Here, we detail the cellular function of tumor suppressors essential in DNA damage repair pathways, present the mechanisms of action of inhibitors used to create synthetic lethality in BRCA carriers, and review the major molecular sources of drug resistance. Finally, we present examples of the many strategies being developed to circumvent drug resistance.
  To obtain public support for the active disinvestment (i.e. policy decision to stop reimbursement) of healthcare interventions, it is important to have insight in what the public thinks about disinvestment and which considerations they find relevant in this context. Currently, evidence on relevant considerations in the disinvestment context is limited. Therefore, this study aimed to explore the societal views in the Netherlands on the active disinvestment of healthcare interventions and obtain insight into the considerations that are relevant for those holding the different views.
 
  A Q-methodology study was conducted among a purposively selected sample of citizens (n=43). Data were collected in June and July 2019. Participants individually ranked a set of 43 statements broadly covering the issues that participants could consider relevant in the disinvestment context, from 'least agree' to 'most agree'. Qualitative feedback on the statement ranking was collected from each participant using a questionnaire. , and can help policymakers to change their approach to disinvestment to increase public support.
 Insight in the distinct viewpoints identified in this study contributes to a better understanding of why it has been considered difficult to obtain public support for disinvestment of healthcare interventions, and can help policymakers to change their approach to disinvestment to increase public support.Income inequality and obesity are both widespread socioeconomic issues, particularly salient in middle-income countries. This article seeks to detect the relationship between local income inequality and excess weight in Mexico, using robust municipal income inequality measures generated through small area estimation method and instrumental variable multilevel estimations. Our results emphasize a negative impact of municipal income inequality on individual bodyweight, especially for women. We also explore the potential channels through which income inequality may decrease bodyweight. Three-stage least squares estimations highlight that the social capital pathway, the public policy pathway and the psychological pathway help to explain the negative effect of inequality on excess weight. Our results are fairly robust to alternative inequality measures and nutritional indicators.
  In a short time, the COVID-19 pandemic turned into a global emergency.  https://www.selleckchem.com/products/Pomalidomide(CC-4047).html  The fear of becoming infected and the lockdown measures have drastically changed people's daily routine. The aim of this study is to establish the psychological impact that the COVID-19 pandemic is entailing, particularly with regards to levels of stress, anxiety and depression, and to the risks of developing Post-Traumatic Stress Disorder (PTSD).
 
  The study, carried out with a sample of 1612 subjects distributed in seven countries (Australia, China, Ecuador, Iran, Italy, Norway and the United States), allowed us to collect information about the psychological impact of COVID-19.
 
  The findings of this study show that the levels of stress, depression and anxiety, as well as the risks of PTSD, are higher than average in over half of the considered sample. The severity of these disorders significantly depends on gender, type of outdoor activities, characteristics of their homes, eventual presence of infected acquaintances, time dedicated to looking for related information (in the news and social networks), type of source information and, in part, to the level of education and income.
 
  We conclude that COVID-19 has a very strong psychological impact on the global population. This appears to be linked to the coping strategies adopted, level of mindful awareness, socio-demographic variables, people's habits and the way individuals use means of communication and information.
 We conclude that COVID-19 has a very strong psychological impact on the global population. This appears to be linked to the coping strategies adopted, level of mindful awareness, socio-demographic variables, people's habits and the way individuals use means of communication and information.
  A number of patient-reported outcomes (PROs) have been developed but insufficient attention has been devoted to the assessment of their clinimetric properties. Clinimetrics, the science of clinical measurements, has been considered an emerging approach for evaluating reliability and validity of PROs. This is the first study using clinimetric principles to compare the construct and criterion validity of the Major Depression Inventory (MDI), the Beck Depression Inventory-II (BDI-II), the World Health Organization Well-Being Index (WHO-5), three of the most widely used PROs for the assessment of depression.
 
  Construct validity was evaluated via Item Response Theory (IRT) models (i.e., combining Rasch and Mokken analyses). Using the ICD-10 diagnostic algorithm for any depression as the gold standard, Receiver Operating Characteristic (ROC) curves were performed to examine the criterion validity of PROs.
 
  One hundred healthy subjects (73% females, 32.6±10.5 years) participated in the study, giving a response rate of 90.1%. When using IRT analyses, MDI and WHO-5 were found to be reliable and unidimensional, while BDI-II showed lack of unidimensionality. ROC analyses supported the diagnostic accuracy of MDI and the screening properties of WHO-5.
 
  The main limitations of the present study are that healthy subjects were assessed only via only self-reported measures and a cross-sectional design was used.
 
  WHO-5 and MDI outperformed BDI-II in terms of construct and criterion validity. WHO-5 should be considered when screening for depression, while MDI should be used as a valid diagnostic instrument and as a unidimensional measure to assess depression severity.
 WHO-5 and MDI outperformed BDI-II in terms of construct and criterion validity. WHO-5 should be considered when screening for depression, while MDI should be used as a valid diagnostic instrument and as a unidimensional measure to assess depression severity.