Clinical and neurogenetic characterisation of autosomal recessive RBL2-associated progressive neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants. To define the phenotypic effects of RBL2 mutations in detail, we identified and clinically characterized a cohort of 28 patients from 18 families carrying LOF variants in RBL2 , including fourteen new variants that substantially broaden the molecular spectrum. The clinical presentation of affected individuals is characterized by a range of neurological and developmental abnormalities. Global developmental delay and intellectual disability were uniformly observed, ranging from moderate to profound and involving lack of acquisition of key motor and speech milestones in most patients. Frequent features included postnatal microcephaly, infantile hypotonia, aggressive behaviour, stereotypic movements and non-specific dysmorphic features. Common neuroimaging features were cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. In parallel, we used the fruit fly, Drosophila melanogaster , to investigate how disruption of the conserved RBL2 orthologueue Rbf impacts nervous system function and development. We found that Drosophila Rbf LOF mutants recapitulate several features of patients harboring RBL2 variants, including alterations in the head and brain morphology reminiscent of microcephaly, and perturbed locomotor behaviour. Surprisingly, in addition to its known role in controlling tissue growth during development, we find that continued Rbf expression is also required in fully differentiated post-mitotic neurons for normal locomotion in Drosophila , and that adult-stage neuronal re-expression of Rbf is sufficient to rescue Rbf mutant locomotor defects. Taken together, this study provides a clinical and experimental basis to understand genotype-phenotype correlations in an RBL2 -linked neurodevelopmental disorder and suggests that restoring RBL2 expression through gene therapy approaches may ameliorate aspects of RBL2 LOF patient symptoms.

Role of Anteromedial Cortical Support for Unstable Intertrochanteric Fractures Being Treated With Cephalomedullary Nails.

INTRODUCTION: Reduction quality is of paramount importance for an optimal outcome in unstable pertrochanteric fractures. The non-anatomical functional anteromedial buttress is proposed to prevent impending mechanical complications. We aimed to evaluate the role of anteromedial cortical support in preventing mechanical complications following fixation with the cephalomedullary nail. MATERIALS AND METHODS: A prospective, single-arm interventional study was conducted in the Orthopaedics Department of a Combined Military Hospital (CMH) in Rawalpindi. The duration of the study was 24 months. Patients were recruited by the purposive sampling technique as per inclusion/exclusion criteria. Preoperatively, the reduction was categorized as per Baumgartner's and Chang's criteria. Post-operatively, weight bearing as tolerated was advised. Radiographs prior to discharge for loss of reduction were evaluated. Follow-up radiographic measurements of neck length, neck shaft angle, and their loss as per protocol were done at three and six months. RESULTS: A total of 202 patients were operated on from October 21 until August 23. Mortality at six months in 39 patients (19.3%) and loss to follow-up in 31 patients (15.3%) resulted in 132 patients with complete follow-up and having developed complications in 12 patients (9.09%). The mean age was 76.3 ± 7.98 years; males were 105 (79.5%), and females were 27 (20.5%). Closed reduction was 58 (43.9%), and additional manoeuvres were required in 74 (56.1%). The mean tip apex distance (TAD) was 24.56 ± 2.76, and the Calcar gap was 5.16 ± 1.27. Cleveland zone centre-centre in 54 (40.9%), inferior-centre in 65 (49.2%), and inferior-posterior (9.9%) were statistically significant for mechanical complications (p≤0.001). There was a significant association between the grading of Chang's and Baumgartner's poor groups for the development of mechanical complications (p≤0.001). The mean time to full weight bearing without support was 21 ± 1.22 weeks. The mean Hip Harris score at six months was 69.27 ± 7.68. CONCLUSION: Results suggest that anteromedial cortical support can lead to fewer potential mechanical complications at six months. A higher Chang's grade drives surgeons to engage in additional manoeuvres. Anteromedial cortical support is worth consideration for unstable pertrochanteric fractures.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians: A United States national experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential therapeutic tool for biliary and pancreatic diseases. Frail and elderly patients, especially those aged ≥ 90 years are generally considered a higher-risk population for ERCP-related complications. AIM: To investigate outcomes of ERCP in the Non-agenarian population (≥ 90 years) concerning Frailty. METHODS: This is a cohort study using the 2018-2020 National Readmission Database. Patients aged ≥ 90 were identified who underwent ERCP, using the international classification of diseases-10 code with clinical modification. Johns Hopkins's adjusted clinical groups frailty indicator was used to classify patients as frail and non-frail. The primary outcome was mortality, and the secondary outcomes were morbidity and the 30 d readmission rate related to ERCP. We used univariate and multivariate regression models for analysis. RESULTS: A total of 9448 patients were admitted for any indications of ERCP. Frail and non-frail patients were 3445 (36.46%) and 6003 (63.53%) respectively. Indications for ERCP were Choledocholithiasis (74.84%), Biliary pancreatitis (9.19%), Pancreatico-biliary cancer (7.6%), Biliary stricture (4.84%), and Cholangitis (1.51%). Mortality rates were higher in frail group [adjusted odds ratio (aOR) = 1.68, P = 0.02]. The Intra-procedural complications were insignificant between the two groups which included bleeding (aOR = 0.72, P = 0.67), accidental punctures/lacerations (aOR = 0.77, P = 0.5), and mechanical ventilation rates (aOR = 1.19, P = 0.6). Post-ERCP complication rate was similar for bleeding (aOR = 0.72, P = 0.41) and post-ERCP pancreatitis (aOR = 1.4, P = 0.44). Frail patients had a longer length of stay (6.7 d vs 5.5 d) and higher mean total charges of hospitalization ($78807 vs $71392) compared to controls (P < 0.001). The 30 d all-cause readmission rates between frail and non-frail patients were similar (P = 0.96). CONCLUSION: There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared to non-frail. Larger studies are warranted to investigate and mitigate modifiable risk factors.

Synthesis, characterization, and BSA binding studies of newfangled 2-phenylacetohydrazide derivatives.

Five 2-phenylacetohydrazide derivatives (BPAH = N'-benzylidene-2-phenylacetohydrazide, HBPAH = N'-(2-hydroxybenzylidene)-2-phenylacetohydrazide), PPAH = 2-phenyl-N'-3-phenylallylideneacetohydrazide, FMPAH = N'-(furan-2-ylmethylene)-2-phenylaceto hydrazide and EPAH = N'-ethylidene-2-phenylacetohydrazide were synthesized by the condensation of 2-phenylacetohydrazide with the corresponding aldehyde. The synthesized compounds were characterized by FTIR, 1D, and 2D NMR spectroscopy. The structure of the BPAH and PPAH were analyzed by single crystal X-ray diffraction analysis and in both crystallized compounds, the molecules adopted trans geometry around the -C[bond, double bond]N- (imine) functional group. To explore the pharmacological significance of these compounds, the binding ability of these compounds with Bovine Serum Albumin (BSA) was investigated using fluorescence spectroscopy. BPAH and PPAH showed the highest binding ability while EPAH, HBPAH, and FMPAH had lower binding ability to BSA molecules. Thermodynamic parameters ΔG, ΔH°, and ΔS° demonstrated that interactions of BSA with compounds BPAH, EPAH, FMAH, and HBPAH were exothermic while for PPAH it was endothermic. The negative enthalpy and entropy of the compounds BPAH, EPAH, FMAH, and HBPAH indicated that van der Waals' forces and hydrogen bonding played a major role in stabilizing the BSA binding with the molecules. Hydrophobic interactions were predominant in the binding of PPAH with BSA tends to interact with two sets of BSA binding sites with an increase in temperature.

Up-gradation of the dielectric, physical & chemical properties of cottonseed-based, non-edible green nanofluids as sustainable alternatives for high-voltage equipment's insulation fluids.

The use of natural ester oils as electrically insulating fluids has gained significant attention from industries and electrical utilities as they aim to replace traditional mineral oils. However, most natural ester oils are derived from edible products, which has the potential to contribute to the food crisis. Therefore, nonedible green nanofluids made from cottonseed oil (CSO) have been targeted as a keen solution to this issue. However, Al2O3, TiO2, Fe2O3, SiO2, and graphene nanoparticles at (0.025, 0.05, and 0.075 wt/vol%) were used as additives, along with surfactant Olic Ac-id and Ethanol (1:5) due to their promising impact on the dielectric and thermal properties of the nanofluid. The nanofluid synthesis process was practically conducted in HV & Chemical Laboratories using one-step and two-step methods, and their breakdown voltage results and chemical properties (e.g., fire point, flash point, cloud point, pour point, viscosity, acidity, moisture content, resistivity, and dissipation factor) were compared. The physical mechanisms underlying these properties were also analyzed and tested. For the validation of the proposed vegetable oil the results have been compared with traditional mineral oil for high-voltage equipment's. The findings suggest that the proposed nonedible green nanofluids-based cottonseed oil (CSO) has a high potential to be used as electrically insulating fluids, providing a sustainable alternative to conventional mineral oils. Overall, this study provides insights into the use of non-edible green nanofluids as a solution to the potential contribution of natural ester oils to the food crisis. The findings highlight the importance of sustainable solutions in the energy industry and the need for further research in this area.

Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are highly prevalent and burdensome for women experiencing menopausal transition. Fezolinetant, a selective neurokinin 3 receptor (NK3R) antagonist, is a potential therapeutic option for mitigating VMS. OBJECTIVES: Our aim is to assess the efficacy and evaluate the safety profile of fezolinetant compared with placebo in post-menopausal women suffering from VMS, by pooling all the relevant data and reflecting the most current evidence. SEARCH STRATEGY/SELECTION CRITERIA: An extensive literature search was performed in the PubMed, Medline and Cochrane Library databases from inception until June 2023 to identify relevant trials. DATA COLLECTION AND ANALYSIS: Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous outcomes. Risk ratios (RRs) were calculated for dichotomous outcomes. All statistical analyses were performed using R Statistical Software. MAIN RESULTS: A total of six randomized controlled trials were added. For the frequency of daily VMS, the combined pooled result favored the fezolinetant group over placebo (MD -2.38, 95% CI -2.64 to -2.12; P < 0.001, I2 = 0%). For the severity of daily VMS, fezolinetant was again found to be superior to the placebo group (MD -0.40, 95% CI -0.51 to -0.29; P < 0.001, I2 = 70%). Fezolinetant (120 mg) consistently demonstrated a significant reduction in the severity of daily moderate/severe VMS compared with other doses at both 4 and 12 weeks. Patient-reported outcomes (PROs) of Greene Climacteric Scale (GCS), PROMIS the Sleep Disturbance Short Form 8b and Menopause-Specific Quality of Life (MENQoL) scores indicated significant improvement with fezolinetant. No significant difference in efficacy of fezolinetant at 4 and 12 weeks were observed in any outcome. As for safety, no significant differences in the treatment emergent adverse events at 12 weeks were found between fezolinetant and placebo. CONCLUSIONS: Our study significantly favors fezolinetant over placebo regarding the primary efficacy outcomes of daily moderate to severe VMS frequency and severity, including PROs, while both the groups are comparable in terms of treatment emergent adverse events. Further studies are needed to confirm these findings.

Aeromonas hydrophila induced necrotizing fasciitis following laparoscopic cholecystectomy.

Necrotizi ng fasciit is [NF] i s a m ultifaceted disease of the muscle fascia and body tissues which demands the earliest intervention. Past reviews have documented ver y few cases of Aeromonas Hydroph ila [AH] induced N F fol lo wing abdominal surgery. AH can cause fatal NF as seen in a 72 year old female patient reported at Liaquat National Hospital &Medical College; a ter tiary care center in Karachi, Pakistan on 2nd April, 2022. She had a k nown comorbidity of hypertension and presented with the chief complaint of symptomatic gallstones for which she unde rwent Laparoscopic Cholecystectomy (LAPCHOL). She developed NF of the lower ab domen post- oper atively. Following uneventful Laparoscopic Cholecystectomy our pati ent presented to the ER two days later with severe lower abdo minal pain and overlyi ng celluliti s. Fasc io to my revealed extensive myonecrosis with necrotizing soft tissue in fe ction. Despite u ndergoing extensive surgical debr idement and broad spectr um antibi ot ic administration; the patient died in the ICU on the fifth postoperat ive day followi ng septic complications. Histopathologica l an alysis, confirmed i nflammat ion and necrosis. Culture sensitivity of the debrided tissue revealed AH. Approach should lie towards analyzing the behaviour of such microbes in high risk patients through collective case studies. This is the first clinical case showcasing such parameters e ncountered in the General Surger y Department.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 µg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

Molecular characterization, immune functions and DNA protective effects of peroxiredoxin-1 gene in Antheraea pernyi.

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H2O2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H2O2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H2O2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H2O2 in ApPrx-1-depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects.

Recent advancements in modifications of metal-organic frameworks-based materials for enhanced water purification and contaminant detection.

Metal-organic frameworks (MOFs) have emerged as a key focus in water treatment and monitoring due to their unique structural features, including extensive surface area, customizable porosity, reversible adsorption, and high catalytic efficiency. While numerous reviews have discussed MOFs in environmental remediation, this review specifically addresses recent advancements in modifying MOFs to enhance their effectiveness in water purification and monitoring. It underscores their roles as adsorbents, photocatalysts, and in luminescent and electrochemical sensing. Advancements such as pore modification, defect engineering, and functionalization, combined synergistically with advanced materials, have led to the development of recyclable MOF-based nano-adsorbents, Z-scheme photocatalytic systems, nanocomposites, and hybrid materials. These innovations have broadened the spectrum of removable contaminants and improved material recyclability. Additionally, this review delves into the creation of multifunctional MOF materials, the development of robust MOF variants, and the simplification of synthesis methods, marking significant progress in MOF sensor technology. Furthermore, the review addresses current challenges in this field and proposes potential future research directions and practical applications. The growing research interest in MOFs underscores the need for an updated synthesis of knowledge in this area, focusing on both current challenges and future opportunities in water remediation.

RETRACTED: Ahmad et al. Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays. Front. Biosci. (Landmark Ed) 2023, 28(8), 184.

The Editors-in-Chief have retracted the article titled "[Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays]" ([1]) due to significant concerns regarding the reliability and integrity of the data presented. After the publication of the article, several issues were brought to our attention regarding the originality and authenticity of the visual data within the manuscript. Specifically, Figure 4 of the article contains images that are identical to those in the previously published papers [2, 3]. This duplication of images raises serious questions about the validity of the results and the adherence to ethical standards of research. Despite multiple attempts to contact the authors for an explanation and an opportunity to address these concerns, no satisfactory response was provided. Given the lack of accountability and the serious nature of the academic misconduct implied, the Editor-in-Chief, after careful consideration and in accordance with the publication's ethical guidelines, has decided to retract the article.

Greenhouse gas emissions, carbon stocks and wheat productivity following biochar, compost and vermicompost amendments: comparison of non-saline and salt-affected soils.

Understanding the impact of greenhouse gas (GHG) emissions and carbon stock is crucial for effective climate change assessment and agroecosystem management. However, little is known about the effects of organic amendments on GHG emissions and dynamic changes in carbon stocks in salt-affected soils. We conducted a pot experiment with four treatments including control (only fertilizers addition), biochar, vermicompost, and compost on non-saline and salt-affected soils, with the application on a carbon equivalent basis under wheat crop production. Our results revealed that the addition of vermicompost significantly increased soil organic carbon content by 18% in non-saline soil and 52% in salt-affected soil compared to the control leading to improvements in crop productivity i.e., plant dry biomass production by 57% in non-saline soil with vermicompost, while 56% with the same treatment in salt-affected soil. The grain yield was also noted 44 and 50% more with vermicompost treatment in non-saline and salt-affected soil, respectively. Chlorophyll contents were observed maximum with vermicompost in non-saline (24%), and salt-affected soils (22%) with same treatments. Photosynthetic rate (47% and 53%), stomatal conductance (60% and 12%), and relative water contents (38% and 27%) were also noted maximum with the same treatment in non-saline and salt-affected soils, respectively. However, the highest carbon dioxide emissions were observed in vermicompost- and compost-treated soils, leading to an increase in emissions of 46% in non-saline soil and 74% in salt-affected soil compared to the control. The compost treatment resulted in the highest nitrous oxide emissions, with an increase of 57% in non-saline soil and 62% in salt-affected soil compared to the control. In saline and non-saline soils treated with vermicompost, the global warming potential was recorded as 267% and 81% more than the control, respectively. All treatments, except biochar in non-saline soil, showed increased net GHG emissions due to organic amendment application. However, biochar reduced net emissions by 12% in non-saline soil. The application of organic amendments increased soil organic carbon content and crop yield in both non-saline and salt-affected soils. In conclusion, biochar is most effective among all tested organic amendments at increasing soil organic carbon content in both non-saline and salt-affected soils, which could have potential benefits for soil health and crop production.

Nutrient retention after crop harvest in a typic hapludults amended with biochar types under no-tillage system.

The utilization of biochar's as soil amendments for enhancing nutrient retention in subsoils present potential limitations. To address this issue, we conducted a greenhouse experiment to assess the effects of various biochar's derived from animal manures (swine manure, poultry litter, cattle manure) and plant residues (rice straw, soybean straw, corn straw) when applied to surface of an acidic soil. Our study focused on wheat crops under a no-tillage system, with a subsequent evaluation of the residual impacts on soybeans. The experimental design involved the application of biochar's at different rates i.e. 10 and 20 Mg ha-1, followed by the assessment of their influence on NPK levels, pH, and exchangeable Al in stratified soil layers (0-5, 5-10, 10-15, and 15-25 cm). Furthermore, we investigated the interplay between biochar doses and the application of nitrogen (N) in the top 5 cm of soil, specifically examining NO 3 - , NH 4 + , P and K levels. Our findings revealed that in the top 5 cm of soil, biochar doses and N application significantly affected NO 3 - , NH 4 + , P and K concentrations. However, in deeper soil layers, no significant differences were observed among biochar doses with or without N application. Interestingly, K levels were impacted throughout all soil depths, regardless of the presence or absence of N application. Moreover, biochar application up to a 5 cm depth induced favorable changes in soil pH and reduced exchangeable Al. In contrast, deeper layers experienced a decrease in soil pH and an increase in exchangeable Al following biochar treatment. In conclusion, our study demonstrates that biochar's can effectively retain NPK nutrients, enhance soil pH, and decrease exchangeable Al, independent of the type and dosage of application under a no-tillage system. Nonetheless, the efficacy of biochar amendments may vary with soil depth and type of nutrient, warranting careful consideration for maximizing their benefits in sustainable agricultural practices.

Investigating the teratogenic potential of diclofenac sodium on chick embryos: A warning for pregnant women.

Teratogenic and embryotoxic effect of diclofenac sodium (DS) on different developmental stages of the chick-embryos was investigated by examining different parameters such as its mortality rate, hatching, morphological measurements, weighing its internal organs and calculation of different indices. Experiment was divided into four trials with different dose (0.1 mL, 0.2 mL, 0.3 mL in groups A, B, and C, respectively and group D received 0.3 mL saline solution (0.9% NaCl) and group E remained un-injected) administration and observation. Results of first and second trial showed statistically (p<0.01) significant difference in bodyweight, body-length, forelimb and hindlimb length between experimental and control groups. In third trial, diclofenac sodium administration showed a statistically (p<0.01) significant difference in the bodyweight, body-length, forelimb, hindlimb length, liver weight, egg weight (EE ratio) and kidney somatic index (KSI). The beak-size, heart weight, kidney weight, cardiac somatic index (CSI) and hepato somatic index (HSI) were not significant (p>0.05) when compared with the control groups. In trial 4, forelimb, hindlimb length, heart weight, CSI and HSI were statistically (p<0.01) significant. Body-length and liver weight were significant (p<0.05). While bodyweight, beak size, kidney weight and KSI were non-significant (p>0.05). The mortality rate was increased with increase dose of DS and also affected the hatching. DS effect on chick embryos can be applied to humans because the early development of mammals and birds are closely related. So, it was concluded that DS should be used with caution during pregnancy especially during first trimester of pregnancy.

Improved Diagnostic Confidence Imparted by Radiologists in Radiology Reports After Educational Interventions on Reporting Styles.

Background Radiology reports are important medico-legal documents facilitating communication between radiologists and referring doctors. Language clarity and precision are crucial for effective communication in these reports. Radiology reporting has changed with the evolution of imaging technology, prompting the adoption of precise terminology. Diagnostic certainty phrases (DCPs) play an important role in communicating diagnostic confidence in radiology reports. Objective The aim of this study was to evaluate the use of DCPs in radiology reports, before and after targeted educational interventions. Materials and methods The study was approved by the Aga Khan University Hospital's Ethical Review Committee and includes cross-sectional radiology reports. It involved three cycles of retrospective evaluation, with educational interventions in between to improve the use of DCPs. Results The study found a dynamic shift in the use of DCPs during the three cycles. Initially, intermediate-certainty phrases prevailed, followed by an increase in high-certainty phrases and a drop in low-certainty phrases. Later cycles showed a significant decline in DCPs and an increase in the use of definitive language. Across all subspecialties, there was a consistent decrease in intermediate- and low-certainty DCPs. Conclusion The study validates the transformative impact of educational interventions on the use of DCPs in radiology reports. The radiology reports frequently used DCPs with intermediate to low diagnostic certainty with improvement in the subsequent cycles of the study after educational interventions. It emphasizes the significance of continuing education to ensure the use of precise nomenclature.

Investigating the Antibacterial and Anti-inflammatory Potential of Polyol-Synthesized Silver Nanoparticles.

Silver nanoparticles (Ag-NPs) were synthesized by using the polyol method. The structural and morphological characteristics of Ag-NPs were studied by using X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM). The XRD analysis revealed the formation of single-phase polycrystalline Ag-NPs with an average crystallite size and lattice constant of ∼23 nm and 4.07 Å, respectively, while the FE-SEM shows the formation of a uniform and spherical morphology. Energy-dispersive X-ray spectroscopy confirmed the formation of single-phase Ag-NPs, and no extra elements were detected. A strong absorption peak at ∼427 nm was observed in the UV-vis spectrum, which reflects the surface plasmon resonance (SPR) behavior characteristic of Ag-NPs with a spherical morphology. Fourier-transform infrared (FTIR) spectra also supported the XRD and EDX results with regard to the purity of the prepared Ag-NPs. Anti-inflammatory activity was tested using HRBCs membrane stabilization and heat-induced hemolysis assays. The antibacterial activity of Ag-NPs was evaluated against four different types of pathogenic bacteria by using the disc diffusion method (DDM). The Gram-negative bacterial strains used in this study are Escherichia coli (E. coli), Klebsiella, Shigella, and Salmonella. The analysis suggested that the antibacterial activities of Ag-NPs have an influential role in inhibiting the growth of the tested Gram-negative bacteria, and thus Ag-NPs can find a potential application in the pharmaceutical industry.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.