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This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710 Neisseria gonorrhoeae (GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains' phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla TEM plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml -1 ), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml -1 ), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml -1 ), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml -1 . This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea.

Objective- Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)-a robust cardiovascular risk marker-is impaired during this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate. Approach and Results- Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning ( P=0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon ( P≤0.01). Both systolic ( P=0.005) and diastolic blood pressure ( P=0.04) were rhythmic with peaks in the late afternoon. Conclusions- The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02202811.

Objective: To understand factors associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) acquisition and infection, we mapped public places (including personal service establishments, fitness centers, pools, schools, and daycares) visited by members of households affected by CA-MRSA skin and soft tissue infection., Results: From January 2012 to October 2015, households of children with CA-MRSA SSTI in metropolitan St. Louis were enrolled in the HOME: Household Observation of MRSA in the Environment study. Addresses of public places visited within 3 months of enrollment were reported by 671 participants and were analyzed using a geographic information system (GIS). The Nearest Neighbor Tool in ArcGIS assessed clustering of public places within the study region. Public places were significantly clustered within the study area compared to the expected distance between locations (p < 0.001). Additionally, one-third (48/150) of participating households visited at least one public place in common with other households. No significant relationship between participants visiting the public places within 3 months of enrollment and subsequent colonization or SSTI were found. Understanding community behavior is critical to informing public health initiatives to reduce the prevalence of CA-MRSA infections.

Melatonin research has primarily utilized blood as the source of samples, but there is now increasing interest in measuring levels of the hormone found in saliva. One impediment to this approach is that several melatonin assays involve a column-extraction step that can prove very time-consuming or even impossible when salivary samples are excessively viscous. We have treated 67 samples with dithiothreitol to enhance their passage through the column. Following this treatment, all samples passed freely through the columns. The minimum and maximum values measured were 0.7 - 50.0 pg/ml for the untreated controls and 1.0 - 51.9 pg/ml for the treated samples. The means (+/-SEM) for these groups were 9.5 +/- 1.6 and 9.9 +/- 1.7, respectively, and were not significantly different from one another as assessed by Student's t-test (P = 0.08). In summary, we have found that this technique permits us to obtain values on samples which would otherwise be unusable and that such treatment does not alter the melatonin values yielded by RIA analysis.