An Unusual Presentation of Immunoglobulin G4-Related Disease (IgG4-RD) Causing Subglottic Stenosis.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that is known to involve multiple organs and was first described as an entity in 2003. It is characterized by lesions with a dense lymphoplasmacytic infiltrate, IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Organs that are commonly involved include the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, retroperitoneum, lungs, pleura, thyroid, aorta, and lymph nodes. Rarer manifestations of IgG4-RD include central nervous system (CNS) involvement, prostatitis, mastitis, midline destructive disease, and nasopharyngeal disease. In this report, we discuss an atypical case of a young woman with laryngeal subglottic involvement leading to stenosis and airway obstruction, which was ultimately successfully managed with systemic immunosuppression.

The role of tocilizumab therapy in critically ill patients with severe acute respiratory syndrome coronavirus 2.

CONTEXT: Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has been approved for use in rheumatoid arthritis and cytokine storm syndrome (CSS) associated with chimeric antigen receptor T cells treatment. Although TCZ is currently utilized in the treatment of critically ill coronavirus 2019 (COVID-19) patients, data on survival impact is minimal. OBJECTIVES: To assess the mortality rate of patients presenting with COVID-19 who received TCZ for suspected CSS. METHODS: This retrospective cohort study was conducted at Henry Ford Health System between March 10, 2020 and May 18, 2020. Data collection began in May 2020 and was completed in June 2020. Patients included in the study required hospital admission and had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction on nasopharyngeal swab. Eligibility criteria to receive TCZ, per hospital protocol, included any of the following: persistent fever, defined as 38.0 °C for at least 6 hours; a diagnosis of the acute respiratory distress syndrome (ARDS); serum ferritin ≥1,000 (ng/mL) or doubling within 24 hours; D-Dimer ≥ 5 (mg/L); serum lactate dehydrogenase ≥500 (IU/L); or interlukin-6 level ≥5 times the upper limit of normal. Dosing was initially determined by weight, then changed to a fixed 400 mg per hospital protocol. A comparator cohort was created from patients with COVID-19 and ARDS who did not receive TCZ. Patient survival was analyzed using the Kaplan-Meier method and compared by log rank test. A multivariable cox regression was applied to evaluate the association between TCZ and mortality. RESULTS: One hundred and thirty patients were evaluated in the study, 54 (41.5%) of whom received TCZ. Patients who received TCZ were younger (mean age, 63.8 vs. 69.4 years; p=0.0083) and had higher body mass indices (mean, 33.9 vs. 30.4; p=0.005). Of the comorbid conditions evaluated, heart disease was more common in the comparator group than the TCZ group (27 patients [35.5%] vs. 10 patients [18.5%]; p=0.034). A Kaplan-Meier survival curve demonstrated no difference in survival between TCZ and comparator patients (log rank p=0.495). In the multivariable Cox regression model for mortality at 30 days, treatment with TCZ was not associated with decreased mortality (hazard ratio, 1.1; 95% confidence interval, 0.53-2.3; p=0.77). Lower mean C-reactive protein (CRP) levels were demonstrated within 48 hours of disposition in the TCZ group (mean TCZ, 4.9 vs. mean comparator, 13.0; p=<0.0001). CONCLUSIONS: In this cohort study, no difference in survival was observed in critically ill patients treated with TCZ.

Response of Multiple Tissues to Drought Revealed by a Weighted Gene Co-Expression Network Analysis in Foxtail Millet [Setaria italica (L.) P. Beauv.].

Characterization of drought-tolerance mechanisms during the jointing stage in foxtail millet under water-limited conditions is essential for improving the grain yield of this C4 crop species. In this trial, two drought-tolerant and two drought-sensitive cultivars were examined using transcriptomic dissections of three tissues (root, stem, and leaf) under naturally occurring water-limited conditions. We detected a total of 32,170 expressed genes and characterized 13,552 differentially expressed genes (DEGs) correlated with drought treatment. The majority of DEGs were identified in the root tissue, followed by leaf and stem tissues, and the number of DEGs identified in the stems of drought-sensitive cultivars was about two times higher than the drought-tolerant ones. A total of 127 differentially expressed transcription factors (DETFs) with different drought-responsive patterns were identified between drought-tolerant and drought-sensitive genotypes (including MYB, b-ZIP, ERF, and WRKY). Furthermore, a total of 34 modules were constructed for all expressed genes using a weighted gene co-expression network analysis (WGCNA), and seven modules were closely related to the drought treatment. A total of 1,343 hub genes (including RAB18, LEA14, and RD22) were detected in the drought-related module, and cell cycle and DNA replication-related transcriptional pathways were identified as vital regulators of drought tolerance in foxtail millet. The results of this study provide a comprehensive overview of how Setaria italica copes with drought-inflicted environments during the jointing stage through transcriptional regulating strategies in different organs and lays a foundation for the improvement of drought-tolerant cereal cultivars through genomic editing approaches in the future.

[Phenotype Analysis of 78 Cases of Abnormal Hemoglobin E Homozygotes].

OBJECTIVE: To analyze the hematological characteristics of HbE homozygotes. METHODS: Complete blood cells count and hemoglobin electrophoresis were used for phenotypic analysis of 78 cases with HbE homozygotes from Yunnan province, China. The PCR-fluorescence hybridization was used to detect the common gene mutation of thalassemia. The hematological indexes, including MCV, MCH, Hb, HbA2, HbF and HbE were statistically analyzed between groups with different sex, ages and compound α thalassemia status. RESULTS: In HbE homozygotes (HbEE), 89.5% (17/19) children presented mild to moderate microcytic hypochromic anemia, and 10.5% of them presented moderate anemia. 39.6% (19/48) of women with HbEE developed mild anemia ,while 11 cases of male with HbE homozygotes were asymptomatic. The levels of MCV and MCH in HbE homozygotes increased by co-inheritance of α thalassemia mutation. CONCLUSION: The clinical phenotype of HbE homozygote shows highly heterogeneous, which is relates with age, sex and co-inheriting α-globin genotypes. In Hb EE women and children are more likely to develop mild to moderate anemia. The microcytic hypochromic anemia degree is relieved when HbEE combined with α- thalassemia.

Risk Factors for Visual Impairment in an Uninsured Population and the Impact of the Affordable Care Act.

PURPOSE: To assess risk factors for visual impairment in a high-risk population of people: those without medical insurance. Secondarily, we assessed risk factors for remaining uninsured after implementation of the Affordable Care Act (ACA) and evaluated whether the ACA changed demand for local safety net ophthalmology clinic services one year after its implementation. METHODS: In a retrospective cohort study of patients who attended a community-academic partnership free ophthalmology clinic in Southeastern, Michigan between September 2012 - March 2015, we assessed the prevalence of presenting with visual impairment, the most common causes of presenting with visual impairment and used logistic regression to assess socio-demographic risk factors for visual impairment. We assessed the initial impact of the ACA on clinic utilization. We also analyzed risk factors for remaining uninsured one year after implementation of the ACA private insurance marketplace and Medicaid expansion in the state of Michigan. RESULTS: Among 335 patients, one-fifth (22%) presented with visual impairment; refractive error was the leading cause for presenting with visual impairment. Unemployment was the single significant risk factor for presenting with visual impairment after adjusting for multiple confounding factors (OR = 3.05, 95% CI 1.19-7.87, p=0.01). There was no difference in proportion of visual impairment or type of vision-threatening disease between the insured and uninsured (p=0.26). Seventy six percent of patients remained uninsured one year after ACA implementation. Patients who were white, spoke English as a first language and were US Citizens were more likely to gain insurance coverage through the ACA in our population (p≤ 0.01). There was a non-significant decline in the mean number of patient treated per clinic (52 to 43) before and after ACA implementation (p=0.69). CONCLUSION: Refractive error was a leading cause for presenting with visual impairment in this vulnerable population, and being unemployed significantly increased the risk for presenting with visual impairment. The ACA did not significantly reduce the need for our free ophthalmology services. It is critically important to continue to support safety net specialty care initiatives and policy change to provide care for those in need.

A virus-based miRNA suppression (VbMS) system for miRNA loss-of-function analysis in plants.

MicroRNAs (miRNAs) play key roles in plant development and defense against pathogens. To establish the function of individual miRNAs, gain-of-function analysis is usually done by overexpressing a specific miRNA in transgenic plants and has proved very effective. Loss-of-function analysis by the target mimic method is now also increasingly being used. The mimics expressed in the transgenic plants sequester a specific miRNA and lead to changed phenotypes that elucidate miRNA function. However, it takes time to obtain the transgenic plants. To avoid using transgenic plants, we have developed a virus-based miRNA suppression system (VbMS) based on a Tobacco rattle virus vector. The target mimic sequences of miR156, miR319, or miR164 were introduced into the viral genomic RNA, which was then inoculated to Arabidopsis thaliana plants. The resulting phenotypes were consistent with previous reports from transgenic plants, and the expression of targets of the miRNAs was also increased showing that the activity of the miRNAs had been inhibited. VbMS developed here is validated for loss-of-function analysis of miRNA in plants. Moreover, since only simple agroinfiltration rather than transformation is needed, VbMS is suitable for large-scale approaches to miRNA function analysis in plants.

Identification of novel Oryza sativa miRNAs in deep sequencing-based small RNA libraries of rice infected with Rice stripe virus.

MicroRNAs (miRNAs) play essential regulatory roles in the development of eukaryotes. Methods based on deep-sequencing have provided a powerful high-throughput strategy for identifying novel miRNAs and have previously been used to identify over 100 novel miRNAs from rice. Most of these reports are related to studies of rice development, tissue differentiation, or abiotic stress, but novel rice miRNAs related to viral infection have rarely been identified. In previous work, we constructed and pyrosequenced the small RNA (sRNA) libraries of rice infected with Rice stripe virus and described the character of the small interfering RNAs (siRNA) derived from the RSV RNA genome. We now report the identification of novel miRNAs from the abundant sRNAs (with a minimum of 100 sequencing reads) in the sRNA library of RSV-infected rice. 7 putative novel miRNAs (pn-miRNAs) whose precursor sequences have not previously been described were identified and could be detected by Northern blot or RT-PCR, and were recognized as novel miRNAs (n-miRNAs). Further analysis showed that 5 of the 7 n-miRNAs were up-expressed while the other 2 n-miRNAs were down-expressed in RSV-infected rice. In addition, 23 pn-miRNAs that were newly produced from 19 known miRNA precursors were also identified. This is first report of novel rice miRNAs produced from new precursors related to RSV infection.