Lung mass density prediction using machine learning based on ultrasound surface wave elastography and pulmonary function testing.

OBJECTIVE: The objective of this study is to predict in vivo lung mass density for patients with interstitial lung disease using different gradient boosting decision tree (GBDT) algorithms based on measurements from lung ultrasound surface wave elastography (LUSWE) and pulmonary function testing (PFT). METHODS: Age and weight of study subjects (57 patients with interstitial lung disease and 20 healthy subjects), surface wave speeds at three vibration frequencies (100, 150, and 200 Hz) from LUSWE, and predicted forced expiratory volume (FEV1% pre) and ratio of forced expiratory volume to forced vital capacity (FEV1%/FVC%) from PFT were used as inputs while lung mass densities based on the Hounsfield Unit from high resolution computed tomography (HRCT) were used as labels to train the regressor in three GBDT algorithms, XGBoost, CatBoost, and LightGBM. 80% (20%) of the dataset was used for training (testing). RESULTS: The results showed that predictions using XGBoost regressor obtained an accuracy of 0.98 in the test dataset. CONCLUSION: The obtained results suggest that XGBoost regressor based on the measurements from LUSWE and PFT may be able to noninvasively assess lung mass density in vivo for patients with pulmonary disease.

Lung US Surface Wave Elastography in Interstitial Lung Disease Staging.

Background Lung US surface wave elastography (SWE) can noninvasively quantify lung surface stiffness or fibrosis by evaluating the rate of surface wave propagation. Purpose To assess the utility of lung US SWE for evaluation of interstitial lung disease. Materials and Methods In this prospective study, lung US SWE was used to assess 91 participants (women, 51; men, 40; mean age ± standard deviation [SD], 62.4 years ± 12.9) with interstitial lung disease and 30 healthy subjects (women, 16; men, 14; mean age, 45.4 years ± 14.6) from February 2016 through May 2017. Severity of interstitial lung disease was graded as none (healthy lung [F0]), mild (F1), moderate (F2), or severe (F3) based on pulmonary function tests, high-resolution CT, and clinical assessments. We propagated surface waves on the lung through gentle mechanical excitation of the external chest wall and measured the lung surface wave speed with a US probe. Lung US SWE performance was assessed, and the optimal cutoff wave speed values for fibrosis grades F0 through F3 were determined with receiver operating characteristic (ROC) curve analysis. Results Lung US SWE had a sensitivity of 92% (95% confidence intervals [CI]: 84%, 96%; P < .001) and a specificity of 89% (95% CI: 81%, 94%; P < .001) for differentiating between healthy subjects (F0) and participants with any grade of interstitial lung disease (F1-F3). It had a sensitivity of 50% and a specificity of 81% for differentiating interstitial lung disease grades F0-F2 from F3. The sensitivity was 88% and the specificity was 97% for differentiating between F0 and F1. The highest area under the ROC curve (AUC) values were obtained at 200 Hz and ranged from 0.83 to 0.94 to distinguish between healthy subjects and study participants with any interstitial lung disease. Conclusion Lung US surface wave elastography may be adjunct to high-resolution CT for noninvasive evaluation of interstitial lung disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1.

Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen-TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ((3)H2O) through porcine vaginal mucosa was determined at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52°C) did not significantly increase flux of (3)H2O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of (3)H2O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment.

Regional european genetic ancestry predicts type I interferon level and risk of severe viral infection.

BACKGROUND: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti-viral cytokine, and we have previously noted differences in type I IFN levels between world populations. METHODS: In this study, we investigate the interrelationship between regional European genetic ancestry, type I IFN levels, and severe viral infection outcomes. RESULTS: In cohorts of European ancestry lupus patients living in Europe, we noted higher IFN in the Northwestern populations as compared to Southeastern populations. In an independent cohort of European ancestry lupus patients from the United States with varying proportional regional European genetic admixture, we observed the same Northwest vs. Southeast European ancestry IFN gradient. We developed a model to predict type I IFN level based on regional European ancestry (AUC = 0.73, p = 6.1e-6). Examining large databases containing serious viral outcomes data, we found that lower predicted IFN in the corresponding European country was significantly correlated with increased viral infection fatality rate, including COVID-19, viral hepatitis, and HIV [Correlation coefficients: -0.79 (p = 4e-2), -0.94 (p = 6e-3), and -0.96 (p = 8e-2) respectively]. CONCLUSIONS: This association between predicted type I IFN level and viral outcome severity suggests a potential causal relationship, as greater intrinsic type I IFN is beneficial in host defense against viruses. Genetic testing could provide insight into individual and population level risk of fatality due to viruses prior to infection, across a wide range of viral pathogens.

High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.

OBJECTIVE: Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the effect of IFN in LN. METHODS: Two hundred and twenty-one patients with systemic lupus erythematosus were studied. Serum IFN activity was measured by WISH bioassay. mRNA in situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, IFN-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C). Podocyte cell line gene expression was measured by real-time PCR. RESULTS: Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (odds ratio 5.40, P = 0.009). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely colocalized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. CONCLUSION: Systemic high IFN is involved in the pathogenesis of severe LN. We did not find colocalization of pDCs with IFN signature in renal tissue, and instead observed the greatest intensity of the IFN signature in glomerular areas, which could suggest a blood source of IFN.

A physical map of Brassica oleracea shows complexity of chromosomal changes following recursive paleopolyploidizations.

BACKGROUND: Evolution of the Brassica species has been recursively affected by polyploidy events, and comparison to their relative, Arabidopsis thaliana, provides means to explore their genomic complexity. RESULTS: A genome-wide physical map of a rapid-cycling strain of B. oleracea was constructed by integrating high-information-content fingerprinting (HICF) of Bacterial Artificial Chromosome (BAC) clones with hybridization to sequence-tagged probes. Using 2907 contigs of two or more BACs, we performed several lines of comparative genomic analysis. Interspecific DNA synteny is much better preserved in euchromatin than heterochromatin, showing the qualitative difference in evolution of these respective genomic domains. About 67% of contigs can be aligned to the Arabidopsis genome, with 96.5% corresponding to euchromatic regions, and 3.5% (shown to contain repetitive sequences) to pericentromeric regions. Overgo probe hybridization data showed that contigs aligned to Arabidopsis euchromatin contain ~80% of low-copy-number genes, while genes with high copy number are much more frequently associated with pericentromeric regions. We identified 39 interchromosomal breakpoints during the diversification of B. oleracea and Arabidopsis thaliana, a relatively high level of genomic change since their divergence. Comparison of the B. oleracea physical map with Arabidopsis and other available eudicot genomes showed appreciable 'shadowing' produced by more ancient polyploidies, resulting in a web of relatedness among contigs which increased genomic complexity. CONCLUSIONS: A high-resolution genetically-anchored physical map sheds light on Brassica genome organization and advances positional cloning of specific genes, and may help to validate genome sequence assembly and alignment to chromosomes.All the physical mapping data is freely shared at a WebFPC site (http://lulu.pgml.uga.edu/fpc/WebAGCoL/brassica/WebFPC/; Temporarily password-protected: account: pgml; password: 123qwe123.

Primary Raynaud phenomenon and small-fiber neuropathy: is there a connection? A pilot neurophysiologic study.

The pathophysiologic factors of primary Raynaud phenomenon (RP) are unknown. Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in primary RP. We aimed to quantitatively assess SFN in participants with primary RP. Consecutive patients with an a priori diagnosis of primary RP presenting to our outpatient rheumatology clinic over a 6-month period were invited to participate. Cases of secondary RP were excluded. All participants were required to have normal results on nailfold capillary microscopy. Assessment for SFN was accomplished with autonomic reflex screening, which includes quantitative sudomotor axonal reflex test (QSART), and cardiovagal and adrenergic function testing, thermoregulatory sweat test (TST), and quantitative sensory test (QST) for vibratory, cooling, and heat-pain sensory thresholds. Nine female participants with a median age of 38 years (range 21-46 years) and a median symptom duration of 9 years (range 5 months-31 years) were assessed. Three participants had abnormal results on QSART, indicating peripheral sudomotor autonomic dysfunction. Two participants had evidence of large-fiber involvement with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep breathing, Valsalva maneuver, and 70° tilt were normal for all participants. Also, all participants had normal TST results. In total, three of the nine participants had evidence of SFN. The presence of SFN raises the possibility that a subset of patients with primary RP have an underlying, subclinical small-fiber dysfunction. These data open new avenues of research and therapeutics for this common condition.

A Four-Component Framework Toward Patient-Centered, Integrated Mental Healthcare in Kenya.

Background: How can we fast-track the global agenda of integrated mental healthcare in low- and middle-income countries (LMICs) such as Kenya? This is a question that has become increasingly important for individuals with lived experiences, policymakers, mental health advocates and health care providers at the local and international levels. Discussion: This narrative synthesis and perspective piece encompasses an overview of mental health care competencies, best practices and capacity building needed to fast track patient responsive services. In that vein we also review key policy developments like UHC to make a case for fast-tracking our four-step framework. Results: While there is an increasingly global impetus for integrated mental healthcare, there is a lack of clarity around what patient-responsive mental healthcare services should look like and how to measure and improve provider readiness appropriately. Here, our collaborative team of local and international experts proposes a simple four-step approach to integrating responsive mental healthcare in Kenya. Our recommended framework prioritizes a clear understanding and demonstration of multidimensional skills by the provider. The four steps are (1) provider sensitization, (2) continuous supervision, (3) continuous professional training, and (4) leadership empowerment. Conclusion: Our proposed framework can provide pointers to embracing patient-centered and provider empowerment focused quality of care improvements. Though elements of our proposed framework are well-known, it has not been sufficiently intertwined and therefore not been integrated. We think in the current times our integrated framework offers an opportunity to "building back better" mental health for all.

Systemic Sclerosis Portends Increased Risk of Conduction and Rhythm Abnormalities at Diagnosis and During Disease Course: A US Population-Based Cohort.

Objectives: To study the incidence, risk factors and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis (SSc) vs. non-SSc comparators. Methods: An incident cohort of patients with SSc (1980-2016) from Olmsted County, MN was compared to age- and sex-matched non-SSc subjects (1:2). Electrocardiograms (ECGs), Holter ECGs, and need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: 78 incident SSc cases and 156 comparators were identified (mean age 56 y, 91% female). The prevalence of any conduction disorder prior to SSc diagnosis compared to non-SSc subjects was 15% vs. 7% (p=0.06), and any rhythm disorder was 18% vs. 13% (p=0.33). During a median follow-up of 10.5 years in patients with SSc and 13.0 years in non-SSc comparators, conduction disorders developed in 25 patients with SSc with cumulative incidence of 20.5% (95% CI: 12.4-34.1%) vs. 28 non-SSc patients with cumulative incidence of 10.4% (95% CI: 6.2-17.4%) (HR: 2.57; 95% CI: 1.48-4.45), while rhythm disorders developed in 27 patients with SSc with cumulative incidence of 27.3% (95% CI: 17.9-41.6%) vs. 43 non-SSc patients with cumulative incidence of 18.0% (95% CI: 12.3-26.4%) (HR: 1.62; 95% CI: 1.00-2.64). Age, pulmonary hypertension and smoking were identified as risk factors. Conclusion: Patients with SSc have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to non-SSc patients. These findings warrant increased vigilance and screening for ECG abnormalities in SSc patients with pulmonary hypertension.

Hospitalization Rates Are Highest in the First 5 Years of Systemic Sclerosis: Results From a Population-based Cohort (1980-2016).

OBJECTIVE: Few studies have estimated the healthcare resource usage of patients with systemic sclerosis (SSc). The purpose of this study was to compare hospitalization among incident cases of SSc vs age- and sex-matched comparators. METHODS: A retrospective, population-based cohort of patients with SSc in Olmsted County, Minnesota, from January 1, 1980, to December 31, 2016, was assembled. A 2:1 cohort of age- and sex-matched patients without SSc from the same population was randomly selected for comparison. All hospitalizations in the geographic area from January 1, 1987, to September 30, 2018, were obtained. Rates of hospitalization, lengths of stay, and readmissions were compared between groups. RESULTS: There were 76 incident SSc cases and 155 non-SSc comparators (mean age 56 ± 16 yrs at diagnosis/index, 91% female) included. Rates of hospitalization among cases and comparators were 31.9 and 17.9 per 100 person-years, respectively (rate ratio [RR] 1.78, 95% CI 1.52-2.08). Hospitalization rates were higher in patients with SSc than comparators during the first 5 years after SSc diagnosis (RR 2.16, 95% CI 1.70-2.74). This difference decreased over time and was no longer significant at ≥ 15 years after SSc incidence/index. Lengths of stay (median [IQR] 4 [2-6] vs 3 [2-6], P = 0.52) and readmission rates (25% vs 23%, P = 0.51) were similar between groups. CONCLUSION: Patients with SSc were hospitalized more frequently than comparators, indicating high inpatient care needs in this population. Hospitalization rates were highest during the first 5 years following SSc diagnosis.

Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes.

BACKGROUND: We performed expression quantitative trait locus (eQTL) analysis in single classical (CL) and non-classical (NCL) monocytes from patients with systemic lupus erythematosus (SLE) to quantify the impact of well-established genetic risk alleles on transcription at single-cell resolution. METHODS: Single-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16- CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles. RESULTS: The SLE-risk alleles demonstrated significantly more eQTLs in NCLs as compared to CLs (p = 0.0004). There were 18 eQTLs exclusive to NCL cells, 5 eQTLs exclusive to CL cells, and only one shared eQTL, supporting large differences in the impact of the risk alleles between these monocyte subsets. The SPP1 and TNFAIP3 loci were associated with the greatest number of transcripts. Patterns of shared influence in which different SNPs impacted the same transcript also differed between monocyte subsets, with greater evidence for synergy in NCL cells. IRF1 expression demonstrated an on/off pattern, in which expression was zero in all of the monocytes studied from some individuals, and this pattern was associated with a number of SLE risk alleles. We observed corroborating evidence of this IRF1 expression pattern in public data sets. CONCLUSIONS: We document multiple SLE-risk allele eQTLs in single monocytes which differ greatly between CL and NCL subsets. These data support the importance of the SPP1 and TNFAIP3 risk variants and the IRF1 transcript in SLE patient monocyte function.

Ultrasound Surface Wave Elastography for Assessing Scleroderma.

Scleroderma, or systemic sclerosis (SSc), is a multi-organ connective tissue disease characterized by immune dysregulation and tissue fibrosis. Skin disease is both a disabling feature of SSc and a predictor of visceral involvement and increased mortality. The Modified Rodnan Skin Score (MRSS) is currently the most common clinical method for assessing skin. We developed ultrasound surface wave elastography (USWE) techniques to measure skin surface wave speeds and analyze skin viscoelasticity. The objective of this research was to determine the correlations of skin surface wave speed and skin viscoelasticity with MRSS. Twenty-six SSc patients were studied using USWE and the MRSS. The subject was tested in a sitting position while his or her left or right forearm and upper arm were placed horizontally on a pillow in a relaxed state. The skin of both left and right forearms and upper arms of patients was tested using USWE. Surface wave speeds are positively correlated with the MRSS. Skin elasticity is also positively correlated with the MRSS. However, there was no correlation between skin viscosity and the MRSS for these SSc patients. We will further study if skin viscosity is sensitive enough to detect early edema from inflammation changes of SSc.

Untreated Takayasu arteritis: an unusual case of widespread disease.

A 38-year-old man with no medical history presented with bilateral flank and epigastric abdominal pain. CT abdomen and pelvis demonstrated diffuse nodules and lymphadenopathy, which were biopsied and showed chronic inflammatory changes. He later presented with pleuritic chest pain and was sent for a CT chest angiogram, which revealed perivascular inflammation involving the thoracic aortic arch, supra-aortic branch vessels and descending thoracic aorta. Further work-up showed vasculitic involvement of the coeliac, superior mesenteric and femoral arteries with heavy collateralisation. These findings were most consistent with widespread Takayasu arteritis that had been untreated for nearly 20 years. It was necessary to define the degree of active inflammation and need for immediate therapy, as the patient had a concomitant latent tuberculosis infection that precluded the use of immunosuppressive medications. This report illustrates an unusual case of Takayasu arteritis and highlights the presentation, diagnosis and work-up of suspected cases.

Cardiovascular Risk Factors and Atherosclerotic Cardiovascular Events Among Incident Cases of Systemic Sclerosis: Results From a Population-Based Cohort (1980-2016).

OBJECTIVE: To characterize cardiovascular (CV) risk factors and outcomes among incident cases of systemic sclerosis (SSc) in a population-based cohort. METHODS: Medical records of patients with SSc diagnosed in Olmsted County, Minnesota, between January 1, 1980, and December 31, 2016, were reviewed to identify 78 incident SSc cases. The comparators were 156 sex- and age-matched individuals from the same population. Data for SSc characteristics, traditional CV risk factors, and CV events were collected. Cumulative incidence was adjusted for the competing risk for death. RESULTS: During a median follow-up of 9.8 (SSc) and 9.2 years (non-SSc), 21 patients with SSc and 17 patients without SSc developed CV events, corresponding to 10-year cumulative incidence of 24.4% and 15.2%, respectively. The risk for incident CV disease was increased by 2-fold (hazard ratio, 2.38; 95% CI, 1.28-4.43) in patients with SSc vs comparators, predominately due to coronary artery disease (hazard ratio, 2.35; 95% CI, 1.17-4.71). Mean body mass index and prevalence of diabetes mellitus were lower in SSc vs non-SSc. There was no significant difference in smoking, hypertension, or hyperlipidemia. Observed CV events were increased compared with CV events predicted by the Framingham Risk Score and American College of Cardiology/American Heart Association score with standardized incident ratios of 4.16 (95% CI, 2.16-7.99) and 5.69 (95% CI, 2.71-11.94), respectively. CONCLUSION: Patients with SSc are at >2-fold increased risk for experiencing a CV event compared with persons without SSc. Framingham Risk Score and American College of Cardiology/American Heart Association score dramatically underestimate CV risk in SSc.

Vaginal microbiota of women with frequent vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is an insidious infection that afflicts a large proportion of women of all ages, and 5 to 8% of affected women experience recurrent VVC (RVVC). The aim of this study was to explore the possible importance of vaginal bacterial communities in reducing the risk of RVVC. The species composition and diversity of microbial communities were evaluated for 42 women with and without frequent VVC based on profiles of terminal restriction fragment polymorphisms of 16S rRNA genes and phylogenetic analysis of cloned 16S rRNA gene sequences from the numerically dominant microbial populations. The data showed that there were no significant differences between the vaginal microbial communities of women in the two groups (likelihood score, 5.948; bootstrap P value, 0.26). Moreover, no novel bacteria were found in the communities of women with frequent VVC. The vaginal communities of most women in both groups (38/42; 90%) were dominated by species of Lactobacillus. The results of this study failed to provide evidence for the existence of altered or unusual vaginal bacterial communities in women who have frequent VVC compared to women who do not have frequent VVC. The findings suggest that commensal vaginal bacterial species may not be able to prevent VVC.

Development of public immortal mapping populations, molecular markers and linkage maps for rapid cycling Brassica rapa and B. oleracea.

Publicly available genomic tools help researchers integrate information and make new discoveries. In this paper, we describe the development of immortal mapping populations of rapid cycling, self-compatible lines, molecular markers, and linkage maps for Brassica rapa and B. oleracea and make the data and germplasm available to the Brassica research community. The B. rapa population consists of 160 recombinant inbred (RI) lines derived from the cross of highly inbred lines of rapid cycling and yellow sarson B. rapa. The B. oleracea population consists of 155 double haploid (DH) lines derived from an F1 cross between two DH lines, rapid cycling and broccoli. A total of 120 RFLP probes, 146 SSR markers, and one phenotypic trait (flower color) were used to construct genetic linkage maps for both species. The B. rapa map consists of 224 molecular markers distributed along 10 linkage groups (A1-A10) with a total distance of 1125.3 cM and a marker density of 5.7 cM/marker. The B. oleracea genetic map consists of 279 molecular markers and one phenotypic marker distributed along nine linkage groups (C1-C9) with a total distance of 891.4 cM and a marker density of 3.2 cM/marker. A syntenic analysis with Arabidopsis thaliana identified collinear genomic blocks that are in agreement with previous studies, reinforcing the idea of conserved chromosomal regions across the Brassicaceae.

Forward and reverse genetics of rapid-cycling Brassica oleracea.

Seeds of rapid-cycling Brassica oleracea were mutagenized with the chemical mutagen, ethylmethane sulfonate. The reverse genetics technique, TILLING, was used on a sample population of 1,000 plants, to determine the mutation profile. The spectrum and frequency of mutations induced by ethylmethane sulfonate was similar to that seen in other diploid species such as Arabidopsis thaliana. These data indicate that the mutagenesis was effective and demonstrate that TILLING represents an efficient reverse genetic technique in B. oleracea that will become more valuable as increasing genomic sequence data become available for this species. The extensive duplication in the B. oleracea genome is believed to result in the genetic redundancy that has been important for the evolution of morphological diversity seen in today's B. oleracea crops (broccoli, Brussels sprouts, cauliflower, cabbage, kale and kohlrabi). However, our forward genetic screens identified 120 mutants in which some aspect of development was affected. Some of these lines have been characterized genetically and in the majority of these, the mutant trait segregates as a recessive allele affecting a single locus. One dominant mutation (curly leaves) and one semi-dominant mutation (dwarf-like) were also identified. Allelism tests of two groups of mutants (glossy and dwarf) revealed that for some loci, multiple independent alleles have been identified. These data indicate that, despite genetic redundancy, mutation of many individual loci in B. oleracea results in distinct phenotypes.

Acrocyanosis from phenazopyridine-induced sulfhemoglobinemia mistaken for Raynaud phenomenon.

Rheumatologists are often asked to evaluate patients with Raynaud phenomenon. Occasionally, an alternate explanation is revealed such as acrocyanosis. Methemoglobinemia and sulfhemoglobinemia are rare causes of cyanosis that can be medication-induced. Both are known complications of therapy with phenazopyridine. We report an unusual case of a 45-year-old woman in whom sulfhemoglobinemia from chronic therapy with phenazopyridine was misdiagnosed as due to Raynaud phenomenon and limited scleroderma. This case illustrates the importance of taking into account medication-related adverse events when evaluating patients with Raynaud-like phenomenon.

Lung Ultrasound Surface Wave Elastography for Assessing Interstitial Lung Disease.

OBJECTIVE: Our goal is to translate lung ultrasound surface wave elastography (LUSWE) for assessing patients with interstitial lung disease (ILD) and various connective tissue diseases including systemic sclerosis (SSc). METHODS: LUSWE was used to measure the surface wave speed of lung at 100, 150, and 200 Hz through six intercostal lung spaces for 91 patients with ILD and 30 healthy control subjects. In addition, skin viscoelasticity was measured on both forearms and upper arms for patients and controls. RESULTS: The surface wave speeds of patients' lungs were significantly higher than those of control subjects. Patient skin elasticity and viscosity were significantly higher than those of control subjects. In dividing ILD patients into two groups, ILD with SSc patients and ILD without SSc patients, significant differences between each patient group with the control group were found for both the lung and skin. No significant differences were found between the two patient groups, although there were some differences at a few locations and at 100 Hz for skin viscoelasticity. CONCLUSION: Significant differences of surface wave speed were found between ILD patients and healthy control subjects for both the lung and skin. SIGNIFICANCE: LUSWE may be useful for assessing ILD and SSc and screening early stage patients.