Divergent Cytokine and Chemokine Responses at Early Acute Simian Immunodeficiency Virus Infection Correlated with Virus Replication and CD4 T Cell Loss in a Rhesus Macaque Model.

Cytokine and chemokine levels remain one of the significant predictive factors of HIV pathogenesis and disease outcome. Understanding the impact of cytokines and chemokines during early acute infection will help to recognize critical changes during HIV pathogenesis and might assist in establishing improved HIV treatment and prevention methods. Sixty-one cytokines and chemokines were evaluated in the plasma of an SIV-infected rhesus macaque model. A substantial change in 11 cytokines/growth factors and 9 chemokines were observed during acute infection. Almost all the cytokines/chemokines were below the baseline values for an initial couple of days of infection. We detected six important cytokines/chemokines, such as IL-18, IP-10, FLT3L, MCP-1, MCP-2, and MIP-3ß, that can be used as biomarkers to predict the peripheral CD4+ T cell loss and increased viral replication during the acute SIV/HIV infection. Hence, regulating IL-18, IP-10, FLT3L, MCP-1, MCP-2, and MIP-3ß expression might provide an antiviral response to combat acute SIV/HIV infection.

Simian Immunodeficiency Virus Infection Mediated Changes in Jejunum and Peripheral SARS-CoV-2 Receptor ACE2 and Associated Proteins or Genes in Rhesus Macaques.

Angiotensin converting enzyme-2 (ACE2) and associated proteins play a pivotal role in various physiological and pathological events, such as immune activation, inflammation, gut barrier maintenance, intestinal stem cell proliferation, and apoptosis. Although many of these clinical events are quite significant in SIV/HIV infection, expression profiling of these proteins has not been well reported. Considering the different pathological consequences in the gut after HIV infection, we hypothesized that the expression of ACE2 and associated proteins of the Renin-angiotensin system (RAS) could be compromised after SIV/HIV infection. We quantified the gene expression of ACE2 as well as AGTR1/2, ADAM17, and TMPRSS2, and compared between SIV infected and uninfected rhesus macaques (Macaca mulatta; hereafter abbreviated RMs). The gene expression analysis revealed significant downregulation of ACE2 and upregulation of AGTR2 and inflammatory cytokine IL-6 in the gut of infected RMs. Protein expression profiling also revealed significant upregulation of AGTR2 after infection. The expression of ACE2 in protein level was also decreased, but not significantly, after infection. To understand the entirety of the process in newly regenerated epithelial cells, a global transcriptomic study of enteroids raised from intestinal stem cells was performed. Interestingly, most of the genes associated with the RAS, such as DPP4, MME, ANPEP, ACE2, ENPEP, were found to be downregulated in SIV infection. HNFA1 was found to be a key regulator of ACE2 and related protein expression. Jejunum CD4+ T cell depletion and increased IL-6 mRNA, MCP-1 and AGTR2 expression may signal inflammation, monocyte/macrophage accumulation and epithelial apoptosis in accelerating SIV pathogenesis. Overall, the findings in the study suggested a possible impact of SIV/HIV infection on expression of ACE2 and RAS-associated proteins resulting in the loss of gut homeostasis. In the context of the current COVID-19 pandemic, the outcome of SARS-CoV-2 and HIV co-infection remains uncertain and needs further investigation as the significance profile of ACE2, a viral entry receptor for SARS-CoV-2, and its expression in mRNA and protein varied in the current study. There is a concern of aggravated SARS-CoV-2 outcomes due to possible serious pathological events in the gut resulting from compromised expression of RAS- associated proteins in SIV/HIV infection.

Comparison of Ketamine and Propofol-Based Regimens for Deep Sedation in Children Undergoing Esophagogastroduodenoscopy.

We retrospectively reviewed the charts of 180 children sedated for esophagogastroduodenoscopy (EGD) with ketamine or propofol-based regimens at our institution. Pre-EGD diagnoses and American Society of Anesthesiology physical status were similar in all subjects. Onset of action and recovery time for both regimens were not statistically significant ( p > 0.05). Mean onset of sedation for all patients was 3.85 ± 3.04 minutes, mean Aldrete score was 6.31 ± 0.61, and mean recovery time was 51.85 ± 31.78 minutes ( p > 0.05). Sedation-related adverse events observed include apnea, hypoxemia, bradycardia, hypotension, laryngospasm, skin rash, and wheezing. Deep sedation for pediatric EGD is safe if patients are carefully screened and properly monitored.

Surgically induced astigmatism and posterior corneal curvature changes following phacoemulsification.

PURPOSE: To primarily compare surgically induced astigmatism (SIA), total and posterior corneal curvature, pachymetry, and their stabilization after 2.2 and 2.8 mm clear corneal incision in phacoemulsification. METHODS: A randomized, prospective interventional study of 130 patients (130 eyes) of either sex having senile cataract (>40 years) divided randomly into two groups. The patients underwent uncomplicated phacoemulsification surgery with foldable intraocular lens implantation using 2.2 mm (group 1) and 2.8 mm incisions (group 2). The patients were evaluated preoperatively and followed-up at first, third, and sixth weeks. RESULTS: Mean SIA was less in group 1 at all the follow-up visits which was not statistically significant (P value - 0.507 (at week 1), 0.626 (at week 3), and 0.312 (at week 6). Mean SIA decreased from week 1 to week 6 in both the groups. Both the groups showed an increase in SIA with the increase in the hardness of cataract. Posterior keratometry (k1 and k2) showed statistically significant steepening in the first postoperative week, followed by gradual flattening which continued till the sixth week postoperatively. Posterior astigmatism increased in both the groups at week 1 (not statistically significant). Thereafter, it decreases and does not change significantly after 3 weeks. Pachymetry increased significantly (P value < 0.001 in both the groups) in the first week in both the groups and thereafter stabilizing at 3 weeks. CONCLUSION: Reducing the incision size does not result in any significant reduction in SIA. We observed that the posterior corneal curvature majorly stabilized by 3 weeks, but some stabilization continued till 6 weeks.

Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques.

Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for the treatment of HIV-mediated enteropathy and immune activation. We have observed a significant increased presence of α defensin5+ (HD5) Paneth cells and proliferating Ki67+ epithelial cells as well as decreased expression of E-cadherin expression in epithelial cells during SIV infection. SIV infection did not significantly influence the frequency of LGR5+ stem cells, but the frequency of HD5+ cells was significantly higher compared to uninfected controls in jejunum. Our global transcriptomics analysis of enteroids provided novel information about highly significant changes in several important pathways like metabolic, TCA cycle, and oxidative phosphorylation, where the majority of the differentially expressed genes were downregulated in enteroids grown from chronically SIV-infected macaques compared to the SIV-uninfected controls. Despite the lack of significant reduction in LGR5+ stem cell population, the dysregulation of several intestinal stem cell niche factors including Notch, mTOR, AMPK and Wnt pathways as well as persistence of inflammatory cytokines and chemokines and loss of epithelial barrier function in enteroids further supports that SIV infection impacts on epithelial cell proliferation and intestinal homeostasis.

Enhanced Intestinal TGF-ß/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques.

Transforming growth factor-ß signaling (TGF-ß) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-ß promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-ß production that attributes to its pathological manifestations remain unknown. Here, we have shown increased production of TGF-ß in a majority of intestinal CD3-CD20-CD68+ cells from acute and chronically SIV infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4+ T cells. No significant changes in intestinal TGF-ß receptor II expression were observed but increased production of the pSMAD2/3 protein and SMAD3 gene expression in jejunum tissues that were accompanied by a downregulation of SMAD7 protein and gene expression. Enhanced TGF-ß production by intestinal CD3-CD20-CD68+ cells and increased TGF-ß/SMAD-dependent signaling might be due to a disruption of a negative feedback loop mediated by SMAD7. This suggests that SIV infection impacts the SMAD-dependent signaling pathway of TGF-ß and provides a potential framework for further study to understand the role of viral factor(s) in modulating TGF-ß production and downregulating SMAD7 expression in SIV. Regulation of mucosal TGF-ß expression by therapeutic TGF-ß blockers may help to create effective antiviral mucosal immune responses.

Effects of Social Housing Changes on Immunity and Vaccine-Specific Immune Responses in Adolescent Male Rhesus Macaques.

Nonhuman primates (NHPs) in research institutions may be housed in a variety of social settings, such as group housing, pair housing or single housing based on the needs of studies. Furthermore, housing may change over the course of studies. The effects of housing and changes in housing on cell activation and vaccine mediated immune responses are not well documented. We hypothesized that animals moved indoors from group to single housing (GH-SH) would experience more stress than those separated from groups into pair housing (GH-PH), or those placed briefly into pair housing and separated 5 weeks later into single housing (GH-PH-SH). We also compared the effects of separation from group to pair housing with the separation from pair to single housing. Eighteen male rhesus macaques were followed over the course of changes in housing condition over 10-14 weeks, as well as prior to and after primary vaccination with a commercially available measles vaccine. We identified two phenotypic biomarkers, namely total CD8 population and proliferating B cells, that differed significantly across treatment groups over time. At 10 weeks post-separation, levels of proliferating B cells were higher in GH-SH subjects compared to GH-PH subjects, and in the latter, levels were lower at 10 weeks than prior to removal from group housing. At 2 weeks post-separation from group to single housing, the frequency of CD8+ T cells was higher in GH-SH subjects compared to one week post separation from pair into single housing in the GH-PH-SH subjects. Comparing the same elapsed time since the most recent separation activated CD20 populations were persistently higher in the GH-SH animals than the GH-PH-SH animals. Housing configuration did not influence vaccine-mediated responses. Overall, our study found benefits of pair housing over single housing, suggesting that perturbations in immune function will be more severe following separation from group to single housing than from pair to single housing, and supporting the use of short-duration pair housing even when animals must subsequently be separated. These findings are useful for planning the housing configurations of research NHPs used for vaccine studies and other studies where immune response is being assessed.

A critical review on current strategies and trends employed for removal of inhibitors and toxic materials generated during biomass pretreatment.

The main objective of biomass pretreatment is to separate biomass components and provide easier access with ultimate aim for lignin removal, hemicellulose protection and cellulose crystallinity reduction. Effective bioconversion with least inhibitory compound production would play a considerable role in economic practicability of the process in order to achieve economic sustainability. In this regard, detoxification is an important condition to make biomass hydrolysate acquiescent to bioconversion; also, understanding of inhibitors effect on growth and fermentation are necessary requirements for system detoxification. A number of physical, chemical and biological methods like feedstock selection, membrane selection, neutralization, use of activated charcoal etc have been recommended and developed for removal or minimizing the inhibitory compounds effect. This work reviews various inhibitory compounds produced during pretreatment methods and their removal by various processes.

Stability, Crystal Chemistry, and Magnetism of U2+xNi21-xB6 and Nb3-yNi20+yB6 and the Role of Uranium in the Formation of the Quaternary U2-zNbzNi21B6 and UδNb3-δNi20B6 Systems.

We investigated the U-Ni-B and Nb-Ni-B systems to search for possible new heavy fermion compounds and superconducting materials. The formation, crystal chemistry, and physical properties of U2Ni21B6 and Nb3-yNi20+yB6 [ternary derivatives of the cubic Cr23C6-type (cF116, Fm3̅m)] have been studied; the formation of the hypothetical "U3Ni20B6" and "Nb2Ni21B6" has been disproved. U2Ni21B6 [a = 10.6701(2) Å] crystallizes in the ordered W2Cr21C6-type, whereas Nb3-yNi20+yB6 [a = 10.5842(1) Å] adopts the Mg3Ni20B6-type. Ni in U2Ni21B6 can be substituted by U, leading to the solid solution U2+xNi21-xB6 (0 ≤ x ≤ 0.3); oppositely, Nb in Nb3Ni20B6 is partially replaced by Ni, forming the solution Nb3-yNi20+yB6 (0 ≤ y ≤ 0.5), none of them reaching the limit corresponding to the hypothetically ordered "U3Ni20B6" and "Nb2Ni21B6". These results prompted us to investigate quaternary compounds U2-zNbzNi21B6 and UδNb3-δNi20B6: strong competition in the occupancy of the 4a and 8c sites by U, Nb, and Ni atoms has been observed, with the 4a site occupied by U/Ni atoms only and the 8c site filled by U/Nb atoms only. U2Ni21B6, U2.3Ni20.7B6, and Nb3Ni20B6 are Pauli paramagnets. Interestingly, Nb2.5Ni20.5B6 shows ferromagnetism with TC ≈ 11 K; the Curie-Weiss fit gives an effective magnetic moment of 2.78 µB/Ni, suggesting that all Ni atoms in the formula unit contribute to the total magnetic moment. The M(H) data at 2 K further corroborate the ferromagnetic behavior with a saturation moment of 10 µB/fu (≈0.49 µB/Ni). The magnetic moment of Ni at the 4a site induces a moment in all of the Ni atoms of the whole unit cell (32f and 48h sites), with all atoms ordering ferromagnetically at 11 K. Density functional theory (DFT) shows that the formation of U2Ni21B6 and Nb3Ni20B6 is energetically preferred. The various electronic states generating ferromagnetism on Nb2.5Ni20.5B6 and Pauli paramagnetism on U2Ni21B6 and Nb3Ni20B6 have been identified.

Transcranial Doppler and Hematoma Expansion in Acute Spontaneous Primary Intracerebral Hemorrhage.

CONTEXT: The data on the role of Transcranial Doppler (TCD) in the management of acute primary intracerebral hemorrhage (ICH) is meager. AIMS: To study TCD variables associated with hematoma expansion in acute primary ICH. SETTINGS AND DESIGN: The study was carried out in the neurosciences department of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh from July 2010 to September 2011 employing a prospective, double blinded non randomized study design. MATERIALS AND METHODS: Acute ICH patients within 24 h of symptom onset were recruited. Baseline neuroimaging study (Computerized tomography, CT scan of brain) was performed to assess the pure hematoma volume by AXBXC/2 method. Baseline TCD parameters were obtained from both the middle cerebral arteries (MCAs; affected and unaffected hemisphere): Peak Systolic velocity, End Diastolic velocity, Mean Flow velocity, Resistance Index, and Pulsatility Index. Follow up (24 h) assessment of hematoma volume and TCD were carried out. Each of the TCD variables were compared in hematoma expansion (>33% increase in hematoma volume on the follow-up CT) and non-expansion group. STATISTICAL ANALYSIS: On univariate analysis, the Student's t-test and contingency tables with the X2 test were used. A forward stepwise multivariate logistic regression analysis with hematoma expansion at 24 h as the dependent variable and ROC analysis was carried out, using SPSS software version 16 (Chicago, IL). P value < 0.05 was considered significant. RESULTS: Twenty-five patients completed the study. Ten patients (40%) had hematoma expansion. Multivariate analysis revealed unaffected hemisphere MCA Pulsatility Index ratio [unaffected hemisphere MCA Follow up Pulsatility Index/baseline Pulsatility Index] of > 1.055 as the lone correlate of hematoma expansion (sensitivity of 90% and specificity of 60%). CONCLUSION: Frequent assessment with TCD could aid in prediction of hematoma expansion by measuring unaffected hemisphere Pulsatility Index ratios.

Regional Differences in the Treatment of Localized Prostate Cancer: An Analysis of Surgery and Radiation Utilization in the United States.

PURPOSE: Men with localized prostate cancer have various treatment options available in their management. The optimal approach is controversial and can be influenced by multiple factors. This study aimed to investigate the influence of geographic region on the selection of treatment for prostate cancer. METHODS AND MATERIALS: Using the National Cancer Database, we identified men diagnosed with localized prostate cancer between 2010 and 2014. The United States was divided into 11 regions per the American Cancer Society Divisions. The first course of treatment was recorded as radiation therapy (RT), radical prostatectomy (RP), or active surveillance (AS). The RT subgroup consisted of patients receiving all forms of RT, including external beam and brachytherapy, or RT plus androgen deprivation therapy. The RP subgroup consisted of patients receiving RP alone or combined with RT or androgen deprivation therapy. A χ2 test was performed to assess the association between region and frequency of RT and RP. RESULTS: This study included 462,811 men with localized prostate cancer who were treated in the United States, of whom 63.46% underwent RP, 31.54% underwent RT, and 5.00% underwent AS. Significant regional differences in RP and RT were observed (P ≤ .0001). RP was used most commonly in the Midwest (75.07%) and High Plains (73.37%) regions, whereas RP was least used in the South Atlantic (59.04%) region. Similarly, RT was used most commonly in South Atlantic (40.96%) and New England (38.98%) regions and least commonly in the Midwest (24.93%) region. AS was used most in the New England (7.27%) and Midwest (6.8%) regions and least used in the High Plains (2.57%) and Mid-South (2.84%) regions. CONCLUSIONS: Regional differences exist in the United States with regard to the definitive treatment of localized prostate cancer. The etiology for these regional differences is likely multifactorial.

Expanding Research Capacity in Sub-Saharan Africa Through Informatics, Bioinformatics, and Data Science Training Programs in Mali.

Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase (p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program's sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics.

Quantification of Viral RNA and DNA Positive Cells in Tissues From Simian Immunodeficiency Virus/Simian Human Immunodeficiency Virus Infected Controller and Progressor Rhesus Macaques.

Eradication of human immunodeficiency virus 1 (HIV-1) from an infected individual cannot be achieved using current antiretroviral therapy (ART) regimens. Viral reservoirs established in early infection remain unaffected by ART and are able to replenish systemic infection upon treatment interruption. Simian immunodeficiency virus (SIV) infected macaque models are useful for studying HIV pathogenesis, treatments, and persistent viral reservoirs. Here, we used the SIV macaque model to examine and quantify RNA and DNA positive cells in tissues from macaques that control viral replication (controllers) and those that have persistently high plasma viremia (progressors). A positive correlation was detected between tissue RNA+ cells and plasma viral load in both mesenteric lymph node (LN) and spleen. Similarly, a positive correlation also observed between DNA+ cells and plasma viral load in ileum and jejunum. Controllers had a lower frequency of both RNA and DNA+ cells in several tissues compared to progressors. However, DNA+ cells were prevalent in mesenteric LN, inguinal LN, colon, midbrain, and bone marrow tissues in both controller and progressors. Organized lymphoid tissues of LNs, spleen, and intestine were found as the major tissues positive for virus. Viral RNA and DNA positive cells were detected in brain and thymus in macaques with high plasma viremia and SIV-encephalitis. Both T cells and macrophages were shown to be infected in several tissues, indicating vaccines and ART should be specifically designed to protect these cells in organized lymphoid tissues. These results indicate ART should target infected cells in secondary lymphoid organs to reduce both productively and latently infected cells.

Lack of T-cell-mediated IL-2 and TNFα production is linked to decreased CD58 expression in intestinal tissue during acute simian immunodeficiency virus infection.

For an effective T-cell activation and response, co-stimulation is required in addition to the antigen-specific signal from their antigen receptors. The CD2/CD58 interaction is considered as one of the most important T-cell co-stimulatory pathways for T-cell activation and proliferation, and its role in regulating intestinal T-cell function in acute and chronic SIV -infected macaques is poorly documented. Here, we demonstrated a significant reduction of CD58 expression in both T- and B-cell populations during acute SIV infection along with high plasma viral load and a loss of intestinal CD4+ T cells compared to SIV-uninfected control macaques. The reduction of CD58 expression in T cells was correlated with the reduced expression of T-cell-mediated IL-2 and TNFα production. Together, these results indicate that reduction in the CD2/CD58 interaction pathway in mucosal lymphocytes might play a crucial role in mucosal T-cell dysfunction during acute SIV/HIV infection.

Pioglitazone's beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study.

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n = 7). The third group received BCNI and Pio treatment (BCNI + Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI + Pio + JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rß (p-IGF-1Rß), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI + Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI + Pio + JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rß was observed in the BCNI + Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI + Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rß. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques.

BACKGROUND: Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. METHODS: Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIVMAC251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. RESULTS: The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma correlated with decreased plasma viremia. Early induction and the breadth of antigen-specific IgG responses were found to be significantly correlated with the control of plasma viral load. Immunoglobulin classes share similar functional linear B-cell epitopes. SIV-specific linear envelope B-cell epitopes were found to be 12 amino-acids in length. CONCLUSIONS: Early induction of combination of peptide-specific IgG responses were found to be responsible for the control of plasma viral load and indicative of disease outcome in SIV-infected rhesus macaques and might be important for the development of therapeutic strategies for control or prevention of HIV/AIDS.

Optimization of Salmonella Typhi biofilm assay on polypropylene microtiter plates using response surface methodology.

The objective of this study was to develop an optimized assay for Salmonella Typhi biofilm that mimics the environment of the gallbladder as an experimental model for chronic typhoid fever. Multi-factorial assays are difficult to optimize using traditional one-factor-at-a-time optimization methods. Response surface methodology (RSM) was used to optimize six key variables involved in S. Typhi biofilm formation on cholesterol-coated polypropylene 96-well microtiter plates. The results showed that bile (1.22%), glucose (2%), cholesterol (0.05%) and potassium chloride (0.25%) were critical factors affecting the amount of biofilm produced, but agitation (275 rpm) and sodium chloride (0.5%) had antagonistic effects on each other. Under these optimum conditions the maximum OD reading for biofilm formation was 3.4 (λ600 nm), and the coefficients of variation for intra-plate and inter-plate assays were 3% (n = 20) and 5% (n = 8), respectively. These results showed that RSM is an effective approach for biofilm assay optimization.

Incidence, Trends, and Outcomes of Cerebral Edema Among Children With Diabetic Ketoacidosis in the United States.

INTRODUCTION: There are limited data regarding the incidence, trends, and outcomes of cerebral edema among patients with diabetic ketoacidosis (DKA). METHODS: NIS database was used from year 2002 to 2012. Cases with primary diagnosis of DKA were identified using International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9 CM) code 250.1 x. Cerebral edema patients were identified using ICD-9 CM code 348.5. We compared the baseline characteristics of both groups to estimate differences using the χ(2) test, Student's t test, Wilcoxon rank-sum test, and survey regression depending on the distributions of variables. For trend analysis, the χ(2) test of trend for proportions was used using the Cochrane Armitage test via the "trend" command in Statistical Analysis Software (SAS). Multivariate odds ratios were calculated. P value for <0.05 was considered as significant for all analysis. RESULTS: In all, 205 (weighted n = 974) cases of cerebral edema were identified among 52 049 (weighted n = 246 925) DKA patients, which estimates the incidence of cerebral edema at 0.39%. Trends of incidence of developing cerebral edema increased almost 2 times, from 0.34 in 2002 to 0.64 in 2012 (P < 0.001). Univariate analysis showed that both length of stay (LOS; 3 vs 2; P < 0.001) and cost of hospitalization ($10 530 vs $3953; P < 0.001) were statistically higher among those who developed cerebral edema. CONCLUSION: Our study shows that over the study period, trend in incidence of cerebral edema among DKA patients has increased. Patients with cerebral edema were found to have longer LOS and higher cost of hospitalization.