Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM: To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn’s disease (CD). METHODS: Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer’s protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS: All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION: We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD. Key Words: Fungiome, Mycobiome, Crohn’s disease, Inflammation, Saudi children Core tip: We found high accuracy of fungal dysbiosis in predicting diagnosis of Crohn’s disease (CD), a finding similar to bacterial dysbiosis. However, the higher area under the curve for the fungal dysbiosis classifier in stool (0.85 ± 0.057) than in mucosa (0.71 ± 0.067) (P < 0.001), contrasts with bacterial studies, suggesting higher accuracy of stool samples. Although the clinical application of this finding is limited at present by the high cost of fungal analysis, such information is important from a scientific viewpoint, to increase the understanding of the role of fungal flora in CD and to stimulate further studies.The authors extend their appreciations to the Deanship of Scientific Research at King Saud University in Riyadh, Kingdom of Saudi Arabia for funding this work through Research Group No [RGP-1436-007]. This work was also supported by a grant from the Simons Foundation [No. 409704] to Kirill Korolev) and by the startup fund from Boston University to Kirill Korolev. Simulations were carried out on Shared Computing Cluster at Boston University. Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston University. Harland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation. (RGP-1436-007 - King Saud University in Riyadh, Kingdom of Saudi Arabia; 409704 - Simons Foundation; Boston University; Hariri Graduate Fellowship from Boston University; Diane and Dorothy Brooks Foundation)Published versio

Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Neisseria meningitidis nasopharyngeal carriage during the Hajj: A cohort study evaluating the need for ciprofloxacin prophylaxis

Background The annual Muslim pilgrimage has the potential of increase risk for acquisition of Neisseria meningitidis. Here, we evaluate the Hajj impact on the prevalence of N. meningitidis carriage in a paired and non-paired cohort of pilgrims. Secondary objectives were to calculate the compliance with recommended vaccination. Methods This is a prospective paired (arriving and departing), non-paired arriving and non-paired departing cohort study with the collection of nasopharyngeal samples at the start and the end of the Hajj. Results The study included unpaired arriving pilgrims at King Abdul Aziz International Airport (N = 1055), unpaired departing cohort (N = 373), and a paired cohort (N = 628) who were tested on arrival and departure. Meningococcal vaccination was received by all pilgrims, 98.2% received quadrivalent polysaccharide vaccine (ACWY), and 1.8% received meningococcal quadrivalent conjugate vaccine (MCV4). Only 1.61% and 23.03% received pneumococcal and influenza vaccines, respectively. Of the 1055 arriving unpaired pilgrim, 36 (3.4%) tested positive for nasopharyngeal carriage of N. meningitidis, and 24 (66.7%) of these were serogroup B, the remainder were non-groupable. Haemophilus influenza was detected among 45 (4.3%), and 11 (1%) carriers were positive for both N. meningitidis and H. influenzae. Out of 373 in the unpaired departing cohort, 6 (1.61%) tested positive for N. meningitidis, and 34 (9.1%) were positive for H. influenzae. Of the 628 paired cohort pilgrims, 36 (5.7%) pilgrims were positive for N. meningitidis at arrival and 16 (2.5%) pilgrims were positive after the hajj. Conclusion This the largest study of the epidemiology of N. meningitidis among pilgrims. The study showed a significant difference in the carriage between pilgrims from high endemicity and other pilgrims with a predominance of serogroup B. The continued use of ciprofloxacin as prophylactic antibiotics should be reconsidered as well as the consideration to add serogroup B as a required vaccination

Seropositivity and Awareness of Toxoplasmosis Among University Students

Toxoplasma gondii is an obligate intracellular parasite that is infecting about one-third of the world population. Awareness about toxoplasmosis and its transmission can help reduce its prevalence. We examined the degree of awareness about toxoplasmosis among female university students. A total of 127 samples were collected, including 44 samples from health colleges students and 83 samples from other colleges. A questionnaire was used to measure the level of awareness about Toxoplasma gondii. Serum samples were analyzed for the presence of anti-Toxoplasma gondii antibody using ELISA technique. Ninety-four (74%) participants were 18-20 years, 27 (21%) were 21-24 years, and 6 (5%) were above 24 years. Only 11 (9%) students eat raw meat and 21 (17%) students had a tendency to eat undercooked meat. Furthermore, only 6 (5%) students received blood transfusion and 33 (26%) students owned a cat at home. Forty-two (33%) students answered that they know about the disease. The majority of participants (n=121, 95%) used bottled water as a source of drinking water. Among the 127 samples collected, only 6 (4.7%) had IgG anti-Toxoplasma gondii antibody. There was statistically significant positive correlation between the level of awareness about toxoplasmosis and the participant\u27s answers about previous knowledge about the disease and a statistically significant negative correlation between the level of awareness about toxoplasmosis and the student\u27s faculty. We recommend that this study is repeated with a larger sample size and a modified questionnaire to include more detailed questions to reveal the true level of awareness

Old World cutaneous leishmaniasis treatment response varies depending on parasite species, geographical location and development of secondary infection

Background: In the Kingdom of Saudi Arabia (KSA), Leishmania major and L. tropica are the main causative agents of Old World cutaneous leishmaniasis (CL). The national CL treatment regimen consists of topical 1% clotrimazole/2% fusidic acid cream followed by 1–2 courses of intralesional sodium stibogluconate (SSG); however, treatment efficacy is highly variable and the reasons for this are not well understood. In this study, we present a complete epidemiological map of CL and determined the efficacy of the standard CL treatment regime in several endemic regions of KSA.Results: Overall, three quarters of patients in all CL-endemic areas studied responded satisfactorily to the current treatment regime, with the remaining requiring only an extra course of SSG. The majority of unresponsive cases were infected with L. tropica. Furthermore, the development of secondary infections (SI) around or within the CL lesion significantly favoured the treatment response of L. major patients but had no effect on L. tropica cases.Conclusions: The response of CL patients to a national treatment protocol appears to depend on several factors, including Leishmania parasite species, geographical location and occurrences of SI. Our findings suggest there is a need to implement alternative CL treatment protocols based on these parameters

Numerical Simulations of Some Real-Life Problems Governed by ODEs

In this chapter, some real-life model problems that can be formulated as ordinary differential equations (ODEs) are introduced and numerically studied. These models are the variable-order fractional Hodgkin–Huxley model of neuronal excitation (VOFHHM) and other models with the variable-order fractional (VOF) time delay, such as the 4-year life cycle of a population of lemmings model, the enzyme kinetics with an inhibitor molecule model, and the Chen system model. A class of numerical methods is used to study the above-mentioned models such as non-standard finite difference (NSFD) and Adams-Bashforth-Moulton (ABM) methods. Numerical test examples are presented

Test-taking Strategies on Reading Comprehension Tests: A Review of Major Research Themes

There is a growing body of thought and research on strategy use on tests of reading comprehension. Nevertheless, there have been few research reviews that have treated major themes involved in thought and research on test-taking strategies, specifically in the context of reading comprehension. Hence, this paper reviews the themes that are central to the discussion of strategy choice and use on reading comprehension tests. Research themes that form the foci of the paper include discussion of test-taking strategies as they relate to the process of reading test-taking, formats of reading tests, validation of reading tests, level of language proficiency, and performance on tests of reading comprehension

Viral shedding and antibody response in 37 patients with MERS-coronavirus infection

Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection

A clinical and ultrastructural investigation of the cornea in keratoconus

Keratoconus is a non-inflammatory corneal disease that progressively causes topographical alteration of the cornea as a result of thinning, and consequently leads to impaired vision. In this thesis, the clinical studies are showed that the incidence rate and severity of keratoconus in Asir province, Saudi Arabia is high with an early onset and more rapid progress to the severe disease stage at a young age compared to other countries. The result also showed that the disease required different contact lens designs to be available in the clinics and the selection of initial back optic zone radius for multiple contact lens designs should be based in the steepest keratometric reading in early stage, and on average keratometric reading on moderate and advanced stages. However, regardless of the stage of disease, tricurve contact lens design should be selected based on average keratometric reading. Ultrastructure investigation of the anterior surface of Bowman's layer using different microscopes revealed that the changes are not limited to the apical cone only, but extend to the periphery of the cornea especially in the advances stage of keratoconus. Also, although the topographical map is usually used in trephination, it was found that the topographical features alone failed to indicate the full extent of the progress of keratoconus towards the corneal periphery. Data from transmission electron microscopy and high-angle X-ray diffraction suggest that the structural abnormalities in the stromal fibrillar matrix might be influential underlying reasons for topographic changes in the keratoconic-like changes of SPARC-null and JKC mice.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Effect of stabilizer on optical band gap of ZnO and their performance in dye-sensitized solar cells

ABSTRACT. In dye-sensitized solar cells, transparent metal oxide working electrodes play a vital role in defining the power conversion efficiency. It was found that the size of nanoparticles influences the electrical, optical properties of these electrodes. Herein, we describe the synthesis of ZnO with zinc acetate dihydrate and different stabilizers (diethylamine and triethylamine) by using a modified solvothermal process. The obtained materials were characterized by XRD, SEM, EDX, TEM, HRTEM, UV-visible, FTIR, and Raman methods. The crystallite sizes for ZnO-1 and ZnO-2 samples were indexed as 39.0 and 40.5 nm for the highest peak intensity with diethylamine and triethylamine stabilizer, respectively. We examine the effect of stabilizers on the morphology, optical band gap, and photovoltaic performance of the prepared ZnO. We found that ZnO prepared using diethylamine stabilizer exhibiting significant efficiency of 1.45%, open-circuit voltage 0.454 V, short-circuit current density 2.128 mA/cm2, and 0.66 fill factor were achieved under 44 mW/cm2 illumination powers with dye-3. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; KEY WORDS: Dye-sensitized solar cells, ZnO, Band gap, Photovoltaic performance &nbsp; Bull. Chem. Soc. Ethiop. 2022, 36(1), 209-222.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; DOI: https://dx.doi.org/10.4314/bcse.v36i1.17 &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp