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Introduction: Consumption of snacks and food can be reduced by placing them further away from an individual, known as the Proximity Effect. This effect is generally thought to be robust, and observable between when snacks are presented at 20cm and 70cm. It is assumed that this effect occurs without conscious awareness or processing, but no study has experimentally tested whether the effect occurs via non-conscious processing. Method: A sample of 84 individuals is targeted, with each individual being assigned to one of four conditions via computerised random number sequence. A 2(Distance; 20cm, 70cm) x 2(Attention State; Distraction/Video, Control/No Video) between subjects design is implemented, with all individuals being presented with a bowl containing 250g of M&M’s. Individuals will either be asked to watch a 5-minute video clip, or sit quietly for 5 minutes. Snack consumption is measured at two levels: likelihood of consumption (any snack consumed vs none consumed), and actual consumption (continuous, measured in grams). Snacks will be removed after the 5 minute period, with individuals then being asked to complete a short questionnaire. Analysis: A binary logistic regression will be conducted to test for differences in likelihood of consumption. Actual consumption will be analysed through a 2x2 ANCOVA. Covariates of Perceived Effort and Visual Salience will be included in models for both analyses to assess the influence of these factors. Sensitivity analysis will be conducted for when outliers, those who were aware of the study intent, and those influenced by their environment are removed from analysis. All outcomes will be reported.Discussion: The proposed study will assess whether individuals consume more snacks when presented closer (proximity effect), as well as if consumption is higher when watching a short video clip, and the interaction between the two factors. Outcomes of the study will allow researchers to determine whether the proximity effect is likely to occur via non-conscious processing and without conscious awareness, or whether the effect occurs while individuals are aware of their behaviour. The results may influence future research and choice architects to ensure less-healthy snacks are placed further away if individuals are distracted with another stimulus to prevent mindless eating.

Lipid peroxidation (LPO) is the molecular mechanism involved in oxidative damage of cellular membranes and the hallmark of a nonapoptotic form of cell death, known as ferroptosis. This iron-dependent cell death is an emerging strategy in cancer treatment and one of the central cell death mechanisms accounting for early cell loss and organ dysfunction in both neurodegenerative disease and ischemia-reperfusion injury. Although the biological roles of LPO products have attracted considerable attention, not only for their pathological mechanisms but also for their potential clinical application as biomarkers, the existence of a common lethal lipid death signal generated during ferroptosis remains poorly explored. A better understanding of the LPO process, however, may unleash unprecedented opportunities for therapeutic intervention of as-yet incurable diseases.

ObjectiveThe rectal microbiome was examined to assess the relationship between the microbiome and liver disease in HIV-infection.DesignEighty-two HIV-1 mono-infected individuals from the PROSPEC-HIV-study (NCT02542020) were grouped into three liver health categories based on results of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) of transient elastography: normal (n = 30), steatosis (n = 30), or fibrosis (n = 22).MethodsLiver steatosis and fibrosis were defined by CAP at least 248 dB/m and LSM at least 8.0 kPa, respectively. 16S rRNA gene and whole genome shotgun metagenomic sequencing were performed on rectal swabs. Bacterial differences were assessed using zero-inflated negative binomial regression and random forests modeling; taxonomic drivers of functional shifts were identified using FishTaco.ResultsLiver health status explained four percentage of the overall variation (r2 = 0.04, P = 0.003) in bacterial composition. Participants with steatosis had depletions of Akkermansia muciniphila and Bacteroides dorei and enrichment of Prevotella copri, Finegoldia magna, and Ruminococcus bromii. Participants with fibrosis had depletions of Bacteroides stercoris and Parabacteroides distasonis and enrichment of Sneathia sanguinegens. In steatosis, functional analysis revealed increases in primary and secondary bile acid synthesis encoded by increased Eubacterium rectale, F. magna, and Faecalibacterium prausnitzii and decreased A. muciniphila, Bacteroides fragilis and B. dorei. Decreased folate biosynthesis was driven by similar changes in microbial composition.ConclusionHIV mono-infection with steatosis or fibrosis had distinct microbial profiles. Some taxa are similar to those associated with non-alcoholic fatty liver disease in HIV-negative populations. Further studies are needed to define the role of the gut microbiota in the pathogenesis of liver disease in HIV-infected persons.

While pregnancy increases the risk for severe COVID19, the clinical and immunological implications of COVID19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID19 show increased inflammation and unique IFNλ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, ESM1, and reducing BGN and CD209. Finally, COVID19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3 and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks., Graphical Abstract, The study performed by Foo et al. unveils distinct immune alterations of mothers and infants induced by SARS-CoV-2 infection during pregnancy. These findings highlight the importance of long-term post-pregnancy clinical follow-up of mother-infant dyads to prevent potential unforeseen health conditions following prenatal SARS-CoV-2 infection.

Mother-to-child transmission (MTCT) through breastfeeding remains a major source of pediatric HIV-1 infection worldwide. To characterize plasma HIV-1 subtype C populations from infected mothers during pregnancy that related to subsequent breast milk transmission, an exploratory study was designed to apply next generation sequencing and a custom bioinformatics pipeline for HIV-1 gp41 extending from heptad repeat region 2 (HR2) through the membrane proximal external region (MPER) and the membrane spanning domain (MSD). MPER harbors linear and highly conserved epitopes that repeatedly elicits HIV-1 neutralizing antibodies with exceptional breadth. Viral populations during pregnancy from women who transmitted by breastfeeding, compared to those who did not, displayed greater biodiversity, more frequent amino acid polymorphisms, lower hydropathy index and greater positive charge. Viral characteristics were restricted to MPER, failed to extend into flanking HR2 or MSD regions, and were unrelated to predicted neutralization resistance. Findings provide novel parameters to evaluate an association between maternal MPER variants present during gestation and lactogenesis with subsequent transmission outcomes by breastfeeding. Importance HIV-1 transmission through breastfeeding accounts for 39% of MTCT and continues as a major route of pediatric infection in developing countries where access to interventions for interrupting transmission is limited. Identifying women who are likely to transmit HIV-1 during breastfeeding would focus therapies, such as broad neutralizing HIV monoclonal antibodies (bn-HIV-Abs), during the breastfeeding period to reduce MTCT. Findings from our pilot study identify novel characteristics of gestational viral MPER quasispecies related to transmission outcomes and raise the possibility for predicting MTCT by breastfeeding based on identifying mothers with high-risk viral populations.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.

Previous research has shown that risk preferences are sensitive to the financial domain in which they are framed. In the present study we explore whether the effect of valence priming on risk taking is moderated by the financial context under consideration. A total of 260 participants completed an online questionnaire where risky choices were elicited for seven different financial scenarios. Participants were allocated to different valence (neutral, positive or negative) and arousal (low or high) priming conditions. Two factors were extracted: Factor 1 (Negative) included insurance and possibility of loss, whilst Factor 2 (Positive) included the remaining five scenarios (investment, salary, pension, possibility of gain, and mortgage). Moreover, only negative priming—regardless of arousal level—influenced people’s risky choices by inducing more risk-averse behavior; this effect was confined only to loss and insurance domains. The findings call into question the generalizability of priming effects on different financial context and show that the effects of priming on financial risk taking are sensitive to the financial context under consideration.

Objective:We employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome.Design:Three hundred and eighty-three MSM were grouped into four HIV viremia cat

Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naı̈ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naı̈ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naı̈ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naı̈ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

We analyzed United States Federal Energy Regulatory Commission (FERC) documents prepared for 29 recently licensed hydropower projects and created two novel datasets to improve understanding of the environmental study life cycle, defined here as the process that begins with an environmental study being requested by a hydropower stakeholder or regulator, and ends with the study either being rejected or approved/conducted. Our two datasets consisted of summaries of information taken from (1), study determination letters prepared by FERC for 23 projects that were using the integrated licensing process, and (2), environmental study submittals and issuances tracked and attributed to seven projects using the FERC record. Our objective was to use the two resulting environmental life cycle datasets to understand which types of environmental studies are approved, rejected, and implemented during FERC licensing, and how consistently those types of studies are required across multiple hydropower projects. We matched the requested studies to a set of 61 river function indicators in eight categories and found that studies related to the category of biota and biodiversity were requested most often across all 29 projects. Within that category, studies related to river function indicators of presence, absence, detection of species and habitat/critical habitat were the most important to stakeholders, based on the relative number of studies requested. The study approval, rejection, and request rates were similar within each dataset, although the 23 projects with study determination letters had many rejected studies, whereas the dataset created from the seven projects had very few rejected studies.

Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) diagnostic testing algorithms recommended by the Centers for Disease Control involve up to three tests and rely mostly on detection of viral antigen and host antibody responses. HIV-1 p24 antigen/HIV-1/HIV-2 antibody-reactive specimens are confirmed with an immunochromatographic HIV-1/HIV-2 antibody differentiation assay, and negative or indeterminate results from the differentiation assay are resolved by an HIV-1-specific nucleic acid amplification test (NAT). The performance of a proposed alternative algorithm using the cobas HIV-1/HIV-2 qualitative NAT as the differentiation assay was evaluated in subjects known to be infected with HIV-1 (n = 876) or HIV-2 (n = 139), at low (n = 6,017) or high (n = 1,020) risk of HIV-1 infection, or at high-risk for HIV-2 infection (n = 498) (study A). The performance of the cobas HIV-1/HIV-2 qualitative test was also evaluated by comparison to an HIV-1 or HIV-2 alternative NAT (study B). The HIV-1 and HIV-2 overall percent agreements (OPA) in study A ranged from 95% to 100% in all groups. The positive percent agreements (PPA) for HIV-1 and HIV-2 were 100% (876/876) and 99.4% (167/168), respectively, for known positive groups. The negative percent agreement in the HIV low-risk group was 100% for both HIV-1 and HIV-2. In study B, the HIV-1 and HIV-2 OPA ranged from 99% to 100% in all groups evaluated (n = 183 to 1,030), and the PPA for HIV-1 and HIV-2 were 100% and 99.5%, respectively, for known positive groups. The cobas HIV-1/HIV-2 qualitative assay can discriminate between HIV-1 and HIV-2 based on HIV RNA and can be included in an alternative diagnostic algorithm for HIV.

Funding Acknowledgements Type of funding sources: None. Background Ventricular arrhythmias in athletes represent an important issue in sport eligibility as they may be a marker of a concealed cardiomyopathy, potentially at risk of sudden cardiac death during sport activity. Purpose to assess the utility of cardiac magnetic resonance (CMR) to identify cardiac abnormalities in athletes with documented frequent premature ventricular beats (PVB) or complex ventricular arrhythmias (VA) undergoing competitive sport eligibility screening. Methods We enrolled 65 athletes with documented ventricular arrhythmias as follows: 1) frequent PVB at 24-hour ambulatory ECG monitoring (>100 PVB/24h); 2) polymorphic PVB; 3) repetitive PVB (couplets, triplets, or nonsustained ventricular tachicardia). All athletes were studied with rest ECG, exercise stress testing, 24-hour ambulatory ECG monitoring, transthoracic echocardiography and contrast-enhanced CMR. Results Sixty-five athletes (56 males, 9 females, age 30 ± 15years) underwent CMR with gadolinium contrast. In 55 patients (84.6%) CMR was normal, in 10 patients (15.4%) the following abnormalities were reported at CMR: four patients with isolated late gadolinium enhancement (LGE) of whom 3 patients with subepicardial LGE in the inferolateral wall and 1 patient with intramyocardial basal inferior LGE; 1 patient with hypertrophic cardiomyopathy with septal LGE; 1 patient with left ventricular non compaction; 3 patients with right ventricular abnormalities (a 13-year-old patient with dilated right ventricle and LGE located at the superior interventricular insertion point, 1 patient with a dilated and hypokinetic right ventricle, 1 patient with a focal right ventricular aneurysm). Transthoracic echocardiography was normal in 7/10 (70%) athletes with CMR abnormalities. Conclusion In athletes with frequent or complex ventricular arrhythmias cardiac magnetic resonance identifies cardiac abnormalities in a significant proportion of subjects and it may offer a diagnostic incremental value.

Background Sentiments of vaccine hesitancy and distrust in public health institutions have complicated the government-led coronavirus disease 2019 (COVID-19) vaccine control strategy in the United States. As the first to receive the vaccine, COVID-19 vaccine attitudes among frontline workers are consequential for COVID-19 control and public opinion of the vaccine. Methods In this study, we used a repeated cross-sectional survey administered at 3 time points between 24 September 2020 and 6 February 2021 to a cohort of employees of the University of California, Los Angeles Health and the Los Angeles County Fire Department. The primary outcome of interest was COVID-19 vaccination intent and vaccine uptake. Results Confidence in COVID-19 vaccines and vaccine uptake rose significantly over time. At survey 1, confidence in vaccine protection was 46.4% among healthcare workers (HCWs) and 34.6% among first responders (FRs); by survey 3, this had risen to 90.0% and 75.7%, respectively. At survey 1, about one-third of participants intended to receive a vaccine as soon as possible. By survey 3, 96.0% of HCWs and 87.5% of FRs had received a COVID-19 vaccine. Conclusions Attitudes toward vaccine uptake increased over the study period, likely a result of increased public confidence in COVID-19 vaccines, targeted communications, a COVID-19 winter surge in Los Angeles County, and ease of access from employer-sponsored vaccine distribution.

Objective A majority of studies evaluating the risk of vertical transmission and adverse outcomes in pregnancies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mostly based on third-trimester infections. There is limited data available on pregnancy sequelae of maternal infection in the first or second trimester. Study Design We present a patient with monochorionic–diamniotic twins that develops coronavirus disease 2019 infection at 15 weeks of gestation. The pregnancy is further complicated by stage II twin–twin transfusion syndrome. She undergoes laser ablation, which is complicated by development of a subchorionic hematoma. The patient then develops Escherichia coli bacteremia, resulting in septic shock and preterm labor followed by previable delivery at 21 weeks of gestation. Amniotic fluid and placenta were negative for SARS-CoV-2 by real-time polymerase chain reaction. Conclusion This case of SARS-CoV-2 argues against transplacental transmission after a second-trimester infection but brings attention to the possible downstream complications that may arise following early infection. Key Points

BackgroundSARS-CoV-2 infections of infants and toddlers are usually mild but can result in life-threatening disease. SARS-CoV-2 RNA been detected in the breast milk of lactating women, but the potential role of breastfeeding in transmission to infants has remained uncertain.MethodsBreast milk specimens were examined for the presence of the virus by RT-PCR and/or culture. Specimens that contained viral RNA (vRNA) were examined for the presence of subgenomic coronavirus RNA (sgRNA), a putative marker of infectivity. Culture methods were used to determine the thermal stability of SARS-CoV-2 in human milk.ResultsBreast milk samples from 110 women (65 confirmed with a SARS-CoV-2 diagnostic test, 36 with symptoms but without tests, and 9 with symptoms but a negative SARS-CoV-2 diagnostic test) were tested by RT-PCR (285 samples) and/or viral culture (160 samples). Although vRNA of SARS-CoV-2 was detected in the milk of 7 of 110 (6%) women with either a confirmed infection or symptomatic illness, and in 6 of 65 (9%) of women with a positive SARS-CoV-2 diagnostic test, virus was not detected in any culture. None of the 7 milk specimens with detectable vRNA contained sgRNA. Notably, when artificially added to human milk in control experiments, infectious SARS-CoV-2 could be cultured despite several freeze-thaw cycles, as occurs in the storage and usage of human milk.ConclusionsSARS-CoV-2 RNA can be found infrequently in the breastmilk of women with recent infection, but we found no evidence that breastmilk contains infectious virus or that breastfeeding represents a risk factor for transmission of infection to infants.Key PointsQuestionSARS-CoV-2 RNA has been detected in a small number of human milk samples collected from recently infected women. The role of breastfeeding in transmission of the virus to infants has remained uncertain due to the small number of specimens analyzed in any study published thus far.FindingsIn a total study group of 110 women, SARS-CoV-2 RNA was detected in milk from 6 of 65 women (9.2%) with recent confirmed infection. Neither infectious virus nor subgenomic RNA (a marker of virus infectivity) were detected in any of the samples.MeaningWe found no evidence that infectious SARS-CoV-2 is present milk from recently infected women, even if SARS-CoV-2 PCR tests are positive, providing reassurance of the safety of breastfeeding.

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31–60 (n = 110) and 61–90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

HIV-1 is present in many secretions including oral, intestinal, genital, and breast milk. However, most people exposed to HIV-1 within these mucosal compartments do not become infected despite often frequent and repetitive exposure over prolonged periods of time. In this review, we discuss what is known about the levels of cell-free HIV RNA, cell-associated HIV DNA and cellassociated HIV RNA in external secretions. Levels of virus are usually lower than contemporaneously obtained blood, increased in settings of inflammation and infection, and decreased in response to antiretroviral therapy. Additionally, each mucosal compartment has unique innate and adaptive immune responses that affect the composition and presence of HIV-1 within each external secretion. We discuss the current state of knowledge about the types and amounts of virus present in the various excretions, touch on innate and adaptive immune responses as they affect viral levels, and highlight important areas for further study.

Beginning April 8, 2020, we enrolled 1787 frontline heath workers who were asymptomatic for COVID-19 into a longitudinal surveillance study. During that time 4 healthcare workers and 6 first responders tested positive for SARS-CoV-2 by RT-PCR. Additionally, 43 healthcare workers and 55 first responders had detectable IgG antibodies to SARS-CoV-2.

ImportanceHealthcare workers (HCW) are slated to be early recipients of SARS-CoV-2 vaccines due to increased risk of exposure to patients with COVID-19, and will be tasked with administering approved vaccines to the general population. As lynchpins of the vaccination effort, HCWs’ opinions of a vaccine’s safety and efficacy may affect both public perception and uptake of the vaccine. Therefore, it is crucial to understand and address potential hesitancy prior to vaccine administration.ObjectiveTo understand healthcare workers’ attitudes about vaccine safety, efficacy, and acceptability in the context of the COVID-19 pandemic, including acceptance of a novel coronavirus vaccine.Design, Setting, ParticipantsA cross-sectional survey was distributed to participants enrolled in a longitudinal cohort study surveilling SARS-CoV-2 infection among 1,093 volunteer sampled University of California, Los Angeles (UCLA) Health System employees. Surveys were completed online between September 24 and October 16, 2020. In total, 609 participants completed this supplemental survey.ResultsWe averaged a 9-statement Likert scale matrix scored from 1 (“strongly disagree”) to 5 (“strongly agree”) and found respondents overwhelmingly confident about vaccine safety (4.47); effectiveness (4.44); importance, self-protection, and community health (4.67). Notably, 47.3% of respondents reported unwillingness to participate in a coronavirus vaccine trial, and most (66.5%) intend to delay vaccination. The odds of reporting intent to delay coronavirus vaccine uptake were 4.15 times higher among nurses, 2.45 times higher among other personnel with patient contact roles, and 2.15 times higher among those without patient contact compared to doctors. Evolving SARS-CoV-2 science (76.0%), current political climate (57.6%), and fast-tracked vaccine development timeline (83.4%) were cited as primary variables impacting HCW decisions to undergo vaccination. Of note, these results were obtained prior to release of Phase III data from companies manufacturing vaccines in the U.S.Conclusions and RelevanceDespite overall confidence in vaccines, a majority of HCW expressed concerns over a novel coronavirus vaccine. A large proportion plan to delay vaccine uptake due to concerns about expedited development, emerging scientific discoveries, and the political climate. Forthcoming vaccination campaigns must address these unique points of coronavirus vaccine hesitancy in order to achieve adequate vaccine coverage.

To describe distributions of immune markers in children and young adults by sex and HIV status, and within groups, investigate associations of immune markers with bone density across Tanner stage. Using data and samples from 353 participants in a cross-sectional study in youth with perinatally acquired HIV (PHIV) and matched HIV-negative controls, distributions of inflammation and activation immune markers were described by sex and HIV status. Correlations and structural equation models (SEM) were used to explore marginal and multivariable associations of the immune markers with bone density and to assess whether patterns of association varied by sex and HIV status. Immune marker distributions did not differ by sex, but there were some differences by HIV status. Correlation patterns among bone, body composition, and immune markers were similar across the sex and HIV status groups. Conclusions from SEMs were limited by small sample sizes, but there was some indication that patterns of association between bone density and certain immune markers differed in male PHIV with more advanced Tanner stage compared to the other three groups. In conclusion, distributions of bone density, body composition, and immune markers may vary by sex and HIV status, although associations among these outcomes within sex and HIV status groups appear similar. Bone density of male PHIV appears to be more negatively affected than females, regardless of female HIV status. Larger longitudinal studies across Tanner stages are needed to further explore potential biological relationships between immune markers and bone density in youth living with HIV.

Covid-19 Antibodies after Mild Infection Among 34 volunteers who had recovered from mild Covid-19 illness, antiviral antibodies to the receptor-binding domain of the viral spike protein declined wi...

To The Editor, Currently, the U.S. Centers for Disease Control and Prevention, American Academy of Pediatrics and the World Health Organization advise that women who are infected with SARS-CoV-2 may choose to breastfeed with appropriate protections to prevent transmission of the virus through respiratory droplets. However, the potential for exposure to SARS-CoV-2 through breastfeeding is currently unknown. To date, case reports on breastmilk samples from a total of 24 SARS-CoV-2-infected women have been published. Of those, viral RNA was detected in ten breastmilk samples from four women. In some but not all cases, environmental contamination as the source of the virus or retrograde flow from an infected infant could not be ruled out. We established a quantitative RT-PCR assay for SARS-CoV-2 in breastmilk with a limit of detection of 250 copies per mL and validated it by spiking breastmilk from uninfected women with known amounts of viral RNA. In addition, we established tissue culture methods to detect replication-competent SARS-CoV-2 in breastmilk. No viral RNA nor culturable virus was detected after Holder pasteurization of breastmilk samples that had been spiked with replication-competent SARS-CoV-2 (see Supplement). Between March 27 and May 6, 2020, we collected and analyzed 64 serial breastmilk samples from 18 SARS-CoV-2-infected women residing in the U.S. (see Supplement for clinical characteristics). Breastmilk samples were collected before and after women had a positive SARS-CoV-2 RT-PCR test and all but one woman had symptomatic disease (see Figure). One of the 64 breastmilk samples had detectable SARS-CoV-2 RNA by RT-PCR. The positive sample was collected on the day of symptom onset but one sample 2 days prior to symptom onset and two subsequent samples, collected 12 and 41 days later, tested negative for viral RNA. In addition, a subset of 26 breastmilk samples from nine women were tested for the presence of replication-competent virus using our established culture methods, and all were negative including the one sample that tested positive for viral RNA by RT-PCR. Although SARS-CoV-2 RNA was detected in one milk sample from one of eighteen infected women, the viral culture for that sample was negative. This suggests that SARS-CoV-2 RNA does not represent replication-competent virus and that breastmilk itself is likely not a source of infection for the infant. Furthermore, when control breastmilk samples spiked with replication-competent SARS-CoV-2 virus were treated by Holder pasteurization, a process commonly performed by donor milk banks, no replication-competent virus nor viral RNA was detectable. Further research to confirm these findings is needed, as well as an examination of convalescent milk for the presence of antibodies against SARS-CoV-2.

ObjectivesThe prevalence of obesity is rising among people living with HIV, which may synergistically increase inflammation and the risk of associated diseases. Disruption of gut bacterial communities may be one of the key drivers of this inflammation; however, the combined effects of HIV and obesity on the microbiome have not been explored.MethodsThis study included 381 men who have sex with men. Thirty-nine were HIV-positive and obese (H+O+), 143 were HIV-positive and nonobese, 64 were HIV-negative and obese, and 135 were HIV-negative and nonobese. Microbiome composition was assessed by targeted sequencing of the V4 region of the 16S ribosomal RNA (rRNA) gene using rectal swab samples. Inverse probability of treatment-weighted marginal structural models wereused to investigate differences in microbial composition between groups while controlling for numerous clinical and behavioural confounders.ResultsSignificant variability in microbial composition was explained by the combination of HIV and obesity, over and above each condition alone (R2 for the marginal contribution of the H+/O+ group=0.008; P=0.001). H+O+ participants had the highest ratios of Prevotella to Bacteroides, a pro-inflammatory enterotype that has been described in HIV infection and obesity independently. H+O+ participants had lower levels of Bacteroides and Veillonella than all other groups, suggesting a synergistic effect of HIV and obesity on these genera.ConclusionsOur findings support the hypothesis that HIV and obesity act together to disrupt gut microbial communities, which may help explain higher levels of generalized inflammation among people living with both HIV and obesity.

To The Editor, Currently, the U.S. Centers for Disease Control and Prevention, American Academy of Pediatrics and the World Health Organization advise that women who are infected with SARS-CoV-2 may choose to breastfeed with appropriate protections to prevent transmission of the virus through respiratory droplets. However, the potential for exposure to SARS-CoV-2 through breastfeeding is currently unknown. To date, case reports on breastmilk samples from a total of 24 SARS-CoV-2-infected women have been published. Of those, viral RNA was detected in ten breastmilk samples from four women. In some but not all cases, environmental contamination as the source of the virus or retrograde flow from an infected infant could not be ruled out. We established a quantitative RT-PCR assay for SARS-CoV-2 in breastmilk with a limit of detection of 250 copies per mL and validated it by spiking breastmilk from uninfected women with known amounts of viral RNA. In addition, we established tissue culture methods to detect replication-competent SARS-CoV-2 in breastmilk. No viral RNA nor culturable virus was detected after Holder pasteurization of breastmilk samples that had been spiked with replication-competent SARS-CoV-2 (see Supplement). Between March 27 and May 6, 2020, we collected and analyzed 64 serial breastmilk samples from 18 SARS-CoV-2-infected women residing in the U.S. (see Supplement for clinical characteristics). Breastmilk samples were collected before and after women had a positive SARS-CoV-2 RT-PCR test and all but one woman had symptomatic disease (see Figure). One of the 64 breastmilk samples had detectable SARS-CoV-2 RNA by RT-PCR. The positive sample was collected on the day of symptom onset but one sample 2 days prior to symptom onset and two subsequent samples, collected 12 and 41 days later, tested negative for viral RNA. In addition, a subset of 26 breastmilk samples from nine women were tested for the presence of replication-competent virus using our established culture methods, and all were negative including the one sample that tested positive for viral RNA by RT-PCR. Although SARS-CoV-2 RNA was detected in one milk sample from one of eighteen infected women, the viral culture for that sample was negative. This suggests that SARS-CoV-2 RNA does not represent replication-competent virus and that breastmilk itself is likely not a source of infection for the infant. Furthermore, when control breastmilk samples spiked with replication-competent SARS-CoV-2 virus were treated by Holder pasteurization, a process commonly performed by donor milk banks, no replication-competent virus nor viral RNA was detectable. Further research to confirm these findings is needed, as well as an examination of convalescent milk for the presence of antibodies against SARS-CoV-2.

BACKGROUND: Infants with gastroschisis require operations and lengthy hospitalizations due to intestinal dysmotility. Dysbiosis may contribute to these problems. Little is known on the microbiome of gastroschisis infants. METHODS: The purpose of this study was to investigate the fecal microbiome in gastroschisis infants. Microbiome profiling was performed by sequencing the V4 region of the 16S rRNA gene. The microbiome of gastroschisis infants was compared to the microbiome of healthy controls, and the effects of mode of birth delivery, gestational age, antibiotic duration, and nutrition type on microbial composition and diversity were investigated. RESULTS: The microbiome of gastroschisis infants (n=13) was less diverse (Chao1, p < 0.001), lacked Bifidobacterium (p = 0.001) and had increased Staphylococcus (p = 0.007) compared to controls (n=83). Mode of delivery (R(2) = 0.04, p = 0.001), antibiotics duration greater than or equal to seven days (R(2) = 0.03, p = 0.003), age at sample collection (R(2) = 0.03, p = 0.009), and gestational age (R(2) = 0.02, p = 0.035) explained a small portion of microbiome variation. In gastroschisis infants, Escherichia-Shigella was the predominate genus, and those delivered via cesarean section had different microbial communities, predominantly Staphylococcus and Streptococcus, from those delivered vaginally. While antibiotic duration contributed to the variation in microbiome composition, there were no significant differences in taxa distribution or alpha diversity by antibiotic duration or nutrition type. CONCLUSION: The microbiome of gastroschisis infants is dysbiotic, and mode of birth delivery, antibiotic duration, and gestational age appear to contribute to microbial variation.

Combinations of antibiotics have shown promise in off-label treatment of Inflammatory Bowel Disease (IBD) flares in adult and pediatric patients1–6. In a small pediatric cohort of moderate-severe medically refractory Ulcerative Colitis (UC), half achieved remission with a regimen of 3–4 antibiotics6. The rationale is to decrease mucosal inflammation by altering intestinal microbiota, however, to date no study has documented these changes. We report our experience with combination oral antibiotics in symptomatic pediatric patients with steroid-dependent or -resistant UC, and demonstrate significant alterations in gut microbiota during and after antibiotic therapy with reductions in inflammatory markers.

On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth. The workshop addressed research and regulatory needs involved in the optimization of POC EID testing and challenges associated with implementation of EID, focusing on testing at birth. Scientific gaps and areas of intervention to accelerate and scale-up EID initiatives and birth testing were identified. These include discussion of the evidence supporting an early mortality peak among HIV-infected infant and justifying a role for birth HIV testing, including POC testing; evaluation of the current POC EID technology pipeline and test performance characteristics required for effective programmatic uptake; mathematical modeling of different testing scenarios and solutions with inclusion of birth testing; the adoption of setting-specific EID testing algorithms to achieve efficient linkage to care including early antiretroviral therapy initiation; the development of appropriate quality assurance programs to ensure accuracy of test results and enable sustainability of the testing program. Addressing these gaps and answering these challenges will be important in helping improve outcomes for HIV-infected infants and accelerate achieving the Joint United Nations Program for HIV and AIDS 90-90-90 targets in children.

Background Carbapenem-resistant Klebsiella pneumoniae infections are increasingly prevalent in North American hospitals. We describe an outbreak of carbapenem-resistant K. pneumoniae containing the blaOXA-232 gene transmitted by contaminated duodenoscopes during endoscopic retrograde cholangiopancreatography (ERCP) procedures. Methods An outbreak investigation was performed when 9 patients with blaOXA-232 carbapenem-resistant K. pneumoniae infections were identified at a tertiary care hospital. The investigation included 2 case-control studies, review of duodenoscope reprocessing procedures, and culture of devices. Carbapenem-resistant Enterobacteriacieae (CRE) isolates were evaluated with polymerase chain reaction analysis for carbapenemase genes, and isolates with the blaOXA-232 gene were subjected to whole-genome sequencing and chromosome single-nucleotide polymorphism analysis. On recognition of ERCP as a key risk factor for infection, targeted patient notification and CRE screening cultures were performed. Results Molecular testing ultimately identified 17 patients with blaOxa-232 carbapenem-resistant K. pneumoniae isolates, including 9 with infections, 7 asymptomatic carriers who had undergone ERCP, and 1 additional patient who had been hospitalized in India and was probably the initial carrier. Two case-control studies established a point-source outbreak associated with 2 specific duodenoscopes. A field investigation of the use, reprocessing, and storage of deuodenoscopes did not identify deviations from US Food and Drug Administration or manufacturer recommendations for reprocessing. Conclusions This outbreak demonstrated the previously underappreciated potential for duodenoscopes to transmit disease, even after undergoing high-level disinfection according to manufacturers' guidelines.

Background: Studies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some. Methods: We designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART 30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART

Author(s): Joseph Davey, Dvora L; Pintye, Jillian; Baeten, Jared M; Aldrovandi, Grace; Baggaley, Rachel; Bekker, Linda-Gail; Celum, Connie; Chi, Benjamin H; Coates, Thomas J; Haberer, Jessica E; Heffron, Renee; Kinuthia, John; Matthews, Lynn T; McIntyre, James; Moodley, Dhayendre; Mofenson, Lynne M; Mugo, Nelly; Myer, Landon; Mujugira, Andrew; Shoptaw, Steven; Stranix-Chibanda, Lynda; John-Stewart, Grace; PrEP in Pregnancy Working Group | Abstract: IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on g6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.

INTRODUCTION: The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time. MATERIALS AND METHODS: Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed. RESULTS: A total of 51 stool samples from 25 infants were analyzed: 7 infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R(2)= 0.044, p=0.002) but later courses did not (R(2)= 0.023, p= 0.114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p=0.06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p

Background Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM). Methods This cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15). Results Pre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure. Conclusions Oral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes.

Both HIV infection and tenofovir disoproxil fumarate (TDF) treatment adversely impact bone metabolism and may lead to osteopenia, which has critical implications for youth with HIV (YWH). This study evaluates changes in the biomarkers of bone metabolism and inflammation among YWH receiving initial treatment with TDF- and non-TDF-containing antiretroviral therapies (ARTs). YWH [n = 23, median age 21 years (range 18–24), 87% male, 61% African American] were assessed for inflammatory and bone metabolism biomarkers at enrollment, after 48 weeks of TDF-containing ART, and 96 weeks of ART without TDF with continued viral suppression. Spearman's rank correlation evaluated biomarker associations. Bone alkaline phosphatase, parathyroid hormone, and osteopontin increased after TDF treatment. All fell after TDF was discontinued. Levels of RANKL and osteoprotegerin did not change throughout the study. There was little correlation between biomarkers of bone metabolism and either macrophage or lymphocyte activation at any time point. Our results establish baseline associations between bone metabolism and immune biomarkers for this population, and find that before CD4 T cell decline chronic inflammation does not perturb biomarkers of bone metabolism among YWH. The adverse effects of TDF on bone health may be marginal for YWH at the early stages of disease.

Background. Whole-genome sequencing (WGS) is an emerging and powerful technique by which to perform epidemiological studies in outbreak situations. Methods. WGS was used to identify and evaluate an outbreak of OXA-232–expressing carbapenem-resistant Klebsiella pneumoniae (CRKP) transmitted to 16 patients over the course of 40 weeks via endoscopic retrograde cholangiopancreatography procedures at a single institution. WGS was performed on 32 OXA-232 CRKP isolates (1–7 per patient) and single-nucleotide variants (SNVs) were analyzed, with reference to the index patient’s isolate. Results. Interhost genetic diversity of isolates was between 0 and 15 SNVs during the outbreak; molecular clock calculations estimated 12.31 substitutions per genome per year (95% credibility interval, 7.81–17.05). Both intra- and interpatient diversification at the plasmid and transposon level was observed, significantly impacting the antibiogram of outbreak isolates. The majority of isolates evaluated (n = 27) harbored a blaCTX-M-15 gene, but some (n = 5) lacked the transposon carrying this gene, which resulted in susceptibility to aztreonam and third- and fourth-generation cephalosporins. Similarly, an isolate from a colonized patient lacked the transposon carrying rmtF and aac(6’)lb genes, resulting in susceptibility to aminoglycosides. Conclusions. This study broadens the understanding of how bacteria diversify at the genomic level over the course of a defined outbreak and provides reference for future outbreak investigations.

BACKGROUND Obesity emerged as a novel risk factor for severe disease during the 2009 H1N1 influenza pandemic. Murine studies indicate that obesity is associated with ineffective response to influenza vaccine, but few human studies exist. We aimed to determine if influenza vaccine is protective against laboratory-confirmed influenza in obese children. METHODS Body mass index, vaccination status, and laboratory-confirmed influenza data were analyzed from a previously conducted prospective study in which active surveillance for influenza-like illness was conducted in 8 elementary schools in Los Angeles County during the 2010-2011 influenza season. Polymerase-chain reaction (PCR) was performed on combined nose/throat swabs collected from children with influenza-like illness at presentation to the school nurse or during absenteeism. RESULTS Of 4260 children with height/weight data, 1191 (28.0%) were obese (body mass index ≥95th percentile). Respiratory specimens were obtained from 858 (20.1%) children. Unvaccinated obese compared with vaccinated obese children acquired 3 times more PCR-confirmed influenza (62 vs. 17 per 1000 children, P = 0.003) and missed more school days (4.6 vs. 3.2 per 100 school days, P < 0.001) during influenza season. Obese children with PCR-confirmed influenza were more likely to present with cough (86.2 vs. 72.4%, P = 0.030) and missed more school per episode (2.4 vs.1.9 days, P = 0.023) compared with nonobese children. Among vaccinated children, rates of PCR-confirmed influenza were similar in obese and nonobese children (17 vs. 20 per 1000 children, P = 0.77). CONCLUSIONS Obese children with PCR-confirmed influenza suffered from more cough and missed more school days than their nonobese peers. Influenza vaccination protected obese children against PCR-proven influenza illness.

Background Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). Methods From 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55–42.04) and mean overall survival (OS) was 24.76 months (3.91–75.49). All patients died of recurrent tumor progression. Results iCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. Conclusions Further investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

PURPOSE: This study compared the role of multislice computed tomography coronary angiography (MSCT-CA) and stress electrocardiography (ECG) in the diagnostic workup of patients with chronic chest pain. MATERIALS AND METHODS: MSCT-CA was performed in 43 patients (31 men, 12 women, mean age 58.8+/-7.7 years) with stable angina after a routine diagnostic workup involving stress ECG and conventional CA. The following inclusion criteria were adopted: sinus rhythm and ability to hold breath for 12 s. Beta-blockers were administered in patients with heart rate>or=70 beats/minute. In order to identify or exclude patients with significant stenoses (>or=50% lumen), we determined posttest likelihood ratios of stress test and MSCT-CA separately and of MSCT-CA performed after the stress test. RESULTS: The pretest probability of significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios were 2.3 [95% confidence interval (CI) 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) for the stress test and 10.0 (95% CI: 1.8-78.4) and 0.0 (95% CI: 0.0-infinity) for MSCT-CA, respectively. MSCT-CA increased the posttest probability of significant CAD after a negative stress test from 50% to 86% and after a positive stress test from 88% to 100%. MSCT-CA correctly detected all patients without CAD. CONCLUSIONS: Noninvasive MSCT-CA is a potentially useful tool in the diagnostic workup of patients with stable angina owing to its capability to detect or exclude significant CAD.

The goal of this article is to illustrate the main invasive and noninvasive diagnostic modalities to image the vulnerable coronary plaque, which is responsible for acute coronary syndrome. The main epidemiologic and histological issues are briefly discussed in order to provide an adequate background. Comprehensive coronary atherosclerosis imaging should involve visualization of the entire coronary artery tree and plaque characterization, including three-dimensional morphology, relationship with the lumen, composition, vascular remodelling and presence of inflammation. No single technique provides such a comprehensive description, and no available modality extensively identifies the vulnerable plaque. In particular, we describe multislice computed tomography, which at present seems to be the most promising noninvasive tool for an exhaustive image-based quantification of coronary atherosclerosis.

OBJECTIVE The aim of this study was to estimate the long-term metabolic effects of initiating a lopinavir/ritonavir (LPV/r)-based regimen as a first-line therapy for HIV-infected children less than 3 years of age in resource-limited settings. DESIGN A prospective cohort study after conclusion of the P1060 randomized clinical trials (ClinicalTrials.gov Identifier: NCT00307151), with an overall follow-up of 7 years. METHODS Longitudinal total cholesterol and triglyceride measures were compared between 222 and 227 children randomized to initiate LPV/r and nevirapine (NVP)-based regimens, respectively. Adipokines (adiponectin and leptin) and biomarkers of inflammation [C-reactive protein and interleukin (IL)-6], microbial translocation (lipopolysaccharide) and immune activation (sCD14), measured in 117 participants at a median of 45 weeks of follow-up, were also compared by a randomized arm. RESULTS Mean total cholesterol and the percentage of participants with borderline or high total cholesterol was higher in the LPV/r arm from years 3 to 7 of follow-up than in the NVP arm (adjusted relative differences ranging from 10.9 to 23.4 mg/dl and adjusted relative risks ranging from a 60% increased risk to a more than four-fold increased risk for cholesterol ≥170 mg/dl at 7 years of follow-up). Initiation of a LPV/r-based regimen was not associated with high triglycerides over follow-up or large differences in markers of metabolic syndrome, inflammation, microbial translocation or immune activation. CONCLUSION Given the virologic superiority of LPV/r-based regimens in young children and open questions regarding the roll-out of dolutegravir in resource-limited settings, children are currently being maintained on LPV/r-based regimens. Our results suggest continual assessment of total cholesterol among young children initiating a LPV/r-based regimen to monitor cardiometabolic health.

OBJECTIVE We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and central nervous system immunoinflammatory mediators contributes to neurocognitive impairment (NCI). DESIGN Cross-sectional. SETTING Six Academic Centers. PARTICIPANTS One hundred fifty-two patients with plasma HIV RNA

"OBJECTIVE: Volatile anesthetics reduce the risk of myocardial infarction and mortality in coronary artery surgery. Recently, the American College of Cardiology\/American Heart Association Guidelines suggested the use of volatile anesthetic agents for the maintenance of general anesthesia during noncardiac surgery in patients at risk for perioperative myocardial ischemia, but no randomized experience to document the cardioprotective effects of these agents exists in this setting. Therefore, the authors performed a prospective, randomized, controlled trial to compare the effects of sevoflurane versus total intravenous anesthesia, in terms of postoperative cardiac troponin I release in patients undergoing noncardiac surgery.. . DESIGN: A randomized, controlled trial.. . SETTING: A teaching hospital.. . PARTICIPANTS: Eighty-eight consecutive patients undergoing noncardiac surgery.. . INTERVENTIONS: Patients were allocated randomly to receive either volatile anesthetic (44 patients) as the main anesthetic agent or total intravenous anesthesia (TIVA) (44 patients).. . MEASUREMENTS: Postoperative cardiac troponin I release was measured as a marker of myocardial necrosis. Patients with detectable postoperative troponin I in the sevoflurane group (12\/44, 27.3%) were similar to those in the propofol group (9\/44, 20.5%; p = 0.6). There was no significant reduction of postoperative median peak cTnI release (0.16 ± 0.71 ng\/mL in the sevoflurane group compared with the TIVA group, 0.03 ± 0.08 ng\/mL; p = 0.4). Three patients died at the 1-year follow-up for noncardiac causes (2 in the TIVA group).. . CONCLUSIONS: In the authors' experience, patients undergoing noncardiac surgery did not benefit from anesthesia based on halogenated anesthetics. Further studies are necessary to evaluate the cardioprotective effects of volatile agents in noncardiac surgery.. . "

Article history: Received 24 January 2016 Accepted 2 February 2016 Available online 4 February 2016 methods were previously published [6]. A high risk plaque was defined at least one of the following criteria: (i) a necrotic core with high attenuation value (attenuation value b30 HU), (ii) positive remodelling. CMR Data Acquisition and Image Analysis: All CMR studies were acquired using a 1.5 T MRI system (Philips Achieva, Philips Medical System, Best, The Netherlands), the LGE images were analyzed by