Uterine Weight as a Modifier of Black/White Racial Disparities in Minimally Invasive Hysterectomy Among Veterans with Fibroids in the Veterans Health Administration

INTRODUCTION: Uterine fibroids are the most common indication for hysterectomy. Minimally invasive hysterectomy (MIH) confers lower risk of complications and shorter recovery than open surgical procedures; however, it is more challenging to perform with larger fibroids. There are racialized differences in fibroid size and MIH rates. We examined the role of uterine size in black-white differences in MIH among Veterans in the Department of Veterans Affairs (VA). METHODS: Using VA clinical and administrative data, we conducted a cross-sectional study among black and white Veterans with fibroids who underwent hysterectomy between 2012 and 2014. We abstracted postoperative uterine weight from pathology reports as a proxy for uterine size. We used a generalized linear model to estimate the association between race and MIH and tested an interaction between race and postoperative uterine weight (≤250 g vs. \u3e250 g). We estimated adjusted marginal effects for racial differences in MIH by postoperative uterine weight. RESULTS: The sample included 732 Veterans (60% black, 40% white). Postoperative uterine weight modified the association of race and MIH (p for interaction=0.05). Black Veterans with postoperative uterine weight ≤250 g had a nearly 12-percentage point decrease in MIH compared to white Veterans (95% CI -23.1 to -0.5), with no difference by race among those with postoperative uterine weight \u3e250 g. DISCUSSION: The racial disparity among Veterans with small fibroids who should be candidates for MIH underscores the role of other determinants beyond uterine size. To eliminate disparities in MIH, research focused on experiences of black Veterans, including pathways to treatment and provider-patient interactions, is needed

Racial Differences in Neighborhood Perceptions and their Influences on Physical Activity among Urban Older Women

Background: Proper levels of physical activity (PA) are important to healthy aging. Little is known about racial differences in influences of neighborhood perceptions (NP) on PA and use of neighborhood resources among community-dwelling older women. Materials and methods: In 2014 and 2015, 49 white and 44 black women of age 65 and older living in Washington, DC were queried about their PA, NP, use of neighborhood resources and sociodemographic characteristics. They wore an accelerometer and a Global Positioning System device concurrently for 7 consecutive days. Data were analyzed by race. Results: Compared to Whites, Blacks had lower NP scores (71% positive vs. 77%, p = 0.01), lower mean daily step counts (mean (SD): 3256 (1918) vs. 5457 (2989), p \u3c 0.001), and lower frequencies of all exercise activities combined (19.7 (8.7) vs. 25.2 (11.8) per week, p = 0.01). For both Whites and Blacks, better NPs were associated with more frequent PA both at (p = 0.05) and away from home (p = 0.01). However, better NPs were associated with higher frequencies of exercise activities, moderate-to-high intensity activities, and utilitarian walking for Whites but not Blacks (p \u3c 0.05 for race-perception interaction terms). Conclusions: In an urban setting, older Black women were more likely than older White women to have poor NPs, less PA, and weaker or no association of positive NPs with higher levels of certain PAs. Such substantial racial differences warrant further investigation and consideration in health promotion programs

Estimated cumulative radiation dose from PET/CT in children with malignancies: a 5-year retrospective review

The increasing use of serial PET/CT scans in the management of pediatric malignancies raises the important consideration of radiation exposure in children. To estimate the cumulative radiation dose from PET/CT studies to children with malignancy and to compare with the data in literature. Two hundred forty-eight clinical PET/CT studies performed on 78 patients (50 boys/28 girls, 1.3 to 18 years old from December 2002 to October 2007) were retrospectively reviewed under IRB approval. The whole-body effective dose (ED) estimates for each child were obtained by estimating the effective dose from each PET/CT exam performed using the ImPACT Patient Dosimetry Calculator for CT and OLINDA for PET. The average number of PET/CT studies was 3.2 per child (range: 1 to 14 studies). The average ED of an individual CT study was 20.3 mSv (range: 2.7 to 54.2), of PET study was 4.6 mSv (range: 0.4 to 7.7) and of PET/CT study was 24.8 mSv (range: 6.2 to 60.7). The average cumulative radiation dose per patient from CT studies was 64.4 mSv (range: 2.7 to 326), from PET studies was 14.5 mSv (range: 2.8 to 73) and from PET/CT studies was 78.9 mSv (range: 6.2 to 399). The radiation exposure from serial PET/CT studies performed in pediatric malignancies was considerable; however, lower doses can be used for both PET and CT studies. The ALARA principle must be applied without sacrificing diagnostic information

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection

Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses

Assessing the effects of a mixed Eimeria spp. challenge on performance, intestinal integrity, and the gut microbiome of broiler chickens

A mixed Eimeria spp. challenge model was designed to assess the effects of challenge on broiler chicken performance, intestinal integrity, and the gut microbiome for future use to evaluate alternative strategies for controlling coccidiosis in broiler chickens. The experimental design involved broiler chickens divided into two groups: a control group (uninfected) and a positive control group, infected with Eimeria acervulina (EA), Eimeria maxima (EM), and Eimeria tenella (ET). At day-of-hatch, 240 off-sex male broiler chicks were randomized and allocated to one of two treatment groups. The treatment groups included: (1) Non-challenged (NC, n = 5 replicate pens); and (2) challenged control (PC, n = 7 replicate pens) with 20 chickens/pen. Pen weights were recorded at d0, d16, d31, d42, and d52 to determine average body weight (BW) and (BWG). Feed intake was measured at d16, d31, d42, and d52 to calculate feed conversion ratio (FCR). Four diet phases included a starter d0–16, grower d16–31, finisher d31–42, and withdrawal d42–52 diet. At d18, chickens were orally challenged with 200 EA, 3,000 EM, and 500 ET sporulated oocysts/chicken. At d24 (6-day post-challenge) and d37 (19-day post-challenge), intestinal lesion scores were recorded. Additionally, at d24, FITC-d was used as a biomarker to evaluate intestinal permeability and ileal tissue sections were collected for histopathology and gene expression of tight junction proteins. Ileal and cecal contents were also collected to assess the impact of challenge on the microbiome. BWG and FCR from d16–31 was significantly (p < 0.05) reduced in PC compared to NC. At d24, intestinal lesion scores were markedly higher in the PC compared to the NC. Intestinal permeability was significantly increased in the PC group based on serum FITC-d levels. Cadherin 1 (CDH1), calprotectin (CALPR), and connexin 45 (Cx45) expression was also upregulated in the ileum of the PC group at d24 (6-day post-challenge) while villin 1 (VIL1) was downregulated in the ileum of the PC group. Additionally, Clostridium perfringens (ASV1) was enriched in the cecal content of the PC group. This model could be used to assess the effect of alternative coccidiosis control methods during the post-challenge with EA, EM, and ET

In vitro and in vivo evaluation of chlorhexidine salts as potential alternatives to potassium dichromate for Eimeria maxima M6 oocyst preservation

IntroductionCoccidiosis caused by the Eimeria spp., an Apicomplexan protozoon, is a major intestinal disease that affects the poultry industry. Although most cases of coccidiosis are subclinical, Eimeria infections impair bird health and decrease overall performance, which can result in compromised welfare and major economic losses. Viable sporulated Eimeria oocysts are required for challenge studies and live coccidiosis vaccines. Potassium dichromate (PDC) is typically used as a preservative for these stocks during storage. Although effective and inexpensive, PDC is also toxic and carcinogenic. Chlorhexidine (CHX) salts may be a possible alternative, as this is a widely used disinfectant with less toxicity and no known carcinogenic associationsMethodsIn vitro testing of CHX gluconate and CHX digluconate exhibited comparable oocyst integrity and viability maintenance with equivalent bacteriostatic and bactericidal activity to PDC. Subsequent use of CHX gluconate or digluconate-preserved Eimeria oocysts, cold-stored at 4°C for 5 months, as the inoculum also resulted in similar oocyst shedding and recovery rates when compared to PDC-preserved oocysts.Results and discussionThese data show that using 0.20% CHX gluconate could be a suitable replacement for PDC. Additionally, autofluorescence was used as a method to evaluate oocyst viability. Administration of artificially aged oocysts exhibiting >99% autofluorescence from each preserved treatment resulted in no oocyst output for CHX salt groups

EXPORTS Measurements and Protocols for the NE Pacific Campaign

EXport Processes in the Ocean from Remote Sensing (EXPORTS) is a large-scale NASA-led and NSF co-funded field campaign that will provide critical information for quantifying the export and fate of upper ocean net primary production (NPP) using satellite information and state of the art technology

Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC

Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRASG12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRASG12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRASG12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies

Evolving norms of protection: China, Libya and the problem of intervention in armed conflict

This article examines the influence of civilian protection norms on China’s response to the 2011 crisis in Libya. It argues that Responsibility to Protect—an emerging norm commonly associated with the Libyan case—did not play a major role in China’s abstention on Resolution 1973 (2011) authorizing international intervention in Libya. For China, Responsibility to Protect is merely a concept and could not serve as the basis for intervention. Instead, Protection of Civilians in Armed Conflict, as a normative foundation for civilian protection endorsed by China, offers a more appropriate lens for understanding China’s vote. Protection of Civilians, however, does not accommodate China’s unprecedented evacuation of Chinese nationals from Libya. This operation proceeded from a third logic of Protection of Nationals Abroad, which poses dilemmas for China’s strict adherence to the principles of sovereignty and non-interference and brings to bear domestic interests and notions of protection