In the last years, the understanding of the pathologic mechanisms of asthma and atopic dermatitis, both characterized by allergic inflammation, has greatly improved. However, it is evident that both diseases present with high heterogeneity, which complicates the diagnosis and the therapeutic approach of the patients. Moreover, some of the currently available strategies to treat asthma and atopic dermatitis are still mostly controlling the symptoms, but not to lead towards full healing, thus having these two diseases labelled as unmet clinical needs by WHO. Therefore, the "one-size-fits-all" strategy is outdated for asthma and atopic dermatitis, and there is the need of better methods to clearly diagnose the disease and tailor the therapy according to the specific symptomatology. In this regard, the use of biomarkers has been advanced in order to characterize both diseases according to their clinical signs and to facilitate the subsequent treatment. Despite the advancements made in this regard, there is still need for better and more sensitive biomarkers and for less invasive sampling methodologies, with the aim to diagnose specifically each manifestation of asthma and atopic dermatitis and to provide the best treatment with the least suffering for the patients.
It is commonly agreed that the Iron Age I–II transition was gradual and that processes of social complexity initiated in the Iron Age I simply matured in the Iron Age II. The emergence of Levantine kingdoms – whether the so-called “United Monarchy” (i.e., the highland polity) or other polities – was therefore seen as an outcome of this gradual maturation, even if the date of their emergence is hotly debated. The present paper challenges both the perceived gradual nature of Iron Age complexity and the dated understanding of state formation processes that lies behind the common scholarly reconstructions of Iron Age political developments. Instead, the paper shows that the Iron Age I–II transition was troubled and was accompanied by drastic changes in many parameters, whether settlement patterns, settlement forms, or various material traits. Acknowledging these transformations is therefore the first step in understanding the process through which local kingdoms emerged.
La Meguilat Esther (le Rouleau d’Esther) est un texte de quelques pages, dix chapitres très courts (neuf chapitres dans les Bibles chrétiennes où le dixième chapitre est inclus dans le neuvième). Sa lecture rituelle pendant la fête de Pourim (14 ou 15 Adar, selon l’endroit où elle se célèbre)1 peut prendre moins d’une demi-heure. Or, ce texte court contient des thèmes qui sont toujours d’une brûlante actualité. Le Rouleau d’Esther est un « grand miroir du monde », une œuvre qui, au-delà de l’histoire spécifique qu’elle raconte, s’ouvre vers l’universel.
This article examines policies adopted by the League of Nations’ Advisory Committee on Traffic in Women and Children (CTW) toward Europe’s Middle Eastern and South Asian colonies. It argues, first, that, under the pretext of protecting women from traffic, the CTW provided colonial powers with justification to monitor and restrict the international mobility of women traveling alone. Second, it demonstrates that the League adopted colonial racial assumptions about the sexuality of colonized women, and thus perceived them as less deserving of protection from forced prostitution. Third, it argues that the CTW thus helped perpetuate and justify differential treatment of foreign and indigenous women in Europe’s overseas colonies. The article relies on the CTW’s protocols, on the traveling commissions it initiated, on country reports to the League, and on protocols of the conferences it initiated dedicated to traffic in women in the “East.”
Criticism of the effects of the international investment regime on state regulatory space (SRS) is on the rise, much of it focusing on the impact of binding arbitration. Specifically, the investor-state dispute settlement (ISDS) provisions found in most bilateral investment treaties (BITs) and other investment agreements have a profound effect on the balance between investor rights and state regulatory space (SRS), raising a debate on their legitimacy. We explore how states perceive the legitimacy of ISDS provisions in light of their experiences with the investment regime through the lens of BIT renegotiation and termination. Renegotiation provides an empirical window for understanding how dissatisfaction with BITs translates into concrete decisions by governments to recalibrate their treaty obligations, perhaps rendering them more legitimate. Based on an original data set comprised of 161 renegotiated agreements, we find that states have not made a systematic effort over the years to recalibrate their BITs for the purpose of preserving more regulatory space. In fact, most renegotiations either leave ISDS provisions unchanged or render them more investor-friendly. However, recent renegotiations show a greater tendency to limit investor protections in ISDS provisions.
Mice lacking the functional cystinosin gene (Ctns(-/-)), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns(-/-) mice. We treated 12-month-old Ctns(-/-) mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns(-/-) mice. PLA attenuated adipose tissue browning in Ctns(-/-) mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns(-/-) mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns(-/-) mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns(-/-) mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.
While many natural and artificial surfaces may appear dry, they are in fact covered by thin liquid films and microdroplets invisible to the naked eye known as microscopic surface wetness (MSW). Central to the formation and the retention of MSW are the deliquescent properties of hygroscopic salts that prevent complete drying of wet surfaces or that drive the absorption of water until dissolution when the relative humidity is above a salt-specific level. As salts are ubiquitous, MSW occurs in many microbial habitats, such as soil, rocks, plant leaf, and root surfaces, the built environment, and human and animal skin. While key properties of MSW, including very high salinity and segregation into droplets, greatly affect microbial life therein, it has been scarcely studied, and systematic studies are only in their beginnings. Based on recent findings, we propose that the harsh micro-environment that MSW imposes, which is very different from bulk liquid, affects key aspects of bacterial ecology including survival traits, antibiotic response, competition, motility, communication, and exchange of genetic material. Further research is required to uncover the fundamental principles that govern microbial life and ecology in MSW. Such research will require multidisciplinary science cutting across biology, physics, and chemistry, while incorporating approaches from microbiology, genomics, microscopy, and computational modeling. The results of such research will be critical to understand microbial ecology in vast terrestrial habitats, affecting global biogeochemical cycles, as well as plant, animal, and human health.
Background Although several studies have demonstrated the associations between lifetime cumulative adversity and late-life physical health, many of them were conducted at a single time point and examined events that occurred in childhood only. Less is known about the effect of lifelong adversity on the aging process over time. This study aimed to investigate the impact of cumulative adversity on the accelerated deterioration in health over time - mobility limitation and self-rated state of health in old age. Methods This study provides a 14-year, 6-time-point follow-up on a representative sample of Europeans using the SHARE Project - longitudinal survey panel. The sample included a total of 7195 respondents aged 65 and older from nine countries in Europe. The outcome measurements were the number of mobility limitations and self-rated health – trajectories along 6 measurements. The independent variable was Lifetime Cumulative Adversity, and the analyses included also control variables – age, gender, socioeconomic status, depression, and country. Results Time-based Latent Growth Curve Modeling has demonstrated that the effects of Lifetime Cumulative Adversity were significant on both health measures, by means of the intercepts and the slopes: Greater experience of adversities correlated with a higher physical health impairment at baseline and a higher decline along time. The effects of self-rated health were weaker than the effects of mobility limitations. Conclusions Given that the populations of numerous countries are rapidly aging, understanding the risk factors associated with health deterioration is important, especially for policymakers and medical health care experts, to raise awareness of the relationship between lifelong adversity and health decline and to build preventive interventions to deal with these consequences.
