The Gynecologic Oncology Group (GOG) has conducted multiple trials related to malignancies of the uterine corpus. Recently, several of these trials have been presented and/or published. Areas of focus included the feasibility of laparoscopic staging for endometrial cancer, the adjuvant management of locally advanced endometrial cancer, whole abdominal irradiation in maximally resected advanced endometrial carcinoma, and combination chemotherapy regimens for stage I and II carcinosarcoma after primary surgery and for advanced or recurrent carcinosarcoma. This article will discuss the background and details of each of these important advances.
Carcinosarcoma ; Drug Therapy, Combination ; Endometrial Neoplasms ; Female

The Gynecologic Oncology Group (GOG) has conducted multiple trials related to malignancies of the uterine corpus. Recently, several of these trials have been presented and/or published. Areas of focus included the feasibility of laparoscopic staging for endometrial cancer, the adjuvant management of locally advanced endometrial cancer, whole abdominal irradiation in maximally resected advanced endometrial carcinoma, and combination chemotherapy regimens for stage I and II carcinosarcoma after primary surgery and for advanced or recurrent carcinosarcoma. This article will discuss the background and details of each of these important advances.
Carcinosarcoma ; Drug Therapy, Combination ; Endometrial Neoplasms ; Female

AIMTo simultaneously determine the localization of histones and protamines within human sperm nuclei.

METHODSImmunofluorescence of the core histones and protamines and fluorescence in situ hybridization of the telomere region of chromosome 16 was assessed in decondensed human sperm nuclei.

RESULTSImmunofluorescent localization of histones, protamine 1 (PRM1) and protamine 2 (PRM2) along with fluorescence in situ hybridization localization of chromosome 16 telomeric sequences revealed a discrete distribution in sperm nuclei. Histones localized to the posterior ring region (i.e. the sperm nuclear annulus), whereas PRM1 and PRM2 appeared to be dispersed throughout the entire nucleus.

CONCLUSIONThe co-localization of the human core sperm histones with the telomeric regions of chromosome 16 is consistent with the reorganization of specific non-protamine regions into a less compacted state.

Cell Nucleus ; metabolism ; Chromosomes, Human, Pair 16 ; metabolism ; Histones ; metabolism ; Humans ; Male ; Protamines ; metabolism ; Spermatozoa ; metabolism ; Telomere ; metabolism

Hazardous work zones (i.e., hot, warm, and cold) are typically established by emergency response teams during hazardous materials (HAZMAT) callsbut less consistently for fire responses to segment personnel and response activities in the immediate geographic area around the fire. Despite national guidelines, studies have documented the inconsistent use of respiratory protective equipment by firefighters at the fire scene. In this case-series report, we describe warm zone gas levels using multigas detectors across five independent fire incident responses all occurring in a large South Florida fire department. Multigas detector data collected at each fire response indicate the presence of sustained levels of volatile organic compounds in the “warm zone” of each fire event. These cases suggest that firefighters should not only implement strategies for multigas detector use within the warm zone but also include respiratory protection to provide adequate safety from toxic exposures in the warm zone.
Emergencies ; Environmental Monitoring* ; Firefighters* ; Fires* ; Florida ; Hazardous Substances ; Humans ; Volatile Organic Compounds

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.
Humans ; Sensitivity and Specificity

Penile fracture (PF) is a surgical emergency. Given its rarity, we queried a national cohort over an 11-year period to study the temporal and demographic variations in presentation, evaluation, and management of patients with PF compared with a cohort of control patients. The National Inpatient Sample was queried between the years 2005 and 2016 for patients with a diagnosis of PF. Appendectomy patients were selected as a control cohort, given the non-discriminatory nature of this disease. Clinical and demographic data of the patients were compared with that of controls. Presenting symptoms, rates of surgical repair, and rates of associated surgical procedures were evaluated in the PF cohort. During the study period, 5802 patients were hospitalized for PF. The annual incidence of PF remained unchanged at 1.0-1.8 cases per 100 000 hospitalizations over the study period. Compared with the control cohort, PF patients were more likely to be younger (38.7 years vs 41.2 years, P ≤ 0.001), have lower rates of comorbidities except erectile dysfunction (1.4% vs 0.1%, P ≤ 0.001), and were more likely of Black race (25.4% vs 6.2%, P ≤ 0.001). Notably, PF patients had significantly higher rates of substance abuse (26.4% vs 18.1%, P ≤ 0.001), despite no difference in the diagnosed psychiatric disorders. PF rarely presented with hematuria (3.5%); however, urethral evaluation was performed in 23.1%, most commonly with cystoscopy (19.2%). PF occurs more commonly in a younger, healthier male population, and among minorities. Importantly, rates of substance abuse appear to be higher in the PF cohort compared with those of controls.

The United States (U.S.) is facing a national opioid epidemic, and medical systems are in need of non-pharmacologic strategies that can be employed to decrease the public's opioid dependence. Acupuncture has emerged as a powerful, evidence-based, safe, cost-effective, and available treatment modality suitable to meeting this need. Acupuncture has been shown to be effective for the management of numerous types of pain conditions, and mechanisms of action for acupuncture have been described and are understandable from biomedical, physiologic perspectives. Further, acupuncture's cost-effectiveness can dramatically decrease health care expenditures, both from the standpoint of treating acute pain and through avoiding addiction to opioids that requires costly care, destroys quality of life, and can lead to fatal overdose. Numerous federal regulatory agencies have advised or mandated that healthcare systems and providers offer non-pharmacologic treatment options for pain. Acupuncture stands out as the most evidence-based, immediately available choice to fulfil these calls. Acupuncture can safely, easily, and cost-effectively be incorporated into hospital settings as diverse as the emergency department, labor and delivery suites, and neonatal intensive care units to treat a variety of commonly seen pain conditions. Acupuncture is already being successfully and meaningfully utilized by the Veterans Administration and various branches of the U.S. Military, in some studies demonstrably decreasing the volume of opioids prescribed when included in care.