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The early-life origins of disease hypothesis has been applied to obesity research and modeled through overnutrition, usually with a high-fat diet (HFD). Since the obesity epidemic coincided with societal change in dietary fat consumption, rather than amount, manipulation of fatty acid (FA) profile is an under-investigated area of study. Additionally, the binding of FAs to nuclear receptors may have persistent intergenerational, extranutritive endocrinological effects that interact with the actions of reproductive steroids causing sex-dependent effects. To determine the role of FA type in the effects underlying maternal HFD, we fed wild-type C57BL6/J mating pairs, from preconception through lactation, a HFD with high saturated fat levels from coconut oil or high linoleic acid (LA) levels from vegetable oil. Male and female offspring body weight and food intake were measured weekly for 25 weeks. Assays for glucose metabolism, body composition, and calorimetry were performed at 25 weeks. Plasma metabolic peptides and liver mRNA were measured terminally. Obesity was primarily affected by adult rather than maternal diet in males, yet in females, maternal HFD potentiated the effects of adult HFD. Maternal HFD high in LA impaired glucose disposal in males weaned onto HFD and insulin sensitivity of females. Plasma leptin correlated with adiposity, but insulin and insulin receptor expression in the liver were altered by maternal LA in males. Our results suggest that maternal FA profile is most influential on offspring glucose metabolism and that adult diet is more important than maternal diet for obesity and other parameters of metabolic syndrome.
Destruction of tropical rainforests reduces many unprotected habitats to small fragments of remnant forests within agricultural matrices. To date, these remnant forest fragments have been largely disregarded as wildlife habitat, and little is known about mammalian use of these areas in Sumatra. Here, we conducted camera trap surveys (2285 trap-nights) within Bukit Barisan Selatan National Park and five surrounding remnant forest fragments during 2010–2013 and used species composition metrics to compare use. We found 28 mammal species in the protected forest and 21 in the fragments. The fragments harboured a subset of species found in the protected forest and several species not observed in the protected forest. Critically endangered species such as Sunda pangolin (Manis javanica) and Sumatran tiger (Panthera tigris sumatrae) were found in the forest fragments, along with species of conservation concern such as marbled cat (Pardofelis marmorata) and Asiatic golden cat (Pardofelis temminckii). The biodiversity found within the fragments suggests that these small patches of remnant forest may have conservation value to certain mammal species and indicates the importance of further research into the role these habitats may play in landscape-level, multispecies conservation planning.
To evaluate the Orange County Clostridium difficile infection (CDI) prevention collaborative’s effect on rates of CDI in acute-care hospitals (ACHs) in Orange County, California.
Controlled interrupted time series.
We convened a CDI prevention collaborative with healthcare facilities in Orange County to reduce CDI incidence in the region. Collaborative participants received onsite infection control and antimicrobial stewardship assessments, interactive learning and discussion sessions, and an interfacility transfer communication improvement initiative during June 2015–June 2016. We used segmented regression to evaluate changes in monthly hospital-onset (HO) and community-onset (CO) CDI rates for ACHs. The baseline period comprised 17 months (January 2014–June 2015) and the follow-up period comprised 28 months (September 2015–December 2017). All 25 Orange County ACHs were included in the CO-CDI model to account for direct and indirect effects of the collaborative. For comparison, we assessed HO-CDI and CO-CDI rates among 27 ACHs in 3 San Francisco Bay Area counties.
HO-CDI rates in the 15 participating Orange County ACHs decreased 4% per month (incidence rate ratio [IRR], 0.96; 95% CI, 0.95–0.97; P < .0001) during the follow-up period compared with the baseline period and 3% (IRR, 0.97; 95% CI, 0.95–0.99; P = .002) per month compared to the San Francisco Bay Area nonparticipant ACHs. Orange County CO-CDI rates declined 2% per month (IRR, 0.98; 95% CI, 0.96–1.00; P = .03) between the baseline and follow-up periods. This decline was not statistically different from the San Francisco Bay Area ACHs (IRR, 0.97; 95% CI, 0.95–1.00; P = .09).
Our analysis of ACHs in Orange County provides evidence that coordinated, regional multifacility initiatives can reduce CDI incidence.
This article summarizes the results of controlled experiments in which flaked-stone points that varied in impact strength by a factor of almost three were shot at media that were increasingly inelastic and therefore likely to break the points. Broken tips were reworked if possible, and used again under the same conditions. Our results show that all damage to low impact-strength materials, especially obsidian, was generally catastrophic, and, consequently, these points could only rarely be reworked. The fact that low-strength stones were commonly used to make small arrowpoints suggests that reworking was not a primary concern for their designers. Furthermore, in those instances when broken tips could be reworked, their performance declined. In addition, reworking broken points also resulted in shapes that are uncommon in many arrowpoint assemblages. Our results suggest that the original design attributes of arrowpoints may have been less affected by reworking, and, consequently, may more accurately suggest temporal and behavioral associations.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.
We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.
Recently in vitro and in situ techniques have been used for assessing forage nutritive value for ruminants instead of laborious in vivo trials. Although, Blummel and Ørskov (1993) have shown that an in vitro gas production technique gives reliable estimates of forage nutritive value, whether the estimates could be correlated with in situ degradation are not well established. There is little known about the differences in degradation characteristics of neutral-detergent fibre (NDF) and cellular contents (CC: soluble carbohydrates, lipids and crude protein) in the rumen, and also about the relationships between component degradation rate in the rumen and gas production rate for different forages. This is because most in situ kinetic studies have followed the disappearance of insoluble cell wall constituents and comparative studies of in vitro and in situ estimates was not performed sufficiently.
The objective of this experiment was to investigate the relationship between in situ degradation of forage components and in vitro gas production rate for the three forages.
Recent analyses use geometric morphometrics (GM), the quantitative study of shape and its variation, to examine aspects of the archaeological record. Our research builds on such applications to examine the organization of production by applying GM analysis to whole ceramic vessels from the Casas Grandes culture of northwest Mexico. We quantify variation in vessel shape and size and conclude that specialists made at least some of the Ramos and Babicora Polychromes, but that the other Casas Grandes ceramic types were generally made by nonspecialists. This bolsters arguments for Medio period (AD 1200 to 1450) specialized production above the household level but indicates that specialized production was limited to a subset of economically valuable goods. We further suggest some Ramos Polychrome was made by attached specialists associated with elites at Paquime, the religious center of the Medio period, whereas some Babicora Polychrome was made by independent specialists. The analysis contributes to three important anthropological topics: (1) the study of the Medio period Casas Grandes culture, and by extension the organization of production in mid-level hierarchically organized societies; (2) geometric morphometric analysis of archaeological collections; and (3) the Standardization Hypothesis and the relationship between artifact standardization and the organization of production.
The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.
Some previous accounts of visual search have emphasized covert attention at the expense of eye movements, and others have focused on eye movements while ignoring covert attention. Both selection mechanisms are likely to contribute to many searches, and a full account of search will probably need to explain how the two interact to find visual targets.