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Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke; however, effective therapies are still lacking. Perfluorocarbons (PFCs) are lipid emulsion particles with great flexibility and their much smaller size as compared to red blood cells (RBCs) allows them to flow more efficiently within the blood circulation. Due to their ability to carry oxygen, a specific PFC-based emulsion, PFC-Oxygent, has been used as a blood substitute; however, its role in cerebral blood flow regulation is unknown. Adult C57BL/6 wildtype male mice were subjected to an endovascular perforation model of SAH followed by an intravenous (i.v.) injection of 9 ml/kg PFC-Oxygent or no treatment at 5 h after SAH. At 48 h after SAH, functional and anatomical outcomes were assessed. We found that SAH resulted in significant neurologic and motor deficits which were prevented by PFC-Oxygent treatment. We found that SAH-induced vasospasm, reduced RBC deformability, and augmented endothelial dysfunction were also restricted by PFC-Oxygent treatment. Moreover, mitochondrial activity and fusion proteins were also markedly decreased as assessed by oxidative phosphorylation (OXPHOS) after SAH. Interestingly, PFC-Oxygent treatment brought the mitochondrial activity close to the basal level. Moreover, SAH attenuated the level of phosphorylated AMP-activated protein kinase (pAMPK), whereas PFC treatment improved pAMPK levels. These data show the beneficial effects of PFC-Oxygent in limiting the severity of SAH. Further studies are needed to fully understand the mechanism through which PFC-Oxygent exerts its beneficial effects in limiting SAH severity., (© 2024. The Author(s).)

Background: Although US research agencies have instituted peer review processes to require participant diversity in clinical trials before funding decisions are made, the underrepresentation of certain populations (eg, racial and ethnic minorities) in clinical trials remains a persistent challenge in biomedical research. This issue has the potential to affect the generalizability of findings and impede efforts to ensure the provision of high-quality healthcare across all populations. In this study, we examined barriers to the recruitment and retention of underrepresented populations in cancer clinical trials from the perspective of research coordinating staff., Methods: Semi-structured interviews were conducted at a US-based academic cancer center and included 6 patient-facing staff (clinical research coordinators) and 6 non-patient-facing staff (regulatory and financial specialists). Interview data were subjected to thematic analysis. To provide additional organizational context, descriptive data were obtained on the characteristics of clinical trials undertaken at the cancer center., Results: The following themes emerged from the staff interviews: 1) absence of a consistent structure for decision-making and problem-solving related to recruitment and retention, 2) staff shortages, 3) administrative burden, and 4) lack of resources. In addition, descriptive data revealed that nearly half the trials, 64/134 (48%), offered informed consent only in English, and only 3/134 (2%) offered participant incentives or reimbursement (eg, for transportation). These interrelated organizational issues were indicative of inadequate systems for ensuring diverse and equitable representation in cancer clinical trials., Conclusion: Results indicate that overcoming barriers to underrepresentation may require dedicated support from sponsoring agencies in the form of evidence-based guidelines, learning collaboratives to facilitate implementation, technical support, resources, and oversight. For progress to be made therefore, both sponsors and cancer centers may need to assume joint responsibility for the implementation of effective systems for ensuring diverse and equitable representation in cancer clinical trials., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yousafi et al.)

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: The use of therapeutic plasma exchange (TPE) for treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) remains controversial in the literature. This study compared the clinical outcomes of TPE versus conventional therapy in patients with HTGP., Methods: Fifty-five patients with HTGP were included. Patients were retrospectively compared in pairs: those who received TPE treatment and those who did not, those whose triglyceride level fell below 500 mg/dL within 48 h, and those who did not, those with and without persistent organ failure. The primary outcome was the percentage of triglyceride reduction within 48 h. Secondary outcomes were the length of hospital stay, mortality, cost-effectiveness, and persistent organ failure., Results: Percentage decrease in triglyceride levels, medical hospitalization costs, and length of hospital stay were higher in the TPE group compared to the non-TPE group (p < 0.05, for each). However, there was no difference regarding persistent organ failure and mortality (p > 0.05, for each). The length of hospital stay, average cost, persistent organ failure, and mortality were similar in both groups whose triglyceride level fell below 500 mg/dL within 48 h and those who did not (p > 0.05, for each). Among patients with persistent organ failure, average cost was higher in the TPE group compared to the non-TPE group (p < 0.05). An independent relation was found between the average cost and persistent organ failure, TPE, length of hospital stay, albumin, and urea values in all patients (p < 0.05, for each)., Conclusions: The approach of using TPE for treatment of HTGP was not found to be superior to the conventional treatment. Randomized controlled studies with larger number of patients are needed to gain better understanding of this issue., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders., (© 2024 Wiley Periodicals LLC.)

Physical activity or structured exercise is beneficial in a wide range of circumstances. Nevertheless, individual-level data on differential responses to various types of activity are not yet sufficient in scale, duration or level of annotation to understand the mechanisms of discrete outcomes nor to support personalized recommendations. The Apple Heart & Movement Study was designed to passively collect the dense physiologic data accessible on Apple Watch and iPhone from a large real-world cohort distributed across the US in order to address these knowledge gaps., (© 2024. The Author(s).)

This present study reports the biogenic synthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and Ag/Au bimetallic nanoparticles (BNPs) using bark extract of plant Tamarix aphylla (T.A). The bark extract contained total polyphenolic compounds and total flavonoids as 0.0362 mg/mg and 0.2928 mg/mg of the dried bark extract respectively. Silver nitrate (AgNO 3 ) and hydrogen tetra chloroaurate trihydrate (HAuCl 4 .3H 2 O) were used as precursors while deionised water and methanol (CH 3 OH) were used as solvents. Synthesized nanoparticles were characterized through UV-visible spectroscopy, SEM (scanning electron microscopy), TEM (transmission electron microscopy) and FTIR (Fourier transform infrared) for their morphology, structure, and identification of different functional groups. The UV-visible spectra of AgNPs, AuNPs and Ag/Au BNPs showed peaks at 436, 532 and 527 nm respectively due to the excitation of Surface Plasmon Resonance. SEM and TEM images showed spherical and well distributed nanoparticles (NPs) with particle size as 29 nm (AgNPs), 13 nm (AuNPs) and 26 nm (Ag/Au BNPs). The synthesized NPs are significantly active against inhibition of free radicals, α-amylase, α-glucosidase and have anti inflammatory potential with AgNPs having the highest percent activity at 400 μg/ml, followed by Ag/Au BNPs. The same trend (AgNPs > Ag/AuBNPs > AuNPs) has been observed at all concentrations i.e. 100 μg/ml, 200 μg/ml and 400 μg/ml. AuNPs have shown lowest activity at all concentrations. So the current study strongly confirms use of T.A bark extract as reducing agent for synthesis of metal NPs and opens up a new possibility of using these green synthesized NPs as biomedicines. We also suggest further in vivo investigation to report any side effects if present., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objective: To evaluate the effectiveness and analyse the influence of YouTube as a learning modality for clinical procedures among medical and dental students in a public-sector setting., Methods: The cross-sectional study was conducted at the medical and dental constituent institutes of Jinnah Sindh Medical University and Jinnah Postgraduate Medical Centre between August and October 2023, and comprised undergraduate, graduate, and postgraduate students of either gender aged 18-40 years. Data was collected using a self-administered, structured, closed-ended 16-item questionnaire, which was developed in the English language and explored the usage of YouTube as a source of information about medical and dental clinical procedures. Data was coded and analysed using SPSS 26., Results: Of the 314 participants, 153(48.7%) were medical students and 161(51.3%) were from the dental stream, 175(55.7%) were females, and 139(44.3%) were males. YouTube was a helpful tool for 143(45.5%) students who used it when needed, 172(54.8%) used it occasionally before attempting procedures, while majority of the dental students 140(44.6%) used it to study for prosthodontics. There were 154(49%) students who supported the idea that faculty should recommend watching relevant videos on YouTube, while 256(81.5%) preferred other websites., Conclusion: YouTube was mostly used for learning clinical procedures by the students.

Hypertension-induced brain renin-angiotensin system (RAS) activation and neuroinflammation are hallmark neuropathological features of neurodegenerative diseases. Previous studies from our lab have shown that inhibition of ACE/Ang II/AT1R axis (by AT1R blockers or ACE inhibitors) reduced neuroinflammation and accompanied neurodegeneration via up-regulating adult hippocampal neurogenesis. Apart from this conventional axis, another axis of RAS also exists i.e., ACE2/Ang (1-7)/MasR axis, reported as an anti-hypertensive and anti-inflammatory. However, the role of this axis has not been explored in hypertension-induced glial activation and hippocampal neurogenesis in rat models of hypertension. Hence, in the present study, we examined the effect of ACE2 activator, Diminazene aceturate (DIZE) at 2 different doses of 10 mg/kg (non-antihypertensive) and 15 mg/kg (antihypertensive dose) in renovascular hypertensive rats to explore whether their effect on glial activation, neuroinflammation, and neurogenesis is either influenced by blood-pressure. The results of our study revealed that hypertension induced significant glial activation (astrocyte and microglial), neuroinflammation, and impaired hippocampal neurogenesis. However, ACE2 activation by DIZE, even at the low dose prevented these hypertension-induced changes in the brain. Mechanistically, ACE2 activation inhibited Ang II levels, TRAF6-NFκB mediated inflammatory signaling, NOX4-mediated ROS generation, and mitochondrial dysfunction by upregulating ACE2/Ang (1-7)/MasR signaling. Moreover, DIZE-induced activation of the ACE2/Ang (1-7)/MasR axis upregulated Wnt/β-catenin signaling, promoting hippocampal neurogenesis during the hypertensive state. Therefore, our study demonstrates that ACE2 activation can effectively prevent glial activation and enhance hippocampal neurogenesis in hypertensive conditions, regardless of its blood pressure-lowering effects., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study demonstrated the synthesis of Fe 2 MnO 4 modified by citric acid, a biodegradable acid, using a simple co-precipitation method. Characterization was performed using qualitative analysis techniques such as Fourier-transformed infrared spectroscopy, scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy, X-ray diffraction, selected-area electron diffraction, N 2 adsorption-desorption, and zero-point charge. The prepared nanoparticles had a rough and porous surface, and contained oxygenous (-OH, -COOH, etc.) functional groups. The specific surface area and average pore size distribution were 83 m 2 /g and 5.17 nm, respectively. Net zero charge on the surface of the prepared nanoparticles was observed at pH 7.5. The prepared nanoparticles were used as an adsorbent to remove methylene blue dye from water under various conditions. Using small amounts of the adsorbent (2.0 g/L), even a high concentration of MB dye (60 mg/L) could be reduced by about ~58%. Exothermic, spontaneous, feasible, and monolayer adsorption was identified based on thermodynamics and isotherm analysis. Reusability testing verified the stability of the adsorbent and found that the reused adsorbent performed well for up to three thermal cycles. Comparative analysis revealed that the modified adsorbent outperformed previously reported adsorbents and unmodified Fe 2 MnO 4 in terms of its partition coefficient and equilibrium adsorption capacity under different experimental conditions.

This study developed a novel molecularly imprinted polymer (MIP) that is both conductive and redox-active for directly quantifying perfluorooctanoic acid (PFOA) electrochemically. We synthesized the monomer 3,4-ethylenedioxythiophene-2,2,6,6-tetramethylpiperidinyloxy (EDOT-TEMPO) for electropolymerization on a glassy carbon electrode using PFOA as a template, which was abbreviated as PEDOT-TEMPO-MIP. The redox-active MIP eliminated the need for external redox probes. When exposed to PFOA, both anodic and cathodic peaks of MIP showed a decreased current density. This observation can be explained by the formation of a charge-assisted hydrogen bond between the anionic PFOA and MIP's redox-active moieties (TEMPO) that hinder the conversion between the oxidized and reduced forms of TEMPO. The extent of the current density decrease showed excellent linearity with PFOA concentrations, with a method detection limit of 0.28 ng·L -1 . PEDOT-TEMPO-MIP also exhibited high selectivity toward PFOA against other per- and polyfluoroalkyl substances (PFAS) at environmentally relevant concentrations. Our results suggest electropolymerization of MIPs was highly reproducible, with a relative standard deviation of 5.1% among three separate MIP electrodes. PEDOT-TEMPO-MIP can also be repeatedly used with good stability and reproducibility for PFOA detection. This study provides an innovative platform for rapid PFAS quantification using redox-active MIPs, laying the groundwork for developing compact PFAS sensors., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Changes in the distribution of species due to global climate change have a critically significant impact on the increase in the spread of invasive species. An in-depth study of the distribution patterns of invasive species and the factors influencing them can help to better predict and combat invasive alien species. Rhynchophorus ferrugineus Olivier is an invasive species that primarily harms plants of Trachycarpus H. Wendl. The pest invades trees in three main ways: by laying eggs and incubating them in the crown of the plant, on roots at the surface and at the base of the trunk or petiole. Most of the plants in the genus Trachycarpus are taller, and the damage is concentrated in the middle and upper parts of the plant, making control more difficult. In this paper, we combine 19 bioclimatic variables based on the MaxEnt model to project the current and future distributions of R. ferrugineus under three typical emission scenarios (2.6 W m -2 (SSP1-2.6), 4.5 W m -2 (SSP2-4.5) and 8.5 W m -2 (SSP5-8.5)) in the 2050s and 2090s. Among the 19 bioclimatic variables, five variables were screened out by contribution rates, namely annual mean temperature (BIO 1), precipitation of driest quarter (BIO 17), minimum temperature of coldest month (BIO 6), mean diurnal range (BIO 2) and precipitation of wettest quarter (BIO 16). These five variables are key environmental variables that influence habitat suitability for R. ferrugineus and are representative in reflecting its potential habitat. The results showed that R. ferrugineus is now widely distributed in the southeastern coastal area of China (high suitability zone), concentrating in the provinces of Hainan, Guangdong, Fujian, Guangxi and Taiwan. In the future, the area of high and low suitability zones will increase and the area of medium suitability zones will decrease. The area of low suitability zone will still be in the largest proportion. This study aims to provide a theoretical reference for the future control of R. ferrugineus from the perspective of geographic distribution.

To this day, there exists skepticism about the reliability and clinical utility of the diagnostic criteria and classification of schizoaffective disorder. In addition, the treatment of schizoaffective disorder, especially of treatment-resistant cases, has been minimally investigated. As a result, formulating official treatment guidelines for schizoaffective disorder has been challenging. We present a case of a 27-year-old female, diagnosed with schizoaffective disorder, bipolar type, for whom, for over 5 years, trials of traditional treatments, to include psychotherapy, pharmacotherapy, and electroconvulsive therapy, were either partially effective or discontinued due to intolerable side effects. The subsequent off-label use of lumateperone led to an adequate response. Lumateperone is an atypical antipsychotic, approved by the Food and Drug Administration for schizophrenia and bipolar depression in adults. Interestingly, it has a similar structure and mechanism of action to paliperidone, the only Food and Drug Administration-approved medication for schizoaffective disorder. Through this case report, as an example of lumateperone's effectiveness and tolerability, as well as a literature review of its pharmacodynamics, we make the case that lumateperone emerges as a promising option for schizoaffective disorder, especially treatment-resistant cases., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Excessive number of dyes in water is becoming the main cause of water pollution, which is very important to remove because it is harmful. Dye contaminated water is being treated by various methods. Adsorption method can be considered best for the study of dye removal due to several technological reasons. The adsorption method has also been emphasized in this study. In the present work, a nano-bio-composite was fabricated by growing manganese oxide nanoparticles on abundant cellulosic guava leaf powder. This allows nanocomposite to be prepared in large quantities at nominal cost. The characterization technique confirmed the irregular growth of manganese oxide nanoparticles onto the guava leaf powder. The electrostatic and non-electrostatic interactions was confirmed in between manganese oxide nanoparticles and the carbon structure of guava leaf powder. The massive functional groups were found to be in the prepared nano-bio-composite. The grain size of prepared material was in nano range. The developed nano-bio-composite was used to remove methylene blue from water. This showed a very good adsorptive capacity for methylene blue. The analyzed adsorption data was modelled through isotherms, kinetics and thermodynamics models. The nature of the adsorption process was determined to be spontaneous and exothermic. The reusability test was carried out for five adsorption-desorption cycles. The reusability results suggested the better removal efficiency (%) in the first two cycles with only 20 % reduction in removal efficiency (%). The leaching test result revealed the good stability of MnO 2 /GL at neutral pH. It was a unique and cheap adsorbent of its kind, which had not been noticed anywhere before., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Enteropathogenic E. coli (EPEC) causes acute infantile diarrhea accounting for significant morbidity and mortality in developing countries. EPEC uses a type three secretion system to translocate more than twenty effectors into the host intestinal cells. At least four of these effectors, namely EspF, Map, EspG1/G2 and NleA, are reported to disrupt the intestinal tight junction barrier. We have reported earlier that the expression of EspF and Map in MDCK cells causes the depletion of the TJ membrane proteins and compromises the integrity of the intestinal barrier. In the present study, we have examined the role of the proline-rich repeats (PRRs) within the C-terminus of EspF in the depletion of the tight junction membrane proteins and identified key endocytosis markers that interact with EspF via these repeats., Results: We generated mutant EspF proteins which lacked one or more proline-rich repeats (PRRs) from the N-terminus of EspF and examined the effect of their expression on the cellular localization of tight junction membrane proteins. In lysates derived from cells expressing the mutant EspF proteins, we found that the C-terminal PRRs of EspF are sufficient to cause the depletion of TJ membrane proteins. Pull-down assays revealed that the PRRs mediate interactions with the TJ adaptor proteins ZO-1 and ZO-2 as well as with the proteins involved in endocytosis such as caveolin-1, Rab5A and Rab11., Conclusions: Our study demonstrates the direct role of the proline-rich repeats of EspF in the depletion of the TJ membrane proteins and a possible involvement of the PRRs in the endocytosis of host proteins. New therapeutic strategies can target these PRR domains to prevent intestinal barrier dysfunction in EPEC infections., (© 2024. The Author(s).)

The scientific community has been drawn towards natural plant resources due to the rising success rates. This work aimed to explore the phytochemical, antioxidant and anti-cancer properties of an ethanolic extract derived from the leaves of Buxus wallichiana Baill. which is utilized in traditional medicine in the treatment of various disease such as respiratory disorders, GI disorders and inflammation. Chemical composition of the ethanolic extract of BW leaves was evaluated by using Gas chromatography-mass spectrometry and phytochemical analysis. Moreover, anti-oxidant and anticancer activity was carried out through 2,2-diphenyl-1-picryl hydrazyl scavenging activity method and 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay against human glioblastoma cell line. ANOVA test was used to analyze the results followed by Bonferoni's post hoc. Results were significant at P <0.05 and demonstrated that, blocking the production of free radicals also caused tumor cell proliferation on the U 87 MG. Thus, the results show the same pattern of toxicity as indicated by the American National Cancer Institute. The minimum dose for cytotoxic activity of the crude extract was less than 30μg/mL. BW leave extract is considered to have promising anticancer potential as well as antioxidant due to the presence of potent compounds and could become a source of treatment with minimum side effects.

Background: Asprosin is an emerging biomarker that plays a role in metabolic diseases. This study investigates asprosin as a predictive marker for coronary artery disease (CAD) severity in diabetic patients., Methods: Diabetic patients (n = 181) and healthy controls (n = 60) were analyzed. CAD severity was assessed using SYNTAX score. Diabetic patients were divided into 3 groups. Group 1 = patients without CAD, group 2 = patients with low SYNTAX score, and group 3 = patients with moderate-high SYNTAX score. Asprosin levels were measured for all participants using an enzyme-linked immunosorbent assay (ELISA)., Results: Asprosin levels were significantly higher in patient group compared to control group (p < 0.001). Asprosin levels were significantly higher in group 3 compared to group 1 and group 2 (p = 0.002). In logistic regression analysis, asprosin levels independently predicted patients with moderate-high SYNTAX scores. According to this analysis, 1 ng/mL increase in asprosin level was found to increase the risk of having moderate-high SYNTAX score by 14.1%. When the threshold value of asprosin level was set as 22.17 ng/mL, it predicted patients with moderate-high SYNTAX score with 63.6% sensitivity and 62.6% specificity. In multivariate regression analysis, SYNTAX score independently correlated with asprosin level., Conclusion: This is the first study in the literature to demonstrate a positive correlation between asprosin levels and SYNTAX scores in diabetic patients with CAD. More comprehensive studies with larger groups are needed., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Thyroid cancer incidences endure to increase even though a large number of inspection tools have been developed recently. Since there is no standard and certain procedure to follow for the thyroid cancer diagnoses, clinicians require conducting various tests. This scrutiny process yields multi-dimensional big data and lack of a common approach leads to randomly distributed missing (sparse) data, which are both formidable challenges for the machine learning algorithms. This paper aims to develop an accurate and computationally efficient deep learning algorithm to diagnose the thyroid cancer. In this respect, randomly distributed missing data stemmed singularity in learning problems is treated and dimensionality reduction with inner and target similarity approaches are developed to select the most informative input datasets. In addition, size reduction with the hierarchical clustering algorithm is performed to eliminate the considerably similar data samples. Four machine learning algorithms are trained and also tested with the unseen data to validate their generalization and robustness abilities. The results yield 100% training and 83% testing preciseness for the unseen data. Computational time efficiencies of the algorithms are also examined under the equal conditions., (© The Author(s) 2024. Published by Oxford University Press.)

Aim: Although there exists substantial epidemiological evidence indicating an elevated risk of dementia in individuals with diabetes, our understanding of the neuropathological underpinnings of the association between Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) remains unclear. This study aims to unveil the microstructural brain changes associated with T2DM in AD and identify the clinical variables contributing to these changes., Methods: In this retrospective study involving 64 patients with AD, 31 individuals had concurrent T2DM. The study involved a comparative analysis of diffusion tensor imaging (DTI) images and clinical features between patients with and without T2DM. The FSL FMRIB software library was used for comprehensive preprocessing and tractography analysis of DTI data. After eddy current correction, the "bedpost" model was utilized to model diffusion parameters. Linear regression analysis with a stepwise method was used to predict the clinical variables that could lead to microstructural white matter changes., Results: We observed a significant impairment in the left superior longitudinal fasciculus (SLF) among patients with AD who also had T2DM. This impairment in patients with AD and T2DM was associated with an elevation in creatine levels., Conclusion: The white matter microstructure in the left SLF appears to be sensitive to the impairment of kidney function associated with T2DM in patients with AD. The emergence of AD in association with T2DM may be driven by mechanisms distinct from the typical AD pathology. Compromised renal function in AD could potentially contribute to impaired white matter integrity., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Cardiovascular diseases (CVDs) are known as life-threatening illnessescaused by severe abnormalities in the cardiovascular system. They are a leading cause of mortality and morbidity worldwide.Nanotechnology integrated substantialinnovations in cardiovascular diagnostic and therapeutic at the nanoscale. This in-depth analysis explores cutting-edge methods for diagnosing CVDs, including nanotechnological interventions and crucial components for identifying risk factors, developing treatment plans, and monitoring patients' progress with chronic CVDs.Intensive research has gone into making nano-carriers that can image and treat patients. To improve the efficiency of treating CVDs, the presentreview sheds light on a decision-tree-based solution by investigating recent and innovative approaches in CVD diagnosis by utilizing nanoparticles (NPs). Treatment choices for chronic diseases like CVD, whose etiology might take decades to manifest, are very condition-specific and disease-stage-based. Moreover, thisreview alsobenchmarks the changing landscape of employing NPs for targeted and better drug administration while examining the limitations of various NPs in CVD diagnosis, including cost, space, time, and complexity. To better understand and treatment of cardiovascular diseases, the conversation moves on to the nano-cardiovascular possibilities for medical research.We also focus on recent developments in nanoparticle applications, the ways they might be helpful, and the medical fields where they may find future use. Finally, this reviewadds to the continuing conversation on improved diagnosis and treatment approaches for cardiovascular disorders by discussing the obstacles and highlighting the revolutionary effects of nanotechnology., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests among them., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : Nigeria is among the top five countries that have the highest gap between people reported as diagnosed and estimated to have developed tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high risk of TB transmission and targeted active case finding (ACF) interventions. Leveraging community-level data together with granular sociodemographic contextual information can unmask local hotspots that could be otherwise missed. This work evaluated whether this approach helps to reach communities with higher numbers of undiagnosed TB. Methodology : A retrospective analysis of the data generated from an ACF intervention program in four southwestern states in Nigeria was conducted. Wards (the smallest administrative level in Nigeria) were further subdivided into smaller population clusters. ACF sites and their respective TB screening outputs were mapped to these population clusters. This data were then combined with open-source high-resolution contextual data to train a Bayesian inference model. The model predicted TB positivity rates on the community level (population cluster level), and these were visualised on a customised geoportal for use by the local teams to identify communities at high risk of TB transmission and plan ACF interventions. The TB positivity yield (proportion) observed at model-predicted hotspots was compared with the yield obtained at other sites identified based on aggregated notification data. Results : The yield in population clusters that were predicted to have high TB positivity rates by the model was at least 1.75 times higher ( p -value < 0.001) than the yield in other locations in all four states. Conclusions : The community-level Bayesian predictive model has the potential to guide ACF implementers to high-TB-positivity areas for finding undiagnosed TB in the communities, thus improving the efficiency of interventions.

The present study was undertaken on the chemical constituents of ethanol extract of aerial parts of Nyctanthes arbor-tristis Linn., and their determination of growth inhibitory activity against glioblastoma multiforme cell line (U87) and urease inhibitory activity. Six constituents were isolated including two new arbortristoside F tetraacetate ( 1 ) and arbortristoside G heptaacetate ( 2 ) and four known arborside A tetraacetate ( 3 ), arborside C pentaacetate ( 4 ), 6,7-di- O -acetyl-6 β -hydroxyloganin hexaacetate ( 5 ) and nyctanthoside heptaacetate ( 6 ) iridoid glycoside acetates. Their structures were elucidated using spectroscopic methods, including 1D and 2D NMR and mass analyses. Compounds 3 and 6 showed significant growth inhibition of U87 cell line (76.41 and 87.62% inhibition) respectively while 2 , 4 and 5 showed moderate inhibition. 3 and 6 showed notable urease inhibition (IC 50 = 17.2 ± 0.4 and 17.2 ± 0.7 µM) respectively, and IC 50 of 2 , 4 and 5 were 23.8 - 56.3 µM. Compound 1 was inactive.

Background and objectives: As microbes are developing resistance to antibiotics, natural, botanical drugs or traditional herbal medicine are presently being studied with an eye of great curiosity and hope. Hence, complementary and alternative treatments for uncomplicated pelvic inflammatory disease (uPID) are explored for their efficacy. Therefore, this study determined the therapeutic efficacy and safety of Sesamum indicum Linn seeds with Rosa damascena Mill Oil in uPID with standard control. Additionally, we analyzed the data with machine learning. Materials and methods: We included 60 participants in a double-blind, double-dummy, randomized standard-controlled study. Participants in the Sesame and Rose oil group (SR group) ( n = 30) received 14 days course of black sesame powder (5 gm) mixed with rose oil (10 mL) per vaginum at bedtime once daily plus placebo capsules orally. The standard group (SC), received doxycycline 100 mg twice and metronidazole 400 mg thrice orally plus placebo per vaginum for the same duration. The primary outcome was a clinical cure at post-intervention for visual analogue scale (VAS) for lower abdominal pain (LAP), and McCormack pain scale (McPS) for abdominal-pelvic tenderness. The secondary outcome included white blood cells (WBC) cells in the vaginal wet mount test, safety profile, and health-related quality of life assessed by SF-12. In addition, we used AdaBoost (AB), Naïve Bayes (NB), and Decision Tree (DT) classifiers in this study to analyze the experimental data. Results: The clinical cure for LAP and McPS in the SR vs SC group was 82.85% vs 81.48% and 83.85% vs 81.60% on Day 15 respectively. On Day 15, pus cells less than 10 in the SR vs SC group were 86.6% vs 76.6% respectively. No adverse effects were reported in both groups. The improvement in total SF-12 score on Day 30 for the SR vs SC group was 82.79% vs 80.04% respectively. In addition, our Naive Bayes classifier based on the leave-one-out model achieved the maximum accuracy (68.30%) for the classification of both groups of uPID. Conclusion: We concluded that the SR group is cost-effective, safer, and efficacious for curing uPID. Proposed alternative treatment (test drug) could be a substitute of standard drug used for Female genital tract infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sumbul, Sultana, Heyat, Rahman, Akhtar, Parveen, Urbano, Lipari, De la Torre Díez, Khan and Malik.)

Introduction: The mulberry industry has thrived in China for millennia, offering significant ecological and economic benefits. However, the prevalence of mulberry ring rot disease poses a serious threat to the quality and yield of mulberry leaves., Methods: In this study, we employed a combination of transcriptomic and metabolomic analyses to elucidate the changes occurring at the transcriptional and metabolic levels in Morus notabilis in response to this disease infestation. Key metabolites identified were further validated through in vitro inhibition experiments., Results: The findings revealed significant enrichment in Kyoto Encyclopedia of Genes and Genomes pathways, particularly those related to flavonoid biosynthesis. Notably, naringenin, kaempferol, and quercetin emerged as pivotal players in M. notabilis ' defense mechanism against this disease pathogen. The upregulation of synthase genes, including chalcone synthase, flavanone-3-hydroxylase, and flavonol synthase, suggested their crucial roles as structural genes in this process. In vitro inhibition experiments demonstrated that kaempferol and quercetin exhibited broad inhibitory properties, while salicylic acid and methyl jasmonate demonstrated efficient inhibitory effects., Discussion: This study underscores the significance of the flavonoid biosynthesis pathway in M. notabilis ' defense response against mulberry ring rot disease, offering a theoretical foundation for disease control measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qian, Deng, Mureed, Gan, Xu, Wang and Ali.)

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities., (© 2024. The Author(s).)

Background: A link between pronated feet (PF) and chronic low back pain (CLBP) has been reported in the literature. However, physical interventions (PI) like physiotherapy and orthotics mainly target the lower back, neglecting the broader biomechanical impacts of PF that affect the feet, ankles, and overall posture. Currently, there is a lack of comprehensive meta-analyses or systematic reviews on this subject., Objectives: This systematic review with a meta-analysis aimed to evaluate the effects of PI on pain and disability in patients having CLBP with PF., Methods: From inception until October 15, 2023, Medline/PubMed, Web of Science, and Scopus databases were searched using the desired keywords for randomized control trials (RCTs). The quality of the RCTs was evaluated using the PEDro scale and risk of bias tool., Results: Four studies involving 268 patients were identified, two compared custom-made foot orthoses to non-biomechanical foot insoles, while the other two used exercises. The meta-analysis included four studies for pain and three for disability. The results showed a significant change in pain [-2.43 (95% CI -2.73 to -2.13, p  < .001)] and disability of -6.69 (95% CI -8.04 to -5.33, p < .001)]., Conclusions: This systematic review and meta-analysis of four RCTs elucidates that PI, specifically targeting PF, significantly alleviate pain and reduce disability in patients having CLBP with PF. These findings advocate for integrating foot-based PI within the treatment protocols for patients suffering from CLBP accompanied by PF.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

Abstract: Transient elastography (TE) and point shear wave elastography (pSWE) are 2 elastographic ultrasound examinations used in liver stiffness (LS) measurement. It was shown that the LS value detected by TE in pediatric β-thalassemia major patients has increased, and there was no LS evaluation obtained with pSWE in literature. Thus, in this study, it was aimed to evaluate LS with pSWE examination in children with thalassemia major and to determine LS-related parameters in these patients. Sixty-three schoolchildren with a diagnosis of β-thalassemia major and 21 healthy controls between the ages of 7 and 18 years were included. In addition to routine anamnesis, physical examination, and laboratory examinations, renal and liver ultrasounds were performed. Liver stiffness values were measured by pSWE examination. Serum levels of urea, aspartate-aminotransferase, alanine-aminotransferase, iron, and ferritin were significantly higher in patients, and serum creatinine, iron binding capacity, and hemoglobin levels were found to be significantly lower (P < 0.05 for each). Liver stiffness values were significantly higher in patients compared with healthy controls. In linear regression analysis, serum iron and iron binding capacity values were found to be closely related with LS (P < 0.001 vs. β = 0.482 and P = 0.047 vs. β = 0.237, respectively). Liver stiffness values obtained by pSWE examination increase significantly in patients. According to the results of our study, in addition to the previously known TE method, we think that the LS evaluation obtained by pSWE, a new method that can make more accurate measurements, can be used in the possible early detection of target organ damage in children with thalassemia major., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Carpal tunnel syndrome (CTS) is the most common type of entrapment neuropathy caused by compression of the median nerve in the carpal tunnel. Epilepsy is characterised by recurrent seizures caused by abnormal neuronal discharges in the brain.This study aimed to investigate whether there is a link between epilepsy and carpal tunnel and, if so, the underlying factors., Materials and Methods: Two hundred patients with epilepsy were included in this study. The patients' history of epilepsy, seizure type, and seizure frequency were assessed. The Tinel, Phalen, and Flick physical examination tests were performed on patients with complaints that matched those of median nerve neuropathy. Patients with epilepsy and clinically diagnosed carpal tunnel syndrome completed the Boston Carpal Tunnel Syndrome Questionnaire, and nerve conduction studies were performed. The relationship between seizure type and frequency in patients with carpal tunnel syndrome was compared., Results: Compared to focal-aware motor-onset seizures, the risk of detecting carpal tunnel syndrome was 88.7 times higher in focal-onset bilateral tonic-clonic seizures. Patients with a seizure frequency of one per month or more had a 0.704 times lower risk of CTS than those with a frequency of one per week or more (p = 0.026)., Discussion: Patients with epilepsy, especially those experiencing frequent seizures or specific seizure types, may be more susceptible to repetitive wrist flexion-extension postures. Therefore, during clinical follow-up, it is important to inquire about the presence of carpal tunnel syndrome in patients with epilepsy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

It is now widely accepted that inflammation is critical in cardiovascular diseases (CVD). Here, studies are being conducted on how cyclic GMP-AMP synthase (cGAS), a component of innate immunity's DNA-sensing machinery, communicates with the STING receptor, which is involved in activating the immune system's antiviral response. Significantly, a growing body of research in recent years highlights the strong activation of the cGAS-STING signalling pathways in several cardiovascular diseases, such as myocardial infarction, heart failure, and myocarditis. This developing collection of research emphasises these pathways' crucial role in initiating and advancing cardiovascular disease. In this extensive narrative, we explore the role of the cGAS-STING pathway in the development of CVD. We elaborate on the basic mechanisms involved in the onset and progression of CVD. This review explores the most recent developments in the recognition and characterization of cGAS-STING pathway. Additionally, it considers the field's future prospects while examining how cGAS-STING pathway might be altered and its clinical applications for cardiovascular diseases., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: High levels of insulin-like growth factor 1 (IGF-1) in patients with acromegaly cause structural and functional changes specific to the disease. These changes lead to mortality if the disease is not treated. Circadian blood pressure (BP) rhythm as measured by 24-h ambulatory blood pressure monitoring (ABPM) can change with a decrease in BP during sleep and a sudden increase in wakefulness., Aim: We aim to evaluate the relationship between changes in BP and IGF-1 levels in patients with acromegaly., Methods: Patients who were diagnosed with acromegaly and the patient group with hypertension were included. Serum biochemistry parameters, serum IGF-1 level and ABPM follow-ups were compared in these patients., Results: In our study, 30 patients with acromegaly and 30 patients with hypertension without acromegaly were included. Thirty of the patients were male and 30 were female. There was a statistically significant difference between the groups in terms of IGF-1(p = < 0.001) and GH(p = 0.004). There was no significant difference between patients' office systolic/diastolic BP measurements, day/night, systolic/diastolic BP measurements and all systolic/diastolic BP measurements in ambulatory blood pressure follow-ups. There was a significant difference in morning blood pressure surge(p = < 0.001). A statistically significant difference was found between the acromegaly patient groups with MBPS below and above 25 mmHg in terms of IGF-1 (p = 0.025) and platelet levels (p = 0.004)., Conclusion: As a result, cardiovascular disease risks can be predicted in patients with high serum IGF-1 levels by planning ambulatory blood pressure in the early period., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Cardiovascular disease is the leading cause of death, medical complications, and healthcare costs. Although recent advances have been in treating cardiovascular disorders linked with a reduced ejection fraction, acutely decompensate cardiac failure remains a significant medical problem. The transient receptor potential cation channel (TRPC6) family responds to neurohormonal and mechanical stress, playing critical roles in cardiovascular diseases. Therefore, TRP C6 channels have great promise as therapeutic targets. Numerous studies have investigated the roles of TRP C6 channels in pain neurons, highlighting their significance in cardiovascular research. The TRPC6 protein exhibits a broad distribution in various organs and tissues, including the brain, nerves, heart, blood vessels, lungs, kidneys, gastrointestinal tract, and other bodily structures. Its activation can be triggered by alterations in osmotic pressure, mechanical stimulation, and diacylglycerol. Consequently, TRPC6 plays a significant role in the pathophysiological mechanisms underlying diverse diseases within living organisms. A recent study has indicated a strong correlation between the disorder known as TRPC6 and the development of cardiovascular diseases. Consequently, investigations into the association between TRPC6 and cardiovascular diseases have gained significant attention in the scientific community. This review explores the most recent developments in the recognition and characterization of TRPC6. Additionally, it considers the field's prospects while examining how TRPC6 might be altered and its clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is a leading cause of death worldwide. In recent years, 3D printing technology has ushered in a new era of innovation in cardiovascular medicine. 3D printing in CVD management encompasses various aspects, from patient-specific models and preoperative planning to customized medical devices and novel therapeutic approaches. In-stent technology, 3D printing has revolutionized the design and fabrication of intravascular stents, offering tailored solutions for complex anatomies and individualized patient needs. The advantages of 3D-printed stents, such as improved biocompatibility, enhanced mechanical properties, and reduced risk of in-stent restenosis. Moreover, the clinical trials and case studies that shed light on the potential of 3D printing technology to improve patient outcomes and revolutionize the field has been comprehensively discussed. Furthermore, regulatory considerations, and challenges in implementing 3D-printed stents in clinical practice are also addressed, underscoring the need for standardization and quality assurance to ensure patient safety and device reliability. This review highlights a comprehensive resource for clinicians, researchers, and policymakers seeking to harness the full potential of 3D printing technology in the fight against CVD., Competing Interests: Declaration of Competing Interest The author declared that they have no competing of interest among them., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prosthetic joint infection (PJI) is a complication of arthroplasty that results in significant morbidity. The presence of biofilm makes treatment difficult, and removal of the prosthesis is frequently required. We have developed a non-invasive approach for biofilm eradication from metal implants using intermittent alternating magnetic fields (iAMF) to generate targeted heating at the implant surface. The goal of this study was to determine whether iAMF demonstrated efficacy in an in vivo implant biofilm infection model. iAMF combined with antibiotics led to enhanced reduction of biofilm on metallic implants in vivo compared to antibiotics or untreated control. iAMF-antibiotic combinations resulted in a > 1 - log further reduction in biofilm burden compared to antibiotics or iAMF alone. This combination effect was seen in both S. aureus and P. aeruginosa and seen with multiple antibiotics used to treat infections with these pathogens. In addition, efficacy was temperature dependent with increasing temperatures resulting in a greater reduction of biofilm. Tissue damage was limited (< 1 mm from implant-tissue interface). This non-invasive approach to eradicating biofilm could serve as a new paradigm in treating PJI., (© 2023. The Author(s).)

Cardiovascular diseases (CVDs) encompass a range of disorders, from congenital heart malformation, cardiac valve, peripheral artery, coronary artery, cardiac muscle diseases, and arrhythmias, ultimately leading to heart failure. Despite therapeutic advancements, CVDs remain the primary cause of global mortality, highlighting the need for a thorough knowledge of CVDs at the level of molecular structure. Gene and microRNA (miRNA) expression variations significantly influence cellular pathways, impacting an organism's physiology. MiRNAs, in particular, serve as regulators of gene expression, playing critical roles in essential cellular pathways and influencing the development of various diseases, including CVD. A wealth of evidence supports the involvement of miRNAs in CVD progression. These findings highlight the potential of miRNAs as valuable diagnostic biomarkers and open new avenues for their therapeutic application in CVDs. This study focuses on the latest advancements in identifying and characterizing microRNAs, exploring their manipulation and clinical application, and discussing future perspectives., Competing Interests: Declaration of Competing Interest The author declared that they have no competing of interest among them., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Given the lingering threat of COVID infection, questions are being raised if coronavirus disease 2019 (COVID-19) vaccine needs annual or regular boosters to maintain high levels of immunity against both the original virus and variants. This study was designed to evaluate the knowledge, acceptance, motivators and barriers of the booster dose of COVID-19 vaccine among the dental patients of District Lucknow, India. A total of 297 respondents were selected by a convenience sampling method in this cross-sectional study from various dental clinics. An anonymous, self-administered, closed-ended questionnaire was used. Overall 37.7% respondents reported to have taken all 3 doses and 57.9% had taken single/double doses. Correct information about booster doses shows a significant association with the number of doses taken. The majority had information about the availability of the Pfizer booster vaccine (69.0%). About 58% of participants had information about the technology used in booster doses. The hesitancy for booster doses and the development of natural immunity by infection show significant associations with the number of doses taken. Only 18.2% patients had hesitation about the booster dose and most of them 78.8% recommended others to take the booster vaccine as soon as possible. The majority assumed that previous COVID-19 vaccines can help them get immune (21.5%) followed by not much research has been done on the booster vaccines (15.5%) and their chronic diseases warn them against the booster dose administration (12.5%). Nearly 18.2% of respondents had hesitation about booster dose and less than one third of the respondents trusted a government source for information about booster dose of COVID vaccine. Nearly 36 % did not know that the booster dose of COVID vaccine is available at health centers. Dental health professionals and policymakers should implement and support strategies to ensure people are vaccinated for COVID-19 booster doses., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer, a serious fatal disease caused by the uncontrolled growth of cells, is the biggest challenge flagging around medicine and health fields. Conventionally, various treatments-based strategies such as radiotherapy, chemotherapy, and alternative cancer therapies possess drugs that cannot reach the cancerous tissues and make them toxic to noncancerous cells. Cancer immunotherapy has made outstanding achievements in reducing the chances of cancer. Our considerable attention towards cancer-directed immune responses and the mechanisms behind which immune cells kill cancer cells have progressively been helpful in the advancement of new therapies. Among them, bacteria-based cancer immunotherapy has achieved much more attention due to smart and robust mechanisms in activating the host anti-tumor response. Moreover, bacterial-based therapy can be utilized as a single monotherapy or in combination with multiple anticancer immunotherapies to accelerate productive clinical results. Herein, we comprehensively reviewed recent advancements, challenges, and future perspectives in developing bacterial-based cancer immunotherapies., Competing Interests: Declaration of Competing Interest The author declared that they have no competing interests among them., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Research on the relationship between the gut microbiome and epilepsy is accumulating. The present study was conducted to evaluate the effect of probiotic supplementation on pentylenetetrazole (PTZ)-induced seizures in rats., Methods: Twenty-one adult male Wistar albino rats were included. The animals were divided into three groups of seven rats. Group 1 was a control group, whereas Group 2 rats received PTZ treatment and Group 3 rats had PTZ+PB (probiotic) treatment. For 6 weeks, Groups 1 and 2 were given saline (1 ml), whereas Group 3 had probiotic supplement. In the 5th week, tripolar electrodes were attached to the rats. Electrophysiological, behavioral, biochemical, and immunohistochemical evaluations were performed in the 6 weeks after the treatment., Results: PB treatment significantly reduced seizures. In the PTZ group, expression levels of brain-derived neurotrophic factor, nerve growth factor (NGF), and Sox2 (SRY sex-determining region Y-box 2) in rat brains decreased significantly compared to the control group, whereas the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), and nitric oxide (NO) levels increased. In the PTZ+PB group, NGF expression increased significantly compared to the PTZ group, whereas TNF-α, IL-6, TOS, and NO levels decreased. In histopathological examination, an abundance of necrotic neurons was notable in the PTZ group, which was less in the PTZ+PB group. In addition, body weight of the group supplemented with probiotics decreased after the treatment., Conclusions: Our results suggest that probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains., (© 2022 European Academy of Neurology.)

Bisphenol-A (BPA) is a toxic chemical largely produced and used in polycarbonate plastics worldwide. Majoon Suranjan ( MS ), a polyherbal formulation, is used as an anti-inflammatory medicine against rheumatoid arthritis. The present study aimed to evaluate BPA-induced toxicity and its possible amelioration by MS . To test our hypothesis, we performed gas chromatography-mass spectrometry (GC-MS) analysis, DNA interaction studies, genotoxicity tests, oxidative stress parameters, and histopathological examinations. GC-MS profiling of MS revealed the presence of various anti-oxidant compounds. DNA interaction studies showed that both chemicals intercalate between DNA base pairs. Next, we observed BPA-induced genotoxicity and oxidative damage. The observed effects might be due to BPA-induced reactive oxygen species production. Further, BPA changed the anti-oxidant enzyme activities, increased the malondialdehyde, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and caused gross damage to the liver and kidney. Interestingly, these effects were significantly reversed by MS . In conclusion, MS shows protective effects against BPA-induced toxicity and could be a potential alternative medicine against BPA toxicity, especially in third-world countries where BPA uses are not strictly regulated.Highlights:Bisphenol-A (BPA) induces multiple toxic effects.BPA induces genotoxicity, oxidative and tissue damage. Majoon Suranjan ( MS ) ameliorates the BPA induced toxic effects.GC-MS profiling show various active anti-oxidant compounds in MS. MS is anti-genotoxic, anti-oxidant, and hepato-renal protective.

Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease with at least 5 recognized molecular subtypes. Cluster 5 (C5)/MCD tumors frequently exhibit concurrent alterations in the toll-like receptor (TLR) and B-cell receptor (BCR) pathway members, MYD88L265P and CD79B, and have a less favorable prognosis. In healthy B cells, the synergy between TLR and BCR signaling pathways integrates innate and adaptive immune responses and augments downstream NF-κB activation. In addition, physiologic TLR9 pathway engagement via MYD88, protein tyrosine kinase 2 (PYK2), and dedicator of cytokinesis 8 (DOCK8) increases proximal BCR signaling in healthy murine B cells. Although C5/MCD DLBCLs are selectively sensitive to Bruton tyrosine kinase (BTK) inhibition in in vitro studies and certain clinical trials, the role of mutated MYD88 in proximal BCR signaling remains undefined. Using engineered DLBCL cell line models, we found that concurrent MYD88L265P and CD79B alterations significantly increased the magnitude and duration of proximal BCR signaling, at the level of spleen tyrosine kinase and BTK, and augmented PYK2-dependent DOCK8 phosphorylation. MYD88L265P DLBCLs have significantly increased colocalization of DOCK8 with both MYD88 and the proximal BCR-associated Src kinase, LYN, in comparison with MYD88WT DLBCLs, implicating DOCK8 in MYD88L265P/proximal BCR cross talk. Additionally, DOCK8 depletion selectively decreased proximal BCR signaling, cellular proliferation, and viability of DLBCLs with endogenous MYD88L265P/CD79BY196F alterations and increased the efficacy of BTK blockade in these lymphomas. Therefore, MYD88L265P/DOCK8-enhanced proximal BCR signaling is a likely mechanism for the increased sensitivity of C5/MCD DLBCLs to BTK blockade., (© 2023 by The American Society of Hematology.)

Here we present the design of the series of quercetin analogues and their molecular docking study involving the binding of quercetin and its analogues with SARS-CoV2 3CLpro. The scientific literature shows that quercetin compound has been successfully used against SARS-CoV by inhibiting the replication of virus in respiratory epithelial cell through the inhibition of the SARS-CoV main protease (3CLpro.) It was suggested that the modification at position 3 in quercetin structure may produce potent compounds against SARS-CoV2. A series of quercetin analogues were designed and screened for physicochemical and pharmacokinetics parameters. The activities of selected compounds against SARS-CoV2 were screened by molecular modelling and evaluated that analogues, Q5, Q6 and Q13 have the best docking scores (-8.01 to -8.17 kcal/mol) and also better than quercetin, α-ketoamide and current available inhibitors of the same target. The structure-activity relationship (SAR) study revealed that the introduction of the amino group in a designed molecule was highly promising for increasing the inhibitory activity against SARS-CoV2 3CL pro. Moreover, to check the stability and orientation of selected compounds inside the binding pocket, the molecular dynamic simulations were performed for 100 ns. Results revealed that the designed analogues Q1, Q6 and Q13 having lowest binding energies (-8.0, -8.17 and -8.06 kcal/mol respectively) as well as better physicochemical properties, pharmacokinetics, and toxicity profile show their potential to synthesize and develop as the therapeutic agents against corona virus.Communicated by Ramaswamy H. Sarma.

Ligninolytic and other oxidative enzymes have emerged as promising biocatalysts in several industries. Since their production at a low cost is necessary for any large-scale application, we demonstrate the use of rice bran (RB), an agricultural waste and agri-food wastes such as potato peelings (PP), banana peelings (BP), and green pea peelings (GPP) for their production. High activity of laccase (12 U/ml), manganese peroxidase (16.11 ± 1.43 U/ml), and aryl alcohol oxidase (1.25 U/ml) was obtained on the PP on the 12th day of growth and ~ 6 U/ml of lytic polysaccharide monooxygenase was obtained on the 14th day of growth demonstrating PP to be a good substrate for their production. RB served as the next best substrate for the production of these enzymes. While the GPP was effective for the production of laccase (9.2 U/ml), this and the BP were not good substrates for the production of other enzymes. Efficient (48-82%) decolorization of several azo-, triarylmethane- dyes, and real textile effluent, without the addition of any mediator, demonstrated the high oxidative ability of the crude culture filtrate produced on the PP (CF-PP), which was a significant improvement compared to the treatment given by the previously reported culture filtrate obtained on wheat bran (CF-WB). An extensive breakdown of Reactive Orange (RO) 16 was demonstrated using CF-PP resulting in the formation of a new product at m/z of 294.05 (6-acetamido-3,4-dioxo-3,4-dihydronapthalene-2-sulfonate), previously reported to be produced on ozonation/advanced oxidation of RO16. The predominant laccase and manganese peroxidase isoforms produced on the PP were also identified., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Cotton is an irreplaceable economic crop currently domesticated in the human world for its extremely elongated fiber cells specialized in seed epidermis, which makes it of high research and application value. To date, numerous research on cotton has navigated various aspects, from multi-genome assembly, genome editing, mechanism of fiber development, metabolite biosynthesis, and analysis to genetic breeding. Genomic and 3D genomic studies reveal the origin of cotton species and the spatiotemporal asymmetric chromatin structure in fibers. Mature multiple genome editing systems, such as CRISPR/Cas9, Cas12 (Cpf1) and cytidine base editing (CBE), have been widely used in the study of candidate genes affecting fiber development. Based on this, the cotton fiber cell development network has been preliminarily drawn. Among them, the MYB-bHLH-WDR (MBW) transcription factor complex and IAA and BR signaling pathway regulate the initiation; various plant hormones, including ethylene, mediated regulatory network and membrane protein overlap fine-regulate elongation. Multistage transcription factors targeting CesA 4, 7, and 8 specifically dominate the whole process of secondary cell wall thickening. And fluorescently labeled cytoskeletal proteins can observe real-time dynamic changes in fiber development. Furthermore, research on the synthesis of cotton secondary metabolite gossypol, resistance to diseases and insect pests, plant architecture regulation, and seed oil utilization are all conducive to finding more high-quality breeding-related genes and subsequently facilitating the cultivation of better cotton varieties. This review summarizes the paramount research achievements in cotton molecular biology over the last few decades from the above aspects, thereby enabling us to conduct a status review on the current studies of cotton and provide strong theoretical support for the future direction., (© 2023. Science China Press.)

Objectives: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection., Design, Setting and Participants: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo., Results: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems., Conclusions: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The achievement of genome-wide association studies (GWAS) has rapidly progressed our understanding of the etiology of coronary artery disease (CAD). It unlocks new strategies to strengthen the stalling of CAD drug development. In this review, we highlighted the recent drawbacks, mainly pointing out those involved in identifying causal genes and interpreting the connections between disease pathology and risk variants. We also benchmark the novel insights into the biological mechanism behind the disease primarily based on outcomes of GWAS. Furthermore, we also shed light on the successful discovery of novel treatment targets by introducing various layers of "omics" data and applying systems genetics strategies. Lastly, we discuss in-depth the significance of precision medicine that is helpful to improve through GWAS analysis in cardiovascular research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Periostin is an emerging biomarker that plays a role in bone metabolism and may be associated with bone mineral density (BMD). This study is aimed to investigate serum periostin levels in patients with primary hyperparathyroidism (PHPT) and its correlation with BMD in these patients., Methods: Forty patients with newly diagnosed PHPT without co-morbidities and 30 healthy controls were included. Laboratory tests for the diagnosis of PHPT and serum levels of periostin were measured for all patients. BMD was measured on lumbar spines L1 and L4 by dual-energy X-ray absorptiometry (DEXA). Serum periostin levels were detected using an enzyme-linked immunosorbent assay (ELISA)., Results: Serum periostin levels were significantly higher in patients with PHPT than in healthy controls (p<0.001). Serum periostin levels were also significantly higher (mean 59.7±11.0 ng/mL) in PHPT patients with osteoporosis than those without osteoporosis (p=0.004). In logistic regression analysis, only serum periostin levels independently predicted the patients with osteoporosis. According to this analysis, every 1 ng/mL increase in serum periostin increased the risk of having osteoporosis by 20.6%. When the cut-off for serum periostin level was 49.75 ng/mL, the patients with osteoporosis were predicted with 71.4% sensitivity and 69.2% specificity. Multivariate regression analysis revealed a negative correlation between serum periostin levels and L1-L4 T scores on DEXA., Conclusion: This is the first study to determine that serum periostin levels are higher in PHPT patients than those without PHPT and to demonstrate a significant association between serum periostin levels and T scores on DEXA in patients with PHPT. These findings will aid in detecting osteoporosis in patients with PHPT and making the decision for surgery in PHPT patients with no need for DEXA imaging that involves radiation., Competing Interests: The authors have no conflict of interest to declare., (Thieme. All rights reserved.)