GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain.

Ca2+/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) is a key neuronal signaling protein and an emerging drug target. The central hub domain regulates the activity of CaMKIIα by organizing the holoenzyme complex into functional oligomers, yet pharmacological modulation of the hub domain has never been demonstrated. Here, using a combination of photoaffinity labeling and chemical proteomics, we show that compounds related to the natural substance γ-hydroxybutyrate (GHB) bind selectively to CaMKIIα. By means of a 2.2-Å x-ray crystal structure of ligand-bound CaMKIIα hub, we reveal the molecular details of the binding site deep within the hub. Furthermore, we show that binding of GHB and related analogs to this site promotes concentration-dependent increases in hub thermal stability believed to alter holoenzyme functionality. Selectively under states of pathological CaMKIIα activation, hub ligands provide a significant and sustained neuroprotection, which is both time and dose dependent. This is demonstrated in neurons exposed to excitotoxicity and in a mouse model of cerebral ischemia with the selective GHB analog, HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid). Together, our results indicate a hitherto unknown mechanism for neuroprotection by a highly specific and unforeseen interaction between the CaMKIIα hub domain and small molecule brain-penetrant GHB analogs. This establishes GHB analogs as powerful tools for investigating CaMKII neuropharmacology in general and as potential therapeutic compounds for cerebral ischemia in particular.

Implementation and evaluation of a mentorship program in clinical master in family medicine during the COVID-19 pandemic at the Arabian Gulf University: a longitudinal study.

BACKGROUND: We implemented a contextualized innovative mentorship program in the Clinical Master in Family Medicine (CMFM) program established in April 2020 at Arabian Gulf University. In this paper, we describe the process of this program and derive the major challenges faced by trainees and related corrective actions and their outcomes on high-risk trainees for optimal performance. METHODS: We conducted a mixed-method longitudinal study of 80 trainees, analyzing information extracted from the Moodle learning platform about five key performance indicators as well as the contents (quantitative and qualitative) of mentoring meeting reports submitted through a validated online form between 2020 and 2022. We analyzed frequencies and themes of challenges and compared trainees' performance according to time and level of risk. RESULTS: The follow-up of all 80 trainees in two cohorts (40 for each cohort) shows that most are female (93.75%) and the mean age is 30.00 ± 2.19 years with a ratio of mentors to mentees of 1 to 5. Meetings are conducted through phone calls, virtually, and face-to-face in 62%, 29%, and 8.3% respectively. The mean number and duration of meetings are 30.88 ± 2.31 and 20.08 ± 9.50 min respectively. Time management is the most reported challenge (41.3%), followed by health, social, and psychological-related issues in 7.6%, 4.6%, and 3% respectively. We extracted four main themes related to trainees, settings of training, e-Portfolio, and the COVID-19 pandemic. The mentorship program captured 12 trainees at high risk for low academic progress (12%) of whom six graduated on time and the remaining had to repeat a few courses the following terms. The performance of the program is stable over time (mean GPA of 3.30 (SE = 0.03), versus 3.34 (SE = 0.05) for cohorts 1 and 2 in the two years respectively, (P = 0.33). However, it is slightly lower among high-risk trainees compared to the remaining (GPA = 3.35 (SE = 0.03) versus 3.14 (SE = 0.08), P = 0.043) though above the minimum of the threshold of 3 out of 4, required for the master's degree. CONCLUSION: The mentorship program captured the struggling trainees and permitted to implement pertinent corrective actions timely, particularly in the context of a two-year intensive CMFM program during the COVID-19 pandemic.

Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures.

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).

Antimicrobial and anti-aflatoxigenic activities of nanoemulsions based on Achillea millefolium and Crocus sativus flower extracts as green promising agents for food preservatives.

BACKGROUND: Although the mechanism of action of nanoemulsion is still unclear, the modern use of nanoemulsions made from natural extracts as antimicrobial and anti-aflatoxigenic agents represents a potential food preservation and a safety target. METHODS: Two natural nanoemulsion extracts of Crocus sativus (the saffron flower) and Achillea millefolium (the yarrow flower) were produced in the current study using a low-energy method that included carboxymethylcellulose and Arabic gum. The synthesized nanoemulsion was fully identified by different analytical methods. Detection of the volatile content was completed using GC-MS analysis. The antioxidant potential, and phenolic compounds content were analyzed in the extractions. The synthesized nanoemulsions were screened for their antimicrobial potential in addition to their anti-aflatoxigenic activity. RESULTS: The droplet size of Saffron flowers was finer (121.64 ± 2.18 nm) than yarrow flowers (151.21 ± 1.12 nm). The Zeta potential measurements of the yarrow flower (-16.31 ± 2.54 mV) and the saffron flower (-18.55 ± 2.31 mV) both showed high stability, along with low PDI values (0.34-0.41). The nanoemulsion of yarrow flower revealed 51 compounds using gas chromatography-mass spectrometry (GCMS), with hexanal (16.25%), ß-Pinene (7.41%), ß-Myrcene (5.24%), D-Limonene (5.58%) and Caryophyllene (4.38%) being the most prevalent. Additionally, 31 compounds were detected in the saffron nanoemulsion, with D-limonene (4.89%), isophorone (12.29%), 4-oxy isophorone (8.19%), and safranal (44.84%) being the most abundant. Compared to the nanoemulsion of the yarrow flower, the saffron nanoemulsion had good antibacterial and antifungal activity. Saffron nanoemulsion inhibited total fungal growth by 69.64-71.90% in a simulated liquid medium and demonstrated the most significant decrease in aflatoxin production. Infected strawberry fruits coated with nanoemulsion extracts exhibited high antimicrobial activity in the form of saffron flower and yarrow flower extract nanoemulsions, which inhibited and/or controlled the growth of Aspergillus fungi. Due to this inhibition, the lag phase was noticeably prolonged, the cell load decreased, and the stability time increased. CONCLUSION: This study will contribute to expanding the theoretical research and utilization of nanoemulsions as green protective agents in agricultural and food industries for a promising protection from the invasion of some pathogenic bacteria and fungi.

Brave new surfactant world revisited by thermoalkalophilic lipases: computational insights into the role of SDS as a substrate analog.

Non-ionic surfactants were shown to stabilize the active conformation of thermoalkalophilic lipases by mimicking the lipid substrate while the catalytic interactions formed by anionic surfactants have not been well characterized. In this study, we combined µs-scale molecular dynamics (MD) simulations and lipase activity assays to analyze the effect of ionic surfactant, sodium dodecyl sulfate (SDS), on the structure and activity of thermoalkalophilic lipases. Both the open and closed lipase conformations that differ in geometry were recruited to the MD analysis to provide a broader understanding of the molecular effect of SDS on the lipase structure. Simulations at 298 K showed the potential of SDS for maintaining the active lipase through binding to the sn-1 acyl-chain binding pocket in the open conformation or transforming the closed conformation to an open-like state. Consistent with MD findings, experimental analysis showed increased lipase activity upon SDS incubation at ambient temperature. Notably, the lipase cores stayed intact throughout 2 µs regardless of an increase in the simulation temperature or SDS concentration. However, the surface structures were unfolded in the presence of SDS and at elevated temperature for both conformations. Simulations of the dimeric lipase were also carried out and showed reduced flexibility of the surface structures which were unfolded in the monomer, indicating the insulating role of dimer interactions against SDS. Taken together, this study provides insights into the possible substrate mimicry by the ionic surfactant SDS for the thermoalkalophilic lipases without temperature elevation, underscoring SDS's potential for interfacial activation at ambient temperatures.

Endoscopic management of low output recurrent colonic fistula or leak after anterior resection for rectal cancer: a randomized controlled trial.

BACKGROUND: Colonic anastomotic leak and fistula following anterior resection surgery for rectal cancer are associated with high mortality rates. The incidence of occurrence varies from 2 to 25% and it is difficult to accurately calculate the incidence of fistula and leak post anterior resection, as most of them are asymptomatic. Endoscopic management of fistula and leak has become the first line of management after conservative management in many gastrointestinal surgical centers with the advantages of being less invasive, shorter length of post-operative hospital stay, effective and rapid recovery in comparison to revision surgery. Effective endoscopic management for colonic fistula or leak depends on the clinical status of the patient and fistula characters (time-to-occur and size and site of defect), and device availability. METHODS: This prospective randomized controlled clinical trial included all patients who developed the manifestations of low output recurrent colonic fistula or leak after colonic anterior resection for rectal cancer at Zagazig University Hospital between (December 2020 and August 2022). Sample size was 78 patients divided into two equal groups. Endoscopic group (EG): included 39 patients who underwent endoscopic management. Surgical group (SG): included 39 patients who underwent surgical management. RESULTS: The investigators randomized eligible 78 patients into two groups: 39 patients in SG and 39 patients in EG. The median size of the fistula or leak was nine (range: 7-14) mm in EG, versus ten (range: 7-12) mm in SG. Clipping and Endo-stitch device were used in 24 patients versus 15 patients, respectively, in EG while primary repair with ileostomy, and resection & anastomosis were used in 15 patients versus 24 patients, respectively, in SG. Recurrence, abdominal collection, and mortality were the post procedure's complications with incidence of occurrence of 10.3, 7.7 and 0%, respectively, in EG versus 20.5, 20.5 and 2.6%, respectively, in SG. Excellent, good, and poor were the parameters for quality of life with incidence of occurrence of 43.6, 54.6 and 0%, respectively, in EG versus 28.2, 33.3 and 38.5%, respectively, in SG. Median hospital stay was one (range: 1-2) day in endoscopic group, and seven (range: 6-8) days in SG. CONCLUSION: Endoscopic intervention may offer a successful modality in managing low output recurrent colonic fistula or leak after anterior resection for rectal cancer that did not respond to conservative measures in stable patients. CLINICALTRIALS: gov ID: NCT05659446.

An Integrated Machine Learning-Based Brain Computer Interface to Classify Diverse Limb Motor Tasks: Explainable Model.

Terminal neurological conditions can affect millions of people worldwide and hinder them from doing their daily tasks and movements normally. Brain computer interface (BCI) is the best hope for many individuals with motor deficiencies. It will help many patients interact with the outside world and handle their daily tasks without assistance. Therefore, machine learning-based BCI systems have emerged as non-invasive techniques for reading out signals from the brain and interpreting them into commands to help those people to perform diverse limb motor tasks. This paper proposes an innovative and improved machine learning-based BCI system that analyzes EEG signals obtained from motor imagery to distinguish among various limb motor tasks based on BCI competition III dataset IVa. The proposed framework pipeline for EEG signal processing performs the following major steps. The first step uses a meta-heuristic optimization technique, called the whale optimization algorithm (WOA), to select the optimal features for discriminating between neural activity patterns. The pipeline then uses machine learning models such as LDA, k-NN, DT, RF, and LR to analyze the chosen features to enhance the precision of EEG signal analysis. The proposed BCI system, which merges the WOA as a feature selection method and the optimized k-NN classification model, demonstrated an overall accuracy of 98.6%, outperforming other machine learning models and previous techniques on the BCI competition III dataset IVa. Additionally, the EEG feature contribution in the ML classification model is reported using Explainable AI (XAI) tools, which provide insights into the individual contributions of the features in the predictions made by the model. By incorporating XAI techniques, the results of this study offer greater transparency and understanding of the relationship between the EEG features and the model's predictions. The proposed method shows potential levels for better use in controlling diverse limb motor tasks to help people with limb impairments and support them while enhancing their quality of life.

Synthesis, Characterization, DFT Studies of Novel Cu(II), Zn(II), VO(II), Cr(III), and La(III) Chloro-Substituted Schiff Base Complexes: Aspects of Its Antimicrobial, Antioxidant, Anti-Inflammatory, and Photodegradation of Methylene Blue.

A new chlorobenzylidene imine ligand, (E)-1-((5-chloro-2-hydroxybenzylidene)amino) naphthalen-2-ol (HL), and its [Zn(L)(NO3)(H2O)3], [La(L)(NO3)2(H2O)2], [VO(L)(OC2H5)(H2O)2], [Cu(L)(NO3)(H2O)3], and [Cr(L)(NO3)2(H2O)2], complexes were synthesized and characterized. The characterization involved elemental analysis, FT-IR, UV/Vis, NMR, mass spectra, molar conductance, and magnetic susceptibility measurements. The obtained data confirmed the octahedral geometrical structures of all metal complexes, while the [VO(L)(OC2H5)(H2O)2] complex exhibited a distorted square pyramidal structure. The complexes were found to be thermally stable based on their kinetic parameters determined using the Coats-Redfern method. The DFT/B3LYP technique was employed to calculate the optimized structures, energy gaps, and other important theoretical descriptors of the complexes. In vitro antibacterial assays were conducted to evaluate the complexes' potential against pathogenic bacteria and fungi, comparing them to the free ligand. The compounds exhibited excellent fungicidal activity against Candida albicans ATCC: 10231 (C. albicans) and Aspergillus negar ATCC: 16404 (A. negar), with inhibition zones of HL, [Zn(L)(NO3)(H2O)3], and [La(L)(NO3)2(H2O)2] three times higher than that of the Nystatin antibiotic. The DNA binding affinity of the metal complexes and their ligand was investigated using UV-visible, viscosity, and gel electrophoresis methods, suggesting an intercalative binding mode. The absorption studies yielded Kb values ranging from 4.40 × 105 to 7.30 × 105 M-1, indicating high binding strength to DNA comparable to ethidium bromide (value 107 M-1). Additionally, the antioxidant activity of all complexes was measured and compared to vitamin C. The anti-inflammatory efficacy of the ligand and its metal complexes was evaluated, revealing that [Cu(L)(NO3)(H2O)3] exhibited the most effective activity compared to ibuprofen. Molecular docking studies were conducted to explore the binding nature and affinity of the synthesized compounds with the receptor of Candida albicans oxidoreductase/oxidoreductase INHIBITOR (PDB ID: 5V5Z). Overall, the combined findings of this work demonstrate the potential of these new compounds as efficient fungicidal and anti-inflammatory agents. Furthermore, the photocatalytic effect of the Cu(II) Schiff base complex/GO was examined.

Therapeutic Potency of Ovothiol A on Ethanol-Induced Gastric Ulcers in Wistar Rats.

Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally produced from sea urchin eggs with special antioxidant activity. Gastric ulcers were induced in rats by a single ethanol dose (5 mL/kg). The rats were divided into control, ulcer, and ulcer with 250 and 500 mg/kg ovothiol A doses. Molecular docking studies were used to examine the interactions between ovothiol A and the H+/K+ ATPase active site residues. Ovothiol A led to a significant decline (p < 0.05) in gastric juice volume, ulcer index, MDA, IL-6, and cytochrome c, while levels of gastric juice pH, GSH, CAT, GST, SOD, and NO increased. Histopathological investigation of stomach sections revealed architecture preservation of the gastric mucosa after ovothiol A administration. The anti-ulcerogenic activity of ovothiol A includes scavenging free radicals, inhibition of inflammation, regulation of apoptosis, and stabilization of fibroblast growth factors to promote gastric ulcers healing.

[Cu(dipicolinoylamide)(NO3)(H2O)] as anti-COVID-19 and antibacterial drug candidate: Design, synthesis, crystal structure, DFT and molecular docking.

For first time the new N-picolinoypicolinlamide was obtained as in situ ligand during the reaction of 2,4,6-ris(2-pyridyl)-,3,5-triazine with aqueous solution of CuNO3·3H2O and formed the corresponding complex [Cu(dipicolinoylamide)(NO3)(H2O)]. The crystal structure of the obtained complex was determined by x-ray structure. The complex crystallizes in space group P21/n, a = 10.2782(9) Å, b = 7.5173(6) Å, c = 17.738(2) Å, α = 90.00°, ß = 91.368(1)°, γ = 90.00°, V = 1370.1(2) Å3, Z = 4. The copper center has a distorted octahedral geometry. DFT calculations show good agreement between theoretical and X-ray data. The Molecular docking studies were executed to consider the nature of binding and binding affinity of the synthesized compounds with the receptor of COVID-19 main protease viral protein (PDB ID: 6lu7), the receptor of gram -ve bacteria (Escherichia coli, PDB ID: 1fj4) and the receptor of gram +ve bacteria (Staphylococcus aureus, PDB ID: 3q8u and Proteus PDB ID: 5i39) and with human DNA. Finally, in silico ADMET predictions was also examined.

Laparoscopic management of infantile hydrocele in pediatric age group.

PURPOSE: To evaluate laparoscopic management of hydroceles in pediatrics, with evaluation of the internal inguinal ring (IIR) and the PPV (patent processus vaginalis) in different types of hydroceles, and the incidence of the contralateral PPV. METHODS: The IIR and the type of hydrocele on the same side of 93 patients with 106 infantile hydroceles were evaluated and managed, in addition to contralateral side. RESULTS: The IIR on same side was closed in 8.5% (Type I) and patent in 91.5% (Type II and III) with different shapes. Contralateral IIR was open in 88.7% of cases. The operative time was 30.99 ± 7.23 min, with no intra-operative complication. The vas deferens and testicular vessels were secured and there were no injuries or bleeding. The conversion rate was zero, and all procedures (Type II and II) were completed totally laparoscopic. No post-operative complications except a case of tense hydrocele developed scrotal edema that managed conservatively. CONCLUSION: Laparoscopic hydrocelectomy is safe, applicable and feasible for management of different types of hydroceles in pediatrics. The IIR is patent in nearly all cases with/out communication to the hydrocele. The contralateral IIR can be managed in the same session. Laparoscopic hydrocelectomy with/out hydrocelectomy and IIR closure is essential in preventing recurrence.

A New Framework for Precise Identification of Prostatic Adenocarcinoma.

Prostate cancer, which is also known as prostatic adenocarcinoma, is an unconstrained growth of epithelial cells in the prostate and has become one of the leading causes of cancer-related death worldwide. The survival of patients with prostate cancer relies on detection at an early, treatable stage. In this paper, we introduce a new comprehensive framework to precisely differentiate between malignant and benign prostate cancer. This framework proposes a noninvasive computer-aided diagnosis system that integrates two imaging modalities of MR (diffusion-weighted (DW) and T2-weighted (T2W)). For the first time, it utilizes the combination of functional features represented by apparent diffusion coefficient (ADC) maps estimated from DW-MRI for the whole prostate in combination with texture features with its first- and second-order representations, extracted from T2W-MRIs of the whole prostate, and shape features represented by spherical harmonics constructed for the lesion inside the prostate and integrated with PSA screening results. The dataset presented in the paper includes 80 biopsy confirmed patients, with a mean age of 65.7 years (43 benign prostatic hyperplasia, 37 prostatic carcinomas). Experiments were conducted using different well-known machine learning approaches including support vector machines (SVM), random forests (RF), decision trees (DT), and linear discriminant analysis (LDA) classification models to study the impact of different feature sets that lead to better identification of prostatic adenocarcinoma. Using a leave-one-out cross-validation approach, the diagnostic results obtained using the SVM classification model along with the combined feature set after applying feature selection (88.75% accuracy, 81.08% sensitivity, 95.35% specificity, and 0.8821 AUC) indicated that the system's performance, after integrating and reducing different types of feature sets, obtained an enhanced diagnostic performance compared with each individual feature set and other machine learning classifiers. In addition, the developed diagnostic system provided consistent diagnostic performance using 10-fold and 5-fold cross-validation approaches, which confirms the reliability, generalization ability, and robustness of the developed system.

Fabrication, DFT Calculation, and Molecular Docking of Two Fe(III) Imine Chelates as Anti-COVID-19 and Pharmaceutical Drug Candidate.

Two tetradentate dibasic chelating Schiff base iron (III) chelates were prepared from the reaction of 2,2'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis(methanylylidene))bis(4-bromophenol) (PDBS) and 2,2'-((1E,1'E)-((4-chloro-1,2-phenylene)bis(azanylylidene))-bis(methanylylidene))bis(4-bromophenol) (CPBS) with Fe3+ ions. The prepared complexes were fully characterized with spectral and physicochemical tools such as IR, NMR, CHN analysis, TGA, UV-visible spectra, and magnetic moment measurements. Moreover, geometry optimizations for the synthesized ligands and complexes were conducted using the Gaussian09 program through the DFT approach, to find the best structures and key parameters. The prepared compounds were tested as antimicrobial agents against selected strains of bacteria and fungi. The results suggests that the CPBSFe complex has the highest activity, which is close to the reference. An MTT assay was used to screen the newly synthesized compounds against a variety of cell lines, including colon cancer cells, hepatic cellular carcinoma cells, and breast carcinoma cells. The results are expressed by IC50 value, in which the 48 µg/mL value of the CPBSFe complex indicates its success as a potential anticancer agent. The antioxidant behavior of the two imine chelates was studied by DPPH assay. All the tested imine complexes show potent antioxidant activity compared to the standard Vitamin C. Furthermore, the in vitro assay and the mechanism of binding and interaction efficiency of the tested samples with the receptor of COVID-19 core protease viral protein (PDB ID: 6lu7) and the receptor of Gram-negative bacteria (Escherichia coli, PDB ID: 1fj4) were investigated using molecular docking experiments.

Docking Analysis of Some Bioactive Compounds from Traditional Plants against SARS-CoV-2 Target Proteins.

COVID-19 is still a global pandemic that has not been stopped. Many traditional medicines have been demonstrated to be incredibly helpful for treating COVID-19 patients while fighting the disease worldwide. We introduced 10 bioactive compounds derived from traditional medicinal plants and assessed their potential for inhibiting viral spike protein (S-protein), Papain-like protease (PLpro), and RNA dependent RNA polymerase (RdRp) using molecular docking protocols where we simulate the inhibitors bound to target proteins in various poses and at different known binding sites using Autodock version 4.0 and Chimera 1.8.1 software. Results found that the chicoric acid, quinine, and withaferin A ligand strongly inhibited CoV-2 S -protein with a binding energy of -8.63, -7.85, and -7.85 kcal/mol, respectively. Our modeling work also suggested that curcumin, quinine, and demothoxycurcumin exhibited high binding affinity toward RdRp with a binding energy of -7.80, -7.80, and -7.64 kcal/mol, respectively. The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with -7.62, -6.81, and -6.70 kcal/mol, respectively. Prediction of drug-likeness properties revealed that all tested ligands have no violations to Lipinski's Rule of Five except cepharanthine, chicoric acid, and theaflavin. Regarding the pharmacokinetic behavior, all ligand predicted to have high GI-absorption except chicoric acid and theaflavin. At the same way chicoric acid, withaferin A, and withanolide D predicted to be substrate for multidrug resistance protein (P-gp substrate). Caffeic acid, cepharanthine, chicoric acid, withaferin A, and withanolide D also have no inhibitory effect on any cytochrome P450 enzymes. Promisingly, chicoric acid, quinine, curcumin, and demothoxycurcumin exhibited high binding affinity on SARS-CoV-2 target proteins and expressed good drug-likeness and pharmacokinetic properties. Further research is required to investigate the potential uses of these compounds in the treatment of SARS-CoV-2.

Chemical Profiling and Nutritional Evaluation of Bee Pollen, Bee Bread, and Royal Jelly and Their Role in Functional Fermented Dairy Products.

Honeybee products, as multicomponent substances, have been a focus of great interest. The present work aimed to perform the nutritional and chemical profiling and biochemical characterization of bee pollen (BP), bee bread (BB), and royal jelly (RJ) and study their applications in the fortification of functional fermented dairy products. Their effects on starter cultures and the physicochemical and sensorial quality of products were monitored. A molecular networking analysis identified a total of 46 compounds in the three bee products that could be potential medicines, including flavonoids, fatty acids, and peptides. BB showed the highest protein and sugar contents (22.57 and 26.78 g/100 g), which cover 45.14 and 53.56% of their daily values (DVs), with considerable amounts of the essential amino acids threonine and lysine (59.50 and 42.03%). BP, BB, and RJ can be considered sources of iron, as 100 g can cover 141, 198.5, and 94.94% of DV%, respectively. BP was revealed to have the highest phenolic and flavonoid contents (105.68 and 43.91 µg/g) and showed a synergetic effect when mixed with RJ, resulting in increased antioxidant activity, while BB showed a synergetic effect when mixed with RJ in terms of both antioxidant and proteolytic powers (IC50 7.54, 11.55, 12.15, 12.50, and 12.65 cP compared to the control (10.55 cP)), reflecting their organoleptic properties and highlighting these health-oriented products as promising natural products for human health care.

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

Efficacy of retinoids alone or in combination with other remedies in the management of warts: A systematic review and network meta-analysis.

The use of combined systemic retinoids and intralesional immunotherapy in the management of warts is still debatable without straightforward evidence. Through network meta-analysis, the current study evaluated the efficacy and safety of systemic retinoids alone or combined with other remedies in the treatment of warts. We searched six literature databases for clinical trials that compared systemic retinoids to local treatments or placebo in wart management. Outcomes were calculated as odds ratios (OR) with 95% confidence-interval. We used the R software to perform conventional and network meta-analyses (with a frequentist approach). Network meta-analysis of eight trials showed that oral acitretin plus intralesional Candida Ag (OR = 367.71), INF-α plus oral isotretinoin (OR = 223.77), oral acitretin (OR = 117), Candida Ag (OR = 91.93), oral isotretinoin (OR = 62.26) and topical isotretinoin (OR = 17.69) had higher complete recovery rates than placebo. Regarding the P-score, oral acitretin plus intralesional Candida Ag had the highest efficacy in achieving complete response (P-score = 0.88), followed by INF-α plus oral isotretinoin (P-score = 0.79), then oral acitretin (P-score = 0.60). Variable baseline characteristics and lack of data on some outcomes. The current study shows the efficacy for systemic retinoids in the treatment of warts, especially reluctant or recurrent types. Moreover, combinations of systemic retinoids with intralesional immunotherapy yield higher rates of complete clearance with lower recurrence.

Innovative application of postbiotics, parabiotics and encapsulated Lactobacillus plantarum RM1 and Lactobacillus paracasei KC39 for detoxification of aflatoxin M1 in milk powder.

This study aimed to evaluate aflatoxin M1 (AFM1) level in milk powder and infant milk formulae, in addition to applying innovative methods for AFM1 & AFB1 detoxification. Fifty random samples of milk powder and infant formulae (25 of each) were collected from the Egyptian markets for assessing AFM1 level using ELISA technique. Bioactive components comprising cell free supernatants (postbiotic), acid-dead cells (parabiotic) and the encapsulated-cells of Lactobacillus plantarum RM1 and Lactobacillus paracasei KC39 were evaluated for their antifungal activity against toxigenic mold strains and their impact on AFB1 and AFM1 reduction in reconstituted milk powder. AFM1 concentration in unpacked milk powder was higher than that of packed samples and infant formulae, although these differences were not significant (P > 0.05). About 96.0, 29.4 and 25.0% of the tested infant formulae, unpacked, and packed milk powder were unacceptable in terms of the AFM1 limit defined by Egyptian and European standards, while all samples were in accordance with the USA/FDA standard. All tested mycotoxigenic strains were sensitive to the different treatments of the probiotics with the highest sensitivity regarding Fusarium strain with L. paracasei KC39 compared to other genera. The degradation ratios of AFM1 using the bioactives of the L. paracasei KC39 were higher than that of L. plantarum RM1 bioactives. Additionally, KC39 parabiotic manifested the best AFB1 reduction (60.56%). In conclusion, the positive and highly significant relationship (P < 0.05) between these effective biocompounds mirrors their major detoxification role which gives a safe solution for AFs contamination issues in milk and milk products.

A guide for evaluation of online learning in medical education: a qualitative reflective analysis.

BACKGROUND: With the strike of Covid-19, an unprecedented rapid shift to remote learning happened worldwide with a paradigm shift to online learning from an institutional adjuvant luxury package and learner choice into a forced solo choice. This raises the question of quality assurance. While some groups have already established standards for online courses, teaching and programs yet very little information is included on methodology of their development and very little emphasis is placed on the online learning experience. Nevertheless, no work has been done specifically for medical education institutions. AIM: To develop a set of descriptors for best practice in online learning in medical education utilizing existing expertise and needs. METHODS: This work utilizes a qualitative multistage approach to identify the descriptors of best practice in online learning starting with a question guided focus group, thematic analysis, Delphi technique and an expert consensus session done simultaneously for triangulation. This was done involving 32 institution in 19 countries. RESULTS: This materialized into the development of a set of standards, indicators, and development of a checklist for each standard area. The standard areas identified were organizational capacity, educational effectiveness, and human resources each of which listed a number of standards. Expert consensus sessions identified the need for qualification of data and thus the development of indicators for best practice. CONCLUSION: Standards are needed for online learning experience and their development and redesign is situational and needs to be enhanced methodologically in axes that are pertaining to the needs of the education community. Taking such axes into consideration by educators and institutions will lead to planning and implementing successful online learning activities, while taking them into consideration by the evaluators will help them conduct comprehensive audits and provide stakeholders with highly informative evaluation reports.

A Comprehensive Computer-Assisted Diagnosis System for Early Assessment of Renal Cancer Tumors.

Renal cell carcinoma (RCC) is the most common and a highly aggressive type of malignant renal tumor. In this manuscript, we aim to identify and integrate the optimal discriminating morphological, textural, and functional features that best describe the malignancy status of a given renal tumor. The integrated discriminating features may lead to the development of a novel comprehensive renal cancer computer-assisted diagnosis (RC-CAD) system with the ability to discriminate between benign and malignant renal tumors and specify the malignancy subtypes for optimal medical management. Informed consent was obtained from a total of 140 biopsy-proven patients to participate in the study (male = 72 and female = 68, age range = 15 to 87 years). There were 70 patients who had RCC (40 clear cell RCC (ccRCC), 30 nonclear cell RCC (nccRCC)), while the other 70 had benign angiomyolipoma tumors. Contrast-enhanced computed tomography (CE-CT) images were acquired, and renal tumors were segmented for all patients to allow the extraction of discriminating imaging features. The RC-CAD system incorporates the following major steps: (i) applying a new parametric spherical harmonic technique to estimate the morphological features, (ii) modeling a novel angular invariant gray-level co-occurrence matrix to estimate the textural features, and (iii) constructing wash-in/wash-out slopes to estimate the functional features by quantifying enhancement variations across different CE-CT phases. These features were subsequently combined and processed using a two-stage multilayer perceptron artificial neural network (MLP-ANN) classifier to classify the renal tumor as benign or malignant and identify the malignancy subtype as well. Using the combined features and a leave-one-subject-out cross-validation approach, the developed RC-CAD system achieved a sensitivity of 95.3%±2.0%, a specificity of 99.9%±0.4%, and Dice similarity coefficient of 0.98±0.01 in differentiating malignant from benign tumors, as well as an overall accuracy of 89.6%±5.0% in discriminating ccRCC from nccRCC. The diagnostic abilities of the developed RC-CAD system were further validated using a randomly stratified 10-fold cross-validation approach. The obtained results using the proposed MLP-ANN classification model outperformed other machine learning classifiers (e.g., support vector machine, random forests, relational functional gradient boosting, etc.). Hence, integrating morphological, textural, and functional features enhances the diagnostic performance, making the proposal a reliable noninvasive diagnostic tool for renal tumors.