Characterization of an intelectin-1 (Itln1) knockout mouse model.

Intelectins are carbohydrate-binding proteins implicated in innate immunity and highly conserved across chordate evolution, including both ascidians and humans. Human intelectin-1 (ITLN1) is highly abundant within the intestinal mucosa and binds microbial but not host glycans. Genome-wide association studies identified SNPs in ITLN1 that are linked to susceptibility for Crohn's disease. Moreover, ITLN1 has been implicated in the pathophysiology of obesity and associated metabolic disease. To gain insight on biological activities of human ITLN1 in vivo, we developed a C57BL/6 mouse model genetically targeting the gene encoding the functional mouse ortholog. In wild-type C57BL/6 mice, both mRNA and protein analysis showed high expression of Itln1 in the small intestine, but manifold lower levels in colon and other extraintestinal tissues. Whereas intestinal expression of human ITLN1 localizes to goblet cells, our data confirm that mouse Itln1 is expressed in Paneth cells. Compared to wild-type littermate controls, mice homozygous for the Itln1 hypomorphic trapping allele had reduced expression levels of Itln1 expression (~10,000-fold). The knockout mice exhibited increased susceptibility in an acute model of experimentally induced colitis with 2% w/v dextran sulfate sodium (DSS). In a model of chronic colitis using a lower dose of DSS (1.5% w/v), which enabled a detailed view of disease activity across a protracted period, no differences were observed in body weight, fecal texture, hemoccult scores, food/water intake, or colon length at necropsy, but there was a statistically significant genotype over time effect for the combined fecal scores of disease activity. In model of diet-induced obesity, using two western-style diets, which varied in amounts of sugar (as sucrose) and saturated fat (as lard), mice with Itln1 expression ablated showed no increased susceptibility, in terms of weight gain, food intake, plasma markers of obesity compared to wildtype littermates. While the mouse genetic knockout model for Itln1 holds promise for elucidating physiological function(s) for mammalian intelectins, results reported here suggest that Itln1, a Paneth cell product in C57BL/6 mice, likely plays a minor role in the pathophysiology of chemically induced colitis or diet-induced obesity.

Blue light phones as potential locations for deploying public access naloxone kits on a college campus.

Objective Opioid use and the risk of opioid overdose are growing public health concerns for college-aged adults. Naloxone can temporarily reverse opioid overdoses, but only if easily accessible. On most college campuses, "blue light" phones (BLPs)-call boxes topped with a blue light-offer visible access to emergency services. We hypothesized that BLPs would provide potential naloxone access points. Participants: A major university campus in Los Angeles, CA. Methods: BLP locations were obtained using Google Maps, and the area of campus within a set distance to each BLP calculated. To model effects of loss or diversion, we simulated the random loss of various BLPs. Results: Placing naloxone kits at the 59 BLP locations could provide access within 100 m to 91.5% of the campus. With loss of half of the BLPs, campus access remained above 70%. Conclusions: Naloxone at BLP locations could be accessed from almost all campus areas.

Investigating the use of ultrasonography for the antenatal diagnosis of structural congenital anomalies in low-income and middle-income countries: a systematic review.

BACKGROUND: Congenital anomalies are the fifth leading cause of under-5 mortality globally. The greatest burden is faced by those in low/middle-income countries (LMICs), where over 95% of deaths occur. Many of these deaths may be preventable through antenatal diagnosis and early intervention. This systematic literature review investigates the use of antenatal ultrasound to diagnose congenital anomalies and improve the health outcomes of infants in LMICs. METHODS: A systematic literature review was conducted using three search strings: (1) structural congenital anomalies; (2) LMICs; and (3) antenatal diagnosis. The search was conducted on the following databases: Medline, Embase, PubMed and the Cochrane Library. Title, abstract and full-text screening was undertaken in duplicate by two reviewers independently. Consensus among the wider authorship was sought for discrepancies. The primary analysis focused on the availability and effectiveness of antenatal ultrasound for diagnosing structural congenital anomalies. Secondary outcomes included neonatal morbidity and mortality, termination rates, referral rates for further antenatal care and training level of the ultrasonographer. Relevant policy data were sought. RESULTS: The search produced 4062 articles; 97 were included in the review. The median percentage of women receiving an antenatal ultrasound examination was 50.0% in African studies and 90.7% in Asian studies (range 6.8%-98.8%). Median detection rates were: 16.7% Africa, 34.3% South America, 34.7% Asia and 47.3% Europe (range 0%-100%). The training level of the ultrasound provider may affect detection rates. Four articles compared morbidity and mortality outcomes, with inconclusive results. Significant variations in termination rates were found (0%-98.3%). No articles addressed referral rates. CONCLUSION: Antenatal detection of congenital anomalies remains highly variable across LMICs and is particularly low in sub-Saharan Africa. Further research is required to investigate the role of antenatal diagnosis for improving survival from congenital anomalies in LMICs. PROSPERO REGISTRATION NUMBER: CRD42019105620.

Investigating the use of ultrasonography for the antenatal diagnosis of structural congenital anomalies in low-income and middle-income countries: systematic review protocol.

INTRODUCTION: Congenital anomalies are the fifth leading cause of mortality in children under 5 years globally. The greatest burden is faced by those in developing countries, where over 95% of deaths occur. Many of these deaths may have been preventable through antenatal diagnosis and early intervention. This study aims to conduct a systematic review that investigates the use of antenatal ultrasound to diagnose congenital anomalies and improve the health outcomes of infants in low-income and middle-income countries (LMICs). METHODS AND ANALYSIS: A systematic literature review will be conducted using three search strings: (1) structural congenital anomalies, (2) LMICs and (3) antenatal diagnosis. Four electronic databases will be searched: MEDLINE, Embase, PubMed and the Cochrane Library. Title, abstract and full-text screening will be undertaken in duplicate by two reviewers independently using Covidence. Consensus will be sought from the wider authorship for discrepancies. Data extraction will be undertaken by the principal investigator. The primary analysis will focus on the availability and effectiveness of antenatal ultrasound for structural congenital anomalies. Secondary outcomes will include neonatal morbidity and mortality, termination rates and referral rates for further antenatal care. Descriptive statistics and a narrative synthesis will be included in the final report. The methodological quality of the included studies will be evaluated using the Cochrane-approved Risk of Bias for Non-Randomised Studies of Intervention and Risk of Bias in Randomised Trials V.2.0 tools. ETHICS AND DISSEMINATION: Ethical approval is not required for conducting the systematic review as there will be no direct collection of data from individuals. The results will be submitted for publication in a scientific journal and presented internationally. CONCLUSION: This is the first study, to our knowledge, to systematically review current literature on the use of antenatal ultrasound for the detection of congenital anomalies in LMICs. This is vital to define current practice, highlight global disparities and evaluate effects on health outcomes for infants in low-resource settings. PROSPERO REGISTRATION NUMBER: CRD42019105620.

An Experimental Approach to Rigorously Assess Paneth Cell α-Defensin (Defa) mRNA Expression in C57BL/6 Mice.

Abundant evidence from many laboratories supports the premise that α-defensin peptides secreted from Paneth cells are key mediators of host-microbe interactions in the small intestine that contribute to host defense and homeostasis. α-defensins are among the most highly expressed antimicrobial peptides at this mucosal surface in many mammals, including humans and mice; however, there is striking variation among species in the number and primary structure of α-defensin paralogs. Studies of these biomolecules in vivo are further complicated by striking variations between laboratory mouse strains. Herein, we report an experimental approach to determine with precision and specificity expression levels of α-defensin (Defa) mRNA in the small intestine of C57BL/6 mice through an optimized set of oligonucleotide primers for qRT-PCR assays and cloned cDNA plasmids corresponding to the Defa paralogs. This approach demonstrated marked differences in α-defensin expression in C57BL/6 mice with respect to proximal/distal anatomical location and developmental stage, which have not been described previously. These data underscore the importance of careful attention to method (primer choice, proximal vs. distal location, and developmental stage) in analysis of antimicrobial peptide expression and their impact.