Consumption of aphrodisiac drugs without prescription among men in Saudi Arabia: cross-sectional study.

Background: The prevalence and patterns of aphrodisiac drug consumption without prescription among men in Saudi Arabia remain underexplored, with limited empirical evidence available. Given the potential health implications and societal considerations, a comprehensive investigation is warranted. Aim: Assess the Prevalence, pattern of use and the associated factors of Aphrodisiac drugs consumption without prescription among men at Najran City, Saudi Arabia. Methods: Employing a cross-sectional descriptive study, 500 participants were included through convenience sampling. The utilized questionnaires covered a range of data, including socio-demographic information, patterns of aphrodisiac use, knowledge about aphrodisiacs, lifestyle details, a sexual health inventory for men, and a perceived stress level scale. Results: The study reveals a significant prevalence of unsanctioned aphrodisiac drug use (31%) among men in Najran City, Saudi Arabia, with a majority (79.3%) consuming these substances four times monthly. Associated disparities in knowledge, lifestyle, stress, and sexual function underscore the urgent need for policy interventions and tailored health education initiatives for this demographic. Conclusion: Approximately one-third of the sampled population engaged in the unsanctioned use of aphrodisiac drugs, with the majority utilizing them four times monthly. Tablets emerged as the most prevalent form of consumption. Commonly cited motives and justifications included peer influence and the perceived safety of aphrodisiacs. Influential factors encompassed levels of knowledge, lifestyle, stress levels, erectile function, age, education, and the number of wives. Recommendations: Urgent policy interventions are warranted to regulate the acquisition and distribution of aphrodisiacs. Tailored health education initiatives should be implemented for married and prospective married men.

Altering Escherichia coli envelope integrity by mimicking the lipoprotein RcsF.

Escherichia coli cell envelope is crucial for stress sensing and signal transduction, mediated by numerous protein-protein interactions to enable adaptation and survival. Interfering with these interactions might affect envelope integrity leading to bacterial death. The outer membrane lipoprotein (RcsF) is the stress sensor of the regulator of capsule synthesis (Rcs) phosphorelay that senses envelope threats. RcsF interacts with two essential proteins, IgaA (repressing the Rcs system) and BamA (inserting ß-barrel proteins in the outer membrane). Disturbing RcsF interactions may alter Rcs signaling and/or membrane integrity thus affecting bacterial survival. Here, we derived the sequence of a peptide mimicking RcsF (RcsFmim), based on the in silico docking of RcsF with IgaA. Expression of rcsFmim caused 3-to-4-fold activation of the Rcs system and perturbation of the outer membrane. Both effects result in decreased E. coli growth rate. We anticipate that RcsFmim present a candidate for future antibacterial peptide development.

Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2.

Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of -11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.

Female Pattern Hair Loss and Negative Psychological Impact: Possible Role of Brain-derived Neurotrophic Factor (BDNF).

INTRODUCTION: Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in females. Women with FPHL may suffer from psychological distress and defective social functioning. Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic marker for negative psychological impact in FPHL patients. OBJECTIVES: Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the severity of alopecia and the degree of psychological impact. METHODS: Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire. Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using the ELISA technique. RESULTS: Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck depression inventory score and PSS questionnaire scores. There is a significant negative correlation between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS questionnaire scores. CONCLUSIONS: Patients with FPHL are at a high risk to develop chronic stress and depression. The serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL patients.

Kinetic of liver enzymes and serum electrolytes in HCV, HBV, and HIV negative chronic phase chronic myeloid leukemia patients treated with imatinib or nilotinib.

The outcome for chronic phase (CP) chronic myeloid leukemia (CML) patients was changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. This study intended to evaluate side effects of TK Imatinib or Nilotinib on liver enzymes and serum electrolytes in relation to hematologic and molecular response in HCV-, HBV-, and HIV-, CP-CML patients. The study was a quasi-experimental pre-post single group design, included 38 HCV-, HBV-, and HIV-newly diagnosed Philadelphia positive CP-CML patients with normal hepatic and renal function. They were divided equally into two groups, 19 received Nilotinib, and 19 received Imatinib. Hematologic, BCR-ABL gene expression by RT-PCR, electrolytes and liver enzymes were measured at baseline and after 6 months of treatment. Patients age ranged between 20 and 62 years. Anemic manifestations represented the highest rate (n=23, 60.5%). The mean WBCs count was significantly reduced after treatment (p < 0.001). The WBCs count was significantly reduced in the Nilotinib group than the Imatinib group (97% and 94%, respectively, p=0.049). The mean hemoglobin level was significantly increased after treatment (p=0.010). The mean platelet level did not change over the treatment period. The mean AST, ALT, and ALP levels were significantly increased after treatment, (p=0.014, p=0.002, and p=0.047, respectively). The ALP level was significantly increased in both groups (p=0.001). The mean sodium potassium, phosphorous, and calcium level was not changed over the treatment period. The mean BCR-ABL gene expression was sharply decreased after treatment (p < 0.001). A higher reduction was observed in the Nilotinib group (99%) than the Imatinib group (91.5%) (p=0.025). Imatinib resulted in rise of AST and ALP levels than Nilotinib, while both had the same effect on the ALT level. Higher reduction in BCR-ABL gene expression was achieved by Nilotinib. Nilotinib and Imatinib did not affect serum levels of sodium, potassium, phosphorous, or calcium.

Rosiglitazone Mitigates Dexamethasone-Induced Depression in Mice via Modulating Brain Glucose Metabolism and AMPK/mTOR Signaling Pathway.

Major depressive disorder (MDD) is a common, complex disease with poorly understood pathogenesis. Disruption of glucose metabolism is implicated in the pathogenesis of depression. AMP-activated protein kinase (AMPK) has been shown to regulate the activity of several kinases, including pAKT, p38MAPK, and mTOR, which are important signaling pathways in the treatment of depression. This study tested the hypothesis that rosiglitazone (RGZ) has an antidepressant impact on dexamethasone (DEXA)-induced depression by analyzing the function of the pAKT/p38MAPK/mTOR pathway and NGF through regulation of AMPK. MDD-like pathology was induced by subcutaneous administration of DEXA (20 mg/kg) for 21 days in all groups except in the normal control group, which received saline. To investigate the possible mechanism of RGZ, the protein expression of pAMPK, pAKT, p38MAPK, and 4EBP1 as well as the levels of hexokinase, pyruvate kinase, and NGF were assessed in prefrontal cortex and hippocampal samples. The activities of pAMPK and NGF increased after treatment with RGZ. The administration of RGZ also decreased the activity of mTOR as well as downregulating the downstream signaling pathways pAKT, p38MAPK, and 4EBP1. Here, we show that RGZ exerts a potent inhibitory effect on the pAKT/p38MAPK/mTOR/4EBP1 pathway and causes activation of NGF in brain cells. This study has provided sufficient evidence of the potential for RGZ to ameliorate DEXA-induced depression. A new insight has been introduced into the critical role of NGF activation in brain cells in depression. These results suggest that RGZ is a promising antidepressant for the treatment of MDD.

MmCMS: mouse models' consensus molecular subtypes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. METHODS: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. RESULTS: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. CONCLUSIONS: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.

Microbotox (Mesobotox) versus microneedling as a new therapeutic modality in the treatment of atrophic post-acne scars.

BACKGROUND: Given that most patients with moderate to severe acne develop post-acne scars, many treatment modalities can be used to ameliorate scaring; chemical peels, surgical excision, dermabrasion, fat transfer, autologous collagen, punch grafting, diverse filler injection, and lasers. Microneedling is one of the promising modalities based on the breaking of dermis-damaged collagen and enhancing new collagen formation. Microbotox (Mesobotox) injection may have a beneficial effect by causing muscular paralysis with subsequent dermal edema due to transient and mild lymphatic insufficiency. The comparison between these two modalities has not been yet assessed. The aim of this study was to evaluate and compare the safety and efficacy of both methods (Microbotox and microneedling) in the treatment of atrophic post-acne scars. METHODS: Between May 2021 to April 2022, patients with atrophic post-acne scars were selected from the out-patients clinics of the Department of Dermatology, Faculty of Medicine. The face was divided into two sides: the right side was treated with Mesobotox for three sessions once monthly and followed up 3 months later after the last session and the left side was treated with dermapen (microneedling) for six sessions every 2 weeks and followed up 3 months after the last session. The feasibility, safety, and efficacy of both lines of treatment were studied. RESULTS: This study included 20 patients with atrophic post-acne scars. They were 13 females (65%) and 7 males (35%), and their ages ranged between 15 and 35 years with a mean ± sd age of 24.40 ± 5.90 based on the significant improvement between S1 (baseline acne scar score) and both S2 (acne scar score at end of treatment) and S3 (acne scar score 3 months after the last session). Microneedling showed also similar results to Mesobotox. CONCLUSIONS: Microbotox and microneedling were effective and tolerated.

The impact of agricultural water salvation investment on economics development: Evidence from Eastern China.

Agricultural water salvation is the lifeblood of the national economy and is of great significance to the high-quality development of the region. In order to maximize the economic assistances of agricultural water salvation investment, this article focuses on panel data from 2005 to 2019 in 14 provinces in Eastern China, this research constructs an economic development evaluation index system from five dimensions: innovative development, coordinated development, green development, open development and shared development, and uses dynamic panel model to explore the influence relationship and path of Eastern Agricultural water salvation investment on economic development. The results represent that: there is a significant non-linear effect between agricultural water salvation investment and economic growth, showing an inverted U-shaped relationship. Which means that with the expansion of agricultural water salvation investment; economic growth has risen first and then declined. At present, the impact of agricultural water salvation investment in the Eastern region on economic development is in the promotion stage of positive and sustained growth. The recommendation of this research will help the state control in the amount of agricultural water salvation investment in the Eastern region, improve the efficiency of agricultural water salvation investment, and provide support in decision making.

Design and synthesis of novel benzoazoninone derivatives as potential CBSIs and apoptotic inducers: In Vitro, in Vivo, molecular docking, molecular dynamics, and SAR studies.

Apparently, tubulin inhibitors binding to the colchicine-binding site (CBS) currently have outstanding attention for cancer treatment. So, a series of benzo[b]azonin-2-one derivatives having the same pharmacophoric features as colchicine binding site inhibitors (CBSIs) were synthesized targeting the CBS of ß-tubulin. The antiproliferative activities of the newly synthesized compounds were assessed against five different cancer cell lines; HepG-2, MCF-7, MDA-MB-231, HCT-116, and Caco-2. Compounds 7a and 7d displayed promising inhibitory activities against all tested cell lines. They were further estimated towards ß-tubulin at CBS along with colchicine (Col) as a reference drug. It was shown that the assessed candidates (7a and 7d) and Col exhibited CBSI activities of 5492, 3771, and 486c.p.m./mg protein, respectively, at a concentration of 10 µM. Furthermore, compound 7d was picked out to assess its effects on apoptosis and cell-cycle profile using Annexin V-FITC and PI staining assay. In addition, the apoptotic activity of 7d was investigated using gene expression analysis of apoptosis-related genes of P53, Bax, Caspases 3 and 9, and Bcl-2 in both treated and untreated cells. Moreover, compound 7d was further assessed through in vivo studies using solid Ehrlich carcinoma (SEC)-bearing mice. Furthermore, both molecular docking and molecular dynamics simulations (for 150 ns) were performed to investigate their mechanism of action as potential CBSIs and give more insights into the behavior of the examined candidates within the ß-tubulin subunit of the CBS. On the other hand, in silico ADMET studies were carried out to assess the pharmacokinetic features, drug/lead likeness, and toxicity parameters of the newly synthesized derivatives. Finally, to anticipate the possible changes in the antimitotic activities upon future structural modifications of the investigated compounds, a structure-activity relationship study (SAR) was accomplished.

CXCR2 inhibition enables NASH-HCC immunotherapy.

OBJECTIVE: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy. DESIGN: Neutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry. RESULTS: Neutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1+ dendritic cell activation and CD8+ T cell numbers which are associated with anti-tumoural immunity, this was confirmed by loss of therapeutic effect on genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8+ T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a protumour to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8+ T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs. CONCLUSION: CXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC.

Adjustment of family planning service statistics reports to support decision-making at central and governorate level, Egypt.

BACKGROUND: The Ministry of Health and Population (MOHP)-Family Planning Sector (FPS) has a strong management information system (MIS) that allows the flow of data from MOHP-FP clinics, health districts, and governorates up to the central level. Yet, family planning (FP) quarterly reports issued at the central level are presented as database/spreadsheet software documents. These data are not used to provide indicators or information that aid in decision-making or the tracking of FP services over time. The objective of the study is to organize data in the database, develop key performance indicators, and design FP reports and policy briefs. METHODS: The study is operations research that is driven by published data derived from MOHP-FP sector-head, and 2014 service statistics quarterly hardcopy reports. The information was entered into an excel program, and 15 key performance indicators (KPIs) were calculated and used to rank Egypt's 27 governorates. We developed an annual FP report form, settled tables, and colored graphs that are liable to rank the governorates from best to least favorable. RESULTS: The quarterly data sheets issued by the MOHP-FP sector were organized for the quarters, and one annual sheet was developed with the organization of Egypt's Governorates into 4 specific regions, with each governorate having a fixed position in all reports. The key performance indicators were as follows: percent of clients aged 35 and up; percent of clients with fewer than three children; proportion of current FP users by method; percent of clients reported as first-time clients; percent of clients defined as new clients (non-FP users and FP discontinuers); and contraceptive coverage rate, i.e., percent coverage of married women of reproductive age with dispensed FP methods expressed as couple years. CONCLUSION: MOHP-FP sector service statistics data could be used for the development of fifteen key performance indicators. Having those indicators at governorate, district, and central levels in quarterly and annual reports and their communication with decision-makers at all levels and their tracking overtime will guide them to timely decision-making for improving performance in FP services at all levels.

Bioinspired synthesis of protein/polysaccharide-decorated folate as a nanocarrier of curcumin to potentiate cancer therapy.

Curcumin is a promising anticancer agent, but its clinical utilization has been hindered by its low solubility and bioaccessibility. To overcome these obstacles, we developed a natural protein-polysaccharide nanocomplex made from casein nanoparticles coated with a double layer of alginate and chitosan and decorated with folic acid (fCs-Alg@CCasNPs) for use as a nanocarrier for curcumin. The developed nanoformulation showed a drug encapsulation efficiency = 75%. The measured size distribution of fCs-Alg@CCasNPs was 333.8 ± 62.35 nm with a polydispersity index (PDI) value of 0.179. The recorded zeta potential value of fCs-Alg@CCasNPs was 28.5 mV. Morphologically, fCs-Alg@CCasNPs appeared spherical, as shown by transmission electron microscopy (TEM). The successful preparation of fCs-Alg@CCasNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy of all the constituents forming the nanoformulation. Further in vitro investigations indicated the stability of fCs-Alg@CCasNPs as well as their controlled and sustained release of curcumin in the tumor microenvironment. Compared with free curcumin, fCs-Alg@CCasNPs induced a higher cytotoxic effect against a pancreatic cancer cell line. The in vivo pharmacokinetics of fCs-Alg@CCasNPs showed a significant AUC0-24 = 2307 ng.h/ml compared to 461 ng.h/ml of free curcumin; these results indicated high curcumin bioavailability in plasma. The in vivo results of tumor weight, the amount of DNA damage measured by comet assay and histopathological examination revealed that treating mice with fCs-Alg@CCasNPs (either intratumorally or intraperitonially) prompted higher therapeutic efficacy against Ehrlich carcinoma than treatment with free curcumin. Therefore, the incorporation of curcumin with protein/polysaccharide/folate is an innovative approach that can synergistically enhance curcumin bioavailability and potentiate cancer therapy with considerable biosafety.

Physalis pubescens L. alleviates testicular disruptions associated with streptozotocin-induced diabetes in male Wistar rats, Rattus norvegicus.

Testicular impairment is a serious complication of diabetes that is mediated by oxidative stress and inflammation. Physalis has antioxidative and anti-inflammatory actions. Thus, the present study investigated the ameliorative role of Physalis juice (PJ) prepared from the fruits against testicular damages in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were divided randomly into five groups (n=6): control, orally administered 5 mL PJ/kg daily (PJ), injected intraperitoneally with a single dose of 55 mg STZ/kg without treatment (STZ), or treated daily with PJ (STZ+PJ) or with 500 mg metformin/kg (STZ+Met), for 28 days. The STZ group showed a marked elevation in the blood glucose level by 230%, whereas remarkable declines in the serum levels of testosterone (44%), follicle-stimulating hormone (FSH) (48%), and luteinizing hormone (LH) (36%), as compared to controls. In comparison to controls, the testis of the STZ group showed remarkable declines in the testis weight (15%), the glutathione (GSH) content (45%), mRNA and protein levels of B-cell lymphoma-2 (Bcl-2) (48 and 35%), mRNA and activities of superoxide dismutase (SOD) (63 and 40%), catalase (CAT) (56 and 31%), glutathione peroxidase (GPx) (51 and 44%), and glutathione reductase (GR) (62 and 43%), whereas marked elevations in the levels of interleukin-1 beta (IL-1ß (169%), tumor necrosis factor-alfa (TNFα) (85%), nitric oxide (NO) (96%), malondialdehyde (MDA) (83%), mRNA and protein levels of Bcl-2-associated X protein (Bax) (400 and 61%), and mRNA level of caspase-3 (Cas-3) (370%). Some histopathological alterations were observed in the testicular tissue of the STZ group. In contrast, PJ markedly alleviated all the abovementioned disturbances. In conclusion, PJ at a dose of 5 mL/kg attenuated the diabetes-associated testicular impairments, which may be due to its antioxidative, anti-inflammatory, and antiapoptotic actions.

Incorporating silver nanoshell-coated mesoporous silica nanoparticles improves physicochemical and antimicrobial properties of chitosan films.

Tailoring nanomaterials with tunable properties is of great importance to develop multifunctional candidates in the biomedical field. In the present study, we aimed to develop a promising nano-hybrid system composed of chitosan (CS) and mesoporous silica nanoparticles with a silver nanoshell coat (CS-AgMSNs). The physicochemical properties of CS-AgMSNs films were characterized using various techniques. Further, the mechanical properties of CS-AgMSNs were evaluated and compared with those of undoped CS film. Moreover, the antimicrobial activities of CS-AgMSNs (with different concentrations) were assessed against E-coli, S. aureus, C. albicans, and A. niger. Our results demonstrated that increasing the concentrations of doped AgMSNs (10 to 40 mg) in CS films lowered their transparency and blocked light transmission effectively. The measured elastic modulus of CS-AgMSNs films (20 and 30 mg) showed a decrease in the stiffness of CS films. Also, the elongation at break for CS-AgMSNs (40 mg) indicated a better flexibility. CS-AgMSNs films (10-40 mg) showed an enhanced antimicrobial activity in a concentration-dependent manner compared to undoped CS films. Collectively, the results suggest that our nano-hybrid CS-AgMSNs matrix has unique and promising properties, and holds potential for use in the biomedical field, food packaging, and textile industry.

Does wearing personal protective equipment affect the performance and decision of physicians? A cross-sectional study during the COVID-19 pandemic.

BACKGROUND: The use of personal protective equipment (PPE) decreased the probability of viral transmission during the COVID-19 pandemic. However, some drawbacks have been observed with its extensive use, such as headaches, anxiety, and stress among physicians, which could affect decision-making processes, the performance of physicians, and consequently patients' safety. Few articles have studied the impact of PPE on physicians from different specialties. This study assessed the effect of wearing PPE on the performance and decision-making of physicians during the COVID-19 pandemic and compared the effects of wearing PPE on physicians from different specialties. METHODS: A descriptive cross-sectional study was carried out through an anonymous 39-item online questionnaire. The physicians were divided according to the probability and frequency of performing invasive procedures. Group 1 included emergency medicine and critical care physicians, intensivists, and anesthetists, group 2 included physicians from different surgical subspecialties, and group 3 included physicians from different medical fields. RESULTS: This study included 272 physicians; group 1 included 54, group 2 included 120, and group 3 included 98 physicians. Approximately, 90.4% of the participants aged between 30 and -40 years, and 72.8% of the participants were specialists. Results indicated that the comfort, vision, and communication were significantly reduced in all groups (81.1%, 88.7%, and 75.5%, respectively). In contrast, the handling of instruments was not significantly affected in the second group only. In addition, the decision-making and the rate of complications were not significantly affected. CONCLUSION: There was a negative impact of wearing PPE on the non-technical skills (vision, communication and overall comfort), and the technical skills of the physicians. The decision-making and patients' safety were not significantly affected. Recommendations include additional improvement of the PPE design due to its crucial effect on both non-technical and technical skills of physicians.

Cytotoxicity and genotoxicity of gold nanorods assisted photothermal therapy against Ehrlich carcinoma in-vivo.

AIM: Preparation of pegylated gold nanorods (PEG-AuNRs) that are capable of converting near infrared (NIR) light into heat. Evaluation of cancer therapeutic efficacy and long-term toxicity of the proposed photothermal therapy in comparison with other conventional modalities. MATERIALS AND METHODS: Prepared PEG-AuNRs were characterized by measuring their absorption spectra, zeta potential, and transmission electron microscope (TEM). Cancer therapeutic efficacy was assessed by monitoring tumor growth, measuring DNA damage and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in addition to examining tumor histopathology. Further analysis concerning the toxicity of all the proposed treatment modalities was also assessed by evaluating the cytotoxicity and genotoxicity in liver and kidney tissues. KEY FINDINGS: The results demonstrated that both photothermal therapy (PEG-AuNRs + NIR laser) and chemotherapy (cisplatin) have higher efficacy in diminishing Ehrlich tumor growth with significance DNA damage over the other treatment modalities. Concerning the biosafety issue, mice treated photothermally exhibited lower MDA level and higher SOD activity in liver and kidney tissues compared with other treated groups. DNA damage represented by tail moment and olive moment of kidney tissues exhibited lower values for photothermal treated group and higher values for cisplatin treated group. SIGNIFICANCE: Photothermal therapy (PEG-AuNRs + NIR laser) potentiates higher efficacy in treating Ehrlich tumor with minimum toxicity in comparison with other conventional treatment modalities.

Alginate-coated caseinate nanoparticles for doxorubicin delivery: Preparation, characterisation, and in vivo assessment.

Natural protein-based nanoparticles are promising nano-vehicles for the delivery of chemotherapeutic drugs. Caseinate nanoparticles loaded with doxorubicin (CasNPs-DOX) have been surface-modified with the natural polysaccharide alginate to generate the novel nanocarrier Alg-CasNPs-DOX. The fabricated nanoparticles have been characterised by transmission electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, fluorescence spectroscopy, and zeta potential measurement. Drug encapsulation and release profiles were also investigated. In vivo studies were conducted to evaluate the therapeutic efficacy of this novel drug delivery system in tumour-bearing mice. The biodistribution and toxicity of the nano-formulation were also assessed. The results showed that encapsulation of DOX in Alg-CasNPs-DOX not only led to controlled and sustained drug release but also significantly enhanced the effectiveness of DOX against Ehrlich carcinoma. Moreover, no significant changes were observed in liver and kidney enzymes, indicating the selective delivery of DOX to the tumour site, thus minimising DOX toxicity to certain vital organs. Accordingly, Alg-CasNPs-DOX was shown as a promising DOX nanocarrier for improving the therapeutic efficacy of DOX against cancer compared to that of free DOX.

APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression.

BACKGROUND: Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation of this key pathway in the adult ovary is associated with subfertility and tumourigenesis. The roles of Adenomatous polyposis coli 2 (APC2), a little-studied WNT signalling pathway regulator, in ovarian homeostasis, fertility and tumourigenesis have not previously been explored. Here, we demonstrate essential roles of APC2 in regulating ovarian WNT signalling and ovarian homeostasis. METHODS: A detailed analysis of ovarian histology, gene expression, ovulation and hormone levels was carried out in 10 week old and in aged constitutive APC2-knockout (Apc2-/-) mice (mixed background). Statistical significance for qRT-PCR data was determined from 95% confidence intervals. Significance testing was performed using 2-tailed Student's t-test, when 2 experimental cohorts were compared. When more were compared, ANOVA test was used, followed by a post-hoc test (LSD or Games-Howell). P-values of < 0.05 were considered statistically significant. RESULTS: APC2-deficiency resulted in activation of ovarian WNT signalling and sub-fertility driven by intra-ovarian defects. Follicular growth was perturbed, resulting in a reduced rate of ovulation and corpora lutea formation, which could not be rescued by administration of gonadotrophins. Defects in steroidogenesis and follicular vascularity contributed to the subfertility phenotype. Tumour incidence was assessed in aged APC2-deficient mice, which also carried a hypomorphic Apc allele. APC2-deficiency in these mice resulted in predisposition to granulosa cell tumour (GCT) formation, accompanied by acute tumour-associated WNT-signalling activation and a histologic pattern and molecular signature seen in human adult GCTs. CONCLUSIONS: Our work adds APC2 to the growing list of WNT-signalling members that regulate ovarian homeostasis, fertility and suppress GCT formation. Importantly, given that the APC2-deficient mouse develops tumours that recapitulate the molecular signature and histological features of human adult GCTs, this mouse has excellent potential as a pre-clinical model to study ovarian subfertility and transitioning to GCT, tumour biology and for therapeutic testing.

Self-assembled tannic acid complexes for pH-responsive delivery of antibiotics: Role of drug-carrier interactions.

Self-assembled particles, based on non-covalent interactions, are attractive drug carriers with a relatively simple structure and easy preparation. Tannic acid (TA) is an anionic polyphenolic compound with a wide range of molecular interactions and diverse applications in drug delivery research. Here, we propose the use of TA complexes with cationic antibiotics as a new pH-responsive drug carrier of high drug loading and optimal stability. TA complexes were prepared with three water-soluble antibiotics; colistin sulfate (COL), gentamicin sulfate (GEN) and gatifloxacin (GAT). Complexes' size ranged from several-hundred nanometers to few microns. For selected particles, drug loading ranged from 30 to 36%. Importantly, we demonstrate the impact of drug-carrier interactions, studied via infrared spectroscopy and molecular modeling, on final complex stability and performance; the complexes resisted dissociation in presence of serum at physiological pH to variable degrees and showed different drug release profiles. However, all complexes dissociated upon medium acidification, releasing their drug payload and demonstrating expected antibacterial effect. These results demonstrate that TA/antibiotic self-assembled complexes represent an excellent carrier for pH-sensitive delivery of water-soluble drugs. In addition to system's simplicity and low cost, complexes were easily prepared with high drug loading and desirable pH-dependent association/dissociation profile.