Safety and efficacy of CRISPR-mediated genome ablation of VEGFA as a treatment for choroidal neovascularization in nonhuman primate eyes.

CRISPR-based genome editing enables permanent suppression of angiogenic factors like vascular endothelial growth factor (VEGF) as potential treatment for choroidal neovascularization (CNV) - a major cause of blindness in age-related macular degeneration. We previously designed adeno-associated viral (AAV) vectors with S. pyogenes Cas 9 (SpCas9) and guide RNAs (gRNAs) to target conserved sequences in VEGFA across mouse, rhesus macaque, and human, with successful suppression of VEGF and laser-induced CNV in mice. Here, we advanced the platform to nonhuman primates and found that subretinal AAV8-SpCas9 with gRNAs targeting VEGFA may reduce VEGF and CNV severity as compared to SpCas9 without gRNAs. However, all eyes that received AAV8-SpCas9 regardless of gRNA presence developed subfoveal deposits, concentric macular rings, and outer retinal disruption that worsened at higher dose. Immunohistochemistry showed subfoveal accumulation of retinal pigment epithelial cells, collagen, and vimentin, disrupted photoreceptor structure, and retinal glial and microglial activation. Subretinal AAV8-SpCas9 triggered aqueous elevations in CCL2, but minimal systemic humoral or cellular responses against AAV8, SpCas9, or GFP reporter. Our findings suggest that CRISPR-mediated VEGFA ablation in NHP eyes may suppress VEGF and CNV, but can also lead to unexpected subretinal fibrosis, photoreceptor damage, and retinal inflammation despite minimal systemic immune responses.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

AIM: The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. METHOD: The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. RESULTS: Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. CONCLUSIONS: Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

Philadelphia-like B-cell acute lymphoblastic Leukaemia: Disease features and outcomes in the era of immunotherapy.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.

2024 UK and Ireland modified Delphi consensus on myopia management in children and young people.

INTRODUCTION: This work aimed to establish the largest UK and Ireland consensus on myopia management in children and young people (CYP). METHODS: A modified Delphi consensus was conducted with a panel of 34 optometrists and ophthalmologists with expertise in myopia management. RESULTS: Two rounds of voting took place and 131 statements were agreed, including that interventions should be discussed with parents/carers of all CYP who develop myopia before the age of 13 years, a recommendation for interventions to be publicly funded for those at risk of fast progression and high myopia, that intervention selection should take into account the CYP's hobbies and lifestyle and that additional training for eye care professionals should be available from non-commercial sources. Topics for which published evidence is limited or lacking were areas of weaker or no consensus. Modern myopia management contact and spectacles are suitable first-line treatments. The role and provision of low-concentration atropine needs to be reviewed once marketing authorisations and funding decisions are in place. There is some evidence that a combination of low-concentration atropine with an optical intervention can have an additive effect; further research is needed. Once an intervention is started, best practice is to monitor non-cycloplegic axial length 6 monthly. CONCLUSION: Research is needed to identify those at risk of progression, the long-term effectiveness of individual and combined interventions, and when to discontinue treatment when myopia has stabilised. As further evidence continues to emerge, this consensus work will be repeated to ensure it remains relevant.

Engagement of the speech motor system in challenging speech perception: Activation likelihood estimation meta-analyses.

The relationship between speech production and perception is a topic of ongoing debate. Some argue that there is little interaction between the two, while others claim they share representations and processes. One perspective suggests increased recruitment of the speech motor system in demanding listening situations to facilitate perception. However, uncertainties persist regarding the specific regions involved and the listening conditions influencing its engagement. This study used activation likelihood estimation in coordinate-based meta-analyses to investigate the neural overlap between speech production and three speech perception conditions: speech-in-noise, spectrally degraded speech and linguistically complex speech. Neural overlap was observed in the left frontal, insular and temporal regions. Key nodes included the left frontal operculum (FOC), left posterior lateral part of the inferior frontal gyrus (IFG), left planum temporale (PT), and left pre-supplementary motor area (pre-SMA). The left IFG activation was consistently observed during linguistic processing, suggesting sensitivity to the linguistic content of speech. In comparison, the left pre-SMA activation was observed when processing degraded and noisy signals, indicating sensitivity to signal quality. Activations of the left PT and FOC activation were noted in all conditions, with the posterior FOC area overlapping in all conditions. Our meta-analysis reveals context-independent (FOC, PT) and context-dependent (pre-SMA, posterior lateral IFG) regions within the speech motor system during challenging speech perception. These regions could contribute to sensorimotor integration and executive cognitive control for perception and production.

Transparent RFID tag wall enabled by artificial intelligence for assisted living.

Current approaches to activity-assisted living (AAL) are complex, expensive, and intrusive, which reduces their practicality and end user acceptance. However, emerging technologies such as artificial intelligence and wireless communications offer new opportunities to enhance AAL systems. These improvements could potentially lower healthcare costs and reduce hospitalisations by enabling more effective identification, monitoring, and localisation of hazardous activities, ensuring rapid response to emergencies. In response to these challenges, this paper introduces the Transparent RFID Tag Wall (TRT-Wall), a novel system taht utilises a passive ultra-high frequency (UHF) radio-frequency identification (RFID) tag array combined with deep learning for contactless human activity monitoring. The TRT-Wall is tested on five distinct activities: sitting, standing, walking (in both directions), and no-activity. Experimental results demonstrate that the TRT-Wall distinguishes these activities with an impressive average accuracy of 95.6 % under four distinct distances (2, 2.5, 3.5 and 4.5 m) by capturing the RSSI and phase information. This suggests that our proposed contactless AAL system possesses significant potential to enhance elderly patient-assisted living.

Assessing disintegration effectiveness: A thorough evaluation using the SeDeM-ODT expert system for doxylamine succinate orodispersible formulation.

BACKGROUND: The SeDeM-ODT expert system is designed to assess the suitability of the pharmaceutical ingredients for their conversion into an orodispersible formulation by direct compression. The tool can be utilized to select the most appropriate excipients that improve the compressibility and buccodispersibility of the formulation. OBJECTIVE: This study aimed to utilize the SeDeM-ODT expert system to evaluate the performance of superdisintegrants and select an appropriate superdisntegrant for Doxylamine Succinate orodispersible formulation. METHOD: The SeDeM-ODT expert system scrutinized the excipients to develop an orodispersible Doxylamine Succinate formulation. Among the 15 parameters of the tool, some of them were determined through experimental work, while the remaining were calculated through the experimental values of other parameters. The central composite design approach was used for formulation development. The prepared powder blends were compressed using the direct compression method and evaluated for different parameters (hardness, thickness, diameter, friability, weight variation, water absorption ratio, wetting time, and disintegration time). RESULTS: The results of the SeDeM-ODT expert system were correlated with the values obtained by the post-compression tests. The Crospovidone formulation (F7) was found to be an optimized formulation as it disintegrated quickly compared with the other formulations containing other superdisintegtrants. The results perfectly endorsed the SeDeM-ODT expert system evaluation, as Crospovidone showed the highest IGCB value of 6.396. CONCLUSION: The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The assessment proved Crospovidone to produce quicker disintegration in Doxylamine Succinate orodispersible formulation.

Enhancement in the antibacterial activity of Rifaximin by delivery through gelatin nanoparticles.

OBJECTIVES: Bacterial infections are a noteworthy global health concern that necessitates the development of new strategies to enhance the potency and efficacy of antibiotics. Rifaximin (RFX), a broad-spectrum antibiotic, exhibits promising antibacterial activity against several bacterial strains. However, its insolubility and impermeability impede the exploitation of its full potential. The objective of the current study is to overcome the inherent caveats of RFX to exploit its maximum potential. SIGNIFICANCE: The exploitation of the full potential of antibiotics is necessary for reduction in their dosage and to minimize antibiotic pollution. This is a preliminary study aiming for maximum utilization of RFX at the target site and reduction in its release in unmetabolized form. METHODS: Gelatin is a biopolymer that has gained significant attention for biomedical applications owing to its inherent biocompatibility and biodegradability. In this study, bovine gelatin nanoparticles (BGNPs) were fabricated by the self-assembly method for their application as a carrier of RFX to enhance its antibacterial activity. The study employs a comprehensive range of experimental techniques to characterize the fabricated BGNPs such as DLS, Zeta Potential, FT-IR, AFM, SEM-EDX, and UV-Vis spectrophotometry. RESULTS: The average size of the fabricated BGNPs was 100 nm with a zeta potential value of -15.3 mV. The loading of RFX on BGNPs rendered an increase in its size to 136 nm with a zeta potential value of -16 mV. In-vitro assays and microscopic analyses were conducted to compare the antibacterial efficacy of RFX and RFX@BGNPs. An excellent loading capacity followed by sustained release of RFX from RFX@BGNPs rendered a significant enhancement in its pharmaceutical efficacy. The release of RFX from RFX@BGNPs followed the Higuchi and Korsmeyer-Peppas models. The antibacterial efficacy of RFX against Staphylococcus aureus has doubled by delivery through RFX@BGNPs, assessed by inhibitory and biofilm inhibitory assays. The enhancement in the antibacterial efficiency was further endorsed by SEM and microscopic imaging of the control and treated bacterial colonies. CONCLUSION: The study demonstrates an enhancement in the antimicrobial efficacy of RFX by its delivery in the form of RFX@BGNPs to exploit its full potential for practical applications.

Unveiling genetic variants: Tetra-primer ARMS-PCR diagnosis and structural insights into BLAD, BC, and DUMPS in Pakistani cattle herds.

BACKGROUND: Bovine leukocyte adhesion deficiency (BLAD), bovine citrullinemia (BC), and deficiency of Uridine monophosphate synthetase (DUMPS) are the common autosomal recessive disorders affecting the global dairy industry. BLAD leads to poor wound healing and recurrent infections. In BC, ammonia builds up leading to neurological disorders and death. DUMPS results in developmental abnormalities. METHODOLOGY: In this study, tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS PCR) based diagnostic tests were optimized for BLAD, BC, and DUMPS. A total of 250 animals (58 indigenous and 192 Holstein Friesian (HF)) were screened from all across Pakistan. In addition to validation of ARMS-PCR results through Sanger sequencing, the protein modeling provided structural insights of the disease-associated reported SNPs. Pathway analysis illustrated gene functions under normal and mutated conditions. Furthermore, haplotype and phylogenetic analysis of ASS1 (Argininosuccinate synthetase) gene were performed on study samples and NCBI retrieved sequences. RESULTS: The study's focus was to screen the herds for prevalence of carriers of genetic disorders, as they are the main source of disease dissemination. One animal was found carrier for BC, whereas no carriers were found for BLAD and DUMPS. The protein models corroborated the reported amino acid change in BLAD, and protein truncation in both BC and DUMPS proteins. SNPs found in NCBI retrieved sequences were either silent or missense and had no effect on protein structure. DNA network presented graphical illustration of haplotype interactions and phylogenetic analysis conferred evolutionary landscape of ASS1 gene. The combination of these approaches produced an in-depth genetic picture of BC in Pakistani cattle. CONCLUSION: The development of diagnostic tests and identification of the heterozygous BC sample underscores the significance of constant monitoring to avoid the unwanted dissemination of mutant alleles among Pakistani cattle, thereby promoting the general well-being and sustainability of the dairy sector.

Extravascular lipoma over the subclavian vein.

A rare instance of extravascular lipomas located over the subclavian vein in a woman in her early 60s presented unique diagnostic and therapeutic challenges due to their close proximity to critical structures. Lipomas, which are the most commonly occurring benign soft tissue tumours, are typically composed of mature adipocytes. Although lipomas can develop in any region of the body, they are most commonly found in the subcutaneous tissues of the trunk and proximal limbs. Extravascular lipomas, especially those near major blood vessels like the subclavian vein, are extremely uncommon.In this particular case, the tumour was extensively in contact with the right subclavian vein, though there was no intravascular involvement. The lipomatous tumour was successfully excised during surgery, with the subclavian vein and surrounding structures being preserved. Histopathological analysis confirmed the diagnosis of a benign lipoma. This case highlights the significance of early diagnosis, meticulous surgical planning and multidisciplinary collaboration to achieve the best possible outcomes.

Beneficial adjunctive effects of the 5HT3 receptor antagonist ondansetron on symptoms, function and cognition in early phase schizophrenia in a double-blind, 2 × 2 factorial design, randomised controlled comparison with simvastatin.

BACKGROUND: Variable benefits have been reported from the adjunctive use of simvastatin and the 5HT3 receptor antagonist, ondansetron, in patients with schizophrenia. We investigated their independent efficacy and possible synergy to improve negative symptoms of schizophrenia within a single trial. METHODS: A 6-month, randomised, double-blind, placebo-controlled trial with a 4-arm, 2 × 2 factorial design, in three centres in Pakistan. In total, 303 people with stable treated schizophrenia aged 18-65 were randomly allocated to add-on ondansetron, simvastatin, both or neither. The primary outcome was a Positive and Negative Syndrome Scale (PANSS) negative score at 3 and 6 months. RESULTS: Mixed model analysis and analysis of covariance revealed no main effects of simvastatin or ondansetron but a significant negative interaction between them (p = 0.03); when given alone, both drugs significantly reduced negative symptoms compared to placebo but they were ineffective in combination. Individual treatment effects versus placebo were -1.9 points (95%CIs -3.23, -0.49; p = 0.01) for simvastatin and -1.6 points for ondansetron (95%CIs -3.00, -0.14; p = 0.03). Combined treatment significantly increased depression and side effects. In those with less than the median 5 years of treatment, ondansetron improved all PANSS subscales, global functioning measures and verbal learning and fluency, whereas simvastatin did not. CONCLUSION: Small improvement in negative symptoms on simvastatin and ondansetron individually are not synergistic in combination in treating negative symptoms of schizophrenia. Ondansetron showed broad efficacy in patients on stable antipsychotic treatment within 5 years of illness. The findings suggest that ondansetron should be evaluated in patients at risk of psychosis or early in treatment.

Estimation of Serum Malondialdehyde (a Marker of Oxidative Stress) as a Predictive Biomarker for the Severity of Coronary Artery Disease (CAD) and Cardiovascular Outcomes.

Background Coronary artery disease (CAD) is influenced by oxidative stress, which is a critical yet often overlooked factor in disease progression. While traditional biomarkers such as cholesterol levels and blood pressure are commonly used, they do not fully capture oxidative damage. Malondialdehyde (MDA), a byproduct of lipid peroxidation, offers additional insights into oxidative stress and CAD severity. Unlike conventional markers, such as low-density lipoprotein (LDL) cholesterol, which primarily reflects lipid levels, and high-sensitivity C-reactive protein (hs-CRP), which indicates inflammation, MDA directly measures oxidative damage. This makes MDA a potentially valuable complement to these traditional biomarkers, providing a more nuanced understanding of CAD risk. Despite its potential, the role of MDA in clinical assessments remains underexplored. This study aims to address this gap by evaluating MDA's effectiveness as a complementary biomarker, enhancing the assessment of CAD risk and progression beyond what is provided by existing markers. Objective This study aims to assess serum MDA levels in relation to CAD severity to explore its potential as a non-invasive biomarker for disease progression and cardiovascular outcomes. Methodology This cross-sectional study was conducted at the Department of Cardiology, Mardan Medical Complex Teaching Hospital, Pakistan, from June 2023 to May 2024. Patients were divided into different groups with varying severity of CAD. The one-way ANOVA was used to assess differences among groups, and Pearson's correlation coefficient explored relationships between MDA and all study variables. Simple linear regression analyzed associations between MDA levels, patient groups, and other variables, controlling for covariates. MDA's potential as a predictive biomarker was assessed through ROC curve analysis, with statistical significance set at a p-value < 0.05. Results A total of 133 patients were included in the study, categorized based on CAD severity into mild (n=71), moderate (n=39), and severe (n=23) groups. Serum MDA levels significantly increased with the severity of CAD. Specifically, MDA levels were 116.61 ± 41.95 in the mild group, 253.45 ± 180.29 in the moderate group, and peaked at 459.91 ± 149.80 in the severe group. The differences in MDA levels among these groups were statistically significant (p < 0.01), supporting the association between higher MDA levels and increased CAD severity. Factors such as BMI, heart rate, blood pressure, and smoking status also significantly influenced MDA levels. Receiver operating characteristic (ROC) curve analysis demonstrated high diagnostic accuracy of MDA for assessing CAD severity, with area under the curve (AUC) values of 0.81 for moderate and 0.94 for severe CAD. Comorbid conditions such as diabetes mellitus were associated with elevated MDA levels. Conclusion Elevated serum MDA serves as a reliable, non-invasive biomarker for predicting CAD severity, with potential applications in clinical risk assessment and management strategies. By identifying patients with elevated oxidative stress early, clinicians can implement timely interventions, potentially slowing disease progression and improving outcomes.

Analytical approaches and advancement in the analysis of natural and synthetic fiber: A comprehensive review.

BACKGROUND: Accurately determining fiber composition is essential for optimizing material properties across diverse applications in textiles, composites, packaging, and other bio-based materials. Fiber performance in textiles, composites, and bio-based materials depends upon their intricate composition. This review explores advanced analytical techniques for the comprehensive characterization of natural (cellulose-hemicellulose-lignin) and synthetic (polymeric) fibers. Natural fibers primarily consist of cellulose, hemicellulose, and lignin, while synthetic fibers are formed by linking small monomer units, such as nylon, polyester, and acrylics. RESULTS: A variety of analytical methods are employed for fiber composition analysis, including microscopy, spectroscopy, chromatography, thermal analysis, and wet chemical methods. A multi-modal approach employing advanced techniques is essential for in-depth fiber analysis. Spectroscopic methods like Fourier Transform Infrared Spectroscopy (FTIR) offer rapid, non-destructive determination of chemical functionalities. Near-infrared spectroscopy (NIR) offers another efficient approach, particularly when integrated with chemometric techniques like Principal Component Regression (PCR) and Partial Least Squares (PLS) for precise quantification of cellulose, hemicellulose, and lignin. Additionally, thermal analysis methods such as Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Dynamic Mechanical Analysis (DMA) provide insights into thermal stability and mechanical characteristics of fibers. SIGNIFICANCE: This review emphasizes the importance of an integrated approach utilizing various analytical methods for comprehensive fiber characterization. While traditional wet chemical methods offer limited advantages, the combined use of advanced techniques provides a more holistic understanding of fiber properties. As technology evolves, this integrated approach is expected to shape the future of fiber analysis and its applications across diverse industries.

Hispidulin-rich fraction of Clerodendrum fragrans Wild. (Sesewanua) dissolving microneedle as antithrombosis candidate: A proof of concept study.

Existing conventional antithrombosis drugs have caused many side effects, opening up opportunities for the development of new thrombotic drugs. There is potential to use the hispidulin-rich fraction of sesewanua (HRFS) as a new antithrombotic. The oral route limitation of hispidulin, as a low water solubility and non-polar compound, can be addressed. This study explores the potential of HRFS in the form of dissolving microneedles (DMN). The formula was created using polymers such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone K-30 (PVP), and non-ionic surfactant. Ex vivo permeation studies found that 184.95 µg/cm2 of hispidulin was released 60 h after the best formulation. After 14 days of applying HRFS-DMN, the anticoagulant and antioxidant activity in male albino rats showed higher Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) values and lower Inter Cellular Adhesion Molecule-1 (ICAM-1) values. No statistically significant differences were found between the effects of two and four HRFS-DMN and the injection of heparin at a dosage of 200 IU per kilogram. However, notable distinctions were observed when comparing HRFS-DMN to negative controls, oral and quercetin as positive controls at anti-ICAM activity. The findings confirmed the feasibility of HRFS-DMN for thrombosis and its effectiveness in delivering Hispidulin (HIS) into the bloodstream. This DMN is non-irritating, safe, and painless, showing promising outcomes in enhancing the efficacy of thrombosis treatment via the transdermal route.

Synergistic effect of biochar and intercropping on lead phytoavailability in the rhizosphere of a vegetable-grass system.

The effects of engineered steam exploded biochar on the phytoavailability of toxic elements in the shared- and nonshared-rhizosphere of vegetable-grass intercropping system have not been investigated yet. Therefore, we explored and elucidated the synergistic effect of pristine rape-straw biochar (BC), steam exploded BC (BCSE), KMnO4-modified BCSE (BCSEMn), and hydroxyapatite-modified BCSE (BCSEHA) on the solubility, fractionation and phytoavailability of lead (Pb) in a vegetable-grass intercropping system. In a rhizosphere box, Brassica chinensis L. (pakchoi; PC, as a vegetable) and Pennisetum polystachion L. (mission grass; MG, as a Pb hyperaccumulator), were grown in the biochar treated soil with (non-shared rhizosphere) or without (shared rhizosphere) root separation. Addition of BCSEMn and BCSEHA, particularly BCSEMn, significantly improved plant growth, photosynthetic pigment levels, and positively influenced the gas exchange attributes by suppressing oxidative stress and boosting antioxidant enzymes activities. Both biochars altered a proportion of Pb in the acid soluble to the immobile fraction and thus significantly decreased its leachability (TCLP-Pb) and bioavailability (CaCl2-extrcated Pb) by 32.7 %-33.9 % and 48.5 %-53.5 %, respectively, as compared to the control. Both biochars, particularly BCSEMn, reduced significantly the Pb content in shoots and roots of PC and MG with a significantly higher efficiency in the PC than in the MG; this was the case more in the shared than in the non-shared rhizosphere. These findings indicate the synergistic effect of BCSEMn and BCSEHA and intercropping for enhancing the grass phytostabilization capacity for Pb and reducing its uptake by edible plants in a vegetables-grass system, which could be used as a promising approach for the phytomanagement of Pb contaminated soils.

Steroid hormones in fish, caution for present and future: A review.

The misuse and overuse of steroid hormones in fish is an emerging problem worldwide. The data on hormonal residue in fish was less due to a lack of effective monitoring programs on hormonal use in fish production. This review revealed the findings of previously published data on different hormonal use and their residue and impact. Steroid hormones were frequently used in fish production to promote growth and reproduction. It was suggested that hormones should be used carefully to ensure environmental, biological, and food safety. The most commonly used steroid hormones in fish production were testosterone, estrogen, progesterone, and cortisol. However, the indiscriminate use left residue in the fish flesh above the FAO/WHO permissible limits. This residue in fish caused many health hazards in consumers, like early puberty in children, advances in bone age, negative repercussions on growth, modification of sexual characteristics, and cancer development such as breast, ovarian, and prostate cancer. It also harmed fish and the aquatic environment. The most common detection methods for these hormones were GC-MS, LC-MS, and UHPLC-MS. Many countries permitted the use of hormones in fish production upon monitoring, whereas many countries prohibited it. Moreover, many countries did not have any rules and regulations on the use of hormones in fish production. Thus, this review is a wake-up call for researchers, policymakers and consumers on the impacts of hormonal residues in food commodities.

Dosage and utilization of dexamethasone in the management of COVID-19: A critical review.

BACKGROUND: The severe respiratory manifestations observed in severe coronavirus disease 2019 (COVID-19) cases are often associated with an excessive inflammatory response. Dexamethasone, a synthetic glucocorticoid, exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells. This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases. Early on in the pandemic, the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support. However, the optimal dosage of corticosteroids remains debatable. Several studies that compare different doses of dexamethasone in COVID-19 exist, but the results are conflicting. AIM: To review the latest evidence regarding dosage, safety, and efficacy of dexamethasone in severe COVID-19. METHODS: We followed preferred reporting items for systematic reviews and meta-analysis guidelines. A detailed literature search was conducted across PubMed, Google Scholar, and Medline to include publications up to March 2024. Our keywords included "COVID-19" "SARS-CoV-2" "dexamethasone" "corticosteroid" "steroid" and "glucocorticoid"-along with their combinations. We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies. A meta-analysis was conducted using a random-effects model, assessing pooled odds ratios and mean differences, with heterogeneity gauged by the I 2 statistic and the χ 2 tests. RESULTS: No statistical differences were found in 28-day all-cause mortality [pooled odds ratio (OR) = 1.109, 95%CI: 0.918-1.340], 60-day all-cause mortality (OR = 0.873, 95%CI: 0.744-1.024; I 2 = 47.29%), mean length of hospital stay (mean difference = -0.08 days, 95%CI: -0.001 to 0.161) and adverse events (OR = 0.877, 95%CI: 0.707-1.087). CONCLUSION: Differing doses of corticosteroids have no clinical implications on mortality, mean length of hospital stay, and adverse events in COVID-19 patients. Additional research is required in patients requiring invasive or non-invasive ventilation.

Pulsed Laser Deposition of Epitaxial SrTiO3/Sr3Al2O6 Templates as a Water-Soluble Sacrificial Layer for GaAs Growth and Lift-Off.

Despite the record-high efficiency of GaAs solar cells, their terrestrial application is limited due to both the particularly high costs related to the required single-crystal substrates and epitaxial growth. A water-soluble lift-off layer could reduce costs by avoiding the need for toxic and dangerous etchants, substrate repolishing, and expensive process steps. Sr3Al2O6 (SAO) is a water-soluble cubic oxide, and SrTiO3 (STO) is a perovskite oxide, where a SAO ≈ 4 × a STO ≈ (2√2)a GaAs. Here, the pulsed laser-deposited epitaxial growth of SrTiO3/Sr3Al2O6 templates on STO and Ge substrates for epitaxial GaAs growth was investigated, where SAO works as a sacrificial layer and STO protects the hygroscopic SAO during substrate transfer between deposition chambers. We identified that the SAO film quality is strongly dependent on the growth temperature and the O2 partial pressure, where either a high T or a high P(O2) improves the quality. XRD spectra of the films with optimized deposition parameters showed an epitaxial STO/SAO stack aligned to the STO (100) substrate, and TEM analysis revealed that the grown films were epitaxially crystalline throughout the thickness. The STO/SAO growth on Ge substrates at a high T with no intentional O2 flow resulted in some nonepitaxial grains and surface pits, likely due to partial Ge oxidation. GaAs was grown by metalorganic vapor-phase epitaxy (MOVPE) on STO/SAO/STO templates. Lift-off after dissolving the sacrificial SAO in water resulted in free-standing ⟨001⟩ preferentially oriented polycrystalline GaAs.