Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway.

Multiple chemotherapies are proposed to cause cell death in part by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs exactly how the resultant ROS function and are sensed is poorly understood. In particular, it's unclear which proteins the ROS modify and their roles in chemotherapy sensitivity/resistance. To answer these questions, we examined 11 chemotherapies with an integrated proteogenomic approach identifying many unique targets for these drugs but also shared ones including ribosomal components, suggesting one mechanism by which chemotherapies regulate translation. We focus on CHK1 which we find is a nuclear H 2 O 2 sensor that promotes an anti-ROS cellular program. CHK1 acts by phosphorylating the mitochondrial-DNA binding protein SSBP1, preventing its mitochondrial localization, which in turn decreases nuclear H 2 O 2 . Our results reveal a druggable nucleus-to-mitochondria ROS sensing pathway required to resolve nuclear H 2 O 2 accumulation, which mediates resistance to platinum-based chemotherapies in ovarian cancers.

Innovating Evaluation and Treatment of Intrapartum Fevers: Where Do We Go from Here?

As intrapartum fevers are not always infectious in origin, determining whether antibiotics are indicated is challenging. We previously sought to create a point-of-care calculator using clinical data available at the time of an intrapartum fever to identify the subset of women who require antibiotic treatment to avoid maternal and neonatal morbidity. Despite the use of a comprehensive dataset from our institutions, we were unable to propose a valid and highly predictive model. In this commentary, we discuss why our model failed, as well as future research directions to identify and treat true intraamniotic infection. Developing a risk-stratification model is paramount to minimizing maternal and neonatal exposure to unnecessary antibiotics while allowing for early identification of women and babies at risk for infectious morbidity. KEY POINTS: · Determining whether antibiotics are indicated in intrapartum fever is challenging.. · Developing a risk-stratification model for febrile laboring women is critical to decreasing harm.. · A point-of-care calculator based on clinical and biomarker data is the necessary approach..

Mixed Epithelial and Stromal Tumor Family of Kidney (Adult Cystic Nephroma, Mixed Epithelial and Stromal Tumor): Retrospective Clinicopathological Evaluation.

OBJECTIVE: Tumors belonging to the mixed epithelial stromal tumor family (MESTF) are rare; thus clinicopathological experience about them are limited. Each epithelial and stromal component shows different patterns in these tumors. MATERIAL AND METHOD: Clinicopathological features of 11 MESTF cases that were diagnosed between 2000 and 2021 at a single center were evaluated. RESULTS: Ten of the 11 patients were female (F:M = 10:1). The mean age of the females was 47 (31-63) years; the male patient was 45 years old. The mean tumor diameter was 6.7 (3.5-19) cm. All tumors had varying proportions of cystic and solid components. Eight cases were well circumscribed, and the others had distinct but irregular borders. Two of the tumors with irregular borders were bulging into the renal sinus. The epithelial component was dominant in most cases. In the epithelial component, macrocyst, microcyst, and tubules were the most common patterns and the most common types of lining epithelium were flat, cuboidal and hobnail. The stromal component was variable in most cases and included hypocellular (mostly collagenous) and cellular areas. In most cases, the cellular stroma had an ovarian-like appearance. Among the other features observed, hyalinization and dystrophic calcification were common. The positivity for estrogen and progesterone receptor in the stromal component was observed in almost all female cases. CONCLUSION: MESTF, which has distinctive features, should be considered in the differential diagnosis of cystic kidney tumors.

Untreated herpes simplex virus encephalitis without a fatal outcome.

Herpes simplex virus encephalitis (HSE) is the most common sporadic fatal encephalitis. Although timely administered acyclovir treatment decreases mortality, neuropsychiatric sequelae is still common among survivors. Magnetic resonance imaging is frequently utilized for the diagnosis of HSE, which typically involves temporal lobe(s) and can be mixed with brain tumors involving the same area. Here, we report a case of HSE, who received acyclovir with a delay of 90 days because of presumptive tumor diagnosis and survived with minimal sequelae.

Follicular lymphoma generating in a patient with non-small cell lung cancer following nivolumab discontinuation.

INTRODUCTION: Immune checkpoint inhibitors have demonstrated the benefit for many cancer types, melanoma, non-small cell lung cancer, urothelial cancer, renal cell cancer, etc. Especially in advanced non-small cell lung cancer, significant improvement in survival results has been shown. CASE REPORT: Here, we report a 66-year-old man with lung adenocarcinoma who received nivolumab for 80 cycles.Management and Outcome: Two months after discontinuing nivolumab, he developed follicular lymphoma. Pneumonitis was also accompanied, which was treated with metilprednisolon, but he died due to progressive respiratory failure. DISCUSSION: Our clinical knowledge with checkpoint inhibitors is increasing day by day, and to the best of our knowledge, this paper presents the first case in the English literature who developed follicular lymphoma after discontinuing nivolumab in non-small cell lung cancer patient.

Effect of Dry Needling Injection and Kinesiotaping on Pain and Quality of Life in Patients with Mechanical Neck Pain.

BACKGROUND: Dry needling (DN) is a commonly used technique by clinicians for the treatment of mechanical neck pain (MNP) by targeting trigger points and nontrigger point structures. It is a skilled intervention that uses a thin ?liform needle to penetrate the skin and stimulate underlying trigger points, muscular and connective tissues without the use of injectate. Another popular treatment technique used in the management of musculoskeletal pathologies is kinesiotaping (KT). Although its popular, there is minimal scientific evidence supporting KT for neck pain. Although there are a few studies regarding KT for neck pain in literature, there is a lack of randomized, controlled studies evaluating KT for neck pain. OBJECTIVES: To evaluate the effect of KT on posterior cervical spine and DN into a posterior paracervical muscle of patients with MNP. STUDY DESIGN: Randomized clinical study. SETTING: Physical medicine and rehabilitation center. METHODS: Seventy-two patients (17 men, 55 women) were randomly assigned to DN or KT treatment groups. Numeric Rating Scale (NPS-11), Neck Disability Index (NDI), range of motion (ROM), Short Form-36 Quality of Life Scale, and Beck Depression Inventory (BDI) were assessed before the intervention and one month postintervention. RESULTS: Before treatment, there was no difference between groups in NPS-11, NDI, and BDI scores; however, ROM of the DN group was greater than ROM of the KT group (P < 0.05). After treatment, significant improvement was observed in all variables for both of the groups, except ROM in the DN group (P < 0.05). The KT group showed greater ROM compared with the DN group (P < 0.05). The pre- and posttreatment results showed that the KT group was significantly superior for the differences on ROM and NDI (P < 0.05); however, each group showed better results after treatment (P < 0.05). LIMITATIONS: First, we did not include a control or placebo group. Second, patients were followed up for only 4 weeks. Third, we used a sample of convenience from one clinic, which may not be representative of the entire population of individuals with MNP. CONCLUSIONS: In this study, both methods were found to be effective on pain, mood, and quality of life, and KT was found to be superior to DN in MNP in terms of increasing ROM and decreasing disability. KEY WORDS: Dry needling, kinesiotaping, mechanical neck pain, quality of life.

Effectiveness of Kinesiotaping and Subacromial Corticosteroid Injection in Shoulder Impingement Syndrome.

OBJECTIVE: The aim of this study was to investigate whether kinesiotaping or subacromial corticosteroid injection provides additional benefit when used with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with shoulder impingement syndrome. DESIGN: Patients with shoulder impingement syndrome were divided into 3 groups as follows: NSAID group (n = 33), kinesiotaping group (kinesiotaping + NSAID) (n = 33), and injection group (subacromial corticosteroid injection + NSAID) (n = 33). Outcome measures including visual analog scale, shoulder ranges of motion, Shoulder Disability Questionnaire, and University of California-Los Angeles (UCLA) scale were evaluated before and after the treatment (fourth week). RESULTS: A total of 99 patients (21 male and 78 female patients) were enrolled in this study. Demographic and baseline clinical characteristics of the groups (except for body mass index and visual analog scale at night, both P = 0.05) were similar between the groups (all P > 0.05). Clinical parameters were found to have improved in the 3 groups (all P < 0.001). While the kinesiotaping and injection groups showed similar improvements (all P > 0.05), each group had better outcome than did the NSAID group as regards pain (activity visual analog scale), ranges of motion, and Shoulder Disability Questionnaire and UCLA scale scores (all P < 0.05). CONCLUSIONS: Addition of kinesiotaping or subacromial corticosteroid injection to NSAID treatment seems to have better/similar effectiveness in patients with shoulder impingement syndrome. Therefore, kinesiotaping might serve as an alternative treatment in case (injection of) corticosteroids are contraindicated. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Delineate appropriate treatment options for shoulder impingement syndrome; (2) Identify treatment benefits of kinesiotaping and corticosteroid injections in shoulder impingement syndrome; and (3) Incorporate kinesiotaping and corticosteroid injections into the treatment plan for patients with shoulder impingement syndrome. LEVEL: Advanced ACCREDITATION: : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for amaximumof 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.