Simulations suggest a constrictive force is required for Gram-negative bacterial cell division

To divide, Gram-negative bacterial cells must remodel cell wall at the division site. It remains debated, however, whether this cell wall remodeling alone can drive membrane constriction, or if a constrictive force from the tubulin homolog FtsZ is required. Previously, we constructed software (REMODELER 1) to simulate cell wall remodeling during growth. Here, we expanded this software to explore cell wall division (REMODELER 2). We found that simply organizing cell wall synthesis complexes at the midcell is not sufficient to cause invagination, even with the implementation of a make-before-break mechanism, in which new hoops of cell wall are made inside the existing hoops before bonds are cleaved. Division can occur, however, when a constrictive force brings the midcell into a compressed state before new hoops of relaxed cell wall are incorporated between existing hoops. Adding a make-before-break mechanism drives division with a smaller constrictive force sufficient to bring the midcell into a relaxed, but not necessarily compressed, state

33356 A multinational chart review to examine gastrointestinal symptoms and their management in patients treated with apremilast for plaque psoriasis

Background: Diarrhea and nausea are the most common adverse events observed in phase 3 clinical trials and real-world studies of apremilast, an oral phosphodiesterase-4 inhibitor indicated for moderate-to-severe plaque psoriasis. Methods: A retrospective chart review was conducted between June and November 2020 in the United States (US) and France among patients with moderate psoriasis experiencing gastrointestinal (GI) symptoms within 3 months of initiating apremilast. Results: Dermatologists in US (200) and in France (52) abstracted patient charts (US: 494, France: 128). The following GI symptoms were reported: ‒diarrhea (US: 67% [331/494]; France: 76% [97/128]) with median time from onset to resolution/improvement of 26 days (US) and 21 days (France) ‒nausea (US: 52% [255/494]; France: 34% [44/128]) with median time from onset to resolution/improvement of 21 days (US) and 24 days (France). Management strategies for diarrhea included pharmacologic (loperamide/bismuth subsalicylate/racecadotril) with or without nonpharmacologic (dietary modifications, taking with food)/fiber (US: 30% [99/331], France: 41% [40/97]) and nonpharmacologic only (US: 32% [105/331], France: 27% [26/97]). Management strategies for nausea included pharmacologic (diphenhydramine/metoclopramide/metopimazine) with or without nonpharmacologic (dietary modifications, taking with food, avoidance of vigorous activity) (US: 5% [14/255], France: 30% [13/44]) and nonpharmacologic only (US: 58% [147/255], France: 36% [16/44]). Resolution/improvement of GI symptoms was observed in patients who used pharmacologic strategies and nonpharmacologic strategies. Conclusions: Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Importance of data structure in comparing two dimension reduction methods for classification of microarray gene expression data

BACKGROUND: With the advance of microarray technology, several methods for gene classification and prognosis have been already designed. However, under various denominations, some of these methods have similar approaches. This study evaluates the influence of gene expression variance structure on the performance of methods that describe the relationship between gene expression levels and a given phenotype through projection of data onto discriminant axes. RESULTS: We compared Between-Group Analysis and Discriminant Analysis (with prior dimension reduction through Partial Least Squares or Principal Components Analysis). A geometric approach showed that these two methods are strongly related, but differ in the way they handle data structure. Yet, data structure helps understanding the predictive efficiency of these methods. Three main structure situations may be identified. When the clusters of points are clearly split, both methods perform equally well. When the clusters superpose, both methods fail to give interesting predictions. In intermediate situations, the configuration of the clusters of points has to be handled by the projection to improve prediction. For this, we recommend Discriminant Analysis. Besides, an innovative way of simulation generated the three main structures by modelling different partitions of the whole variance into within-group and between-group variances. These simulated datasets were used in complement to some well-known public datasets to investigate the methods behaviour in a large diversity of structure situations. To examine the structure of a dataset before analysis and preselect an a priori appropriate method for its analysis, we proposed a two-graph preliminary visualization tool: plotting patients on the Between-Group Analysis discriminant axis (x-axis) and on the first and the second within-group Principal Components Analysis component (y-axis), respectively. CONCLUSION: Discriminant Analysis outperformed Between-Group Analysis because it allows for the dataset structure. An a priori knowledge of that structure may guide the choice of the analysis method. Simulated datasets with known properties are valuable to assess and compare the performance of analysis methods, then implementation on real datasets checks and validates the results. Thus, we warn against the use of unchallenging datasets for method comparison, such as the Golub dataset, because their structure is such that any method would be efficient

Toward an understanding of tourists’ authentic heritage experiences: Evidence from Hong Kong

Authenticity in tourism has been a topic of discussion since the 1960s, but the concept is still to be fully developed. This study focuses on tourists’ perceptions of authenticity, and in particular how they evaluate authentic heritage experiences. The appearance and physical settings of attractions were found to be the initial and most important indicators of authentic or inauthentic experiences. Other criteria for assessing the authenticity of heritage experiences include the presence of local culture and customs, constructed elements, commodification, and atmosphere

Simulations suggest a constrictive force is required for Gram-negative bacterial cell division

To divide, Gram-negative bacterial cells must remodel cell wall at the division site. It remains debated, however, whether this cell wall remodeling alone can drive membrane constriction, or if a constrictive force from the tubulin homolog FtsZ is required. Previously, we constructed software (REMODELER 1) to simulate cell wall remodeling during growth. Here, we expanded this software to explore cell wall division (REMODELER 2). We found that simply organizing cell wall synthesis complexes at the midcell is not sufficient to cause invagination, even with the implementation of a make-before-break mechanism, in which new hoops of cell wall are made inside the existing hoops before bonds are cleaved. Division can occur, however, when a constrictive force brings the midcell into a compressed state before new hoops of relaxed cell wall are incorporated between existing hoops. Adding a make-before-break mechanism drives division with a smaller constrictive force sufficient to bring the midcell into a relaxed, but not necessarily compressed, state

The impact of low input DNA on the reliability of DNA methylation as measured by the Illumina Infinium MethylationEPIC BeadChip

DNA methylation (DNAm) is commonly assayed using the Illumina Infinium MethylationEPIC BeadChip, but there is currently little published evidence to define the lower limits of the amount of DNA that can be used whilst preserving data quality. Such evidence is valuable for analyses utilizing precious or limited DNA sources. We used a single pooled sample of DNA in quadruplicate at three dilutions to define replicability and noise, and an independent population dataset of 328 individuals (from a community-based study including US-born non-Hispanic Black and white persons) to assess the impact of total DNA input on the quality of data generated using the Illumina Infinium MethylationEPIC BeadChip. We found that data are less reliable and more noisy as DNA input decreases to 40ng, with clear reductions in data quality; and that low DNA input is associated with a reduction in power to detect EWAS associations, requiring larger sample sizes. We conclude that DNA input as low as 40ng can be used with the Illumina Infinium MethylationEPIC BeadChip, provided quality checks and sensitivity analyses are undertaken

Evolution of Highly Pathogenic H5N1 Avian Influenza Viruses in Vietnam between 2001 and 2007

Highly pathogenic avian influenza (HPAI) H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA), continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA) and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes

The prevalence of pain and disability one year post fracture of the distal radius in a UK population: A cross sectional survey

<p>Abstract</p> <p>Background</p> <p>A fracture of the distal radius is a commonly occurring fracture and accounts for a third of all fractures in the elderly. Thus far, one year estimates of pain and disability following a fracture of the distal radius have been reported on Canadian populations. The primary aim of this study is to investigate the prevalence of pain and disability in a UK population one year post fracture of the distal radius.</p> <p>Methods</p> <p>A cross-sectional survey was undertaken, of all subjects suffering a fracture of the distal radius between October 2005 and February 2006 in Nottingham, UK. Primary outcomes used were the VAS for pain and the DASH for disability. Prevalence of pain and disability were calculated and odds ratios presented for associations between demographics, pain and disability.</p> <p>Results</p> <p>93/264 (35%) subjects responded to the questionnaire. 6 subjects did not fulfill the inclusion criteria and were excluded from further analysis. 11% of subjects reported moderate to very severe pain. 16% of subjects reported moderate to very severe disability. Statistically significant associations were found between pain medication usage for the wrist fracture and moderate to very severe pain (OR 11.20, 95% CI 2.05 – 61.23). Moderate to very severe disability was associated with older age (OR 6.53, 95%CI 1.65 – 25.90) and pain medication usage for the wrist fracture (OR 4.75, 95% CI 1.38 – 16.37). Working was associated with a reduction in risk of moderate to very severe disability (OR 0.14, 95% CI 0.03 – 0.67).</p> <p>Conclusion</p> <p>This study demonstrates that there are a small proportion of patients who are still suffering moderate to very severe pain and disability one year post fracture of the distal radius. The study also demonstrates that there are significant associations between characteristics of the patients and the level of pain and disability. This highlights the need for further research into the most appropriate management of these patients in order to reduce this burden of pain and disability, particularly as this is a predominantly elderly patient group.</p

Chinese heritage tourists to heritage sites: what are the effects of heritage motivation and perceived authenticity on satisfaction?

Much of the literature on authenticity is Western-centric, while little work addresses the concept in the Asian environment. The literature relating to authenticity from Asian tourists’ point of view is even underdeveloped. This study therefore aims to fill the knowledge gap by investigating Chinese tourists’ perspective of authenticity. It also examines tourists’ perceived authenticity as a multi-dimensional construct in a consumer-based model, the relationship with heritage motivation and tourist satisfaction. Findings indicate that Chinese tourists’ perceptions of authenticity are closely related to objective and constructive authenticity. The study demonstrates that heritage motivation has a significant positive influence on perceived authenticity and that perceived authenticity has a strong ability to predict tourist satisfaction