A build team in Ohio is in the process of turning an old Porsche Boxster into a supercar that was limited to just seven units worldwide and originally priced at $3.4 million. The car we're talking about is the W Motors Lykan Hypersport that bowed in 2013, and a replica was recently acquired by a workshop in Bowling Green, Ohio. The replica was...

In recent months, a veritable open patent war has erupted between Tesla Motors and Toyota. Both companies have been widely cited in the industry and financial press for their respective announcements opening up their electric vehicle (Tesla) and fuel cell (Toyota) patents. Tesla CEO Elon Musk opened the first salvo with a blog post last June in which he announced that Tesla would “not initiate patent lawsuits against anyone who, in good faith, wants to use our technology.”

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Australia, India and UK Pursuing Centralized Approach Many Privacy Experts Warn Against
Technology is no panacea, including for combating COVID-19. While that might sound obvious, it's worth repeating because some governments continue to hype contact-tracing apps. Such apps won't magically identify every potential exposure. But they could make manual contact-tracing programs more effective.

Iran's parliament has voted to slash four zeros from the national currency, the rial, to fight hyperinflation caused by crippling U.S. sanctions and the coronavirus pandemic. Lawmakers also decided on May 4 that the rial, which has been Iran's national currency since 1925, will be replaced by the toman, which will be equal to 10,000 rials, according to the IRNA and ISNA news agencies.

In January, a plethora of companies and brands were in Las Vegas to kick off the New Year at the Consumer Electronics Show (CES). From smart TVs and refrigerators to digital assistants, robots, and more, CES is the place to be to experience the latest...

Title: Hyperthyroidism
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 11/20/2019 12:00:00 AM

Title: Hypertension Takes Huge Toll in Developing Countries
Category: Health News
Created: 5/2/2008 2:00:00 AM
Last Editorial Review: 5/2/2008 12:00:00 AM

Title: Death Rate Declines for Americans With Hypertension
Category: Health News
Created: 4/26/2011 1:54:00 PM
Last Editorial Review: 4/27/2011 12:00:00 AM

Title: AHA News: Director John Singleton's Fatal Stroke Spotlights Black Americans' Hypertension Risk
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: After Trump Hypes Use of a Lupus Med Against COVID-19, Lupus Patients Face Shortages
Category: Health News
Created: 4/25/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Taking Steroids for Rheumatoid Arthritis, IBD? Your Odds for Hypertension May Rise
Category: Health News
Created: 3/23/2020 12:00:00 AM
Last Editorial Review: 3/24/2020 12:00:00 AM

ABSTRACT

Toxoplasma gondii is a ubiquitous, intracellular protozoan parasite with a broad range of intermediate hosts, including humans and rodents. In many hosts, T. gondii establishes a latent long-term infection by converting from its rapidly dividing or lytic form to its slowly replicating and encysting form. In humans and rodents, the major organ for encystment is the central nervous system (CNS), which has led many to investigate how this persistent CNS infection might influence rodent and human behavior and, more recently, neurodegenerative diseases. Given the interest in this topic, here we seek to take a global approach to the data for and against the effects of latent T. gondii on behavior and neurodegeneration and the proposed mechanisms that might underlie behavior modifications.

ABSTRACT

Host persistence of bacteria is facilitated by mutational and recombinatorial processes that counteract loss of genetic variation during transmission and selection from evolving host responses. Genetic variation was investigated during persistent asymptomatic carriage of Neisseria meningitidis. Interrogation of whole-genome sequences for paired isolates from 25 carriers showed that de novo mutations were infrequent, while horizontal gene transfer occurred in 16% of carriers. Examination of multiple isolates per time point enabled separation of sporadic and transient allelic variation from directional variation. A comprehensive comparative analysis of directional allelic variation with hypermutation of simple sequence repeats and hyperrecombination of class 1 type IV pilus genes detected an average of seven events per carrier and 2:1 bias for changes due to localized hypermutation. Directional genetic variation was focused on the outer membrane with 69% of events occurring in genes encoding enzymatic modifiers of surface structures or outer membrane proteins. Multiple carriers exhibited directional and opposed switching of allelic variants of the surface-located Opa proteins that enables continuous expression of these adhesins alongside antigenic variation. A trend for switching from PilC1 to PilC2 expression was detected, indicating selection for specific alterations in the activities of the type IV pilus, whereas phase variation of restriction modification (RM) systems, as well as associated phasevarions, was infrequent. We conclude that asymptomatic meningococcal carriage on mucosal surfaces is facilitated by frequent localized hypermutation and horizontal gene transfer affecting genes encoding surface modifiers such that optimization of adhesive functions occurs alongside escape of immune responses by antigenic variation.

IMPORTANCE Many bacterial pathogens coexist with host organisms, rarely causing disease while adapting to host responses. Neisseria meningitidis, a major cause of meningitis and septicemia, is a frequent persistent colonizer of asymptomatic teenagers/young adults. To assess how genetic variation contributes to host persistence, whole-genome sequencing and hypermutable sequence analyses were performed on multiple isolates obtained from students naturally colonized with meningococci. High frequencies of gene transfer were observed, occurring in 16% of carriers and affecting 51% of all nonhypermutable variable genes. Comparative analyses showed that hypermutable sequences were the major mechanism of variation, causing 2-fold more changes in gene function than other mechanisms. Genetic variation was focused on genes affecting the outer membrane, with directional changes in proteins responsible for bacterial adhesion to host surfaces. This comprehensive examination of genetic plasticity in individual hosts provides a significant new platform for rationale design of approaches to prevent the spread of this pathogen.

ABSTRACT

Mobile elements—plasmids and phages—are important components of microbial function and evolution via traits that they encode and their capacity to shuttle genetic material between species. We here report the unusually rich array of mobile elements within the genome of Arsenophonus nasoniae, the son-killer symbiont of the parasitic wasp Nasonia vitripennis. This microbe’s genome has the highest prophage complement reported to date, with over 50 genomic regions that represent either intact or degraded phage material. Moreover, the genome is predicted to include 17 extrachromosomal genetic elements, which carry many genes predicted to be important at the microbe-host interface, derived from a diverse assemblage of insect-associated gammaproteobacteria. In our system, this diversity was previously masked by repetitive mobile elements that broke the assembly derived from short reads. These findings suggest that other complex bacterial genomes will be revealed in the era of long-read sequencing.

IMPORTANCE The biology of many bacteria is critically dependent on genes carried on plasmid and phage mobile elements. These elements shuttle between microbial species, thus providing an important source of biological innovation across taxa. It has recently been recognized that mobile elements are also important in symbiotic bacteria, which form long-lasting interactions with their host. In this study, we report a bacterial symbiont genome that carries a highly complex array of these elements. Arsenophonus nasoniae is the son-killer microbe of the parasitic wasp Nasonia vitripennis and exists with the wasp throughout its life cycle. We completed its genome with the aid of recently developed long-read technology. This assembly contained over 50 chromosomal regions of phage origin and 17 extrachromosomal elements within the genome, encoding many important traits at the host-microbe interface. Thus, the biology of this symbiont is enabled by a complex array of mobile elements.

ABSTRACT

The capsule is the dominant Streptococcus pneumoniae virulence factor, yet how variation in capsule thickness is regulated is poorly understood. Here, we describe an unexpected relationship between mutation of adcAII, which encodes a zinc uptake lipoprotein, and capsule thickness. Partial deletion of adcAII in three of five capsular serotypes frequently resulted in a mucoid phenotype that biochemical analysis and electron microscopy of the D39 adcAII mutants confirmed was caused by markedly increased capsule thickness. Compared to D39, the hyperencapsulated adcAII mutant strain was more resistant to complement-mediated neutrophil killing and was hypervirulent in mouse models of invasive infection. Transcriptome analysis of D39 and the adcAII mutant identified major differences in transcription of the Sp_0505-0508 locus, which encodes an SpnD39III (ST5556II) type I restriction-modification system and allelic variation of which correlates with capsule thickness. A PCR assay demonstrated close linkage of the SpnD39IIIC and F alleles with the hyperencapsulated adcAII strains. However, transformation of adcAII with fixed SpnD39III alleles associated with normal capsule thickness did not revert the hyperencapsulated phenotype. Half of hyperencapsulated adcAII strains contained the same single nucleotide polymorphism in the capsule locus gene cps2E, which is required for the initiation of capsule synthesis. These results provide further evidence for the importance of the SpnD39III (ST5556II) type I restriction-modification system for modulating capsule thickness and identified an unexpected linkage between capsule thickness and mutation of adcAII. Further investigation will be needed to characterize how mutation of adcAII affects SpnD39III (ST5556II) allele dominance and results in the hyperencapsulated phenotype.

IMPORTANCE The Streptococcus pneumoniae capsule affects multiple interactions with the host including contributing to colonization and immune evasion. During infection, the capsule thickness varies, but the mechanisms regulating this are poorly understood. We have identified an unsuspected relationship between mutation of adcAII, a gene that encodes a zinc uptake lipoprotein, and capsule thickness. Mutation of adcAII resulted in a striking hyperencapsulated phenotype, increased resistance to complement-mediated neutrophil killing, and increased S. pneumoniae virulence in mouse models of infection. Transcriptome and PCR analysis linked the hyperencapsulated phenotype of the adcAII strain to specific alleles of the SpnD39III (ST5556II) type I restriction-modification system, a system which has previously been shown to affect capsule thickness. Our data provide further evidence for the importance of the SpnD39III (ST5556II) type I restriction-modification system for modulating capsule thickness and identify an unexpected link between capsule thickness and adcAII, further investigation of which could further characterize mechanisms of capsule regulation.

The past 20 years have seen major advances in the understanding and treatment of pulmonary arterial hypertension (PAH; group 1 of the pulmonary hypertension (PH) clinical classification) [1]. A strong basis of knowledge has been acquired in: 1) large randomised clinical trials for drug development; 2) national registries for epidemiology and outcome; and 3) smaller studies on the pathophysiological mechanisms of the disease. This knowledge has been reviewed at World Symposia on Pulmonary Hypertension (the most recent in 2018 [2]) and summarised in European Respiratory Society (ERS)/European Society of Cardiology (ESC) clinical guidelines (the most recent in 2015 [3, 4]). We are, however, much less knowledgeable on specific aspects such as 1) the implementation of guidelines and access to therapies in different European countries; 2) the management of PH crises and progressive (acute on chronic) heart failure; and 3) other groups of PH, such as PH due to lung diseases. Therapeutic strategies also need to be optimised, in particular regarding the combination of drugs, the use of anticoagulants, the place for new medications targeting different pathophysiological pathways, etc.

Systemic sclerosis sine scleroderma (ssSSc) is a rare variant of systemic sclerosis, with only one pediatric case reported in the medical literature to date. Pulmonary arterial hypertension as the presenting feature of ssSSc is extremely rare, even in adults, and so far has never been reported in children. We report, for the first time, a case of pediatric ssSSc in a 3-year-old girl, who presented with interstitial lung disease and pulmonary hypertension. The patient was prescribed early aggressive pulmonary vasodilators combined with anti-inflammatory medications. The clinical response was good, and her current condition at 12 years of age is remarkable, considering the high mortality rates reported in adults. We underscore the importance of early aggressive treatment in future cases of similar presentation.

Staphylococcus aureus is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in S. aureus, and mutations in purR result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype. Here, we show that hypervirulent strains containing purR mutations can be attenuated with the addition of purine biosynthesis mutations, implicating the necessity for de novo purine biosynthesis in this phenotype and indicating that S. aureus in the mammalian host experiences purine limitation. Using cell culture, we showed that while purR mutants are not altered in epithelial cell binding, compared to that of wild-type (WT) S. aureus, purR mutants have enhanced invasion of these nonprofessional phagocytes, consistent with the requirement of FnBPs for invasion of these cells. This correlates with purR mutants having increased transcription of fnb genes, resulting in higher levels of surface-exposed FnBPs to promote invasion. These data provide important contributions to our understanding of how the pathogenesis of S. aureus is affected by sensing of purine levels during infection of the mammalian host.

Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that...

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (A-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized KPR-5714 (N-[(R)-3,3-difluoro-4-hydroxy-1-(2H-1,2,3-triazol-2-yl)butan-2-yl]-3-fluoro-2-[5-(4-fluorophenyl)-1H-pyrazol-3-yl]benzamide), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels. Intravenously administered KPR-5714 inhibited the hyperactivity of mechanosensitive C-fibers of bladder afferents and dose-dependently increased the intercontraction interval shortened by intravesical instillation of acetic acid in anesthetized rats. Furthermore, we examined the effects of KPR-5714 on voiding behavior in conscious rats with cerebral infarction and in those exposed to cold in metabolic cage experiments. Cerebral infarction and cold exposure induced a significant decrease in the mean voided volume and increase in voiding frequency in rats. Orally administered KPR-5714 dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume in these models. This study demonstrates that KPR-5714 improves OAB in three different models by inhibiting exaggerated activity of mechanosensitive bladder C-fibers and suggests that KPR-5714 may provide a new and useful approach to the treatment of OAB.

Decreased release of palmitic acid methyl ester (PAME), a vasodilator, from perivascular adipose tissue (PVAT) might contribute to hypertension pathogenesis. However, the PAME biosynthetic pathway remains unclear. In this study, we hypothesized that PAME is biosynthesized from palmitic acid (PA) via human catechol-O-methyltransferase (COMT) catalysis and that decreased PAME biosynthesis plays a role in hypertension pathogenesis. We compared PAME biosynthesis between age-matched normotensive Wistar Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHRs) and investigated the effects of losartan treatment on PAME biosynthesis. Computational molecular modeling indicated that PA binds well at the active site of COMT. Furthermore, in in vitro enzymatic assays in the presence of COMT and S-5'-adenosyl-L-methionine (AdoMet), the stable isotope [¹³C₁₆]-PA was methylated to form [¹³C₁₆]-PAME in incubation medium or the Krebs–Henseleit solution containing 3T3-L1 adipocytes or rat PVAT. The adipocytes and PVATs expressed membrane-bound (MB)-COMT and soluble (S)-COMT proteins. [¹³C₁₆]-PA methylation to form [¹³C₁₆]-PAME in 3T3-L1 adipocytes and rat PVAT was blocked by various COMT inhibitors, such as S-(5'-adenosyl)-L-homocysteine, adenosine-2',3'-dialdehyde, and tolcapone. MB- and S-COMT levels in PVATs of established SHRs were significantly lower than those in PVATs of age-matched normotensive WKY rats, with decreased [¹³C₁₆]-PA methylation to form [¹³C₁₆]-PAME. This decrease was reversed by losartan, an angiotensin II (Ang II) type 1 receptor antagonist. Therefore, PAME biosynthesis in rat PVAT is dependent on AdoMet, catalyzed by COMT, and decreased in SHRs, further supporting the role of PVAT/PAME in hypertension pathogenesis. Moreover, the antihypertensive effect of losartan might be due partly to its increased PAME biosynthesis.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

OBJECTIVE

To report U.S. national population-based rates and trends in diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) among adults, in both the emergency department (ED) and inpatient settings.

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together they regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom had been previously treated for Hodgkin lymphoma (HL). To investigate MKL1 and B-cell responses in the pathogenesis of HL, we generated Epstein-Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the patients with treated HL had a phenotype close to that of the healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This profile was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for HL in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B-cell transformation and the pathogenesis of HL.