ABSTRACT
Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.
Subject(s)
Autophagy , Genital Neoplasms, Female/diagnosis , Leukocytes, Mononuclear/physiology , Adult , Aged , Biomarkers, Tumor/metabolism , Body Fluids , Cells, Cultured , Female , Genital Neoplasms, Female/metabolism , Humans , Middle Aged , RNA-Binding Proteins/metabolism , ROC Curve , Vagina/pathologyABSTRACT
Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients..
Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Quality of Life/psychology , Restless Legs Syndrome/therapy , Sleep Apnea, Obstructive/therapy , Sleep Initiation and Maintenance Disorders/therapy , Cross-Sectional Studies , Hematologic Neoplasms/complications , Hematologic Neoplasms/psychology , Hospitalization , Humans , Physical Therapy Modalities , Psychotherapy/methods , Restless Legs Syndrome/complications , Restless Legs Syndrome/psychology , Risk Factors , Severity of Illness Index , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/psychology , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/psychology , Surveys and Questionnaires , Transplantation, HomologousABSTRACT
Most malaria research in sub-Saharan Africa has focused on children and pregnant women, but malaria among hospitalized adults in this region is poorly characterized. In this prospective study, we assessed the prevalence and clinical characteristics of malaria among the inpatient adults in two hospitals in Tanzania. We enrolled adults admitted with suspected malaria and performed routine thick blood smear (BS) and malaria rapid diagnostic tests (RDT). We also assessed malaria parasite clearance rates. We considered malaria status 'confirmed' or 'excluded' only in patients with two concordant tests. Malaria polymerase chain reaction (PCR) was performed in a subset of patients with discordant BS and RDT. After BS and RDT were performed on 579 adults with suspected malaria, malaria was excluded in 458/579 (79.1%) and confirmed in 16/579 (2.8%). One hundred and five out of 579 (18.1%) had discordant results. The prevalences of positive BS and positive RDT were 102/579 (17.6%) and 35/579 (6.0%), respectively, with only fair agreement (Kappa=0.354, p<0.0001). PCR results agreed with RDT in 35/35 (100%) of patients with a negative RDT but positive BS. PCR results also agreed with RDT in 9/13 (69.2%) of cases with a positive RDT but negative BS. Clinical correlates of malaria by multivariable analysis included subjective fever (OR 3.6 [1.0-12.3], p=0.04), headache (OR 3.1 [1.2-8.0], p=0.02) and vomiting (OR 2.7 [1.2-6.4], p=0.02). Malaria parasite clearance was significantly delayed in the HIV-infected group. Our study demonstrated only fair agreement between RDT and BS malaria tests among Tanzanian adult inpatients with suspected malaria. PCR generally agreed with RDT results. HIV was associated with delayed parasite clearance in adults with malaria. We recommend the routine use of RDTs for malaria diagnosis among adults admitted to hospitals in sub-Saharan Africa.
