Formulation of biodegradable alginate-based nano-carriers for in-vitro drug delivery and antibacterial activity.

Evaluation of the controlled release of ciprofloxacin (CIP.HCl) and the antibacterial efficacy of alginate (ALG)-based nanocarriers constitute the primary objectives of the current work. Herein, ALG-based nano-structures were prepared by the co-precipitation method and thoroughly analyzed using different characterization techniques, i.e., fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and zeta potential (ZP). The intense peaks emerged at 500, 545, and 750 cm-1 due to the CeO bond. Peaks that appeared at 550-600 cm-1 and 525 cm-1 are due to the stretching vibrations of FeO and ZnO bonds, respectively. Lowering of the peaks from 1640 to 1630 cm-1 and 1420 to 1384 cm-1 were observed in ALG-based nanocomposite (NC) due to the interaction of ALG with metal oxides (MO), which confirmed the formulation of CeO2/ZnFe2O4/ALG nanocomposite. The diffraction peaks at 28.6°, 56.6°, 76.5°, 37°, 47.9°, 62.3°, 74°, 13°, 21° confirmed the synthesis of MO (crystallite size 15.74 nm) and CeO2/ZnFe2O4/ALG (12 nm). In accordance with morphological studies, CeO2/ZnFe2O4 oxides had a uniform distribution throughout the relatively smooth and permeable surface of the ALG-based NC. Ciprofloxacin (CIP) was used as a model drug. Negative values of ZP revealed that CIP-loaded nanocomposite (CeO2/ZnFe2O4/ALG/CIP) had more stability than CeO2/ZnFe2O4/ALG. The maximum percentage of loading around 25 % on ALG NC was examined using the optical density (OD) method at pH 5.5. Correlation coefficients from the first order (0.971), Korsmeyer (0.9858), and Hixson (0.9021) models show the best-fitted models of the release profile in all circumstances. The release mechanism was investigated using various kinetics models. The controlled drug released was observed around 17 % at 40 °C after 3 h at pH 7.4, which is almost identical to the body temperature of a human, which is 37 °C. Similarly, after 24 h, sustained and controlled in-vitro release of the drug was studied, and it was 37, 72, and 74 % at pH 2.2, 7.4, and 9.4, respectively. Thus, prepared ALG-based NC is suitable for the controlled in-vitro release of (CIP.HCl). Metal oxides (CeO2/ZnFe2O4) and ALG-based nanocomposite (CeO2/ZnFe2O4/ALG) showed great antibacterial activity against Staphylococcus aureus (S. aureus) like 15 mm and 14 mm than Escherichia coli (E. coli).

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Risk Factors For MACE And Bleeding In Atrial Fibrillation Patients Undergoing Surgery: Insights From The Bridge Trial.

INTRODUCTION: -Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: -We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: -Among A total of 1,813 participants (mean age 71.6±8.8, 73.3% male), MACE occurred in 25 (1.4%) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95% CI 2.63-22.72, p<0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95% CI 1.26-6.63, p=0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1%) individuals, with bridge therapy (aHR 1.84, 95% CI 1.07-3.19, p=0.029), renal disease (aHR 2.50, 95% CI 1.34-4.67, p=0.004), post-procedure aspirin use (aHR 2.86, 95% CI 1.66-4.91, p<0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95% CI 1.22-9.43, p=0.019), and major surgery (aHR 3.94, 95% CI 2.26-6.85, p<0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p>0.05). CONCLUSION: -We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

Oral health of chemotherapy patients before and after provision of oral hygiene instructions at a tertiary care hospital: pre-post design.

OBJECTIVE: Disturbances in the oral mucosa is a major concern among patients undergoing chemotherapy. One of the most significant barriers in the implementation of oral care is the lack of knowledge. The aim of the study was to assess gingival and periodontal health status of chemotherapy patients before and after the provision of oral hygiene instructions. METHODS: A single group, pre-post test was conducted to assess oral health status of patients at the daycare chemotherapy, Aga Khan University Hospital, Karachi, Pakistan. Oral hygiene instructions were given with study models and leaflets. Patients were followed for 6-weeks. Oral health was assessed by using Simplified-Oral Hygiene Index (OHI-S) and Community Periodontal Index (CPI). Differences in indices were analyzed in STATA version-15.0 using Generalized Estimating Equation (GEE) and Wilcoxon Signed-rank test. RESULTS: Out of 74, 53 (72%) patients completed study follow-up. Improvement in the OHI-S was found in 14 (26%) patients (p-value < 0.001). GEE showed that age [adjusted OR = 1.10; 95% CI: 1.03-1.11], current chemotherapy cycle [adjusted OR = 1.19; 95% CI: 0.98-1.46], highest education level [Adjusted OR = 1.37; 95% CI: 1.08-12.7] and cancer therapy [Adjusted OR = 0.12; 95% CI: 0.24-0.55] were significantly associated with the change in OHI-S. Wilcoxon signed-rank test showed positive changes in the CPI (p-value < 0.001). CONCLUSIONS: Basic oral hygiene instructional intervention can be effective in improving the oral hygiene of chemotherapy patients. Nurses should also play a key role in providing psychological and nutritional support to patients.

Community structure and function during periods of high performance and system upset in a full-scale mixed microalgal wastewater resource recovery facility.

Microalgae have the potential to exceed current nutrient recovery limits from wastewater, enabling water resource recovery facilities (WRRFs) to achieve increasingly stringent effluent permits. The use of photobioreactors (PBRs) and the separation of hydraulic retention and solids residence time (HRT/SRT) further enables increased biomass in a reduced physical footprint while allowing operational parameters (e.g., SRT) to select for desired functional communities. However, as algal technology transitions to full-scale, there is a need to understand the effect of operational and environmental parameters on complex microbial dynamics among mixotrophic microalgae, bacterial groups, and pests (i.e., grazers and pathogens) and to implement robust process controls for stable long-term performance. Here, we examine a full-scale, intensive WRRF utilizing mixed microalgae for tertiary treatment in the US (EcoRecover, Clearas Water Recovery Inc.) during a nine-month monitoring campaign. We investigated the temporal variations in microbial community structure (18S and 16S rRNA genes), which revealed that stable system performance of the EcoRecover system was marked by a low-diversity microalgal community (DINVSIMPSON = 2.01) dominated by Scenedesmus sp. (MRA = 55 %-80 %) that achieved strict nutrient removal (effluent TP < 0.04 mg·L-1) and steady biomass concentration (TSSmonthly avg. = 400-700 mg·L-1). Operational variables including pH, alkalinity, and influent ammonium (NH4+), correlated positively (p < 0.05, method = Spearman) with algal community during stable performance. Further, the use of these parameters as operational controls along with N/P loading and SRT allowed for system recovery following upset events. Importantly, the presence or absence of bacterial nitrification did not directly impact algal system performance and overall nutrient recovery, but partial nitrification (potentially resulting from NO2- accumulation) inhibited algal growth and should be considered during long-term operation. The microalgal communities were also adversely affected by zooplankton grazers (ciliates, rotifers) and fungal parasites (Aphelidium), particularly during periods of upset when algal cultures were experiencing culture turnover or stress conditions (e.g., nitrogen limitation, elevated temperature). Overall, the active management of system operation in order to maintain healthy algal cultures and high biomass productivity can result in significant periods (>4 months) of stable system performance that achieve robust nutrient recovery, even in winter months in northern latitudes (WI, USA).

Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies.

By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecules demonstrated their potent mushroom tyrosinase inhibition relative to the standard used. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c, inhibited mushroom tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.016 µM. The computational study was also consistent with the experimental results and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to mushroom tyrosinase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for the diseases associated with the over-expression of this enzyme.

Stat5b/Ezh2 axis governs high PD-L1 expressing tolerogenic dendritic cell subset in autoimmune diabetes.

Dendritic cells (DCs) are specialized antigen-presenting cells that play an important role in inducing and maintaining immune tolerance. The altered distribution and/or function of DCs contributes to defective tolerance in autoimmune diseases such as type 1 diabetes (T1D). In human T1D and in NOD mouse models, DCs share some defects and are often described as less tolerogenic and excessively immunogenic. In the NOD mouse model, the autoimmune response is associated with a defect in the Stat5b signaling pathway. We have reported that expressing a constitutively active form of Stat5b in DCs of transgenic NOD mice (NOD.Stat5b-CA), re-established their tolerogenic function, restored autoimmune tolerance and conferred protection from diabetes. However, the role and molecular mechanisms of Stat5b signaling in regulating splenic conventional DCs tolerogenic signature remained unclear. In this study, we reported that, compared to immunogenic splenic DCs of NOD, splenic DCs of NOD.Stat5b-CA mice exhibited a tolerogenic profile marked by elevated PD-L1 and PD-L2 expression, reduced pro-inflammatory cytokine production, increased frequency of the cDC2 subset and decreased frequency of the cDC1 subset. This tolerogenic profile was associated with increased Ezh2 and IRF4 but decreased IRF8 expression. We also found an upregulation of PD-L1 in the cDC1 subset and high PD-L1 and PD-L2 expression in cDC2 of NOD.Stat5b-CA mice. Mechanistically, we demonstrated that Ezh2 plays an important role in the maintenance of high PD-L1 expression in cDC1 and cDC2 subsets and that Ezh2 inhibition resulted in PD-L1 but not PD-L2 downregulation which was more drastic in the cDC2 subset. Additionally, Ezh2 inhibition severely reduced the cDC2 subset and increased the cDC1 subset and Stat5b-CA.DC pro-inflammatory cytokine production. Together our data suggest that the Stat5b-Ezh2 axis is critical for the maintenance of tolerogenic high PD-L1-expressing cDC2 and autoimmune tolerance in NOD.Stat5b-CA mice.

Association of polymorphism in the promotor area of the caprine BMPR1B gene with litter size and body measurement traits in Damani goats.

This study aimed to explore polymorphisms in the promoter region of the caprine BMPR1B (Bone morphogenetic protein receptor 1 beta) gene and its association with body measurement and litter size traits in Damani does. A total of 53 blood samples were collected to analyze the association between the BMPR1B gene polymorphism and 11 phenotypic traits in Damani female goats. The results revealed that three novel SNPs were identified in the promoter region of the caprine BMPR1B gene, including g.67 A > C (SNP1), g.170 G > A(SNP2), and g.501A > T (SNP3), among which the SNP1 and SNP2 were significantly (p < 0.05) associated with litter size and body measurement traits in Damani goats. In SNP1 the AC genotype could be used as a marker for litter size, and the CC genotype for body weight in Damani goats. In SNP2, the genotype GG was significantly (p < 0.05) associated with ear and head length. Therefore, we can conclude from the present study, that genetic variants AC and CC of the caprine BMPR1B gene could be used as genetic markers for economic traits through marker-assisted selection for the breed improvement program of the Damani goat.

Oral mucositis & oral health related quality of life in women undergoing chemotherapy for breast cancer in Karachi, Pakistan: A multicenter hospital based cross-sectional study.

BACKGROUND: Oral mucositis is an inflammatory condition of oral cavity which is a common and serious side effect of cancer treatment. Severe oral mucositis compromises basic functions like eating and swallowing causing malnutrition also affecting overall patient's oral health related quality of life. The aim of the study was to find the frequency of oral mucositis in patients with breast cancer during their chemotherapy, the factors associated with oral mucositis & the overall patient's oral health related quality of life. METHODS: A cross-sectional study was conducted and a total of 160 women diagnosed with breast cancer, receiving chemotherapy and who had undergone at least one cycle of chemotherapy were recruited from two hospital settings. In-person interviews were done, patients were asked questions about their sociodemographic history, personal habits, oral history and oral findings, breast cancer stage, chemotherapy history and Oral Health Related Quality of Life. Their oral examination was done at the end of the interview to assess presence or absence of oral mucositis, using World Health Organization oral mucositis tool. Oral Health Related Quality of Life was assessed using Oral Health Impact Profile-14 questionnaire. RESULTS: Our results showed that out of 160 patients 88 (55%) of the breast cancer cases developed oral mucositis during chemotherapy. The mean Oral Health Impact Profile -14 scores in patients with oral mucositis was high 18.36±0.96 showing poor Oral Health Related Quality of Life. Occasional frequency of brushing was significantly associated with oral mucositis (Prevalence ratio:2.26, 95%_CI 1.06-4.84) compared to those patients who brushed once and twice daily. Low level of education showed negative association with oral mucositis (Prevalence ratio:0.52, 95%_CI 0.31-0.88). CONCLUSION: Our study showed significant positive association of occasional brushing with OM and protective association of low level of education with the development of OM. Emphasis should be given to oral hygiene instructions and dental education to cancer patients in oncology clinics with the prescription of mouth washes, gels and toothpaste to patients to decrease OM during chemotherapy.

Association of periodontal disease with gestational diabetes mellitus among postpartum women at a private tertiary care hospital of Karachi, Pakistan: a cross-sectional study.

Due to the overlapping aetiology of Gestational Diabetes Mellitus (GDM) and Periodontal disease (PD), which are prevalent metabolic disorder and chronic inflammatory disorder in pregnant women respectively, they are often at risk of developing both diseases simultaneously. This study aims to evaluate the association of periodontal disease and gestational diabetes mellitus among post-partum women who delivered within 24 h at private tertiary care hospital, Karachi, Pakistan. Analytical cross sectional study with sample size of 178 by non- probability purposive sampling, a total of 101 postpartum women (57%) were diagnosed with periodontal disease and 50 (28%) were GDM positive. Of those who had PD, 35% (n = 35/101) were GDM positive. An insignificant association of the prevalence ratio of GDM in women with periodontal disease was found. [PR = 1.7; 95% CI: 0.2-3.2; p-value 0.07] A statistically significant association was found between the prevalence ratio of GDM in women with obesity. It was 2.6 times compared to women who were not obese (p value < 0.01, 95% CI: 1.3-5.1). There is insignificant association found between the prevalence ratio of GDM in women with periodontal disease in our setting. Women who are overweight or tend to gain weight should be closely monitored and guided to take dietary measures.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study.

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1ß (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Biochemical and computational inhibition of α-glucosidase by novel metronidazole-linked 1H-1,2,3-triazole and carboxylate moieties: kinetics and dynamic investigations.

In the current study, metronidazole derivatives containing 1H-1,2,3-triazole and carboxylate moieties were evaluated in vitro and by computational methods for their anti-diabetic potential to insight into their medicinal use for the management of type II diabetes mellitus. Interestingly all 14 compounds displayed high to significant inhibitory capability against the key carbohydrate's digestive enzyme α-glucosidase with IC50 values in range of 9.73-56.39 µM, as compared to marketed drug acarbose (IC50 = 873.34 ± 1.67 µM). Compounds 5i and 7c exhibited the highest inhibition, therefore, these two compounds were further evaluated for their mechanistic studies to explore its type of inhibition. Compounds 5i and 7c both displayed a concentration-dependent (competitive type of inhibition) with Ki values 7.14 ± 0.01, 6.15 ± 0.02 µM, respectively, which conclude their favourable interactions with the active site residues of the α-glucosidase. Interestingly all compounds are non-cytotoxic against BJ cell line. To further validate our findings, in-silico approaches like molecular docking, and molecular dynamic simulations were applied to investigate the mode of bindings of compounds with the enzyme and identifies their inhibition mechanism, which strongly complements our experimental findings.Communicated by Ramaswamy H. Sarma.

Understanding the Landscape of Bronchoscopy in Lung Cancer: Insights From Lesion Location, Gender, and Diagnostic Efficacy.

INTRODUCTION: Lung cancer constitutes a critical global health concern. According to the International Agency for Research on Cancer's (IARC) GLOBOCAN 2020 estimates, lung cancer is the leading cause of death in cancer patients. In areas where tuberculosis is prevalent, misdiagnosis and mistreatment frequently result from overlap, creating significant difficulties that delay diagnosis and treatment. Amid this complication, bronchoscopic techniques emerge as critical diagnostic tools, though their efficacy varies between studies. METHOD: Our retrospective study, conducted from July 2021 to December 2022 at the Department of Respiratory Medicine, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, examined 156 participants with malignancies. Our focus encompassed diverse lesions within the bronchial landscape, revealing intriguing findings. RESULTS: Bronchoscopic examinations unravelled prevalent abnormalities: 52 (33.3%) manifested as intraluminal growth, 48 (31.6%) as mucosal irregularities, and a less frequent (16, 10.3%) as an intraluminal bulge. Transbronchial needle aspiration stood out with a 10/11 (91%) positivity rate, biopsy came in second at 38/46 (83%), and bronchoalveolar lavage showed a 44/152 (29%) positivity rate. It was interesting to see how the lesions were spread out among the different types of histology. For example, squamous cell carcinoma showed 17/37 (46%) intraluminal growth, while adenocarcinoma showed 22/60 (36.7%) intraluminal growth and 4/60 (6.7%) intraluminal bulge. Moreover, a significant absence of abnormalities was observed in various lesions, underlining the intricacies of characterising bronchial lesions. CONCLUSION: Our study shows that direct tissue sampling is better and that new bronchoscopic technologies are important for diagnosing lesions that were hard to get to in the past. However, limitations in patient selection biases and the single-centre focus caution against generalised interpretations. Our research illuminates the pivotal role of bronchoscopic methods in diagnosing lung lesions, emphasising the necessity for continued advancements to enhance diagnostic accuracy and treatment efficacy in lung cancer subtypes.

Comparing redo surgery and stereotactic radiosurgery for recurrent, residual, and/or tumors showing progression in nonfunctioning pituitary adenomas: A systematic review and meta-analysis.

Background: Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with headaches, visual disorders, or cranial nerve deficits. NFPAs can recur, progress, or present as residual tumors. We, therefore, conducted this review to compare the effects of both revision surgery and stereotactic surgery on tumor size, visual status, endocrine status, and complications. Methods: A systematic review of published literature on recurrent, residual, or progressing NFPAs that underwent redo surgery or stereotactic radiosurgery from the inception till June 2020 was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen records (1209 patients) were included, and risk ratio (RR) and 95% confidence intervals (CIs) estimated from each study were pooled using a random-effects meta-analysis model. Results: Redo surgery was the preferred intervention in patients presenting with larger tumor sizes and was more effective in reducing the tumor size as compared to stereotactic radiosurgery (SRS) (risk ratio [RR] 56.14; 95% CI, 16.45-191.58). There was more visual loss with revision surgery as compared to SRS (risk ratio [RR] 0.08; 95% CI, 0.03-0.20). However, SRS was associated with fewer complications, such as new diabetes insipidus, as compared to the redo surgery (risk ratio [RR] 0.01; 95% CI 0.01-0.03). Conclusion: Redo surgery is the superior choice in the treatment of recurrent/residual or progressing NFPAs if the tumor size is large and an immediate reduction in tumor burden through debulking is warranted. However, redo surgery is associated with a higher risk of visual loss, new endocrinopathies, and other complications, in contrast to SRS.

The emerging role of noncoding RNAs in the PI3K/AKT/mTOR signalling pathway in breast cancer.

Breast cancer persists as a major problem for the world's healthcare, thus it is essential to fully understand the complex molecular processes that cause its growth and development. ncRNAs had been discovered to serve critical roles in a variety of cellular functions, including the regulation of signalling pathways. Within different pathways, the AKT/PI3K/mTOR signalling cascade has received a lot of interest because of its role in cancer. A complex interaction between ncRNAs, notably miRNAs, lncRNAs, and circRNAs, and the AKT/PI3K/mTOR signalling pathway exerts both oncogenic and tumor-suppressive activities by targeting critical components of the pathway directly or indirectly. Through miRNA-mediated post-transcriptional regulation, lncRNA-guided chromatin remodelling, and circRNA sequestration, ncRNAs modulate the activity of PI3K, AKT, and mTOR, influencing cell proliferation, survival, and metastasis. Furthermore, ncRNAs can serve as promising biomarkers for breast cancer prognosis, diagnosis, and treatment response, as their dysregulation is commonly observed in breast cancer patients. Harnessing the potential of ncRNAs as therapeutic targets or tools for restoring pathway homeostasis holds promise for innovative treatment strategies in breast cancer. Understanding the intricate regulatory networks orchestrated by ncRNAs in this context may pave the way for novel diagnostic approaches, therapeutic interventions, and a deeper comprehension of breast cancer's molecular landscape, ultimately improving patient outcomes. This abstract underscores the emerging significance of ncRNAs in the AKT/PI3K/mTOR signaling pathway in breast cancer.

Impact of fixed dental prosthesis on neuroimaging: assessment of artefacts.

Objectives: To determine the frequency and extent of artefacts in magnetic resonance imaging and/or computed tomography scans of head caused by fixed dental prosthesis. METHODS: The retrospective study was conducted at Aga Khan University Hospital from July to December 2021, and comprised magnetic resonance imaging and/or computed tomography scans from January 2015 to December 2020 of the head of individuals with existing fixed dental prosthetic work at the time of exposure. They were analysed for the presence of artefacts. The association between artefacts and the presence of fixed dental prosthesis was explored. Data was analysed using SPSS 23. RESULTS: Of the 297 images evaluated, 173 (58%) were magnetic resonance imaging scans, and 124(42%) were computed tomography scans. The most common artefacts was grade I 148(49.8%), followed by grade II 140(47.1%) and grade III 9(3%). There was no significant association between fixed dental prosthesis and the artefacts (p>0.05). Conclusion: There should be no reservations in placing fixed metal prosthesis in individuals on account of future brain scans.

In silico assessment of a natural small molecule as an inhibitor of programmed death ligand 1 for cancer immunotherapy: a computational approach.

Programmed cell death ligand 1 (PD-L1) is a crucial target for cancer therapy. Here, an in silico study investigates PD-L1 to inhibit its interaction with PD1, thereby promoting an immune response to eliminate cancer cells. The study employed machine learning (ML) -based QSAR to detect PDL1 inhibitors. Morgan's fingerprint with docking score showed a 0.83 correlation with the experimental IC50, enabling the screening of 3200 natural compounds. The top three compounds, considered 2819, 2821 and 3188, were selected from the ML-based QSAR and subjected to molecular docking and simulation. The binding scores for 2819, 2821 and 3188 were -7.0, -9.0 and -8.9 kcal/mol, respectively. The stability of the ligands during a 100 ns simulation was assessed using RMSD, showing that 2819 and 2821 maintained stable patterns comparable to the control inhibitor. Notably, 2819 exhibited a consistent stable pattern throughout the simulation, while 2821 showed stability in the last 40 ns. The control compound showed the highest number of hydrogen bonds with proteins, whereas compounds 2819 and 2821 formed continuous H-bonds. 3188 was separated from the protein in later phases and is not regarded as a potential PD-L1-binding molecule. MMGBSA binding free energy for complexes was computed. Control had the lowest binding free energy, while 2819 and 2821 also had lower binding energies. In contrast, 3188 showed poor binding free energy, causing protein separation. Principal component analysis showed a loss of entropy and reduced protein conformational variation. Overall, 2819 and 2821 are potential binders for PD-L1 inhibition and immune response triggering.Communicated by Ramaswamy H. Sarma.

Does the sagittal root position of maxillary anterior teeth affect the decision making on immediate implants in the anterior maxilla? A CBCT-based study.

BACKGROUND: Immediate implant placement in the maxillary esthetic zone is a challenging and demanding task. To achieve favorable results, proper case selection and treatment planning are necessary. Variables like the sagittal root position (SRP) and the labial bone thickness (LBT) of maxillary anterior teeth are of paramount importance for predictable outcomes. OBJECTIVES: The aim of the present study was to evaluate the SRP and LBT of maxillary anterior teeth in the context of immediate implant placement by using cone-beam computed tomography (CBCT) in a sample of the Pakistani population. MATERIAL AND METHODS: A cross-sectional study was conducted using the CBCT scans of patients. The SRP of each tooth (maxillary canine to canine) was evaluated in the sagittal section of a CBCT scan according to the classification by Kan et al. The LBT of each tooth was measured perpendicularly to the long axis of tooth at 3 sites: at the alveolar crest (P1); 2 mm from the alveolar crest (P2); and 4 mm from the alveolar crest (P3). Descriptive statistics were reported for SRP and LBT. The χ2 test was employed to assess any association between the variables. RESULTS: Class I SRP was the most prevalent (n = 196, 81.7%), while Class III was the least frequent (n = 1, 0.4%). The association between the tooth type and SRP was statistically non-significant (p = 0.510). CONCLUSIONS: In the evaluated sample of the Pakistani population, the most frequent type of the SRP of maxillary anterior teeth was Class I, which is most favorable for immediate implant placement. Furthermore, the labial bone in the maxillary esthetic zone was found to be mostly thin - LBT was within the range of 0.5-0.9 mm - which makes immediate implant placement in the anterior maxilla a challenge. The results of the present study could serve as a guide for clinicians in terms of appropriate patient selection for immediate implant placement in the maxillary esthetic zone.