Superficial Femoral Artery Endothelial Responses to a Short-Term Altered Shear Rate Intervention in Healthy Men

In animal and in-vitro models, increased oscillatory shear stress characterized by increased retrograde shear-rate (SR) is associated with acutely decreased endothelial cell function. While previous research suggests a possible detrimental role of elevated retrograde SR on endothelial-function in the brachial artery in humans, little research has been conducted examining arteries in the leg. Examinations of altered shear pattern in the superficial femoral artery (SFA) are important, as this vessel is both prone to atherosclerosis and leg exercise is a common form of activity in humans. Seven healthy men participated; bilateral endothelial-function was assessed via flow-mediated-dilation (FMD) before and after 30-minute unilateral inflations of a thigh blood pressure cuff to either 75 mmHg or 100 mmHg on two separate visits. Inflation of the cuff induced increases in maximum anterograde (p<0.05), maximum retrograde (p<0.01), and oscillatory shear index (OSI) (p<0.001) in the cuffed leg at both inflation pressures. At 100 mmHg the increases in SR were larger in the retrograde than the anterograde direction evidenced by a decrease in mean SR (p<0.01). There was an acute decrease in relative FMD in the cuffed leg alone following inflation to both pressures. These results indicate that in the SFA, altered SR profiles incorporating increased retrograde and OSI influence the attenuation in FMD after a 30-minute unilateral thigh-cuff inflation intervention. Novel information highlighting the importance of OSI calculations and assessments of flow profiles add to current body of knowledge regarding the influence of changes in SR patterns on FMD. Findings from the current study may provide additional insight when designing strategies to combat impaired vascular function in the lower extremity where blood vessels are more prone to atherosclerosis in comparison to the upper extremity.     

Antifungal treatment: Recent advances in dermatology.

In this paper we discuss the published relevant mycology dermatological reports which appeared in 1997 and 1998. The aims of this review is to give an actual view on antifungal therapy with a critical discussion on the efficacy of antifungals.     

Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines.

Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.     

Mitochondrial genome size variation and restriction fragment length polymorphisms in threePhaseolus species

Summary Restriction patterns of mitochondrial DNA (mtDNA) from threePhaseolus species were examined to estimate their relative genome sizes and to determine the level of interspecific variability and relatedness. Three restriction endonucleases that produced relatively simple profiles were identified and used to determine the genome size of the three species. Taking into account fragment stoichiometries, the average estimates across enzymes were 456, 324, and 400 kb, respectively, forP. vulgaris, P. coccineus, andP. acutifolius. Restriction fragment length polymorphisms (RFLPs) differentiated the species when the mtDNAs were digested with seven endonucleases and hybridized with five cosmid clones covering ca. 200 kb of mtDNA sequences. Proportions of shared restriction fragments between every two species were computed as F-values and demonstrated thatP. vulgaris andP. coccineus are more related to each other than either is toP. acutifolius, and that the latter has a similar degree of relationship to the other two species.     

Modeling scenarios for mitigating outbreaks in congregate settings

The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings.     

Embryonic evidence uncovers convergent origins of laryngeal echolocation in bats

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Induction of ciliary orientation by matrix patterning and characterization of mucociliary transport

Impaired mucociliary clearance (MCC) is a key feature of many airway diseases, including asthma, bronchiectasis, chronic obstructive pulmonary disease, cystic fibrosis, and primary ciliary dyskinesia. To improve MCC and develop new treatments for these diseases requires a thorough understanding of how mucus concentration, mucus composition, and ciliary activity affect MCC, and how different therapeutics impact this process. Although differentiated cultures of human airway epithelial cells are useful for investigations of MCC, the extent of ciliary coordination in these cultures varies, and the mechanisms controlling ciliary orientation are not completely understood. By introducing a pattern of ridges and grooves into the underlying collagen substrate, we demonstrate for the first time, to our knowledge, that changes in the extracellular matrix can induce ciliary alignment. Remarkably, 90% of human airway epithelial cultures achieved continuous directional mucociliary transport (MCT) when grown on the patterned substrate. These cultures maintain transport for months, allowing carefully controlled investigations of MCC over a wide range of normal and pathological conditions. To characterize the system, we measured the transport of bovine submaxillary gland mucin (BSM) under several conditions. Transport of 5% BSM was significantly reduced compared with that of 2% BSM, and treatment of 5% BSM with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) reduced viscosity and increased the rate of MCT by approximately twofold. Addition of a small amount of high-molecular-weight DNA increased mucus viscosity and reduced MCT by ～75%, demonstrating that the composition of mucus, as well as the concentration, can have significant effects on MCT. Our results demonstrate that a simple patterning of the collagen substrate results in highly coordinated ciliated cultures that develop directional MCT, and can be used to investigate the mechanisms controlling the regulation of ciliary orientation. Furthermore, the results demonstrate that this method provides an improved system for studying the effects of mucus composition and therapeutic agents on MCC.