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Abstract Background Purine nucleoside phosphorylase (PNP) deficiency is a rare, autosomal recessive, inborn error of immunity. It is characterized by progressive immune abnormalities ranging from severe combined immunodeficiency (SCID) to combined immunodeficiency less profound than SCID, neurological abnormalities and autoimmunity. Early detection and diagnosis before the development of life-threatening complications are crucial. Methods Immune cell subsets were assessed by flow cytometry, serum immunoglobulins and uric acid levels were evaluated, and genetic testing was performed for all patients. Results Herein, we present six Egyptian PNP deficiency patients from four different families. We describe the patients’ clinical phenotypes, their immunological profile as well as their genetic results. Sequence analysis results detected 4 different variants in the PNP gene; 1 likely pathogenic frameshift deletion c.452del; p.Asn151MetfsTer20 was found in one family, 1 pathogenic nonsense variant c.172C > T; p.Arg58Ter, and 2 likely pathogenic missense variants c.682G > C; p.Ala228Pro and c.722T > C; pIle2241Thr. Conclusion In conclusion, PNP deficiency is a variable immunodeficiency and should be considered in various clinical contexts, with or without neurological manifestations. Hematopoietic stem cell transplantation offers a good treatment option, with excellent clinical outcomes, when performed in a timely manner.

Abstract Background Caspase recruitment domain family, member 11 (CARD11) is an important protein which plays a fundamental role in the activation of NF-κβ pathway in lymphocytes. CARD11 deficiency can be inherited in either autosomal dominant or autosomal recessive forms and present with different phenotypes including combined immunodeficiency, atopic dermatitis, and other variable manifestations. The present report describes clinical phenotypes and immunological defects of two unrelated patients with missense homozygous variants in CARD11 presenting with combined immunodeficiency (CID) and atopic skin disease resembling that reported in dominant negative CARD11 deficiency. The patients underwent next generation sequencing, immunophenotyping of T and B subsets by flow cytometry, T cell stimulation, and evaluation of CARD11 expression. Results Both patients had features suggesting CID including repeated pneumoniae with ICU admissions, chronic diarrhea, and itchy atopic skin disease. Patient-1 has homozygous missense variant in the C terminal domain (c.2839G > A, p.Glu947Lys), and patient-2 has homozygous variant in the inhibitory domain (c.1073C > G, p.Pro568Arg). Both have profound defects in Tregs with normal recent thymic emigrants, memory, and naïve CD4+ T cells. However, in response to stimulation, T cells failed to upregulate the expression of CD25. CARD11 expression by flow cytometry was decreased rather than abolished as previously described in patients with autosomal recessive CARD11 deficiency. B cells showed marked deficiency of switched memory and increase in transitional B cells. Conclusion Missense variants causing CARD11 deficiency may affect the protein function rather than the expression and can result in a phenotype combining the atopic skin disease and the features of CID.

As the global population increases, the expansion of road networks has led to the destruction and disturbance of terrestrial and aquatic habitats. Road-related stressors have significant effects on both lotic and lentic habitats. While there are several systematic reviews that evaluate the effects of roads on lotic environments, there are none that consider their effects on lentic habitats only. We conducted a literature review to achieve two objectives: (1) to summarize the effects of roads on the physical, chemical, and biological properties of lentic environments; and (2) to identify biases and gaps in our current knowledge of the effects of roads on lentic habitats, so that we could find promising areas for future research. Our review found 172 papers published between 1970 and 2020. The most frequently studied stressors associated with roads included road salt and heavy metal contamination (67 and 43 papers, respectively), habitat fragmentation (37 papers), and landscape change (14 papers). These stressors can lead to alterations in conductivity and chloride levels, changes in lake stratification patterns, increases in heavy metal concentrations in water and organisms, and significant mortality as amphibians disperse across roadways. We also identified a variety of other stressors that may be understudied based on their frequency of appearance in our search results, including polycyclic aromatic hydrocarbons, road dust, increased accessibility, hydrological changes, noise pollution, dust suppressants, sedimentation, invasive species introductions, and water withdrawal. Our review indicated that there are strong geographic biases in published studies, with 57.0% examining North American sites and 30.2% examining European sites. Furthermore, there were taxonomic biases in the published literature, with most studies focusing on amphibians (41.7%), fish (15.6%), and macroinvertebrates (14.6%), while few considered zooplankton (8.3%), diatoms (7.3%), amoebas (5.2%), water birds (3.1%), reptiles (2.1%), and macrophytes (1.0%). Based on our review, we have identified promising areas for future research for each of the major stressors related to roadways. However, we speculate that rectifying the geographic and taxonomic bias of our current knowledge could significantly advance our understanding of the impacts of roads on lentic environments, thereby better informing environmental management of these important habitats. Key words: lakes, ponds, roads, lentic, habitat, anthropogenic stress Avec l'augmentation de la population mondiale, l'expansion des reseaux routiers a entraine la destruction et la perturbation des habitats terrestres et aquatiques. Les facteurs de stress lies aux routes ont des effets importants sur les habitats lotiques et lentiques. Alors que plusieurs revues systematiques evaluent les effets des routes sur les environnements lotiques, aucune ne considere leurs effets sur les habitats lentiques uniquement. Les auteurs ont effectue une revue de la litterature pour atteindre deux objectifs : (1) resumer les effets des routes sur les proprietes physiques, chimiques et biologiques des milieux lentiques; et (2) identifier les biais et les lacunes des connaissances actuelles quant aux effets des routes sur les habitats lentiques afin de trouver des domaines prometteurs pour les recherches futures. Leur examen a permis de repertorier 172 articles publies entre 1970 et 2020. Les facteurs de stress associes aux routes les plus frequemment etudies sont le sel de deneigement et la contamination par les metaux lourds (67 et 43 articles respectivement), la fragmentation de l'habitat (37 articles) et la modification du paysage (14 articles). Ces facteurs de stress peuvent entrainer des modifications de la conductivite et des niveaux de chlorure, des changements dans les patrons de stratification des lacs, des augmentations des concentrations de metaux lourds dans l'eau et les organismes, et une mortalite significative lorsque les amphibiens se dispersent sur les routes. Ils ont egalement identifie une variete d'autres facteurs de stress qui peuvent etre sous-etudies en fonction de leur frequence d'apparition dans leurs resultats de recherche, notamment les hydrocarbures aromatiques polycycliques, la poussiere des routes, l'accessibilite accrue, les changements hydrologiques, la pollution sonore, les depoussierants, la sedimentation, l'introduction d'especes envahissantes et le retrait de l'eau. Leur examen a indique qu'il existe de forts biais geographiques dans les etudes publiees, 57,0 % d'entre elles portant sur des sites nord-americains et 30,2 % sur des sites europeens. De plus, il existe des biais taxonomiques dans la litterature publiee, la plupart des etudes se concentrant sur les amphibiens (41,7 %), les poissons (15,6 %) et les macroinvertebres (14,6 %), tandis que peu d'entre elles consideraient le zooplancton (8,3 %), les diatomees (7,3 %), les amibes (5,2 %), les oiseaux aquatiques (3,1 %), les reptiles (2,1 %) et les macrophytes (1,0 %). Sur la base de cet examen, ils ont identifle des domaines prometteurs pour la recherche future pour chacun des principaux facteurs de stress lies aux routes. Cependant, ils supposent que la rectification des biais geographiques et taxonomiques des connaissances actuelles pourrait faire progresser de maniere significative notre comprehension des impacts des routes sur les environnements lentiques, et ainsi mieux eclairer les decision en matiere de gestion environnementale de ces habitats importants. [Traduit par la Redaction] Mots-cles : lacs, etangs, routes, lentique, habitat, stress anthropique, 1 Introduction The Earth currently contains over 21 million km of roads, and models predict that several million more km will be constructed by the year 2050 (Meijer et al. [...]

Abstract Background Human inborn errors of immunity (IEI) are a group of inherited genetic disorders of the immune system. IEI Patients suffer from severe repeated infections, autoimmunity, lymphadenopathy and/or increased susceptibility to malignancies. IEI are due to absence, disproportion, or loss of function of immune cells; mostly inherited in autosomal recessive manner, hence are more common in countries with high rate of consanguinity. Definite diagnosis of IEI is achieved by genetic analysis, however it is not always available. Aim: to report on different IEI categories and impact of expanding the use of flow cytometry (FCM) in diagnosis, categorization and follow up of IEI patients in a highly consanguineous population. Methods Retrospective chart review on different IEI categories diagnosed at the primary immunodeficiency center in Cairo University Specialized Pediatric hospital from 2011 to 2021 based on expanding the use of FCM. Results 1510 IEI patients were diagnosed; 480 were diagnosed genetically with FMF, 11 with cystic fibrosis and 1019 patients were diagnosed with other IEI disorders. Phagocytic defects were the commonest (30%) followed by severe combined immunodeficiency (22%) and combined immunodeficiency (18.3%). FCM testing properly diagnosed and categorized 73% of the cases. Conclusion Using multi-color FCM to evaluate immune cells populations, subpopulations, functions, and intracellular proteins expression is proved a useful cost-effective method for screening, categorization and follow up of IEI patients. FCM can improve the diagnosis of IEI significantly when tests are properly targeted and well designed. This study presents a 10-year experience in diagnosis of IEI using FCM at a tertiary referral center in a setting of limited resources and yet high prevalence of IEI.

Background: Surface smoothness considered to be a significant part of the appearance and success of the restorative materials. The aim of this study was to assess the influence of four different polishing systems on surface roughness of four resin composite materials when subjected to thermocycling. Materials and Methods: This research was designed as a comparative study. Four resin composites were used which are: Nanofill composite (Filtek Supreme XT), nanohybrid composite (Tetric EvoCeram), microfill composite (Renamel Microfill), and microhybrid composite (Filtek Z250). Sixty disk-shaped specimens of each resin composite were prepared then divided into four groups according to the polishing system (n = 15); which were Sof-Lex Spiral, Diatech Shapeguard, Venus Supra, and Astropol. The specimens of each group were polished following the manufactures' instructions, then surface roughness, Ra values in μm were measured initially and after the specimens subjected to thermal cycling. The influence of resin composites, polishing systems, thermocycling, and their interaction effects on surface roughness (Ra mean values) was statistically analyzed mainly by using the repeated measures two-way analysis of variance test, whereas the Bonferroni''s post hoc test was applied for pair-wise comparisons. P ≤ 0.05 was used as the significant level. Results: The results of this study revealed that Filtek Supreme XT recorded significantly the lowest mean surface roughness (Ra) of 0.2533 ± 0.073 μm (P < 0.001). The Sof-Lex Spiral polishing system revealed significantly the lowest mean surface roughness (Ra) of 0.2734 ± 0.0903 μm (P = 0.004). Regardless of composite type and polishing system, there was a statistically significant increase in mean surface roughness values (Ra) in μm after thermocycling (0.2251 ± 0.0496 μm and 0.3506 ± 0.0868 μm, respectively) (P < 0.001). Conclusion: Resin composite type, polishing method, and thermocycling aging significantly affected the surface roughness of composites; Nanofill composite and Sof-Lex Spiral polishing system provided the lowest values of surface roughness which increased after thermocycling.

Abstract Objective Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described. Results Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.