Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

Evolution of antibody immunity to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.

Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-21-4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small-but significant-margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5-8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy.

Convergent antibody responses to SARS-CoV-2 in convalescent individuals.

During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC50 values) as low as 2 ng ml-1. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits.

Despite the growing number of genome-wide association studies (GWASs), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWASs are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci. Specifically, we test whether SNPs in regions of European ancestry shared between European American and admixed African American individuals have the same causal effect sizes. We hypothesize that in African Americans, the presence of genetic interactions will drive the causal effect sizes of SNPs in regions of European ancestry to be more similar to those of SNPs in regions of African ancestry. We apply our method to two traits: gene expression in 296 African Americans and 482 European Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) and low-density lipoprotein cholesterol (LDL-C) in 74K African Americans and 296K European Americans in the Million Veteran Program (MVP). We find significant evidence for genetic interactions in our analysis of gene expression; for LDL-C, we observe a similar point estimate, although this is not significant, most likely due to lower statistical power. These results suggest that gene-by-gene or gene-by-environment interactions modify the effect sizes of causal variants in human complex traits.

A Qualitative Study of Drivers for Use of the Primary Care Exception Among Internal Medicine Teaching Faculty.

BACKGROUND: The Primary Care Exception (PCE) is a billing rule from the Centers for Medicare and Medicaid Services (CMS) that allows supervising physicians to bill for ambulatory care provided by a resident without their direct supervision. There has been increased focus on entrustment as a method to assess readiness for unsupervised practice. OBJECTIVE: To understand the factors influencing attending physicians' use of the PCE in ambulatory settings and identify common themes defining what motivates faculty preceptors to use the PCE. APPROACH: This was a qualitative exploratory study. Participants were interviewed one-on-one using a semi-structured template informed by the entrustment literature. Analysis was conducted using a thematically framed, grounded theory-based approach to identify major themes and subthemes. PARTICIPANTS: Twenty-seven internal medicine teaching faculty took part in a multi-institutional study representing four residency training programs across two academic medical centers in Connecticut. KEY RESULTS: Four predominant categories of themes influencing PCE use were identified: (1) clinical environment factors, (2) attending attitudes, (3) resident characteristics, and (4) patient attributes. An attending's "internal rules" drawn from prior experiences served as a significant driver of PCE non-use regardless of the trainee, patient, or clinical context. A common conflict existed between using the PCE to promote resident autonomy versus waiving the PCE to promote safety. CONCLUSIONS: The PCE can serve as a tool to support resident autonomy, confidence, and overall clinical efficiency. Choice of PCE use by attendings involved complex internal decision-making schema balancing internal, patient, resident, and environmental-related factors. The lack of standardized processes in competency evaluation may increase susceptibility to biases, which could be mitigated by applying standardized modes of assessment that encompass shared principles.

ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer.

INTRODUCTION: ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated. METHODS: ATF4 expression was evaluated at genomic and transcriptomic levels using METABRIC (n = 1,980), GeneMiner (n = 4,712), and KM-Plotter datasets. Proteomic expression was assessed via immunohistochemistry (n = 2,225) in the Nottingham Primary Breast Cancer Series. ATF4 genomic copy number (CN) variation and mRNA/protein in association with clinicopathological parameters, amino acid transporters (AATs), and patient outcome were investigated. RESULTS: Genomic, transcriptomic, and proteomic overexpression of ATF4 was associated with more aggressive ER-negative tumours. ATF4 mRNA and protein expression were significantly associated with increased expression of glutamine related AATs including SLC1A5 (p < 0.01) and SLC7A11 (p < 0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p < 0.01), especially in ER+ tumours (p < 0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p < 0.01). CONCLUSION: These findings suggest a complex interplay between ATF4 and AATs in breast cancer biology and underscore the potential role for ATF4 as a prognostic marker in ER+ breast cancer, offering a unique opportunity for risk stratification and personalized treatment strategies.

Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

Thauera sp. for efficient nitrate removal in continuous denitrifying moving bed biofilm reactor.

Thauera is the most widely found dominant denitrifying genus in wastewater. In earlier study, MBBR augmented with a specially developed denitrifying five-membered bacterial consortium (DC5) where Thauera was found to be the most abundant and persistent genus. Therefore, to check the functional potential of Thauera in the removal of nitrate-containing wastewater in the present study Thauera sp.V14 one of the member of the consortium DC5 was used as the model organism. Thauera sp.V14 exhibited strong hydrophobicity, auto-aggregation ability, biofilm formation and denitrification ability, which indicated its robust adaptability short colonization and nitrate removal efficiency. Continuous reactor studies with Thauera sp.V14 in 10 L dMBBR showed 91% of denitrification efficiency with an initial nitrate concentration of 620 mg L-1 within 3 h of HRT. Thus, it revealed that Thauera can be employed as an effective microorganism for nitrate removal from wastewater based on its performance in the present studies.

The early determinants of career choices for medical students following an obstetrics and gynaecology placement: Mixed methods study.

OBJECTIVE: To explore the impact of attending a clinical placement in considering a career in obstetrics and gynaecology. DESIGN: Mixed methods study. SETTING: London Medical School. POPULATION: Fifth year medical students attending a clinical placement in obstetrics and gynaecology. METHODS: Between January 2021 and January 2022, questionnaires were used and semi-structured focus groups conducted, which were audio-recorded. Descriptive statistics were conducted and a framework analysis on transcribed focus groups. MAIN OUTCOME MEASURE: The impact of the clinical placement on career choice. RESULTS: Six main themes were identified from the analysis; three contributing to considering a career in obstetrics and gynaecology; pregnancy is not an illness, extraordinary experience of observing childbirth and variable specialty and three themes emerged contributing to not considering a career; lack of work-life balance, high stakes specialty and the emotional toll. Even at an undergraduate level, medical students exhibited concerns about the long-term feasibility of achieving work-life balance and avoiding professional burnout, which was partly attributed to the responsibility of looking after both the woman and their baby. CONCLUSIONS: Obstetrics and gynaecology is perceived as an exciting and variable speciality by medical students. Students' experiences on the labour ward during a clinical placement appear to contribute to the consideration of a career in obstetrics and gynaecology. Students should be given opportunities to discuss their concerns about obstetrics, particularly over the potential psychological impact of adverse/traumatic birth events. It is crucial to provide a realistic introduction to obstetrics, to recruit enthusiastic junior doctors who will be resilient to the pressures of the speciality, to avoid burnout and minimise attrition rates.

Modifiable Risk Factors for Alzheimer Disease and Related Dementias Among Adults Aged ≥45 Years - United States, 2019.

Alzheimer disease,* the most common cause of dementia, affects an estimated 6.5 million persons aged ≥65 years in the United States (1). A growing body of evidence has identified potential modifiable risk factors for Alzheimer disease and related dementias (ADRD) (1-3). In 2021, the National Plan to Address Alzheimer's Disease (National Plan) introduced a new goal to "accelerate action to promote healthy aging and reduce risk factors for Alzheimer's disease and related dementias" to help delay onset or slow the progression of ADRD (3). To assess the status of eight potential modifiable risk factors (i.e., high blood pressure, not meeting the aerobic physical activity guideline, obesity, diabetes, depression, current cigarette smoking, hearing loss, and binge drinking), investigators analyzed data from the cognitive decline module that was administered to adults aged ≥45 years in 31 states and the District of Columbia (DC)† in the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Among the risk factors, prevalence was highest for high blood pressure (49.9%) and lowest for binge drinking (10.3%) and varied by selected demographic characteristics. Adults with subjective cognitive decline (SCD),§ an early indicator of possible future ADRD (4), were more likely to report four or more risk factors than were those without SCD (34.3% versus 13.1%). Prevalence of SCD was 11.3% overall and increased from 3.9% among adults with no risk factors to 25.0% among those with four or more risk factors. Implementing evidence-based strategies to address modifiable risk factors can help achieve the National Plan's new goal to reduce risk for ADRD while promoting health aging.¶,*.

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.

Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 µg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

The impact of COVID-19 on service delivery systems: evidence from a survey of United States refugee resettlement agencies.

BACKGROUND: Key to the US refugee resettlement effort is the role of non-governmental organizations (NGOs) who receive, place, and provide transitional programs and referrals to new and recently resettled refugees. Yet only one rapid assessment study thus far examined the impact of COVID-19 on service delivery systems of US refugee resettlement agencies. This exploratory study describes the capability and preparedness of US refugee resettlement agencies to provide services and care to clients during the COVID-19 pandemic. METHODS: Using both telephone interviews and an internet survey, we assessed the impact of COVID-19 on service delivery, agency capacity, and preparedness of 101 US refugee resettlement agencies. Descriptive statistics were used to describe the dataset, while chi-square (χ2) tests were used to examine relationships by resettlement agency size (number of employees in each agency). RESULTS: Despite a temporary pause on refugee admissions, restrictive stay-at-home orders, and refugee travel restrictions, the majority of responding US refugee resettlement agencies continued to provide specialized services and care to resettled refugees and other immigrants. Among the more important findings was that agencies that continued to provide refugee services and care onsite in their existing facilities or office rather than moving such services offsite differed by agency size [χ2 (9.494, n = 101), p < 0.05]. Almost all agencies (93.1%) strongly agreed or agreed that staff have timely access to COVID-19 information. Most of the refugee services were provided offsite (n = 72 agencies, some with multiple offices across the US). CONCLUSIONS: US refugee resettlement agencies continued to perform admirably despite a lack of funding. Future research is underway to obtain a more balanced understanding of the impact of COVID-19 on practice or operations.

Prevalence and Characteristics of Subjective Cognitive Decline Among Unpaid Caregivers Aged ≥45 Years - 22 States, 2015-2019.

Approximately 20% of U.S. adults are unpaid caregivers (caregivers) (1) who provide support to a family member or friend with a health condition or disability. Although there are benefits to caregiving, it can negatively affect caregivers' physical and mental health (2-4). Much of the assistance caregivers provide, such as administering medications or financial management, relies on cognitive ability, but little is known about caregivers' cognitive functioning. Subjective cognitive decline (SCD), the self-reported experience of worsening or more frequent confusion or memory loss over the past year (5), could affect caregivers' risk for adverse health outcomes and affect the quality of care they provide. CDC analyzed SCD among caregivers aged ≥45 years through a cross-sectional analysis of data from 22 states in the 2015-2019 Behavioral Risk Factor Surveillance System (BRFSS). Among adults aged ≥45 years, SCD was reported by 12.6% of caregivers who provided care to a family member or friend with a health condition or disability in the past 30 days compared with 10.2% of noncaregivers (p<0.001). Caregivers with SCD were more likely to be employed, men, aged 45-64 years, and have chronic health conditions than were noncaregivers with SCD. Caregivers with SCD were more likely to report frequent mental distress, a history of depression, and frequent activity limitations than were caregivers without SCD. SCD among caregivers could adversely affect the quality of care provided to care recipients. Understanding caregivers' cognitive health and the types of care provided is critical to maintaining the health, well-being, and independence of the caregiving dyad. Health care professionals can support patients and their patients' caregivers by increasing awareness among caregivers of the need to monitor their own health. The health care team can work with caregivers to identify potential treatments and access supports that might help them in their caregiving role and compensate for SCD.

Testing for and identification of Multisystem Inflammatory Syndrome in children in the pediatric emergency department.

PURPOSE OF REVIEW: The current article summarizes updates on multisystem inflammatory syndrome in children (MIS-C) research and focuses on strategies to diagnose and manage these patients in the emergency department. RECENT FINDINGS: MIS-C is an inflammatory syndrome that occurs approximately 4-5 weeks after severe acute respiratory syndrome coronavirus 2 infection. It is associated with symptoms such as fever, shock, abdominal pain, rash, and conjunctivitis along with laboratory abnormalities such as elevated inflammatory markers, coagulation factors, and cytokines. Patients fall into the following three subcategories: first, classic or incomplete Kawasaki; second, cardiogenic or distributive shock; or third, an inflammatory response that does not initially meet criteria of the other subcategories. Immediate treatment largely focuses on supportive care through fluid resuscitation and pressor support; however, inpatient management may also include intravenous immunoglobulin, steroids, anticoagulation and at times anti-inflammatory biologics. SUMMARY: Overall fatality rate remains low and short-term research has demonstrated self-limited sequelae. Pediatricians should focus on the timely diagnosis and identification of this inflammatory disease via clinical findings and laboratory evidence to best treat these patients.

Postpartum Care Utilization Among Women with Medicaid-Funded Live Births in Oregon.

INTRODUCTION: Postpartum care is an important strategy for preventing and managing chronic disease in women with pregnancy complications (i.e., gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP)). METHODS: Using a population-based, cohort study among Oregon women with Medicaid-financed deliveries (2009-2012), we examined Medicaid-financed postpartum care (postpartum visits, contraceptive services, and routine preventive health services) among women who retained Medicaid coverage for at least 90 days after delivery (n = 74,933). We estimated postpartum care overall and among women with and without GDM and/or HDP using two different definitions: 1) excluding care provided on the day of delivery, and 2) including care on the day of delivery. Pearson chi-square tests were used to assess differential distributions in postpartum care by pregnancy complications (p < .05), and generalized estimating equations were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Of Oregon women who retained coverage through 90 days after delivery, 56.6-78.1% (based on the two definitions) received any postpartum care, including postpartum visits (26.5%-71.8%), contraceptive services (30.7-35.6%), or other routine preventive health services (38.5-39.1%). Excluding day of delivery services, the odds of receiving any postpartum care (aOR 1.26, 95% CI 1.08-1.47) or routine preventive services (aOR 1.32, 95% CI 1.14-1.53) were meaningfully higher among women with GDM and HDP (reference = neither). DISCUSSION: Medicaid-financed postpartum care in Oregon was underutilized, it varied by pregnancy complications, and needs improvement. Postpartum care is important for all women and especially those with GDM or HDP, who may require chronic disease risk assessment, management, and referrals.

Brief Resolved Unexplained Event: Not Just a New Name for Apparent Life-Threatening Event.

OBJECTIVES: This study aimed to evaluate patients who presented to the pediatric emergency department with an apparent life-threatening event (ALTE) to (1) determine if these patients would meet the criteria for brief resolved unexplained event (BRUE), a new term coined by the American Academy of Pediatrics in May, 2016; (2) risk stratify these patients to determine if they meet the BRUE low-risk criteria; and (3) evaluate outcomes of patients meeting the criteria for BRUE. METHODS: We conducted a retrospective chart review of patients who presented to a large urban academic center pediatric emergency department with an ALTE from January 2013 to May 2015 (before the publication of the BRUE guideline). Children ≤12 months of age were identified by the International Classification of Diseases, Ninth/Tenth Revision. Two physician reviews were performed to determine if patients met the ALTE diagnostic criteria. Data were then extracted from these charts to complete objectives. RESULTS: Seventy-eight patients met the diagnostic criteria for ALTE. Only 1 of those patients met the diagnostic criteria for BRUE, but not for low-risk BRUE. This patient underwent an extensive inpatient evaluation and was eventually discharged after monitoring with a benign diagnosis. Most patients did not meet the criteria for BRUE because the event was not unexplained. CONCLUSIONS: Only 1 patient who presented to the ED with ALTE met the criteria for BRUE, and this patient did not meet the low-risk criteria. This study corroborates previous research on BRUE and continues to highlight the importance of conducting a thorough history and physical examination on all patients presenting to the ED with concerning events.

Moving bed biofilm reactor developed with special microbial seed for denitrification of high nitrate containing wastewater.

Biological denitrification is the most promising alternative approach for the removal of nitrate from wastewater. MBBR inoculated with activated sludge is a widely studied approach, but very few studies have focused on the bioaugmentation of biofilm forming bacteria in MBBR. Our study revealed that the use of special microbial seed of biofilm forming denitrifying bacteria Diaphorobacter sp. R4, Pannonibacter sp. V5, Thauera sp. V9, Pseudomonas sp.V11, and Thauera sp.V14 to form biofilm on carriers enhanced nitrate removal performance of developed MBBR. Various process parameters C/N ratio 0.3, HRT 3 h at Nitrate loading 2400 mg L-1, Filling ratio 20%, operated with Pall ring carrier were optimized to achieve highest nitrate removal. After 300 days of continuous operation results of whole genome metagenomic studies showed that Thauera spp. were the most dominant and key contributor to the denitrification of nitrate containing wastewater and the reactor was totally conditioned for denitrification. Overall, findings suggest that bench-scale MBBR developed with biofilm forming denitrifying microbial seed accelerated the denitrification process; therefore in conclusion it is suggested as one of the best suitable and effective approach for removal of nitrate from wastewater.

Should women with gestational diabetes be screened at delivery hospitalization for type 2 diabetes?

BACKGROUND: Less than one-half of women with gestational diabetes mellitus are screened for type 2 diabetes postpartum. Other approaches to postpartum screening need to be evaluated, including the role of screening during the delivery hospitalization. OBJECTIVE: To assess the performance of an oral glucose tolerance test administered during the delivery hospitalization compared with the oral glucose tolerance test administered at a 4- to 12-week postpartum visit. STUDY DESIGN: We conducted a combined analysis of patient-level data from 4 centers (6 clinical sites) assessing the utility of an immediate postpartum 75-g oral glucose tolerance test during the delivery hospitalization (PP1) for the diagnosis of type 2 diabetes compared with a routine 4- to 12-week postpartum oral glucose tolerance test (PP2). Eligible women underwent a 75-g oral glucose tolerance test at both PP1 and PP2. Sensitivity, specificity, and negative and positive predictive values of the PP1 test were estimated for diagnosis of type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. RESULTS: In total, 319 women completed a PP1 screening, with 152 (47.6%) lost to follow-up for the PP2 oral glucose tolerance test. None of the women with a normal PP1 oral glucose tolerance test (n=73) later tested as having type 2 diabetes at PP2. Overall, 12.6% of subjects (n=21) had a change from normal to impaired fasting glucose/impaired glucose tolerance or a change from impaired fasting glucose/impaired glucose tolerance to type 2 diabetes. The PP1 oral glucose tolerance test had 50% sensitivity (11.8-88.2), 95.7% specificity (91.3-98.2%) with a 98.1% (94.5-99.6%) negative predictive value and a 30% (95% confidence interval, 6.7-65.3) positive predictive value for type 2 diabetes vs normal/impaired fasting glucose/impaired glucose tolerance result. The negative predictive value of having type 2 diabetes at PP2 compared with a normal oral glucose tolerance test (excluding impaired fasting glucose/impaired glucose tolerance) at PP1 was 100% (95% confidence interval, 93.5-100) with a specificity of 96.5% (95% confidence interval, 87.9-99.6). CONCLUSION: A normal oral glucose tolerance test during the delivery hospitalization appears to exclude postpartum type 2 diabetes mellitus. However, the results of the immediate postpartum oral glucose tolerance test were mixed when including impaired fasting glucose or impaired glucose tolerance. As a majority of women do not return for postpartum diabetic screening, an oral glucose tolerance test during the delivery hospitalization may be of use in certain circumstances in which postpartum follow-up is challenging and resources could be focused on women with an abnormal screening immediately after the delivery hospitalization.

Sex-Specific Differences of Steroid Receptors Following Exposure to Environmentally Relevant Concentrations of Phenothiazine in Fundulus heteroclitus.

Phenothiazine (PTZ) is a heterocyclic thiazine compound used for industrial and medical purposes. Through environmental surveillance studies, PTZ was found being discharged into a local river in Connecticut. Phenothiazine has been shown to act similarly to endocrine disrupting chemicals. This study sought to identify sex specific hormone receptor changes in Fundulus heteroclitus in response to PTZ exposure. Fundulus heteroclitus, also known as mummichog, are small fish native to the Atlantic coast of the United States and Canada. They reside in brackish waters and can survive harsh toxic environments. This model organism is native to the polluted waters found in Connecticut. In this study, fish were exposed to PTZ concentrations of 0.5 ppm, 1.0 ppm, and 2.0 ppm for 1 week. Following exposure, brain, liver, and gonad tissues were harvested; cDNA was synthesized; and mRNA expression was assessed for 6 different hormone receptors. Compared with vehicle control (ethanol) differences in mRNA expression, levels of hormone receptors were observed in various tissues from male and female fish. Many of the tissues assessed showed changes in expression level, while only female liver and testis showed no change. These results implicate PTZ as a potential endocrine disrupting compound to mummichog at environmentally relevant concentrations.