DeepRiPP integrates multiomics data to automate discovery of novel ribosomally synthesized natural products.

Microbial natural products represent a rich resource of evolved chemistry that forms the basis for the majority of pharmacotherapeutics. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a particularly interesting class of natural products noted for their unique mode of biosynthesis and biological activities. Analyses of sequenced microbial genomes have revealed an enormous number of biosynthetic loci encoding RiPPs but whose products remain cryptic. In parallel, analyses of bacterial metabolomes typically assign chemical structures to only a minority of detected metabolites. Aligning these 2 disparate sources of data could provide a comprehensive strategy for natural product discovery. Here we present DeepRiPP, an integrated genomic and metabolomic platform that employs machine learning to automate the selective discovery and isolation of novel RiPPs. DeepRiPP includes 3 modules. The first, NLPPrecursor, identifies RiPPs independent of genomic context and neighboring biosynthetic genes. The second module, BARLEY, prioritizes loci that encode novel compounds, while the third, CLAMS, automates the isolation of their corresponding products from complex bacterial extracts. DeepRiPP pinpoints target metabolites using large-scale comparative metabolomics analysis across a database of 10,498 extracts generated from 463 strains. We apply the DeepRiPP platform to expand the landscape of novel RiPPs encoded within sequenced genomes and to discover 3 novel RiPPs, whose structures are exactly as predicted by our platform. By building on advances in machine learning technologies, DeepRiPP integrates genomic and metabolomic data to guide the isolation of novel RiPPs in an automated manner.

Liquid Biopsy-based Precision Therapy in Patients with Advanced Solid Tumors: A Real-world Experience from a Community-based Oncology Practice.

BACKGROUND: Liquid biopsy testing offers a significant potential in selecting signal-matched therapies for advanced solid malignancies. The feasibility of liquid biopsy testing in a community-based oncology practice, and its actual impact on selecting signal-matched therapies, and subsequent survival effects have not previously been reported. PATIENTS AND METHODS: A retrospective chart review was conducted on adult patients with advanced solid cancer tested with a liquid-biopsy assay between December 2018 and 2019, in a community oncology practice. The impact of testing on treatment assignment and survival was assessed at 1-year follow-up. RESULTS: A total of 178 patients underwent testing. A positive test was reported in 140/178 patients (78.7%), of whom 75% had an actionable mutation. The actual overall signal-based matching rate was 17.8%. While 85.7% of patients with no actionable mutation had a signal-based clinical trial opportunity, only 10% were referred to a trial. Survival analysis of lung, breast, and colorectal cancer patients with actionable mutations who received any therapy (n = 66) revealed a survival advantage for target-matched (n = 22) compared to unmatched therapy (n = 44): patients who received matched therapy had significantly longer progression-free survival (PFS) (mPFS: 12 months; 95%CI, 10.6-13.4 vs. 5.0 months; 95%CI, 3.4-6.6; P = .029), with a tendency towards longer overall survival (OS) (mOS: 15 months; 95%CI, 13.5-16.5 vs. 13 months; 95%CI: 11.3-14.7; P = .087). CONCLUSIONS: Implementation of liquid biopsy testing is feasible in a US community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched therapies conferred added survival benefits.

Effectiveness of Incentives for Improving Diabetes-Related Health Indicators in Chronic Disease Lifestyle Modification Programs: a Systematic Review and Meta-Analysis.

INTRODUCTION: We examined the effectiveness of providing incentives to participants in lifestyle modification programs to improve diabetes-related health indicators: body weight, body mass index (BMI), blood pressure, cholesterol, and hemoglobin A1C (HbA1C). We also examined the potential effect of 4 different incentive domains (ie, type, monetary value, attainment certainty, and schedule) on those indicators. METHODS: We searched Medline, Embase, PsycINFO, and Cochrane Library to identify relevant studies published from January 2008 through August 2021. We used a random-effects model to pool study results and examine between-study heterogeneity by using the I2 statistic and the Cochran Q test. We also conducted moderator analyses by using a mixed-effects model to examine differences between subgroups of incentive domains (eg, incentive type [cash vs other types]). RESULTS: Our search yielded 10,965 articles, of which 19 randomized controlled trials met our selection criteria. The random-effects model revealed that, relative to the control group, the incentive group had significant reductions in weight (-1.85kg; 95% CI, -2.40 to -1.29; P < .001), BMI (-0.47kg/m2; 95% CI, -0.71 to -0.22; P < .001), and both systolic blood pressure (-2.59 mm HG; 95% CI, -4.98 to -0.20; P = .03) and diastolic blood pressure (-2.62 mm Hg; 95% CI, -4.61 to -0.64; P = .01). A reduction in cholesterol level was noted but was not significant (-2.81 mg/dL; 95% CI, -8.89 to -3.28; P = .37). One study found a significant reduction in hemoglobin A1c (-0.17%; 95% CI, -0.30% to -0.05%; P < .05). The moderator analyses showed that the incentive effect did not vary significantly between the subgroups of the incentive domains, except on weight loss for the attainment certainty domain, suggesting that a variety of incentive subgroups could be equally useful. CONCLUSION: Providing incentives in lifestyle modification programs is a promising strategy to decrease weight, BMI, and blood pressure.

A Statistically Significant Reduction in Length of Stay and Hospital Costs with Equivalent Quality of Care Metrics for ERCPs Performed During the Weekend Versus Postponed to Weekdays: A 6-Year Study of 533 ERCPs at Four Teaching Hospitals.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a diagnostic/therapeutic endoscopic procedure for numerous pancreaticobiliary diseases. Data regarding performing ERCP on weekend (WE; Saturday/Sunday) versus postponing ERCP to first two available weekdays (WD; Monday/Tuesday) are scarce. ERCP requires costly resources including specialized nurses, endoscopy room equipped with fluoroscopy, anesthesia services, and highly trained therapeutic endoscopists. Hospitals frequently do not have these resources readily available during WE, leading to postponing ERCPs to WD. AIMS: This study analyzes the effect of performing ERCP on WE versus postponement to WD on hospital efficiency, and on patient safety/outcomes. METHODS: A computerized search of electronic medical records, January 2011-December 2016, at four Beaumont Hospitals retrospectively identified all gastroenterology consults performed on Friday or Saturday before 12:00 noon, which resulted in ERCP performed for any indication on WE versus postponing ERCP to WD. Length of stay (LOS), hospital costs, hospital charges, and hospital reimbursements were compared between both groups, as were quality of care measures. RESULTS: Among 5196 patients undergoing ERCPs, 533 patients were identified, including 315 patients in the WE group and 218 patients in the WD group. Comparing WE versus WD groups, median LOS was shorter (4.5 days vs. 6.9 days, p < 0.0001); median hospital costs were less ($9208 vs. $11,657, p < 0.0001); and median hospital charges were less ($28,026 vs. $37,899, p < 0.0001). Median hospital reimbursements were not significantly different in WE versus WD groups ($10,277 vs. $10,362, p = 0.65). Median hospital charges were lower than median hospital reimbursements (net profit) in WE but not in WD. WE versus WD had no significant differences in morbidity, mortality, ≤ 30-day readmission rates, need for repeat ERCP ≤ 30 days, or post-ERCP complications. LIMITATIONS: This is a retrospective study. CONCLUSIONS: Performing ERCPs during weekends significantly reduced LOS, hospital costs, and hospital charges compared to postponing ERCP to WD and resulted in net hospital profits, without impairing quality of medical care.

CMV on surfaces in homes with young children: results of PCR and viral culture testing.

BACKGROUND: Caring for young children is a known risk factor for cytomegalovirus (CMV) infection mainly through exposure to their saliva and urine. In a previous study, 36 CMV-seropositive children 2 mo. to 4 years old were categorized as CMV shedders (n = 23) or non-shedders (n = 13) based on detection of CMV DNA in their saliva and urine. The current study evaluated the presence of CMV on surfaces in homes of the children. METHODS: Study staff made 4 visits to homes of the 36 enrolled children over 100 days. Saliva was collected by swabbing the mouth and urine was collected on filter paper inserted into diapers. In addition, five surface specimens were collected: three in contact with children's saliva (spoon, child's cheek, washcloth) and two in contact with children's urine (diaper changing table, mother's hand). Samples were tested by PCR and viral culture to quantify the presence of CMV DNA and viable virus. RESULTS: A total of 654 surface samples from 36 homes were tested; 136 were CMV DNA positive, 122 of which (90%) were in homes of the children shedding CMV (p < 0.001). Saliva-associated samples were more often CMV positive with higher viral loads than urine-associated samples. The higher the CMV viral load of the child in the home, the more home surfaces that were PCR positive (p = 0.01) and viral culture positive (p = 0.05). CONCLUSIONS: The main source for CMV on surfaces in homes was saliva from the child in the home. Higher CMV viral loads shed by children correlated with more viable virus on surfaces which could potentially contribute to viral transmission.

Sudden Cardiac Arrest Due to Hemophagocytic Lymphohistiocytosis in a Child.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon hyperinflammatory condition in children that may acutely mimic septic shock. Sudden out-of-hospital cardiac arrest in children is also uncommon and may be of unclear etiology upon initial presentation. CASE REPORT: A 10-year-old previously healthy child presented with sudden cardiac arrest after an insidious course of throat pain, fever, and progressive altered mental status. He was subsequently diagnosed with Epstein-Barr virus-associated HLH and suffered cerebral edema and death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: HLH has not previously been described as a cause of sudden out-of-hospital cardiac arrest in children. Rapid diagnosis of underlying cause of an unexpected cardiac arrest may help guide appropriate therapy to salvage organ function.

Clinical Effects of Stabilized Stannous Fluoride Dentifrice in Reducing Plaque Microbial Virulence II: Metabonomic Changes.

OBJECTIVES: The clinical effects of stannous fluoride (SnF2) dentifrice in reducing symptoms of gingivitis and reducing the virulence of subgingival plaque through suppression of activation of gene expression in toll receptor based reporter cells were previously reported. This study expanded analysis of the clinical study to include evaluation of dentifrice effects on salivary metabolites using 1H Nuclear Magnetic Resonance (1H NMR) systems biology-based metabonomics. METHODS: The clinical design was reported previously (J Clin Dent2017;28:16-26). Participants included a cohort exhibiting high and low levels of gingival disease as presented at initiation of the study. Participants provided morning lavage saliva samples at baseline. Following this, participants were provided with a hygiene intervention, including a stabilized SnF2 dentifrice and a new soft bristle manual toothbrush. Following two and four weeks of assigned dentifrice use, participants again collected morning lavage saliva samples. Samples were analyzed by 1HNMR spectroscopy on a Bruker 600MHz NMR spectrometer. System-wide analyses were carried out by partial least squared (PLS) comparisons of aggregate spectra, and discrete metabolites with established spectral signatures were likewise directly compared. RESULTS: PLS analysis showed significant differences in saliva composition for saliva collected from high bleeding and low bleeding cohorts. Clear shifts in saliva composition were observed in system-wide PLS analysis following intervention of SnF2 dentifrice for both cohorts. A number of discrete spectral changes were consistently observed with SnF2 dentifrice intervention, most notably including reductions in propionic acid and butyric acid, key short chain fatty acids associated with anaerobic metabolism in dental plaques. CONCLUSIONS: These results collectively demonstrate that SnF2 dentifrice treatment was associated with broad scale modifications in saliva composition following intervention in both high and low diseased cohorts. Changes in overall salivary composition and specific reductions in saliva concentrations of propionic and butyric acid reductions occurred coincident with clinical improvements in gingivitis and gingival bleeding. These results provide support for the hypothesis that the effectiveness of SnF2 dentifrice in improving gingival health is associated with a modification of microbiome metabolism, including suppression of short chain fatty acid metabolites.

Folate Deficiency Is Prevalent in Women of Childbearing Age in Belize and Is Negatively Affected by Coexisting Vitamin B-12 Deficiency: Belize National Micronutrient Survey 2011.

Background: Folate deficiency, vitamin B-12 deficiency, and anemia can have adverse effects on birth outcomes. Also, low vitamin B-12 reduces the formation of metabolically active folate.Objectives: We sought to establish the baseline prevalence of and factors associated with folate deficiency and insufficiency, vitamin B-12 deficiency, and anemia among women of childbearing age (WCBA) in Belize.Methods: In 2011, a national probability-based survey was completed among Belizean nonpregnant WCBA aged 15-49 y. Blood samples for determination of hemoglobin, folate (RBC and serum), and vitamin B-12 (plasma) and sociodemographic and health information were collected from 937 women. RBC and serum folate concentrations were measured by microbiologic assay (MBA). Folate status was defined based on both the WHO-recommended radioproteinbinding assay and the assay adjusted for the MBA.Results: The national prevalence estimates for folate deficiency in WCBA, based on serum and RBC folate concentrations by using the assay-matched cutoffs, were 11.0% (95% CI: 8.6%, 14.0%) and 35.1% (95% CI: 31.3%, 39.2%), respectively. By using the assay-matched compared with the WHO-recommended cutoffs, a substantially higher prevalence of folate deficiency was observed based on serum (6.9% absolute difference) and RBC folate (28.9% absolute difference) concentrations. The prevalence for RBC folate insufficiency was 48.9% (95% CI: 44.8%, 53.1%). Prevalence estimates for vitamin B-12 deficiency and marginal deficiency and anemia were 17.2% (95% CI: 14.2%, 20.6%), 33.2% (95% CI: 29.6%, 37.1%), and 22.7% (95% CI: 19.5%, 26.2%), respectively. The adjusted geometric means of the RBC folate concentration increased significantly (P-trend < 0.001) in WCBA who had normal vitamin B-12 status relative to WCBA who were vitamin B-12 deficient.Conclusions: In Belize, the prevalence of folate and vitamin B-12 deficiencies continues to be a public health concern among WCBA. Furthermore, low folate status co-occurred with low vitamin B-12 status, underlining the importance of providing adequate vitamin B-12 and folic acid intake through approaches such as mandatory food fortification.

Using theory-based messages to motivate U.S. pregnant women to prevent cytomegalovirus infection: results from formative research.

BACKGROUND: An estimated 1 in 150 infants is born each year with congenital cytomegalovirus (CMV); nearly 1 in 750 suffers permanent disabilities. Congenital CMV is the result of a pregnant woman becoming infected with CMV. Educating pregnant women about CMV is currently the best approach to prevention. Limited research is available on how to effectively communicate with women about CMV. We conducted formative research on fear appeals theory-based messages about CMV and prevention with U.S. women. Fear appeal theories suggest that message recipients will take action if they feel fear. METHODS: First, we conducted in-depth interviews (N = 32) with women who had young children who tested positive for CMV. Second, we conducted eight focus groups (N = 70) in two phases and two cities (Phase 2: Atlanta, GA; Phase 3: San Diego, CA) with pregnant women and non-pregnant women who had young children. Few participants knew about CMV before the focus groups. Participants reviewed and gave feedback on messages created around fear appeals theory-based communication concepts. The following concepts were tested in one or more of the three phases of research: CMV is severe, CMV is common, CMV is preventable, CMV preventive strategies are similar to other behavior changes women make during pregnancy, CMV preventive strategies can be incorporated in moderation to reduce exposure, and CMV is severe but preventable. RESULTS: Participants recommended communicating that CMV is common by using prevalence ratios (e.g., 1 in 150) or comparing CMV to other well-known disabilities. To convey the severity of CMV, participants preferred stories about CMV along with prevention strategies. Participants also welcomed prevention strategies when it included a message about risk reduction. In general, participants said messages were motivating, even if they felt that it could be difficult to make certain behavior changes. CONCLUSIONS: Findings from this research can contribute to future efforts to educate pregnant women about CMV, especially regarding use of fear appeals-based messages. Pregnant women may face certain challenges to practicing prevention strategies but, overall, are motivated make changes to increase their chances of having a healthy baby.

Chronological evidence fails to support claim of an isochronous widespread layer of cosmic impact indicators dated to 12,800 years ago.

According to the Younger Dryas Impact Hypothesis (YDIH), ∼ 12,800 calendar years before present, North America experienced an extraterrestrial impact that triggered the Younger Dryas and devastated human populations and biotic communities on this continent and elsewhere. This supposed event is reportedly marked by multiple impact indicators, but critics have challenged this evidence, and considerable controversy now surrounds the YDIH. Proponents of the YDIH state that a key test of the hypothesis is whether those indicators are isochronous and securely dated to the Younger Dryas onset. They are not. We have examined the age basis of the supposed Younger Dryas boundary layer at the 29 sites and regions in North and South America, Europe, and the Middle East in which proponents report its occurrence. Several of the sites lack any age control, others have radiometric ages that are chronologically irrelevant, nearly a dozen have ages inferred by statistically and chronologically flawed age-depth interpolations, and in several the ages directly on the supposed impact layer are older or younger than ∼ 12,800 calendar years ago. Only 3 of the 29 sites fall within the temporal window of the YD onset as defined by YDIH proponents. The YDIH fails the critical chronological test of an isochronous event at the YD onset, which, coupled with the many published concerns about the extraterrestrial origin of the purported impact markers, renders the YDIH unsupported. There is no reason or compelling evidence to accept the claim that a cosmic impact occurred ∼ 12,800 y ago and caused the Younger Dryas.

Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection - United States, 2016.

CDC has developed interim guidelines for health care providers in the United States who are caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. These guidelines include recommendations for the testing and management of these infants. Guidance is subject to change as more information becomes available; the latest information, including answers to commonly asked questions, can be found online (http://www.cdc.gov/zika). Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission [http://wwwnc.cdc.gov/travel/notices]), and review fetal ultrasounds and maternal testing for Zika virus infection (see Interim Guidelines for Pregnant Women During a Zika Virus Outbreak*) (1). Zika virus testing is recommended for 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended. Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition.

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?

Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions.

Prevalence and characteristics of women at risk for an alcohol-exposed pregnancy (AEP) in the United States: estimates from the National Survey of Family Growth.

Non-pregnant women can avoid alcohol-exposed pregnancies (AEPs) by modifying drinking and/or contraceptive practices. The purpose of this study was to estimate the number and characteristics of women in the United States who are at risk of AEPs. We analyzed data from in-person interviews obtained from a national probability sample (i.e., the National Survey of Family Growth) of reproductive-aged women conducted from January 2002 to March 2003. To be at risk of AEP, a woman had to have met the following criteria in the last month: (1) was drinking; (2) had vaginal intercourse with a man; and (3) did not use contraception. During a 1-month period, nearly 2 million U.S. women were at risk of an AEP (95 % confidence interval 1,760,079-2,288,104), including more than 600,000 who were binge drinking. Thus, 3.4 %, or 1 in 30, of all non-pregnant women were at risk of an AEP. Most demographic and behavioral characteristics were not clearly associated with AEP risk. However, pregnancy intention was strongly associated with AEP risk (prevalence ratio = 12.0, P < 0.001) because women often continued to drink even after they stopped using contraception. Nearly 2 million U.S. women are at AEP risk and therefore at risk of having children born with fetal alcohol spectrum disorders. For pregnant women and women intending a pregnancy, there is an urgent need for wider implementation of prevention programs and policy approaches that can reduce the risk for this serious public health problem.

Response of chronic gingivitis to hygiene therapy and experimental gingivitis. Clinical, microbiological and metabonomic changes.

PURPOSE: To compare the clinical, microbiological and metabonomic profiles of subjects with high and low levels of chronic gingival bleeding during a controlled oral hygiene regimen intervention including sequential phases of rigorous therapeutic oral hygiene followed by experimental gingivitis (EG). METHODS: Two cohorts of qualified study subjects with differences in gingival bleeding on probing levels at their baseline clinical examination were entered into the study. These two cohorts were followed through three separate study phases including a 1-week baseline phase, a 2-week phase of rigorous oral hygiene including dental prophylaxis, and a 3-week EG phase of no oral hygiene to encourage relapse of gingivitis. The 58 subjects were assessed during each phase of the study for clinical presentation of gingivitis and concurrently had plaque sampled for real-time polymerase chain reaction (RTPCR) microbiological characterization and salivary lavage samples for 'systems biology' metabonomics assessment by 1H-NMR. RESULTS: Subjects presenting with different levels of gingival bleeding on probing when they entered the study responded differently to rigorous oral hygiene and EG. Specifically, the high bleeding cohort responded sluggishly to rigorous oral hygiene and exhibited markedly greater relapse to gingivitis during EG. RTPCR analysis showed changes in bacterial populations that were associated with study phases, particularly the increases in putative periodontal pathogens during EG. However, the microbiological profiles of high- and low-susceptibility gingival bleeding patients were largely similar. Metabonomic analysis likewise revealed significant changes in metabolite composition during study phases associated with differences in plaque toxicity, especially the short chain carboxylic acids propionate and n-butyrate, which tracked clinical changes in gingivitis severity. Systems analysis of metabonomic changes suggested differences between cohorts, although analysis to date has not elucidated whether these differences are causative (population predictive) or simply diagnostic of clinical status within populations.

King v. Burwell: Desperately Seeking Ambiguity in Clear Statutory Text.

Does the Patient Protection and Affordable Care Act (ACA) of 2010 authorize tax credits within the thirty-six states that failed to establish health insurance exchanges? That is the question presented in Pruitt v. Burwell, Halbig v. Burwell, King v. Burwell, and Indiana v. IRS. The plaintiffs argue that the statute is clear and forecloses any possibility of tax credits in federal exchanges. The government argues that the statute plainly authorizes tax credits in federal exchanges, or is at least ambiguous on the question. Mere disagreement is not evidence of ambiguity. Reaching the truth requires wading deep into each side's arguments. Whether the relevant text is viewed in isolation or in its full statutory context, the ACA authorizes tax credits only in exchanges established by the states.

Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 10(5) infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands.

Cross-sectional study of cytomegalovirus shedding and immunological markers among seropositive children and their mothers.

BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. To better understand factors that may influence CMV transmission risk, we compared viral and immunological factors in healthy children and their mothers. METHODS: We screened for CMV IgG antibodies in a convenience sample of 161 children aged 0-47 months from the Atlanta, Georgia metropolitan area, along with 32 mothers of children who screened CMV-seropositive. We assessed CMV shedding via PCR using saliva collected with oral swabs (children and mothers) and urine collected from diapers using filter paper inserts (children only). RESULTS: CMV IgG was present in 31% (50/161) of the children. Half (25/50) of seropositive children were shedding in at least one fluid. The proportion of seropositive children who shed in saliva was 100% (8/8) among the 4-12 month-olds, 64% (9/14) among 13-24 month-olds, and 40% (6/15) among 25-47 month-olds (P for trend=0.003). Seropositive mothers had a lower proportion of saliva shedding (21% [6/29]) than children (P<0.001). Among children who were shedding CMV, viral loads in saliva were significantly higher in younger children (P <0.001); on average, the saliva viral load of infants (i.e., <12 months) was approximately 300 times that of two year-olds (i.e., 24-35 months). Median CMV viral loads were similar in children's saliva and urine but were 10-50 times higher (P<0.001) than the median viral load of the mothers' saliva. However, very high viral loads (> one million copies/mL) were only found in children's saliva (31% of those shedding); children's urine and mothers' saliva specimens all had fewer than 100,000 copies/mL. Low IgG avidity, a marker of primary infection, was associated with younger age (p=0.03), higher viral loads in saliva (p=0.02), and lower antibody titers (p=0.005). CONCLUSIONS: Young CMV seropositive children, especially those less than one year-old may present high-risk CMV exposures to pregnant women, especially via saliva, though further research is needed to see if this finding can be generalized across racial or other demographic strata.

Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children.

BACKGROUND: To better understand potential transmission risks from contact with the body fluids of children, we monitored the presence and amount of CMV shedding over time in healthy CMV-seropositive children. METHODS: Through screening we identified 36 children from the Atlanta, Georgia area who were CMV-seropositive, including 23 who were shedding CMV at the time of screening. Each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine daily. RESULTS: Prevalence of shedding was highly correlated with initial shedding status: children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those not shedding at the screening visit had CMV DNA in 16% of follow-up saliva specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730 copies/mL in urine (P=0.01), while the viral load for the 75th percentile was nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine. Younger age was significantly associated with higher viral loads, especially for saliva (P<0.001). Shedding prevalence and viral loads were relatively stable over time. All children who were shedding at the screening visit were still shedding at least some days during weeks 11 and 12, and median and mean viral loads did not change substantially over time. CONCLUSIONS: Healthy CMV-seropositive children can shed CMV for months at high, relatively stable levels. These data suggest that behavioral prevention messages need to address transmission via both saliva and urine, but also need to be informed by the potentially higher risks posed by saliva and by exposures to younger children.

Educating women about congenital cytomegalovirus: assessment of health education materials through a web-based survey.

BACKGROUND: Congenital cytomegalovirus (CMV) is the most common congenital infection in the U.S. and can result in permanent disabilities, such as hearing and vision loss, intellectual disability, and psychomotor and language impairments. Women can adopt prevention behaviors in an attempt to reduce their exposure to CMV. Currently, few women are familiar with CMV. To increase awareness of CMV, the Centers for Disease Control and Prevention (CDC) developed draft health education materials. The purpose of this study was to pilot test two health education materials to gauge their appeal and to determine if they increase knowledge about CMV and motivate audiences to seek additional information on CMV and adopt CMV prevention behaviors. METHODS: African-American (n = 404) and Caucasian women (n = 405), who had a young child and were either pregnant or planning a pregnancy, were recruited to participate in a 15-minute web survey. Participants were randomly assigned to view one of two CMV health education materials, either a factsheet or video. Pre and post survey measures were used to assess changes in knowledge of CMV and motivation to adopt prevention behaviors. We also examined audience preferences regarding materials and motivation. RESULTS: CMV knowledge score increased significantly after presentation of either the video or factsheet (from 3.7 out of 10 to 9.1 out of 10, p <0.001). The average materials appeal score was high, with a mean of 3.6 on a four-point scale, indicating women responded very positively to both materials. Regression analyses indicated that appeal, message involvement (e.g., information seeking, discussing with others), post materials knowledge score, and viewing the video (vs. factsheet) were significantly positively associated with increased support for CMV prevention behaviors. CONCLUSIONS: Overall, we found that the health education materials improved women's knowledge of CMV and encouraged them to adopt prevention behaviors. Given the low awareness levels among women currently, these findings suggest that appropriate education materials have the potential to greatly increase knowledge of CMV. As women become more knowledgeable about CMV and transmission routes, we expect they will be more likely to adopt prevention behaviors, thereby reducing their risk of CMV infection.