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Occurrence level comparison of catastrophic failures due to radiation effects on electronic components or collision with space debris are studied in two types of satellites: cubesats and microsats. Low Earth Orbit (LEO) case studies are proposed, and the level of catastrophic failure occurrence is quantified for the same mission duration. The variation in the occurrence of failures is studied and there is a determination of which is more likely. Emphasis is placed on examining how an increase in space debris would affect the reliability of future space missions.

Key Points Advances in treatment have increased the number of childhood cancer survivors with late-occurring, treatment-related cardiovascular complications Treatment-induced cardiovascular events associated with chemotherapy and radiotherapy include cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea, and exercise intolerance The likelihood that subclinical damage will progress to clinically important events emphasizes the importance of reducing or eliminating this early damage Protective strategies that have been partially tested include administering cardioprotective agents, using less-toxic anthracycline derivatives and correcting therapy-related endocrinopathies that affect cardiovascular disease development Traditional cardiovascular risk factors, in addition to factors directly related to cancer treatments, can further increase the risk of cardiovascular complications in survivors Cancer treatment protocols should be refined to minimize cardiovascular and other adverse effects while maintaining acceptable cancer treatment response rates In this Review, the authors describe the pathophysiological effects of chemotherapy and radiotherapy that affect the heart and treatment-related cardiovascular effects in children with cancer. They argue that 5-year event-free oncological survival is no longer the paradigm of successful treatment of childhood cancer; instead overall quality of life is and maximizing oncological efficacy while minimizing toxicity and late-effects should be the ultimate goal. Treatment advances and higher participation rates in clinical trials have rapidly increased the number of survivors of childhood cancer. However, chemotherapy and radiation treatments are cardiotoxic and can cause cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea and exercise intolerance later in life. These cardiotoxic effects are often progressive and irreversible, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Medical interventions, such as angiotensin-converting enzyme inhibitors, β-blockers, and growth hormone therapy, might be used to treat cardiotoxicity in childhood cancer survivors. Preventative strategies should include the use of dexrazoxane, which provides cardioprotection without reducing the oncological efficacy of doxorubicin chemotherapy; less-toxic anthracycline derivatives and the use of antioxidant nutritional supplements might also be beneficial. Continuous-infusion doxorubicin provides no benefit over bolus infusion in children. Identifying patient-related (for example, obesity and hypertension) and drug-related (for example, cumulative dose) risk factors for cardiotoxicity could help tailor treatments to individual patients. However, all survivors of childhood cancer are at increased risk of cardiotoxicity, suggesting that survivor screening recommendations for assessment of global risk of premature cardiovascular disease should apply to all survivors. Optimal, evidence-based monitoring strategies and multiagent preventative treatments still need to be identified.

IntroductionAmyotrophic lateral sclerosis (ALS), the most common disease within motor neuron diseases (MND), and frontotemporal dementia (FTD) belong to a broad spectrum of neurodegenerative diseases that are sometimes clinically overlapping.ObjectivesThe aim of the description of this case report is to sensitize professionals to this type of presentation and encourage the investigation of signs and symptoms of motor decline in patients with suspected FTD.MethodsResearch in the patient’s clinical process. Framing the clinical case in the current literature, searching the terms “frontotemporal dementia” and “amyotrophic lateral sclerosis” in the Pubmed database.ResultsA 71-year-old patient, followed in psychiatry for several years for Dysthymic Disorder. At the end of 2020, he presented cognitive and behavioral changes, with rapid progression, with a marked loss of functionality, compatible with dementia. In 2021, it was noticed a motor decline, which progressively worsened. In this sense, an electromyographic study of the limbs was performed with an abnormal result, compatible with a diagnosis of Motor Neuron Disease.ConclusionsA significant overlap of these two disorders has been observed clinically. Thus, the presentation of a patient with dementia, specifically suspected of having FTD, should ring the bell to the presence of signs and symptoms of motor impairment.Several studies have been carried out in order to understand the relationship between these entities, and the discussion remains whether their presentation together constitutes or not a form of phenotypic presentation of ALS.Disclosure of InterestNone Declared

Either the triggering of large earthquakes on a fault hosting aseismic slip or the triggering of slow slip events (SSE) by passing seismic waves involve seismological questions with important hazard implications. Just a few observations plausibly suggest that such interactions actually happen in nature. In this study we show that three recent devastating earthquakes in Mexico are likely related to SSEs, describing a cascade of events interacting with each other on a regional scale via quasi-static and/or dynamic perturbations across the states of Guerrero and Oaxaca. Such interaction seems to be conditioned by the transient memory of Earth materials subject to the “traumatic” stress produced by seismic waves of the great 2017 (Mw8.2) Tehuantepec earthquake, which strongly disturbed the SSE cycles over a 650 km long segment of the subduction plate interface. Our results imply that seismic hazard in large populated areas is a short-term evolving function of seismotectonic processes that are often observable. This study shows how seismic and aseismic events are related in Mexico between 2017 and 2019. Based on a series of observations and models, the study suggests that the Mw 8.2 intraslab earthquake of 8 September 2017 severely altered the mechanical properties of the plate interface, facilitating the interaction between the events and disrupting the slow slip cycles at a regional scale.

Over the past decade the phosphoinositide-3 kinase (PI3K) signaling pathway emerged as an important player for tumor initiation and growth and, currently, PI3K inhibition constitutes a promising therapeutic approach for solid and hematological tumors. Beside its role in tumor cell evolution, PI3K signaling also provides integral functions for noncancerous cells that reside in healthy tissues surrounding the tumor, also referred as tumor microenvironment (TME). This review will address how PI3K signaling participates to the tumorigenic process and discuss the interaction between tumor cells and the surrounding TME, with particular focus on the role of PI3Ks in tumor-associated immune responses, tumor angiogenesis and metastasis formation.

Atopic dermatitis (AD) is a common, chronic, relapsing-remitting inflammatory disease that can be challenging to treat. Patients with mild disease are usually managed well with good skin care practices including moisturization and appropriate bathing along with intermittent use of topical therapies such as topical corticosteroids and/or topical calcineurin inhibitors during flares. Patients with frequent flares may benefit from proactive application of topical therapies twice a week to the most troublesome areas. Patients with severe disease often present significant treatment challenges. Systemic therapies are usually required for severe AD but have varying degrees of success and can be associated with side-effect profiles that require counseling and close monitoring. Phototherapy has been shown to have success in treating moderate-to-severe AD, but several factors can limit its utility and efficacy including cost and access. New therapies are in development targeting specific pathways relevant for AD. Dupilumab was the first biologic treatment approved in North America, Europe, and Japan for adults with moderate-to-severe AD. Although this treatment can lead to rapid improvement in the majority of patients, there are inadequate responders. In this review, we discuss the clinical challenges and treatment options for moderate-to-severe refractory AD.

Background:Fibromyalgia (FM) is one of the most common causes of chronic widespread pain. Although pain is the most distinctive feature of this syndrome, FM is characterized by a complex polysymptomatology that also comprises fatigue, sleep disturbances and other functional symptoms that negatively affect the overall quality of life. Since FM can negatively affect personal well-being, self-image and interpersonal relationship, it can also impact sexual functioning and pleasure. When interrogated regarding sexuality, female FM patients answer that it is important for their quality of life and, for the majority of them, it appears as a physical, psychological, emotional and relational need. For these reason, women require support and understanding from both their partners and health care professionals. In this context, the availability of a simple and rapidly administered questionnaire, such as the Qualisex, for the evaluation of sexual disfunction on these patients might be considered an acceptable method of communication of this sensitive issue.Objectives:The aim of this study was to evaluate sexual disfunctions in a large cohort of FM women through Qualisex questionnaire, which has been originally created for French patients with rheumatoid arthritis and recently adapted and validated to Italian language for FM patients.Methods:In this cross-sectional study, consecutive women with a diagnosis of FM (2016 ACR criteria) referring to our out-patients Fibromyalgia Clinic were asked to answer an anonymous online survey, including demographic characteristics, medical and pharmacological history, Hospital Anxiety and Depression Scale (HADS) and Qualisex questionnaire for sexual dysfunction.Results:The cohort enrolled in this study was composed by 489 FM women, median age 50. The results of the univariate analysis showed a worse sexual functioning in women with lower educational level, housekeepers and retired patients but also in women who referred a concomitant diagnosis of chronic pelvic pathology or a psychiatric disorder. Among women who were in an active relationship, the referred sexual understanding with the partner was inversely associated with sexual functioning. Finally, the consumption of drugs known to be associated with a reduction of sexual desire resulted significantly associated with a worse sexual functioning (Table 1). The multivariate linear model showed a significant influence of the presence of a partner in women’s life, the referred sexual understanding and the use of drugs associated with a reduction of sexual desire on women’s quality of life (Table 2).Conclusion:Qualisex questionnaire represents a good test to detect the impaired sexuality in FM female patients, to establish a more correct intervention, pharmacological, psychotherapeutic (single or couple) and supportive, reducing the destructive circle that FM and poor sexual quality determine. Different aspects contribute to sexual dysfunction, with an important impact of FM on sexual quality and consequently a worsening of FM symptoms.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS). NUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14. 98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD. The intervention strategy was the assignment of a LGIMD or a control diet. The main outcome measure was NAFLD score, defined by LUS. After randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed. LGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.

Background A population health approach to depression screening using patient portals may be a promising strategy to proactively engage and identify patients with depression. Objective To determine whether a population health approach to depression screening is more effective than screening during clinic appointments alone for identifying patients with depression. Design A pragmatic clinical trial at an adult outpatient internal medicine clinic at an urban, academic, tertiary care center. Patients Eligible patients ( n = 2713) were adults due for depression screening with active portal accounts. Patients with documented depression or bipolar disorder and those who had been screened in the year prior to the study were excluded. Intervention Patients were randomly assigned to usual ( n = 1372) or population healthcare ( n = 1341). For usual care, patients were screened by medical assistants during clinic appointments. Population healthcare patients were sent letters through the portal inviting them to fill out an online screener regardless of whether they had a scheduled appointment. The same screening tool, the Computerized Adaptive Test for Mental Health (CAT-MH™), was used for clinic- and portal-based screening. Main Measures The primary outcome was the depression screening rate. Key Results The depression screening rate in the population healthcare arm was higher than that in the usual care arm (43% ( n = 578) vs. 33% ( n = 459), p < 0.0001). The rate of positive screens was also higher in the population healthcare arm compared to that in the usual care (10% ( n = 58) vs. 4% ( n = 17), p < 0.001). Conclusion Findings suggest depression screening via a portal as part of a population health approach can increase screening and case identification, compared to usual care. Trial Registration ClinicalTrials.gov Identifier: NCT03832283

The province of Formosa, Argentina, is endemic for leprosy. In the present paper, we assessed the trend (T, 2002-2016 time series) and the forecast for 2022 of new case detection rate (NCDR) and determined the spatial distribution of new cases detected (NCD) of leprosy. This is a descriptive observational study of 713 NCD of leprosy from provincial medical records between January 2002 and December 2016. The whole dataset from the provincial medical record was used to independently estimate the NCDR trends of the general population, age groups, sexes and Departments. This same database was used to estimate the NCDR forecast of the general population for 2022, applying a dynamic linear model with a local linear trend, using the MCMC algorithm. The NCDR was higher in men (p<0.05), increased with age (0.20, 8.17, 21.04, and 29.49 for the 0-14, 15-44, 45-64 and over 65-year-old age groups, respectively; p<0.05) and showed a downward trend (negative values) of estimated slopes for the whole province and each Department. Bermejo Department showed the highest (T:-1.02, 95%CI: [-1.42, -0.66]) and Patiño the lowest decreasing trend (T:-0.45, 95%CI: [-0.74, -0.11]). The NCDR trend for both sexes was similar (T:-0.55, 95%CI: [-0.64, -0.46]), and age groups showed a decreasing trend (S15-44:-103, S45-64:-81, S>65:-61, p<0.05), except for the 0-14 age group (S:-3, p>0.05), which showed no trend. Forecasts predicted that leprosy will not be eliminated by 2022 (3.64, 95%CI: [1.22, 10.25]). Our results highlight the status of leprosy in Formosa and provide information to the provincial public health authorities on high-risk populations, stressing the importance of timely detection of new cases for further elimination of the disease in the province.