Acetaminophen Protects Against Iron-Induced Cardiac Damage in Gerbils

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (−22%), and fractional shortening (−31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology

Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients

BACKGROUND: Although rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Eave tubes for malaria control in Africa : an introduction

In spite of massive progress in the control of African malaria since the turn of the century, there is a clear and recognized need for additional tools beyond long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying (IRS) of insecticides, to progress towards elimination. Moreover, widespread and intensifying insecticide resistance requires alternative control agents and delivery systems to enable development of effective insecticide resistance management strategies. This series of articles presents a novel concept for malaria vector control, the ‘eave tube’, which may fulfil these important criteria. From its conceptualization to laboratory and semi-field testing, to demonstration of potential for implementation, the stepwise development of this new vector control approach is described. These studies suggest eave tubes (which comprise a novel way of delivering insecticides plus screening to make the house more ‘mosquito proof’) could be a viable, cost-effective, and acceptable control tool for endophilic and endophagic anophelines, and possibly other (nuisance) mosquitoes. The approach could be applicable in a wide variety of housing in sub-Saharan Africa, and possibly beyond, for vectors that use the eave as their primary house entry point. The results presented in these articles were generated during an EU-FP7 funded project, the mosquito contamination device (MCD) project, which ran between 2012 and 2015. This was a collaborative project undertaken by vector biologists, product developers, modellers, materials scientists, and entrepreneurs from five different countries

Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis : a systematic literature review

Background Diagnosis of intrathoracic tuberculosis (ITB) is limited in children partly by their difficulty to produce sputum specimen. Objective To systematically review the detection yields of mycobacterial culture and Xpert MTB/RIF from induced sputum (IS), nasopharyngeal aspirate (NPA) and gastric aspirate (GA) in children with presumptive ITB. Design Pubmed, Embase and Biosis databases and grey literature were searched. Randomised controlled trials, cohort, cross-sectional or case control studies using IS, GA and NPA for diagnosis of ITB published between January 1990 and January 2018 were included. Data were extracted on study design, case definition of presumptive ITB, sample collection methods, outcome measures and results. Results 30 studies were selected, including 11 554 children. Detection yields for culture ranged between 1% and 30% for IS, 1% and 45% for GA and 4% and 24% for NPA. For Xpert MTB/RIF, it was between 2% and 17% for IS, 5% and 51% for GA and 3% and 8% for NPA. There was a tendency of better yields with IS when the pretest probability of ITB was low to moderate and with GA when it was high. Sampling a second specimen contributed for 6%-33% of the cumulative yield and combination of different methods significantly increase the detection yields. Conclusions Despite the important study heterogeneity, any of the specimen collection methods offers good potential to confirm childhood ITB. However, their operational challenges were poorly evaluated. In the absence of a sensitive non-sputum based test, only a minority of children with ITB can be confirmed

Screening for active and latent TB among migrants in France

International audienceMigrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France. METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants. RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and highincidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries. CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB