Unveiling the Antiviral Efficacy of Forskolin: A Multifaceted In Vitro and In Silico Approach.

Coleus forskohlii (Willd.) Briq. is a medicinal herb of the Lamiaceae family. It is native to India and widely present in the tropical and sub-tropical regions of Egypt, China, Ethiopia, and Pakistan. The roots of C. forskohlii are edible, rich with pharmaceutically bioactive compounds, and traditionally reported to treat a variety of diseases, including inflammation, respiratory disorders, obesity, and viral ailments. Notably, the emergence of viral diseases is expected to quickly spread; consequently, these data impose a need for various approaches to develop broad active therapeutics for utilization in the management of future viral infectious outbreaks. In this study, the naturally occurring labdane diterpenoid derivative, Forskolin, was obtained from Coleus forskohlii. Additionally, we evaluated the antiviral potential of Forskolin towards three viruses, namely the herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), hepatitis A virus (HAV), and coxsackievirus B4 (COX-B4). We observed that Forskolin displayed antiviral activity against HAV, COX-B4, HSV-1, and HSV-2 with IC50 values of 62.9, 73.1, 99.0, and 106.0 µg/mL, respectively. Furthermore, we explored the Forskolin's potential antiviral target using PharmMapper, a pharmacophore-based virtual screening platform. Forskolin's modeled structure was analyzed to identify potential protein targets linked to its antiviral activity, with results ranked based on Fit scores. Cathepsin L (PDB ID: 3BC3) emerged as a top-scoring hit, prompting further exploration through molecular docking and MD simulations. Our analysis revealed that Forskolin's binding mode within Cathepsin L's active site, characterized by stable hydrogen bonding and hydrophobic interactions, mirrors that of a co-crystallized inhibitor. These findings, supported by consistent RMSD profiles and similar binding free energies, suggest Forskolin's potential in inhibiting Cathepsin L, highlighting its promise as an antiviral agent.

Unravelling the Antimicrobial, Antibiofilm, Suppressing Fibronectin Binding Protein A (fnba) and cna Virulence Genes, Anti-Inflammatory and Antioxidant Potential of Biosynthesized Solanum lycopersicum Silver Nanoparticles.

Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 µg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.

Lifespan neurodegeneration of the human brain in multiple sclerosis.

Atrophy related to multiple sclerosis (MS) has been found at the early stages of the disease. However, the archetype dynamic trajectories of the neurodegenerative process, even prior to clinical diagnosis, remain unknown. We modeled the volumetric trajectories of brain structures across the entire lifespan using 40,944 subjects (38,295 healthy controls and 2649 MS patients). Then, we estimated the chronological progression of MS by assessing the divergence of lifespan trajectories between normal brain charts and MS brain charts. Chronologically, the first affected structure was the thalamus, then the putamen and the pallidum (around 4 years later), followed by the ventral diencephalon (around 7 years after thalamus) and finally the brainstem (around 9 years after thalamus). To a lesser extent, the anterior cingulate gyrus, insular cortex, occipital pole, caudate and hippocampus were impacted. Finally, the precuneus and accumbens nuclei exhibited a limited atrophy pattern. Subcortical atrophy was more pronounced than cortical atrophy. The thalamus was the most impacted structure with a very early divergence in life. Our experiments showed that lifespan models of most impacted structures could be an important tool for future preclinical/prodromal prognosis and monitoring of MS.

Thymoquinone, a Novel Multi-Strike Inhibitor of Pro-Tumorigenic Breast Cancer (BC) Markers: CALR, NLRP3 Pathway and sPD-L1 in PBMCs of HR+ and TNBC Patients.

Breast cancer (BC) is not only a mass of malignant cells but also a systemic inflammatory disease. BC pro-tumorigenic inflammation has been shown to promote immune evasion and provoke BC progression. The NOD-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome is activated when pattern recognition receptors (PRRs) sense danger signals such as calreticulin (CALR) from damaged/dying cells, leading to the secretion of interleukin-1ß (IL-1ß). CALR is a novel BC biological marker, and its high levels are associated with advanced tumors. NLRP3 expression is strongly correlated with an elevated proliferative index Ki67, BC progression, metastasis, and recurrence in patients with hormone receptor-positive (HR+) and triple-negative BC (TNBC). Tumor-associated macrophages (TAMs) secrete high levels of IL-1ß promoting endocrine resistance in HR+ BC. Recently, an immunosuppressive soluble form of programmed death ligand 1 (sPD-L1) has been identified as a novel prognostic biomarker in triple-negative breast cancer (TNBC) patients. Interestingly, IL-1ß induces sPD-L1 release. BC Patients with elevated IL-1ß and sPD-L1 levels show significantly short progression-free survival. For the first time, this study aims to investigate the inhibitory impact of thymoquinone (TQ) on CALR, the NLRP3 pathway and sPD-L1 in HR+ and TNBC. Blood samples were collected from 45 patients with BC. The effect of differing TQ concentrations for different durations on the expression of CALR, NLRP3 complex components and IL-1ß as well as the protein levels of sPD-L1 and IL-1ß were investigated in the peripheral blood mononuclear cells (PBMCs) and TAMs of TNBC and HR+ BC patients, respectively. The findings showed that TQ significantly downregulated the expression of CALR, NLRP3 components and IL-1ß together with the protein levels of secreted IL-1ß and sPD-L1. The current findings demonstrated novel immunomodulatory effects of TQ, highlighting its potential role not only as an excellent adjuvant but also as a possible immunotherapeutic agent in HR+ and TNBC patients.

Effect of Telehealth Nursing Intervention on Psychological Status and Coping Strategies Among Parents During COVID-19 Pandemic.

Given the serious threats posed by the COVID-19 virus, preventive measures and coping strategies are critical in lowering infection rates, managing disease transmission, and improving people's psychological well-being. This study aimed to evaluate the effect of telehealth nursing intervention on psychological status and coping strategies among parents during the second wave of COVID-19. A quasi-experimental (one group pre-/posttest) design was used. A purposive sample of 209 parents in Menoufia governorate, Egypt, was collected using Google Form. Tools: (1) Structured questionnaire for parents (a) Demographic data (b) Parents' knowledge regarding COVID-19. (2) Parents' preventive practices of the COVID-19 questionnaire. (3) Parents" coping strategies with COVID-19 pandemic questionnaire. (4) Depression, Anxiety, and Stress Scale (Arabic DASS-21). Approximately 82.8% of the participants had normal to mild depression after the telehealth nursing intervention compared with 62.6% before the telehealth nursing intervention. Approximately 55.4% of them had moderate to extremely severe level of anxiety before the telehealth nursing intervention compared with (21.6%) after the telehealth nursing intervention. Approximately 85.2% reported a normal level of stress after the telehealth nursing intervention compared with (62.7%) before the telehealth nursing. Telehealth nursing intervention was effective for improving parents' knowledge, preventive practice, and coping strategies during the second wave of COVID-19.

Bioaugmentation with As-transforming bacteria improves arsenic availability and uptake by the hyperaccumulator plant Pteris vittata (L).

Inorganic arsenic (As) is a toxic and carcinogenic pollutant that has long-term impacts on environmental quality and human health. Pteris vittata plants hyperaccumulate As from soils. Soil bacteria are critical for As-uptake by P. vittata. We examined the use of taxonomically diverse soil bacteria to modulate As speciation in soil and their effect on As-uptake by P. vittata. Aqueous media inoculated with Pseudomonas putida MK800041, P. monteilii MK344656, P. plecoglossicida MK345459, Ochrobactrum intermedium MK346993 or Agrobacterium tumefaciens MK346997 resulted in the oxidation of 5-30% As(III) and a 49-79% reduction of As(V). Soil inoculated with P. monteilii increased extractable As(III) and As(V) from 0.5 and 0.09 in controls to 0.9 and 0.39 mg As kg-1 soil dry weight, respectively. Moreover, and P. vittata plants inoculated with P. monteilii, P. plecoglossicida, O. intermedium strains, and A. tumefaciens strains MK344655, MK346994, MK346997, significantly increased As-uptake by 43, 32, 12, 18, 16, and 14%, respectively, compared to controls. The greatest As-accumulation (1.9 ± 0.04 g kg-1 frond Dwt) and bioconcentration factor (16.3 ± 0.35) was achieved in plants inoculated with P. monteilii. Our findings indicate that the tested bacterial strains can increase As-availability in soils, thus enhancing As-accumulation by P. vittata. Novelty statement Pteris vittata, a well-known As-hyperaccumulator, has the remarkable ability to accumulate higher levels of As in their above-ground biomass. The As-tolerant bacteria-plant interactions play a significant role in bioremediation by mediating As-redox and controlling As-availability and uptake by P. vittata. Our studies indicated that most of the tested bacterial strains isolated from As-impacted soil significantly enhanced As-uptake by P. vittata. P. monteilii oxidized 20% of As(III) and reduced 50% of As(V), increased As-extraction from soils, and increased As-uptake by 43% greater compared with control. Therefore, these strains associated with P. vittata can be used in large-scale field applications to remediate As-contaminated soil.

Diterpenes and sterols from the Red Sea soft coral Sarcophyton trocheliophorum and their cytotoxicity and anti-leishmanial activities.

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene (1), two known analogues [sarcotrocheliol (2) and sarcophine (3)], and two sterols [(24S)-24-methylcholesterol (4) and gorgosterol (5)]. The structure of the new diterpene (1) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC50 17.4 ± 1.9 µg/ml) and HepG2 (IC50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC50 >100 µg/ml).

Bioactive constituents from Thunbergia erecta as potential anticholinesterase and anti-ageing agents: Experimental and in silico studies.

Acetylcholinesterase (AChE) inhibitor and telomerase reverse transcriptase (TERT) potentiator phytochemicals are highly targeted as anti-Alzheimerꞌs disease and as an anti-ageing process. A phytochemical study of Thunbergia erecta aerial parts resulted in the isolation of ten compounds (1-10). Their structures were identified based on spectral data and comparison with literature values. The activity of our pure isolates on AChE and TERT enzymes by documented in vitro assay methods were evaluated. The results indicated that apigenin (2), vanillic acid (4), and acacetin-7-O-ß-D-glucoside (7) exhibited potent inhibition of AChE (IC50 37.33, 30.80 and 49.57 ng/mL, respectively), compared to the standard drug donepezil (IC50 31.25 ng/mL). In the TERT enzyme assay, compound 7 triggered a 1.66­fold increase in telomerase activity at the concentration of 2.85 ng/ml. This is the first study that demonstrates that compound 7 isolated from T. erecta can lead to such telomerase activity relative to control cells. Virtual screening studies including docking, rapid overlay chemical structure (ROCS), and calculated structure-property relationships (SPR) were implemented in this work. Molecular docking studies supported the binding of compounds 2, 4, and 7 through hydrogen bonds (HBs) formation to essential amino acid residues namely ARG:24 A, SER:347 A, LYS:51 A, PHE:346 A, and GLY:345 A of acetylcholinesterase. ROCS and SPR analyses realized compound 2 as a possible treatment of Alzheimer's disease and as a lead compound for drug development process through applying semisynthetic modifications.

The severity and atypical presentations of COVID-19 infection in pediatrics.

BACKGROUND: Emergence of 2019-nCoV attracted global attention and WHO declared COVID-19 a public health emergency of international concern. Therefore we aimed to explore the severity and atypical manifestations of COVID-19 among children. METHODS: This is an observational cohort study conducted on 398 children with confirmed COVID-19 by using real-time reverse transcriptase polymerase chain reaction assay for detection of 2019-nCoV nucleic acid during the period from March to November 2020. Patients were subdivided regarding the severity of COVID-19 presentation into Group I (Non-severe COVID-19) was admitted into wards and Group II (Severe COVID-19) admitted into the PICU. RESULTS: Non- severe cases were 295cases (74.1%) and 103cases (25.9%) of severe cases. There was a significant difference between age groups of the affected children (P < 0.001) with a median (0-15 years). Boys (52%) are more affected than girls (48%) with significant differences (P < 0.001). 68.6%of confirmed cases had contact history to family members infected with COVID-19. 41.7% of severe patients needed mechanical ventilation. Death of 20.4% of severe cases. In COVID-19 patients, fever, headache, fatigue and shock were the most prominent presentations (95, 60.3, 57.8, and 21.8% respectively). 3.5% of children were manifested with atypical presentations; 1.25% manifested by pictures of acute pancreatitis, 1.25% presented by manifestations of deep venous thrombosis and 1.0% had multisystem inflammatory syndrome (MIS-C). Multivariate regression analysis showed that COVID-19 severity in children was significantly higher among children with higher levels of D-dimer, hypoxia, shock and mechanical ventilation. CONCLUSION: Most children had a non-severe type of COVID-19 and children with severe type had higher levels of D-dimer, hypoxia, shock and mechanical ventilation.

An Ultrasound Scoring Model for the Prediction of Intrapartum Morbidly Adherent Placenta and Maternal Morbidity: A Cross-Sectional Study.

OBJECTIVE: To design an ultrasound scoring model for the prediction of the intrapartum morbidly adherent placenta (MAP) and maternal morbidity. PATIENTS AND METHODS: 114 females with singleton pregnancies ≥ 28 weeks of gestation referred for suspicion of MAP were included. All patients underwent examination by two-dimensional ultrasound with the color Doppler setting. Five signs were evaluated: the retroplacental echolucent space, placental lacunae, the hyperechoic uterine-bladder interface, retroplacental myometrium thickness, and subplacental, uterine serosa-bladder wall, intraplacental and bladder wall vascularity. We designed a score ranging from 0-8.5 points, including the five signs according to their odds ratios and evaluated its prediction for MAP and maternal morbidity. RESULTS: Using multivariate logistic regression, all ultrasound signs were significant dependent predictors for both MAP and maternal morbidity (myometrium thickness < 1 mm followed by lacunae ≥ 4 and lost retroplacental echolucent space). The only independent predictors for MAP were myometrium thickness < 1 mm and lacunae ≥ 4, while myometrium thickness < 1 mm and lost retroplacental echolucent space were predictive for maternal morbidity. The score showed a perfect agreement with MAP and a good one for maternal morbidity. CONCLUSION: Application of the score we designed can improve the ultrasound diagnosis of MAP and the maternal outcome.

Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.

Intranasal In Situ Gel of Apixaban-Loaded Nanoethosomes: Preparation, Optimization, and In Vivo Evaluation.

The present study was conducted to formulate ethosomal thermoreversible in situ gel of apixaban, an anticoagulant drug, for nasal delivery. Ethosomes were formed, of lecithin, cholesterol, and ethanol, by using thin-film hydration method. The prepared ethosomes were characterized by Zetasizer, transmission electron microscope, entrapment efficiency, and in vitro study. The selected ethosomal formula (API-ETHO2) was incorporated in gel using P407 and P188 as thermoreversible agents and carbopol 934 as mucoadhesive agent. Box-Behnken design was used to study the effect of independent variables (concentration of P407, P188, and carbopol 934) on gelation temperature, mucoadhesive strength, and in vitro cumulative percent drug released at 12h (response variables). The optimized formulation was subjected to compatibility study, ex vivo permeation, histopathological examination for the nasal mucosa, and in vivo study. API-ETHO2 was spherical with an average size of 145.1±12.3 nm, zeta potential of -20±4 mV, entrapment efficiency of 67.11%±3.26, and in vitro % release of 79.54%±4.1. All gel formulations exhibited an acceptable pH and drug content. The optimum gel offered 32.3°C, 1226.3 dyne/cm2, and 53.50% for gelation temperature, mucoadhesive strength, and in vitro percent released, respectively. Apixaban ethosomal in situ gel evolved higher ex vivo permeation (1.499±0.11 µg/cm2h) through the nasal mucosa than pure apixaban gel. Histopathological study assured that there is no necrosis or tearing of the nasal mucosa happened by ethosomal gel. The pharmacokinetic parameters in rabbit plasma showed that intranasal administration of optimized API-ethosomal in situ gel achieved higher Cmax and AUC0-∞ than unprocessed API nasal gel, nasal suspension, and oral suspension. The ethosomal thermoreversible nasal gel established its potential to improve nasal permeation and prolong anticoagulant effect of apixaban.

Nerve conduction study findings and their predictors in clinically diagnosed patients with carpal tunnel syndrome in a Saudi population.

BACKGROUND: Despite the reports of carpal tunnel syndrome (CTS) being commonplace in Saudi Arabia, there is scarcity of cross-sectional or prospective studies detailing the profile of nerve conduction study (NCS) findings in patients with CTS. OBJECTIVE: The study aimed to evaluate the neurophysiologic profile of CTS with the view to finding the determinant of abnormal findings in clinically diagnosed cases of CTS in a population of Saudis. METHODS: Nerve conduction study was performed on consecutive patients with clinically diagnosed CTS. Median sensory, ulnar sensory, radial sensory median motor and ulnar motor nerves were assessed. The nerve conduction parameters measured were median and ulnar sensory peak latency, amplitude and velocity. Median conduction velocity, distal latency, and amplitude were also measured. Comparative median-ulnar and median-ulnar-digit 4 studies were done and the severity of CTS was determined. Data was analyzed using STATA software version 12. RESULTS: A total of 152 patients, comprising 59 males and 93 females (mean age of 42.7 years) with clinically diagnosed CTS were seen during the study period. About 72.4% patients had numbness and paresthesia in the affected fingers, 66.5% had pain in the hands, and 10.5% had weakness in the affected hands. Majority of the patients (62%) had bilateral clinical features. Carpal tunnel syndrome was confirmed with NCS in 84 (55.26%) patients. Presence of weakness in the affected hand, positive Phalen' sign, and positive Tinel's sign in patients appear to predict [6.1 (1.2-30.7), 3.9 (1.2-30.2), and 4.9 (1.4-17.0) respectively] abnormal NCS findings after adjustment for age, gender and the presence of DM. CONCLUSION: The study revealed that over half of the patients with CTS had NCS/ Electromyography (EMG) abnormalities. Presence of hand muscles weakness, positive Phalen and Tinel's signs predict abnormal findings on NCS/EMG in patients with CTS.

The impact of catalase and glutathione peroxidase-1 genetic polymorphisms on their enzyme activities among Egyptian patients with keratoconus.

BACKGROUND: Elevated oxidative stress plays a significant role in pathophysiology of keratoconus (KC). Polymorphisms of the antioxidant enzymes as CAT and GPX-1 might alter their antioxidant enzyme capacities leading to increase in the oxidative damage induced KC. AIM: To analyze the impact of CAT rs7943316 A/T and GPX-1 rs1050450 C/T single nucleotide polymorphisms (SNPs) on the risk and severity of KC among a group of Egyptian population. SUBJECT & METHODS: CAT rs7943316 and GPX-1 rs1050450 SNPs were examined using polymerase chain reaction-restriction fragment length polymorphism in 100 control subjects and 150 KC patients [50 patients (KC stages 1&2), 50 patients (KC stage 3) and 50 patients (KC stage 4)]. RESULTS: Patients with TT genotype of CAT rs7943316 were at high risk of developing KC. T allele of GPX-1 rs1050450 was significantly associated with KC risk (P ˂0.001). The frequency of CAT TT genotype and T allele was significantly higher among severe stages of KC compared to mild and moderate stages. GPX-1 T allele frequency was significantly higher among severe stages of KC compared to mild and moderate stages. A very significant decrease in the antioxidant enzyme activities was observed in association with these SNPs. Age of the patients, CAT and GPX-1 SNPs as well as their enzyme activities were independent predictors of KC severity. CONCLUSION: Our study suggests that CAT (rs7943316) and GPX-1 (rs1050450) SNPs act as independent predictors for different grades of KC and that these SNPs might have a role in the pathogenesis of the disease.

Association of CXCR4 Expression and Clinical Outcome in Different Subsets of De Novo Acute Myeloid Leukemia Patients.

BACKGROUND: Acute myeloid leukemia is a heterogeneous group of diseases characterized by the uncontrolled proliferation of hematopoietic stem cells (HSCs) and progenitor cells with a reduced capacity to differentiate into mature cells. CXC chemokine receptor (CXCR4) and its ligand stromal derived factor-1 (SDF-1/CXCL12) are important players involved in cross-talk between leukemia cells and the bone marrow (BM) microenvironment. The aim to study the association between the immunohistochemical CXCR4 expression and the clinical outcome of AML in adult Egyptian patients. METHODS: Fifty-eight patients suffering from AML were recruited for this study, with an age range from 18 to 60 years and presenting from January 2013 to March 2017. All patients were subjected to complete blood count, BM aspiration, immunophenotyping, BM trephine biopsy, immunohistochemical staining with CXCR4 McAb and cytogenetics when feasible. RESULTS: CXCR4 was widely expressed (55.2%) among the studied patients. There was a significant relationship between CXCR4 and patients' outcomes. Fifteen (71.4%) patients who died were CXCR4 positive. The estimated mean time until death among CXCR4 negative cases was 37.6 ± 4.04 months which was longer than that of CXCR4 positive cases who had mean of 20.04 ± 4.9 months p = 0.016. The risk for death among CXCR4 positive cases was higher than CXCR4 negative cases with hazard ratio (HR) = 2.147 (p = 0.048). CONCLUSIONS: These results suggest that CXCR4 was expressed in a subset of AML patients and was associated with poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients.

Indigenous soil bacteria and the hyperaccumulator Pteris vittata mediate phytoremediation of soil contaminated with arsenic species.

Arsenic (As) is a pollutant of major concern worldwide, posing as a threat to both human health and the environment. Phytoremediation has been proposed as a viable mechanism to remediate As-contaminated soil environments. Pot experiments were performed to evaluate the phytoextraction efficiency of As by Pteris vittata, a known As hyperaccumulating fern, from soil amended with different concentrations of arsenate [As(V)] and arsenite [As(III)], the more common, inorganic As forms in soil. The greatest accumulation of As (13.3 ± 0.36 g/kg Dwt) was found in fronds of plants grown in soil spiked with 1.0 g As(V)/kg. The maximum As-bioaccumulation factor (27.3 ± 1.9) was achieved by plants grown in soil amended with 0.05 g As(V)/kg. A total of 864 bacterial cultures were isolated and examined for their ability to enhance phytoremediation of As-contaminated soils. Traits examined included tolerance to As (III and V), production of siderophores, and/or ability to solubilize calcium phosphate and indole acetic acid (IAA) production. A culture-based survey shows greater numbers of viable and As-resistant bacteria were found in the rhizosphere of As-grown plants compared to bulk and unplanted soils. The percentage of bacteria resistant to As(V) was greater (P < 0.0001) than those resistant to As(III) in culture medium containing 0.5, 1, 1.5, and 2 g As/L. Higher (P < 0.0001) percentages of siderophore producing (77%) and phosphate solubilizing (61%) bacteria were observed among cultures isolated from unplanted soil. About 5% (44 of 864) of the isolates were highly resistant to both As (III) and As (V) (2 g/L), and were examined for their As-transformation ability and IAA production. A great proportion of the isolates produced IAA (82%) and promoted As (V)-reduction (95%) or As(III)-oxidation (73%), and 71% exhibited dual capacity for both As(V) reduction and As(III) oxidation. Phylogenetic analysis indicated that 67, 23, and 10% of these isolates belonged to Proteobacteria, Actinobacteria, and Firmicutes, respectively. Analysis of the 16S rRNA gene sequences confirmed that these isolates were closely related to 12 genera and 25 species of bacteria and were dominated by members of the genus Pseudomonas (39%). These results show that these isolates could potentially be developed as inocula for enhancing plant uptake during large scale phytoremediation of As-impacted soils.

Morphological Characteristics of the Developing Cecum of Japanese Quail (Coturnix coturnix japonica).

The current investigation was carried out to record the final stages of the development of both middle and distal parts of quail ceca, Coturnix coturnix japonica to understand the role of ceca in digestion, immune system, and absorption. The cellular and subcellular structures, including epithelial cell height, microvillus surface area, the proportion of goblet cells, the thickness of muscle layer, and cecum diameter showed great variations during the development. An undeveloped smooth muscularis mucosa was observed for the first time on the ED5. Primordia of glands were observed on the ED7. On the ED15, the middle part exhibited two shapes of mucosal villi: tongue-shaped villi and U-shaped. The plicae and crypts of Lieberkühn were demonstrated on the hatching day. The lymphatic tissues appeared in the wall of both parts of the ceca at the 4 weeks of age. Scanning electron microscopy revealed a great difference in the mucosal surface between different regions. Telocytes were observed in-between the muscle fibers and formed a network during the post-hatching period. Because of fermentation and other bacterial or chemical processes that have been shown to occur in the ceca, this study supports two hypotheses: the cecal development is related to diet and the cecal epithelium act as a site for primary absorption of nutrients or for re-absorption of electrolytes or amino acids derived from the urine.

Gabapentin for the management of chronic pelvic pain in women.

BACKGROUND: Chronic pelvic pain (CPP) is a frequent presenting symptom in gynaecology outpatient clinics. Neuromodulator pharmacological agents could be an option for treatment based on its efficacy in treating chronic pain in other conditions. PURPOSE: This study aimed at evaluating the efficacy of oral Gabapentin to alleviate pain in women with CPP. METHODS: In a randomized double-blinded placebo-controlled trial, 60 women suffering from chronic pelvic pain were randomly divided into two equal arms. The study group received Gabapentin 300 mg three times daily initially (900 mg), with 300 mg weekly incremental dose till pain was controlled, severe side effects occurred or maximum daily dose of 2700 mg was reached. The Primary outcome was the pain score improvement of CPP, defined as a 30% reduction in the pain score assessed by the 10-cm Visual Analogue Scale compared to baseline score. RESULTS: In Gabapentin group, pain was significantly reduced at 12 and 24 weeks (mean = 5.12 ± 0.67 and 3.72 ± 0.69, respectively) than in placebo group (mean = 5.9 ± 0.92 and 5.5 ± 1.13, respectively); this difference was significant. At 24 weeks, there was significantly higher proportion of patients reporting 30% or more reduction in pain scores; 19 out of 20 patients (95%) in Gabapentin group compared to 8 out of 14 patients (57.1%) in placebo group. The relative risk for pain after gabapentin treatment was 0.5 with 95% confidence interval = 0.34 to 0.75 and number needed to treat = 3 (p = 0.007). Regarding adverse effects there was significantly higher incidence of dizziness with Gabapentin (26.1%) compared to placebo (3.3%). CONCLUSION: Chronic pelvic pain in women may be treated sufficiently with Gabapentin. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov registry with clinical trial registration number: NCT02918760.

Algae as a green technology for heavy metals removal from various wastewater.

Urbanization, industrialization, and natural earth processes have potentially increased the contamination of heavy metals (HMs) in water bodies. These HMs can accumulate in human beings through the consumption of contaminated water and food chains. Various clean-up technologies have been applied to sequester HMs, especially conventional methods including electrolytic technologies, ion exchange, precipitation, chemical extraction, hydrolysis, polymer micro-encapsulation, and leaching. However, most of these approaches are expensive for large-scale projects and require tedious control and constant monitoring, along with low efficiency for effective HMs removal. Algae offer an alternative, sustainable, and environmentally friendly HMs remediation approach. This review presents a state-of-the-art technology for potential use of algae as a low-cost biosorbent for the removal of HMs from wastewater. The mechanisms of HMs removal, including biosorption and bioaccumulation along with physical and chemical characterization of the algae are highlighted. The influence of abiotic factors on HMs removal and changes in algal biocomponents (including, carbohydrate, lipid, and protein) are discussed. Recent progresses made in the development of HMs-tolerant algal strains and the direction of future research toward the development of sustainable technology for advanced wastewater treatment and biomass production are covered.

Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy.

STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 ± 3.8 [mean ± SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 ± 5.0 [mean ± SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes >10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a non-malignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 ± 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 ± 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 ± 1.0, n = 8 and 4.1 ± 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to non-alkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Förening För Barnasjukvård/ Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Väre Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.