Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes.

Zulresso (brexanolone) is an aqueous formulation of the neurosteroid, allopregnanolone, and the only FDA-approved medication for the treatment of postpartum depression (PPD). While brexanolone is effective for the treatment of PPD, lengthy infusion time and high cost can be prohibitive. Failure of GABAA receptors to adapt to fluctuating neurosteroid levels is considered to predispose women to mood disorders in the postpartum period. Brexanolone is thought to act via stimulation of δ subunit-containing GABAA receptors, which are extrasynaptic and localized to particular brain regions. Neurosteroid stimulation of δ subunit-containing GABAA receptors leads to sustained inhibition (hyperpolarization) of GABAergic neurons, which makes δ subunit-containing GABAA receptors a potentially important pharmacologic target. Barbiturates and pyrazolopyridines are potent stimulators of δ subunit-containing GABAA receptors and therefore potentially cost-effective treatments for PPD. Barbiturates are often not prescribed, owing to risk of dependence and respiratory depression. The pyrazolopyridines were tested several decades ago for anxiety and depression but never developed commercially. Herein we use the FDA-approved dosing schedule of brexanolone and GABAA receptor binding data from various animal models to examine the safety, efficacy, and potential clinical utility of barbiturates and pyrazolopyridines for the treatment of PPD. We suggest consideration of repurposing barbiturates and pyrazolopyridines as safe and readily available treatment alternatives for PPD.

Behavioral variant frontotemporal dementia in a 23-year-old man.

A 23-year-old man presented with behavioral disinhibition, stereotypies, motor apathy, flattened affect, and inappropriate laughter. CT demonstrated generalized cerebral atrophy. He was admitted with a diagnosis of unspecified psychosis and discharged on antipsychotic medication. He was readmitted 3 months later, was diagnosed with schizophrenia, and antipsychotic medication was continued. Owing to symptom progression and aggressive behavior, he was readmitted 2 months later. CT again demonstrated moderate central and cortical cerebral atrophy. MRI showed severe, stable atrophy with frontotemporal predominance, and he was diagnosed with probable behavioral variant frontotemporal dementia (bvFTD).  Over the next year he rapidly deteriorated, with loss of cognitive abilities. Genetic testing revealed several variants, none of which are clearly disease-causing.

Formation of a fringe: A look inside baleen morphology using a multimodal visual approach.

Filter-feeding has been present for hundreds of millions of years, independently evolving in aquatic vertebrates' numerous times. Mysticete whales are a group of gigantic, marine filter-feeders that are defined by their fringed baleen and are divided into two groups: balaenids and rorquals. Recent studies have shown that balaenids likely feed using a self-cleaning, cross-flow filtration mechanism where food particles are collected and then swept to the esophagus for swallowing. However, it is unclear how filtering is achieved in the rorquals (Balaenopteridae). Lunging rorqual whales engulf enormous masses of both prey and water; the prey is then separated from the water through baleen plates lining the length of their upper jaw and positioned perpendicular to flow. Rorqual baleen is composed of both major (larger) and minor (smaller) keratin plates containing embedded fringe that extends into the whale's mouth, forming a filtering fringe. We used a multimodal approach, including microcomputed tomography (µCT) and scanning electron microscopy (SEM), to visualize and describe the variability in baleen anatomy across five species of rorqual whales, spanning two orders of magnitude in body length. For most morphological measurements, larger whales exhibited hypoallometry relative to body length. µCT and SEM revealed that the major and minor plates break away from the mineralized fringes at variable distances from the gums. We proposed a model for estimating the effective pore size to determine whether flow scales with body length or prey size across species. We found that pore size is likely not a proxy for prey size but instead, may reflect changes in resistance through the filter that affect fluid flow.

Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis.

INTRODUCTION: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). METHODS: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. RESULTS: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. CONCLUSIONS: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

Circadian cortisol secretion in adolescent girls with conduct disorder.

Severe antisocial behavior in girls, best exemplified by conduct disorder (CD), is a serious clinical and public health problem. Treatment is difficult, particularly in girls with comorbid internalizing disorders. Identifying biological correlates may help to develop new treatments or diagnostic, prognostic, or treatment response biomarkers. Based on our earlier work and research from others occurring primarily in boys with severe antisocial behavior, it is possible that abnormalities in the hypothalamic pituitary adrenal (HPA) axis circadian cortisol cycle may be associated with female CD. Additionally, research suggests that the presence of comorbid internalizing disorders may be related to differences in cortisol secretion, compared to subjects who only have CD. Our study aimed: 1) to compare the circadian cortisol cycle in 98 girls with CD, 15-16 years of age to 47 girls without any psychiatric disorder (ND) and 2) to compare the cycle in girls with CD and comorbid internalizing disorders (CD + INT) to those without such comorbidity (CD Only). Salivary cortisol was collected over 24 h during weekdays at scheduled times, with protocol adherence measures in place. Unstructured covariance pattern modeling, controlling for effects of age, social class, IQ, and awakening time was used to analyze cortisol data. CD was associated with overall lower cortisol secretion (p = 0.03), but this difference was due to a lower volume of cortisol secreted 30 min after awakening (area under the curve with respect to ground, p = 0.01). Circadian cortisol secretion was no different in the CD+INT group compared to the CD Only group (p = 0.52). Our findings need to be replicated using current consensus guidelines for the assessment of the CAR. We also suggest two new avenues of research in this field.

The rate, cost and outcomes of parathyroidectomy in the united states dialysis population from 2016-2018.

BACKGROUND: In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. METHODS: This was a retrospective observational cohort study using US Renal Data System data for 2015-2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. RESULTS: The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). CONCLUSIONS: Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.

Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity. We analyzed pooled and stratified exposure and outcome data from Navajo (n = 68) and Nicaraguan (n = 47) men of similar age and health status in order to characterize urinary concentrations of metals, compare concentrations with the US National Health and Nutrition Examination Survey (NHANES) male population, and examine the associations with biomarkers of autoimmunity. Urine samples were analyzed for metals via inductively coupled plasma mass spectrometry (ICP-MS) at the US Centers for Disease Control and Prevention. Serum samples were examined for antinuclear antibodies (ANA) at 1:160 and 1:40 dilutions, using an indirect immunofluorescence assay and for specific autoantibodies using enzyme-linked immunosorbent assay (ELISA). Logistic regression analyses evaluated associations of urinary metals with autoimmune biomarkers, adjusted for group (Navajo or Nicaraguan), age, and seafood consumption. The Nicaraguan men had higher urinary metal concentrations compared with both NHANES and the Navajo for most metals; however, tin was highest among the Navajo, and uranium was much higher in both populations compared with NHANES. Upper tertile associations with ANA positivity at the 1:160 dilution were observed for barium, cesium, lead, strontium and tungsten.

Calcimimetic Use in Dialysis-Dependent Medicare Fee-for-Service Beneficiaries and Implications for Bundled Payment.

Background: Patients who are dialysis dependent and have secondary hyperparathyroidism (SHPT) may require calcimimetics to reduce parathyroid hormone levels to treatment goals. Medicare currently uses the Transitional Drug Add-on Payment Adjustment (TDAPA) designation under the ESKD Prospective Payment System ("bundled payment") to pay for calcimimetics (the first products eligible for the adjustment); this payment designation for calcimimetics is expected to conclude after 2020. This study explores variability in calcimimetic use across key patient characteristics and its potential effect on policy options for incorporating calcimimetics permanently into the bundle. Methods: This descriptive analysis used the 100% sample of Medicare FFS Part B (outpatient) 2018 claims to describe national-, regional-, and patient-level variation (including race, dual eligibility, and dialysis vintage) in calcimimetic use among beneficiaries who are dialysis dependent. Results: A total of 373,874 beneficiaries were analyzed, 28% had ≥90 days of calcimimetic use during 2018. At the national level, the proportion of patients on dialysis using calcimimetics was roughly 80% higher in Black versus non-Black patients on dialysis, 30% higher in patients on dialysis who were dual eligible versus non-dual eligible, and three times higher in patients with a dialysis vintage ≥3 years versus <3 years (all results unadjusted). Calcimimetic use was similar across census regions, however, substantial variation in calcimimetic use was observed at the facility level. Medicare spending for calcimimetic therapies as a proportion of total Medicare dialysis spending was >10% in approximately 20% of dialysis facilities. Conclusions: Although less than a third of beneficiaries use calcimimetics, certain patient-level characteristics are associated with higher rates of maintenance calcimimetic use. Due to the financial pressure many dialysis facilities face, how calcimimetics are incorporated into the bundle may have a direct effect on facility reimbursement for, and patient access to, therapy. Careful consideration will be required to ensure patients who are vulnerable and require treatment for SHPT do not face barriers to appropriate care.

First description of a giant manta ray fetus Mobula birostris (Walbaum 1792) from Tumbes, Peru (Southeast Pacific).

The population of Mobula birostris ("giant manta ray") found in the waters of northern Peru and Ecuador is believed to be the largest in the world (Harding Beirwagen, 2009). This species is considered to be the largest within the group of manta rays, as they attains at least 670 cm disc width (reported to 910 cm) (White et al., 2006) and there is a record of an individual weighing 2000 kg (Kunjipalu Boopendranath, 1981). This species is ovoviviparous (matrotrophic viviparious) (Herbert, 2012). A single pup follows a gestation period of approximently one year, (Marshall et al., 2008, Mendonça et al., 2012). Sucessive pregnancies are speculated to be separated by a refactory period of two or more years (Mendonça et al., 2012). The objective of this study is to record the measurements of a M. birostris fetus of a female caught accidentally in the region of Tumbes, Peru. This is the first record of morphological and morphometric data regarding a manta fetus in Peru.

Proteomic Investigations of Autism Brain Identify Known and Novel Pathogenetic Processes.

Autism Spectrum Disorder (ASD) is a set of heterogeneous neurodevelopmental conditions defined by impairments in social communication and restricted, repetitive behaviors, interests or activities. Only a minority of ASD cases are determined to have a definitive etiology and the pathogenesis of most ASD is poorly understood. We hypothesized that a global analysis of the proteomes of human ASD vs. control brain, heretofore not done, would provide important data with which to better understand the underlying neurobiology of autism. In this study, we characterized the proteomes of two brain regions, Brodmann area 19 (BA19) and posterior inferior cerebellum (CB), from carefully selected idiopathic ASD cases and matched controls using label-free HPLC-tandem mass spectrometry. The data revealed marked differences between ASD and control brain proteomes for both brain regions. Unlike earlier transcriptomic analyses using frontal and temporal cortex, however, our proteomic analysis did not support ASD attenuating regional gene expression differences. Bioinformatic analyses of the differentially expressed proteins between cases and controls highlighted canonical pathways involving glutamate receptor signaling and glutathione-mediated detoxification in both BA19 and CB; other pathways such as Sertoli cell signaling and fatty acid oxidation were specifically enriched in BA19 or CB, respectively. Network analysis of both regions of ASD brain showed up-regulation of multiple pre- and post-synaptic membrane or scaffolding proteins including glutamatergic ion channels and related proteins, up-regulation of proteins involved in intracellular calcium signaling, and down-regulation of neurofilament proteins, with DLG4 and MAPT as major hub proteins in BA19 and CB protein interaction networks, respectively. Upstream regulator analysis suggests neurodegeneration-associated proteins drive the differential protein expression for ASD in both BA19 and CB. Overall, the proteomic data provide support for shared dysregulated pathways and upstream regulators for two brain regions in human ASD brain, suggesting a common ASD pathophysiology that has distinctive regional expression.

Elevated autoimmunity in residents living near abandoned uranium mine sites on the Navajo Nation.

Specific autoantibodies were assessed among residents of the Navajo Nation in New Mexico chronically exposed to metal mixtures from uranium mine wastes and in drinking water supplies. Age and the extent of exposure to legacy waste from 100 abandoned uranium mine and mill sites were associated with antibodies to denatured DNA, previously known to be an early indicator of medication-induced autoimmunity. Surprisingly, autoantibodies to native DNA and/or chromatin were also linked to environmental exposure, specifically uranium consumption through drinking water for both men and women, while urinary arsenic was negatively associated with these autoantibodies in women. These findings suggest that contaminants derived from uranium mine waste enhanced development of autoantibodies in some individuals, while arsenic may be globally immunosuppressive with gender-specific effects. Specific autoantibodies may be a sensitive indicator of immune perturbation by environmental toxicants, an adverse effect not considered in current drinking water standards or regulatory risk assessment evaluations.

Variability in Cinacalcet Prescription across US Hemodialysis Facilities.

BACKGROUND AND OBJECTIVES: Calcimimetic drugs used to treat secondary hyperparathyroidism are being considered for inclusion in the Medicare ESRD Prospective Payment System bundle after an evaluation period. Understanding of utilization patterns of calcimimetics across dialysis facilities may help align financial incentives with clinical objectives. Our study's purpose was to describe the distribution of cinacalcet prescription across United States hemodialysis facilities and to explore factors that may influence cinacalcet utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used monthly cross-sectional data from the Dialysis Outcomes and Practice Patterns Study in 2014 to characterize the distribution of cinacalcet prescription across 203 United States hemodialysis facilities (10,521 patients). On the basis of associations with parathyroid hormone levels from patient-level analyses, we used linear mixed-effects regressions to estimate the associations between three facility-level exposures (black race, <65 years old, and having ≥3 years on dialysis [vintage]) and the prevalence of cinacalcet prescription, adjusting for facility- and patient-level potential confounders. RESULTS: The mean percentage of patients in each facility with cinacalcet prescription was 23% in June 2014 (median, 22%; interquartile range, 13%-30%). Adjusted for facility-level and nonexposure patient-level variables, the difference in prevalence of cinacalcet prescription between facilities with the highest and lowest quartiles of percentage of black patients was 7.8% (95% confidence interval [95% CI], 0.8% to 14.8%; P for trend =0.03). The adjusted prevalence difference was 7.3% for the percentage of patients aged <65 years (95% CI, -0.1% to 14.7%; P for trend =0.06) and 11.9% for the percentage of patients with ≥3 years of dialysis (95% CI, 2.4% to 21.4%; P for trend =0.02). These associations changed appreciably, becoming much weaker or even reversing, after further adjusting for the patient-level exposure variables. CONCLUSIONS: Facilities treating more patients who are black, under age 65 years, and having dialysis vintage ≥3 years have higher average levels of cinacalcet prescription. However, these differences were strongly attenuated after accounting for the unbalanced distributions of these patient case-mix variables.

Prices For Common Cardiovascular Drugs In The US Are Not Consistently Aligned With Value.

Health care reimbursement agencies in countries other than the US often rely on cost-effectiveness evidence for drug coverage decisions, signaling to drug manufacturers their expectations for value-based pricing. To see whether drug prices in the US are influenced by value, we estimated the range of cost-effectiveness for thirty frequently prescribed cardiovascular drugs. We extrapolated evidence from randomized controlled trials to determine average lifetime quality-adjusted life-years (QALYs) and payer-related costs and to calculate incremental cost-effectiveness ratios (ICERs), the principal metric of cost-effectiveness studies. Across the thirty drugs, the ICERs ranged from cost-saving with increased QALYs to more costly with decreased QALYs. This range suggests that drug pricing is not consistently influenced by value, or that such influence is masked by inaccessible factors, such as price discounts. Our findings highlight the need to debate how to define and use value-based evidence to inform US coverage and reimbursement decision making.

Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study.

Autism spectrum disorder (ASD) is a developmental disorder which is currently only diagnosed through behavioral testing. Impaired folate-dependent one carbon metabolism (FOCM) and transsulfuration (TS) pathways have been implicated in ASD, and recently a study involving multivariate analysis based upon Fisher Discriminant Analysis returned very promising results for predicting an ASD diagnosis. This article takes another step toward the goal of developing a biochemical diagnostic for ASD by comparing five classification algorithms on existing data of FOCM/TS metabolites, and also validating the classification results with new data from an ASD cohort. The comparison results indicate a high sensitivity and specificity for the original data set and up to a 88% correct classification of the ASD cohort at an expected 5% misclassification rate for typically-developing controls. These results form the foundation for the development of a biochemical test for ASD which promises to aid diagnosis of ASD and provide biochemical understanding of the disease, applicable to at least a subset of the ASD population.

Sexually diergic hypothalamic-pituitary-adrenal axis responses to selective and non-selective muscarinic antagonists prior to cholinergic stimulation by physostigmine in rats.

Central cholinergic systems regulate the hypothalamic-pituitary-adrenal (HPA) axis differentially in males and females (sexual diergism). We previously investigated the role of muscarinic receptors in this regulation by administering physostigmine (PHYSO), an acetylcholinesterase inhibitor, to male and female rats pretreated with scopolamine (SCOP), a nonselective muscarinic antagonist. SCOP pretreatment enhanced adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses in both sexes, but males had greater ACTH responses while females had greater CORT responses. In the present study, we further explored the role of muscarinic receptor subtypes in HPA axis regulation by administering PHYSO to male and female rats following SCOP or various doses of either the M1 or the M2 selective muscarinic receptor antagonists, pirenzepine (PIREN) or methoctramine (METHO). Blood was sampled before and at multiple times after PHYSO. ACTH and CORT were determined by highly specific immunoassays. M1 antagonism by PIREN prior to PHYSO resulted in sustained, dose-dependent increases in ACTH and CORT: ACTH responses were similar in both sexes, and CORT responses were greater in females. M2 antagonism by METHO prior to PHYSO resulted in overall decreases in ACTH and CORT: ACTH and CORT responses were higher in females but lower in both sexes than the hormone responses following PIREN or SCOP pretreatment. Area under the curve analyses supported these findings. These results suggest that specific muscarinic receptor subtypes differentially influence the HPA axis in a sexually diergic manner.

Mice Housed at Elevated Vivarium Temperatures Display Enhanced T-cell Response and Survival to Francisella tularensis.

The inability to translate findings from studies performed in mouse models to the corresponding human condition is well known, especially those involving infectious, atherosclerotic, and other inflammatory diseases. We hypothesize that mice fail to a mount robust or adequate immune response to infectious agents because of physiologic effects of cold stress due to housing temperatures below the mouse thermoneutral zone (TNZ). This hypothesis was tested by comparing the immune response to the Francisella tularensis live vaccine strain in mice housed at a typical vivarium temperature, which is below the TNZ, with that of mice housed at a temperature near their TNZ. Mice maintained at 28 °C displayed elevated antigen-specific T-cell responses compared with mice housed at 22 °C and survived intranasal challenge that was fatal to immunized mice at 22 °C. These results demonstrate that cold stress due to housing below the mouse TNZ results in a blunted immune response and may compromise their translational value a models for infectious diseases and vaccine development.

Indole signalling and (micro)algal auxins decrease the virulence of Vibrio campbellii, a major pathogen of aquatic organisms.

Vibrios belonging to the Harveyi clade are major pathogens of marine vertebrates and invertebrates, causing major losses in wild and cultured organisms. Despite their significant impact, the pathogenicity mechanisms of these bacteria are not yet completely understood. In this study, the impact of indole signalling on the virulence of Vibrio campbellii was investigated. Elevated indole levels significantly decreased motility, biofilm formation, exopolysaccharide production and virulence to crustacean hosts. Indole furthermore inhibited the three-channel quorum sensing system of V. campbellii, a regulatory mechanism that is required for full virulence of the pathogen. Further, indole signalling was found to interact with the stress sigma factor RpoS. Together with the observations that energy-consuming processes (motility and bioluminescence) are downregulated, and microarray-based transcriptomics demonstrating that indole decreases the expression of genes involved in energy and amino acid metabolism, the data suggest that indole is a starvation signal in V. campbellii. Finally, it was found that the auxins indole-3-acetic acid and indole-3-acetamide, which were produced by various (micro)algae sharing the aquatic environment with V. campbellii, have a similar effect as observed for indole. Auxins might, therefore, have a significant impact on the interactions between vibrios, (micro)algae and higher organisms, with major ecological and practical implications.

The universe of ANA testing: a case for point-of-care ANA testing.

Testing for total antinuclear antibodies (ANA) is a critical tool for diagnosis and management of autoimmune diseases at both the primary care and subspecialty settings. Repurposing of ANA from a test for lupus to a test for any autoimmune condition has driven the increase in ANA requests. Changes in ANA referral patterns include early or subclinical autoimmune disease detection in patients with low pre-test probability and use of negative ANA results to rule out underlying autoimmune disease. A positive result can lead to further diagnostic considerations. Currently, ANA tests are performed in centralized laboratories; an alternative would be ANA testing at the clinical point-of-care (POC). By virtue of its near real-time data collection capability, low cost, and ease of use, we believe the POC ANA has the potential to enable a new paradigm shift in autoimmune serology testing.