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.

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.

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.

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.

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.

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.

Systematic Review: Impact of point sources on antibiotic-resistant bacteria in the natural environment.

Point sources such as wastewater treatment plants and agricultural facilities may have a role in the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARG). To analyse the evidence for increases in ARB in the natural environment associated with these point sources of ARB and ARG, we conducted a systematic review. We evaluated 5,247 records retrieved through database searches, including both studies that ascertained ARG and ARB outcomes. All studies were subjected to a screening process to assess relevance to the question and methodology to address our review question. A risk of bias assessment was conducted upon the final pool of studies included in the review. This article summarizes the evidence only for those studies with ARB outcomes (n = 47). Thirty-five studies were at high (n = 11) or at unclear (n = 24) risk of bias in the estimation of source effects due to lack of information and/or failure to control for confounders. Statistical analysis was used in ten studies, of which one assessed the effect of multiple sources using modelling approaches; none reported effect measures. Most studies reported higher ARB prevalence or concentration downstream/near the source. However, this evidence was primarily descriptive and it could not be concluded that there is a clear impact of point sources on increases in ARB in the environment. To quantify increases in ARB in the environment due to specific point sources, there is a need for studies that stress study design, control of biases and analytical tools to provide effect measure estimates.

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.

Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos.

Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus ( TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association ( P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American ( n = 4,402) and African-American ( n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

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.

Oxidative Stress and IgG Antibody Modify Periodontitis-CRP Association.

In a previous report, we demonstrated the inverse association of high serum 8-isoprostane levels, a marker for oxidative stress, with decreased serum IgG antibodies to oral bacteria. The association between increased serum IgG with increased plaque and periodontitis (increased probing depths) was attenuated by high systemic oxidative stress. Other investigations have reported a role for systemic oxidative stress as a stimulus of hepatic C-reactive protein (CRP) response. These observations led us to hypothesize that the reported relationship of periodontitis to elevated serum CRP, a systemic inflammatory marker, may be modified by oxidative stress and that the levels of serum antibodies to oral bacteria might be an intermediary explanatory variable linking the association of systemic oxidative stress, periodontal disease, and levels of CRP. This hypothesis was explored as a secondary analysis of the Dental ARIC (Atherosclerosis Risk in Communities) study using serum levels of CRP, serum IgG levels to 16 oral organisms, serum levels of 8-isoprostane, and periodontal status. The findings indicate periodontitis is associated with high CRP in the presence of elevated oxidative stress that serves to suppress the IgG response. Only within the highest 8-isoprostane quartile was periodontitis (pocket depth) associated with increased serum CRP levels (P = 0.0003). Increased serum IgG antibody levels to oral bacteria were associated with lowered serum CRP levels. Thus, systemic oxidative stress, which has been demonstrated to be associated with increased levels of CRP in other studies, appears to be associated with the suppression of bacterial-specific IgG levels, which in the presence of periodontal disease can result in an enhanced systemic CRP response. Conversely, individuals with increased serum IgG antibodies to plaque bacteria exhibit lowered serum CRP levels. These 2 factors, oxidative stress and the serum IgG response, appear to function in opposing directions to modify serum levels of CRP and the association with periodontitis.

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.

Cerebrovascular collaterals correlate with disease severity in adult North American patients with Moyamoya disease.

BACKGROUND AND PURPOSE: Cerebrovascular collaterals have been increasingly recognized as predictive of clinical outcomes in Moyamoya disease in Asia. The aim of this study was to characterize collaterals in North American adult patients with Moyamoya disease and to assess whether similar correlations are valid. MATERIALS AND METHODS: Patients with Moyamoya disease (n = 39; mean age, 43.5 ±10.6 years) and age- and sex-matched control subjects (n = 33; mean age, 44.3 ± 12.0 years) were graded via angiography. Clinical symptoms of stroke or hemorrhage were graded separately by imaging. Correlations between collateralization and disease severity, measured by the modified Suzuki score, were evaluated in patients with Moyamoya disease by fitting a regression model with clustered ordinal multinomial responses. RESULTS: The presence of leptomeningeal collaterals (P = .008), dilation of the anterior choroidal artery (P = .01), and the posterior communicating artery/ICA ratio (P = .004) all correlated significantly with disease severity. The presence of infarct or hemorrhage and posterior steno-occlusive disease did not correlate significantly with the modified Suzuki score (P = .1). Anterior choroidal artery changes were not specific for hemorrhage. Patients with Moyamoya disease were statistically more likely than controls to have higher posterior communicating artery/ICA ratios and a greater incidence of leptomeningeal collaterals. CONCLUSIONS: As with Moyamoya disease in Asian patients, the presence of cerebrovascular collaterals correlated with the modified Suzuki score for disease severity in North American patients with Moyamoya disease. However, anterior choroidal artery changes, which correlated with increased rates of hemorrhage in Asian studies, were not specific to hemorrhage in North Americans.

Risk factors for exposure to influenza a viruses, including subtype H5 viruses, in Thai free-grazing ducks.

Free-grazing ducks (FGD) have been associated with highly pathogenic avian influenza (HPAI) H5N1 outbreaks and may be a viral reservoir. In July-August 2010, we assessed influenza exposure of Thai FGD and risk factors thereof. Serum from 6254 ducks was analysed with enzyme-linked immunosorbent assay (ELISA) to detect antibodies to influenza A nucleoprotein (NP), and haemagglutinin H5 protein. Eighty-five per cent (5305 ducks) were seropositive for influenza A. Of the NP-seropositive sera tested with H5 assays (n = 1423), 553 (39%) were H5 ELISA positive and 57 (4%) suspect. Twelve per cent (74 of 610) of H5 ELISA-positive/suspect ducks had H5 titres ≥ 1 : 20 by haemagglutination inhibition. Risk factors for influenza A seropositivity include older age, poultry contact, flock visitors and older purchase age. Study flocks had H5 virus exposure as recently as March 2010, but no HPAI H5N1 outbreaks have been identified in Thailand since 2008, highlighting a need for rigorous FGD surveillance.

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.

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.

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.