Patient-Reported Outcomes in Asthma.

Food and Drug Administration's Center for Drug Evaluation and Research defines patient-reported outcomes as "any report of the status of a patient's health condition, health behavior, or experience with healthcare that comes directly form the patient, without interpretation of the patient's response by a clinician or anyone else." Validated patient-reported outcome measures are used extensively in pediatric and adult asthma across clinical and research settings to assess the impact of treatments on patient outcomes over time. This work aims to review some of the most commonly used asthma patient-reported outcomes across the following criteria: validity, reliability, responsiveness, time to complete, ease of administration, target population, recall period, scoring method, availability in different languages, use in clinical practice or research settings, licensing requirements, and cost of use.

Maternal plasma and salivary anelloviruses in pregnancy and preterm birth.

Introduction: Human anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth. Methods: This is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel. Results: TTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants. Conclusion: Anellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.

Is human labor at term an inflammatory condition?†.

Parturition at term in normal pregnancy follows a predictable sequence of events. There is some evidence that a state of inflammation prevails in the reproductive tissues during labor at term, but it is uncertain whether this phenomenon is the initiating signal for parturition. The absence of a clear temporal sequence of inflammatory events prior to labor casts doubt on the concept that normal human labor at term is primarily the result of an inflammatory cascade. This review examines evidence linking parturition and inflammation in order to address whether inflammation is a cause of labor, a consequence of labor, or a separate but related phenomenon. Finally, we identify and suggest ways to reconcile inconsistencies regarding definitions of labor onset in published research, which may contribute to the variability in conclusions regarding the genesis and maintenance of parturition. A more thorough understanding of the processes underlying normal parturition at term may lead to novel insights regarding abnormal labor, including spontaneous preterm labor, preterm premature rupture of the fetal membranes, and dysfunctional labor, and the role of inflammation in each.

Toxic effects of trace phenol/guanidine isothiocyanate (P/GI) on cells cultured nearby in covered 96-well plates.

BACKGROUND: A mixture of phenol and guanidine isothiocyanate ("P/GI", the principal components of TRIzol™ and similar products) is routinely used to isolate RNA, DNA, and proteins from a single specimen. In time-course experiments of cells grown in tissue culture, replicate wells are often harvested sequentially and compared, with the assumption that in-well lysis and complete aspiration of P/GI has no effect on continuing cultures in nearby wells. METHODS: To test this assumption, we investigated morphology and function of RAW 264.7 cells (an immortalized mouse macrophage cell line) cultured in covered 96-well plates for 4, 8, or 24 h at varying distances from a single control well or a well into which P/GI had been deposited and immediately aspirated completely. RESULTS: Time- and distance-dependent disruptions resulting from proximity to a single well containing trace residual P/GI were seen in cell morphology (blebbing, cytoplasmic disruption, and accumulation of intracellular vesicles), cell function (pH of culture medium), and expression of genes related to inflammation (Tnfα) and autophagy (Lc3b). There was no transcriptional change in the anti-apoptotic gene Mcl1, nor the pro-apoptotic gene Hrk, nor in P/GI-unexposed control cultures. LPS-stimulated cells incubated near P/GI had lower expression of the cytokine Il6. These effects were seen as early as 4 h of exposure and at a distance of up to 3 well units from the P/GI-exposed well. CONCLUSIONS: Exposure to trace residual quantities of P/GI in covered tissue culture plates leads to substantial disruption of cell morphology and function in as little as 4 h, possibly through induction of autophagy but not apoptosis. This phenomenon should be considered when planning time-course experiments in multi-well covered tissue culture plates.