Neutrophil function in psoriasis: effects of retinoids

The present investigation focused on the oxidative response of polymorphonuclear neutrophil leukocytes in psoriasis, in particular pustular psoriasis and how this response was affected by different retinoid compounds. In the active phase of pustular psoriasis, the neutrophil chemiluminescence response to the chemotactic peptide f-met-leu-phe and to phorbol myristate acetate was enhanced and correlated to the development of pustules, whereas cells from psoriasis vulgaris patients showed normal chemiluminescence response. Retinoids, particularly tretinoin (= retinoic acid) and isotretinoin caused a pronounced inhibition of the chemiluminescence response only in primed neutrophils in vivo and in vitro, whereas etretinate and the metabolite Ro 10-1670 was less inhibitory. Retinoic acid furthermore inhibited the Fc-mediated phagocytosis, but did not affect C3bi-mediated phagocytosis. These data suggest that the antiinflammatory effect of retinoids may operate by affecting neutrophil activation and function.     

Limitation of inverse probability-of-censoring weights in estimating survival in the presence of strong selection bias

In time-to-event analyses, artificial censoring with correction for induced selection bias using inverse probability-of-censoring weights can be used to 1) examine the natural history of a disease after effective interventions are widely available, 2) correct bias due to noncompliance with fixed or dynamic treatment regimens, and 3) estimate survival in the presence of competing risks. Artificial censoring entails censoring participants when they meet a predefined study criterion, such as exposure to an intervention, failure to comply, or the occurrence of a competing outcome. Inverse probability-of-censoring weights use measured common predictors of the artificial censoring mechanism and the outcome of interest to determine what the survival experience of the artificially censored participants would be had they never been exposed to the intervention, complied with their treatment regimen, or not developed the competing outcome. Even if all common predictors are appropriately measured and taken into account, in the context of small sample size and strong selection bias, inverse probability-of-censoring weights could fail because of violations in assumptions necessary to correct selection bias. The authors used an example from the Multicenter AIDS Cohort Study, 1984-2008, regarding estimation of long-term acquired immunodeficiency syndrome-free survival to demonstrate the impact of violations in necessary assumptions. Approaches to improve correction methods are discussed.     

Occupational exposure to magnetic fields and the risk of brain tumors

We investigated the association between occupational exposure to extremely low-frequency magnetic fields (MFs) and the risk of glioma and meningioma. Occupational exposure to MF was assessed for 489 glioma cases, 197 meningioma cases, and 799 controls enrolled in a hospital-based case–control study. Lifetime occupational history questionnaires were administered to all subjects; for 24% of jobs, these were supplemented with job-specific questionnaires, or “job modules,” to obtain information on the use of electrically powered tools or equipment at work. Job-specific quantitative estimates for exposure to MF in milligauss were assigned using a previously published job exposure matrix (JEM) with modification based on the job modules. Jobs were categorized as ≤1.5 mG, >1.5 to <3.0 mG, and ≥3.0 mG. Four exposure metrics were evaluated: (1) maximum exposed job; (2) total years of exposure >1.5 mG; (3) cumulative lifetime exposure; and (4) average lifetime exposure. Odds ratios (ORs) were calculated using unconditional logistic regression with adjustment for the age, gender, and hospital site. The job modules increased the number of jobs with exposure ≥3.0 mG from 4% to 7% relative to the JEM. No statistically significant elevation in ORs or trends in ORs across exposure categories was observed using four different exposure metrics for the three tumor types analyzed. Occupational exposure to MFs assessed using job modules was not associated with an increase in the risk for glioma, glioblastoma, or meningioma among the subjects evaluated in this study.     

Harmful by Design—a Qualitative Study of the Health Impacts of Immigration Detention

BackgroundThe USA has the largest immigration detention system in the world with over 20,000 individuals imprisoned by Immigration and Customs Enforcement (ICE) daily. Numerous reports have documented human rights abuses in immigration detention, yet little is known about its health impacts.ObjectiveTo characterize how the US immigration detention system impacts health from the perspective of people who were recently detained by ICE.DesignQualitative study using anonymous, semi-structured phone interviews in English or Spanish conducted between July 2020 and February 2021.ParticipantsAdults who had been detained by ICE for at least 30 days in the New York City metropolitan area within the previous 2 years, and that were fluent in English and/or Spanish.ApproachWe explored participants’ health histories and experiences trying to meet physical and mental health needs while in detention and after release. We conducted a reflective thematic analysis using an inductive approach.Key ResultsOf 16 participants, 13 identified as male; five as lesbian, gay, bisexual, or queer; and four as Black; they were from nine countries. Participants had spent a median of 20 years living in the USA and spent a median of 11 months in immigration detention. Four themes emerged from our analysis: (1) poor conditions and inhumane treatment, (2) a pervasive sense of injustice, (3) structural barriers limiting access to care, and (4) negative health impacts of immigration detention.ConclusionsThe narratives illustrate how structural features of immigration detention erode health while creating barriers to accessing needed medical care. Clinicians caring for immigrant communities must be cognizant of these health impacts. Community-based alternatives to immigration detention should be prioritized to mitigate health harms.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07914-6.KEY WORDS: immigration, detention, structural vulnerability, COVID-19     

Electroencephalographic sleep diagnosis of primary depression.

Studies of severely depressed hospitalized patients suggest a shortened rapid eye movement (REM) latency as a specific biological marker for primary affective disease. To assess the validity of these findings, 40 outpatients referred to our Electroencephalographic Sleep Center for evaluation of depressive symptoms were studied. Concurrent with the all night EEG sleep studies, all patients received a brief clinical interview and a battery of self-rating scales. The entire sample was then subdivided into primary and secondary depressives on the basis of follow-up diagnoses. While there were no significant differences between groups on self-ratings of depressive symptoms, the group of primary depressives had significantly shorter REM latencies and higher measures of phasic REM than the secondary depressives. Furthermore, in this patient group, the delineation of primary vs secondary depression was greater than 80% on the basis of only two nights of EEG sleep. Such objective biological measures, if replicated, could provide a method for increasing the accuracy of differential diagnosis among depressed populations in clinical research.     

Application of automated REM and slow wave sleep analysis: I. Normal and depressed subjects

Computerized analysis of rapid eye movement (REM) and delta electroencephalographic (EEG) sleep patterns in normal and depressed subjects offers opportunities to examine sleep more precisely than previously possible. In the present study, automated REM analyses demonstrated good reliability with traditional manual procedures in both normal and depressed subjects. However, automated delta analyses correlated well with traditional scoring in normal subjects, but not in depressed patients. These findings suggest the use of automated delta techniques similar to those employed in this report or spectral analytic techniques in the following types of studies: specificity of delta sleep in various psychiatric syndromes, changes in delta sleep produced by the administration of psychotropic agents, relationships between delta sleep and sleep-related neuroendocrine patterns, and, finally, relationships between delta sleep patterns and other biological rhythms such as activity and temperature.     

Long-term effect of naproxen on cancellous bone in ovariectomized rats.

Previous work shows that at 42 d post-ovariectomy (OX) in aged rats, naproxen, a nonsteriodal anti-inflammatory drug (NSAID) prevents cancellous bone loss. The purpose of this study was to evaluate the effects of naproxen on cancellous bone of aged OX and sham-OX rats, at 90 days post-OX. Six-month-old Sprague-Dawley retired breeder female rats underwent either sham-OX (n = 49) or OX (n = 65). Sham-OX rats were randomized into five groups and OX rats into six groups. The first five groups of both were given ad lib access to water containing 0, 4, 10, 25, or 62.5 mg/l of naproxen sodium. The sixth group of OX rats was given water containing 156.25 mg naproxen sodium/l. After ninety days, the rats were killed following in vivo dual calcein labeling. Terminal serum naproxen was measured by HPLC. In the proximal tibial metaphysis, trabecular bone volume, trabecular thickness, trabecular number, mineralizing surface (double label), osteoclast surface, and bone formation rate were measured. Sham-OX and OX rats were compared by t-test of means. Kruskal-Wallis tests and, as necessary, Dunnett's t-tests, were applied separately to the groups of Sham-OX and OX rats. Dose-related serum levels of naproxen up to 9.4 mcg/ml were achieved in the 156.25 mg/ml group. OX rats had significantly lower bone volume, trabecular thickness, and trabecular number than Sham-OX groups (p less than .001). OX rats had significantly higher mineralizing surface, formation rate, and osteoclast surface than sham-OX rats (p less than .001). No differences related to naproxen treatment existed in sham-OX rats. Naproxen treatment producing a serum level of 9.4 mcg/ml reduced bone volume in OX rats consuming water with 156.25 mg/l (p less than .05). At 90 days post-OX, naproxen, at serum levels of 9.4 mcg/ml or less, did not diminish estrogen-depletion cancellous bone loss in rats. Naproxen lacks lasting ability to halt estrogen-depletion bone loss in aged OX rats.     

Aromatization of testosterone by epithelial tumor cells cultured from patients with ovarian carcinoma

Ovarian epithelial carcinoma originates from the surface mesothelium. It is controversial whether these tumors possess steroidogenic enzymes, similar to malignancies of other ovarian cell types. This study reports aromatase enzymatic activity for three epithelial cell lines, OV1225, OV166, and 2774, established from patients with ovarian adenocarcinoma. Aneuploidy of the cells was demonstrated by flow cytometric DNA analyses which showed OV1225 tetraploid, OV166 near diploid, and 2774 triploid. Estrogen synthesis was confirmed by measurement of estradiol (6 to 11 pg/10(7) cells/24 h) by radioimmunoassay in extracts of conditioned medium. To directly assay aromatase enzymatic activity, intact cells were incubated with tritiated testosterone. Medium was extracted with organic solvent after addition of trace 14C-labeled 17 beta-estradiol and 14C-labeled estrone. Androgen was separated from estrogen by celite column chromatography. Estrogen was further purified by silica gel thin-layer chromatography and derivatization of separate products to acetates. Purity of compounds was confirmed by consistency of the 3H:14C ratio of acetylated product versus that of product recrystallized with authentic standard. Conversion of testosterone to estradiol proceeded with apparent Michaelis-Menten kinetics. The apparent Km was 4 microM, 15 microM, and 59 microM, and the Vmax was 20 pmol/h/mg of cell protein, 52 pmol/h/mg of cell protein, and 152 pmol/h/mg of cell protein for 2774, OV166, and OV1225, respectively. We conclude that at least a portion of ovarian adenocarcinoma possesses sufficient aromatase activity to convert ovarian stromal androgen to estrogen.