Resource use among patients with diabetes, diabetic neuropathy, or diabetes with depression

BACKGROUND: Diabetes is often associated with complications and comorbidities. The purpose of this research is to compare medical resources used by patients with the following diagnoses: diabetes mellitus (DM), diabetic neuropathy (DN), and diabetes mellitus combined with comorbid depression (DD). METHODS: Adult patients who were diagnosed with DM, DN, or DD were included in the study. There were 55,972 patients in the DM cohort, 2,146 in the DN, and 2,379 in the DD. P values for comparisons between the three mutually exclusive cohorts were conducted using the Tukey-Kramer method. Cost comparisons among the cohorts were conducted using a stepwise multivariate regression that controlled for patient characteristics and comorbid conditions. RESULTS: Individuals in the DM or DN cohorts were generally more likely to use antidiabetic medications than patients in the DD group. Those diagnosed with DN or DD generally used more pain medications than individuals in the DM cohort. The DM cohort had significantly lower diabetes-related total medical costs ($1,297 v$5,125, p < 0.0001) and lower total medical costs ($4,819 v$24,765, p < 0.0001) than the DN cohort. The DM cohort also had significantly lower diabetes-related total medical costs ($1,297 v$3,264, p < 0.0001) as well as significantly lower total medical costs ($4,819 v$19,298, p < 0.0001) than the DD cohort. CONCLUSION: Results from this study indicated significant differences in demographic characteristics, comorbidities, and medication use among individuals diagnosed with DM, DN, or DD. These differences translated into significant cost differences. Patients diagnosed with DN or DD had higher diabetes-related costs than patients diagnosed with DM

First record of Cantharellus minor from Vietnam with identification support from a combination of nrLSU and nrSSU phylogenetic analysis

Background: A previously identified sample XC02, which was collected from a pine forest (Pinus kesiya Royle ex Gordon), in Xuan Tho Commune, Da Lat, Lam Dong Province, Vietnam, was identified as Cantharellus minor based on morphology and nrLSU phylogeny analysis. Sequence analysis of multiple genes are becoming more and more common for phylogenetic analysis of mushrooms.Method: Total DNA was isolated from sample XC02. The primer NS1, NS4 were applied to amplify the target gene the nuclear ribosomal small subunit DNA (nrSSU). For phylogenetic analysis, individual and concatenated datasets (nrSSU and nrLSU-nrSSU) were constructed. Phylogenetic tree was constructed with MEGA 6.0 with a 1000 replicate bootstrap based on the neighbor joining, maximum likelihood, maximum parsimony method.  Results: A concatenated dataset containing a total of 14 sequences from Cantharellus, Craterellus (Cantharellaceae, Canthraellales) and Hydnum (Hydnaceae, Cantharellales) were constructed. For the specimen XC02, the phylogenies based on the first, second, and third datasets (nrLSU, nrSSU, and nrLSU-nrSSU) and the morphological analysis, reported in our previous study, strongly confirmed the identity of XC02 as Cantharellus minor.Conclusion: The combination between the morphological analysis and phylogenetic analysis is confirmed as the best approach for the identification of Cantharellus and other mushroom species that we collected in the Central Highlands, Vietnam.Keywords: nrLSU; Cantharellus, Cantharellus minor; nrSSU; nrLSU; phylogeny analysis; Vietna

Интеллектуальная радиосеть с нечеткой конфигурацией

В статье обсуждаются возможности применения одноранговой радиосети стандарта IEEE 802.15.4 (ZigBee) диапазона 2,4 ГГц для работы системы, состоящей из группы малогабаритных мобильных роботов и одного командного пункта. Основная задача группы роботов – проведение разведки во время спасательных операций после техногенных и природных катастроф и аварий. Для сохранения управляемости отдельными роботами и системой в целом предлагается повысить «интеллект» системы связи за счет гибкой маршрутизации каналов между командным пунктом и конкретным мобильным роботом с тем, чтобы иметь систему с автоматическим, интеллектуальным восстановлением канала обмена данных.У статті обговорюються можливості застосування однорангової радіомережі стандарту ІЕЕ 802.15.4 (ZigBee) діапазону 2,4 Ггу для роботи системи, що складається з групи малогабаритних мобільних роботів та одного командного пункту. Основна задача групи роботів – проведення розвідки під час рятувальних операцій після техногенних та природних катастроф і аварій. Для збереження керованості окремими ротами та системою в цілому пропонується підвищити інтелект системи зв’язку за рахунок гнучкої маршрутитизації каналів між командним пунктом та конкретним мобільним роботом з тим, щоб мати систему з автоматичним, інтелектуальним відновлюванням каналу обміну даних.In the article the possibilities of application peer-to-peer radio networks of standard IEEE 802.15.4 (ZigBee) a range of 2,4 GHz for work of the system consisting of small-sized mobile robots group and one command point are discussed. The primary goal of group of robots – is carrying out of investigation during rescue operations after technogenic and natural accidents and failures. For controllability preservation by separate robots and system as a whole, it is offered to raise “intelligence” of a communication system at the expense of flexible routeing of channels between command point and the concrete mobile robot to have system with automatic, intellectual restoration of the channel of data exchange

Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human Patient-Derived IgE Antibodies.

This is the accepted, uncopyedited version of the manuscript. The definitive version was published in The Journal of Immunology August 28, 2019, ji1900509; DOI: https://doi.org/10.4049/jimmunol.1900509Originally published in The Journal of Immunology. Bucaite G, Kang-Pettinger T, Moreira J, et al. Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human Patient-Derived IgE Antibodies. J Immunol. 2019;203(7):1693-1700. doi:10.4049/jimmunol.1900509 The American Association of Immunologists, Inc.An allergic reaction is rapidly generated when allergens bind and cross-link IgE bound to its receptor FcεRI on effector cells, resulting in cell degranulation and release of proinflammatory mediators. The extent of effector cell activation is linked to allergen affinity, oligomeric state, valency, and spacing of IgE-binding epitopes on the allergen. Whereas most of these observations come from studies using synthetic allergens, in this study we have used Timothy grass pollen allergen Phl p 7 and birch pollen allergen Bet v 4 to study these effects. Despite the high homology of these polcalcin family allergens, Phl p 7 and Bet v 4 display different binding characteristics toward two human patient-derived polcalcin-specific IgE Abs. We have used native polcalcin dimers and engineered multimeric allergens to test the effects of affinity and oligomeric state on IgE binding and effector cell activation. Our results indicate that polcalcin multimers are required to stimulate high levels of effector cell degranulation when using the humanized RBL-SX38 cell model and that multivalency can overcome the need for high-affinity interactions.This work was supported by Medical Research Council Grant G1100090. G.B. was supported by a studentship from the King’s Bioscience Institute and by the Guy’s and St. Thomas’ Charity Prize Ph.D. Program in Biomedical and Translational Science. We acknowledge the support of the Centre for Biomolecular Spectroscopy, King’s College London, established with a Capital Award from the Wellcome Trust (Grant 085944)

The Bacterial Fimbrial Tip Acts as a Mechanical Force Sensor

The subunits that constitute the bacterial adhesive complex located at the tip of the fimbria form a hook-chain that acts as a rapid force-sensitive anchor at high flow

Structure of a Chaperone-Usher Pilus reveals the molecular basis of rod uncoiling

Types 1 and P pili are prototypical bacterial cell-surface appendages playing essential roles in mediating adhesion of bacteria to the urinary tract. These pili, assembled by the chaperone-usher pathway, are polymers of pilus subunits assembling into two parts: a thin, short tip fibrillum at the top, mounted on a long pilus rod. The rod adopts a helical quaternary structure and is thought to play essential roles: its formation may drive pilus extrusion by preventing backsliding of the nascent growing pilus within the secretion pore; the rod also has striking spring-like properties, being able to uncoil and recoil depending on the intensity of shear forces generated by urine flow. Here, we present an atomic model of the P pilus generated from a 3.8 Å resolution cryo-electron microscopy reconstruction. This structure provides the molecular basis for the rod’s remarkable mechanical properties and illuminates its role in pilus secretion

Uropathogenic Escherichia coli P and Type 1 Fimbriae Act in Synergy in a Living Host to Facilitate Renal Colonization Leading to Nephron Obstruction

The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here we used multiphoton microscopy-based live animal imaging, combined with advanced surgical procedures, to investigate the role of uropathogenic Escherichia coli (UPEC) attachment organelles P and Type 1 fimbriae in renal bacterial infection. A GFP+ expressing variant of UPEC strain CFT073 and genetically well-defined isogenic mutants were microinfused into rat glomerulus or proximal tubules. Within 2 h bacteria colonized along the flat squamous epithelium of the Bowman's capsule despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow in the proximal tubule, the P and Type 1 fimbriae appeared to act in synergy to promote colonization. P fimbriae enhanced early colonization of the tubular epithelium, while Type 1 fimbriae mediated colonization of the center of the tubule via a mechanism believed to involve inter-bacterial binding and biofilm formation. The heterogeneous bacterial community within the tubule subsequently affected renal filtration leading to total obstruction of the nephron within 8 h. Our results reveal the importance of physiological factors such as filtration in determining bacterial colonization patterns, and demonstrate that the spatial resolution of an infectious niche can be as small as the center, or periphery, of a tubule lumen. Furthermore, our data show how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis

Genetic characterization of 2008 reassortant influenza A virus (H5N1), Thailand

In January and November 2008, outbreaks of avian influenza have been reported in 4 provinces of Thailand. Eight Influenza A H5N1 viruses were recovered from these 2008 AI outbreaks and comprehensively characterized and analyzed for nucleotide identity, genetic relatedness, virulence determinants, and possible sites of reassortment. The results show that the 2008 H5N1 viruses displayed genetic drift characteristics (less than 3% genetic differences), as commonly found in influenza A viruses. Based on phylogenetic analysis, clade 1 viruses in Thailand were divided into 3 distinct branches (subclades 1, 1.1 and 1.2). Six out of 8 H5N1 isolates have been identified as reassorted H5N1 viruses, while other isolates belong to an original H5N1 clade. These viruses have undergone inter-lineage reassortment between subclades 1.1 and 1.2 and thus represent new reassorted 2008 H5N1 viruses. The reassorted viruses have acquired gene segments from H5N1, subclade 1.1 (PA, HA, NP and M) and subclade 1.2 (PB2, PB1, NA and NS) in Thailand. Bootscan analysis of concatenated whole genome sequences of the 2008 H5N1 viruses supported the reassortment sites between subclade 1.1 and 1.2 viruses. Based on estimating of the time of the most recent common ancestors of the 2008 H5N1 viruses, the potential point of genetic reassortment of the viruses could be traced back to 2006. Genetic analysis of the 2008 H5N1 viruses has shown that most virulence determinants in all 8 genes of the viruses have remained unchanged. In summary, two predominant H5N1 lineages were circulating in 2008. The original CUK2-like lineage mainly circulated in central Thailand and the reassorted lineage (subclades 1.1 and 1.2) predominantly circulated in lower-north Thailand. To prevent new reassortment, emphasis should be put on prevention of H5N1 viruses circulating in high risk areas. In addition, surveillance and whole genome sequencing of H5N1 viruses should be routinely performed for monitoring the genetic drift of the virus and new reassorted strains, especially in light of potential reassortment between avian and mammalian H5N1 viruses

Structural Basis for Type VI Secretion Effector Recognition by a Cognate Immunity Protein

The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, type VI secretion exported 1–3 (Tse1–3), to recipient Gram-negative cells. The Tse2 protein is a cytoplasmic effector that acts as a potent inhibitor of target cell proliferation, thus providing a pronounced fitness advantage for P. aeruginosa donor cells. P. aeruginosa utilizes a dedicated immunity protein, type VI secretion immunity 2 (Tsi2), to protect against endogenous and intercellularly-transferred Tse2. Here we show that Tse2 delivered by the T6SS efficiently induces quiescence, not death, within recipient cells. We demonstrate that despite direct interaction of Tsi2 and Tse2 in the cytoplasm, Tsi2 is dispensable for targeting the toxin to the secretory apparatus. To gain insights into the molecular basis of Tse2 immunity, we solved the 1.00 Å X-ray crystal structure of Tsi2. The structure shows that Tsi2 assembles as a dimer that does not resemble previously characterized immunity or antitoxin proteins. A genetic screen for Tsi2 mutants deficient in Tse2 interaction revealed an acidic patch distal to the Tsi2 homodimer interface that mediates toxin interaction and immunity. Consistent with this finding, we observed that destabilization of the Tsi2 dimer does not impact Tse2 interaction. The molecular insights into Tsi2 structure and function garnered from this study shed light on the mechanisms of T6 effector secretion, and indicate that the Tse2–Tsi2 effector–immunity pair has features distinguishing it from previously characterized toxin–immunity and toxin–antitoxin systems

Patient characteristics, comorbidities, and medication use for children with ADHD with and without a co-occurring reading disorder: A retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) often have a co-occurring reading disorder (RD). The purpose of this research was to assess differences between children with ADHD without RD (ADHD-only) and those with ADHD and co-occurring RD (ADHD+RD).</p> <p>Methods</p> <p>Using data from the U.S. Thomson Reuter Marketscan^®Databases for the years 2005 through 2007, this analysis compared the medical records--including patient demographics, comorbidities, and medication use--of children (age < 18) with ADHD-only to those with ADHD+RD.</p> <p>Results</p> <p>Patients with ADHD+RD were significantly younger, more likely to have received a procedure code associated with formal psychological or non-psychological testing, and more likely to have been diagnosed with comorbid bipolar disorder, conduct disorder, or depression. They were no more likely to have received an antidepressant, anti-manic (bipolar), or antipsychotic, and were significantly less likely to have received a prescription for a stimulant medication.</p> <p>Conclusions</p> <p>Relying on a claims database, there appear to be differences in the patient characteristics, comorbidities, and medication use when comparing children with ADHD-only to those with ADHD+RD.</p