or ineffective the use statistical control charts. A possible approach to this problem is to adapt seasonal adjustment methods used for the analysis of economic and demographic seasonal time series. The aim of the present work is to evaluate a seasonal decomposition technique called X-11 on milk parameters routinely collected also in small farms (fat, protein, and lactose content, solids-not-fat, freezing point, somatic cell count, total bacterial count) and to test the efficacy of different seasonal removal methods to improve the effectiveness of statistical control charting. Method: Data collection was carried out for 3 years on routinely monitored bulk tank milk parameters of a small farm. Seasonality presence was statistically assessed on milk parameters and, for those parameters showing seasonality, control charts for individuals were applied on raw data, on X-11 seasonally adjusted data, and on data smoothed with a symmetric moving average filter. Correlation of seasonally influenced parameters with daily mean temperature was investigated. Results: Presence of seasonality in milk parameters was statistically assessed for fat, protein, and solids-non-fat components. The X-11 seasonally-adjusted control charts showed a reduced number of violations (false alarms) with respect to non-seasonally adjusted control chart (from 5 to 1 violation for fat, from 17 to 1 violation for protein, and from 9 to none violation for solids-non-fat.). This result was achieved despite stricter control chart limits: with respect to raw data charts, the interval of control chart allowed variation (UCL–LCL) was reduced by 43% for fat, by 33.1% for protein, and by 14.3% for solids-not-fat. Conclusions: X-11 deseasonalization of routinely collected milk parameters was found to be an effective method to improve control chart application effectiveness in farms and milk collecting centers.