A comparative analysis of chronic inducible urticaria in 423 patients: Clinical and laboratory features and comorbid conditions.

BACKGROUND: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non-physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU. OBJECTIVES: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU. METHODS: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU). RESULTS: A total of 423 patients (~70% isolated CIndU, ~30% CSU plus CIndU, ~5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 ± 12.72 vs. 37.06 ± 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 ± 12.2 vs. 34.47 ± 12.12 vs. 31.38 ± 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006). CONCLUSIONS: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies.

Alkaloid content in microsporidia-infected Adalia bipunctata (Coleoptera: Coccinellidae) life stages, and pathogen spore load in adults after exposure to physical stress.

The two-spotted lady beetle, Adalia bipunctata L., displays warning colouration that is reinforced by the production of adaline and adalinine. These alkaloids are thought to provide defense against predation throughout all life stages of A. bipunctata and may play a role in the insect immune system. Vairimorpha (Nosema) adaliae, a microsporidium described from A. bipunctata, has minimal effects on its host (delayed larval development) when reared under optimum conditions but stress factors are shown to affect the development of microsporidiosis. The objectives of this study were to determine the effects of V. adaliae on relative alkaloid content (adaline) during A. bipunctata development, and to evaluate the combined effects of physical stress and infection on adult beetles (relative alkaloid content and infection load). First-instar larvae were isolated from uninfected and V. adaliae-infected colonies. Eggs and first-instar larvae were immediately prepared for alkaloid analysis, whereas late-instar larvae, pupae and adults were systematically processed when each reached their designated developmental stage. Upon eclosion, a subsample of beetles was exposed to varying amounts of physical agitation: control (no shaking), alternate shaking (every other day), and daily shaking. Immediately following these stress trials, alkaloid samples were collected for analysis and spore loads were assessed. Overall, relative adaline proportions increased from egg to adult. Uninfected individuals had significantly higher relative proportions of adaline than did infected individuals during early development; however, adaline content was higher in infected A. bipunctata from the third-instar onwards, when compared to their uninfected counterparts. Following exposure to physical agitation on alternate days, uninfected adults had a significantly higher relative proportion of adaline than did infected adults. Interestingly, exposure to different levels of agitation had no significant effect on alkaloid production for either uninfected or infected beetles. Mean spore counts were significantly higher for adults that were exposed to daily shaking when compared to individuals from the control and alternate shaking groups. From a biological perspective, one would expect to observe differences in alkaloid production through coccinellid development, as each successive life stage faces different external pressures and risks. When infected with the microsporidium V. adaliae, however, adaline production was reduced during early development but increased significantly in late life stages.

Effects of temperature on larval development, alkaloid production and microsporidiosis in the two-spotted lady beetle, Adalia bipunctata L. (Coleoptera: Coccinellidae).

Nosema adaliae, a microsporidian pathogen described from the two-spotted lady beetle, Adalia bipunctata L., delays larval development when A. bipunctata is reared under laboratory conditions at 25 °C. In nature, lady beetles often experience a wide range of environmental temperatures, but little is known regarding the effects of microsporidian pathogens on lady beetles when they are reared at higher and lower temperatures. In this study, the effects of elevated rearing temperatures and microsporidiosis were observed on larval development time and mortality, sex ratios, alkaloid content (adaline and adalinine), and adult morphometrics. Uninfected larvae (24 h-old) were provided either an uninfected or N. adaliae-infected conspecific egg and subsequently reared at three temperatures (25 °C, 27.5 °C or 30 °C). After the egg was eaten, larvae were provided a diet of green peach aphids and their development was recorded daily. Following eclosion, a subsample of adults were photographed for microscopic measurements and reflex-fluid was collected for alkaloid analysis using gas chromatography-mass spectrometry. Afterwards, all individuals were examined to determine the number that had become infected, and the same subsample was used to assess the severity of infection. Development time was delayed significantly for larvae that consumed a N. adaliae-infected egg, and infected larvae took significantly longer to develop at 25 °C than at 27.5 °C or 30 °C. No differences were observed for larval mortality or sex ratios. The relative proportion of adaline increased when larvae were reared at 30 °C, but adaline concentration was not affected by the pathogen, N. adaliae. Adults reared at 25 °C had larger body measurements when compared to those reared at 27.5 °C and 30 °C. Overall, adults that had eaten a N. adaliae-infected A. bipunctata egg as larvae had similar body measurements to those that ate an uninfected egg. When comparing male and female measurements, a significant interaction between infection status, temperature and sex was observed for elytra length and head capsule width only. These measurements were similar for uninfected and N. adaliae-infected females across all temperatures. However, when reared at 25 °C, uninfected males had significantly smaller elytra and head capsules than did infected males; but when reared at 30 °C, no significant difference was observed for these measurements. Both percent infection and average spore count decreased at 27.5 °C and 30 °C. These results suggest that temperatures above 25 °C have a mitigating effect against N. adaliae in A. bipunctata.

Effects of food availability on microsporidiosis and alkaloid production in the two-spotted lady beetle, Adalia bipunctata L.

The effects of food availability and infection with the microsporidium Nosema adaliae on alkaloid production in the two-spotted lady beetle, Adalia bipunctata L., was examined. Alkaloid production (relative percent adaline in reflex-fluid) and pathogen load (spore counts) were quantified for both uninfected and N. adaliae-infected A. bipunctata. Alkaloid content was significantly higher for beetles fed irregularly than for those fed daily. For beetles infected with N. adaliae, spore counts were significantly higher for those fed irregularly compared to those fed daily. These results suggest that adaline content in reflex-fluid is influenced by infection and that irregular food supply increases pathogen load.

A date with telomerase: pick you up at S phase.

Using the MS2 system for labeling mRNA, in this issue, Gallardo et al. (2011) find that telomere lengthening depends on a stable accumulation of multiple telomerase complexes in late S phase and that this process is temporally regulated by Rif1/2 proteins.

Animal production, animal health and food safety: Gaps and challenges in the chilean industry.

This paper summarizes the gaps and challenges related to animal production, health, and food safety as discussed by a panel at the 1st International Symposium of Food Safety (ISFS) in Santiago, Chile, in December 2016. Participating representatives of academia, industry, and government and statements from the audience confirmed that food safety is essential for increasing food security. First, panelists identified the need for a science-based regulatory framework to implement effective regulations. Second, they highlighted the importance of a risk analysis framework to quantify the risk of the potential for antimicrobial resistance associated with the use of antimicrobials, and the need of studies to evaluate foodborne prevention/control strategies. Third, the challenges of filling the gaps between industry and academia were addressed, including examples of successful collaboration, opportunities, and weakness identified by industry. Finally, challenges in animal food production included issues related to changing consumer preferences, animal welfare, the use of antimicrobials, and sustainable animal production. The symposium provided a regional platform to share experiences from the implementation of methods and approaches for food safety. The roundtable successfully explored the future science and technology challenges that are of strategic importance for Chile and the region in animal health and food safety.

Time to endoscopic intervention in patients with upper gastrointestinal patients can be improved with pathway provision.

BACKGROUND: Patients with upper gastrointestinal malignancy often require admission to hospital with dysphagia or jaundice requiring therapeutic endoscopy. Endoscopic intervention is often effective permitting rapid discharge. An efficient service would permit rapid discharge for patients who are often at the end of life. We noted that a majority of patients in hospital under the gastroenterological oncology were admitted with symptoms requiring therapeutic endoscopy. METHODS: We conducted an audit cycle of the inpatient days before and after pathway implementation. A wait of 1 day was set as acceptable for patients with bleeding as defined by NICE guidance and we set an arbitrary standard of 2 days for patients without bleeding but requiring therapeutic endoscopy. Between the audit cycles, a pathway was built to accommodate these patients. RESULTS: Inpatient waits improved from a median of 3 days to 1 day. There was no difference in outcome between those presenting with bleeding and other symptoms or any difference in patients requiring different procedures. CONCLUSIONS: Waiting times for endoscopy can be improved with the introduction of a targeted pathway of cancer patients. Further issues including cost, quality of life and nutrition require further intervention.

Modeling the spread of polio in an IPV-vaccinated population: lessons learned from the 2013 silent outbreak in southern Israel.

BACKGROUND: Polio eradication is an extraordinary globally coordinated health program in terms of its magnitude and reach, leading to the elimination of wild poliovirus (WPV) in most parts of the world. In 2013, a silent outbreak of WPV was detected in Israel, a country using an inactivated polio vaccine (IPV) exclusively since 2005. The outbreak was detected using environmental surveillance (ES) of sewage reservoirs. Stool surveys indicated the outbreak to be restricted mainly to children under the age of 10 in the Bedouin population of southern Israel. In order to curtail the outbreak, a nationwide vaccination campaign using oral polio vaccine (OPV) was conducted, targeting all children under 10. METHODS: A transmission model, fitted to the results of the stool surveys, with additional conditions set by the ES measurements, was used to evaluate the prevalence of WPV in Bedouin children and the effectiveness of the vaccination campaign. Employing the parameter estimates of the model fitting, the model was used to investigate the effect of alternative timings, coverages and dosages of the OPV campaign on the outcome of the outbreak. RESULTS: The mean estimate for the mean reproductive number was 1.77 (95 % credible interval, 1.46-2.30). With seasonal variation, the reproductive number maximum range was between zero and six. The mean estimate for the mean infectious periods was 16.8 (8.6-24.9) days. The modeling indicates the OPV campaign was effective in curtailing the outbreak. The mean estimate for the attack rate in Bedouin children under 10 at the end of 2014 was 42 % (22-65 %), whereas without the campaign the mean projected attack rate was 57 % (35-74 %). The campaign also likely shortened the duration of the outbreak by a mean estimate of 309 (2-846) days. A faster initiation of the OPV campaign could have reduced the incidence of WPV even if a lower coverage was reached, at the risk of prolonging the outbreak. CONCLUSIONS: OPV campaigns are essential for interrupting WPV transmission, even in a developed country setting with a high coverage of IPV. In this setting, establishing ES of WPV circulation is particularly crucial for early detection and containment of an outbreak.

A simple technique to estimate best- and worst-case survival in patients with metastatic colorectal cancer treated with chemotherapy.

BACKGROUND: Patients with incurable cancer usually want specific information about prognosis, and clinicians' estimates are often inaccurate. Studies in breast and lung cancer have suggested that simple multiples of the median overall survival (OS) can accurately estimate the time at which 90%, 75%, 25% and 10% of patients are alive. PATIENTS AND METHODS: We identified 46 phase III randomised clinical trials of chemotherapy in metastatic colorectal cancer, representing data from 29 011 patients. We extracted data on demographics, treatment and survival from 96 patient cohorts and assessed agreement with the estimated survival time points, calculated as 0.25, 0.5, 2 and 3 times the median OS. RESULTS: Median OS was 16.8 months in the trials. There were 342 assessable time points. For 301 of these, the estimated survival time was within 0.75-1.33 of the actual survival time (88% agreement). The worst agreement (76%) was at the earliest (90%) level of survival. CONCLUSIONS: Simple multiples of the median OS give reasonable estimates of the times at which different survival levels are reached in patients with metastatic colorectal cancer. Taken with previous studies, these findings are likely to be valid across a large range of patients. We would encourage clinicians to think of prognosis as a trajectory, and to consider quoting survival ranges instead of point estimates, in discussions with patients.

Maps and missing malaria--if in doubt request a blood film.

The severe sequelae of infection from the conventionally termed 'benign' forms of malaria are being increasingly recognised, and delayed diagnosis and treatment lead to worse outcomes. The clinical picture can be non-specific and malaria epidemiology is constantly changing, presenting challenges for the acute clinician. The most critical step in the diagnosis of patients presenting in the U.K. is the clinician's awareness of the disease and its key presenting features. We describe a case of Plasmodium vivax malaria in a young man who presented with fever and diarrhoea, who had never travelled to a recognised malaria-endemic area.

Acculturation and Dental Care-Related Anxiety: An Exploratory Assessment from the Hispanic Community Health Study / Study of Latinos.

This study aimed to determine the associations between acculturation, dental anxiety, and dental utilization among Hispanics/Latinos living in the US. A proxy measure of dental anxiety was available for 7539 adults who had not visited a dentist within the last year. All completed the Short Acculturation Scale for Hispanics (SASH). Bivariate logistic regression and adjusted multivariable logistic regression analysis were conducted. Approximately 22% of the sample was dentally anxious. Dental anxiety was significantly associated with SASH language scale score (OR 1.09, 95%CI 1.02, 1.18, p = 0.04), years in US (OR 1.53, 95%CI 1.23, 1.91, p < 0.0001), and preferred Spanish language (OR 1.30, 95%CI 1.05, 1.63, p = 0.0192); lower acculturation corresponded to higher dental anxiety. Adjusting for sex, age, education, income, insurance, and oral health status, level of acculturation was associated with dental anxiety (AOR 0.87, 95%CI 0.75, 0.91, p = 0.009), but neither were associated with utilization. Acculturation may be an important predictor of dental anxiety for Hispanics/Latinos living in the US.

The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques.

Development of a microbicide that prevents rectal transmission of human immunodeficiency virus (HIV) is a vital component in reducing HIV spread. We recently demonstrated that a formulation of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan reduced vaginal infection of macaques with simian immunodeficiency virus SIVmac239 with HIV-1(HxB2) reverse transcriptase (SHIV-RT). Herein, we performed the first testing of MIV-150-carrageenan against rectal infection. Rhesus macaques were treated rectally with MIV-150-carrageenan or methyl cellulose (MC) placebo gel up to 4 h prior to rectal challenge with 10³ or 10(4) 50% tissue culture infective doses (TCID50) of SHIV-RT. Infection was assessed by measuring plasma virus RNA as well as T and B cell responses. MIV-150-carrageenan protected all animals challenged with 10³ TCID(50 when gel was applied either 30 min or 4 h prior to challenge, while 100% of the MC-treated animals became infected (n = 4 each; P < 0.03). Partial protection (2 of 4 animals) by MIV-150-carrageenan was observed for rectal challenge with 10-fold more virus applied 4 h after the gel. Sequencing of the RT gene from plasma virus RNA isolated at peak viremia confirmed that both of these animals (like infected MC controls) were infected with wild-type virus. Infection correlated with the development of SIV-specific T and B cell responses. MIV-150 was detected in the rectal fluids and tissues 4 h after gel application but was not detected in the blood at any time (0.5 to 24 h). These data are promising for the development of NNRTI-containing gels to prevent rectal HIV transmission.

SARS-CoV-2 prevalence and immunity: a hospital-based study from Malawi.

BACKGROUND: COVID-19 transmission and disease dynamics in sub-Saharan Africa are not well understood. Our study aims to provide insight into COVID-19 epidemiology in Malawi by estimating SARS-CoV-2 prevalence and immunity after SARS-CoV-2 infection in a hospital-based setting. METHODS: We conducted a hospital-based, convenience sampling, cross-sectional survey for SARS-CoV-2 in Lilongwe, Malawi. Participants answered a questionnaire and were tested for SARS-CoV-2 by enzyme-linked immunosorbent assay and real-time reverse-transcription polymerase chain reaction (RT-PCR). A surrogate virus neutralization test (sVNT) was performed in seropositive samples to estimate immunity. Poisson regression was used to assess SARS-CoV-2 point prevalence association with demographic and behavioral variables. FINDINGS: The study included 930 participants. We found a combined point prevalence of 10.1%. Separately analyzed, RT-PCR positivity was 2.0%, and seropositivity was 9.3%. Of tested seropositive samples, 90.1% were sVNT positive. We found a high rate (45.7%) of asymptomatic SARS-CoV-2 infection. SARS-CoV-2 point prevalence was significantly associated with being a healthcare worker. INTERPRETATION: Our study suggests that official data underestimate COVID-19 transmission. Using sVNTs to estimate immunity in Malawi is feasible and revealed considerable post-infection immunity in our cohort. Subclinical infection and transmission are probably a game-changer in surveillance, mitigation and vaccination strategies.

Spin Interactions in bcc and fcc Fe beyond the Heisenberg Model.

Usually, the adiabatic magnetic exchange-energy hypersurface is parametrized in terms of the bilinear Heisenberg interactions in pairs of atoms. For general magnetic configurations, this model is not complete even if it includes pairs with up to infinite interatomic distances. In contrast, the modeling by an in principle infinite spin-cluster expansion is complete for all conceivable magnetic configurations. In the present Letter, it is shown for bcc and fcc iron that a very accurate representation can be reached with a finite expansion with 20 terms which include biquadratic or multispin non-Heisenberg interactions.

The cytoskeleton and mRNA localization.

The localization of mRNA appears to facilitate protein sorting, so that proteins are synthesized in specific cellular regions. The spatial information on the mRNA may be transduced by proteins that recognize specific localizing sequences on the 3' end and then chaperone the mRNA, presumably along filaments, to its destination. Additional sequences such as poly(A), or the nascent chains of cytoskeleton-associated proteins, may then anchor mRNAs on the cytoskeleton.

mRNA and cytoskeletal filaments.

The localization of some mRNAs to distinct intracellular regions is achieved through interactions of the mRNA with cytoskeletal filaments. RNA-cytoskeletal interactions exist that influence the transport, anchoring and translation of mRNA. Recent analysis of RNA movements in living cells suggests the formation of RNA granules and their active transport along microtubules. The anchoring and translation of mRNA may be mediated by interactions with orthogonal networks of F-actin and elongation factor 1alpha.

Determinants of mRNA localization.

RNA localization provides a mechanism for protein targeting within developing or differentiating cells. Specific cis-acting sequences on mRNA mediate this process. Such 'localizer' or 'zipcode' nucleic acid sequences have been restricted to the 3' untranslated region of several mRNAs. The presence of genetic information denoting a spatial component of translation adds a new dimension to gene expression.

Mitochondria-associated yeast mRNAs and the biogenesis of molecular complexes.

The coherence of mitochondrial biogenesis relies on spatiotemporally coordinated associations of 800-1000 proteins mostly encoded in the nuclear genome. We report the development of new quantitative analyses to assess the role of local protein translation in the construction of molecular complexes. We used real-time PCR to determine the cellular location of 112 mRNAs involved in seven mitochondrial complexes. Five typical cases were examined by an improved FISH protocol. The proteins produced in the vicinity of mitochondria (MLR proteins) were, almost exclusively, of prokaryotic origin and are key elements of the core construction of the molecular complexes; the accessory proteins were translated on free cytoplasmic polysomes. These two classes of proteins correspond, at least as far as intermembrane space (IMS) proteins are concerned, to two different import pathways. Import of MLR proteins involves both TOM and TIM23 complexes whereas non-MLR proteins only interact with the TOM complex. Site-specific translation loci, both outside and inside mitochondria, may coordinate the construction of molecular complexes composed of both nuclearly and mitochondrially encoded subunits.

Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD.

Surfactant protein (SP)-D is a lung-derived protein that has been proposed as a biomarker for inflammatory lung disease. Serum SP-D was evaluated as a biomarker for components of chronic obstructive pulmonary disease (COPD) in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort and its response assessed to the administration of the anti-inflammatory agent prednisolone. The median level of serum SP-D was significantly elevated in 1,888 individuals with COPD compared to 296 current and former smokers without airflow obstruction (121.1 and 114.3 ng x mL(-1), respectively; p = 0.021) and 201 nonsmokers (82.2 ng x ml(-1); p<0.001). There was no correlation with the severity of COPD. Individuals with COPD who had a serum SP-D concentration that was greater than the 95th percentile of nonsmokers (175.4 ng x mL(-1)) showed an increased risk of exacerbations over the following 12 months (adjusted OR 1.30; 95% CI 1.03-1.63). Treatment with 20 mg x day(-1) prednisolone for 4 weeks resulted in a fall in serum SP-D levels (126.0 to 82.1 ng x mL(-1); p<0.001) but no significant change in post-bronchodilator forced expiratory volume in 1 s. Serum SP-D concentration is raised in smokers and may be useful in identifying individuals who are at increased risk of exacerbations of COPD. It may represent an intermediate measure for the development of novel anti-inflammatory agents.

RNA localization: different zipcodes, same postman?

RNA-localization mechanisms involve specific sequences in the localized RNA and proteins that bind to these sequences and mediate the interaction with cytoskeletal elements. Until recently, it seemed as though two separate types of mechanisms were operating for mRNA localization--involving interaction with either microtubules or actin microfilaments. However, it is now clear that some of the protein components involved in mRNA localization can participate in both microtubule- and actin-dependent localization pathways. This, combined with new evidence for evolutionary conservation of some of these proteins, suggests a previously unanticipated uniformity in mRNA-localization mechanisms.