Synthesis of gamma irradiated acrylic acid-grafted-sawdust (SD-g-AAc) for trivalent chromium adsorption from aqueous solution.

Water pollution caused by chromium released from tannery is a serious concern to the environment and public health. Chromium removal from tannery effluent is a crying need before discharging to the surface water. In this study, acrylic acid-grafted sawdust was prepared by Tectona grandis sawdust grafting with acrylic acid employing gamma irradiation in the presence of air and Mohr's salt. It was treated with NaOH and the characterization of surface morphology and functional groups of modified sawdust was studied by SEM and FTIR.. The effects of solution pH, adsorbent dosage, adsorption time, and initial Cr(III) ion concentration were investigated by batch sorption studies. The process was found to be pH, temperature and concentration dependent. Langmuir and Freundlich isotherms were applied to realize the adsorption process in depth, and it was found that the Langmuir isotherm model fitted well with experimental data (R2 value of 0.983). The maximum monolayer adsorption capacity of acrylic acid-grafted sawdust for Cr(III) from aquous solution was found to be 21.55 mg g-1 at 25 °C. Pseudo-first-order and pseudo-second-order kinetic models were employed to analyze the kinetics of the process, and it was found that the experimental process followed the pseudo-second-order kinetic model, i.e. chemisorption. This study revealed that acrylic acid-grafted sawdust has a decent potential for the removal of Cr(III) from tannery effluents.

Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study.

Background: Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)-based microbiologic end points for vaccine trials. Methods: We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated. Conclusions: The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.

Microbiological Methods Used in the Enterics for Global Health Shigella Surveillance Study.

Background: Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella. We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella, compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium. Conclusions: Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Bangladesh.

Background: Shigella is an important cause of diarrhea in Bangladeshi children <5 years of age, with an incidence rate of 4.6 per 100 person-years. However, the report was more than a decade old, and data on Shigella consequences are similarly outdated and heterogeneously collected. Methods: Facility-based disease surveillance is planned to be carried out under the Enterics for Global Health (EFGH) Shigella Surveillance Study consortium for 2 years with aims to optimize and standardize laboratory techniques and healthcare utilization and coverage survey, clinical and anthropometric data collection, safety monitoring and responsiveness, and other related activities. The EFGH is a cohesive network of multidisciplinary experts, capable of operating in concert to conduct the study to generate data that will pave the way for potential Shigella vaccine trials in settings with high disease burden. The study will be conducted within 7 country sites in Asia, Africa, and Latin America. Conclusions: We outline the features of the Bangladesh site as part of this multisite surveillance network to determine an updated incidence rate and document the consequences of Shigella diarrhea in children aged 6-35 months, which will help inform policymakers and to implement the future vaccine trials.

Immune responses in children after vaccination with a typhoid Vi-tetanus toxoid conjugate vaccine in Bangladesh.

A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection.

Unusual presentation of gastric cancer during treatment of hairy cell leukemia: Exploring the etiological basis of this rare phenomenon.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Patients typically present with cytopenia and splenomegaly. We describe the case of a 78-year-old patient with refractory HCL who acutely developed a cystic lesion on the back while receiving moxetumomab pasudotox therapy. Biopsy of the lesion revealed the presence of adenocarcinoma, which prompted a detailed evaluation resulting in a diagnosis of stage IV gastric cancer. Nevertheless, to establish any association between moxetumomab pasudotox therapy and secondary cancer development, a satisfactory number of studies need to be conducted.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Cell-type-specific disruption of PERK-eIF2α signaling in dopaminergic neurons alters motor and cognitive function.

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) has been shown to activate the eIF2α kinase PERK to directly regulate translation initiation. Tight control of PERK-eIF2α signaling has been shown to be necessary for normal long-lasting synaptic plasticity and cognitive function, including memory. In contrast, chronic activation of PERK-eIF2α signaling has been shown to contribute to pathophysiology, including memory impairments, associated with multiple neurological diseases, making this pathway an attractive therapeutic target. Herein, using multiple genetic approaches we show that selective deletion of the PERK in mouse midbrain dopaminergic (DA) neurons results in multiple cognitive and motor phenotypes. Conditional expression of phospho-mutant eIF2α in DA neurons recapitulated the phenotypes caused by deletion of PERK, consistent with a causal role of decreased eIF2α phosphorylation for these phenotypes. In addition, deletion of PERK in DA neurons resulted in altered de novo translation, as well as changes in axonal DA release and uptake in the striatum that mirror the pattern of motor changes observed. Taken together, our findings show that proper regulation of PERK-eIF2α signaling in DA neurons is required for normal cognitive and motor function in a non-pathological state, and also provide new insight concerning the onset of neuropsychiatric disorders that accompany UPR failure.

Factors associated with sexually transmitted infection diagnosis in women who have sex with women, women who have sex with men and women who have sex with both.

INTRODUCTION: Many US women report same sex behaviour, yet data on risk factors and STIs in women who have sex with women (WSW), women who have sex with both men and women (WSB) and how these compare to women who have sex with men only (WSM) remain limited. Here we compared self-identified WSW, WSB and WSM attending two STI clinics in Baltimore, Maryland. METHODS: This was a retrospective analysis using a database of first clinic visits 2005-2016. WSW and WSB were compared with an age-matched random sample of WSM. Proportions were compared using the χ2 test. Acute STI (aSTI) was defined as gonorrhoea (Neisseria gonorrhoeae, GC), chlamydia (Chlamydia trachomatis, CT), trichomonas (Trichomonas vaginalis, TV) or early syphilis. Logistic regression was used to assess aSTI predictors. CT testing was not uniformly done, so a sensitivity analysis removing CT from the aSTI definition was conducted. RESULTS: Visits from 1095 WSW, 1678 WSB and 2773 WSM were analysed. WSB had equal or higher test positivity for all STIs except urogenital chlamydia, had more sexual partners, were more likely to engage in transactional sex and were more likely to report drug use and binge drinking than WSM (p≤0.01). WSW had lower test positivity for urogenital GC and CT than WSM or WSB, but comparable test positivity for TV, higher reported binge drinking and comparable reported substance use as WSM. Younger age and cocaine use predicted STI diagnosis only in WSM. CONCLUSIONS: WSB in these clinics bear an equal or higher burden of most STIs, have more partners and report more substance use than WSM. WSW carry a lower, but still substantial burden of STIs, and many report substance use. Factors predicting STI diagnosis differ between WSW, WSB and WSM suggesting that tailored STI prevention and testing approaches are needed in these groups.

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.

There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.

Biomedical Response to Neisseria gonorrhoeae and Other Sexually Transmitted Infections in the US Military.

INTRODUCTION: Sexually transmitted infections (STIs) continue to plague militaries and defense forces. While the historical recognition of the impact of STIs on operations is evident, contemporary surveillance and research activities are limited. As Neisseria gonorrhoeae and other sexually transmitted pathogens become increasingly resistant to antibiotics, the role of the Department of Defense (DoD) in disease surveillance and clinical research is essential to military Force Health Protection. METHODS: The Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences partnered with the DoD Global Emerging Infections Surveillance (GEIS) program to monitor the distribution of gonorrhea antimicrobial resistance (AMR) both domestically and abroad. The DoD gonococcal reference laboratory and repository was established in 2011 as a resource for confirmatory testing and advanced characterization of isolates collected from sites across the continental United States (CONUS) and GEIS-funded sites outside the continental United States (OCONUS). The IDCRP is currently implementing surveillance efforts at CONUS military clinics, including Madigan Army Medical Center, Naval Medical Center Camp Lejeune, Naval Medical Center Portsmouth, Naval Medical Center San Diego, and San Antonio Military Medical Center (efforts were also previously at Womack Army Medical Center). The reference laboratory and repository receives specimens from OCONUS collaborators, including Armed Forces Research Institute of Medical Sciences (AFRIMS; Bangkok, Thailand), Naval Medical Research Unit No. 3 (NAMRU-3), Ghana Detachment (Accra, Ghana), Naval Medical Research Unit No. 6 (NAMRU-6; Lima, Peru), U.S. Army Medical Research Unit - Georgia (USAMRD-G; Tbilisi, Republic of Georgia), and U.S. Army Medical Research Directorate - Kenya (USAMRD-K; Nairobi, Kenya). The gonococcal surveillance program, to include findings, as well as associated clinical research efforts are described. RESULTS: Among N. gonorrhoeae isolates tested within the United States, 8% were resistant to tetracycline, 2% were resistant to penicillin, and 30% were resistant to ciprofloxacin. To date, only one of the 61 isolates has demonstrated some resistance (MIC=1 µg/ml) to azithromycin. No resistance to cephalosporins has been detected; however, reduced susceptibility (MIC=0.06-0.125 µg/ml) has been observed in 13% of isolates. Resistance is commonly observed in N. gonorrhoeae isolates submitted from OCONUS clinical sites, particularly with respect to tetracycline, penicillin, and ciprofloxacin. While no azithromycin-resistant isolates have been identified from OCONUS sites, reduced susceptibility (MIC=0.125-0.5 µg/ml) to azithromycin was observed in 23% of isolates. CONCLUSION: Continued monitoring of circulating resistance patterns on a global scale is critical for ensuring appropriate treatments are prescribed for service members that may be infected in the U.S. or while deployed. Domestic surveillance for gonococcal AMR within the Military Health System has indicated that resistance patterns, while variable, are not dramatically different from what is seen in U.S. civilian data. Global patterns of gonococcal AMR have been described through the establishment of a central DoD gonococcal reference laboratory and repository. This repository of global isolates provides a platform for further research and development into biomedical countermeasures against gonococcal infections.

Removal of Cu(II), Pb(II) and Cr(VI) ions from aqueous solution using amidoximated non-woven polyethylene-g-acrylonitrile fabric.

Pre-irradiation method was applied to graft acrylonitrile (AN) onto non-woven polyethylene film. Graft yield reached 130% at 70 kGy radiation dose, 60% monomer concentration and 4 h reaction time when H2SO4 was used as an additive. The modification of AN grafted films with hydroxyl amine hydrochloride was done for the preparation of amidoxime adsorbent. The constructed adsorbent was characterized using FTIR, DMA and SEM. The amidoxime adsorbent was used for adsorption of Cu(II), Pb(II) and Cr(VI). Adsorption capacity was investigated under different conditions: contact time, pH and initial metal ion concentration. The optimum condition for maximum adsorption was found to be contact time 72 h and initial metal concentration 500 ppm for all the metal ions studied and pH 5.2 for Cu(II), 5.4 for Pb(II), 1.5 for Cr(VI). Kinetic adsorption data was elucidated using pseudo-first-order and pseudo-second-order equations. The equilibrium experimental data of metal adsorption matched Langmuir isotherm model. From the Langmuir equation, the monolayer saturation adsorption capacity (highest adsorption capacity) of the adsorbent was found to be 74.62 mg/g for Cu(II), 107 mg/g for Pb(II) and 156.25 mg/g for Cr(VI). The thermodynamics of metal adsorption was also investigated. Furthermore, desorption and reuse of the adsorbent film was studied. The results suggest that the adsorbent can be effective for adsorption of Cu(II), Pb(II) and Cr(VI).

Plasma Immunoglobulin A Responses Against 2 Salmonella Typhi Antigens Identify Patients With Typhoid Fever.

BACKGROUND: There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immunoscreening technologies, we previously identified several immunoreactive Salmonella Typhi antigens that seem promising for possible inclusion in a new diagnostic assay: hemolysin E (HlyE), cytolethal distending toxin, S. Typhi lipopolysaccharide (LPS), and S. Typhi membrane preparation. METHODS: We assessed plasma antibody responses (immunoglobulin [Ig] M, IgA, and IgG) to these antigens by means of enzyme-linked immunosorbent assay in patients with suspected enteric fever, controls with other febrile illnesses, and healthy controls in Dhaka, Bangladesh and performed Tubex and Typhidot tests, the Widal assay, and the typhoid/paratyphoid test (TPTest) in each patient. Using machine learning methods, we identified a parsimonious serology signature to distinguish acute typhoid cases from controls and then validated our findings in an independent test cohort from Nepal of patients with culture-confirmed S. Typhi and controls with other bacteremic illnesses. RESULTS: We demonstrated that the use of 2 antigens (HlyE and LPS) with 1 antibody isotype (IgA) could distinguish typhoid from other invasive bacterial infections (area under the receiver operating characteristic curve [AUC], 0.95; sensitivity, 90%, specificity, 92%). Use of a single antigen (HlyE) and isotype (IgA) had an AUC of 0.93. CONCLUSION: Our results suggest that development of a diagnostic assay for acute typhoid fever focused on detecting IgA responses against HlyE, with or without LPS, is warranted.

Clinical Indicators of Late-Onset Sepsis Workup in Very Low-Birth-Weight Infants in the Neonatal Intensive Care Unit.

Background Late-onset sepsis (LOS) in very low-birth-weight (VLBW) infants is associated with significant morbidity and mortality. Objectives To determine the incidence of LOS workup, association, and predictive value of clinical indicators leading to culture-positive versus culture-negative sepsis workup. Methods All sepsis workups performed after 7 days of life, in neonates with birth weight of < 1,500 g were included. Each case (culture-positive workup) was matched with a control (culture-negative workup) for gestational age (GA), birth weight, corrected gestational age, and chronological age, at the time of workup. The clinical indicators leading to the performance of sepsis workup were compared between cases and controls. Results The incidence of culture-positive workup was 87/345 (25.2%) and that of LOS was 84/279 (30.1%). Among various clinical indicators, hypothermia and apnea were significantly associated with culture-positive sepsis workup (p = 0.015 and 0.004, respectively), with a positive predictive value of 81.2 and 71.4%, respectively. Conclusion In VLBW infants, one-fourth of sepsis workups resulted in a positive culture. Apnea and hypothermia were the most significant predictors of culture-positive workup after matching for GA, birth weight, chronological age, and corrected GA at the time of the workup.

Selective Hg(II) adsorption from aqueous solutions of Hg(II) and Pb(II) by hydrolyzed acrylamide-grafted PET films.

Selective Hg(II) adsorption from aqueous solutions of Hg(II) and Pb(II) using hydrolyzed acrylamide (AAm)-grafted polyethylene terephthalate (PET) films was examined to explore the potential reuse of waste PET materials. Selective recovery of Hg(II) from a mixture of soft acids with similar structure, such as Hg(II) and Pb(II), is important to allow the reuse of recovered Hg(II). An adsorbent for selective Hg(II) adsorption was prepared by γ-ray-induced grafting of AAm onto PET films followed by partial hydrolysis through KOH treatment. The adsorption capacity of the AAm-grafted PET films for Hg(II) ions increased from 15 to 70 mg/g after partial hydrolysis because of the reduction of hydrogen bonding between -CONH2 groups and the corresponding improved access of metal ions to the amide groups. The prepared adsorbent was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The absorbent film showed high selectivity for the adsorption of Hg(II) over Pb(II) throughout the entire initial metal concentration range (100-500 mg/L) and pH range (2.2-5.6) studied. The high selectivity is attributed to the ability of Hg(II) ions to form covalent bonds with the amide groups. The calculated selectivity coefficient for the adsorbent binding Hg(II) over Pb(II) was 19.2 at pH 4.5 with an initial metal concentration of 100 mg/L. Selective Hg(II) adsorption equilibrium data followed the Langmuir model and kinetic data were well fitted by a pseudo-second-order equation. The adsorbed Hg(II) and Pb(II) ions were effectively desorbed from the adsorbent film by acid treatment, and the regenerated film showed no marked loss of adsorption capacity upon reuse for selective Hg(II) adsorption.