Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.     

Outcome of children with respiratory symptoms without objective evidence of asthma: a two-year, prospective, follow-up study

This study evaluated the outcome of 33 children with asthma-like symptoms without objective evidence of asthma, and the role of certain factors in predicting the development of clinical asthma in these children. Data on symptom histories, lung functions (flow-volume spirometry, free running test and methacholine inhalation challenge test) and atopic sensitization (skin prick tests and markers of eosinophilic inflammation) were collected twice with an interval of 2 y, and the diagnoses were re-evaluated after the follow-up period. Based on the results, it was concluded that one-third of the children with prolonged or recurrent lower airway symptoms, such as cough or wheeze, either have mild asthma or will develop asthma in the near future. Children who had a significant response [≥ 10% fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a risk group for active asthma, whereas other baseline characteristics seemed not to predict the outcome.     

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵mm³) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵mm³) with differences in volumes (p = .0055).     

Hypersensitivity to aeroallergens in patients with recurrent vulvovaginitis of undetermined etiology

AIM: Recent findings show that the vaginal mucosa can develop an allergic response to environmental allergens and there is a strong association between atopy and some recurrent vulvovaginal infections. In this study, we investigated prospectively the rate of atopy in patients with recurrent vulvovaginitis of undetermined etiology (RVV). MATERIAL AND METHODS: After being investigated by a gynecologist, 35 patients with RVV who were considered as undetermined etiology formed the study group. The control group consisted of 150 healthy females. Study and control groups were investigated for atopy by means of skin prick test for common aeroallergens. Associated allergic disease and familial atopy history of the subjects were recorded. RESULTS: The rate of atopy (11/35; 31.4% vs 9/150; 6%) was significantly higher (P < 0.001) in the study group than in the controls. Familial history of atopy was significantly more frequent in the study group than in the controls (10/35; 28.6% vs 8/150; 5.3%, P < 0.05). RVV in atopics is more associated with seasonal rhinitis than in nonatopics (5/11; 45.4% vs 2/24; 8.3%, P < 0.05). CONCLUSION: We concluded that a significant number of RVV is associated with atopy. Although the exact mechanism(s) of this relationship remains to be investigated atopy might be a causative and/or contributing factor in the pathogenesis of RVV.     

Microstructural Evolution,Tensile Failure,Fatigue Behavior and Wear Properties of Al2O3 Reinforced Al2014 Alloy T6 Heat Treated Metal Composites

The paper focused on an experimental study on the microstructural, mechanical, and wear characteristics of 15 wt.% alumina (Al₂O₃) particulates with an average particle size of 20 µm, reinforced in Al2014 alloy matrix composite as-cast and heat-treated samples. The metal matrix composite (MMC)samples were produced via a novel two-stage stir-casting technique. The fabricated composite samples were subjected to evaluate hardness, tensile strength, fatigue behavior and wear properties for both as cast and T6 heat-treated test samples. The Al2014 alloy and Al2014-15 wt.% Al₂O₃ MMCs were in solution for 1 h at a temperature of 525 °C, quenched instantly in cold water, and then artificially aged for 10 h at a temperature of 175 °C. SEM and X-ray diffraction analyses were used to investigate the microstructure and dispersion of the reinforced Al₂O₃ particles in the composite and the base alloy Al2014. The obtained results indicated that the hardness, tensile and fatigue strength and wear resistance increased when an amount of Al₂O₃ particles was added, compared to the as-cast Al2014 alloy and it was observed that after subjecting the same composite samples to heat treatment, there was further enhancement in the mechanical and wear properties in the Al2014 matrix alloy and Al2014-15 wt.% Al₂O₃ composite samples.     

Prevalence and correlates of COVID-19 vaccine hesitancy among the elderly in Qatar: A cross-sectional study

Older individuals are more vulnerable to severe coronavirus disease 2019 and medical complications. Vaccination stands as an efficient and safe vanguard against infection. However, negative attitudes and perceptions pertaining to available vaccines might hinder community inoculation. The aim of this study was to assess vaccine hesitancy and its psychosocial determinants among the elderly in Qatar.We conducted a cross-sectional study between October 15 and November 15, 2020, using a composite online survey including the Vaccine Attitudes Examination Scale in addition to questions on sociodemographic correlates and the role of healthcare professionals.The vaccine hesitancy rate was 19.5%. The main reasons for willingness to vaccinate included understanding the nature of disease and role of vaccination, in addition to information provided by physicians. Fears mainly centered around vaccine safety. Vaccine hesitators were more likely to be non-Qatari and having received the influenza vaccine at least once. Gender, marital status, socioeconomic status, educational level, and having completed childhood vaccinations were not associated with vaccine hesitancy.Efforts should be directed toward raising awareness of vaccine efficacy and safety profiles. Physicians should additionally be educated about their pivotal role in advocating vaccine acceptance. We recommend reassessing vaccine hesitancy and its associated factors following a year of campaigning and vaccine administration to identify and target vulnerable groups.     

Prediction of Compressive Strength of Sustainable Foam Concrete Using Individual and Ensemble Machine Learning Approaches

The entraining and distribution of air voids in the concrete matrix is a complex process that makes the mechanical properties of lightweight foamed concrete (LFC) highly unpredictable. To study the complex nature of aerated concrete, a reliable and robust prediction model is required, employing different machine learning (ML) techniques. This study aims to predict the compressive strength of LFC by using a support vector machine (SVM) as an individual learner along with bagging, boosting, and random forest (RF) as a modified ensemble learner. For that purpose, a database of 191 data points was collected from published literature, where the mix design ingredients, i.e., cement content, sand content, water to cement ratio, and foam volume, were chosen to predict the compressive strength of LFC. The 10-K fold cross-validation method and different statistical error and regression tools, i.e., mean absolute error (MAE), root means square error (RMSE), and coefficient of determinant (R²), were used to evaluate the performance of the developed ML models. The modified ensemble learner (RF) outperforms all models by yielding a strong correlation of R² = 0.96 along with the lowest statistical error values of MAE = 1.84 MPa and RMSE = 2.52 MPa. Overall, the result suggests that the ensemble learners would significantly enhance the performance and robustness of ML models.