Cervical cancer screening and treatment capacity: A survey of members of the African Organisation for Research and Training in Cancer (AORTIC).

BACKGROUND: Cervical cancer is the second most common cancer among women in Africa, and in half of the sub-Saharan African countries, it is the most common cancer. Currently, there are scarce resources and limited infrastructure to support cervical cancer screening and treatment in many African countries. OBJECTIVES: The aim of this study is to investigate the capacity of cervical cancer screening and treatment among members of the African Organization for Research and Training in Cancer (AORTIC). METHODS: Data were collected from 183 participants through online surveys over a 3-month study period in 2016. RESULTS: The respondents reported large variations among different African countries. This study highlights the differences between African countries in the availability of screening programs as a result of the resources allocated to healthcare development. Radiation therapy capacity remained the most limited treatment modality available, followed by the lack of gynecologists or gynecologic oncologists who can perform radical hysterectomy. CONCLUSIONS: This information is critical for physicians, public health educators, and policymakers aiming to improve the outcomes among women with cervical cancer in Africa.

Initial review of pregnancy and neonatal outcomes of pregnant women with COVID-19 infection.

OBJECTIVES: Data regarding the pathogenesis and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, however, there's limited data in regard to maternal and neonatal outcomes. Therefore, we conducted a retrospective analysis of all pregnant women who tested positive for SARS-CoV-2 within Nuvance Health system. METHODS: Data were abstracted from the medical records of each patient and descriptive analysis was performed. Variables included demographics, COVID testing results, symptoms, management, labor course, neonatal information, and complications. RESULTS: Total of 40 patients were identified. Average age was 29.6 years old, 35% were Hispanic, and approximately one in three patients had comorbidities. Of the patients who had repeated testing, the average number of days between first positive test and negative test was 36.8 days (± 19.9 days). Three out of four women reported symptoms. Of the 40 pregnant women who were positive for SARS-CoV-2, 25 of them delivered. About 84% of the women delivered after 37 weeks. Twelve percent of the women delivered under 33 and 6/7 weeks. Most patients had vaginal deliveries (68%) and the remaining had cesarean deliveries. Neonatal outcomes included: mean 1 and 5 min Apgar scores of 8 and 8.8, respectively and the mean birth weight was 3212 g. Twenty neonates were tested for SARS-CoV-2 and were all found to be negative. CONCLUSIONS: Overall, with routine prenatal care and preventive measures, pregnant patients and neonates in our study had good outcomes. At this time, there appears to be no evidence of vertical transmission.

Resources That Improve Medical Board Licensing Examination Performance.

Purpose Examine the factors improving performance on national medical licensing board examinations. Rationale Accreditation Council for Graduate Medical Education (ACGME) accredited residency programs report the United States Medical Licensing Examination (USMLE) Step 1 and Comprehensive Osteopathic Licensing Examination-USA (COMLEX-USA) Level 1 scores as the most important criteria in selecting candidates to interview. Hypotheses (1) Certain resources are superior for exam preparation. (2) Certain practice tests better assess exam preparedness. (3) USMLE performance will correlate with the COMLEX-USA. Methods One-hundred and two (102) medical students were surveyed regarding preparation for and performance on COMLEX-USA Level 1 and USMLE Step 1. Results USMLE-specific question banks were positively correlated with performance on COMLEX-USA Level 1 and USMLE Step 1 while COMLEX-specific question banks showed no correlation. National Board of Medical Examiners (NBME) Comprehensive Basic Science Self Assessment (CBSSA) and National Board of Osteopathic Medical Examiners (NBOME) Comprehensive Osteopathic Medical Self-Assessment Examination (COMSAE) practice examinations were positively correlated with performance on the USMLE Step 1 and the COMLEX-USA Level 1. Scores on USMLE Step 1 and COMLEX-USA Level 1 were highly correlated. Students who took USMLE Step 1 performed better on COMLEX-USA Level 1 than those who did not. Conclusion COMLEX-specific resources may not adequately prepare students for COMLEX-USA Level 1. Students studying for COMLEX-USA Level 1 may benefit by preparing for USMLE Step 1.

Governing roles for Trib3 pseudokinase during stress erythropoiesis.

In response to anemia, the heightened production of erythropoietin (EPO) can sharply promote erythroid progenitor cell (EPC) formation. Specific mediators of such EPO- accelerated erythropoiesis, however, are not well understood. Presently, we first report that the expression of Trib3 in adult bone marrow EPCs in vivo is nominal at steady state, but strongly activated on EPO challenge. In a knockout mouse model, Trib3 disruption modestly increased steady-state erythrocyte numbers and decreased mean corpuscular volume. Following 5-fluorouracil myeloablation, however, rebound red blood cell production and hemoglobin levels were substantially (and selectively) compromised in Trib3-/- mice versus Trib3+/+ congenic controls. Erythrocytes from 5-fluorouracil-treated Trib3-/- mice additionally were more prone to lysis and exhibited elevated peroxide-induced reactive oxygen species. Ex vivo, the development of CD71posTer119pos erythroblasts from Trib3-/- bone marrow progenitors was attenuated, and this was associated with heightened EPO-dependent Erk1/2 activation and moderately increased Akt activation. For developmentally staged EPCs, gene profiling provided further initial insight into candidate mediators of EPO-induced Trib3 gene expression, including Cebp-beta, Atf4, Egr-1, and Nab1. Overall, Trib3 is indicated to act as a novel EPC-intrinsic governor of stress erythropoiesis.

Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.

INTRODUCTION: Recombinant human erythropoietin (rhEPO) is a first-line therapeutic for the anemia of chronic kidney disease, cancer chemotherapy, AIDS (Zidovudine therapy), and lower-risk myelodysplastic syndrome. However, rhEPO frequently elevates hypertension, is costly, and may affect cancer progression. Potentially high merit therefore exists for defining new targets for anti-anemia agents within erythropoietin (EPO) and EPO receptor (EPOR) regulatory circuits. AREAS COVERED: EPO production by renal interstitial fibroblasts is subject to modulation by several regulators of hypoxia-inducible factor 2a (HIF2a) including Iron Response Protein-1, prolyl hydroxylases, and HIF2a acetylases, each of which holds potential as anti-anemia drug targets. The cell surface receptor for EPO (EPOR) preassembles as a homodimer, together with Janus Kinase 2 (JAK2), and therefore it remains attractive to develop novel agents that trigger EPOR complex activation (activating antibodies, mimetics, small-molecule agonists). Additionally, certain downstream transducers of EPOR/JAK2 signaling may be druggable, including Erythroferrone (a hepcidin regulator), a cytoprotective Spi2a serpin, and select EPOR-associated protein tyrosine phosphatases. EXPERT OPINION: While rhEPO (and biosimilars) are presently important mainstay erythropoiesis-stimulating agents (ESAs), impetus exists for studies of novel ESAs that fortify HIF2a's effects, act as EPOR agonists, and/or bolster select downstream EPOR pathways to erythroid cell formation. Such agents could lessen rhEPO dosing, side effects, and/or costs.

Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.

Prime regulation over hematopoietic progenitor cell (HPC) production is exerted by hematopoietins (HPs) and their Janus kinase-coupled receptors (HP-Rs). For HP/HP-R studies, one central challenge in determining specific effects involves the delineation of nonredundant signal transduction factors and their lineage restricted actions. Via loss-of-function studies, we define roles for an HP-regulated Serpina3g/Spi2A intracellular serpin during granulomyelocytic, B-cell, and hematopoietic stem cell (HSC) formation. In granulomyelocytic progenitors, granulocyte macrophage colony stimulating factor (GMCSF) strongly induced Serpina3g expression with Stat5 dependency. Spi2A-knockout (KO) led to 20-fold decreased CFU-GM formation, limited GMCSF-dependent granulocyte formation, and compromised neutrophil survival upon tumor necrosis factor alpha (TNF-α) exposure. In B-cell progenitors, Serpina3g was an interleukin-7 (IL7) target. Spi2A-KO elevated CFU-preB greater than sixfold and altered B-cell formation in competitive bone marrow transplant (BMT), and CpG challenge experiments. In HSCs, Serpina3g/Spi2A expression was also elevated. Spi2A-KO compromised LT-HSC proliferation (as well as lineage(neg) Sca1(pos) Kit(pos) (LSK) cell lysosomal integrity), and skewed LSK recovery post 5-FU. Spi2A therefore functions to modulate HP-regulated immune cell and HSC formation post-5-FU challenge.