Discovery of 9H-pyrimido[4,5-b]indole derivatives as dual RET/TRKA inhibitors.

Aberrant RET kinase signaling is activated in numerous cancers including lung, thyroid, breast, pancreatic, and prostate. Recent approvals of selective RET inhibitors, pralsetinib and selpercatinib, has shifted the focus of RET kinase drug discovery programs towards the development of selective inhibitors. However, selective inhibitors invariably lose efficacy as the selective nature of the inhibitor places Darwinian-like pressure on the tumor to bypass treatment through the selection of novel oncogenic drivers. Further, selective inhibitors are restricted for use in tumors with specific genetic backgrounds that do not encompass diverse patient classes. Here we report the identification of a pyrimido indole RET inhibitor found to also have activity against TRK. This selective dual RET/TRK inhibitor can be utilized in tumors with both RET and TRK genetic backgrounds and can also provide blockade of NTRK-fusions that are selected for from RET inhibitor treatments. Efforts towards developing dual RET/TRK inhibitors can be beneficial in terms of encompassing more diverse patient classes while also achieving blockade against emerging resistance mechanisms.

Effect of Intermittent Fasting on Improve Body Composition and Anthropometric Measurements of Women with Polycystic Ovarian Syndrome / Efecto del ayuno intermitente para mejorar la composición corporal y las medidas antropométricas de mujeres con síndrome de ovario poliquístico

Introduction: Polycystic ovary syndrome is a metabolicdisorder that affects women of reproductive age and is associated with insulin resistance.Objectives: The study aims to evaluate the effect of intermittent fasting and dietary intervention in improving anthropometric measures and body composition.Material and Methods: An interventional trial was carriedout on eighty-six women between the ages of 19 and 40 with a body mass index of more than 25 kg/m2 were assigned to two intervention groups: the first group (n = 57) followed intermittent fasting plus dietary restriction, and the second group (n = 29) followed dietary restriction without intermittent fasting.Results: The results show that the fasting polycystic ovarian syndrome women experienced a significant (P < 0.05) increase in muscle mass (2.2 ± 2.4) compared to the non-fasting group (0.01 ± 1.5). At the end of the intervention, fasting women with the polycystic ovarian syndrome had significantly (P < 0.05) lost weight (9.2 ± 4.5kg), fat mass % (4.6 ± 3.4), and visceral fat (2.3 ± 2.1 kg), while gaining muscle mass (2.2 ± 2.4 kg). However, non-fasting women with polycystic ovarian syndrome showed significantly reduced body weight (2.4 ± 0.4 kg), fat mass % (1.2 ± 1.1), and visceral fat (0.5 ± 0.7). The results of the linear regression model showed that the highest effect of intermittent fasting was seen in weight, fat-free mass, and muscle mass. Body fat mass changed by 93% under the effect of intermittent fasting.Conclusion: Intermittent fasting may improve health outcomes, reduce body fat, maintain muscle mass, and aidweight loss in women with polycystic ovarian syndrome.Large-scale randomized controlled trials can improve our understanding of intermittent fasting in polycystic ovarian syndrome.(AU)

Assessment of toxicity and antimicrobial performance of polymeric inorganic coagulant and evaluation for eutrophication reduction.

In this study, the efficacy of the promising iron-based polymeric inorganic coagulant (POFC) was assessed for the reduction of eutrophication effect (freshwater toxicity) and the microbial loads from wastewater. Toxicity assessment for POFC was conducted on mice and skin cell lines. The results confirm the lower toxicity level of POFC. The POFC showed excellent antibacterial efficacy against Gram-positive and Gram-negative bacteria. Moreover, it demonstrated a remarkable effectiveness against black fungus such as Aspergillus niger and Rhizopus oryzae. Additionally, POFC showed antiviral effectiveness against the highly pathogenic H5N1 influenza virus as well as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). POFC-based treatment gives excellent removal percentages for phosphate, and phosphorus at doses below 60 ppm with a low produced sludge volume that leads to 84% decrease in the rate of eutrophication and freshwater toxicity. At a POFC concentration of 60 ppm, remarkable reduction rates for total coliforms, fecal coliforms, and E. coli were achieved. After POFC-based coagulation, the produced sludge retains a lower bacterial density due to the antibacterial activity of POFC. Furthermore, it revealed that the observed removal efficiencies for fungi and yeasts in the produced sludge reached 85% at a POFC dose of 60 ppm. Overall, our research indicates that POFC has potential for application in pre-treatment of wastewater and serves as an antimicrobial agent.

Kinase inhibitor macrocycles: a perspective on limiting conformational flexibility when targeting the kinome with small molecules.

Methods utilized for drug discovery and development within the kinome have rapidly evolved since the approval of imatinib, the first small molecule kinase inhibitor. Macrocycles have received increasing interest as a technique to improve kinase inhibitor drug properties evident by the FDA approvals of lorlatinib, pacritinib, and repotrectinib. Compared to their acyclic counterparts, macrocycles can possess improved pharmacodynamic and pharmacokinetic properties. This review highlights clinical success stories when implementing macrocycles in kinase-based drug discovery and showcases that macrocyclization is a clinically validated drug discovery strategy when targeting the kinome.

Estimate a patient's 10 years cardiovascular risk using the Arteriosclerotic cardiovascular disease tool in a cross-sectional study in Al-Harja, Asser, Saudi Arabia, 2021.

Introduction: Recently, the cases of arteriosclerotic cardiovascular disease (ASCVD) have been increasing in the rural areas of southwest Saudi Arabia. Therefore, this study sought to consider the relevant contributing factors, such as traditional dietary habits and a diet rich in cholesterol and fat, few opportunities for disease screening, false beliefs about chronic disease management medications, delays in diagnosis, and the great distances required for travel to cardiac specialist centers. Methods: A cross-sectional study was conducted at 12 primary health care (PHC) centers, using the ASCVD tool. The total required sample was determined to be 440 participants after calculating based on the total population of Al-Harja. Systematic random sampling was performed using a list of PHC centers and fixed intervals. The study's outcome is ASCVD risk score divided into four categories: low risk <5%, borderline risk 5%-7.5%, intermediate risk >7.5%-20%, and high risk >20%. Data were collected through interview questionnaires, measurements, and laboratory sample investigations. Result: It was revealed that 16.59% of the participants were classified in the high-risk category for having ASCVD in the next 10 years. There was a significant association between the ASCVD risk score and obesity (P = 0.03). Prior diagnoses for either hypertension or diabetes mellitus (P = 0.00) were significantly associated with an increased ASCVD risk score. Conclusion: An alarmingly high prevalence of high-risk ASCVD scores was seen among male participants, with 54 (22.78%) in the high-risk category, while 19 female participants (9.36%) were in the same category. Therefore, we can conclude that male participants are two times as likely to have a high ASCVD risk than female participants.

Selenium- and/or copper-substituted hydroxyapatite: A bioceramic substrate for biomedical applications.

Atomic substitution or doping of a bioceramic material hydroxyapatite (HA) with specific ions is an appealing approach for improving its biocompatibility and activity, as well as imparting antibacterial properties. In this study, selenium- and/or copper-substituted hydroxyapatite powders were synthesized by an aqueous precipitation method and using the freeze-drying technique. The molar concentrations of constituents were calculated based on the proposed mechanism whereby selenium (Se4+) ions partially substitute phosphorus (P5+) sites, and copper (Cu2+) ions partially substitute (Ca2+) sites in the HA lattice. Dried precipitated samples were characterized using Inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field-emission scanning electron microscopy with energy dispersive X-ray spectroscopy (FESEM-EDX). Accordingly, substitution of Se4+ and/or Cu2+ ions took place in the crystal lattice of HA without the formation of any impurities. The presence of sulphur (S2-) ions in the hydroxyapatite was detected by ICP-OES in all samples with copper substituted in the lattice. The cytotoxicity of the powders on osteoblastic (MC3T3-E1) cells was evaluated in vitro. Selenium substituted hydroxyapatite (SeHA), at the concentration (200 µg/mL), demonstrated higher populations of the live cells than that of control (cells without powders), suggesting that selenium may stimulate the proliferation of these cells. In addition, the copper substituted hydroxyapatite (CuHA) and the selenium and copper substituted hydroxyapatite (SeCuHA) at the concentrations (200 and 300 µg/mL) and (200 µg/mL), respectively demonstrated better results than the unsubstituted HA. Antimicrobial activity was assessed using a well-diffusion method against Streptococcus mutans and Candida albicans, and superior results has obtained with SeCuHA samples. Presented findings imply that selenium and/or copper substituted modified hydroxyapatite nanoparticles, may be an attractive antimicrobial and cytocompatible substrate to be considered for use in a range of translational applications.

Self-crosslinked polyvinyl alcohol/cellulose nanofibril cryogels loaded with synthesized aminophosphonates as antimicrobial wound dressings.

Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs). Initially, the antimicrobial activity of four α-aminophosphonate derivatives against selected skin bacterial species was tested and their minimum inhibitory concentration was determined based on which the most effective compound was loaded into the cryogels. Next, the physical and mechanical properties of cryogels with various blending ratios of PVA-P/PVA-F and fixed amounts of CNFs were assessed, and drug release profiles and biological activities of drug-loaded cryogels were analyzed. Assessment of α-aminophosphonate derivatives showed the highest efficacy of a cinnamaldehyde-based derivative (Cinnam) against both Gram-negative and Gram-positive bacteria compared to other derivatives. The physical and mechanical properties of cryogels showed that PVA-P/PVA-F with a 50/50 blending ratio had the highest swelling ratio (1600%), surface area (523 m2 g-1), and compression recoverability (72%) compared to that with other blending ratios. Finally, antimicrobial and biofilm development studies showed that the cryogel loaded with a Cinnam amount of 2 mg (relative to polymer weight) showed the most sustained drug release profile over 75 h and had the highest efficacy against Gram-negative and Gram-positive bacteria. In conclusion, self-crosslinked tri-component cryogels loaded with the synthesized α-aminophosphonate derivative, having both antimicrobial and anti-biofilm formation properties, can have a significant impact on the management of uprising wound infection.

Risk factors for carpal tunnel syndrome in patients attending the primary care center of a tertiary hospital in Riyadh, Saudi Arabia: A case-control study.

BACKGROUND: Carpal tunnel syndrome (CTS), the most common entrapment neuropathy in the upper extremity, is known to be a multi-factorial disease that raises medical and nonmedical risk factors. The aim of the current study was to determine the risk factors of CTS in patients attending the primary care center at a tertiary hospital. MATERIALS AND METHODS: A case-control study was conducted by reviewing all medical records of patients above the age of 18 years old diagnosed with CTS from 2015 to 2021. The selected cases were evaluated by physical examination and confirmed by a nerve conduction study. Cases and controls were matched by age, gender, and nationality, with a case-to-control ratio of 1:2. Odds ratios were calculated for association between carpel tunnel syndrome and various factors and Chi-sqauare test determined statistical significance. Multiple logistic regression was performed to adjust for confounding. RESULTS: The study recruited 144 cases with a mean age of 53.38 ± 12.20 years and 288 controls with a mean age of 53.80 ± 12.27 years. The majority of subjects were female (84.7%) and of Saudi nationality (68.3%). There was a significant difference in body mass index, employment status, number of years of employment, occupation, mean systolic blood pressure, mean low-density lipoprotein cholesterol level, and mean blood urea level between cases and controls (P < 0.05). Laboratory tests that were found to be significantly associated with CTS in univariate analysis were thyroid-stimulating hormone (crude odds ratio [COR] = 0.828) and urea level (COR = 0.802). In fully adjusted analyses, obesity (adjusted odds ratio [AOR] =3.080), chronic kidney disease (AOR = 3.629), and the use of corticosteroid (AOR = 0.470) were also significantly associated with CTS. CONCLUSION: Similar to the findings of other studies, this study identified several potential risk factors for CTS. More large-scale longitudinal studies are required to establish a precise causal association.

Enhancing durability and sustainable preservation of Egyptian stone monuments using metabolites produced by Streptomyces exfoliatus.

Despite their threatens for Egyptian stone monuments, A few studies focused on using biocontrol agents against deteriorative fungi and bacteria instead of using chemical assays that leave residuals leading to human toxicity and environmental pollution. This work aims to isolate and identify fungal and bacterial isolates that showed deteriorative activities from stone monuments in Temple of Hathor, Luxor, Egypt, as well as determine the inhibitory activity of metabolites produced by Streptomyces exfoliatus SAMAH 2021 against the identified deteriorative fungal and bacterial strains. Moreover, studying the spectral analysis, toxicological assessment of metabolites produced by S. exfoliatus SAMAH 2021 against health human cell fibroblast, and colorimetric measurements on the selected stone monuments. Ten samples were collected from Temple of Hathor, Luxor, Egypt. Three fungal isolates and one bacterial isolate were obtained and identified as A. niger isolate Hathor 2, C. fioriniae strain Hathor 3, P. chrysogenum strain HATHOR 1, and L. sphaericus strain Hathor 4, respectively. Inhibitory potential of the metabolites in all concentrations used (100-25%) against the recommended antibiotics (Tetracycline 10 µg/ml and Doxycycline (30 µg/ml) showed an inhibitory effect toward all tested deteriorative pathogens with a minimum inhibition concentration (MIC) of 25%. Cytotoxicity test confirmed that microbial filtrate as the antimicrobial agent was safe for healthy human skin fibroblast with IC50 of < 100% and cell viability of 97%. Gas chromatography analysis recorded the existence of thirteen antimicrobial agents, Cis-vaccenic acid; 1,2-Benzenedicarboxylic acid; ç-Butyl-ç-butyrolactone and other compounds. Colorimetric measurements confirmed no color or surface change for the limestone-treated pieces. The use of the metabolite of microbial species antimicrobial as a biocontrol agent raises contemporary issues concerning the bio-protection of the Egyptian monuments to reduce chemical formulas that are toxic to humans and pollute the environment. Such serious problems need further investigation for all kinds of monuments.

Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities.

The leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown to have medicinal benefits and are extensively employed in traditional folk medicine. Herein, HPLC analysis of the ethyl acetate fraction of the total methanolic extract emphasized the enrichment of both A. indica L., and M. azedarach L. leaves extracts with phenolic and flavonoids composites, respectively. Besides, 4 limonoids and 2 flavonoids were isolated using column chromatography. By assessing the in vitro antiviral activities of both total leaves extracts against Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2), it was found that A. indica L. and M. azedarach L. have robust anti-SARS-CoV-2 activities at low half-maximal inhibitory concentrations (IC50) of 8.451 and 6.922 µg/mL, respectively. Due to the high safety of A. indica L. and M. azedarach L. extracts with half-maximal cytotoxic concentrations (CC50) of 446.2 and 351.4 µg/ml, respectively, both displayed extraordinary selectivity indices (SI>50). A. indica L. and M. azedarach L. leaves extracts could induce antibacterial activities against both Gram-negative and positive bacterial strains. The minimal inhibitory concentrations of A. indica L. and M. azedarach L. leaves extracts varied from 25 to 100 mg/mL within 30 min contact time towards the tested bacteria. Our findings confirm the broad-spectrum medicinal value of A. indica L. and M. azedarach L. leaves extracts. Finally, additional in vivo investigations are highly recommended to confirm the anti-COVID-19 and antimicrobial activities of both plant extracts.

Sorption and transport characteristics of europium on sandy soils.

Radioactive europium can be released as a fission product during nuclear incidents and pose a threat to the human and surrounding environment because of its biological activity and long decay half-lives. For safe design issues and human health protection demands in construction of the planned nuclear power plants (NPPs) at Al-Dabaa site, it is necessary to study the sorption and transport of different radionuclides as europium within the selected area for predicting their fate at any crisis. Many soil samples were collected from different locations at the area selected along the northwestern coast of Egypt. The samples were transported to the laboratory, preserved, and characterized using X-Ray fluorescence (XRF), Fourier transform infrared spectroscopy (FT-IR), and X-Ray diffraction (XRD). Experiments were performed to study the sorption and transport kinetics of Eu(III) ions on two sandy soil samples from the collected ones. The effect of different parameters (e.g. contact time, pH, initial europium concentration, and temperature) on the sorption behavior europium was explored in a static condition. The maximum sorption capacity was determined and found to be 3.4 and 7.0 mg g-1 for sorption of Eu(III) ions onto soil-1 and soil-2, respectively. Different models were applied to assess the sorption of europium onto the surface of the investigated soils. Data confirmed that Eu retention was attained through a chemisorption process. Further, the thermodynamic parameters were determined and their values confirmed the endothermic nature of the sorption process. The transport of europium radionuclides, with groundwater, through homogeneous porous media with uniform one-dimensional flow in the geosphere was processed and the relative migration velocity was determined in presence of both distilled and seawater media. The transport of Eu(III) radionuclides was higher in presence of seawater than that in presence of distilled water by about two order of magnitude. This obviously clarified the effect of seawater in accelerating the transport of radionuclides with groundwater in the geosphere of studied area. The role of different competing ions have various valances on the relative migration velocity was explored. Further, the time required for studied radionuclides to reach Mediterranean Sea was determined.

Bacterial community structure of electrogenic biofilm developed on modified graphite anode in microbial fuel cell.

Formation of electrogenic microbial biofilm on the electrode is critical for harvesting electrical power from wastewater in microbial biofuel cells (MFCs). Although the knowledge of bacterial community structures in the biofilm is vital for the rational design of MFC electrodes, an in-depth study on the subject is still awaiting. Herein, we attempt to address this issue by creating electrogenic biofilm on modified graphite anodes assembled in an air-cathode MFC. The modification was performed with reduced graphene oxide (rGO), polyaniline (PANI), and carbon nanotube (CNTs) separately. To accelerate the growth of the biofilm, soybean-potato composite (plant) powder was blended with these conductive materials during the fabrication of the anodes. The MFC fabricated with PANI-based anode delivered the current density of 324.2 mA cm-2, followed by CNTs (248.75 mA cm-2), rGO (193 mA cm-2), and blank (without coating) (151 mA cm-2) graphite electrodes. Likewise, the PANI-based anode supported a robust biofilm growth containing maximum bacterial cell densities with diverse shapes and sizes of the cells and broad metabolic functionality. The alpha diversity of the biofilm developed over the anode coated with PANI was the loftiest operational taxonomic unit (2058 OUT) and Shannon index (7.56), as disclosed from the high-throughput 16S rRNA sequence analysis. Further, within these taxonomic units, exoelectrogenic phyla comprising Proteobacteria, Firmicutes, and Bacteroidetes were maximum with their corresponding level (%) 45.5, 36.2, and 9.8. The relative abundance of Gammaproteobacteria, Clostridia, and Bacilli at the class level, while Pseudomonas, Clostridium, Enterococcus, and Bifidobacterium at the genus level were comparatively higher in the PANI-based anode.

The survivorship and factors affecting the outcome of the use of spring plates in multifragmentary posterior wall acetabular fractures at a single academic institution.

BACKGROUND: Multifragmentary posterior wall fractures are not uncommon after posterior hip fracture-dislocation. They can be elementary but are commonly associated with transverse acetabular fractures. Specific technical challenges are encountered when managing these fracture patterns. The loss of the posterior landmarks due to the associated comminution may render achieving an anatomical reduction and stable fixation difficult. The application of spring plates can provide a good buttress with multiple anchor points and creates a new cortex for the bridging plate. PURPOSE OF THE STUDY: -To assess the outcome and survivorship of the use of spring plates for the fixation of multi-fragmentary posterior wall fractures. -To analyse the factors affecting the outcome of the fixation of these challenging injuries. PATIENTS AND METHODS: We retrospectively reviewed all the patients who underwent posterior wall acetabular fixation using a spring plate between December 2009 and March 2020 at our institution. Forty-seven patients had a minimum follow-up of 1 year and were included in the study with a mean age of 36 ± 10 years (range:17-60) and a mean follow-up period of 4.4 ± 3.5 years. Seventeen patients had an associated transverse acetabular fracture, and an anterior columnar screw was used for additional fixation. Functional outcome was assessed using the Oxford hip score (OHS). Radiological assessment was undertaken for the images done immediately post-operatively and at the last follow-up. Patients with advanced post-traumatic arthritis and complications such as avascular necrosis (AVN), nerve injuries, non-union, heterotopic ossification and fixation failure were identified. The hazard rate of re-operation on the native hip was estimated using the life tables. Kaplan Meier analysis was used to assess survival with THR or excision arthroplasty as an endpoint. RESULTS: Six patients underwent a total hip replacement: secondary to AVN in four and infection in two patients. The hazard of THR was estimated at 6% (SE = 0.02) during the first three years, then decreased dramatically afterwards. The five-year survival of native hip was 83% (SE = 0.06). Native hip was expected to survive for 10.67 years (95% CI 9.49-11.83) without joint replacement. The mean OHS in our cohort was 33.66 (3-48), and 29 patients (61.70%) had an OHS of more than 30. CONCLUSION: The use of spring plates to fix multifragmentary posterior wall fractures has excellent mid-term results, high survivorship and a low complication rate. Combining an anterior columnar screw and a posterior spring plate has shown to be a suitable fixation construct in selected patients with associated transverse acetabular fractures. A longer-term follow-up with a larger cohort using this fixation construct is needed.

New insights for tracking bacterial community structures in industrial wastewater from textile factories to surface water using phenotypic, 16S rRNA isolates identifications and high-throughput sequencing.

Industrial wastewater can possibly change the microbial ecological environment. There are few studies that focus on the bacterial variety in textile wastewater effluents and after combination with domestic wastewater. Thus, this study aimed to determine dye degrading bacteria from textile wastewater and environmental water samples using cultural method followed by phenotypic using BIOLOG and genotypic identification (16S rRNA) for dye degrading isolates identifications. Moreover, the bacterial communities in three textile and four environmental samples using Illumina MiSeq high-throughput sequencing were investigated. The findings revealed that in textile water samples, the ratio of dye-degrading bacteria (DDB) to total bacterial counts (TBC) was 27%. The identified DDB genera by 16S rRNA based on the cultural approach were Citrobacter spp., Klebsiella spp., Enterobacter spp., Pseudomonas spp., and Aeromonas spp. Regarding to the metagenomics analyses, the environmental samples had 5,598 Operational Toxanomic Units (OTUs) more than textile wastewater samples (1,463 OTUs). Additionally, the most abundant phyla in the textile wastewater were Proteobacteria (24.45-94.83%), Bacteriodetes (0.5-44.84%) and Firmicutes (3.72-67.40%), while, Proteobacteria (30.8-76.3%), bacteroidetes (8.5-50%) and Acentobacteria (0.5-23.12%) were the most abundant phyla in the environmental samples. The maximum abundant bacteria at species level in environmental samples were Aquabacterium parvum (36.71%), Delftia tsuruhatensis (17.61%), Parabacteriodes chartae (15.39%) and Methylorubrum populi (7.51%) in El-Rahawy Drain water (RDW), River Nile water (RNW), wastewater (RWW) from WWTP in Zennin and El-Rahawy Drain sediment (RDS), respectively, whereas the maximum abundant bacteria at species level in textile wastewater were Alkalibacterium pelagium (34.11%), Enterobacter kobei (26.09%) and Chryseobacterium montanum (16.93%) in factory 1 (HBT) sample, SHB sample (before mixing with domestic wastewater) and SHB sample (after mixing with domestic wastewater), respectively. In conclusion, the microbial communities in textile wastewaters are similar to those in environmental samples at the phylum level but distinct at the genus and species levels because they are exposed to a wider range of environmental circumstances.

Investigating PSMA differential expression in canine uroepithelial carcinomas to aid disease-based stratification and guide therapeutic selection.

BACKGROUND: In male dogs, uroepithelial cancers include invasive urothelial carcinoma (iUC) and prostate carcinoma (PCA). The inability to distinguish iUC involving the prostate from PCA results in indiscriminate clinical management strategies that could be suboptimal as first-line chemotherapy for iUC (cisplatin) and PCA (docetaxel) differ in people. Prostate specific membrane antigen (PSMA) is a transmembrane protein, and its overexpression has been identified in human prostate carcinoma and neovasculature associated with solid tumor growth. This study investigates whether differential PSMA expression exists between presumptive canine iUC and PCA among cell lines and archived patient samples, which might allow for improved accuracy in disease-based stratification and optimal chemotherapy selection. Additionally, in vitro sensitivities of reported canine iUC and PCA cell lines to uroepithelial directed chemotherapeutic agents were characterized. RESULTS: Normalized PSMA gene and protein expressions were not significantly different between 5 iUC and 4 PCA cell lines. PSMA protein expression was uniformly observed in uroepithelial cancers regardless of anatomic origin from archived patient samples, further confirming that PSMA cannot differentiate iUC from PCA. In vitro sensitivity of cell lines to uroepithelial directed chemotherapeutics revealed that vinblastine exerted the broadest cytotoxic activity. CONCLUSIONS: Differential expression of PSMA was not identified between canine iUC and PCA cell lines or archived patient samples, and PSMA alone cannot be used for disease stratification. Nonetheless given its conserved overexpression, PSMA may be a targetable surface marker for both canine iUC and PCA. Lastly, in uroepithelial carcinomas, vinblastine might exert the broadest anticancer activity regardless of cellular origin.

Microbial Degradation, Spectral analysis and Toxicological Assessment of Malachite Green Dye by Streptomyces exfoliatus.

Malachite green (MG) dye is a common environmental pollutant that threatens human health and the integrity of the Earth's ecosystem. The aim of this study was to investigate the potential biodegradation of MG dye by actinomycetes species isolated from planted soil near an industrial water effluent in Cairo, Egypt. The Streptomyces isolate St 45 was selected according to its high efficiency for laccase production. It was identified as S. exfoliatus based on phenotype and 16S rRNA molecular analysis and was deposited in the NCBI GenBank with the gene accession number OL720220. Its growth kinetics were studied during an incubation time of 144 h, during which the growth rate was 0.4232 (µ/h), the duplication time (td) was 1.64 d, and multiplication rate (MR) was 0.61 h, with an MG decolorization value of 96% after 120 h of incubation at 25 °C. Eleven physical and nutritional factors (mannitol, frying oil waste, MgSO4, NH4NO3, NH4Cl, dye concentration, pH, agitation, temperature, inoculum size, and incubation time) were screened for significance in the biodegradation of MG by S. exfoliatus using PBD. Out of the eleven factors screened in PBD, five (dye concentration, frying oil waste, MgSO4, inoculum size, and pH) were shown to be significant in the decolorization process. Central composite design (CCD) was applied to optimize the biodegradation of MG. Maximum decolorization was attained using the following optimal conditions: food oil waste, 7.5 mL/L; MgSO4, 0.35 g/L; dye concentration, 0.04 g/L; pH, 4.0; and inoculum size, 12.5%. The products from the degradation of MG by S. exfoliatus were characterized using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The results revealed the presence of several compounds, including leuco-malachite green, di(tert-butyl)(2-phenylethoxy) silane, 1,3-benzenedicarboxylic acid, bis(2-ethylhexyl) ester, 1,4-benzenedicarboxylic acid, bis(2-ethylhexyl) ester, 1,2-benzenedicarboxylic acid, di-n-octyl phthalate, and 1,2-benzenedicarboxylic acid, dioctyl ester. Moreover, the phytotoxicity, microbial toxicity, and cytotoxicity tests confirmed that the byproducts of MG degradation were not toxic to plants, microbes, or human cells. The results of this work implicate S. exfoliatus as a novel strain for MG biodegradation in different environments.

Psychological impact of the COVID-19 pandemic on waitlisted pre-bariatric surgery patients in Saudi Arabia: A cross-sectional study.

Background: During the COVID-19 pandemic, the number of bariatric surgeries was decreased to ensure patient safety. This study aimed to evaluate the effect of such delays on the psychological status and weight management behaviors of waitlisted pre-bariatric surgery patients in Jeddah, Saudi Arabia. Materials and methods: A web-based cross-sectional survey was conducted. Results were then evaluated with simple descriptive statistics and inferential analyses through the Chi-square test, one-way ANOVA, and the general linear regression model. Results: Of 437 patients, 208 successfully completed the survey. Approximately half of the participants reported weight change (46.6%, n = 97), while other weight management behaviors remained unchanged. The mean Patient Health Questionnaire-9 (PHQ-9) total score of the respondents was 8.29 ± 6.3, indicating mild depression. Higher PHQ-9 scores were associated with being a student, unhealthy dietary habits, physical inactivity, worsened psychological status, and weight gain. Among these factors, being a student was the strongest predictor of the total PHQ-9 score. Conclusion: The COVID-19 pandemic significantly affected the psychological status of patients with obesity on the bariatric surgery waitlist. Since delays in bariatric surgeries could worsen patients' psychological status, as substantiated in this study, the provision of virtual care through telemedicine and the development of policies for reintroducing bariatric surgeries for future lockdowns are highly recommended.

Novel electro-oxidation unit for electro-disinfection of E. coli and some waterborne pathogens during wastewater treatment: batch and continuous experiments.

The prime objective of the current investigation is to evaluate a promising alternative method for disinfection wastewater using a novel electro-oxidation unit. The study focused on determining the best-operating conditions from a techno-economic point of view to be applied to continuous flow simulating actual disinfection modules. The treatment unit consisted of a Plexiglas container with a 3 L volume containing nine cylindrical shape electrodes (6 graphite as anode and 3 stainless steel as a cathode) connected to a variable DC power supply. Determination of the best operating parameters was investigated in batch mode on synthetic wastewater by studying the effect of contact time, current density (CD), total dissolved solids concentration (TDS), and bacterial density. Moreover, the continuous mode experiment was considered on real wastewater from an agricultural drain and the secondary wastewater treatment plant effluent before chlorination. The batch mode results revealed that the best applicable operational conditions that achieved the complete removal of E. coli were at a contact time of less than 5 min, TDS of 2000 mg/L, and CD of 4 mA/cm2. Application of these conditions on the continuous mode experiment indicated the complete removal of all bacterial indicators after 5 min in the drainage wastewater and after 3 min in the secondary treated wastewater. Physico-chemical characterization also suggested that no chlorine by-products displaying the hydroxide ion formed due to water electrolysis is the main reason for prohibiting the growth of pathogenic microbes. The electrical consumption was calculated in the continuous mode and found to be 0.5 kWh/m3 with an operational cost of about 0.06 $/m3, including the cost of adding chemicals to increase the TDS. The results proved that this novel electro-oxidation unit is a robust and affordable disinfection method for complete bacterial removal from wastewater and is more environmentally benign than other conventional disinfection methods.

Perception of primary caregiver toward virtual pediatric clinics for type 1 diabetes mellitus during COVID-19 pandemic in Jeddah, Saudi Arabia: A cross-sectional study.

Background: Virtual phone clinics were adopted at King Abdulaziz Medical City, Jeddah, Saudi Arabia, as an alternative to in-person routine outpatient visits amid the COVID-19 pandemic. This study aimed to assess primary caregiver perceptions of the virtual phone clinics towards routine care of pediatric patients with type 1 diabetes mellitus (T1DM). Methods: A cross-sectional research design was employed through a web-based research tool where the primary caregivers of pediatric patients with T1DM participated. Data were analyzed descriptively and statistically using independent t-tests and one-way analysis of variance. Results: In total, 214 participants were included in this study. The average primary caregiver perception value towards virtual phone clinics was 66.71 ± 23.1%, which suggested a satisfactory perception of their experience. Statistically significant differences (p > 0.05) were not found between the mean perception values and demographic characteristics. Higher mean primary caregiver perception values were associated with those who: (1) agreed or strongly agreed to be contented with their current state of health, (2) did not ask their physicians to be physically seen during a virtual visit, (3) preferred having four virtual visits or more, and (4) preferred having single to no in-person visits at all. Conclusion: This study revealed a generally acceptable primary caregiver perception regarding virtual clinics. Telemedicine is recommended for routine treatment alongside regular in-clinic appointments to improve the quality of care for pediatric patients with T1DM.