Intraspecies warfare restricts strain coexistence in human skin microbiomes.

Determining why only a fraction of encountered or applied bacterial strains engraft in a given person's microbiome is crucial for understanding and engineering these communities1. Previous work has established that metabolism can determine colonization success in vivo2-4, but relevance of bacterial warfare in preventing engraftment has been less explored. Here, we demonstrate that intraspecies warfare presents a significant barrier to strain transmission in the skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis cultured from eighteen human subjects from six families. We find that intraspecies antagonisms are abundant; these interactions are mechanistically diverse, independent of the relatedness between strains, and consistent with rapid evolution via horizontal gene transfer. Ability to antagonize more strains is associated with reaching a higher fraction of the on-person S. epidermidis community. Moreover, antagonisms are significantly depleted among strains residing on the same person relative to random assemblages. Two notable exceptions, in which bacteria evolved to become sensitive to antimicrobials found on the same host, are explained by mutations that provide phage resistance, contextualizing the importance of warfare among other lethal selective pressures. Taken together, our results emphasize that accounting for intraspecies bacterial warfare is essential to the design of long-lasting probiotic therapeutics.

Understanding the sleep-pain relationship in patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition with critical symptoms of urinary urgency and frequency, persistent bladder-related pain, and reduced quality of life. Poor-quality sleep can lead to significant disturbances in daily life and increased pain in IC/BPS patients. Resilience, depressive symptoms, and pain catastrophizing have univariate associations with sleep and pain in IC/BPS, suggesting they may be mechanisms in this sleep and pain relationship. METHODS: This online study recruited patients self-reporting a diagnosis of IC/BPS through support groups, social media posts (Facebook, Reddit, and Instagram), and urology clinic advertisements. Participants completed questionnaires on demographics, urologic symptoms, pain, pain catastrophizing, depressive symptoms, and resilience. Only those participants who met the RAND Interstitial Cystitis Epidemiology (RICE) criteria for IC/BPS diagnosis were included. A multiple mediation model was first examined, followed by a serial mediation model. RESULTS: Seventy-four participants (Mage= 47.0, standard deviation [SD ] 16.7, range 18-83 years) met inclusion criteria. A multiple mediation model showed greater sleep disturbance was associated with greater pain severity through depressive symptoms and pain catastrophizing, but not resilience (b=0.79, bootSE =0.26, bootCI [0.33, 1.35]). A serial mediation showed that the sleep-to-pain relationship had a significant indirect effect through pain catastrophizing and depressive symptoms (b=0.78, bootSE =0.26, bootCI [0.35, 1.32]). CONCLUSIONS: Findings suggest depressive symptoms and pain catastrophizing may be important psychosocial mechanisms in the sleep-to-pain relationship. These results help guide future sleep and pain research in IC/BPS and aid in developing and refining treatments.

Highly-resolved within-species dynamics in the human facial skin microbiome.

Human facial skin microbiomes (FSMs) on adults are dominated by just two bacterial species, Cutibacterium acnes and Staphylococcus epidermidis. Underlying this apparent simplicity, each FSM harbors multiple strains of both species whose assembly dynamics on individuals are unknown. Here, we use 4,055 isolate genomes and 360 metagenomes to trace the dynamics of strains on individuals and their transmission. Strains are shared amongst family members of all ages, but each individual harbors unique strain consortia. Strain stability changes upon formation of the adult-type FSM: S. epidermidis lineage turnover slows, and the rate of C. acnes colonization increases before stabilizing, suggesting this transitional window could facilitate engraftment of therapeutic strains. Our work reveals previously undetectable community dynamics and informs the design of therapeutic interventions.

Anatomy promotes neutral coexistence of strains in the human skin microbiome.

What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin. We reconstruct on-person evolution and migration using whole-genome sequencing of C. acnes colonies acquired from healthy subjects, including from individual skin pores, and find considerable spatial structure at the level of pores. Although lineages (sets of colonies separated by <100 mutations) with in vitro fitness differences coexist within centimeter-scale regions, each pore is dominated by a single lineage. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity. We therefore propose that pore anatomy imposes random single-cell bottlenecks; the resulting population fragmentation reduces competition and promotes coexistence. Our findings suggest that therapeutic interventions involving pore-dwelling species might focus on removing resident populations over optimizing probiotic fitness.

Fever and production of cytokines in response to repeated injections of muramyl dipeptide in guinea-pigs.

Fever and systemic plasma levels of the cytokines tumour necrosis factor alpha (TNF) and interleukin-6 (IL-6) were measured in guinea-pigs in response to single or repeated intramuscular injections of 100 micrograms/kg muramyl-dipeptide (MDP). In a pilot study (experiment 1), MDP-induced fever was monitored for 8 h. The first fever phase 90-360 min after injection of MDP was followed by the second phase which continued beyond the duration of this experiment. High circulating levels of TNF and IL-6 were detected just before body core temperature started to rise. Within the next 90 min TNF declined again by more than 90% while IL-6 remained elevated. In experiment 2, the effects of repeated injections of MDP (5 times at intervals of 3 days) on the same parameters were investigated. In this paradigm, the febrile response started earlier (60 min after injection) and the first phase of fever remained manifest until 360 min after injection, while the late phase, measured 360-720 min after injection, was attenuated. Circulating, bioactive TNF and IL-6, measured 60 and 180 min after MDP was administered, were the same in response to the first, third, and fifth injection. In experiment 3, the influence of five repeated MDP injections on the abdominal temperature was measured for 22 h, and circulating cytokines were analysed before (360 min after injection) and during (480 min after injection) the late phase of MDP-induced fever. The late phase of MDP-induced fever 7-22 h after injection was attenuated in response to the second and further administrations of this pyrogen. At 6 h after the first, third, and fifth administration of MDP, only traces of TNF alpha were measured, 2 h later no bioactive TNF was detected at all. At these times also IL-6 declined again, compared with the activity of this cytokine measured during the early phase of MDP fever, but was still present in elevated amounts. Compared with the values measured in response to the third and fifth injections of MDP, circulating IL-6 was higher 360 min and 480 min after the first injection. It remains speculative whether the longer duration of elevated IL-6 in plasma is related to the development of the long-lasting, late phase of MDP-induced fever, which was only observed after the first of five repeated injections of MDP at intervals of 3 days.

Comparison of attitudes of regular and adapted physical educators toward disabled individuals.

The Attitudes Toward Disabled Persons Scale (Form B) and a ranking survey of 10 disabling conditions were administered to 38 physical education teachers and 47 adapted physical education teachers. Both groups of teachers' attitudes toward the disabled were below the scale median. Both groups of teachers were more accepting of individuals with physical disabilities such as, amputee, harelip, and epilepsy, than individuals who were mentally retarded, cerebral palsied, and emotionally disturbed.

Are complex multiple-choice options more difficult and discriminating than conventional multiple-choice options?

Differences in item difficulty between conventional and complex multiple-choice (M-C) items measuring objectives written at the six levels of the cognitive domain and three content areas within a basic health professions subject matter area were investigated. Conventional and complex M-C items were also compared in terms of item discrimination. Five hundred fifteen senior baccalaureate nursing students randomly responded to one of two packages of 18 one-item pharmacology achievement tests. Items in the two packages were matched in all respects except for the type of option. A 2 X 3 X 6 repeated measures ANCOVA with method of pharmacology as the covariate showed a statistically significant (p less than .01) interaction of option X content X cognitive level. Scheffé tests revealed that complex items were more difficult than conventional option items at the knowledge level only across all content areas investigated. No statistically significant differences were found between the two option types discriminating ability. Results of this research question the validity of the assumption that complex items are more difficult and discriminating than conventional M-C items.

Iron Deficiency in Adolescent Cross-Country Runners.

In brief: Results of screening for iron deficiency in 18 female adolescent runners and two case reports of iron deficiency are described. Eleven of eighteen girls had ferritin values of less than 20 ng· ml(-2) before treatment with oral ferrous sulfate. The case reports show that the two girls with iron deficiency anemia improved their performances after their anemia was treated. Serum ferritin determinations were a sensitive indicator of iron deficiency. Only two cases would have been diagnosed if the usual criteria for iron deficiency anemia were used. Close observation of this age-group for iron deficiency seems warranted.

Discriminant analysis to predict graduation--nongraduation in a master's degree program in nursing.

Discriminant analysis was used to predict graduation and two categories of nongraduation from readily available admissions data at the University of Kansas nursing master's degree program. The traditional admissions indices, baccalaureate grade point average (GPA) and Graduate Record Examination (GRE)-verbal and -quantitative scores, were used as predictors. Criterion categories were composed of 102 graduates, 103 individuals who dropped out of the program, and 65 individuals who were not accepted. The first discriminant function was, chi 2 (6) = 87.567, p less than .0001, and extracted 98% of the variance of the discriminant space. Follow-up procedures using one-way ANOVA's and Scheffé multiple comparisons indicated that the baccalaureate GPA and GRE-verbal and -quantitative scores independently differentiated the graduate and dropout groups from the not-accepted group at a statistically significant level (p less than .05). Practical significance of the independent contribution of these variables to group differentiation, as measured by omega 2 was 22% for the baccalaureate GPA, 13% for the GRE-verbal scores, and 10% for the GRE-quantitative scores. Implications for future research are discussed.