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This study investigated the corrosion inhibition and scale control properties of both natural extracts and chemical inhibitors for C25 galvanized steel sheets with an 85-μm thick zinc coating steel exposed to seawater. The inhibitors, including Foeniculum vulgare (AF-Sha), Pimpinella anisum (AF-Sim), M640, and Veo, underwent rigorous evaluation through techniques such as Tafel extrapolation, potentiodynamic polarization analysis, concentration factor scale, seawater analysis, X-ray diffraction (XRD), infrared spectroscopy (IR), and conductivity-temperature analysis. Notably, AF-Sha and AF-Sim exhibited outstanding corrosion prevention capabilities, achieving inhibitory efficiencies of 87% and 85%, respectively. Comparative analyses with chemical inhibitors, M640 and Veo, demonstrated promising performance, positioning natural inhibitors as environmentally friendly alternatives. Corrosion rates, inhibition efficiency, and concentration factor scale results provided insights into the inhibitory effectiveness of each compound, with Veo showing superior performance. The study also explored the antiscalant behavior of inhibitors, revealing their ability to prevent corrosion and scale formation. XRD analysis indicated the impact of inhibitors on the crystal structure of scales, while IR spectra provided insights into vibration properties. Conductivity and temperature analyses illustrated the inhibitors' role in reducing ion exchange and gypsum concentration in seawater. These findings suggest that the inhibitors offered robust protection for ferrous metal surfaces and hold significant potential for practical applications. Additionally, our weight loss investigation extends this understanding, demonstrating the practical applicability of corrosion inhibitors like AF-Sha and AF-Sim in real-world scenarios. The presented results contribute significantly to the understanding of galvanized steel corrosion behavior in seawater, offering valuable insights for corrosion engineering applications.

Background: During the preoperative evaluation of a patient being considered for spinal surgery, Dual-energy x-ray absorptiometry (DEXA) has been traditionally used to diagnose poor bone mineral density (BMD) as a risk factor. As ordering a DEXA can add cost and delay diagnosis, spine surgeons have more recently began to use Hounsfield Units (HU) measured on computed tomography scans (CT) as a measure of BMD. The aim of our study was to evaluate associations between DEXA and HU on lumbar spine CT scans. Methods: Forty-two patients (32 female, 10 male, mean age = 67.7 years) with DEXA and lumbar spine CT scans performed within one year of each other were identified. DEXA T-scores were collected from the hip, forearm and L1-L4. HU was determined using the maximum region of interest within the cancellous area in the mid-vertebral body from L1-L4 in the sagittal and axial planes. Results: Using the lowest T-score, 8 (19 %) cases were osteoporotic and 25 (60 %) were osteopenic. Statistically significant differences in HU were seen in osteoporotic cases (Axial HU = 59.2, Sagittal HU = 61.1, p = 0.006) compared to osteopenic (Axial HU = 119.8, Sagittal HU = 122.9) and normal cases (Axial HU = 141.2, Sagittal HU = 142.3). There were moderate associations between the spine T-scores and CT HUs (Axial HU:r2 = 0.50, Sagittal HU:r2 = 0.49, p

Abstract Background This study aimed to assess the role of community pharmacists and their perception toward antimicrobial stewardship, in addition to identifying factors influencing their perception and practices in community pharmacy. Methods A cross‐sectional study was carried out among community pharmacists regarding antimicrobial stewardship. Convenience sampling was used to obtain the required sample from a community pharmacy in Baghdad. In total, 381 participants have completed the survey. Results The majority of the participants (85.6%) strongly agreed/agreed that “antimicrobial stewardship programs reduce the problems of antibiotic resistance”; and 85.5% of them strongly agreed/agreed that community pharmacists required adequate training on antibiotics use. In addition, high percent of community pharmacists (88.4%) strongly agreed/agreed that pharmacists have a responsibility to take a prominent role in antimicrobial stewardship programs and infection‐control programs in the health system. The total score of perception was significantly influenced by older age groups, postgraduate degrees, and experience of 6–10 years (p

The development of resistance to carbapenems in Klebsiella pneumoniae due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing K. pneumoniae. Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant K. pneumoniae isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes blaNDM and blaVIM. A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing K. pneumoniae.

Abstract Background Flavin monoamine oxidase gene encodes a protein (MAOB) that forms a part of the flavin monoamine oxidase family in the outer membrane of mitochondria. It plays a role in the tissue metabolism of neuroactive and vasoactive amines as well as the oxidative deamination of xenobiotic and biogenic amines. However, overexpression of the receptor reduced apoptosis in cells, resulting in the progress of prostate sarcoma. Therefore, various kinds of MAOB antagonists are often used to fix an apoptosis mechanism that makes it hard to get rid of cancer from live tissues. Moreover, chemical compounds that have been discovered to be MAOB inhibitors to date exhibit side effects that are causing problems in chemotherapy treatment. The study aims to discover new purchasable compound that induces apoptosis by allowing caspases to operate at their maximum efficiency and is low toxic. Methods With the assistance of virtual screening, molecular docking, and molecular dynamics simulation (MD), a structure-based pharmacophore model of the protein active site cavity was made. Twenty hits were found, and then a molecular docking strategy was used to choose four molecules to study in more depth. MD simulations were used to check the stability of the four compounds, and they were all shown to be stable when bound to the target protein. Results Four newly discovered compounds, included with ZINC ID Such as ZINC12143050, ZINC08301324, ZINC16743012, and ZINC64165826 with binding scores of − 11.7, − 11.4, − 11.2 and − 11.1 kcal/mol, respectively, may serve as lead compounds for the treatment of prostate cancer associated with MAOB; however, further evaluation through wet lab is needed to determine the compounds effectiveness. Conclusion A structure-based model was initially developed, followed by molecular docking, ADMET analysis, and MD simulation. The top four natural compounds identified in the A-to-Z virtual screening process could serve as lead molecules in the fight against prostate cancer.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

Environmental enrichment (EE) is an important factor that helps improve both the physical and psychological behavior of farmed animals. This factor also controls social interactions and provides more stimulants to influence the reproductive performance of animals in captivity. As EE plays an important role in animal reproduction, the present study was designed to investigate the effects of different types of tank bottom enrichments on the ovarian development of Buitta (Sperata sp.) catfish in captivity. Barren (TA), muddy (TB), and sandy (TC) enrichments were utilized for four months to observe the physical and psychological changes of the catfish. The results showed significant differences (p

Purpose: The purpose of this study is to evaluate and assess the effect of intermittent tamsulosin treatment as a trial to increase the drug safety (in terms of reducing the drug side effects, particularly retrograde ejaculation) while maintaining the effect in reducing the symptoms and assess its impact on the patients' quality of life. Materials and Methods: Patients who enrolled in this study were suffering from lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and were using 0.4 mg tamsulosin daily to relieve their symptoms but complained of ejaculatory problems. A baseline assessment involves medical history and evaluation of ejaculatory function abdominopelvic ultrasound, postvoid residual volume (PVR) estimation, the International Prostate Symptom Score (IPSS), quality of life assessed using global satisfaction, vital signs, physical examination including digital rectal examination, and renal function. During the study, patients consented to take 0.4 mg tamsulosin intermittently every other day and to proceed with their sexual activities on the days they did not take the drug in. Baseline assessment was repeated and recorded after 3 months from starting the treatment. The adverse effects and compliance were analyzed in all patients. Results: Twenty-five patients had a mean baseline IPSS of 6.6 ± 1 and baseline PVR of 87.6 ± 15.1 ml. At the 3rd month, the mean PVR was 100.4 ± 15.1 ml and the mean IPSS was 7.3 ± 1.1. Moreover, 20 out of the total number of 25 patients (80%) reported improvement in their ejaculation. All our 20 patients who showed improvement in their ejaculatory function are either satisfied or very satisfied (4 or 5), in regard to the global satisfaction rate. Conclusion: Intermittent tamsulosin therapy (0.4 mg/every other day) is well-tolerated and shows a potential advantage in recovery in patients who suffer from LUTS/BPH and complaining from abnormal ejaculation, especially absent ejaculate. Although there was a significant change in PVR and IPSS after using intermittent tamsulosin therapy. Most patients show a higher overall satisfaction with the treatment compared to the standard dose (0.4 mg/daily). A study on a larger scale is still needed to confirm our results.

Leaching scheduling techniques are one of the suggested solutions for water scarcity problems .The aim of the study is to show the possibility of using leaching scheduling, when applying the irrigation scheduling program for a certain irrigation project, which was prepare by Water Resources Engineering –University of Baghdad with some modifications to generalized it and it make applicable to various climatic zone and different soil types. The objectives of this research is to build a system that concerns the prediction of the leaching scheduling (depth and date of leaching water), illustrating the main problems (soil salinity, save the amount of leaching requirement, and to maintain crops growth).The other objective is to compare between the calculated amount of leaching water with the amount of water that is suggested by designers. The program includes, the calculating of predicted daily soil salinity ,the depth of leaching water that should be applied to remove the salt from the soil when it reaches a harmful level, and the total annual volume of leaching water. The results showed, that the use of predicted leaching scheduling with its applicable constrains require high attention when choosing the cropping pattern for each climate zone. Also, it was found that the leaching program is a useful tool for saving irrigation water if cropping pattern has been adapted carefully. This means the leaching water depth should be added only when needed, and may not be necessary with each irrigation event.

The human intestinal microbiota, also known as the gut microbiota, comprises more than 100 trillion organisms, mainly bacteria. This number exceeds the host body cells by a factor of ten. The gastrointestinal tract, which houses 60%–80% of the host’s immune cells, is one of the largest immune organs. It maintains systemic immune homeostasis in the face of constant bacterial challenges. The gut microbiota has evolved with the host, and its symbiotic state with the host’s gut epithelium is a testament to this co-evolution. However, certain microbial subpopulations may expand during pathological interventions, disrupting the delicate species-level microbial equilibrium and triggering inflammation and tumorigenesis. This review highlights the impact of gut microbiota dysbiosis on the development and progression of certain types of cancers and discusses the potential for developing new therapeutic strategies against cancer by manipulating the gut microbiota. By interacting with the host microbiota, we may be able to enhance the effectiveness of anticancer therapies and open new avenues for improving patient outcomes.

In the original publication [...]

Background:. Little is known about the levels of health literacy (HL) among plastic and reconstructive surgery (PRS) patients compared with the general population. This study aimed to characterize HL levels in patients interested in plastic surgery and identify potential risk factors associated with inadequate levels of HL among this population. Methods:. Amazon’s Mechanical Turk was used to distribute a survey. The Chew’s Brief Health Literacy Screener was used to evaluate the level of HL. The cohort was divided into two groups: non-PRS and PRS groups. Four subgroups were created: cosmetic, noncosmetic, reconstructive, and nonreconstructive groups. A multivariable logistic regression model was constructed to assess associations between levels of HL and sociodemographic characteristics. Results:. A total of 510 responses were analyzed in this study. Of those, 34% of participants belong to the PRS group and 66% to the non-PRS group. Inadequate levels of HL were evidenced in 52% and 50% of the participants in the non-PRS and PRS groups, respectively (P = 0.780). No difference in HL levels was found in the noncosmetic versus cosmetic groups (P = 0.783). A statistically significant difference in HL levels was evidenced between nonreconstructive versus reconstructive groups after holding other sociodemographic factors constant (0.29, OR; 95% CI, 0.15–0.58; P < 0.001). Conclusions:. Inadequate levels of HL were present in almost half of the cohort, which highlights the importance of adequately assessing HL levels in all patients. It is of utmost importance to evaluate HL in clinical practice using evidence-based criteria to better inform and educate patients interested in plastic surgery.

Tilapia Lake Virus (TiLV) is a disease that affects tilapia fish, causing a high rate of sudden death at any stage in their life cycle. Unfortunately, there are currently no effective antiviral drugs or vaccines to prevent or control the progression of this disease. Researchers have discovered that the CRM1 protein plays a critical function in the development and spreading of animal viruses. By inhibiting CRM1, the virus's spread in commercial fish farms can be suppressed. With this in mind, this study intended to identify potential antiviral drugs from two different tropical mangrove plants from tropical regions: Heritiera fomes and Ceriops candolleana. To identify promising compounds that target the CRM1 protein, a computer-aided drug discovery approach is employed containing molecular docking, ADME (absorption, distribution, metabolism and excretion) analysis, toxicity assessment as well as molecular dynamics (MD) simulation. To estimate binding affinities of all phytochemicals, molecular docking is used and the top three candidate compounds with the highest docking scores were selected, which are CID107876 (-8.3 Kcal/mol), CID12795736 (-8.2 Kcal/mol), and CID12303662 (-7.9 Kcal/mol). We also evaluated the ADME and toxicity properties of these compounds. Finally, MD simulation was conducted to analyze the stability of the protein-ligand complex structures and confirm the suitability of these compounds. The computational study demonstrated that the phytochemicals found in H. fomes and C. candolleana could potentially serve as important inhibitors of TiLV, offering practical utility. However, further in vivo investigations are necessary to investigate and potentially confirm the effectiveness of these compounds as antiviral drugs against the virus TiLV.

Background: Healthcare-associated infections (HAI) are considered one of the most common adverse events in health care service provision. In order to prevent the occurrence of HAIs, it is important to implement several prevention strategies. Objectives: This study aims to determine the incidence of healthcare-associated infections in a military hospital in Alkharj and the adherence to the HAIs’ prevention strategies. Methods: This study included exporting data for all infected cases confirmed by the infection disease specialists in 2019. The data were collected from the reports that were written by infection control unit and infectious disease department. Results: The rate of healthcare associated infections (HAIs) in 2019 was 0.43% of total patient admissions. The rate of central line associated bloodstream infections in 2019 was 1.15 per 1000 central line days. The rate of catheter associated urinary tract infections in 2019 was 1.00 per 1000 catheter days. The rate of ventilator associated pneumonia in 2019 was 2.11 per 1000 ventilator days and the rate of surgical site infections in 2019 was 0.41 %. Conclusion: The rate of overall healthcare-associated infections (HAI) was low. The compliance rate of health care workers to preventive measures that control HAIs was generally high but there was a need for more awareness particularly regarding personal protective equipment and hand hygiene. So it is important to attend more awareness activities and workshops particularly regarding personal protective equipment and hand hygiene. Furthermore, infection control unit and infectious disease department in the hospital should support the robust HAI prevention programs.

Abstract Introduction Preoperative autophagy inhibition with hydroxychloroquine (HCQ) in combination with gemcitabine in pancreatic adenocarcinoma (PDAC) has been shown to be safe and effective in inducing a serum biomarker response and increase resection rates in a previous phase I/II clinical trial. We aimed to analyze the long‐term outcomes of preoperative HCQ with gemcitabine for this cohort. Methods A review of patients enrolled between July 2010 and February 2013 in the completed phase I/II single arm (two doses of fixed‐dose gemcitabine (1500 mg/m2) in combination with oral hydroxychloroquine administered for 31 consecutive days until the day of surgery for high‐risk pancreatic cancer) was undertaken. Progression‐free survival (PFS) and overall survival analysis (OS) using Kaplan–Meier estimates were performed. Results Of 35 patients initially enrolled, 29 patients underwent surgical resection (median age at diagnosis: 62 years, 45% females). Median duration of follow‐up was 7.5 years. There was a median 15% decrease in the serum CA19‐9 levels following completion of neoadjuvant therapy and 83% of the cohort underwent a pancreaticoduodenectomy, 7 (24%) patients had a concomitant venous resection. On histopathology, 14 (48%) patients had at least a partial treatment response. The median PFS and OS were 11 months (95% Confidence interval [CI]: 7–28) and 31 months (95% CI: 13–47), respectively, while 9 (31%) patients survived beyond 5 years from diagnosis; a rate that compares very favorably with contemporaneous series. Conclusion Compared to historical data, neoadjuvant autophagy inhibition with HCQ plus gemcitabine is associated with encouraging long‐term survival for patients with PDAC.

Abstract Background Clinical pharmacy interventions (CPI) usually require prior medical authorization. Physicians approve 80% of CPI and reject 20%. If pharmacists show that physicians should authorize all 100% CPI, the profession will step closer to a fully independent prescriber status. This study used an artificial neural network (ANN) model to determine whether clinical pharmacy (CP) may improve outcomes associated with rejected CPI. Method This is a non-interventional, retrospective analysis of documented CPI in a 100-bed, acute-care private hospital in Amman, Jordan. Study consisted of 542 patients, 574 admissions, and 1694 CPI. Team collected demographic and clinical data using a standardized tool. Input consisted of 54 variables with some taking merely repetitive values for each CPI in each patient whereas others varying with every CPI. Therefore, CPI was consolidated to one rejected and/or one accepted per patient per admission. Groups of accepted and rejected CPI were compared in terms of matched and unmatched variables. ANN were, subsequently, trained and internally as well as cross validated for outcomes of interest. Outcomes were length of hospital and intensive care stay after the index CPI (LOSTA & LOSICUA, respectively), readmissions, mortality, and cost of hospitalization. Best models were finally used to compare the two scenarios of approving 80% versus 100% of CPI. Variable impacts (VI) automatically generated by the ANN were compared to evaluate the effect of rejecting CPI. Main outcome measure was Lengths of hospital stay after the index CPI (LOSTA). Results ANN configurations converged within 18 s and 300 trials. All models showed a significant reduction in LOSTA with 100% versus 80% accepted CPI of about 0.4 days (2.6 ± 3.4, median (range) of 2 (0–28) versus 3.0 ± 3.8, 2 (0–30), P-value = 0.022). Average savings with acceptance of those rejected CPI was 55 JD (~ 78 US dollars) and could help hire about 1.3 extra clinical pharmacist full-time equivalents. Conclusions Maximizing acceptance of CPI reduced the length of hospital stay in this model. Practicing Clinical Pharmacists may qualify for further privileges including promotion to a fully independent prescriber status.

In this study, the effect of adding two different types of reinforcing natural fibers (jute and cotton) singly and in combination as a hybrid to unsaturated polyester resin was investigated. At the first discontinuous random fibers used in (5)mm length are added separately with different weight fraction as (3, 4.5, 6, and 7.5 wt.%) for both types fibers, then these fibers were mixed at (3.75 wt.% jute, 3.75 wt.% cotton) in (5)mm long. and The mechanical tests (hardness, Impact, and compression), as well as moisture absorption, are performed. The results show an increase in these properties with increasing weight fraction of fibers (jute & cotton) and reach the maximum amount at the addition of weight fraction of (7.5 wt.%) of both fibers (jute and cotton) separately. All composite specimens reinforced with jute fibers showed the highest hardness, Impact, compression, and moisture absorption among the composite specimen reinforced by cotton fibers and higher than in combination as a hybrid it was (93.1, 28.81 KJ/m2, 205 Mpa., and 1.4%) respectively.

Abstract SMAD4, a tumor suppressor gene, is lost in up to 60%–90% of pancreatic adenocarcinomas (PDAs). Loss of SMAD4 allows tumor progression by upregulating autophagy, a cell survival mechanism that counteracts apoptosis and allows intracellular recycling of macromolecules. Hydroxychloroquine (HCQ) is an autophagy inhibitor. We studied whether HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. We retrospectively analyzed the SMAD4 status of patients with PDA enrolled in two prospective clinical trials evaluating pre‐operative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ (NCT01128296). More recently, a randomized trial of gemcitabine/nab‐paclitaxel +/− HCQ evaluated Evans Grade histopathologic response (NCT01978184). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher’s exact test and log‐rank test were used to assess response and survival. Fifty‐two patients receiving HCQ with neoadjuvant chemotherapy were studied. Twenty‐five patients had SMAD4 loss (48%). 76% of HCQ‐treated patients with SMAD4 loss obtained a histopathologic response greater than or equal to 2A, compared with only 37% with SMAD4 intact (p = 0.006). Although loss of SMAD4 has been associated with worse outcomes, in the current study, loss of SMAD4 was not associated with a detriment in median overall survival in HCQ‐treated patients (34.43 months in SMAD4 loss vs. 27.27 months in SMAD4 intact, p = 0.18). The addition of HCQ to neoadjuvant chemotherapy in patients with PDA may improve treatment response in those with SMAD4 loss. Further study of the relationship among SMAD4, autophagy, and treatment outcomes in PDA is warranted.

BackgroundLeptospirosis is the most common anthropozoonosis worldwide and imposes a major public health problem in many tropical countries. It is a leading cause of disease burden in form of mortality, morbidity and hospital admission. Identifying patients at high risk for mortality or for prolonged hospitalization may save lives and preserve economy. The aim of the current study is to identify significant factors associated with disease mortality and prolonged hospitalization.DesignCress-sectional retrospective study.SettingsTertiary care teaching hospitals in Kelantan, Peninsular Malaysia.ParticipantsAdult patients proven to have leptospirosis depending on IgM ELISA were classified into two classes depending on prolonged hospitalization (>7 days or ≤ 7 days) and mortality (fatal cases or non-fatal cases). Patients' clinico-laboratory data were compared according to these two outcomes using the appropriate statistical test.ResultsOf the 525 patients enrolled, 136 (25.9%) had prolonged hospitalization. The mean length of stay was 6.77 ± 5.68 days. Logistic regression analysis identified acute kidney injury (AKI) (OR 2.3), Jaundice (OR 2.7), elevated alanine aminotransferase (ALT) (OR 2), and prolonged prothrombin time (PT) (OR 1.9) independently associated with prolonged hospitalization. Case fatality rate was 6.48% and around one third of fatal cases had prolonged hospitalization of more than seven days. Factors associated with leptospirosis mortality included age >40 years (p < 0.001), patients presented with tachypnea (p = 0.002), pulmonary infiltrate (p < 0.001), T-wave changes (p < 0.001), atrial fibrillation (p = 0.013), conducting abnormality (p < 0.001), chronic kidney diseases (p < 0.001), multiple organ dysfunctions (p < 0.0010), respiratory failure (p < 0.001), pneumonia (p < 0.001), sepsis (p = 0.004), low venous PH (p = 0.042), AKI (P < 0.001), elevated AST (p < 0.001) or ALT (p = 0.004), hypoalbuminemia (p < 0.001), rhabdomyolysis (p < 0.001), severe thrombocytopenia (p = 0.042), prolonged PT (p < 0.001) or prolonged aPTT (p < 0.017).ConclusionsSignificant proportion of leptospirosis patients (25.9%) had prolonged hospital stay and less proportion died (6.48%). Early identifying patients with factors associated with prolonged hospitalization and death will positively impact practitioners' decisions regarding the proper and fast course of management including ICU admission.

Lichens have widely been used as bioindicators to reflect the quality of the environment. The present study was conducted to investigate the lichens diversity that grows on the surface of waste heaps from an abandoned old copper mine in Mlynky, Slovakia. In spite of the heavy metal-contaminated environment, we documented twenty species of lichens in the selected site. Taxonomically the most numerous group were represented by Cladonia with seven species, as well other species; namely, Acarospora fuscata, Cetraria islandica, Dermatocarpon miniatum, Hypogymnia physodes, Hypogymnia tubulosa, Lecanora subaurea, Lepraria incana, Physcia aipolia, Porpidia macrocarpa, Pseudevernia furfuracea, Rhizocarpon geographicum and Xanthoria parietina. The content of selected heavy metals (Cu, Fe, and Zn) in the predominant lichens Cetraria islandica, Cladonia digitata, Cladonia pyxidata, Hypogymnia physodes and Pseudevernia furfuracea were analyzed. The highest content of Cu, Fe, and Zn was found in Cladonia pyxidata collected from mine-spoil heaps with concentration 46 ± 4.4, 82.5 ± 22.6, 4.8 ± 1.6 mg/kg, respectively. Interestingly, Cladonia pyxidata collected from the forest surrounding the location showed 15 times lower concentration for Cu. Additionally, similar results were found for Fe and Zn.

A new series of substituted ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e were prepared by utilizing ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (1) and replacing of the 2-chlorine with anions obtained from phenol (2a), salicylaldehyde derivatives 2b–d or thiophenol (2e), leading to the respective ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e. The new compounds were evaluated for their in vitro cytotoxicity towards sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. The screening revealed that compounds 3a, 3b, and 3e inhibited the growth of both cell lines. Compound 3b, with a phenol moiety, exhibited the highest growth inhibitory activity against CEM/ADR5000 and CCRF-CEM cells with IC50 values 4.486 ± 0.286 and 2.580 ± 0.550 µM, respectively. Collectively, the presented results demonstrate that the synthesized thieno[2,3-b]pyridines warrant further exploration for potential use as anti-cancer agents.

Abstract Cardiolipin (CL) is a lipid that is found in the membranes of bacteria and the inner membranes of mitochondria. CL can increase the activity of integral membrane proteins, in particular components of respiratory pathways. We here report that CL activated detergent-solubilized cytochrome bd, a terminal oxidase from Escherichia coli. CL enhanced the oxygen consumption activity ~ twofold and decreased the apparent K M value for ubiquinol-1 as substrate from 95 µM to 35 µM. Activation by CL was also observed for cytochrome bd from two Gram-positive species, Geobacillus thermodenitrificans and Corynebacterium glutamicum, and for cytochrome bo 3 from E. coli. Taken together, CL can enhance the activity of detergent-solubilized cytochrome bd and cytochrome bo 3.

Abstract Background Growing evidence for the advantages of robotic pancreatoduodenectomy (RPD) has been demonstrated internationally. However, there has been no structured training program for RPD in Japan. Herein, we present the surgical training model of RPD and a standardized protocol for surgical technique. Methods The surgical training model and surgical technique were standardized in order to implement RPD safely, based on the Dutch training system collaborated with the University of Pittsburgh Medical Center. Results The surgical training model included various trainings such as basic robotic training, simulation training, biotissue training, and a surgical video review. Furthermore, a standardized protocol on the surgical technique was established to understand the tips, tricks, and pitfalls of RPD. Conclusions Safe implementation of RPD can be achieved through the completion of a structured training program and learning surgical technique. A nationwide structured training system should be developed to implement the program safely in Japan.

Introduction: The implementation of antibiotic stewardship programs (ASPs) can improve the treatment of infections and can decrease the adverse events that result from antibiotics use. In the last decades, there is an increasing interest of the researchers in the implementation of ASPs. Materials and Methods: The articles published in different journals were retrieved by searching many research databases such as Cochrane library, Europe PMC, PubMed, and Web of Science; we searched these databases for all published articles till November 2018. Results and Discussion: The searching results using Cochrane library showed an increase in the number of randomized clinical trials that related to the keyword of “antimicrobial stewardship” specially in the last 5 years.Using Europe PMC, we found 6178 results. From these results, there are 3874 free full texts. In addition, there are 2132 original articles in PubMed and by searching Web of Science database till November 8 there are 3085 results.These results show that the number of trusted published articles was increased continuously; this shows the increasing interest of the researchers in ASPs. These researches will help health-care providers to use antibiotics appropriately and to overcome the barriers of implementing ASPs. Conclusion: The results of this study show that the researchers had high levels of interest in participating in research activities related to the appropriate use on antibiotics and the implementation of antimicrobial stewardship programs.

The cannabinoid receptor 2 (CB2 receptor) has attracted considerable interest, mainly due to its potential as a target for therapeutics for treating various diseases that have a neuroinflammatory or neurodegenerative component while avoiding the adverse psychotropic effects that accompany CB1 receptor-based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this research, we are interested in the discovery of new chemotypes as highly selective CB2 modulators, which may serve as good starting points for further optimization towards the development of CB2 therapeutics. In search of new chemotypes as CB2 selective agents, we screened a series of triazole derivatives with interesting bioactive scaffolds, which led to the discovery of two novel and highly selective ligands for CB2 receptors. Compounds 6 and 11 produced a concentration-dependent inhibition of specific [3H]-CP55,940 (CB2) binding with Ki ± SEM values of 105.3 ± 22.6 and 116.4 ± 19.5 nM, respectively, while no binding affinity towards CB1 receptors or opioid receptors was observed. The CB2 functional activity of 6 and 11, as measured by a GPCR Tango assay (G-protein independent β-arrestin translocation assay), revealed that these compounds act as CB2 agonists with EC50 values ± SEM of 1.83 ± 0.16 and 1.14 ± 0.52 µM, respectively. Molecular modeling results showed that both compounds fit well into the active site of the CB2 receptor and showed strong hydrophobic interactions with key residues. In conclusion, the new triazole derivatives (6 and 11) showed promising activity towards CB2 receptors and have great potential to be developed into therapeutically useful CB2 agonists through hit-to-lead optimization.

Objective: Prescribers usually authorize 80% of clinical pharmacy interventions (CPI). Current study aimed to determine if full authorization of CPI (i.e. 100% acceptance) would rather reduce the length of intensive care stay and readmissions. Data source/study setting: This is usual care CPI data obtained in a 100-bed, tertiary, acute care private hospital with 12-bed intensive care unit. Study design: Observational artificial neural network model of CPI data. Data collection/extraction methods: Clinical pharmacists documented CPI data using a special Excel sheet on a daily basis. Data analyst consolidated CPI to one accepted (124 of 167) and/or one rejected (43 of 167) per patient per admission to intensive care unit (ICU). Then analyst compared the two groups at two alpha levels (0.10 and 0.05) of significance. Artificial neural networks (ANN) were trained and validated for length of intensive care stay after the index CPI (LOSICUA, primary outcome) as well as for the secondary outcomes of mortality, readmissions and costs. Finally, we used the best ANN to compare the outcomes with 80% vs. 100% approval of CPI. Principal findings: Models had significant reduction in LOSICUA with 100% versus 80% authorization. At alpha of 0.05 (8 variables model), we observed ∼0.8 days reduction in LOSICUA (1.4 days (0.3–22.9) to 0.6 days (0.0–39.0), respectively, P-value = 0.001). Readmissions were less likely with 100% (16 of 167) versus 80% (22 of 167) approval (P-value = 0.041). Costs saved with 100% approval in this model would be almost 100 US dollars and would help hire 1.6 full time equivalents of competent doctor of pharmacy. Conclusions: Maximizing acceptance of CPI in this model reduced LOSICUA, readmissions, and costs. Pharmacists qualify for independent prescribing with further privileging and definitions of scopes of practice.

Medicinal plants provide a wide range of active compounds that can be exploited to create novel medicines with minimal side effects. The current study aimed to identify the anticancer properties of Juniperus procera (J. procera) leaves. Here, we demonstrate that J. procera leaves’ methanolic extract suppresses cancer cells in colon (HCT116), liver (HepG2), breast (MCF-7), and erythroid (JK-1) cell lines. By applying GC/MS, we were able to determine the components of the J. procera extract that might contribute to cytotoxicity. Molecular docking modules were created that used active components against cyclin-dependent kinase 5 (Cdk5) in colon cancer, aromatase cytochrome P450 in the breast cancer receptor protein, the -N terminal domain in the erythroid cancer receptor of the erythroid spectrin, and topoisomerase in liver cancer. The results demonstrate that, out of the 12 bioactive compounds generated by GC/MS analysis, the active ingredient 2-imino-6-nitro-2H-1-benzopyran-3-carbothiamide proved to be the best-docked chemical with the chosen proteins impacted by DNA conformational changes, cell membrane integrity, and proliferation in molecular docking studies. Notably, we uncovered the capacity of J. procera to induce apoptosis and inhibit cell growth in the HCT116 cell line. Collectively, our data propose that J. procera leaves’ methanolic extract has an anticancer role with the potential to guide future mechanistic studies.

Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of −10.4, −10.1, and −9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.

Healthcare-associated infections are widely considered one of the most common unfavorable outcomes of healthcare delivery. Ventilator-associated pneumonia, central line-associated bloodstream infections, and catheter-associated urinary tract infections are examples of healthcare-associated infections. The current study was a retrospective study conducted at a public hospital in Unaizah, Saudi Arabia, to investigate the frequency of healthcare-associated illnesses and adherence to healthcare-associated infection prevention techniques in the year 2021. Surgical site infections occurred at a rate of 0.1%. The average number of catheter-associated urinary tract infections per 1000 catheter days was 0.76. The average number of central line-associated bloodstream infections per 1000 central line days was 2.6. The rate of ventilator-associated pneumonia was 1.1 per 1000 ventilator days on average. The average number of infections caused by multidrug-resistant organisms per 1000 patient days was 2.8. Compliance rates were 94%, 100%, 99%, and 76% for ventilator-associated pneumonia, central line-associated bloodstream infections, catheter-associated urinary tract infections, and hand hygiene bundles, respectively. It is critical to participate in more educational events and workshops, particularly those that emphasize hand cleanliness and personal safety equipment.

In this work, we design and then synthesis of new derivatives of nucleosides, oxadiazoline derivatives containing acetylated sugars and α-aminophosphonate derivatives. The synthesized compounds have been elucidated by different spectroscopic analysis, such as, elemental analysis, 13C NMR, infrared (IR) and 1H NMR. The compounds previously synthesized were purified and then tested against breast cancer cells (MCF-7). The results showed that the compounds 5d, 6b, 7a and 9h showed moderate to very high activity against breast cancer, with incidence rates of 78.45%, 84.60%, 93.45% and 95.78%, respectively. The reference ratio of 5-fluorouracil was inhibitory of 96.02%. The binding potential of synthesized compounds against thymidylate synthase (TS) and Cathepsin B (CB) has been investigated and the compounds 7a and 9h exhibits highly binding with thymidylate synthase (TS) and Cathepsin B (CB).

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Surgical site infections are among the most prevalent and costly healthcare-associated infections, resulting in poor patient outcomes and even death. Cefazolin is a first-generation cephalosporin antibiotic that is widely used for surgical prophylaxis in a variety of surgical disciplines. Although previous studies showed that cefazolin is effective in preventing surgical site infections, other agents, such as cefuroxime and ceftriaxone, were used excessively for surgical patients. The present analysis included only clinical trials comparing the efficacy of cefazolin to cefuroxime, ceftriaxone, and cefamandole in lowering SSIs using PubMed, Google Scholar, and ClinicalTrials.gov. Review Manager software (RevMan version 5.4) was used to conduct the meta-analyses. A total of 12,446 patients were included in the study. Among these patients, 6327 patients received cefazolin and 6119 patients received cefamandole, cefuroxime, or ceftriaxone. Our analysis showed that cefazolin is as effective as cefuroxime, cefamandole, and ceftriaxone in preventing surgical site infections. Hence, our findings have provided evidence for the use of cefazolin before surgeries because of its efficacy, as previous studies showed that it is inexpensive and safer than other agents.

Background:. Interviews for the integrated plastic surgery residency match took place in a virtual format for the 2020–2021 application cycle. Current literature lacks the perspectives of program directors (PDs) on virtual interviews compared with traditional in-person interviews. Methods:. Following institutional review board approval, an anonymous 17-question survey was distributed by email to 82 program directors of integrated plastic surgery residency programs in the United States. Participants were asked baseline program information, the number of positions and interview invites offered, and their perspectives on various aspects of the virtual interview process. Results:. Sixty-two (75.6%) PDs completed the survey. Thirty-seven percent reported increasing the number of interview offers per available residency spot. On a five-point Likert scale (1, not well at all; 5, extremely well), PDs showed no significant differences in their ability judge an applicant’s professionalism (3.1 ± 1.1), interpersonal and communication skills (3.2 ± 1.1), and “fit” with their program (2.9 ± 0.9) during virtual interviews (P = 0.360). Sixty-eight percent reported being satisfied (15.3% extremely satisfied, 52.5% somewhat satisfied) with the virtual interview process, though 76.3% preferred in-person interviews. Conclusions:. This study is the first to provide insight into PDs’ impressions of virtual residency interviews. Although most reported being satisfied with the virtual interview process, the majority still preferred in-person interviews. Further long-term studies evaluating the pros and cons of each interview modality may provide more information on whether virtual interviews could become a sustainable alternative to the traditional in-person residency interview.

Leptospirosis is the most widely spread zoonosis and Leptospirosis Associated Acute Kidney Injury (LAKI) is common and fatal if not properly and swiftly treated. The aim of this review is to evaluate the mortality of LAKI and to identify the risk factors for its development. An electronic search was performed to identify the studies included LAKI patients series. Only studies which investigated mortality or risk factors for LAKI development in adults were included. Twenty-three studies with 24 patients series were included in the final analysis and included 1698 patients. The median series mortality was 10.05% (range 0–33.3%) with a total of 223 death. Only four studies identified the independent risk factors for LAKI development which were oliguria, jaundice, arrhythmia, crackles, elevated direct bilirubin level, elevated activated prothrombin time, hyperbilirubinemia and leukocytosis. Although the mortality of LAKI is high, its predictors are not studied enough in literature. Keywords: Leptospirosis associated acute kidney injury, Predictors, Mortality, Clinical characters, Adults, Systematic review

Ghada E Ali,1 Marwa A Ibrahim,1 Ayman H El-Deeb,2 Hassan Amer,1 Said M Zaki11Cairo University, Faculty of Veterinary Medicine, Department of Biochemistry and Chemistry of Nutrition, Giza 12211, Egypt; 2Cairo University, Faculty of Veterinary Medicine, Department of Virology, Giza 12211, EgyptBackground: Gold nanoparticles (AuNPs) have been considered as an ideal candidate in various biomedical applications due to their ease of tailoring into different size, shape, and decorations with different functionalities. The current study was conducted to investigate the epigenetic alteration in the lung in response to AuNPs administration regarding microRNA-155 (miR-155) gene which can be involved in AuNP-induced lung pathogenesis.Methods: Thirty-two Wister rats were divided into two equal groups, control group and AuNPs treated group which received a single intravenous (IV) injection of plain spherical AuNPs (0.015 mg/kg body wt) with an average diameter size of 25±3 nm. Lung samples were collected from both the control and injected groups at one day, one week, one month and two months post-injection. The alteration of relative expression of miR-155 gene and two of its putative target genes; tumor protein 53 inducible nuclear protein 1 (TP53INP1) and protein S (PROS1) was investigated by real time PCR and protein S (PS) expression was analyzed by Western blotting technique.Results: The obtained results revealed that AuNPs administration significantly increases the expression level of miR-155 and reduce relative mRNA expression of TP53INP1 and PROS1 genes at one day post-injection. In contrast, a significant down-regulation of miR-155 level of expression concurrent with up-regulation of expression level of TP53INP1 and PROS1 genes were shown at one week, one month and two months post-injection. PS levels were mirrored to their PROS1 mRNA levels except for two month post-injection time point.Conclusions: These findings indicate epigenetic modulation in the lung in response to AuNPs administration regarding the miR-155 gene which can be involved in AuNP-induced lung pathogenesis.Keywords: AuNPs, MiR-155, epigenetic, PROS1, TP53INP1

Effective screening provides efficient and quick diagnoses of COVID-19 and could alleviate related problems in the health care system. A prediction model that combines multiple features to assess contamination risks was established in the hope of supporting healthcare workers worldwide in triaging patients, particularly in situations with limited health care resources. Furthermore, a lack of diagnosis kits and asymptomatic cases can lead to missed or delayed diagnoses, exposing visitors, medical staff, and patients to 2019-nCoV contamination. Non-clinical techniques including data mining, expert systems, machine learning, and other artificial intelligence technologies have a crucial role to play in containment and diagnosis in the COVID-19 outbreak. This study developed Enhanced Gravitational Search Optimization with a Hybrid Deep Learning Model (EGSO-HDLM) for COVID-19 diagnoses using epidemiology data. The major aim of designing the EGSO-HDLM model was the identification and classification of COVID-19 using epidemiology data. In order to examine the epidemiology data, the EGSO-HDLM model employed a hybrid convolutional neural network with a gated recurrent unit based fusion (HCNN-GRUF) model. In addition, the hyperparameter optimization of the HCNN-GRUF model was improved by the use of the EGSO algorithm, which was derived by including the concepts of cat map and the traditional GSO algorithm. The design of the EGSO algorithm helps in reducing the ergodic problem, avoiding premature convergence, and enhancing algorithm efficiency. To demonstrate the better performance of the EGSO-HDLM model, experimental validation on a benchmark dataset was performed. The simulation results ensured the enhanced performance of the EGSO-HDLM model over recent approaches.

Fish represent an excellent source of animal protein as well as a biomedical research model as a result of their evolutionary relatedness and similarity with the human genome. Commercial and ornamental fish culture has achieved popularity, but reproductive dysfunctions act as a limiting factor for quality fry production, interfering with the sustainability of the aquaculture industry. Fish reproduction is crucial for any species’ existence, and reproductive performance can potentially be improved through applications of epigenetics and probiotics. Epigenetics is a highly sensitive molecular approach that includes chromatin structure and function alteration, DNA methylation, and modification of non-coding RNA molecules for the transfer of desired information from parents to offspring. DNA methyltransferase improves reproductive cyp11a1, esr2b, and figla gene expression and feminizes zebrafish (Danio rerio). Moreover, epigenetics also contributes to genome stability, environmental plasticity, and embryonic development. However, methylation of specific genes can negatively affect sperm quality, resulting in poor fertilization. Probiotic administration is able to induce responsiveness of incompetent follicles to maturation-inducing hormones and can change oocyte chemical composition during vitellogenic development. The positive role of probiotics on testicular cells is validated by upregulating the transcription levels of leptin, bdnf, and dmrt1 genes facilitating the spermatogenesis. This review not only discusses the effects and mechanism of epigenetics and probiotics for improving fish reproduction, but also presents an overview of the causal factors and current techniques used to eradicate dysfunction. Moreover, key genes and hormones related to fish reproduction along with research gaps and future prospects are also considered. This review provides an overview of necessary information for students, scientists, researchers, and breeders to resolve fish reproduction-related problems to ensure profitable and sustainable aquaculture.

Candida albicans is the most dominant and prevalent cause of fungal infections in humans. Azoles are considered as first-line drugs for the treatment of these infections. However, their prolonged and insistent use has led to multidrug resistance and treatment failures. To overcome this, modification or derivatization of the azole ring has led to the development of new and effective antifungal molecules. In a previous study, we reported on the development of new triazole-based molecules as potential antifungal agents against Candida auris. In this study, the most potent molecules from the previous study were docked and simulated with lanosterol 14-alpha demethylase enzyme. These compounds were further evaluated for in vitro susceptibility testing against C. albicans. In silico results revealed favorable structural dynamics of the compounds, implying that the compounds would be able to effectively bind to the target enzyme, which was further manifested by the strong interaction of the test compounds with the amino acid residues of the target enzyme. In vitro studies targeting quantification of ergosterol content revealed that pta1 was the most active compound and inhibited ergosterol production by >90% in both drug-susceptible and resistant C. albicans isolates. Furthermore, RT-qPCR results revealed downregulation of ERG11 gene when C. albicans cells were treated with the test compound, which aligns with the decreased ergosterol content. In addition, the active triazole derivatives were also found to be potent inhibitors of biofilm formation. Both in silico and in vitro results indicate that these triazole derivatives have the potential to be taken to the next level of antifungal drug development.

The conventional drug discovery approach is an expensive and time-consuming process, but its limitations have been overcome with the help of mathematical modeling and computational drug design approaches. Previously, finding a small molecular candidate as a drug against a disease was very costly and required a long time to screen a compound against a specific target. The development of novel targets and small molecular candidates against different diseases including emerging and reemerging diseases remains a major concern and necessitates the development of novel therapeutic targets as well as drug candidates as early as possible. In this regard, computational and mathematical modeling approaches for drug development are advantageous due to their fastest predictive ability and cost-effectiveness features. Computer-aided drug design (CADD) techniques utilize different computer programs as well as mathematics formulas to comprehend the interaction of a target and drugs. Traditional methods to determine small-molecule candidates as a drug have several limitations, but CADD utilizes novel methods that require little time and accurately predict a compound against a specific disease with minimal cost. Therefore, this review aims to provide a brief insight into the mathematical modeling and computational approaches for identifying a novel target and small molecular candidates for curing a specific disease. The comprehensive review mainly focuses on biological target prediction, structure-based and ligand-based drug design methods, molecular docking, virtual screening, pharmacophore modeling, quantitative structure–activity relationship (QSAR) models, molecular dynamics simulation, and MM-GBSA/MM-PBSA approaches along with valuable database resources and tools for identifying novel targets and therapeutics against a disease. This review will help researchers in a way that may open the road for the development of effective drugs and preventative measures against a disease in the future as early as possible.

Lemongrass (Cymbopogon citratus) plant belongs to the Gramineae family. Lemongrass leaves essential oils were extracted by Clevenger method, antibacterial, MIC and MBC were evaluated against some gram positive and gram negative bacteria. Bacillus cereus, Staphylococcus aureus, and micrococcus spp., recorded high sensitivity to essential oil with inhibition zone reached (40, 32, and 28) mm respectively. While Pseudomonas spp., Salmonella typhimurium, and Escherichia coli recorded (20, 20, and 22) mm respectively. MIC and MBC values reached (3, 6.5) % respectively for gram-positive bacteria and (25,50) % respectively for gram-negative bacteria. C.citratus leaves essential oil showed superior efficiency in reduction count of total microorganisms, coliform bacteria, psychrotrophic bacteria, Staphylococcus aureus, and molds and yeasts, as well as the elongated shelf life for 15 days of fish balls treated with (5,10) µl\gram of essential oil under refrigerated storage compared with control treatment ( no oil added) which excluded for test after 6 days of refrigerated storage because microbial load and bad quality. Fish balls samples Lg10 (treated with 10µl\g of essential oil) gained best sensorial properties of color, texture, flavor, taste and overall acceptability were recorded 9/9 at the end of storage compared with treatment Lg5 (5µl\g essential oil added) which gained acceptable sensorial score through refrigerated storage periods.

Fungi are renowned as a fountainhead of bio-metabolites that could be employed for producing novel therapeutic agents, as well as enzymes with wide biotechnological and industrial applications. Stachybotrys chartarum (black mold) (Stachybotriaceae) is a toxigenic fungus that is commonly found in damp environments. This fungus has the capacity to produce various classes of bio-metabolites with unrivaled structural features, including cyclosporins, cochlioquinones, atranones, trichothecenes, dolabellanes, phenylspirodrimanes, xanthones, and isoindoline and chromene derivatives. Moreover, it is a source of various enzymes that could have variable biotechnological and industrial relevance. The current review highlights the formerly published data on S. chartarum, including its metabolites and their bioactivities, as well as industrial and biotechnological relevance dated from 1973 to the beginning of 2022. In this work, 215 metabolites have been listed and 138 references have been cited.

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between −6.5 and −7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.

Perioperative antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs); however, non-adherence to surgical antimicrobial prophylaxis protocols can lead to several negative outcomes. We performed a before-and-after intervention study with the aim of improving the process outcome, including adherence to guidelines. Another objective of this study was to investigate improvement in patient outcomes as a result of adherence to a surgical antimicrobial prophylaxis programme. The indicators of improved patient outcomes were a reduction in overall SSI rate and the decreased cost of antibiotics. SSI rate was calculated as a percentage by dividing the number of SSIs by the total number of surgeries and then multiplying the value obtained by 100%. The interventions implemented in the surgical antimicrobial prophylaxis programme included establishment of a guideline, educational sessions, and a monthly revision of prescriptions. Our findings show that implementation of the interventions resulted in reduced antibiotic consumption, a considerable decrease in the cost of prophylaxis, and a decrease in the incidence of SSIs.

Candida auris, an evolving multidrug-resistant pathogenic yeast, is known for causing severe invasive infections associated with high mortality rates in hospitalized individuals. Distinct from other Candida species, C. auris can persist for longer periods on different surfaces and is resistant to all of the major classes of antifungal drugs. Therefore, there is an urgent need for new antimycotic drugs with improved efficacy and reduced toxicity. The development of new antifungals based on antimicrobial peptides from various sources is considered a promising alternative. In this study, we examined the in vitro anti-yeast activity of the human cathelicidin peptides LL-37 against clinical strains of C. auris alone and in combination with different antifungal drugs by broth microdilution assay. To understand the antifungal mechanism of action, cell envelopes, cell cycle arrest, and effect on oxidative stress enzymes were studied using standard protocols. The minimum inhibitory and fungicidal concentrations of cathelicidin LL-37 ranged from 25–100 and 50–200 µg/mL, respectively. A combination interaction in a 1:1 ratio (cathelicidin LL-37: antifungal drug) resulted in 70% synergy with fluconazole and 100% synergy with amphotericin B and caspofungin. Assessment of the C. auris membrane by using propidium iodide assay after exposure to cathelicidin LL-37 linked membrane permeabilization with inhibition of C. auris cell growth and viability. These results were backed up by scanning electron microscopy studies demonstrating that exposure with cathelicidin LL-37 caused C. auris cells to undergo extensive surface changes. Spectrophotometric analysis revealed that cathelicidin LL-37 caused oxidative stress in C. auris, as is evident from the significant increase in the activity of primary antioxidant enzymes. In addition, cathelicidin LL-37 inhibited the cell cycle and accumulated cells in the S phase. Therefore, these results specify the potential of cathelicidin LL-37 for developing a new and effective anti-Candida agent.

Abstract Mycobacterial energy metabolism currently attracts strong attention as new target space for development of anti-tuberculosis drugs. The imidazopyridine Q203 targets the cytochrome bcc complex of the respiratory chain, a key component in energy metabolism. Q203 blocks growth of Mycobacterium tuberculosis at nanomolar concentrations, however, it fails to actually kill the bacteria, which may limit the clinical applicability of this candidate drug. In this report we show that inhibition of cytochrome bd, a parallel branch of the mycobacterial respiratory chain, by aurachin D invoked bactericidal activity of Q203. In biochemical assays using inverted membrane vesicles from Mycobacterium tuberculosis and Mycobacterium smegmatis we found that inhibition of respiratory chain activity by Q203 was incomplete, but could be enhanced by inactivation of cytochrome bd, either by genetic knock-out or by inhibition with aurachin D. These results indicate that simultaneously targeting the cytochrome bcc and the cytochrome bd branch of the mycobacterial respiratory chain may turn out as effective strategy for combating M. tuberculosis.

The gut microbiota consists of a community of microorganisms that inhabit the large intestine. These microbes play important roles in maintaining gut barrier integrity, inflammation, lipid and carbohydrate metabolism, immunity, and protection against pathogens. However, recent studies have shown that dysfunction in the gut microbiota composition can lead to the development of several diseases. Urolithin A has recently been approved as a functional food ingredient. In this study, we examined the potentials of urolithin A (Uro-A) and B (Uro-B) in improving metabolic functions and their impact on gut microbiota composition under a metabolically unchallenged state in normal rats. Male Wistar rats (n = 18) were randomly segregated into three groups, with Group 1 serving as the control group. Groups 2 and 3 were administered with 2.5 mg/kg Uro-A and Uro-B, respectively, for four weeks. Our results showed that both Uro-A and B improved liver and kidney functions without affecting body weight. Metagenomic analysis revealed that both Uro-A and B induced the growth of Akkermansia. However, Uro-A decreased species diversity and microbial richness and negatively impacted the composition of pathogenic microbes in normal rats. Taken together, this study showed the differential impacts of Uro-A and B on the gut microbiota composition in normal rats and would thus serve as a guide in the choice of these metabolites as a functional food ingredient or prebiotic.