NAD+-metabolizing ecto-enzymes shape tumor–host interactions: The chronic lymphocytic leukemia model

AbstractNicotinamide adenine dinucleotide (NAD+) is an essential co-enzyme that can be released in the extracellular milieu. Here, it may elicit signals through binding purinergic receptors. Alternatively, NAD+ may be dismantled to adenosine, up-taken by cells and transformed to reconstitute the intracellular nucleotide pool. An articulated ecto-enzyme network is responsible for the nucleotide–nucleoside conversion. CD38 is the main mammalian enzyme that hydrolyzes NAD+, generating Ca2+-active metabolites. Evidence suggests that this extracellular network may be altered or used by tumor cells to (i) nestle in protected areas, and (ii) evade the immune response. We have exploited chronic lymphocytic leukemia as a model to test the role of the ecto-enzyme network, starting by analyzing the individual elements that make up the whole picture

The ODHIN assessment tool: a tool to describe the available services for the management of hazardous and harmful alcohol consumption at the country and regional level

Optimizing Delivery of Health care Interventions (ODHIN) is an ongoing European project (EC, FP7) involving research institutions from 9 European countries using the implementation of Early Identification and Brief Intervention (EIBI) programmes for Hazardous and Harmful Alcohol Consumption (HHAC) in Primary Health Care (PHC) as a case study to better understand how to translate the results of clinical research into everyday practice. The Italian National Health Service (ISS) is the project leader of the Work Package 6 assessment tool. The aim of the ODHIN assessment tool is to formalise, operationalise and test the questionnaire developed under the PHEPA project in order to produce an update instrument to assess the extent of implementation of EIBIs for HHAC throughout PHC settings. The ODHIN assessment tool has been conceived as a semi-structured questionnaire for the identification of the state of the art, gaps and areas in the country that need further work and strengthening; to monitor the adequacy of brief intervention programmes for HHAC in order to provide recommendations to improve and optimize delivery of health care interventions. It analyses 24 questions distributed across 7 key sections. Data have been collected from 9 ODHIN collaborating countries (Catalonia, Czech Republic, Italy, Poland, Portugal, Slovenia, Sweden, The Netherlands and United Kingdom) and from other 14 European countries who have agreed to share their national experience with the ODHIN partners (Belgium, Croatia, Cyprus, Estonia, Finland, Fyrom-Yugoslav Republic of Macedonia, Germany, Greece, Iceland, Ireland, Latvia, Malta, Romania, and Switzerland). Preliminary data on the state of the art of the implementation and the extent of EIBI for HHAC throughout PHC settings across 23 European participating countries will be presented. Identified areas where services require development or strengthening across the participating countries as well as examples of good practices between countries will be also discussed

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Aim: Demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recom-mendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BRPeer reviewe

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

"Doctor, can I drink an alcohol-free beer?" Low-alcohol and alcohol-free drinks in people with heavy drinking or alcohol use disorders: systematic review of the literature.

No- and low-alcohol drinks (NoLo) have been proposed as a potential way forward for the reduction in the alcohol burden of disease. So far, there is scarce synthesized evidence on the effects of these products on people with alcohol use disorder (AUD), or with a heavy or high-risk drinking pattern. The aim of the present study is to systematically review the evidence of the use of NoLo drinks in these populations. A total of 4045 records were screened and 10 studies were included in the review. Craving and desire to drink have been found to increase after the consumption of NoLo drinks in patients with AUD. The increase in craving correlates with the severity of alcohol dependence. In addition, in this population, alcohol-related cues might trigger physiological responses similar to those experienced when using alcohol. Furthermore, as mentioned, in some of the studies, consumption was shown to increase as the %ABV or verbal descriptors indicate lower alcohol. Last, according to the epidemiological data, heavy drinkers tend to use NoLo drinks on top of their usual alcohol consumption rather than as part of regular drinking patterns. Further studies should be conducted in people with AUD or people with a high-risk drinking pattern to provide new insight to guide clinicians, patients, and other stakeholders to make evidence-based informed decisions

Training primary health care providers in Colombia, Mexico and Peru to increase alcohol screening:: Mixed-methods process evaluation of implementation strategy

Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice