Ponesimod to treat multiple sclerosis

Ponesimod (ACT-128800) is a directly bioavailable, rapidly reversible sphingosine-1-phosphate (S1P) receptor modulator, highly selective for the subtype 1 (S1P1 receptor). It acts by blocking the egress of lymphocytes from the lymphoid organs, thus limiting the entry of autoreactive cells into the central nervous system. Unlike fingolimod, ponesimod does not require monitoring of the first dose, thanks to a 14-day uptitration regimen, which markedly reduces the incidence of cardiodynamic effects related to the initiation of therapy. Results from the OPTIMUM phase III trial demonstrated the superiority of ponesimod over teriflunomide on disease activity markers, without unexpected safety concerns. Furthermore, the drug is eliminated within 1 week of discontinuation, allowing for the reversibility of its effects. Ponesimod was recently approved in both the U.S. and E.U. for the treatment of relapsing forms of multiple sclerosis. This review summarizes the pharmacological characteristics of ponesimod and the main studies that led to its approval

Alopecia universalis occurring after alemtuzumab treatment for multiple sclerosis. A two-year follow-up of two patients

Alopecia Universalis (AU) is the most severe form of Alopecia Areata and is caused by cytotoxic T-cells reacting with follicular autoantigens, producing complete loss of scalp and body hair. Alemtuzumab is a highly efficacious monoclonal antibody used in the treatment of Multiple Sclerosis (MS), but it causes secondary autoimmunity in up to 40% of patients. Many factors are believed to contribute to this process, but pathogenic mechanisms are not well clear. To date, three cases of AU after treatment with Alemtuzumab have been reported. In this paper we report the cases of two patients who developed AU 12 months after the second cycle of Alemtuzumab, with a review of the literature. One year after the end of the second cycle, two female patients in their thirties experienced complete hair loss. The first case was temporally associated with a significant drop in vitamin D (VD) levels. The second case was accompanied by joint swelling. Both patients had thyroid alterations and showed no hair regrowth after a 2-year follow-up. AU must be considered among the secondary autoimmune manifestations of Alemtuzumab treatment. We emphasize the need for appropriate patient screening and thorough clinical surveillance for factors predisposing patients to secondary autoimmunity

The culture of the project in view of new synergies for the (r)evolution of the healthcare sector

The contemporary era, defined by Schwad (2015) as the "Fourth Industrial Revolution '' is the era that is outlined on the theme of major innovations and a growth of technologies of exponential type. At the social level, we are witnessing a progressive aging of the population, aging or rejuvenation, as some would argue (OECD, 2020). Technological growth and innovation is evolving the standards of health in which the population falls, is reshaping life expectancy and with it, also the age of seniority. Technological growth and population increase bring with them clear concerns about health management: we will face an increasing number of chronic diseases, and the demand for higher standards of personalized care, precision medicine, regenerative medicine, all of which will increase demands and put great stress on our health systems. The two years marked by the Covid-19 pandemic have already provided us with a demonstration of the consequences associated with extremes of demand for care. The Fourth Industrial Revolution, which holds the advent of Information Technologies and Artificial Intelligence, tells us of a future that will see an increasing interaction between humans, machines and computational intelligences, to alleviate us and empower our existence. This era will also speak about the increasingly imperative need to assert in the design treatment the component of acceptance and exaltation of human values in order to mitigate the possible outcomes of human alienation in the face of indefinable technological availability. Also in this case we can refer to the examples of degenerations resulting from the Covid-19 pandemic, with generalizing crisis phenomena and dismissive visions from the surrounding reality, such as the No-Vax, movements or other phenomena of technological alienation as in the case of the increase in the percentage of adolescents now in a cycle of self-induced isolation. Considering the areas of light and shadow of the challenges of our future, it is clear how we will need the increasingly synergistic action of the various disciplines of human knowledge, in order to arrive at the delineation of a correct exploitation of human values. With regard to this, the discipline of design, understood as that discipline useful to generate with efficiency, a bridge between technological innovation and human interaction, will be fundamental as able to bring positive and empathic elements to the design, to derive a generalized improvement in the quality of life, and in the case of healthcare, of care. Our research highlights the etymologically new figure of the "Medical Designer" and asserts in the design process new functions on the theme of medical devices: among them, the theme of autonomy and automation. In full response to the "trend" and aimed at assimilating to the already established potential of industries, they will be crucial elements of designs and investments of new devices. The research that derives from it has had practical implications arriving at the definition of forms of care that subjugate in a single device both the function of reading parameters, and the function of administration of care

Temperature and respiration affect the growth and stress resistance of Lactobacillus plantarum C17

Aims: The aim of the study is to gain further insight on the respiratory behaviour of Lactobacillus plantarum and its consequences on stress tolerance. Methods and Results: We investigated the effect of temperature and respiration on the growth and stress (heat, oxidative, freezing, freeze-drying) response of Lact. plantarum C17 during batch cultivations. Temperature as well as respiration clearly affected the physiological state of cells, and generally, cultures grown under respiratory conditions exhibited improved tolerance of some stresses (heat, oxidative, freezing) compared to those obtained in anaerobiosis. Our results revealed that the activities in cell-free extracts of the main enzymes related to aerobic metabolism, POX (pyruvate oxidase) and NPR (NADH peroxidase), were significantly affected by temperature. POX was completely inhibited at 37°C, while the activity of NPR slightly increased at 25°C, indicating that in Lact. plantarum, the temperature of growth may be involved in the activation and modulation of aerobic/respiratory metabolism. Conclusions: We confirmed that respiration confers robustness to Lact. plantarum cells, allowing a greater stress tolerance and advantages in the production of starter and probiotic cultures. Significance and Impact of the Study: This is the first study on respiratory metabolism on a strain other than the model strains WCFS1; novel information on the role of temperature in the modulation of aerobic/ respiratory metabolism in Lact. plantarum is presented

Occurrence of gas phase ammonia in the area of Beijing (China)

The atmospheric concentrations of gaseous ammonia have been measured during two field campaigns in the winter and in the summer of 2007 at Beijing (China). These measurements were carried out by means of diffusion annular denuders coated with phosphorous acid. The results were discussed from the standpoint of temporal and diurnal variations and meteorological effects. The daily average NH<sub>3</sub> concentrations were in the range of 0.20–44.38 μg/m<sup>3</sup> and showed regular temporal variations with higher concentrations during summer and with lower during winter. The temporal trends seemed to be largely affected by air temperature because of agricultural sources. No diurnal variability was observed for gaseous NH<sub>3</sub> levels in both winter and summer seasons. The highest ammonia value of 105.67 μg/m<sup>3</sup> was measured in the early morning during the summer period when stable atmospheric conditions occurred. The diurnal winter and summer trends of ammonia showed a weak dependence on the air temperature and they were affected nearly by wind direction suggesting regional and local source influences. Ammonia was also correlated with the atmospheric mixing in the boundary layer, and, with NO<sub>x</sub>, CO and PM<sub>2.5</sub> air concentrations supporting the hypothesis that the traffic may be also an important source of ammonia in Beijing

Coronary Artery Disease: A Study on the Joint Role of Birth Weight, Adenosine Deaminase, and Gender

An inverse relationship between birth weight and coronary artery diseases is well documented but it remains unclear which exposure in early life might underlie such association. Recently it has been reported an association between adenosine deaminase genetic polymorphism and coronary artery diseases. Gender differences in the degree of this association have been also observed. These observations prompted us to study the possible joint effects of BW, ADA, and gender on the susceptibility to coronary artery diseases. 222 subjects admitted to hospital for nonfatal coronary artery diseases, and 762 healthy consecutive newborns were studied. ADA genotypes were determined by DNA analysis. A highly significant complex relationship has emerged among ADA, birth weight, and gender concerning their role on susceptibility to coronary artery diseases in adult life. Odds ratio analysis suggests that low birth weight is more important in females than in males. ADA∗2 allele appears protective in males, while in females such effect is obscured by birth weight

Seasonal variation of antiretroviral drug exposure during the year: The experience of 10 years of therapeutic drug monitoring

Although studies show an annual trend for immunosuppressive drugs, particularly during different seasons, no data are available for antiretroviral drugs exposures in different periods of the year. For this reason, the aim of this study was to investigate an association between seasonality and antiretroviral drugs plasma concentrations. Antiretroviral drugs exposures were measured with liquid chromatography validated methods. A total of 4148 human samples were analysed. Lopinavir, etravirine and maraviroc levels showed seasonal fluctuation. In detail, maraviroc and etravirine concentrations decreased further in summer than in winter. In contrast, lopinavir concentrations had an opposite trend, increasing more in summer than in winter. The etravirine efficacy cut-off value of 300 ng/mL seems to be affected by seasonality: 77.1% and 22.9% of samples achieved this therapeutic target, respectively, in winter and summer, whereas 30% in winter and 70% in summer did not reach this value. Finally, age over 50 years and summer remained in the final multivariate regression model as predictors of the etravirine efficacy cut-off. This study highlights the seasonal variation in antiretroviral drugs plasma concentrations during the year, leading to a better understanding of inter-individual variability in drug exposures. Studies are required in order to confirm these data, clarifying which aspects may be involved