Takotsubo cardiomyopathy in the setting of severe hyponatremia and beer potomania: A case report.

Takotsubo cardiomyopathy (TC), an acute cardiac event is often associated with acute emotional stress, usually in the setting of cardiovascular risk factors. This case report attempts to review one of the triggers of TC beer potomania-induce hyponatremia with imaging findings that shows the link between severe hyponatremia and TC.

PDMS-PEG Block Copolymer and Pretreatment for Arresting Drug Absorption in Microphysiological Devices.

Poly(dimethylsiloxane) (PDMS) is a commonly used polymer in organ-on-a-chip devices and microphysiological systems. However, due to its hydrophobicity and permeability, it absorbs drug compounds, preventing accurate drug screening applications. Here, we developed an effective and facile method to prevent the absorption of drugs by utilizing a PDMS-PEG block copolymer additive and drug pretreatment. First, we incorporated a PDMS-PEG block copolymer into PDMS to address its inherent hydrophobicity. Next, we addressed the permeability of PDMS by eliminating the concentration gradient via pretreatment of the PDMS with the drug prior to experimentally testing drug absorption. The combined use of a PDMS-PEG block copolymer with drug pretreatment resulted in a mean reduction of drug absorption by 91.6% in the optimal condition. Finally, we demonstrated that the proposed method can be applied to prevent drug absorption in a PDMS-based cardiac microphysiological system, enabling more accurate drug studies.

Reducing Anxiety with Nature and Gardening (RANG): Evaluating the Impacts of Gardening and Outdoor Activities on Anxiety among U.S. Adults during the COVID-19 Pandemic.

The COVID-19 pandemic impacted mental health. Growing research has identified the mental health benefits of nature contact, including gardening. We used a cross-sectional survey to investigate the association between gardening and other outdoor activities with anxiety among U.S. adults. The RANG (Reducing Anxiety with Nature and Gardening) survey was distributed online from June−September 2020 through social media (Twitter and Facebook) and a national Master Gardeners listserv. Survey questions captured demographics, COVID-19 experiences, gardening, outdoor activities, and anxiety using the Generalized Anxiety Disorder 7-item scale. Data were analyzed using chi-square, Fisher's exact, and Kruskal−Wallis tests, as well as logistic regression. Among participants, 46% reported anxiety symptoms. Participants who had gardened ≥ 15 years and those gardening > 8 h over two weeks had lower anxiety scores. Spending more time outdoors on weekdays also decreased anxiety scores. After adjusting for covariates, lower odds of anxiety were identified for 50−69 and 70−89-year-olds vs. 18−29-year-olds; males vs. females; and Texas vs. Maryland residents. These findings confirm increased anxiety during the COVID-19 pandemic and suggest that sustained gardening and other outdoor activities could help reduce anxiety.

Can natural language processing models extract and classify instances of interpersonal violence in mental healthcare electronic records: an applied evaluative study.

OBJECTIVE: This paper evaluates the application of a natural language processing (NLP) model for extracting clinical text referring to interpersonal violence using electronic health records (EHRs) from a large mental healthcare provider. DESIGN: A multidisciplinary team iteratively developed guidelines for annotating clinical text referring to violence. Keywords were used to generate a dataset which was annotated (ie, classified as affirmed, negated or irrelevant) for: presence of violence, patient status (ie, as perpetrator, witness and/or victim of violence) and violence type (domestic, physical and/or sexual). An NLP approach using a pretrained transformer model, BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) was fine-tuned on the annotated dataset and evaluated using 10-fold cross-validation. SETTING: We used the Clinical Records Interactive Search (CRIS) database, comprising over 500 000 de-identified EHRs of patients within the South London and Maudsley NHS Foundation Trust, a specialist mental healthcare provider serving an urban catchment area. PARTICIPANTS: Searches of CRIS were carried out based on 17 predefined keywords. Randomly selected text fragments were taken from the results for each keyword, amounting to 3771 text fragments from the records of 2832 patients. OUTCOME MEASURES: We estimated precision, recall and F1 score for each NLP model. We examined sociodemographic and clinical variables in patients giving rise to the text data, and frequencies for each annotated violence characteristic. RESULTS: Binary classification models were developed for six labels (violence presence, perpetrator, victim, domestic, physical and sexual). Among annotations affirmed for the presence of any violence, 78% (1724) referred to physical violence, 61% (1350) referred to patients as perpetrator and 33% (731) to domestic violence. NLP models' precision ranged from 89% (perpetrator) to 98% (sexual); recall ranged from 89% (victim, perpetrator) to 97% (sexual). CONCLUSIONS: State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.

Engineering Three-Dimensional Vascularized Cardiac Tissues.

Heart disease is one of the largest burdens to human health worldwide and has very limited therapeutic options. Engineered three-dimensional (3D) vascularized cardiac tissues have shown promise in rescuing cardiac function in diseased hearts and may serve as a whole organ replacement in the future. One of the major obstacles in reconstructing these thick myocardial tissues to a clinically applicable scale is the integration of functional vascular networks capable of providing oxygen and nutrients throughout whole engineered constructs. Without perfusion of oxygen and nutrient flow throughout the entire engineered tissue not only is tissue viability compromised, but also overall tissue functionality is lost. There are many supporting technologies and approaches that have been developed to create vascular networks such as 3D bioprinting, co-culturing hydrogels, and incorporation of soluble angiogenic factors. In this state-of-the-art review, we discuss some of the most current engineered vascular cardiac tissues reported in the literature and future directions in the field. Impact statement The field of cardiac tissue engineering is rapidly evolving and is now closer than ever to having engineered tissue models capable of predicting preclinical responses to therapeutics, modeling diseases, and being used as a means of rescuing cardiac function following injuries to the native myocardium. However, a major obstacle of engineering thick cardiac tissue remains to be the integration of functional vasculature. In this review, we highlight seminal and recently published works that have influenced and pushed the field of cardiac tissue engineering toward achieving vascularized functional tissues.

Cognitive Impairments in Schizophrenia: A Study in a Large Clinical Sample Using Natural Language Processing.

Background: Cognitive impairments are a neglected aspect of schizophrenia despite being a major factor of poor functional outcome. They are usually measured using various rating scales, however, these necessitate trained practitioners and are rarely routinely applied in clinical settings. Recent advances in natural language processing techniques allow us to extract such information from unstructured portions of text at a large scale and in a cost effective manner. We aimed to identify cognitive problems in the clinical records of a large sample of patients with schizophrenia, and assess their association with clinical outcomes. Methods: We developed a natural language processing based application identifying cognitive dysfunctions from the free text of medical records, and assessed its performance against a rating scale widely used in the United Kingdom, the cognitive component of the Health of the Nation Outcome Scales (HoNOS). Furthermore, we analyzed cognitive trajectories over the course of patient treatment, and evaluated their relationship with various socio-demographic factors and clinical outcomes. Results: We found a high prevalence of cognitive impairments in patients with schizophrenia, and a strong correlation with several socio-demographic factors (gender, education, ethnicity, marital status, and employment) as well as adverse clinical outcomes. Results obtained from the free text were broadly in line with those obtained using the HoNOS subscale, and shed light on additional associations, notably related to attention and social impairments for patients with higher education. Conclusions: Our findings demonstrate that cognitive problems are common in patients with schizophrenia, can be reliably extracted from clinical records using natural language processing, and are associated with adverse clinical outcomes. Harvesting the free text from medical records provides a larger coverage in contrast to neurocognitive batteries or rating scales, and access to additional socio-demographic and clinical variables. Text mining tools can therefore facilitate large scale patient screening and early symptoms detection, and ultimately help inform clinical decisions.

A prospective cohort study of two predictor models for 30-day emergency readmission in older patients.

AIM: To undertake a prospective study of the accuracy of two models (LACE and BOOST) in predicting unplanned hospital readmission in older patients (>75 years). METHODS: Data were collected from a single centre prospectively on 110 patients over 75 years old admitted to the acute medical unit. Follow-up was conducted at 30 days. The primary outcome was the c-statistic for both models. RESULTS: The readmission rate was 32.7% and median age 82 years, and both BOOST and LACE scores were significantly higher in those readmitted compared with those who were not. C-statistics were calculated for both tools with BOOST score 0.667 (95% CI 0.559-0.775, P = .005) and LACE index 0.685 (95% CI 0.579-0.792, P = .002). CONCLUSION: In this prospective study, both the BOOST and LACE scores were found to be significant yet poor, predictive models of hospital readmission. Recent hospitalisation (within the previous 6 months) was found to be the most significant contributing factor.

Reduced Vitellogenesis and Female Fertility in Gper Knockout Zebrafish.

The role G-protein coupled estrogen receptor (GPER) plays in vertebrate reproduction remains controversial. To investigate GPER's reproductive role, we generated a gper zebrafish mutant line (gper-/- ) using TALENs. Gper mutant females exhibited reduced fertility with a 40.85% decrease in embryo production which was associated with a significant decrease in the number of Stage V (730-750 µm) ovulated oocytes. Correspondingly, the number of early vitellogenic follicles (Stage III, 400-450 µm) in gper-/- ovaries was greater than that in wildtypes (wt), suggesting that subsequent follicle development was retarded in the gper-/- fish. Moreover, plasma vitellogenin levels were decreased in gper-/- females, and epidermal growth factor receptor (Egfr) expression was lower in Stage III vitellogenic oocytes than in wt counterparts. However, hepatic nuclear estrogen receptor levels were not altered, and estrogen levels were elevated in ovarian follicles. These results suggest that Gper is involved in the control of ovarian follicle development via regulation of vitellogenesis and Egfr expression in zebrafish.

Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review.

BACKGROUND: The cognitive impacts of resective surgery for epilepsy have been well-studied. While seizure outcomes for less invasive, neuromodulatory treatments are promising, there is a paucity of data for cognitive outcomes. METHODS: Medline, EMBASE, and the Cochrane Library were searched on November 2019. Inclusion criteria were studies reporting cognitive outcomes following chronic (>6 months) vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS) for epilepsy in at least five patients. Studies reporting acute on-off effects of stimulation were also included. Studies were screened, extracted of data, and assessed for bias using the Joanna Briggs Institute Critical Appraisal Tools by two independent reviewers. Prospero ID: CRD42020184432. RESULTS: Of 8443 studies screened, 29 studies were included. Nineteen investigated the effects of chronic stimulation (11 VNS, 6 DBS, 2 RNS): 10 (53 %) reported no change compared to preoperative baseline; 8 (42 %) reported some improvement in one or more cognitive domain; 1 (5%) reported decline. Ten investigated the effects of acute stimulation (5 VNS, 5 DBS): 3 (30 %) reported no change; 4 reported improvement (40 %); 3 (30 %) reported decline. Eight (28 %) did not report statistical analysis. CONCLUSIONS: Long-term cognitive outcomes are at least stable following VNS, DBS and RNS. Acute effects of stimulation are less clear. However, data are limited by number, size, and quality. More robust evidence is needed to properly assess the cognitive effects of each of these treatments.

Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson's disease: A pilot study.

BACKGROUND: There is significant evidence for cognitive decline following deep brain stimulation (DBS). Current stimulation paradigms utilize gamma frequency stimulation for optimal motor benefits; however, little has been done to optimize stimulation parameters for cognition. Recent evidence implicates subthalamic nucleus (STN) theta oscillations in executive function, and theta oscillations are well-known to relate to episodic memory, suggesting that theta frequency stimulation could potentially improve cognition in Parkinson's disease (PD). OBJECTIVE: To evaluate the acute effects of theta frequency bilateral STN stimulation on executive function in PD versus gamma frequency and off, as well as investigate the differential effects on episodic versus nonepisodic verbal fluency. METHODS: Twelve patients (all males, mean age 60.8) with bilateral STN DBS for PD underwent a double-blinded, randomized cognitive testing during stimulation at (1) 130-135 Hz (gamma), (2) 10 Hz (theta) and (3) off. Executive functions and processing speed were evaluated using verbal fluency tasks (letter, episodic category, nonepisodic category, and category switching), color-word interference task, and random number generation task. Performance at each stimulation frequency was compared within subjects. RESULTS: Theta frequency significantly improved episodic category fluency compared to gamma, but not compared to off. There were no significant differences between stimulation frequencies in other tests. CONCLUSION: In this pilot trial, our results corroborate the role of theta oscillations in episodic retrieval, although it is unclear whether this reflects direct modulation of the medial temporal lobe and whether similar effects can be found with more canonical memory paradigms. Further work is necessary to corroborate our findings and investigate the possibility of interleaving theta and gamma frequency stimulation for concomitant motor and cognitive effects.

Is there a dry season in the Southeast US?

Fill et al. (Global Change Biology, 25, 3562-3569, 2019) reported significant increases in dry season length over the past 120 years in the Southeast US, suggesting increased wildfire risk in a region associated with a frequent fire regime. We identified two flaws that call into question the findings and their relevance to regional wildfire risk. First, with the exception of Florida, there is little evidence for a climatologically meaningful 'dry season' in the Southeast because most areas experience relatively evenly distributed monthly precipitation. Second, the sampling method used to derive Cumulative Rainfall Anomalies does not appear to actually reflect a bootstrap sample as described.

An RNA pseudoknot stimulates HTLV-1 pro-pol programmed -1 ribosomal frameshifting.

Programmed -1 ribosomal frameshifts (-1 PRFs) are commonly used by viruses to regulate their enzymatic and structural protein levels. Human T-cell leukemia virus type 1 (HTLV-1) is a carcinogenic retrovirus that uses two independent -1 PRFs to express viral enzymes critical to establishing new HTLV-1 infections. How the cis-acting RNA elements in this viral transcript function to induce frameshifting is unknown. The objective of this work was to conclusively define the 3' boundary of and the RNA elements within the HTLV-1 pro-pol frameshift site. We hypothesized that the frameshift site structure was a pseudoknot and that its 3' boundary would be defined by the pseudoknot's 3' end. To test these hypotheses, the in vitro frameshift efficiencies of three HTLV-1 pro-pol frameshift sites with different 3' boundaries were quantified. The results indicated that nucleotides included in the longest construct were essential to highly efficient frameshift stimulation. Interestingly, only this construct could form the putative frameshift site pseudoknot. Next, the secondary structure of this frameshift site was determined. The dominant structure was an H-type pseudoknot which, together with the slippery sequence, stimulated frameshifting to 19.4(±0.3)%. The pseudoknot's critical role in frameshift stimulation was directly revealed by examining the impact of structural changes on HTLV-1 pro-pol -1 PRF. As predicted, mutations that occluded pseudoknot formation drastically reduced the frameshift efficiency. These results are significant because they demonstrate that a pseudoknot is important to HTLV-1 pro-pol -1 PRF and define the frameshift site's 3' boundary.

Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish.

Progestin receptor membrane component (Pgrmc1 & 2) is a heme-binding protein. Studies on Pgrmc1 have suggested possible roles in heme binding, activation of steroid-synthesizing P450s, along with binding and transferring of membrane proteins. However, the studies of Pgrmc1's paralog, Pgrmc2 are still lacking. In order to determine the physiologic function(s) of Pgrmc2, we generated a zebrafish mutant line (pgrmc2-/-). We found a reduction in both spawning frequency and the number of embryos produced in female pgrmc2-/-. This subfertility is caused by reduced oocyte maturation (germinal vesicle breakdown, GVBD) in pgrmc2-/- in vivo. Nonetheless, oocytes from pgrmc2-/- had similar sensitivity to 17α,20ß-dihydroxy-4-pregnen-3-one (DHP, a maturation induced progestin in zebrafish) compared with wildtype (wt) in vitro. Therefore, we hypothesized that oocyte maturation tardiness found in vivo, could be due to lack of progestin in pgrmc2-/-. Interestingly, we found significant reduced expression of hormones, receptors, and steroid synthesizing enzymes including lhcgr, egfra, ar, and esr2, cyp11a1 and hsd3b1. In addition, DHP levels in pgrmc2-/- ovaries showed a significant decrease compared to those in wt. In summary, we have provided a plausible molecular mechanism for the physiological functions of Pgrmc2 in the regulation of female fertility, likely via regulation of receptors and steroids in the ovary, which in turn regulates oocyte maturation in zebrafish.

The Association of Black Cardiologists (ABC) Cardiovascular Implementation Study (CVIS): A Research Registry Integrating Social Determinants to Support Care for Underserved Patients.

African Americans, other minorities and underserved populations are consistently under- represented in clinical trials. Such underrepresentation results in a gap in the evidence base, and health disparities. The ABC Cardiovascular Implementation Study (CVIS) is a comprehensive prospective cohort registry that integrates social determinants of health. ABC CVIS uses real world clinical practice data to address critical gaps in care by facilitating robust participation of African Americans and other minorities in clinical trials. ABC CVIS will include diverse patients from collaborating ABC member private practices, as well as patients from academic health centers and Federally Qualified Health Centers (FQHCs). This paper describes the rationale and design of the ABC CVIS Registry. The registry will: (1) prospectively collect socio-demographic, clinical and biospecimen data from enrolled adults, adolescents and children with prioritized cardiovascular diseases; (2) Evaluate the safety and clinical outcomes of new therapeutic agents, including post marketing surveillance and pharmacovigilance; (3) Support National Institutes of Health (NIH) and industry sponsored research; (4) Support Quality Measures standards from the Center for Medicare and Medicaid Services (CMS) and Commercial Health Plans. The registry will utilize novel data and technology tools to facilitate mobile health technology application programming interface (API) to health system or practice electronic health records (EHR). Long term, CVIS will become the most comprehensive patient registry for underserved diverse patients with cardiovascular disease (CVD) and co morbid conditions, providing real world data to address health disparities. At least 10,000 patients will be enrolled from 50 sites across the United States.

Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification.

BACKGROUND: We conducted two independent nested case-control studies to identify circulating inflammation markers reproducibly associated with lung cancer risk and to investigate the utility of replicated markers for lung cancer risk stratification. METHODS: Nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the previously published discovery study included 526 lung cancer patients and 592 control subjects and the replication study included 526 lung cancer case patients and 625 control subjects. Control subjects were matched by sex, age, smoking, study visit, and years of blood draw and exit. Serum levels of 51 inflammation markers were measured. Odds ratios (ORs) were estimated with conditional logistic regression. All statistical tests were two-sided. RESULTS: Of 11 markers identified in the discovery study, C-reactive protein (CRP) (odds ratio [OR] [highest vs. lowest category] = 1.77, 95% confidence interval [CI] = 1.23 to 2.54), serum amyloid A (SAA) (OR = 1.88, 95% CI = 1.28 to 2.76), soluble tumor necrosis factor receptor-2 (sTNFRII) (OR = 1.70, 95% CI = 1.18 to 2.45), and monokine induced by gamma interferon (CXCL9/MIG) (OR = 2.09, 95% CI = 1.41 to 3.00) were associated with lung cancer risk in the replication study (P trend < .01). In pooled analyses, CRP, SAA, and CXCL9/MIG remained associated with lung cancer more than six years before diagnosis (P trend < .05). The incorporation of an inflammation score combining these four markers did not improve the sensitivity (77.6% vs 75.8%, P = .33) or specificity (56.1% vs 56.1%, P = .98) of risk-based lung cancer models. CONCLUSIONS: Circulating levels of CRP, SAA, sTNFRII, and CXCL9/MIG were reproducibly associated with lung cancer risk in two independent studies within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, underscoring an etiologic role for inflammation in lung carcinogenesis, though replication is needed in other populations. Markers did not improve lung cancer risk stratification beyond standard demographic and behavioral characteristics.

Immune status of patients with inherited bone marrow failure syndromes.

Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome (SDS), and Diamond-Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared the results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid treatment, and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes, and CD4 T cells than reference values or adult relatives (P < 0.001); children with FA had normal values. Both children and adults with FA had lower B- and NK cells (P < 0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T-, B-, and NK-cells; these changes were more marked in children than adults (P < 0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including tumor necrosis factor-α and interferon-γ, and cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and lower RANTES levels compared with all other groups or relatives (P < 0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease-related progression, and in children with DC, which may be a feature of early-onset severe disease phenotype.

Reductions in neuronal peroxisomes in multiple sclerosis grey matter.

BACKGROUND: Peroxisomes are organelles in eukaryotic cells with multiple functions including the detoxification of reactive oxygen species, plasmalogen synthesis and ß-oxidation of fatty acids. Recent evidence has implicated peroxisomal dysfunction in models of multiple sclerosis (MS) disease progression. OBJECTIVES: Our aims were to determine whether there are changes in peroxisomes in MS grey matter (GM) compared to control GM. METHODS: We analysed cases of MS and control GM immunocytochemically to assess peroxisomal membrane protein (PMP70) and neuronal proteins. We examined the expression of ABCD3 (the gene that encodes PMP70) in MS and control GM. Analyses of very long chain fatty acid (VLCFA) levels in GM were performed. RESULTS: PMP70 immunolabelling of neuronal somata was significantly lower in MS GM compared to control. Calibration of ABCD3 gene expression with reference to glyceraldehyde 3-phsophate dehydrogenase (GAPDH) revealed overall decreases in expression in MS compared to controls. Mean PMP70 counts in involved MS GM negatively correlated to disease duration. Elevations in C26:0 (hexacosanoic acid) were found in MS GM. CONCLUSIONS: Collectively, these observations provide evidence that there is an overall reduction in peroxisomal gene expression and peroxisomal proteins in GM neurons in MS. Changes in peroxisomal function may contribute to neuronal dysfunction and degeneration in MS.

Clinical evaluation and follow-up of body mass and blood pressure in pre-elementary school children: program review.

While administrators of pre-elementary school programs throughout the country recognize the importance of screening and monitoring body mass and hypertension in early childhood populations, typically, few efforts are undertaken to systematically, retrospectively, and critically review them. A retrospective cross-sectional analysis of measures, reflective of body mass and blood pressure, collected from a targeted group of 10 urban pre-elementary schools in the Midwestern region of the country, was therefore undertaken. Overweight, obesity, and blood pressure readings suggestive of pre-hypertension and hypertension were found to be more prevalent among both boys and children whose school and residences were located in low-income neighborhoods. More surprising, however, was the lack of documentation of notations in their health records about their BMI status, blood pressure status, and/or need for re-assessment, referral, or follow-up.

Oral Immunoglobulin Levels are Not a Good Surrogate for Cervical Immunoglobulin Levels.

BACKGROUND: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig) levels. To do so, we examined (1) whether oral IgG and IgA levels correlated with those observed at the cervix, and (2) whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. METHODS: We obtained oral samples from a group of 85 Costa Rican woman 25-35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. RESULTS: We did not observe an association between oral and cervical IgG [linear regression coefficient (LRC) 0.01; 95% CI, -0.05 to 0.07] and IgA levels (LRC 0.02; 95% CI, -0.04 to 0.08). Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. CONCLUSION: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites.

Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study.

BACKGROUND: Chronic inflammation is etiologically related to several cancers. We evaluated the performance [ability to detect concentrations above the assay's lower limit of detection, coefficients of variation (CV), and intraclass correlation coefficients (ICC)] of 116 inflammation, immune, and metabolic markers across two Luminex bead-based commercial kits and three specimen types. METHODS: From 100 cancer-free participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Trial, serum, heparin plasma, and EDTA plasma samples were utilized. We measured levels of 67 and 97 markers using Bio-Rad and Millipore kits, respectively. Reproducibility was assessed using 40 blinded duplicates (20 within-batches and 20 across-batches) for each specimen type. RESULTS: A majority of markers were detectable in more than 25% of individuals on all specimen types/kits. Of the 67 Bio-Rad markers, 51, 52, and 47 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. Likewise, of 97 Millipore markers, 75, 69, and 78 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. When results were combined across specimen types, 45 Bio-Rad and 71 Millipore markers had acceptable performance (>25% detectability on all three specimen types and across-batch CVs <20% on at least two of three specimen types). Median concentrations and ICCs differed to a small extent across specimen types and to a large extent between Bio-Rad and Millipore. CONCLUSIONS: Inflammation and immune markers can be measured reliably in serum and plasma samples using multiplexed Luminex-based methods. IMPACT: Multiplexed assays can be utilized for epidemiologic investigations into the role of inflammation in cancer etiology.