Influenza and Pregnant Women: Hospitalization Burden, United States, 1998–2002

Women in later stages of pregnancy are at increased risk for serious influenza-related morbidity; thus, universal influenza vaccination of pregnant women is recommended. However, vaccine uptake in the United States has been suboptimal. We previously described the burden of severe influenza-related morbidity during pregnancy in the United States by examining hospitalizations of pregnant women with respiratory illness during influenza season. Nondelivery hospitalizations with respiratory illness had significantly longer lengths of stay than those without respiratory illness. Hospitalization characteristics associated with greater likelihood of respiratory illness were the presence of a high-risk condition for which influenza vaccination is recommended, Medicaid/Medicare as primary expected payer, and hospitalization in a rural area. These findings may be explained by these women being at higher risk of influenza-related morbidity or reflect disparities in receipt of influenza immunization. Universal vaccination of pregnant women to decrease influenza-related morbidity should be encouraged.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63171/1/jwh.2006.15.891.pd

Complications of Common Gynecologic Surgeries among HIV-Infected Women in the United States

Objective. To compare frequencies of complications among HIV-infected and-uninfected women undergoing common gynecological surgical procedures in inpatient settings. Methods. We used 1994–2007 data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, a nationally representative sample of inpatient hospitalizations. Our analysis included discharge records of women aged ≥15 undergoing hysterectomy, oophorectomy, salpingectomy for ectopic pregnancy, bilateral tubal sterilization, or dilation and curettage. Associations between HIV infection status and surgical complications were evaluated in multivariable logistic regression models, adjusting for key covariates. Results. For each surgery, HIV infection was associated with experiencing ≥1 complication. Adjusted ORs ranged from 2.0 (95% confidence interval (CI): 1.7, 2.2) for hysterectomy with oophorectomy to 3.1 (95% CI: 2.4, 4.0) for bilateral tubal sterilization with no comorbidity present. HIV infection was positively associated with extended length of stay and infectious complications of all of the surgeries examined. For some surgeries, it was positively associated with transfusion and anemia due to acute blood loss. Among HIV-infected women, the odds of infectious and other complications did not decrease between 1994–2000 and 2001–2007. Conclusion. HIV infection was associated with elevated frequencies of complications of gynecologic surgeries in the US, even in the era of HAART

Controlling anal incontinence in women by performing anal exercises with biofeedback or loperamide (CAPABLe) trial: Design and methods

The goals of this trial are to determine the efficacy and safety of two treatments for women experiencing fecal incontinence. First, we aim to compare the use of loperamide to placebo and second, to compare the use of anal sphincter exercises with biofeedback to usual care. The primary outcome is the change from baseline in the St. Mark's (Vaizey) Score 24 weeks after treatment initiation. As a Pelvic Floor Disorders Network (PFDN) trial, subjects are enrolling from eight PFDN clinical centers across the United States. A centralized data coordinating center supervises data collection and analysis. These two first-line treatments for fecal incontinence are being investigated simultaneously using a two-by-two randomized factorial design: a medication intervention (loperamide versus placebo) and a pelvic floor strength and sensory training intervention (anal sphincter exercises with manometry-assisted biofeedback versus usual care using an educational pamphlet). Interventionists providing the anal sphincter exercise training with biofeedback have received standardized training and assessment. Symptom severity, diary, standardized anorectal manometry and health-related quality of life outcomes are assessed using validated instruments administered by researchers masked to randomized interventions. Cost effectiveness analyses will be performed using prospectively collected data on care costs and resource utilization. This article describes the rationale and design of this randomized trial, focusing on specific research concepts of interest to researchers in the field of female pelvic floor disorders and all other providers who care for patients with fecal incontinence

High-throughput screening of monoclonal antibodies against plant cell wall glycans by hierarchical clustering of their carbohydrate microarray binding profiles

Antibody-producing hybridoma cell lines were created following immunisation with a crude extract of cell wall polymers from the plant Arabidopsis thaliana. In order to rapidly screen the specificities of individual monoclonal antibodies (mAbs), their binding to microarrays containing 50 cell wall glycans immobilized on nitrocellulose was assessed. Hierarchical clustering of microarray binding profiles from newly produced mAbs, together with the profiles for mAbs with previously defined specificities allowed the rapid assignments of mAb binding to antigen classes. mAb specificities were further investigated using subsequent immunochemical and biochemical analyses and two novel mAbs are described in detail. mAb LM13 binds to an arabinanase-sensitive pectic epitope and mAb LM14, binds to an epitope occurring on arabinogalactan-proteins. Both mAbs display novel patterns of recognition of cell walls in plant materials

Comparative in situ analyses of cell wall matrix polysaccharide dynamics in developing rice and wheat grain

Cell wall polysaccharides of wheat and rice endosperm are an important source of dietary fibre. Monoclonal antibodies specific to cell wall polysaccharides were used to determine polysaccharide dynamics during the development of both wheat and rice grain. Wheat and rice grain present near synchronous developmental processes and significantly different endosperm cell wall compositions, allowing the localisation of these polysaccharides to be related to developmental changes. Arabinoxylan (AX) and mixed-linkage glucan (MLG) have analogous cellular locations in both species, with deposition of AX and MLG coinciding with the start of grain filling. A glucuronoxylan (GUX) epitope was detected in rice, but not wheat endosperm cell walls. Callose has been reported to be associated with the formation of cell wall outgrowths during endosperm cellularisation and xyloglucan is here shown to be a component of these anticlinal extensions, occurring transiently in both species. Pectic homogalacturonan (HG) was abundant in cell walls of maternal tissues of wheat and rice grain, but only detected in endosperm cell walls of rice in an unesterified HG form. A rhamnogalacturonan-I (RG-I) backbone epitope was observed to be temporally regulated in both species, detected in endosperm cell walls from 12 DAA in rice and 20 DAA in wheat grain. Detection of the LM5 galactan epitope showed a clear distinction between wheat and rice, being detected at the earliest stages of development in rice endosperm cell walls, but not detected in wheat endosperm cell walls, only in maternal tissues. In contrast, the LM6 arabinan epitope was detected in both species around 8 DAA and was transient in wheat grain, but persisted in rice until maturity

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)