Pneumococcal meningitis before the introduction of 10-valent pneumococcal conjugate vaccine into the National Childhood Immunization Program in Poland

Background

Poland introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into the childhood immunization program in January 2017. During previous decades, considerable changes had occurred in the surveillance system for invasive pneumococcal disease. Therefore, to provide baseline data on pneumococcal diseases before PCV10 introduction, we evaluated the epidemiology of pneumococcal meningitis (PM), the only syndrome monitored consistently since 1970.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease.     

The roles of basic psychological needs,self-compassion,and self-efficacy in the development of mastery goals among medical students

Abstract

Aim: Competency-based medical education aims to foster mastery goals in learners. We examined medical students’ mastery approach (beneficial) and mastery avoidance (maladaptive) goals and their associations with students’ basic psychological needs, self-compassion, and self-efficacy.

Methods: This was a cross-sectional study employing an online questionnaire. Two hundred medical students in all four years of the medical program completed the questionnaire, containing measures of mastery goals, basic psychological needs (autonomy, competence, relatedness), self-compassion, and self-efficacy. Regression analyses were performed.

Results: Of the three basic psychological needs, the need for competence was significant in explaining both types of mastery goals. Self-efficacy and self-compassion were significant in explaining mastery approach and mastery avoidance goals, respectively.

Conclusions: Creating learning environments that are supportive of students’ need for competence, raising students’ awareness of the value of learning from mistakes in competency acquisition, and providing opportunities for students to experience self-efficacy may foster beneficial mastery approach goals in medical students.     

Racialized Risk in Clinical Care: Clinician Vigilance and Patient Responsibility

Racial/ethnic identity is contingent and arbitrary, yet it is commonly used to evaluate disease risk and treatment response. Drawing on open-ended interviews with patients and clinicians in two US clinics, we explore how racialized risk is conceptualized and how it impacts patient care and experience. We found that racial/ethnic risk was a common but poorly defined construct for both patients and clinicians, who intermingled concepts of genetics, biology, behavior, and culture, while disregarding historical or structural context. We argue that racializing risk embodies social power in marked and unmarked bodies, reinforcing inequality along racial lines and undermining equitable health care.