Why I Write.

A practicing physician and oft-published columnist, the author reflects on her journey as a writer. For doctors who like or wish to write, reflections are offered about using writing as a public platform from which to elevate issues important to the doctor-patient relationship. At the same time, the public platform also constitutes a responsibility to be accurate, ethical, and respectful. The author shares guiding questions that writers can ask before or as they write. Attending to these questions will support compassionate, respectful, factually accurate, relevant, and insightful commentary that embodies physician integrity and reflects a thoughtful doctor-patient relationship.

Aeromonas hydrophila infection induces Toll-like receptor 2 (tlr2) and associated downstream signaling in Indian catfish, Clarias magur (Hamilton, 1822).

Motile Aeromonas septicaemia (MAS), caused by Aeromonas hydrophila, is one of the most significant bacterial disease responsible for mortality in Indian catfish, Clarias magur, a potential aquaculture species in the Indian subcontinent. In fish, innate immunity elicited by pathogen recognition receptors (PRRs) plays an important role in providing protection against bacterial infection. Information on PRRs including Toll-like receptors (tlrs) and their response to bacterial pathogens remains unexplored in magur. Toll-like receptor 2 (tlr2), a phylogenetically conserved germ-line encoded PRR recognizes specific microbial structure and trigger MyD88-dependent signaling pathway to induce release of various cytokines responsible for innate immune response. In the present study, tlr2 gene of magur was characterized and downstream signaling was studied following challenge with A. hydrophila. The full-length cDNA of magur tlr2 (mtlr2) comprised of 3,066 bp with a single open reading frame of 2,373 bp encoding 790 amino acids having a theoretical pI value of 6.11 and molecular weight of 90 kDa. Structurally, it comprised of signal peptide (1-42aa), one leucine-rich repeat region (LRR) at N-terminal (LRR1-NT: 50-73 aa) and C-terminal (LRR-CT: 588-608 aa), twenty LRRs in between, one trans-membrane (Tm) domain (609-631aa) followed by cytoplasmic TIR domain (670-783aa). Phylogenetically, mtlr2 is closely related to pangasius and channel catfish. Highest basal expression of mtlr2, myd88 and il-1ß in spleen, nf-kb in anterior kidney was observed. Lowest basal expression of mtlr2 in skin and myd88, nf-kb and il-1ß in muscle was detected. Significant up-regulation of mtlr2 and downstream expression occurred at 3, 8, 24 h post infection to A. hydrophila in important immune organs such as liver, spleen, intestine and kidney. These findings highlight the vital role of tlr2 in eliciting innate immune defence against A. hydrophila infection.

Dosimetric analysis of cervical cancer stage IIB patients treated with volumetric modulated arc therapy using plan uncertainty parameters module of Varian Eclipse treatment planning system.

Introduction. The present study aims to investigate the dosimetric and radiobiological impact of patient setup errors (PSE) on the target and organs at risk (OAR) of the cervix carcinoma stage IIB patients treated with volumetric-modulated arc therapy (VMAT) delivery technique using plan uncertainty parameters module of Varian Eclipse treatment planning system and in-house developed DVH Analyzer program.Materials and Methods. A total of 976 VMAT plans were generated to simulate the PSE in the base plan that varies from -10 mm to 10 mm in a step size of 1 mm in x- (lateral), y- (craniocaudal), and z- (anteroposterior) directions. The different OAR and tumor (PTV) volumes were delineated in each case. Various plan quality metrics, such as conformity index (CI) and homogeneity index (HI), as well as radiobiological quantities, such as tumor control probability (TCP) and normal tissue control probability (NTCP), were calculated from the DVH bands generated from the cohort of treatment plans associated with each patient case, using an in-house developed 'DVH Analyzer' program. The extracted parameters were statistically analyzed and compared with the base plan's dosimetric parameters having no PSE.Results. The maximum variation of (i) 2.4%, 21.5%, 0.8%, 2.5% in D2ccof bladder, rectum, small bowel and sigmoid colon respectively; (ii) 19.3% and 18.9% in Dmaxof the left and right femoral heads (iii) 16.9% in D95%of PTV (iv) 12.1% in NTCP of sigmoid colon were observed with change of PSE in all directions. TCP was found to be considerably affected for PSEs larger than 4 mm in x+, y+, z+directions and 7 mm in x-, y-and z-directions, respectively.Conclusion. This study presents the effect of PSE on TCP and NTCP for the cervix carcinoma cases treated with VMAT technique and also recommends daily image guidance to mitigate the effects of PSE.

Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature.

Current first-line systemic treatment in most patients with metastatic hormone receptor-positive, HER-2 negative breast cancer is an aromatase inhibitor in combination with a cyclin dependant kinase (CDK) 4/6 inhibitor. Frequently, these patients require palliative radiotherapy (RT) for symptomatic disease management. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative RT, with conflicting case reports in the literature. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when palliative doses of RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. After review of pre-clinical and mechanistic data, we hypothesise that the effects of CDK4/6 inhibition on normal tissue and the tumour microenvironment may impede tissue recovery and exacerbate acute radiation and radiation recall toxicities. Further studies are required to clarify the potential toxicities of this combination. Clinicians should consider the potential risks when combining CDK 4/6 inhibitors with palliative RT and individualise patient management accordingly.

Caring for Our Trainees: Lessons From Around the World.

Continuing progress in the science of oncology must be matched by an increased responsibility toward providing oncology trainees around the world with the academic guidance, emotional support, and lifelong mentoring needed to navigate an increasingly complex environment. Although the realities on the ground determine the practicalities, there are important universal lessons to be learned from heeding diverse experiences. In this paper, three faculty at different stages of their careers from countries with different resources and infrastructure share their insights into caring for trainees.

Reflection of a Physician-Writer: On Why I Write.

In the course of their increasingly busy lives, physicians encounter many emotions that move and challenge them. Writing is a valuable tool for self-expression and making sense of the world. Physicians are often concerned about patients' confidentiality and not upsetting their colleagues, but writing can be one of the best ways of sustaining a healthy and meaningful career and effecting change.

Caring for Colleagues and Loved Ones With Cancer.

Throughout the arc of a career in medicine, physicians are universally faced with the difficult decision of when to provide care for a colleague and when to refer to another physician. Gauging the magnitude of your relationship, both professionally and personally, and then weighing how to add the roles of physician and patient to your preexisting relationship is complex. We review and discuss care of family and colleagues, address ethical boundaries both firm and flexible, and explore the emotional weight of those relationships.

For Our Patients, for Ourselves: The Value of Personal Reflection in Oncology.

Caring for patients with cancer is a great privilege as well as an emotionally and intellectually challenging task. Stress and burnout are prevalent among oncology clinicians, with serious repercussions for the care of patients. Professional societies must provide guidance for trainees and practicing physicians to mitigate the negative consequences of stress on their personal lives and medical practice. Reflection, reading, and writing about personal experiences provide outlets for fortifying personal reserves and promoting resilience to allow us to recognize the joy and meaning of our work and to forge connections with our peers. Herein, we present some of our own reflections on how and why one might take time to write, and about the power of the written word in oncology and medicine.

Gallic acid induces apoptosis in human cervical epithelial cells containing human papillomavirus type 16 episomes.

The high-risk human papillomaviruses (HPV) that infect the anogenital tract are strongly associated with the development of cervical carcinoma, which is the second most common cancer in women worldwide. Therapeutic drugs specifically targeting HPV are not available. Polyphenolic compounds have gained considerable attention because of their cytotoxic effects against a variety of cancers and certain viruses. In this study, we examined the effects of several polyphenols on cellular proliferation and death of the human cervical cancer cells and human cervical epithelial cells containing stable HPV type 16 episomes (HPVep). Our results show that three polyphenols inhibited proliferation of HeLa cells dose-dependently. Furthermore, one of the examined polyphenols, gallic acid (GA), also inhibited the proliferation of HPVep cells and exhibited significant specificity towards HPV-positive cells. The anti-proliferative effect of GA on HPVep and HeLa cells was associated with apoptosis and upregulation of p53. These results suggest that GA can be a potential candidate for the development of anti-HPV agents.