Human Cutaneous Melanomas Lacking MITF and Melanocyte Differentiation Antigens Express a Functional Axl Receptor Kinase

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A case of twins affected by psoriasis, psoriatic arthritis and autism: five years of efficacious and safe treatment with Secukinumab

We report the case of two monozygotic twins, which were diagnosed as ASDs and psoriasis at the age of 4 years. At the time of diagnosis, the first of the homozygote twins (“twin A"—80 kg, BMI 35), had a severe psoriasis affecting the entire body surface, with a Psoriasis Area Severity Index score (PASI) 35; the second twin (“twin B”—78 kg, BMI 34) had a less severe form (PASI 17), with a delayed onset (2 months later). Their medical history revealed that they had both previously been treated with topical therapy (corticosteroid and calcipotriol) followed by methotrexate 15 mg/week, for approximal 1 year, experiencing only a partial response. When assessed at our unit, they were 31-year-old men, with a severe psoriasis (respectively PASI 25 and PASI 20) and symptoms of symmetric peripheral polyarthritis, rheumatoid factor negative. Before starting biological therapy, routinary laboratory tests, physical examination, an X-ray and a neuropsychiatric counseling were performed

The emergence of Exercise Addiction, Body Dysmorphic Disorder, and other image-related psychopathological correlates in fitness settings: A cross sectional study.

INTRODUCTION: In a society that perpetuates the strive for a perfect appearance, a fit body has become synonymous with success, but simultaneously hard to achieve. This represents a fertile ground for the development of Exercise Addiction (EA) alongside other disorders, such as Body Dysmorphic Disorder (BDD). This study aims to explore the diffusion of EA in fitness settings in the United Kingdom, Italy, Netherlands, Hungary and the previously unexplored association with appearance anxiety, BDD, self-esteem and the use of fitness supplements. METHODS: A large cross-sectional sample (N = 1711) was surveyed in fitness settings using the Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI) and Rosenberg's Self Esteem Scale (RSE) in addition to questions surrounding the use of fitness supplements. RESULTS: Compulsive exercise, appearance anxiety and low self-esteem were present in this sample according to the psychometric measures used (EAI, AAI, RSE). 11.7% scored over the cut off for EA, with alarming peaks in the Netherlands (20.9%) and the United Kingdom (16.1%). 38.5% were found at risk of BDD, mainly female (47.2%). 39.8% used fitness enhancing supplements without medical consultation (95.5%). This cohort of supplement users scored higher in both EAI and AAI. The logistic regression model revealed a strong association between the consumption of sport products and the level of EA across the sample with an odds ratio (OR) of 3.03. Other co-variable factors among female were appearance anxiety (AAI; OR 1.59) and to a lesser extent self-esteem (RSE) (OR 1.08). CONCLUSIONS: This study identified a high risk of EA, appearance anxiety and BDD amongst a cohort of gym users internationally. The previously-unexplored association between these disorders and the unsupervised use of a variety of fitness products, including illicit drugs, highlights the need for informed and integrated responses targeting such vulnerable individuals

An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Exploring the Relationship Between Mental Well-Being, Exercise Routines, and the Intake of Image and Performance Enhancing Drugs During the Coronavirus Disease 2019 Pandemic : A Comparison Across Sport Disciplines

Funding Information: This research was supported by the European Network for the Problematic Use of the Internet, the COST European Cooperation in Science and Technology, a Grant-in-Aid for Scientific Research on Innovative Areas (Ministry of Education, Culture Sports, Science and Technology, Japan, 16H06400, 16H06402, 16H06395, and 16H06397), a Grant-in-Aid for Scientific Research (A) (Japan Society for The Promotion of Science, 19H00518), a Grant-in-Aid by the Smoking Research Foundation, and Grant-in-Aid for Young Scientists (20K13821), the Hungarian National Research, Development and Innovation Office (KKP126835; ELTE Thematic Excellence Programme 2020, KP2020-IKA-05). Publisher Copyright: © Copyright © 2021 Shibata, Burkauskas, Dores, Kobayashi, Yoshimura, Simonato, De Luca, Cicconcelli, Giorgetti, Carvalho, Barbosa, Monteiro, Murai, Gómez-Martínez, Demetrovics, Ábel, Szabo, Ventola, Arroyo-Anlló, Santos-Labrador, Griskova-Bulanova, Pranckeviciene, Bersani, Fujiwara and Corazza.Introduction: Physical distancing under the coronavirus disease 2019 (COVID-19) pandemic had a significant impact on lifestyles, including exercise routines. In this study, we examined the relationship between mental health and addictive behaviors, such as excessive exercise and the use of image and performance enhancing drugs (IPEDs) across 12 sport disciplines. Materials and methods: A large cross-sectional sample of the adult population (N = 2,295) was surveyed. The mean age was 33.09 (SD = 11.40). The number of male participants was 668 (30.0%). The use of IPEDs was assessed in conjunction with psychometric measures such as the Exercise Addiction Inventory (EAI) and the Appearance Anxiety Inventory (AAI). The participants were grouped into activity group (AG) and non-activity group (NAG) according to the presence or absence of their exercise habits. The results were compared between these groups, as well as across sport disciplines, while taking into account the relationship between different psychological measures and IPEDs consumption. Results: The frequency of IPEDs use was higher among AG (34.6%) than NAG (14.6%), although AG participants reported less history of addictions (7.1%) than NAG (11.8%). The logistic regression analysis revealed that scores equal to or above cutoff points, in both the EAI and AAI, predicted the IPEDs use. Regarding the differences across the various sport disciplines, those who were involved in practicing Weight Lifting and Cross Fit were found to be more at risk of excessive exercising and more inclined to use a wide range of IPEDs. Conclusions: Although exercise could help to increase well-being and prevent addictions during the COVID-19 pandemic, our results show that those in the AG are particularly vulnerable to excessive IPEDs use. Sport disciplines associated with higher EAI and AAI scores have also shown a higher tendency to excessive IPEDs use. Furthermore, the factor of having above the cutoff scores in EAI or AAI in each sport could indicate larger IPEDs consumption regardless of the discipline. In light of the current findings, it is necessary to better define the “non-excessive” levels of exercise in various sport disciplines and an adequate intake of IPEDs to ensure the safety and well-being of people during a pandemic.Peer reviewe

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work