A Diagnostic Dilemma: A Case of Complicated Pneumonia With Pyelonephritis and Subclinical Myocarditis.

A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.

F-box protein FBXO41 suppresses breast cancer growth by inducing autophagic cell death through facilitating proteasomal degradation of oncogene SKP2.

F-box proteins form SCF (Cullin1, SKP1 and F-box-protein) ubiquitin ligase complexes to ubiquitinate cellular proteins. They play key role in several biological processes, including cell cycle progression, cellular signaling, stress response and cell death pathways. Therefore, deregulation of F-box proteins is closely associated with cancer progression. However, the role of most of the F-box proteins, including FBXO41, in cancer progression remains elusive. Here, we unravel the role of FBXO41 in cancer progression. We show that FBXO41 suppresses cancer cell proliferation and tumor growth by inducing autophagic cell death through an alternative pathway. Results revealed that FBXO41-mediated autophagic cell death induction is dependent on accumulation of cell cycle checkpoint protein p21. We found that FBXO41 increases the expression levels of p21 at the post-translational level by promoting the proteasomal degradation of SKP2, an oncogenic F-box protein. Mechanistically, FBXO41 along with p21 disrupts the inhibitory BCL2 (anti-apoptotic protein)-Beclin1 (autophagy initiating factor) complex of autophagy induction to release Beclin1, thereby inducing autophagy. Overall, the present study establishes a new FBXO41-SKP2-p21 axis for induction of autophagic cell death to prevent cancer growth, which could be explored to develop promising cancer therapeutics.

Damsel in distress calling on her knights: Illuminating the pioneering role of E3 ubiquitin ligases in guarding the genome integrity.

The maintenance of genomic integrity is of utmost importance for the organisms to survive and to accurately inherit traits to their progenies. Any kind of DNA damage either due to defect in DNA duplication and/ or uncontrolled cell division or intracellular insults or environment radiation can result in gene mutation, chromosomal aberration and ultimately genomic instability, which may cause several diseases including cancers. Therefore, cells have evolved machineries for the surveillance of genomic integrity. Enormous exciting studies in the past indicate that ubiquitination (a posttranslational modification of proteins) plays a crucial role in maintaining the genomic integrity by diverse ways. In fact, various E3 ubiquitin ligases catalyse ubiquitination of key proteins to control their central role during cell cycle, DNA damage response (DDR) and DNA repair. Some E3 ligases promote genomic instability while others prevent it, deregulation of both of which leads to several malignancies. In this review, we consolidate the recent findings wherein the role of ubiquitination in conferring genome integrity is highlighted. We also discuss the latest discoveries on the mechanisms utilized by various E3 ligases to preserve genomic stability, with a focus on their actions during cell cycle progression and different types of DNA damage response as well as repair pathways.

Patient satisfaction with patient-led follow-up for endometrial cancer.

BACKGROUND: The 5-year hospital follow-up after treatment for endometrial cancer can increase anxiety for patients and not directly pick up cancer recurrence. AIMS: The aim of this study was to assess patient satisfaction with a patient-led follow-up and identify cancer recurrence. METHODS: This study population was 104 women with early uterine cancer who had undergone surgery. They were given information regarding symptoms suspicious for recurrence and started on a patient-led follow-up, which included a yearly phone call from the nursing team, and a questionnaire was completed. FINDINGS: Most patients (92%) scored ≥9 on the 10-point satisfaction survey. Nine women came back to the clinic for pain or bleeding. There was no recurrence of cancer in this study population. CONCLUSION: Patients are satisfied with a patient-led, telephone follow-up. This data has influenced a change in the regional Cancer Alliance guidance on cancer follow-up emphasising risk stratification.

Impact of a National Journal Club and Letter Writing Session on Improving Medical Students' Confidence with Critical Appraisal.

BACKGROUND: Critical appraisal is an important skill for clinicians of the future which medical students often have limited opportunities to develop. This study aimed to evaluate whether a national journal club session could improve medical students' confidence with critical appraisal. METHODS: 98 medical students attended a critical appraisal lecture and supervised journal article discussions. Junior doctor mentors supported students to submit discussion points as a letter-to-the-editor. An online cross-sectional survey was administered before and after the conference. RESULTS: 74 students responded, reporting increased confidence with critically appraising research articles (median score 2 vs 4, p<0.01) and increased understanding of why critical appraisal was important to their careers (median score 3 vs 5, p<0.01). DISCUSSION: This is the first study to demonstrate that a single national journal club session can significantly improve UK medical students' confidence with the critical appraisal process. These opportunities are valued by medical students.