Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

An advanced form of magnesium-rich hydroxyapatite (Mg·HAP) was modified with two types of biopolymers, namely chitosan (CH/Mg·HAP) and ß-cyclodextrin (CD/Mg·HAP), producing two types of bio-composites. The synthesized materials were developed as enhanced carriers for levofloxacin to control its loading, release, and anti-inflammatory properties. The polymeric modification significantly improved the loading efficiency to 281.4 mg g-1 for CH/Mg·HAP and 332.4 mg g-1 for CD/Mg·HAP compared with 218.3 mg g-1 for Mg·HAP. The loading behaviors were determined using conventional kinetic and isotherm models and mathematical parameters of new equilibrium models (the monolayer model of one energy). The estimated density of effective loading sites (Nm (LVX) = 88.03 mg g-1 (Mg·HAP), 115.8 mg g-1 (CH/Mg·HAP), and 138.5 mg g-1 (CD/Mg·HAP)) illustrates the markedly higher loading performance of the modified forms of Mg·HAP. Moreover, the loading energies (<40 kJ mol-1) in conjunction with the capacity of each loading site (n > 1) and Gaussian energies (<8 kJ mol-1) signify the physical trapping of LVX molecules in vertical orientation. The addressed materials validate prolonged and continuous release behaviors. These behaviors accelerated after the modification procedures, as the complete release was identified after 160 h (CH/Mg·HAP) and 200 h (CD/Mg·HAP). The releasing behaviors are regulated by both diffusion and erosion mechanisms, according to the kinetic investigations and diffusion exponent analysis (>0.45). The entrapping of LVX into Mg·HAP induces its anti-inflammatory properties against the generation of cytokines (IL-6 and IL-8) in human bronchial epithelia cells (NL20), and this effect displays further enhancement after the integration of chitosan and ß-cyclodextrin.

Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.

Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine.

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury. Pre-treatment with AGM remarkably ameliorated Cd-induced lung histopathological abrasions. AGM decreased reactive oxygen species (ROS) production, lipid peroxidation, suppressed NDAPH oxidase, and boosted the antioxidants. AGM increased Nrf2, GCLC, HO-1, and TNXRD1 mRNA, as well as HO-1 activity and downregulated Keap1. AGM downregulated Bax and caspase-3 and upregulated Bcl-2, SIRT1, and FOXO3 expression levels in the lung. In conclusion, AGM has a protective effect against Cd-induced lung injury via its antioxidant and anti-apoptotic effects mediated via regulating Nrf2/HO-1 and SIRT1/FOXO3 signaling.

Unanticipated Radiation Replanning for Stage III Non-small Cell Lung Cancer.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Characterization of Chitosan-Hybridized Diatomite as Potential Delivery Systems of Oxaliplatin and 5-Fluorouracil Drugs: Equilibrium and Release Kinetics.

The current work involves the modification of diatomite's biosiliceous frustules employing chitosan polymer chains (CS/Di) to serve as low-cost, biocompatible, multifunctional, and enhanced pharmaceutical delivery systems for 5-fluorouracil (5-Fu) together with oxaliplatin (OXPL). The CS/Di carrier displayed strong loading characteristics, notably at saturation (249.17 mg/g (OXPL) and 267.6 mg/g (5-Fu)), demonstrating a substantial 5-Fu affinity. The loading of the two types of medications onto CS/Di was conducted based on the kinetic behaviors of the conventional pseudo-first-order theory (R2 > 0.90). However, while the loading of OXPL follows the isotherm assumptions of the classic Langmuir model (R2 = 0.99), the loading of 5-Fu displays Fruendlich isotherm properties. Therefore, the 5-Fu loading displayed physical, heterogeneous, and multilayer loading properties, whereas the loading of OXPL occurred in homogeneous and monolayer form. The densities of occupied active sites of CS/Di were 37.19 and 32.8 mg/g for the sequestrations of OXPL and 5-Fu, respectively. Furthermore, by means of multimolecular processes, each loading site of CS/Di can bind up to 8 molecules of OXPL and 9 molecules of 5-Fu in a vertical orientation. This observation explains the higher loading capacities of 5-Fu in comparison to OXPL. The loading energies, which exhibit values <40 kJ/mol, provide confirmation of the dominant and significant consequences of physical processes as the regulating mechanisms. The release patterns of OXPL and 5-Fu demonstrate prolonged features over a duration of up to 120 h. The release kinetic simulation and diffusion exponents which are more than 0.45 provide evidence of the release of OXP and 5-Fu via non-Fickian transportation characteristics and the erosion/diffusion mechanism. The CS/Di carrier exhibited a substantial enhancement in the cytotoxicity of OXPL and 5-Fu against HCT-116 carcinoma cell lines, resulting in a reduction in cell viability by 4.61 and 2.26% respectively.

Recommendation for Long-term Management of Adult Attention-Deficit/Hyperactivity Disorder in Military Populations, Veterans, and Dependents: A Narrative Review.

INTRODUCTION: In addition to the higher burden of mental health disease in the military, there is a compounding antecedent association between behavioral health comorbidities and the treatment of attention-deficit/hyperactivity disorder (ADHD) in this population. Despite the low prevalence of new-onset ADHD in adults globally, the rate of stimulant (i.e., amphetamines) prescription is increasing. Stimulants can exacerbate mental health disease (often masquerading as ADHD symptomatology), precluding optimal treatment of the underlying etiology and imposing unnecessary dangerous side effects. This study aimed to evaluate the long-term safety and efficacy of stimulants for managing adult ADHD. METHODS: A nine-member multidisciplinary team reviewed a PubMed search with the terms "adult," "ADHD," and "stimulant." Targeted PubMed and Google Scholar searches for "adult ADHD" paired with Food and Drug Administration -approved ADHD medications and Google Scholar literature using forward and reverse snowballing methods were performed for high-quality studies focusing on long-term treatment in ADHD. An evidence table and clinical algorithm were developed from the review. RESULTS: Of the 1,039 results, 50 articles were fully reviewed, consisting of 21 descriptive and experimental studies, 18 observational, and 11 systematic reviews and meta-analyses. Illustrative cases within the structured discussion of the results highlighted ADHD and psychiatric comorbidities, risks, harms, and benefits of stimulant use, medication mechanisms of action, and limitations of the current evidence. DISCUSSION: The dearth of high-quality studies on long-term ADHD management in adults fails to establish a causal relationship between stimulant use and physiological harm. Despite mixed evidence supporting the benefit of stimulants, there is clear evidence regarding the risk of harm. The serious risks of stimulants include arrhythmias, myocardial infarction, stroke/transient ischemic attack, sudden death, psychosis, and worsening of behavioral health disease. Additionally, there is a possible long-term risk of harm due to chronic sympathetic load (i.e., cardiovascular system remodeling). Stimulants pose a greater risk for addiction and abuse compared to other evidence-based nonstimulant medications that have similar effectiveness. Both stimulants and nonstimulants might promote favorable neuroanatomical changes for long-term improvement of ADHD symptoms, but nonstimulants (atomoxetine) have the pharmacological advantage of also mitigating the effects of sympathetic load (sympatholysis) and anxiety (anxiolysis). Given the physiological uncertainty of extended stimulant use for adults, especially older adults with vulnerable cardiovascular systems, clinicians should proceed cautiously when considering initiating or sustaining stimulant therapy. For long-term treatment of ADHD in adults, clinicians should consider nonstimulant alternatives (including behavioral therapy) due to the comparatively lower side effect risk and the possible additional benefit in patients with behavioral health comorbidities. CONCLUSION: Long-term safety of stimulant use for adults with ADHD is uncertain, as existing studies are limited in quality and duration. This is particularly important for military populations with higher rates of mental health conditions. Managing ADHD and related conditions requires prioritizing cardiovascular safety, especially for older adults. Nonstimulant options can be helpful, especially in comorbid psychiatric disease. Before treating ADHD, ruling out and controlling other behavioral health conditions is essential to avoid masking or worsening underlying issues and reducing unnecessary medication side effects.

Water chemistry poses health risks as reliance on groundwater increases: A systematic review of hydrogeochemistry research from Ethiopia and Kenya.

Reliance on groundwater is increasing in Sub-Saharan Africa as development programmes work towards improving water access and strengthening resilience to climate change. In lower-income areas, groundwater supplies are typically installed without water quality treatment infrastructure or services. This practice is underpinned by an assumption that untreated groundwater is typically suitable for drinking due to the relative microbiological safety of groundwater compared to surface water; however, chemistry risks are largely disregarded. This article systematically reviews groundwater chemistry results from 160 studies to evaluate potential health risk in two case countries: Ethiopia and Kenya. Most studies evaluated drinking water suitability, focusing on priority parameters (fluoride, arsenic, nitrate, or salinity; 18 %), pollution impacts (10 %), or overall suitability (45 %). The remainder characterised general hydrogeochemistry (13 %), flow dynamics (10 %), or water quality suitability for irrigation (3 %). Only six studies (4 %) reported no exceedance of drinking water quality thresholds. Thus, chemical contaminants occur widely in groundwaters that are used for drinking but are not regularly monitored: 78 % of studies reported exceedance of contaminants that have direct health consequences ranging from hypertension to disrupted cognitive development and degenerative disease, and 81 % reported exceedance of aesthetic parameters that have indirect health impacts by influencing perception and use of groundwater versus surface water. Nevertheless, the spatiotemporal coverage of sampling has substantial gaps and data availability bias is driven by a) the tendency for research to concentrate in areas with known water quality problems, and b) analytical capacity limitations. Improved in-country analytical capacity could bolster more efficient assessment and prioritisation of water chemistry risks. Overall, this review demonstrates that universal and equitable access to safe drinking water (Sustainable Development Goal target 6.1) will not be achieved without wider implementation of groundwater treatment, thus a shift is required in how water systems are designed and managed.

Stigmatisation of Obesity and its Relation to the Perception of Controllability in Riyadh, Saudi Arabia: A cross-sectional study.

Objectives: This study assessed the stigmatisation of obesity among a sample of the general population in Riyadh and its association with the perception of controllability. Methods: A cross-sectional analytical study was conducted in Riyadh, Saudi Arabia, during January-February 2021. The data were collected through a self-administrated online questionnaire. Statistical analysis was performed using John's Macintosh Project, Version 16.0.0. Results: A total of 525 participants were recruited via convenience sampling. The majority of the participants exhibited a low level of stigma towards obesity (72.8%), and gender and BMI were significantly associated with the level of stigma (P = 0.0023 and 0.0360, respectively). The association between the perception of controllable factors and the level of stigma was also significant (P = 0.0001). Conclusion: A significant association was found between the stigmatisation of obesity and the perception of controllability among the general population in Riyadh. Recommendations should be based on joint international consensus statements for ending obesity stigmatisation in different settings and categories; healthcare service providers and obese patients should be educated on the relationships demonstrated in these findings.

Cadmium cardiotoxicity is associated with oxidative stress and upregulated TLR-4/NF-kB pathway in rats; protective role of agomelatine.

Cardiotoxicity is one of the hazardous effects of the exposure to the heavy metal cadmium (Cd). Inflammation and oxidative injury are implicated in the cardiotoxic mechanism of Cd. The melatonin receptor agonist agomelatine (AGM) showed promising effects against oxidative and inflammatory responses. This study evaluated the effect of AGM on Cd-induced cardiotoxicity in rats, pointing to its modulatory effect on TLR-4/NF-kB pathway and HSP70. Rats received AGM for 14 days and a single dose of Cd on day 7 and blood and heart samples were collected for analyses. Cd increased serum CK-MB, AST and LDH and caused cardiac tissue injury. Cardiac malondialdehyde (MDA), nitric oxide (NO) and MPO were elevated and GSH, SOD and GST decreased in Cd-administered rats. AGM ameliorated serum CK-MB, AST and LDH and cardiac MDA, NO and MPO, prevented tissue injury and enhanced antioxidants. AGM downregulated serum CRP and cardiac TLR-4, NF-kB, iNOS, IL-6, TNF-α and COX-2 in Cd-administered rats. HSP70 was upregulated in the heart of Cd-challenged rats treated with AGM. In silico findings revealed the binding affinity of AGM with TLR-4 and NF-kB. In conclusion, AGM protected against Cd cardiotoxicity by preventing myocardial injury and oxidative stress and modulating HSP70 and TLR-4/NF-kB pathway.

Synthesis and Characterization of Methoxy-Exfoliated Montmorillonite Nanosheets as Potential Carriers of 5-Fluorouracil Drug with Enhanced Loading, Release, and Cytotoxicity Properties.

Natural bentonite clay (BE) underwent modification steps that involved the exfoliation of its layers into separated nanosheets (EXBE) and further functionalization of these sheets with methanol, forming methoxy-exfoliated bentonite (Mth/EXBE). The synthetically modified products were investigated as enhanced carriers of 5-fluorouracil as compared to raw bentonite. The modification process strongly induced loading properties that increased to 214.4 mg/g (EXBE) and 282.6 mg/g (Mth/EXBE) instead of 124.9 mg/g for bentonite. The loading behaviors were illustrated based on the kinetic (pseudo-first-order model), classic isotherm (Langmuir model), and advanced isotherm modeling (monolayer model of one energy). The Mth/EBE carrier displays significantly higher loading site density (95.9 mg/g) as compared to EXBE (66.2 mg/g) and BE (44.9 mg/g). The loading numbers of 5-Fu in each site of BE, EXBE, and Mth/EXBE (>1) reflect the vertical orientation of these loaded ions involving multi-molecular processes. The loading processes that occurred appeared to be controlled by complex physical and weak chemical mechanisms, considering both Gaussian energy (<8 KJ/mol) as well as loading energy (<40 KJ/mol). The releasing patterns of EXBE and Mth/EXBE exhibit prolonged and continuous properties up to 100 h, with Mth/EXBE displaying much faster behaviors. Based on the release kinetic modeling, the release reactions exhibit non-Fickian transport release properties, validating cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/BE (8.6% cell viability), 5-Fu/EXBE (2.21% cell viability), and 5-Fu/Mth/EXBE (0.73% cell viability).

Synthesis and Characterization of ß-Cyclodextrin-Hybridized Exfoliated Kaolinite Single Nanosheets as Potential Carriers of Oxaliplatin with Enhanced Loading, Release, and Cytotoxic Properties.

Natural kaolinite was subjected to a successful exfoliation process into separated kaolinite nanosheets (KNs), followed by hybridization with ß-cyclodextrin biopolymer (ß-CD), forming an advanced bio-nanocomposite (ß-CD/KNs). The synthetic products were evaluated as enhanced delivery structures for oxaliplatin chemotherapy (OXAPN). The hybridization of KNs with ß-CD polymer notably enhanced the loading capacity to 355.3 mg/g (ß-CD/KNs) as compared to 304.9 mg/g for KNs. The loading of OXAPN into both KNs and ß-CD/KNs displayed traditional pseudo-first-order kinetics (R2 > 0.85) and a conventional Langmuir isotherm (R2 = 0.99). The synthetic ß-CD/KNs validates a greater occupied effective site density (98.7 mg/g) than KNs (66.3 mg/g). Furthermore, the values of the n steric parameter (4.7 (KNs) and 3.6 (ß-CD/KNs)) reveal the vertical orientation of the loaded molecules and the loading of them by multi-molecular mechanisms. These mechanisms are mainly physical processes based on the obtained Gaussian energy (<8 KJ/mol) and loading energy (<40 KJ/mol). The release profiles of both KNs and ß-CD/KNs extend for about 120 h, with remarkably faster rates for ß-CD/KNs. According to the release kinetic findings, the release of OXAPN displays non-Fickian transport behavior involving the cooperation of diffusion and erosion mechanisms. The KNs and ß-CD/KNs as free particles showed considerable cytotoxicity and anticancer properties against HCT-116 cancer cell lines (71.4% cell viability (KNs) and 58.83% cell viability (ß-CD/KNs)). Additionally, both KNs and ß-CD/KNs significantly enhanced the OXAPN's cytotoxicity (2.04% cell viability (OXAPN/KNs) and 0.86% cell viability (OXAPN/ß-CD/KNs).

Insights into the Effect of Chitosan and ß-Cyclodextrin Hybridization of Zeolite-A on Its Physicochemical and Cytotoxic Properties as a Bio-Carrier for 5-Fluorouracil: Equilibrium and Release Kinetics Studies.

Synthetic zeolite-A (ZA) was hybridized with two different biopolymers (chitosan and ß-cyclodextrin) producing biocompatible chitosan/zeolite-A (CS/ZA) and ß-cyclodextrin/zeolite-A (CD/ZA) biocomposites. The synthetic composites were assessed as bio-carriers of the 5-fluorouracil drug (5-Fu) with enhanced properties, highlighting the impact of the polymer type. The hybridization by the two biopolymers resulted in notable increases in the 5-Fu loading capacities, to 218.2 mg/g (CS/ZA) and 291.3 mg/g (CD/ZA), as compared to ZA (134.2 mg/g). The loading behaviors using ZA as well as CS/ZA and CD/ZA were illustrated based on the classic kinetics properties of pseudo-first-order kinetics (R2 > 0.95) and the traditional Langmuir isotherm (R2 = 0.99). CD/ZA shows a significantly higher active site density (102.7 mg/g) in comparison to CS/ZA (64 mg/g) and ZA (35.8 mg/g). The number of loaded 5-Fu per site of ZA, CS/ZA, and CD/ZA (>1) validates the vertical ordering of the loaded drug ions by multi-molecular processes. These processes are mainly physical mechanisms based on the determined Gaussian energy (<8 kJ/mol) and loading energy (<40 kJ/mol). Both the CS/ZA and CD/ZA 5-Fu release activities display continuous and controlled profiles up to 80 h, with CD/ZA exhibiting much faster release. According to the release kinetics studies, the release processes contain non-Fickian transport release properties, suggesting cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/ZA (11.72% cell viability), 5-Fu/CS/ZA (5.43% cell viability), and 5-Fu/CD/ZA (1.83% cell viability).

Insight into the Morphological Properties of Nano-Kaolinite (Nanoscrolls and Nanosheets) on Its Qualification as Delivery Structure of Oxaliplatin: Loading, Release, and Kinetic Studies.

Natural kaolinite underwent advanced morphological-modification processes that involved exfoliation of its layers into separated single nanosheets (KNs) and scrolled nanoparticles as nanotubes (KNTs). Synthetic nanostructures have been characterized as advanced and effective oxaliplatin-medication (OXAP) delivery systems. The morphological-transformation processes resulted in a remarkable enhancement in the loading capacity to 304.9 mg/g (KNs) and 473 mg/g (KNTs) instead of 29.6 mg/g for raw kaolinite. The loading reactions that occurred by KNs and KNTs displayed classic pseudo-first-order kinetics (R2 > 0.90) and conventional Langmuir isotherms (R2 = 0.99). KNTs exhibit a higher active site density (80.8 mg/g) in comparison to KNs (66.3 mg/g) and raw kaolinite (6.5 mg/g). Furthermore, compared to KNs and raw kaolinite, each site on the surface of KNTs may hold up to six molecules of OXAP (n = 5.8), in comparison with five molecules for KNs. This was accomplished by multi-molecular processes, including physical mechanisms considering both the Gaussian energy (<8 KJ/mol) and the loading energy (<40 KJ/mol). The release activity of OXAP from KNs and KNTs exhibits continuous and regulated profiles up to 100 h, either by KNs or KNTs, with substantially faster characteristics for KNTs. Based on the release kinetic investigations, the release processes have non-Fickian transport-release features, indicating cooperative-diffusion and erosion-release mechanisms. The synthesized structures have a significant cytotoxicity impact on HCT-116 cancer cell lines (KNs (71.4% cell viability and 143.6 g/mL IC-50); KNTs (11.3% cell viability and 114.3 g/mL IC-50). Additionally, these carriers dramatically increase OXAP's cytotoxicity (2.04% cell viability, 15.4 g/mL IC-50 (OXAP/KNs); 0.6% cell viability, 4.5 g/mL IC-50 (OXAP/KNTs)).

Silver Nanoparticles of Artemisia sieberi Extracts: Chemical Composition and Antimicrobial Activities.

BACKGROUND: Artemisia sieberi (mugwort) is a member of the daisy family Asteraceae and is widely propagated in Saudi Arabia. A. sieberi has historical medical importance in traditional societies. The current study aimed to assess the antibacterial and antifungal characteristics of the aqueous and ethanolic extracts of A. sieberi. In addition, the study investigated the effect of silver nanoparticles (AgNPs) synthesized from the A. sieberi extract. METHODS: The ethanolic and aqueous extracts and AgNPs were prepared from the shoots of A. sieberi. The characteristics of AgNPs were assessed by UV-visible spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The antibacterial experiments were performed against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The fungal species used were Candida parapsilosis, Candida krusei, Candida famata, Candida rhodotorula, and Candida albicans. The antibacterial and antifungal characteristics were evaluated by measuring the diameter of growing organisms in Petri dishes treated with different concentrations of either extracts or AgNPs compared to the untreated controls. Furthermore, TEM imaging was used to investigate any ultrastructure changes in the microbes treated with crude extracts and AgNO3. RESULTS: The ethanolic and aqueous extracts significantly decreased the growth of E. coli, S. aureus, and B. subtilis (p < 0.001), while P. aeruginosa was not affected. Unlike crude extracts, AgNPs had more substantial antibacterial effects against all species. In addition, the mycelial growth of C. famata was reduced by the treatment of both extracts. C. krusei mycelial growth was decreased by the aqueous extract, while the growth of C. parapsilosis was affected by the ethanolic extract and AgNPs (p < 0.001). None of the treatments affected the growth of C. albicans or C. rhodotorula. TEM analysis showed cellular ultrastructure changes in the treated S. aureus and C. famata compared to the control. CONCLUSION: The biosynthesized AgNPs and extracts of A. sieberi have a potential antimicrobial characteristic against pathogenic bacterial and fungal strains and nullified resistance behavior.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators.

PURPOSE: Surface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALS: Planning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3-5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTS: Ten patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7-40.6), mean CTV D0.1cc 49.2 Gy (range 45.6-53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0-1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONS: SMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

Prenatal alcohol exposure risk perception dimensions and influencing factors: A systematic review and conceptual model.

OBJECTIVE: This paper aims to explore the available literature to understand how risks regarding prenatal alcohol exposure are perceived. METHODS: A systematic review (PROSPERO; CRD 42020212887) was undertaken. PubMed, Embase, PsycINFO, and CINAHL were searched for relevant quantitative and qualitative studies. A thematic analysis of the studies was performed. RESULTS: Fifteen articles-nine quantitative and six qualitative studies met the inclusion criteria. Three dimensions of risk perceptions were identified-perceived susceptibility, perceived severity, and affective risk perception. Three influencing factors of these dimensions were also identified: information (i.e., consistency, confirmation bias, strength of the evidence, and perceived relevance), sociocultural (i.e., social inclusivity, cultural context, and risk interpretation), and individual (i.e., risks versus benefits, controllability, and experience). These dimensions and influencing factors were brought together to create the proposed novel Pregnancy Alcohol Risk Perception (PARP) conceptual model. CONCLUSIONS: The novel PARP conceptual model developed from the current literature provides a framework to guide understanding of risk perceptions, which includes a wide range of potential influencing factors. IMPLICATIONS FOR PUBLIC HEALTH: The novel PARP conceptual model provides the groundwork for further refinement with stakeholders, which could in turn be used to inform the design of interventions and health promotional materials to support harm reduction approaches and prevention of prenatal alcohol exposure.

Developmentally regulated mitochondrial biogenesis and cell death competence in maize pollen.

BACKGROUND: Cytoplasmic male sterility (CMS) is a maternally inherited failure to produce functional pollen that most commonly results from expression of novel, chimeric mitochondrial genes. In Zea mays, cytoplasmic male sterility type S (CMS-S) is characterized by the collapse of immature, bi-cellular pollen. Molecular and cellular features of developing CMS-S and normal (N) cytoplasm pollen were compared to determine the role of mitochondria in these differing developmental fates. RESULTS: Terminal deoxynucleotidyl transferase dUTP nick end labeling revealed both chromatin and nuclear fragmentation in the collapsed CMS-S pollen, demonstrating a programmed cell death (PCD) event sharing morphological features with mitochondria-signaled apoptosis in animals. Maize plants expressing mitochondria-targeted green fluorescent protein (GFP) demonstrated dynamic changes in mitochondrial morphology and association with actin filaments through the course of N-cytoplasm pollen development, whereas mitochondrial targeting of GFP was lost and actin filaments were disorganized in developing CMS-S pollen. Immunoblotting revealed significant developmental regulation of mitochondrial biogenesis in both CMS-S and N mito-types. Nuclear and mitochondrial genome encoded components of the cytochrome respiratory pathway and ATP synthase were of low abundance at the microspore stage, but microspores accumulated abundant nuclear-encoded alternative oxidase (AOX). Cytochrome pathway and ATP synthase components accumulated whereas AOX levels declined during the maturation of N bi-cellular pollen. Increased abundance of cytochrome pathway components and declining AOX also characterized collapsed CMS-S pollen. The accumulation and robust RNA editing of mitochondrial transcripts implicated translational or post-translational control for the developmentally regulated accumulation of mitochondria-encoded proteins in both mito-types. CONCLUSIONS: CMS-S pollen collapse is a PCD event coincident with developmentally programmed mitochondrial events including the accumulation of mitochondrial respiratory proteins and declining protection against mitochondrial generation of reactive oxygen species.

Twin-arginine translocase component TatB performs folding quality control via a chaperone-like activity.

The twin-arginine translocation (Tat) pathway involves an inbuilt quality control (QC) system that synchronizes the proofreading of substrate protein folding with lipid bilayer transport. However, the molecular details of this QC mechanism remain poorly understood. Here, we hypothesized that the conformational state of Tat substrates is directly sensed by the TatB component of the bacterial Tat translocase. In support of this hypothesis, several TatB variants were observed to form functional translocases in vivo that had compromised QC activity as evidenced by the uncharacteristic export of several misfolded protein substrates. These variants each possessed cytoplasmic membrane-extrinsic domains that were either truncated or mutated in the vicinity of a conserved, highly flexible α-helical domain. In vitro folding experiments revealed that the TatB membrane-extrinsic domain behaved like a general molecular chaperone, transiently binding to highly structured, partially unfolded intermediates of a model protein, citrate synthase, in a manner that prevented its irreversible aggregation and stabilized the active species. Collectively, these results suggest that the Tat translocase may use chaperone-like client recognition to monitor the conformational status of its substrates.

Metabolomics based inferences to unravel phenolic compound diversity in cereals and its implications for human gut health.

Background: Whole grain cereals are a good source of nutrients. Several cutting-edge metabolomic platforms have been deployed to identify various phenolic compounds and enhance cereal bioactive bioavailability. A diet rich in cereal phenolics may modify the microbial composition, support gut homeostasis, and increase gut health, thereby lowering the risk of non-communicable illness. Scope and approach: In this work, we reviewed current metabolomic breakthroughs in cereal phenolic profiling and their effects on human health via gut microbiota modulation. We argue that the information presented in this paper will assist in the development of nutritionally superior cereal breeds and functional foods. Key findings and conclusion: Most cereal grains contain ferulic acid derivatives, caffeoyl glycerides, and feruloyl and coumaroyl esters. While there has been significant progress in discovering novel phenolic compounds in cereals, quantifying these molecules, and translating their therapeutic effects from animal model systems to humans remains a challenge. To this end, metabolomics, and other high-throughput-omics-based platforms must be integrated to further examine the structure and functionality of phenolic metabolites to breed nutritionally rich cereals as well as map their influence on human health benefits. Rare alleles must be introduced to improve bioactive content in cereal grains while maintaining yield. Following that, these exceptional varieties must be effectively processed to maximize phenolic bioavailability.