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Background Immunocompromised patients face reactivation of latent viruses that increase the risk of morbidity. Aim The study aimed to detect human herpes virus 6 (HHV-6) reactivation among allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT) recipients and to correlate potentially attributed clinical manifestations to HHV-6 DNA plasma level. Methods A prospective study included all (forty) patients undergoing allo and auto-HSCT from Jan 2020 till June 2022. Plasma samples were collected for HHV-6 serology, and for HHV-6 quantitative PCR at post-transplantation weeks 2, 4, 6. Demographic and clinical data were recorded. Results Out of 40 peripheral blood stem cell transplant (PBSCT) recipients, 34 (85%) were HHV-6 IgG positive pre-HSCT. Of which, fourteen patients (14/34, 41.2%) showed positive HHV-6 DNaemia. HHV-6 DNAemia (15/40, 37.5%) was significantly higher among allo (8/12, 66.7%) versus auto (7/28, 25%) HSCT recipients (p = 0.030). Patients with HHV-6 DNAemia developed fever, delayed engraftment and bone marrow suppression in 6/15, 40%, thrombocytopenia (5/15, 33.3%), rash and pneumonitis (2/15, 13.3%), acute GVHD (aGVHD) (1/15, 6.7%). HHV-6 DNAemia ranged from 101 to 102,000 copies/mL. Univariate analysis identified conditioning with busulfan–cyclophosphamide as a significant risk (p = 0.043), while receiving BEAM protocol was a protective factor (p = 0.045). In multivariate analysis, receiving BEAM protocol retained significance (p = 0.040). Conclusion Frequent HHV-6 reactivation was detected after HSCT, especially in allo-HSCT recipients with clinical manifestations which could not be otherwise explained. To our best knowledge this is the first study of HHV6 reactivation in HSCT recipients from Egypt. Raising awareness for HHV-6 reactivation manifestations and screening in HSCT recipients could be lifesaving.

This research uses a form-based code (FBC) to affect the townscape through its procedures and components. Impacts of the FBC’s features on the townscape are classified into three categories the effect on urban spaces, buildings, and landscape architecture. This research explores the components of the categories and makes reference to those components within the 6th of October City, Egypt, from 2020 to 2021. Urban spaces are included, regulating plan, and public realm standards were investigated in the central axis and the inner streets. Buildings were also explored; block and lot and building type standards have been inspected at Al-Hossary Square and the 7th District, while survey field observations investigated the frontage type and architectural standards. In addition, landscape architecture components of the FBC were explored through fieldwork observed throughout the city. This research employs an inductive approach of the literature base, a comparative analytical approach to compare the unified building law (UBL) with the FBC components, and a documentary survey method for fieldwork. The results extracted a proposed townscape code and some modifications of the building law (modifying some existing articles and adding new ones) to make FBC applicable in the surveyed city.

Occupant-centric control (OCC) strategies rely on different algorithms to learn and predict occupants’ patterns and preferences, then utilize these predictions to optimize building operations. However, testing different OCC algorithms or fine-tuning their configurations in real buildings can be a lengthy process. To this end, we present a framework for testing OCCs in a simulation environment prior to field implementation. The proposed workflow entails using synthetic occupant behaviour models and simulating OCC strategies to learn their preferences. The goal is to enable quick comparison of different OCC configurations under various scenarios by modifying occupant behaviour assumptions, as well as climate and design parameters. For proof-of-concept, the proposed method was applied in a case-study to simulate OCCs for lighting and heating/cooling setpoint adjustments in a single office under various occupant types, as well as OCC settings and design configurations. Results demonstrated the benefits of the proposed framework and its potential for providing a more holistic evaluation of OCCs under different scenarios. Using the proposed framework, building designers and operators can identify potential issues with OCCs and fine-tune their settings prior to field implementation.

To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western population. Immunohistochemistry for ERG, PTEN and SPINK1 was performed in a cohort of localized PCA (n = 340). The data were correlated to pathological and clinical outcomes and compared to Western populations. ERG expression and PTEN loss were noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression was assessed in a subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in the lower grade groups (1–3 vs 4–5; p = 0.04). In contrast to the Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI 1.10–726, p = 0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI 0.98–7.33, p = 0.05), after adjusting for GG, path stage and surgical margin. This study documents significant differences in key molecular events in PCA in Middle Eastern population compared to Western populations that could explain differences in PCA incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest risk for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCA and add further insight to understanding PCA molecular pathways.

A global concern claims that activities and functions that once filled traditional public spaces are privatized being less and less oriented to the public. In Cairo’s new settlements, public spaces don’t seem to contribute to its public life. Each community’s most valuable assets are the ones they already have; thus, urbanisms advocate the role of retaining traditional street patterns, vistas, and landscape of a community’s distinct character. The research aim is to identify design attributes to be added to the literature in terms of designing public spaces for the specific cultural context of Cairo, Egypt, and its new suburban settlements. The methodology then follows a comparative analysis study to reach the desired objectives of buildings a community character approach. In an exploratory method, two case studies of public spaces in Cairo are chosen following a purposive selection most relevant to the study. The target is to choose two cases in proximity for users to be familiar with the two of them and enable a reliable comparison. It then conducts a survey that involves the user’s evaluation of their public spaces in correlation to their needs. Jan Gehl’s twelve criteria are adopted by this paper’s field investigation for the assessment of public spaces’ quality. Findings of the study include an elaboration on Jan Gehl’s twelve criteria either by highlighting the importance of existing aspects or the addition of further criteria that showed value to public space quality and their users. The findings provide guidelines that help in designing quality public spaces in Cairo’s new settlements. The added value from this study is in identifying a set of factors or attributes that consider users’ needs for a given cultural context.

Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease. 228 radical prostatectomies (RP) and 318 transurethral resection of prostate (TURP) samples were assessed by immunohistochemistry (IHC) for TFF3 and by IHC and fluorescent in situ hybridization (FISH) for PTEN. Results of biomarkers expression were correlated with various pathological and clinical outcome parameters including biochemical recurrence (BCR) in the RP cohort and cancer-specific mortality (PCSM) and overall survival (OS) in the TURP cohort. TFF3 expression was detected in 131/226 (57.9%) RP samples and 148/318 (46.5%) of TURP cases. In general, TFF3 positivity was less frequently observed with advanced Gleason Groups. TFF3 expression was also assessed in relation to PTEN expression. Only 15–16% of TFF3-expressed cases were present in association with complete loss of PTEN expression in the TURP and localized cohorts, respectively. Loss of TFF3 expression was not related to BCR after RP, but was prognostic in the non-surgical cohort and associated with decrease OS and PCSM (HR 2.31, CI: 1.67–3.18, p

Since the opening of the Suez Canal in 1869, a plethora of Red Sea fishes have entered the Mediterranean Sea (Lessepsian migration). The Comber Serranus cabrilla is considered to have moved in the opposite direction as anti-Lessepsian migrant and has an established population in the northern Red Sea. Mitochondrial (COI) and nuclear DNA from 49 individuals from Red Sea (Gulf of Suez) and Mediterranean populations (Cyprus, Egypt and Lebanon), as well as GenBank sequences from other Mediterranean and Atlantic populations were analyzed to study phylogenetic relationships. COI sequencing resulted in a phylogenetic tree that isolated the Red Sea population from all Mediterranean and Atlantic populations. Furthermore, sequence divergence within the Red Sea population was significantly lower than in Atlantic and Mediterranean populations. Moreover, none of the Mediterranean haplotypes were present in the Red Sea. SNPs and MIG-seq analyses of nuclear DNA confirmed that the Red Sea population is genetically different from the Mediterranean populations. A rough estimate of divergence time suggested that Mediterranean and Red Sea populations separated 194,055 years ago, at the latest. Serranus cabrilla must, therefore, have existed in the Red Sea prior to the opening of the Suez Canal and can no longer be considered as an anti-Lessepsian migrant.

Dibenzenesulphonyl diethyl amine has been prepared and used as a starting material to be introduced as an alkylating agent. Reaction of dibenzenesulphonyl diethyl amine with indole in the presence of sodium and absolute ethanol gave seven unexpected products, five of which were separated by flash chromatography. The structure of product 5 was established on the basis of elemental analysis and spectral data [IR, 1H-NMR, 13C-NMR, distortionless enhancement by polarization transfer (DEPT), 1H-1H correlation spectroscopy (COSY) NMR, 1H/13C heteronuclear multiple quantum coherence (HMQC) NMR and mass spectra (CI/Ms and EI/Ms)]. The antibacterial activity of compound 5 is very compatible with ampicillin.

Despite the research advances and demonstrated benefit of occupant modelling and simulation in recent years, its uptake in building simulation practice has been relatively slow. One of the underlying causes of this issue is limited occupant-related features of building performance simulation (BPS) tools. To this end, we present a detailed breakdown of occupant-related features and compare them between common BPS tools. Based on the outcomes of a stakeholder workshop, and an international survey that focused on occupant modelling, we provide detailed recommendations to improve occupant-related features in BPS tools. We finally present a case study demonstrating the suggested occupant-related features to apply multiple occupancy assumptions, and integrate occupant behaviour models from the literature. Results are presented as part of a non-functional mock-up graphical user interface (GUI) to demonstrate potential features of BPS tools given the suggested occupant-related improvements. These suggested improvements for BPS tools would enable users to quickly assess proposed designs’ sensitivity to different occupancy scenarios, and ultimately increase the robustness of their final designs. The presented recommendations are relevant to practitioners, researchers, and BPS tool developers as part of the efforts to increase the uptake of detailed occupant modelling in building simulation practice.

To validate a previously characterized 10-gene signature in prostate cancer with implication to distinguish aggressive and indolent disease within low and intermediate patients’ risk groups. A case–control study design used to select 545 patients from the Mayo clinic tumor registry who underwent radical prostatectomy. A training set from this cohort (n = 359) was used to build a 10-gene model, based on high-dimensional discriminant analysis (HDDA10) to predict several endpoints of clinical patients’ outcome. An independent set (n = 219) from the same institution was used as validation set. HDDA10 showed significant performance for predicting metastasis (Mets) (AUC 0.68, p = 6.4E – 6) and biochemical recurrence (BCR) (AUC = 0.65, p = 0.003) in the validation set outperforming Gleason grade grouping (GG) for BCR (AUC 0.57, p = 0.03) and with comparable performance for Mets endpoint (GG AUC 0.66, p = 8.1E – 5). HDDA10 prognostic significance was superior to any clinical–pathological parameter within GG2 + 3 (GS7) patients achieving an AUC of 0.74 (p = 0.0037) for BCR compared to Gleason pattern 4 (AUC 0.64) (p = 0.015) and AUC for Mets of 0.68 versus AUC of 0.65 for Gleason pattern 4 (p = 0.01). HDDA10 remained significant for both BCR and Mets in multivariate analysis, suggesting that it can be used to increase accuracy in stratifying patients eligible for active surveillance. HDDA10 is of added value to GG and other clinical–pathological parameters in predicting BCR and Mets endpoint, especially in the low to intermediate patients’ risk groups. HDDA10 prognostic value should be further validated prospectively in stratifying patients specifically in low to intermediate GS (GG1-2), such as active surveillance programs.

Water quality and bacterial contamination from 18 drinking water municipal plants in three locations at Giza governorate were investigated. The average total count of bacteria detected after four stages of treatments in the investigated plants was 32 CFU/1 mL compared to 2330 cfu/mL for raw water, with a reduction percentage of 98.6. Although there is a relatively high removal percent of bacterial contamination from the water sources, however, several bacterial pathogens were identified in the produced water prepared for drinking including Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Shigella spp. After 3 days of water incubation at 30 °C, the amount of bacterial endotoxins ranged from 77 to 137 ng/mL in the water produced from the municipal plants compared to 621-1260 ng/mL for untreated water. The main diseases reported from patients attending different clinics and hospitals during summer 2014 at the surveyed locations and assuredly due to drinking water from these plants indicated that diarrheas and gastroenteritis due to E. coli and Campylobacter jejuni constituted 65.7% of the total patients followed by bacillary dysentery or shigellosis due to Shigella spp. (7.9%) and cholera due to Vibrio cholera (7.2%). There was an increase in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) as well as urea and creatinine values of guinea pigs consuming water produced from the non-governmental plants for 6 months indicating remarkable liver and kidney damages. Histological sections of liver and kidney from the tested animal revealed liver having ballooning degeneration of hepatocytes and distortion and fragmentation of the nuclei, while the section of the kidney showed irregularly distributed wrinkled cells, degenerated Bowman's capsule, congested blood vessels, and inflammatory cells.

Background Cancer and infectious diseases are problematic because of continuous emergence of drug resistance. One way to address this enormous global health threat is bioprospecting the unlikeliest environments, such as extreme marine niches, which have tremendous biodiversity that is barely explored. One such environment is the Red Sea brine pool, Atlantis II Deep (ATII). Here, we functionally screened a fosmid library of metagenomic DNA isolated from the ATII lower convective layer (LCL) for antibacterial and anticancer activities. Results Selected clones, 14-7E and 10-2G, displayed antibacterial effects on the marine strain Bacillus sp. Cc6. Moreover, whole cell lysates from 14-7E and 10-2G exhibited decreased cell viability against MCF-7 (39.1% ± 6.6, 42% ± 8.1 at 50% v/v) and U2OS cells (35.7% ± 1.9, 79.9% ± 5.9 at 50% v/v), respectively. By sequencing the insert DNA from 14-7E and 10-2G, we identified two putative orphan biosynthetic gene clusters. Both clusters harbored putative ATP-binding cassette (ABC) transporter permeases and S-adenosylmethionine-related genes. Interestingly, the biosynthetic gene cluster identified on 14-7E is of archaeal origin and harbors a putative transcription factor. Several identified genes may be responsible for the observed antibacterial and anticancer activities. The 14-7E biosynthetic gene cluster may be encoding enzymes producing a specialized metabolite (effect of detected genes involved in C–C bond formation and glycosylation). The bioactivity may also be due to predicted subtilases encoded by this cluster. The 10-2G cluster harbored putative glycosyltransferase and non-ribosomal peptide synthase genes; thus the observed activity of this clone could be caused by a bioactive peptide. Conclusions The ATII LCL prokaryotic metagenome hosts putative orphan biosynthetic gene clusters that confer antibiotic and anticancer effects. Further biochemical studies should characterize the detected bioactive components, and the potential use of 14-7E metabolite for antibiosis and 10-2G metabolite as a selective anti-breast cancer drug. Electronic supplementary material The online version of this article (10.1186/s12934-019-1103-3) contains supplementary material, which is available to authorized users.

The α7 nicotinic acetylcholine receptor (α7nAChR) has been a promising target for diseases affecting cognition and higher cortical functions; however, the effect observed in animal models failed to translate into human clinical trials identifying a translational gap. CHRFAM7A is a human-specific fusion gene with properties that enable incorporation into the α7nAChR and, being human specific, CHRFAM7A effect was not accounted for in preclinical studies. We hypothesized that CHRFAM7A may account for this translational gap and understanding its function may offer novel insights when exploring α7nAChR as a drug target. CHRFAM7A is present in different copy number variations (CNV) in the human genome with high frequency. To study the functional consequences of the presence of the CHRFAM7A, two induced pluripotent stem cell (iPSC) lines (0 copy and 1 copy direct) were developed. The 0 copy line was rescued with CHRFAM7A transfection to control for genetic heterogeneity. As readouts for genotype–phenotype correlation, α7nAChR synaptic transmission and amyloid beta 1–42 (Aβ1–42) uptake were tested. Synaptic transmission in the presence of CHRFAM7A demonstrated that PNU-modulated desensitization of α7nAChR currents increased as a function of CHRFAM7A dosage. CHRFAM7A mitigated the dose response of Aβ1–42 uptake suggesting a protective effect beyond physiological concentrations. Furthermore, in the presence of CHRFAM7A Aβ1–42 uptake activated neuronal interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) without activating the canonical inflammasome pathway. Lead optimization may identify more potent molecules when the screen has a model harboring CHRFAM7A. Incorporating pharmacogenetics into clinical trials may enhance signals in efficacy measures.

Dermatophytes are classified in three genera, Epidermophyton, Microsporum and Trichophyton. They have the capacity to invade keratinized tissue to produce a cutaneous infection known as dermatophytoses. This investigation was performed to study the effect of gaseous ozone and ozonized oil on three specific properties of six different dermatophytes. These properties included sporulation, mycelia leakage of sugar and nutrients and the activity of their hydrolytic enzymes. Generally, ozonized oil was found to be more efficacious than gaseous ozone. Microsporum gypseum and Microsporum canis were the most susceptible, while Trichophyton interdigitale and T. mentagrophytes were relatively resistant. The study revealed a steady decline in spore production of M. gypseum and M. canis on application of ozonated oil. An increase in leakage of electrolytes and sugar was noticed after treatment with ozonized oil in the case of M. gypseum, M. canis, T. interdigitale, T. mentagrophytes and T. rubrum. The results also revealed loss in urease, amylase, alkaline phosphatase, lipase and keratinase enzyme producing capacity of the investigated fungi.

The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.

A series of the newly substituted pyrano[1,2,3]triazine derivatives 3–14 were synthesized using compounds 1 and 2 as starting materials. Compound 2 was methylated using methyl iodide to compound 3, which was treated with aromatic aldehydes to give acryloyl derivatives 4a–c. Compounds 4a,b were reacted with ethyl cyano-acetate to give pyran-3-carboxylates 5a,b which were reacted with ethyl glycinate hydrochloride to give 6a,b. Treatment of 6a,b with hydrazine hydrate gives acid hydrazides 7a,b, which were reacted with 5,5-dimethyl-1,3-cyclohexanedione to give acetohydrazides 8a,b. Cyclization of 8b with 2-(4-nitrobenzylidene)malononitrile afforded hexahydroquinoline 9. However, the acridindione 10 was synthesized by heating of 8b with 2-(4-nitrobenzylidene)malononitrile in acetic acid containing few drops of triethylamine. Treatment of 7a,b with phenyl isothiocyanate or 2,5-hexanedione or phthalic anhydride gave compounds 11a,b, 13a,b and 14a,b, respectively. In the present work, all the selected pyrano[1,2,3]trizine derivatives were soluble in DMSO at concentrations high enough to allow cell experiments, and the in vitro biological activity of these compounds was evaluated by their growth inhibitory potency in liver HEPG2 cancer cell lines. The cytotoxic potency of compounds 3–14 was studied in comparison to the known anticancer drugs 5-fluorouracil and doxorubicin.

Multicomponent phenol hydroxylases (mPHs) are diiron enzymes that use molecular oxygen to hydroxylate a variety of phenolic compounds. The DNA sequence of the alpha subunit (large subunit) of mPH from 4-chlorophenol (4-CP)-degrading bacterial strain PT3 was determined. Strain PT3 was isolated from oil-contaminated soil samples adjacent to automobile workshops and oil stations after enrichment and establishment of a chlorophenol-degrading consortium. Strain PT3 was identified as a member of Pseudomonas sp. based on sequence analysis of the 16S rRNA gene fragment. The 4-CP catabolic pathway by strain PT3 was tentatively proposed to proceed via a meta-cleavage pathway after hydroxylation to the corresponding chlorocatechol. This hypothesis was supported by polymerase chain reaction (PCR) detection of the LmPH encoding sequence and UV/VIS spectrophotometric analysis of the culture filtrate showing accumulation of 5-chloro-2-hydroxymuconic semialdehyde (5-CHMS) with λmax 380. The detection of catabolic genes involved in 4-CP degradation by PCR showed the presence of both mPH and catechol 2,3-dioxygenase (C23DO). Nucleotide sequence analysis of the alpha subunit of mPH from strain PT3 revealed specific phylogenetic grouping to known mPH. The metal coordination encoding regions from strain PT3 were found to be conserved with those from the homologous dinuclear oxo-iron bacterial monooxygenases. Two DE(D)XRH motifs was detected in LmPH of strain PT3 within an approximate 100 amino acid interval, a typical arrangement characteristic of most known PHs.