Inhibition of the renal apical sodium dependent bile acid transporter prevents cholemic nephropathy in mice with obstructive cholestasis.

BACKGROUND & AIMS: Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there is no specific treatment. We revisited its pathophysiology with the aim of identifying novel therapeutic strategies. METHODS: Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI mass spectrometry imaging and liquid chromatography-tandem mass spectrometry. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed in kidney biopsies from patients with CN, mice with a humanized bile acid (BA) spectrum, and via analysis of serum BAs and KIM-1 (kidney injury molecule 1) in patients with liver disease and hyperbilirubinemia. RESULTS: Proximal tubular epithelial cells (TECs) reabsorbed and enriched BAs, leading to oxidative stress and death of proximal TECs, casts in distal tubules and collecting ducts, peritubular capillary leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TECs and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In patients with advanced liver disease, serum BAs were the main determinant of KIM-1 levels. ASBT expression in TECs was preserved in biopsies from patients with CN, further highlighting the translational potential of targeting ASBT to treat CN. CONCLUSIONS: BA enrichment in proximal TECs followed by oxidative stress and cell death is a key early event in CN. Inhibiting renal ASBT and consequently BA enrichment in TECs prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS: Cholemic nephropathy (CN) is a severe complication of cholestasis and an unmet clinical need. We demonstrate that CN is triggered by the renal accumulation of bile acids (BAs) that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells of the kidney take up BAs via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in tubular epithelial cells, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for patients with CN.

Mitigation of drought stress in maize and sorghum by humic acid: differential growth and physiological responses.

BACKGROUND: Drought is a major determinant for growth and productivity of all crops, including cereals, and the drought-induced detrimental effects are anticipated to jeopardize world food security under the ongoing global warming scenario. Biostimulants such as humic acid (HA) can improve drought tolerance in many cereals, including maize and sorghum. These two plant species are genetically related; however, maize is more susceptible to drought than sorghum. The physiological and biochemical mechanisms underlying such differential responses to water shortage in the absence and presence of HA, particularly under field conditions, are not fully understood. RESULTS: Herein, the effects of priming maize and sorghum seeds in 100 mg L-1 HA on their vegetative growth and physiological responses under increased levels of drought (100%, 80%, and 60% field capacity) were simultaneously monitored in the field. In the absence of HA, drought caused 37.0 and 58.7% reductions in biomass accumulation in maize compared to 21.2 and 32.3% in sorghum under low and high drought levels, respectively. These responses were associated with differential retardation in overall growth, relative water content (RWC), photosynthetic pigments and CO2 assimilation in both plants. In contrast, drought increased root traits as well as H2O2, malondialdehyde, and electrolyte leakage in both species. HA treatment significantly improved the growth of both plant species under well-watered and drought conditions, with maize being more responsive than sorghum. HA induced a 29.2% increase in the photosynthetic assimilation rate in maize compared to 15.0% in sorghum under high drought level. The HA-promotive effects were also associated with higher total chlorophyll, stomatal conductance, RWC, sucrose, total soluble sugars, total carbohydrates, proline, and total soluble proteins. HA also reduced the drought-induced oxidative stress via induction of non-enzymic and enzymic antioxidants at significantly different extents in maize and sorghum. CONCLUSION: The current results identify significant quantitative differences in a set of critical physiological biomarkers underlying the differential responses of field-grown maize and sorghum plants against drought. They also reveal the potential of HA priming as a drought-alleviating biostimulant and as an effective approach for sustainable maize and sorghum production and possibly other crops in drought-affected lands.

Acetaminophen overdose causes a breach of the blood-bile barrier in mice but not in rats.

Acetaminophen (APAP) is known to cause a breach of the blood-bile barrier in mice that, via a mechanism called futile bile acid (BA) cycling, increases BA concentrations in hepatocytes above cytotoxic thresholds. Here, we compared this mechanism in mice and rats, because both species differ massively in their susceptibility to APAP and compared the results to available human data. Dose and time-dependent APAP experiments were performed in male C57BL6/N mice and Wistar rats. The time course of BA concentrations in liver tissue and in blood was analyzed by MALDI-MSI and LC-MS/MS. APAP and its derivatives were measured in the blood by LC-MS. APAP-induced liver damage was analyzed by histopathology, immunohistochemistry, and by clinical chemistry. In mice, a transient increase of BA in blood and in peri-central hepatocytes preceded hepatocyte death. The BA increase coincided with oxidative stress in liver tissue and a compromised morphology of bile canaliculi and immunohistochemically visualized tight junction proteins. Rats showed a reduced metabolic activation of APAP compared to mice. However, even at very high doses that caused cell death of hepatocytes, no increase of BA concentrations was observed neither in liver tissue nor in the blood. Correspondingly, no oxidative stress was detectable, and the morphology of bile canaliculi and tight junction proteins remained unaltered. In conclusion, different mechanisms cause cell death in rats and mice, whereby oxidative stress and a breach of the blood-bile barrier are seen only in mice. Since transient cholestasis also occurs in human patients with APAP overdose, mice are a clinically relevant species to study APAP hepatotoxicity but not rats.

Does hematology rotation impact the interest of internal medicine residents in considering hematology as a career?

BACKGROUND: The ongoing need for hematologists is not met in many parts of the world. The hematology rotation during internal medicine residency is an opportunity to attract more physicians to the hematology field. This study aimed to assess the impact of a hematology rotation on internal medicine residents' interest in considering a hematology career. METHODS: Internal medicine residents were invited to complete an anonymous questionnaire before and after a mandatory hematology rotation. Their interest in pursuing a hematology career was assessed by asking them to rate "Consider hematology as a career" on a 0 to 10 scale (0 = never, 10 = strongly agree). In addition, viewing the hematology workload as manageable, comfort in dealing with cancer and satisfaction with the hematologist lifestyle were assessed before and after the rotation. RESULTS: Sixty out of 62 IM residents completed the pre- and post-hematology rotation questionnaire (response rate 97%). 80% were in the age range of 25-29 years and 73% were males. Two-thirds were in the senior level (3rd and 4th year) of their residency program and 40% had a prior rotation in a hematology unit. Rating considering hematology as a career increased significantly from a median of 7 (IQR: 5-9) pre-rotation to 8.5 (IQR: 7-10) post-rotation (p = 0.0018). Subgroup analysis showed a significant increase in interest among subgroups except residents > 29 years of age, those with prior hematology rotation and junior residents (1st and 2nd year residency). The change in viewing hematology workload as manageable, comfort in dealing with cancer patients and perceiving the hematologist lifestyle as satisfactory were strongly positively correlated with the change in considering hematology as a career (p = 0.0014, < 0.0001 and < 0.0001; respectively). CONCLUSIONS: A hematology rotation is associated with an increase in the interest of internal medicine residents in considering hematology as a career. Further research is needed to Identify factors that may make hematology rotations an effective tool in attracting residents to the hematology field.

Exploring Ventilator-Associated Pneumonia: Microbial Clues and Biomarker Insights from a Retrospective Study.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

Student engagement in health professions education: A commentary on AMEE Guide No. 152.

It is critical to emphasize the significance of student engagement in health professions as part of our judgment of the program's success. A recent AMEE Guide No. 152 on student engagement has provided a comprehensive understanding of a range of aspects, including the application of this topic. This article discusses specific issues that can add to the value of the Guide. When defining student engagement, it is crucial to establish aspects of 'active; engagement' and 'passive, non-engagement' student reaction to learning. The Job demands-resources (JD-R) and academic demands-resources (AD-R) model fits with the determinants of student engagement. Determinant elements of students' engagement have been incorporated into a model and methods used in measuring student engagement. The model has been applied to problem-based learning and virtual (online learning) program.

Can pharmacy students use Wikipedia as a learning resource? Critical assessment of articles on chemotherapeutic drugs.

Pharmacy students tend to use Wikipedia as a quick resource of knowledge. This study aimed to evaluate the accuracy of content and readability level of Wikipedia articles on chemotherapeutics, using quality and readability tools. Using the British National Formulary (BNF-2018) and ClinicalTrials.gov, we identified 188 chemotherapeutic drugs. We randomly selected 100 drugs with an Excel randomization program. The English Wikipedia was searched for the selected 100 drugs, and prints of the identified articles were obtained. Readability was calculated with an online instrument (http://www.readabilityformulas.com/). Articles were independently scored by two researchers using the modified DISCERN tool for content assessment. The modified DISCERN scores had a median value of 24 [interquartile range (IQR) = 7.5]. Two articles (2%) had good quality (DISCERN score 36-40), thirty-eight (38%) were moderate (DISCERN 26-35), and sixty (60%) were poor in score (DISCERN ≤25). The articles covered drug indications and most side effects. However, the majority lacked information on the routes of administration, contraindications, pharmacokinetics, and mechanisms of action. We found a correlation between DISCERN scores and number of edits (P value = 0.00033, R2 = 0.1238). The number of references varied from 2 to 150 (median= 17, IQR = 17). Several problems were identified in the lists of references and citations. Most articles lacked tables and figures. The readability of the articles was 14.35 ± 3.13, consistent with the readability level of university students. In conclusion, the Wikipedia articles on chemotherapeutic drugs were not written for professional pharmacy students. Although they matched the expected readability level of university students, most were incomplete and lacked essential information.NEW & NOTEWORTHY Pharmacy students use Wikipedia as a quick resource of knowledge. However, Wikipedia articles are not written for professional pharmacy students. The study shows that although Wikipedia articles on chemotherapeutic drugs matched the expected readability level of university students, most needed to be completed and lacked essential information.

Exploring the relationship between burnout and emotional intelligence among academics and clinicians at King Saud University.

BACKGROUND: Academics and clinicians are exposed to significant workload pressures and are at a high risk of stress and burnout. OBJECTIVES: This study aimed to examine the relationship between burnout and emotional intelligence (EI) by comparing and corelating burnout and EI scores among academics and clinicians against several factors. METHODS: In this cross-sectional study, academics and clinicians at King Saud University and King Saud University Medical City and Affiliated Hospitals were invited to complete anonymous questionnaires: Maslach Burnout Inventory-Human Services Survey and the Trait Emotional Intelligence Questionnaire Short Form. The collected data were analyzed using the SPSS software for descriptive studies, group comparisons, regression analyses, and Pearson's (r) correlation tests. RESULTS: Study participants included 126 individuals (men = 65, 51.6%; women = 61, 48.4%). Of these, 65% were Saudi nationals and 35% were expatriates, and 76 were academics while 50 were clinicians. The mean (minimum to maximum) burnout total score was 55 ± 18.9 (8 to 97) and the global TEIQue-SF score ranged between 2.8 and 6.7 (5.04 ± 0.7). Burnout scores varied between departments and were higher among younger participants and non-Saudis. Age had a small direct correlation with self-control (r = .17, p = .05), and there was no statistically significant correlation with other EI factors. However, there was a moderate inverse correlation between age and emotional exhaustion (EE) (r = -0.33, p < 0.0001), and a small inverse correlation with depersonalization (DP) (r = -0.21, p = 0.02). T-tests demonstrated a statistically significant difference in EI factor "emotionality" among Saudis (5.2 ± .8) and non-Saudis (4.9 ± .8) (t124 = 2.2, p = 0.03), and for burnout subscales, there was a statistically significant difference in DP among Saudis (6.4 ± 4.8) and non-Saudis (8.5 ± 5.6), (p = 0.03). Moderate (r = -0.3, p = 0.01) and weak (r = -0.2, p = 0.05) negative correlations were found between EI factors and burnout subscales (EE, DP). CONCLUSION: This study confirmed an inverse relationship between burnout and EI scores among academics and clinicians. The findings suggest the need for introducing measures and implementing a system for early detection of burnout among staff and providing support to enhance EI and requisite care for those undergoing burnout episodes.

The challenges imposed by artificial intelligence: are we ready in medical education?

Artificial intelligence (AI) is the science and engineering of making intelligent machines. In medical education, the usefulness of AI and its applications is being explored in training, learning, simulation, curriculum, and developing new assessment tools. This editorial encourages authors to submit their research on AI concerning medical education to enrich our knowledge.

Online learning resources and social media platforms used by medical students during the COVID-19 pandemic.

BACKGROUND: The unprecedented COVID-19 pandemic has caused significant disruption to medical students' education. It imposed challenges that required rapid adaptation to enforced lockdowns and remote learning and changed curriculum delivery from in-person to online learning and virtual technology. OBJECTIVE: This study aimed to determine the trends and ratings of using Internet resources and social media platforms by medical students during the COVID-19 pandemic. METHODS: A validated questionnaire was used to explore preferences for Internet resources and social media platforms among undergraduate medical students (years 1, 3, and 5) at King Saud University. The questionnaire comprised three sections- (i) demographic information, (ii) access and use of Internet resources/social media platforms, and (iii) students' ratings and reasons for using technology-enabled learning during the COVID-19 pandemic. RESULTS: A total of 320 undergraduate medical students responded to the online questionnaire. The difference in the number of students using the Internet daily across academic years increased significantly as they progressed in the medical course (p = 0.025). For learning, YouTube and Videoconferencing (e.g. Zoom) were used by 83.1% and 73.4% of students, respectively, followed by WhatsApp 198 (61.9%). For social interaction, WhatsApp, 310 (96.6%); YouTube, 296 (92.8%); Twitter, 288 (90%); and Zoom, 269 (84.1%) were the platforms used by most students. Regarding concerns about the impact of COVID-19 and social isolation, 250 (78.1%) agreed that technology helped them gain a sense of connectedness to their peers. Over half of students, 187 (58.4%) wished that technologies be integrated more often in their courses, as 245 (76.7%) agreed that it helped engage them with classes. CONCLUSION: The study shows that the use of the Internet and social media resources is increasing at all levels to fill the gap in learning and social interaction because of the COVID-19 pandemic. Medical institutions should embrace the effective use of Internet resources and use the experience gained and lessons learned in guiding educators on what type of online resources should be created to add value to students learning even post-pandemic.

Physicians' knowledge, attitude and perceptions towards vaccine-hesitant parents: a cross-sectional study.

OBJECTIVES: Research has shown that physicians are encountering an increase in vaccine-hesitant parents (VHPs) numbers. This study examined physicians' vaccination knowledge, vaccine-related discussions with VHPs, beliefs about and responses to vaccine hesitancy, and challenges faced while discussing immunization with VHPs. METHODS: This cross-sectional, descriptive study was performed at King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia, in September 2020. The data were collected through a questionnaire distributed via email. The sample comprised 90 physicians who routinely treat children and reported they frequently have appropriate vaccine discussions when encountering VHPs. RESULTS: Ninety participants (59% were females) completed the questionnaire. Of these, 37.8% were from family medicine, 7.8% from primary care, and 54.4% from paediatrics. The most discussed topics were vaccine necessity, reasons for vaccine refusal, and vaccine safety. Seventeen participants (18.8%) reported being extremely confident, and (42.2%) were confident in their vaccine-specific knowledge. Regarding confidence in communication skills, 22.2% reported being extremely confident and (45.6%) were confident. Determinants of higher confidence in the knowledge and communication skills were physician age (p = 0.001 and p = 0.0001, respectively), years of practice (p = 0.002 and (p = 0.005), and patients seen per workday (p = 0.0001 and p = 0.024). Other factors such as physician sex (p = 0.062), the field of practice (p = 0.329), and hours of work per week (p = 0.061) were not significantly different. Forty-six (51%) physicians sometimes find it challenging to conduct appropriate vaccine-related discussions because of having too many other issues to discuss during the consultation. Furthermore, 53 (59%) participants agreed/strongly agreed that parental refusal to vaccinate would raise suspicions of negligence. On the other hand, 59 (65%) disagreed/strongly disagreed that parental refusal of vaccines is a parental right. Participants expressed the need to refer VHPs to a specialised advisory clinic with excellent experience and negotiation skills to overcome the challenges. CONCLUSION: Vaccine safety and necessity are the topics of most concern to VHPs, and a knowledgeable physician with competent communication skills is critical in responding to such situations. This study highlights the most reported barriers to successful vaccine-related discussions. It raises underlying ethical principles such as parental autonomy and the need to train physicians in VHPs. To train physians for succucful vaccine counceling of VHPs.

Thymus Vulgaris Oil Nanoemulsion: Synthesis, Characterization, Antimicrobial and Anticancer Activities.

Essential oil nanoemulsions have received much attention due to their biological activities. Thus, a thyme essential oil nanoemulsion (Th-nanoemulsion) was prepared using a safe and eco-friendly method. DLS and TEM were used to characterize the prepared Th-nanoemulsion. Our findings showed that the nanoemulsion was spherical and ranged in size from 20 to 55.2 nm. The micro-broth dilution experiment was used to evaluate the in vitro antibacterial activity of a Th-emulsion and the Th-nanoemulsion. The MIC50 values of the thymol nanoemulsion were 62.5 mg/mL against Escherichia coli and Klebsiella oxytoca, 250 mg/mL against Bacillus cereus, and 125 mg/mL against Staphylococcus aureus. Meanwhile, it emerged that the MIC50 values of thymol against four strains were not detected. Moreover, the Th-nanoemulsion exhibited promising antifungal activity toward A. brasiliensis and A. fumigatus, where inhibition zones and MIC50 were 20.5 ± 1.32 and 26.4 ± 1.34 mm, and 12.5 and 6.25 mg/mL, respectively. On the other hand, the Th-nanoemulsion displayed weak antifungal activity toward C. albicans where the inhibition zone was 12.0 ± 0.90 and MIC was 50 mg/mL. Also, the Th-emulsion exhibited antifungal activity, but lower than that of the Th-nanoemulsion, toward all the tested fungal strains, where MIC was in the range of 12.5-50 mg/mL. The in vitro anticancer effects of Taxol, Th-emulsion, and Th-nanoemulsion were evaluated using the standard MTT method against breast cancer (MCF-7) and hepatocellular carcinoma (HepG2). Additionally, the concentration of VEGFR-2 was measured, and the activities of caspase-8 (casp-8) and caspase-9 (casp-9) were evaluated. The cytotoxic effect was the most potent against the MCF-7 breast cancer cell line after the Th-nanoemulsion treatment (20.1 ± 0.85 µg/mL), and was 125.1 ± 5.29 µg/mL after the Th-emulsion treatment. The lowest half-maximal inhibitory concentration (IC50) value, 20.1 ± 0.85 µg/mL, was achieved when the MCF-7 cell line was treated with the Th-nanoemulsion. In addition, Th-nanoemulsion treatments on MCF-7 cells led to the highest elevations in casp-8 and casp-9 activities (0.66 ± 0.042 ng/mL and 17.8 ± 0.39 pg/mL, respectively) compared to those with Th-emulsion treatments. In comparison to that with the Th-emulsion (0.982 0.017 ng/mL), the VEGFR-2 concentration was lower with the Th-nanoemulsion treatment (0.672 ± 0.019ng/mL). In conclusion, the Th-nanoemulsion was successfully prepared and appeared in nanoform with a spherical shape according to DLS and TEM, and also exhibited antibacterial, antifungal, as well as anticancer activities.

Exploring the Influence of Chemical Conditions on Nanoparticle Graphene Oxide Adsorption onto Clay Minerals.

High concentrations of graphene oxide (GO), a nanoparticle substance with rapid manufacturing development, have the ability to penetrate the soil surface down to the mineral-rich subsurface layers. The destiny and distribution of such an unusual sort of nanomaterial in the environment must therefore be fully understood. However, the way the chemistry of solutions impacts GO nanoparticle adsorption on clay minerals is still unclear. Here, the adsorption of GO on clay minerals (e.g., bentonite and kaolinite) was tested under various chemical conditions (e.g., GO concentration, soil pH, and cation valence). Non-linear Langmuir and Freundlich models have been applied to describe the adsorption isotherm by comparing the amount of adsorbed GO nanoparticle to the concentration at the equilibrium of the solution. Our results showed fondness for GO in bentonite and kaolinite under similar conditions, but the GO nanoparticle adsorption with bentonite was superior to kaolinite, mainly due to its higher surface area and surface charge. We also found that increasing the ionic strength and decreasing the pH increased the adsorption of GO nanoparticles to bentonite and kaolinite, mainly due to the interaction between these clay minerals and GO nanoparticles' surface oxygen functional groups. Experimental data fit well to the non-linear pseudo-second-order kinetic model of Freundlich. The model of the Freundlich isotherm was more fitting at a lower pH and higher ionic strength in the bentonite soil while the lowest R2 value of the Freundlich model was recorded at a higher pH and lower ionic strength in the kaolinite soil. These results improve our understanding of GO behavior in soils by revealing environmental factors influencing GO nanoparticle movement and transmission towards groundwater.

Purification, characterization, immobilization and applications of an enzybiotic ß-1,3-1,4-glucanase produced from halotolerant marine Halomonas meridiana ES021.

Extracellular ß-1,3-1,4-glucanase-producing strain Halomonas meridiana ES021 was isolated from Gabal El-Zeit off shore, Red Sea, Egypt. The Extracellular enzyme was partially purified by precipitation with 75% acetone followed by anion exchange chromatography on DEAE-cellulose, where a single protein band was determined with molecular mass of approximately 72 kDa. The Km value was 0.62 mg ß-1,3-1,4-glucan/mL and Vmax value was 7936 U/mg protein. The maximum activity for the purified enzyme was observed at 40 °C, pH 5.0, and after 10 min of the reaction. ß-1,3-1,4-glucanase showed strong antibacterial effect against Bacillus subtilis, Streptococcus agalactiae and Vibrio damsela. It also showed antifungal effect against Penicillium sp. followed by Aspergillus niger. No toxicity was observed when tested on Artemia salina. Semi-purified ß-1,3-1,4-glucanase was noticed to be effective in clarification of different juices at different pH values and different time intervals. The maximum clarification yields were 51.61% and 66.67% on mango juice at 40 °C and pH 5.3 for 2 and 4 h, respectively. To our knowledge, this is the first report of ß-1,3-1,4-glucanase enzyme from halotolerant Halomonas species.

Plasmonic Surface of Metallic Gold and Silver Nanoparticles Induced Fluorescence Quenching of Meso-Terakis (4-Sulfonatophenyl) Porphyrin (TPPS) and Theoretical-Experimental Comparable.

Colloidal metallic nanoparticles have attracted a lot of interest in the last two decades owing to their simple synthesis and fascinating optical properties. In this manuscript, a study of the effect of both gold nanoparticles (Au NPs) and silver nanoparticles (Ag NPs) on the fluorescence emission (FE) of TPPS has been investigated utilizing steady-state fluorescence spectroscopy and UV-Vis spectrophotometry. From the observed electronic absorption spectra, there is no evidence of the ground state interaction between metallic Au NPs or Ag NPs with TPPS. On the other side, the FE spectra of TPPS have been quenched by both Ag and Au NPs. Via applying quenching calculations, Ag NPs showed only traditional static fluorescence quenching of TPPS with linear Stern-Volmer (SV) plots. On the contrary, quenching of TPPS emission by Au NPs shows composed models. One model is the sphere of action static quenching model that prevails at high quencher concentrations leading to non-linear SV plots with positive deviation. However, at low Au NPs concentrations, traditional dynamic quenching occurs with linear SV plots. The quantum calculations for TPPS structure have been obtained using Gaussian 09 software: in which the TPPS optimized molecular structure was achieved using DFT/B3LYP/6-311G (d) in a gaseous state. Also, the calculated electronic absorption spectra for the same molecule in water as a solvent are obtained using TD/M06/6-311G + + (2d, 2p). Furthermore, the theoretical and experimental results comparable to UV-Vis spectra have been investigated.

Spectroscopic Behavior and Photophysical Parameters of 2-(Acetoxymethyl)-6-(1,2,4-triazinylaminodihydroquinazolinyl)tetrahydropyran Derivative in Different Solid Hosts.

Optical and photophysical properties of 6-substituted-1,2,4-Triazine fluorescent derivative dye doped in silicate based sol-gel, homopolymer of methyl methacrylate (PMMA), and copolymer (MMA/diethylene glycol dimethacrylate) (DEGDMA) were investigated. The pores of different hosts and caging of the dye were found to effect on the parameters such as molar absorptivity, cross sections of singlet-singlet electronic absorption and emission spectra, excited state lifetime, quantum yield of fluorescence. The dipole moment of electronic transition, the length of attenuation and oscillator strength of electronic transition from So → S1 have been calculated. The dye was pumped with different powers using 3rd harmonic Nd: YAG laser of 355 nm and pulse duration 8 ns, with repetition rate 10 Hz. Good photo stability for dye was attained. After 55,000 pumping pulses of (10 mJ/pulse), the photo-stabilities were decreased to 53%, 48%, and 45% of the initial ASE of dye in sol gel, PMMA, and Co-polymer respectively. The dye in sol-gel matrix showed improvement of photo stability compared with those in organic polymeric matrices.

Contribution of Eastern Mediterranean Region countries to palliative care journals from 1991 to 2020 and its relationship to the development of palliative care.

BACKGROUND: Palliative care (PC) is in an early stage of development in the Eastern Mediterranean Region (EMR) of the World Health Organization. A metric based on publishing in specialized PC journals may be useful in assessing PC development. This study was conducted to describe the contribution of EMR countries to PC research and to study the relationship between this contribution and the levels of PC development. METHODS: The Scopus database was used to search 21 PC journals (1991-2020) for articles with at least one EMR-affiliated author independently of his/her position in the article. As an indicator, the 3-year average articles per million population per year (AAMY) was calculated. Changes over time were calculated through a regression analysis. The relationship between the AAMY and the level of PC development and opioid consumption were assessed through Mann-Witney test using the worldmap PC development categories as a proxy, and Spearman analysis, respectively. RESULTS: The number of articles published during the 30-year period was 31,108 of which 402 (1.3%) were EMR-affiliated. There was a steady rise in the AAMY of the EMR (R2 = 0.894). The number of EMR-affiliated articles increased from 3 in the period 1991-1995 to 191 in 2016-2020. The 2018-2020 AAMY was significantly higher in countries with greater PC development than in those without (median [IQR] = 0.0975 [0.0254-0.1802] and 0.0098 [0-0.0256], p = 0.042). Also, it was significantly higher in countries that progressed to a higher level of PC development between 2006 and 2017 (p = 0.0159). There was a significant positive correlation between the average opioid consumption for the years 2017-2019 and the AAMY for the same period (p = 0.0043). CONCLUSIONS: There is a slow steady progress in the contribution of EMR countries to PC journals, which corresponds to the level of PC development and its progress in the region. A metric based on the contribution to specialized PC journals may be a useful indicator of PC development.

Outcome comparison between thoracodorsal artery perforator flap and muscle-sparing latissimus dorsi flap in axillary reconstruction after hidradenitis suppurativa excision.

BACKGROUND: Thoracodorsal artery perforator (TDAP) flap and muscle-sparing latissimus dorsi (MSLD) flap have been frequently used for axillary coverage after hidradenitis suppurativa (HS) excision. However, none showed superiority to others. This study compared both flaps to define the ideal option, highlighting flap outcomes and functional and aesthetic results. METHODS: A retrospective study was conducted to compare both flaps that were used for axillary reconstruction in nine patients with bilateral HS Hurley stage III between 2017 and 2020. Eight TDAP and 10 MSLD flaps underwent functional evaluation using shoulder abduction angle (SA); the Disabilities of the Arm, Shoulder, and Hand (DASH) score; visual analog scale (VAS) for pain; and the Dermatology Life Quality Index (DLQI) questionnaires. Aesthetic assessment included the Scar Cosmesis Assessment and Rating (SCAR) scale and arm-chest interval. RESULTS: The mean operating time was 194.4 ± 51.58 and 128.5 ± 31.45 min for TDAP and MSLD (p = .009), respectively. Flap complications were significantly higher in the TDAP group (p = .034). There was no significant difference between both groups regarding SA; DASH, DLQI, VAS, and SCAR scale (p > .05). The mean arm-chest interval was significantly longer in the MSLD than in the TDAP group by 6.9 mm (p = .001). CONCLUSIONS: TDAP and MSLD are comparable versatile flaps to eradicate axillary HS with higher TDAP flap complications. Although the TDAP flap is less bulky than the MSLD flap, the MSLD flap shortens the harvesting time without a significant difference in functional outcomes and scar results.

Assessment of RACGAP1 as a Prognostic and Immunological Biomarker in Multiple Human Tumors: A Multiomics Analysis.

Several recent studies have pointed out that arc GTPase activating protein 1 (RACGAP1) is a putative oncogene in many human tumors. However, to date, no pan-cancer analysis has been performed to study the different aspects of this gene expression and behavior in tumor tissues. Here, we applied several bioinformatics tools to perform a comprehensive analysis for RACGAP1. First, we assessed the expression of RACGAP1 in several types of human tumors and tried to correlate that with the stage of the tumors analyzed. We then performed a survival analysis to study the correlation between RACGAP1 upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, the phosphorylation status of the interested protein in normal and tumor tissues, and the potential molecular mechanisms of RACGAP1 in cancerous tissue. The results demonstrated that RACGAP1, a highly expressed gene across several types of tumors, correlated with a poor prognosis in several types of human cancers. Moreover, it was found that RACGAP1 affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of RACGAP1, where our results nominate it as a potential prognostic biomarker and a target for antitumor therapy development.

Spectral Behavior and Photophysical Parameters of Dihydrophenanthro[9,10-e][1,2,4]Triazine Derivative Dyes in Sol-Gel and Methyl Methacrylate Polymer Matrices.

This paper deals with the optical and photophysical properties of dihydrophenanthro[9,10-e][1,2,4]triazine fluorescent dyes doped in Silicate based sol-gel and homo-poly methyl methacrylate (PMMA). Solid hosts were found to effect on the optical and photophysical parameters such as molar absorptivity, cross sections of singlet-singlet electronic absorption and emission spectra, excited state lifetime, quantum yield of fluorescence. The dipole moment of electronic transition, the length of attenuation and oscillator strength of electronic transition from So → S1 have been calculated. The dyes were pumped with different powers using 3rd harmonic Nd:YAG laser of 355 nm and pulse duration 8 ns, with a repetition rate at (10 Hz). Good photostability for compounds 1 and 2 were attained. It was decreased to 49% & 54% and 46% & 40% of the initial ASE of dyes in sol gel and PMMA, respectively, after 55,000 pumping pulses at (10 mJ/pulse). The dyes in sol-gel showed improved photostability compared with those in organic polymeric matrices.