Targeting oncogenic Src homology 2 domain-containing phosphatase 2 (SHP2) by inhibiting its protein-protein interactions

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2

Raccomandazioni per l’identificazione e la gestione dei risultati critici nei laboratori clinici

Critical results (also known as panic or alarm results) identify a laboratory test result associated with a serious risk for the patient's health, requiring immediate communication to the physician to establish appropriate therapeutic interventions. The adoption of an efficient procedure for the communication of critical values/results is crucial for clinical, ethical, organizational reasons, because it is a requirement for laboratory accreditiation and because of potential legal consequences related to the lack of notification of harmful laboratory results. In 2008, the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC) published its first consensus-based recommendation for the detection and management of critical values in clinical laboratories, with the aim to improve the implementation of standardized and universally accepted procedures, promoting an essential policy toward rational and efficient solutions to this issue. These new recommendations represent a complete review of the first document. Using the same consensus conference method between experts of scientific societies, the main aspects of clinical risk, patient safety and legal liability of health care workers were re-considered. The SIBioC and the Italian Society of Laboratory Medicine (SIPMeL), Intersociety Study Group on Standardization of extra-analytical variability of laboratory results, together with the Italian Society of Ergonomics and Human Factors (SIE) collaboration, issued the present join document

The impact of type 2 diabetes on health related quality of life in Bangladesh: results from a matched study comparing treated cases with non-diabetic controls

Background Little is known about the association between diabetes and health related quality of life (HRQL) in lower-middle income countries. This study aimed to investigate HRQL among individuals with and without diabetes in Bangladesh. Methods The analysis is based on data of a case-control study, including 591 patients with type 2 diabetes (cases) who attended an outpatient unit of a hospital in Dhaka and 591 age -and sex-matched individuals without diabetes (controls). Information about socio-demographic characteristics, health conditions, and HRQL were assessed in a structured interview. HRQL was measured with the EuroQol (EQ) visual analogue scale (VAS) and the EQ five-dimensional (5D) descriptive system. The association between diabetes status and quality of life was examined using multiple linear and logistic regression models. Results Mean EQ-VAS score of patients with diabetes was 11.5 points lower (95 %-CI: −13.5, −9.6) compared to controls without diabetes. Patients with diabetes were more likely to report problems in all EQ-5D dimensions than controls, with the largest effect observed in the dimensions ‘self-care’ (OR = 5.9; 95 %-CI: 2.9, 11.8) and ‘mobility’ (OR = 4.5; 95 %-CI: 3.0, −6.6). In patients with diabetes, male gender, high education, and high-income were associated with higher VAS score and diabetes duration and foot ulcer associated with lower VAS scores. Other diabetes-related complications were not significantly associated with HRQL. Conclusions Our findings suggest that the impact of diabetes on HRQL in the Bangladeshi population is much higher than what is known from western populations and that unlike in western populations comorbidities/complications are not the driving factor for this effect

Predictors of Health-Related Quality of Life in Patients at Risk for Cardiovascular Disease in European Primary Care

Contains fulltext : 96207.pdf (publisher's version ) (Open Access)BACKGROUND: Cardiovascular risk management plays an important role in primary care. In patients at high risk for cardiovascular diseases (CVD) lifestyle and, where appropriate, medical interventions are recommended in guidelines. Health-related quality of life (HRQoL) is an important outcome in clinical practice. This study aimed to assess the HRQoL of this patient group and to investigate the impact of both patients' characteristics and practice quality scores on their assessments of HRQoL. METHODS AND FINDINGS: An observational study in 218 general practices from 8 European countries was conducted. 2142 patients at risk for CVD (33.5% female) with a mean age of 66.3 (SD 9.1) years completed a questionnaire including the EQ-5D instrument and provided data from medical record. Validated quality indicators of general practices were assessed using practice questionnaires and face-to-face interviews. A hierarchical multilevel analysis was performed to identify predictors of EQ-5D scores at patient and practice level. The mean EQ-5D score was 0.78 (SD 0.19). Female gender (r = -0.03, p<0.0016), age (r = -0.01, p = 0.0387) and lower educational level (r = -0.03, p<0.0001) were correlated negatively with EQ-5D scores. Clinically more important was the correlation of HRQoL with the frequency of practice contacts (r = -0.12, p<0.0001) and the number of uncontrolled risk factors (r = -0.01, p<0.0039). Medication adherence (r = 0.032, p<0.0001), and physical activity (r = 0.02, p<0.0001) were identified as positive predictors of HRQoL. The EUPROPEP-score category 'organization' (r = 0.02, p<0.0001) was positively related to EQ-5D scores, whereas other practice scores were not correlated to EQ-5D-scores. CONCLUSIONS: In patients at risk for CVD, good medication adherence, regular physical activity, controlling of biomedical risk factor levels and patient-centered practice organization have been shown to be positively correlated to HRQoL and should therefore be targeted in interventions not only to reduce morbidity but also to sustain or even to ameliorate HRQoL