A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity

p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two functional screens to isolate genes which bypassed either p53-mediated growth arrest or apoptosis. In both screens, we isolated cDNAs encoding macrophage migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppressed its activity as a transcriptional activator. The observation that a proinflammatory cytokine, MIF, is capable of functionally inactivating a tumor suppressor, p53, may provide a link between inflammation and tumorigenesis

fBLS \textemdash a fast folding algorithm to produce BLS periodograms in search for transiting planets

International audienceWe present fBLS \textendash a novel technique for detecting transiting planets. fBLS is based on the fast-folding algorithm (FFA; Staelin 1969), extensively used in pulsar astronomy (e.g., Morello et al. 2020). fBLS simultaneously produces all the binned phase-folded lightcurves for an array of Np 'sufficiently different' trial periods, with O(Np*log(N)) arithmetic operations (while regular BLS requires O(Np*N) operations). We compute the standard BLS statistic for each folded lightcurve produced by fBLS, creating a standard BLS periodogram. We present fBLS capabilities by applying it to Kepler data, finding known and new planets. When applied to PLATO lightcurves, it will detect small rocky transiting planets, with periods shorter than one day, a period range for which the computation is extensive. fBLS will also be used to detect transiting planets with varying duration and transit timing

Is There an Association between BMI, Height, and Gender and Long-Bone Fractures during Childhood and Adolescence? A Large Cross-Sectional Population Study of 911,206 Subjects

Introduction: Traumatic long-bone fractures (TLFs) among children and adolescents are relatively common, with morbidity and economic consequences. Obesity has become a significant global concern. Studies have found an association between TLFs and BMI in the past but not in a large cross-sectional population study. Our study objective was to measure the incidence of TLFs in the 17-year-old general population and evaluate its association with BMI, body height, and gender. Methods: Data from a medical database containing all 17-year-old candidates’ records before recruitment into mandatory military service were retrieved as BMI, height, gender, and history of TLFs. Logistic regression models assessed the association between BMI and height to TLFs. Results: The records of 911,206 subjects (515,339 males) were reviewed. In total, 9.65% had a history of TLFs (12.25% and 6.25% for males/females, respectively). Higher BMI was associated with TLF, with a linear trend in the odds ratio (OR) for having TLFs. The strongest association was found between obese females and TLFs (OR = 1.364, p p p < 0.001) for females compared to the lowest quintile. Although TLFs were more common in males, the OR for TLFs was more prominent in females. Conclusions: There is an association between BMI, body height, and TLFs in healthy adolescents. TLFs are more common in males, but the strongest association between overweight and obesity is evident in females

Platelet-Rich Plasma for Knee Osteoarthritis: Internet Marketing and Patient Education—An Appraisal of Content for Websites with the Greatest Search Engine Visibility

Objective The internet is increasingly being used as a resource for health-related information by the general public. We sought to establish the authorship, content, and accuracy of the information available online regarding platelet-rich plasma (PRP) therapy for knee osteoarthritis. Design Top 200 search results from each of the 3 leading search engines available online (Google, Yahoo!, Bing) were screened, and 181 websites were finally reviewed for content with emphasis on specific claims, comparing between websites authored by private physicians/groups and other authorship types. Results Nearly 80% of the websites claimed that PRP injections for osteoarthritis of the knee improve patients’ pain. A total of 42.8% of the private websites and 27.6% of nonprivate websites have stated that the procedure can delay or eliminate the need for future surgery. Costs were only mentioned by few (11.6%), and mainly by the nonprivate websites. Both website groups were unlikely to mention that PRP therapy is not the treatment of choice for end-stage knee osteoarthritis (7.9% of private and 17.2% of the nonprivate sites), or to state that patients with less advanced disease may benefit more from the treatment (11.8% and 20.6%, respectively). Private websites were less likely to refer to peer-reviewed literature (18.4% vs. 41.4%) and were more than 3 times less likely to mention lack of adequate evidence (13.2% vs. 48.2%). Conclusions Patients seeking online information regarding PRP therapy are vulnerable to websites presenting a narrow viewpoint of this treatment modality, putting emphasis on unsubstantiated benefits while disregarding potential drawbacks and concerns

Analysis of clinical characteristics, treatment patterns, and outcome of patients with bilateral testicular germ cell tumors

Abstract Introduction Bilateral testicular germ cell tumor (BGCT) is a rare disease, occasionally considered to be more aggressive than unilateral germ cell tumors (GCT) in some reports. Among BGCT, a synchronous disease might be diagnosed at a higher stage than a metachronous disease, resulting in lower cancer-specific survival. Hence, our study aimed to perform a comparative analysis between unilateral testicular GCT, bilateral synchronous GCT, and bilateral metachronous GCT, aiming to verify the possibility that BGCT is diagnosed with a higher stage and may require more aggressive management. Material and methods In our multicenter retrospective study we reviewed medical records of 40 patients with BGCT (24 metachronous and 16 synchronous). Clinical characteristics, pathological features of the primary and secondary tumors, adjuvant treatments (chemotherapy and radiotherapy)and sperm quality were evaluated as well as cancer-specific survival and overall survival. A cohort of one-to-one matched patients with unilateral GCT were used to determine risk factors for developing BGCT. Results Patients with BGCT were slightly younger compared to those with unilateral GCT and had more advanced disease. Despite similar T-stage distribution between the two groups, nodal involvement was nearly twofold more frequent in patients with BGCT disease (42% vs 22%, p = 0.056). Additionally, although similar histological subtypes distribution at presentation among the two groups, the synchronous disease was diagnosed with a higher local T-stage (OR = 3.4), higher proportions of patients with elevated serum BHCG levels, and more frequent nodal involvement (OR = 2.2). This was later translated into an 18% higher disease-specific mortality rate. The median time to develop a contralateral tumor was 92 months. Pathological local T-stage (T2–T3) of the primary tumor predicted a shorter time interval to a diagnosis of a second contralateral tumor (HR 0.92, P < 0.05). Conclusion BGCT presents at a younger age and potentially with more advanced disease. Synchronous BGCT is diagnosed at a later stage compared to metachronous BGCT and has higher disease-specific mortality. Metachronous tumors might have a long time interval for the development of a contralateral neoplasm. The main predictor of developing an early metachronous disease is a high primary T stage

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with &ldquo;negative&rdquo; prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with &ldquo;negative&rdquo; pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an &ldquo;intense&rdquo; prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a &ldquo;negative&rdquo; uptake (in the study group), and 45 (46%) had a &ldquo;positive&rdquo; uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p &lt; 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP &ge; 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates

Reply to Veerman et al. Comment on &ldquo;Rosenzweig et al. Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates. J. Pers. Med. 2022, 12, 410&rdquo;

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