Search

Metabolomics involves the identification and quantitative analysis of all small metabolites present in cells, tissues, and bodily fluids that are formed as a result of biochemical reactions within the cell. These metabolites form a large pool of substrates and can be modified by serving as a substrate for enzymes involved in other metabolic pathways. Therefore, the metabolome in an organism is so dynamic that there is variation in their quantity and chemical composition over time. Nuclear Magnetic Resonance (NMR), Gas Chromatography Mass Spectrometry (GC-MS), and Liquid Chromatography Mass Spectrometry (LC-MS) are the most commonly used technologies in metabolomics. The metabolites are first isolated based on their polarity, chemical composition, and structural resemblances, after which they undergo specialised processes and are then analysed. Metabolomics, coupled with MS, has advanced rapidly and found widespread use in periodontal research. The presence of distinct metabolic and microbiological profiles in different types of periodontitis, as well as their link to clinical indicators of periodontal inflammation, has demonstrated the usefulness of metabolomics in screening, preventing, and monitoring prognosis. Conventional diagnostics fail to detect periodontitis in its early stages, cannot discriminate between past and present disease activity, and are incapable of analysing the entire repertoire of biomarkers in the biological system. Therefore, metabolomics, in conjunction with other omics technologies, can provide tailored periodontal disease therapy. The present review aimed to explore metabolomics, its applications in periodontics, and the potential for personalised treatment.

Periodontitis is a multifactorial chronic inflammatory disease associated with increased secretion of several proinflammatory mediators such as Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-17 (IL-17), Tumour Necrosis Factor-α (TNF-α), Prostaglandins (PGs) in response to increased bacterial load on the tooth surface and within the gingival sulcus leading to the destruction of both hard and soft tissue of the periodontium. The Receptor for Advanced Glycation End products (RAGE) binds multiple ligands, has a transmembrane configuration and is a part of the immunoglobulin receptor family. In healthy individuals RAGE is expressed at lower levels when compared to those with periodontitis and diabetes mellitus. Binding of RAGE to its ligands plays a key role in the inflammatory reactions that lead to disruption of a multitude of cellular processes. One such RAGE ligand involved in inducing hyperinflammatory phenotype is High Mobility Group Box 1 (HMGB1). HMGB1 is a chromatin binding protein predominantly localised in the nucleus and is associated with multiple functions such as Deoxyribonucleic Acid (DNA) repair, nuclear homeostasis, genome stability. In the presence of stressors, it migrates extracellularly and behaves like a Damage Associated Molecular Pattern (DAMP), has chemokine and cytokine activity. Extracellular HMGB1 binds to Toll Like Receptors (TLR)- 2,4 and RAGE, the HMGB1-RAGE interaction in particular has been associated with hyper inflammatory responses and currently hypothesised to be a bigger player in the pathogenesis of periodontitis as well as diabetes associated periodontitis. Therefore, understanding thoroughly the molecular mechanisms driving the tissue destruction in periodontal disease will effectively enable novel therapeutic drug based interventions based on interrupting the HMGB1-RAGE axis which in turn could mitigate the inflammation mediated tissue destruction.

Lesions of the gingiva are very common, and they vary in their clinical presentation and histological appearances. However, at times, the clinical features of these lesions appear to be similar and overlapping leading to a difficulty in diagnosis. Gingival Cyst of Adult (GCA) is a rare, abnormal, non inflammatory lesion in the oral cavity that arises mostly from the cell rests of the dental lamina. These lesions are usually solitary, sessile, painless, slow growing swelling usually involving the attached gingiva and interdental papilla and more frequently found in the canine and premolar region of the mandible. The GCA usually does not show any radiographic evidence of bone resorption. Histopathologic presentation significantly contributes to the diagnosis of the lesion. The present case report discusses about the GCA, involving the marginal gingiva and interdental papilla on the facial aspect of maxillary central incisors region in a 37-year-old female patient. Treatment plan included scaling, root planing, re-evaluation followed by surgical excision of the lesion. The lesion was sent for histopathological examination and a final diagnosis of GCA was made. Healing was uneventful without any complications. The patient was reviewed for nine months and no recurrence of the lesion was observed during the follow-up period.

A field experiment was conducted at the Field Crops Research and Development Institute, Mahailluppllama to identify an optimum seed rate and the respective nitrogen level for broadcast blackgram grown on rainfed uplands during Maha 2009/2010 with the variety MI-1. The study was carried out as a two factor factorial experiment. Six seed rates (25 kg/ha, 37.5 kg/ha, 50 kg/ha, 62.5 kg/ha, 75 kg/ha, 87.5 kg/ha) with two rates of nitrogen (30 kg of N/ha, Zero N) were the two factors tested in the experiment. The results revealed that the plant height, leaf area per plant and canopy diameter did not vary with the seed rate but significantly varied with fertilizer rates. Number of pods per plant, number of seeds per pod and 1000 seed weight did not vary with the seed rate but number of pods per plant and 1000 seed weight varied with the fertilizer level. The maximum yield was recorded at a seed rate of 64 kg/ha. Economic analysis revealed that the optimum seed rate is 62.5 kg/ha. The number of plants/ m2 at which maximum yield was obtained was estimated as 93 plants/m2 which is also comparable to this seed rate. As there were no differences observed in yield components except for the number of plants per unit area, the main contributing factor for yield increments with increasing seed rate was the number of plants per unit area. Therefore, it can be concluded that the optimum seed rate for broadcast crop of black gram under rain-fed conditions is 62.5 kg/ha when N is supplied at the rate of 30 kg/ha. Key words: Blackgram; Nitrogen requirement; Optimum rate seed DOI: 10.4038/tar.v22i2.2825Tropical Agricultural Research Vol. 22 (2): 165-171 (2011)

Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode of inheritance; however, recent evidence demonstrates that a single CNV in PARK2 (but not a single missense mutation) may increase risk for PD. We recently performed a genome-wide association study for PD that excluded individuals known to have either a LRRK2 mutation or two PARK2 mutations. Data from the Illumina370Duo arrays were re-clustered using only white individuals with high quality intensity data, and CNV calls were made using two algorithms, PennCNV and QuantiSNP. After quality assessment, the final sample included 816 cases and 856 controls. Results varied between the two CNV calling algorithms for many regions, including the PARK2 locus (genome-wide p = 0.04 for PennCNV and p = 0.13 for QuantiSNP). However, there was consistent evidence with both algorithms for two novel genes, USP32 and DOCK5 (empirical, genome-wide p-values

BackgroundThe aim of this work was to identify early clinical predictors of important outcomes in Parkinson's disease (PD). In PD, treatment-resistant (e.g., dementia, falling) and other important functional outcomes (e.g., declines in quality of life [QOL] and activities of daily living [ADL]) emerge and become increasingly disabling.MethodsWe analyzed longitudinal data from 491 early, untreated PD subjects who enrolled in the PreCEPT trial, had baseline SPECT dopamine transporter deficit, and have continued in the PostCEPT observational cohort. After PreCEPT, antiparkinsonian medications were added if needed. Baseline clinical precursors were examined as potential predictors of selected outcomes. Separate and multivariate logistic regressions, adjusted for certain baseline factors, were performed for dichotomized outcomes evaluated at the last PostCEPT visit.ResultsOn enrollment, subjects had average disease duration of 0.8 years and were followed for an average of 5.5 years. Some baseline precursors were found to be predictive: disease stage, cognitive, and ADL scores for dementia; disease stage, ADL, and motor and freezing scores for hallucinations; disease stage, depression, ADL, and freezing and walking scores for falling; and ADL, depression, and motor and walking scores and disease stage for QOL decline. No baseline clinical feature predicted decline in ADL. Being on levodopa was not a significant predictor of any outcome, but subjects on a dopamine agonist were significantly less impaired with respect to falling, abnormal Mini-Mental State Examination, and QOL.ConclusionsAlthough there are limitations, results support the value of longitudinal follow-up of clinical trial populations to identify early clinical precursors of important outcomes and thereby identify high-risk patients early on.

Purpose: Whilst survival in paediatric critical care has improved, clinicians lack tools capable of predicting long-term outcomes. We developed a machine learning model to predict poor school outcomes in children surviving intensive care unit (ICU). Methods: Population-based study of children < 16 years requiring ICU admission in Queensland, Australia, between 1997 and 2019. Failure to meet the National Minimum Standard (NMS) in the National Assessment Program-Literacy and Numeracy (NAPLAN) assessment during primary and secondary school was the primary outcome. Routine ICU information was used to train machine learning classifiers. Models were trained, validated and tested using stratified nested cross-validation. Results: 13,957 childhood ICU survivors with 37,200 corresponding NAPLAN tests after a median follow-up duration of 6 years were included. 14.7%, 17%, 15.6% and 16.6% failed to meet NMS in school grades 3, 5, 7 and 9. The model demonstrated an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.8 (standard deviation SD, 0.01), with 51% specificity to reach 85% sensitivity [relative Area Under the Precision Recall Curve (rel-AUPRC) 3.42, SD 0.06]. Socio-economic status, illness severity, and neurological, congenital, and genetic disorders contributed most to the predictions. In children with no comorbidities admitted between 2009 and 2019, the model achieved a AUROC of 0.77 (SD 0.03) and a rel-AUPRC of 3.31 (SD 0.42). Conclusions: A machine learning model using data available at time of ICU discharge predicted failure to meet minimum educational requirements at school age. Implementation of this prediction tool could assist in prioritizing patients for follow-up and targeting of rehabilitative measures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of two hydrodynamic sinus lifting procedures and to successfully place immediate implants in maxillary posterior sites that have a compromised native bone as a result of periodontal or endodontic disease. Patients and Methods: A total of 26 patient sites were enrolled with 13 sites each in the Minimally Invasive Antral Membrane Balloon Elevation (MIAMBE) and Drill Integrated Hydrodynamics for the transcrestal sinus floor elevation (DIHSFE) groups who received transcrestal sinus floor elevation followed by immediate implant placement. Clinical parameters such as sinus membrane perforations, nasal bleeding, postoperative sinusitis, VAS scores at Day-7 for pain and discomfort, primary implant stability and time taken were evaluated. Results: The DIHSFE had greater sinus membrane perforations and incidence of nasal bleeding when compared with MIAMBE with (p = 0.066) and (p = 0.141). Post-operative sinusitis was evident in both the groups with (p = 0.619). The mean VAS score was statistically significant between both the groups (p ≤ 0.005). The insertion torque values, and mean time taken for surgical procedure was not statistically significant between groups. Conclusion: The present study highlighted that MIAMBE is superior to DIHSFE in its ability to cause less severe patient morbidities and post-operative complications. [ABSTRACT FROM AUTHOR]

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685).Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392. [ABSTRACT FROM AUTHOR]

Purpose: Data on childhood intensive care unit (ICU) deaths are needed to identify changing patterns of intensive care resource utilization. We sought to determine the epidemiology and mode of pediatric ICU deaths in Australia and New Zealand (ANZ).Methods: This was a retrospective, descriptive study of multicenter data from pediatric and mixed ICUs reported to the ANZ Pediatric Intensive Care Registry and binational Government census. All patients < 16 years admitted to an ICU between 1 January 2006 and 31 December 2016 were included. Primary outcome was ICU mortality. Subject characteristics and trends over time were evaluated.Results: Of 103,367 ICU admissions, there were 2672 (2.6%) deaths, with 87.6% of deaths occurring in specialized pediatric ICUs. The proportion of ANZ childhood deaths occurring in ICU was 12%, increasing by 43% over the study period. Unadjusted (0.1% per year, 95% CI 0.096-0.104; p < 0.001) and risk-adjusted (0.1%/year, 95% CI 0.07-0.13; p < 0.001) ICU mortality rates fell. Across all admission sources and diagnostic groups, mortality declined except following pre-ICU cardiopulmonary arrest where increased mortality was observed. Half of the deaths followed withdrawal of life-sustaining therapy (51%), remaining constant throughout the study. Deaths despite maximal resuscitation declined (0.92%/year, 95% CI 0.89-0.95%; p < 0.001) and brain death diagnoses increased (0.72%/year, 95% CI 0.69-0.75%; p = 0.001).Conclusions: Unadjusted and risk-adjusted mortality for children admitted to ANZ ICUs is declining. Half of pediatric ICU deaths follow withdrawal of life-sustaining therapy. Epidemiology and mode of pediatric ICU death are changing. Further investigation at an international level will inform benchmarking, resource allocation and training requirements for pediatric critical care. [ABSTRACT FROM AUTHOR]

Abstract The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

Nanotechnology is a cutting-edge concept that is evolving manifolds in various fields of science and medicine and is by no means exceptional to dentistry. Nanotechnology is popularly known as the ‘science of the small’ that deals with particles of size 1-10nm. Methods like top-down or bottom-up approaches are used in manufacturing nanoparticles and nanorobots, catering to the needs of medical diagnostics and therapeutics. Nanorobotics advances medicine through miniaturization from microelectronics to nanoelectronics. Nanotechnology can be applied to all fields of dentistry such as to create nano implants, nano-drug delivery systems, nanocomposites and nano impression materials. Additionally, it helps in orthodontic tooth movement, alleviating hypersensitivity, and effective anesthesia. This paper highlights the various applications of nanotechnology in dentistry and also mentions the clinical trials performed to have a more focused approach to practicing nanodentistry. Apart from this the paper briefly explains the benefits of integrating artificial intelligence and nanotechnology for creating more personalized treatment options and also its role in Covid 19 vaccines.

Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy (“metabolic resuscitation”) in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU).Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers.Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.

Objective: To evaluate the efficacy of solifenacin succinate in Parkinson's disease (PD) patients suffering from overactive bladder (OAB).Background: Urinary dysfunction is a commonly encountered non-motor feature in PD that significantly impacts patient quality of life.Design/methods: This was a double-blind, randomized, placebo-controlled, 3-site study with an open label extension phase to determine the efficacy of solifenacin succinate in idiopathic PD patients with OAB. Patients were randomized to receive solifenacin succinate 5-10 mg daily or placebo for 12 weeks followed by an 8-week open label extension. The primary outcome measure was the change in the mean number of micturitions per 24 h period. Secondary outcome measures included the change in the mean number of urinary incontinence episodes and the mean number of nocturia episodes.Results: Twenty-three patients were randomized in the study. There was no significant improvement in the primary outcome measure in the double-blind phase, but there was an improvement in the number of micturitions per 24 h period in the solifenacin succinate group compared to placebo at a mean dose of 6 mg/day (p = 0.01). In the open label phase, the mean number of urinary incontinence episodes per 24 h period decreased (p = 0.03), as did the number of nocturia episodes per 24 h period (p = 0.01). Adverse events included constipation and xerostomia, which resolved after treatment was discontinued.Conclusions: In this pilot trial, solifenacin succinate treatment led to an improvement in urinary incontinence, despite persistence in other OAB symptoms. [ABSTRACT FROM AUTHOR]

Background: Malpositioning of the acetabular cup during total hip arthroplasty (THA) can lead to complications. Robotic surgery and navigation techniques aim to address this issue, but there is limited evidence regarding which method can achieve better clinical outcomes. Therefore, this network meta-analysis (NMA) aimed to compare the efficacy of various navigation methods., Methods: This NMA of prospective randomized controlled trials compared robot-assisted systems (RAS), computer-assisted navigation systems (CAS), augmented reality-based portable navigation (AR), patient-specific instrumentation (PSI), portable accelerometer-based navigation (PN), and conventional methods (C) for THA procedures. We searched MEDLINE, EMBASE, Cochrane, Central Register of Controlled Trials, International Clinical Trials Platform Search Portal, and ClinicalTrials.gov. databases. The primary outcomes included revision surgery and postoperative clinical scores, and the secondary outcomes encompassed cup placement accuracy, acetabular cup placement outliers from the Lewinnek safe zone, surgical time, and complications. We used a Bayesian random-effects NMA, and confidence of evidence was assessed using confidence in NMA., Results: We identified 45 studies including 2,122 patients. We did not find large differences in revision surgery, clinical outcome scores, cup inclination, or anteversion angle accuracy among the modalities. AR, CAS, and PSI exhibited a lower risk of outliers from safe zones than C. In addition, RAS and CAS had a longer surgical time than C., Conclusions: Robotic and navigation tools did not reduce the revision risk or enhance clinical outcomes. AR, CAS, PSI, and PN may decrease the risk of cup placement outliers in safe zones. However, the cup placement accuracy was equivalent, and the surgical time may be longer in RAS and CAS than in C., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B164)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

The present study aims to prepare and evaluate solid lipid nanoparticles (SLNs) loaded with irinotecan (IRN) drug and daidzein (DZN) isoflavonoid and surface coated with ligand materials such as hyaluronic acid (HA) and bovine serum albumin (BSA) with additional coating of chitosan for active targeting to receptors present on colon surface epithelium for oral targeted delivery. The optimized batch was evaluated for particle size, zeta potential exhibiting nanometric size with good entrapment efficiency. Nanoparticles were found to be spherical. FTIR and DSC revealed that all the excipients and formulation were compatabile to each other and showed better encapsulation exhibiting amorphous and crystallinity forms. In vitro drug release of SLNs confirmed that initially a burst release, followed by sustained release pattern was exhibited. Cell lines studied performed on HT-29 cells showed demonstrated that conjugated SLNs inhibited cytotoxicity at 75 μg/ml, indicating that cells were taken up through a receptor-mediated endocytosis process. Cell cycle analysis showed that cell arrest was done at 67.8 % (G0/G1 phase) and inhibited apoptosis by 56 %. Further during In vivo studies, RT-PCR study revealed downregulation of Carcinoembryonic antigen (CEA), a non-specific serum biomarker overexpressed in tumor cells and upregulation of pro-inflammatory cytokine TNF-α. Histopathological study revealed that conjugated (HA-BSA) coated with chitosan SLNs restored normal mucosa and colon architecture, depicting all mucosal layers. Hence, these conjugated SLNs may serve as a novel combination for the treatment of colon cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanostructured lipid carriers (NLC) have low storage and gastrointestinal stability, limiting their applicability. The work aimed to elevate the stability and behaviour of NLC in the alimentary tract by creating an alginate bead. Through the extrusion dropping procedure, Resveratrol (RES)-loaded NLC were efficiently integrated into alginate beads. The incorporation had no significant impact on the particle size, morphology, or inner structure of NLC, as assessed using DLS (Dynamic Light Scattering), SEM (Scanning Electron Microscopy), Differential Scanning Calorimetry (DSC) and FT-IR (Fourier Transform Infra-Red). Incorporating NLC into alginate beads improves its physical stability compared to dispersion of NLC as well as NLC-Sol. An in vitro release investigation found that the NLC-alginate beads released RES more slowly than optimized NLC formulation (RES-NLCs-opt) and NLC-alginate sol. Research on simulated in vitro digestive models revealed that just a small amount of integrated NLC may permeate stomach fluid due to its tiny size. The slow diffusion of NLC from alginate to intestinal fluid prevented aggregation and allowed for gentle hydrolysis of the lipid matrix. Incorporating NLC in alginate beads shows promise for improving stability, modifying gastrointestinal behaviour, and controlling release throughout the process of digestion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, caprine forestomach native collagen (CFNC) isolated from rumen tissues is reported for the first time with subsequent surface modifications with varying concentrations of silver nanowires (AgNWs). Accordingly, CFNC/AgNWs scaffolds were prepared to be used as suitable wound healing dressing materials through a sequential isolation and decellularization process, followed by step-wise AgNW surface modification and ultraviolet (UV) crosslinking. The significant outcomes of this research highlight that CFNC/AgNWs scaffolds exhibit a highly porous three-dimensional (3D) network structure with favourable physicochemical characteristics. Also, the comprehensive tensile testing demonstrated that there were changes in mechanical properties based on the AgNW content. The CFNC/AgNWs scaffolds also exhibited strong antibacterial action against E. coli and S. aureus in a dose-dependent manner. The release of Ag + ions from CFNC/AgNWs scaffolds exhibited a slow and sustained release pattern over an extended period of time. The cell-biomaterial interaction studies on CFNC/AgNWs scaffolds using L929 fibroblast cells showed dose-dependent and time-dependent toxicity when the concentration exceeded above 1 mg mL -1 . The cytotoxicity is mainly due to the higher concentration of Ag + ions which initiates cell death through lipid peroxidation and causes cell membrane damage. The biocompatibility test results serve as a reference point to select the optimal dosage of AgNWs with balanced antibacterial and biocompatibility properties. Thus, the developed CFNC/AgNWs scaffolds will serve as a versatile wound dressing material similar to other metallic or conjugated reconstituted collagen systems with the added benefit of strong antimicrobial properties, and as a biomimetic xenograft for skin regeneration.

Introduction: Continuing Medical Education (CME) is vital for healthcare professionals to remain current with advancements and maintain their competence. In India, CME remains in its early stages, lacking a systematic approach. There is a pressing need for a comprehensive framework that addresses needs assessment, program development, accreditation, and credit allocation. Specifically, there is a gap in delivering targeted CME that meets the needs of different medical professionals at appropriate times. The aim of this study is to employ Kern's six steps of curriculum design to plan and evaluate a faculty development program focused on Entrustable Professional Activities (EPAs) for MD (Doctor of Medicine) Biochemistry professionals., Methods: This study utilized Kern's six-step approach to design a training program on Entrustable Professional Activities (EPAs) tailored for MD Biochemistry professionals. Approval was obtained from the Institutional Human Ethics Committee. Following problem identification, a targeted needs assessment was conducted through expert consultations. The goal of the program was established, focusing on the development and delivery of an interactive online CME program. The program was developed, implemented and evaluated using surveys and feedback questionnaires., Results: A comprehensive literature review revealed a notable gap in EPA-related works for MD Biochemistry program. Expert consultations highlighted significant training needs and barriers, such as limited resources and professional commitments. Consequently, the program's primary objective was to raise awareness and sensitize participants to EPA development. A 4-h online CME was designed, featuring expert-led sessions and collaborative group activities. The program attracted 152 participants and utilized interactive elements, such as polls and chats, to foster engagement. Group activities allowed participants to apply concepts in EPA validation. Pre- and post-program surveys demonstrated significant improvements in participants' knowledge and confidence. Feedback highlighted the practical relevance of the content and the interactive, hands-on nature of the sessions., Conclusion: Kern's six-step approach provided a structured and effective framework for developing the CME program, addressing identified needs and barriers, and enhancing faculty development in MD Biochemistry. This study underscores the importance of a systematic approach in CME to improve program effectiveness., Trial Registration: Not applicable., (© 2024. The Author(s).)

Epilepsy is a common neurological disorder affecting around 70 million people worldwide. Despite significant research and advancements in pharmaceutical therapies, the exact mechanisms underlying epileptogenesis remain unclear. As a result, current antiepileptic drug treatments are ineffective for approximately 30% of patients, providing only symptomatic relief. The epileptic process is influenced by the signaling of tumor necrosis factor alpha (TNFα), which affects neuronal excitability. The TNFα/TNFR1 signaling pathway and the role of RIPK1 in initiating inflammatory cell death pathways are well studied in human disorders. Dysregulation of RIPK1 is linked to inflammation and neurodegenerative diseases. Necrostatin-1 (Nec-1) selectively inhibits RIPK1 in various pathological conditions. The current study aimed to investigate the anticonvulsant properties of Nec-1 (a selective RIPK1 inhibitor) in PTZ-induced seizures in zebrafish larvae. Before the onset of seizures, zebrafish were treated with Nec-1 (15 µM) for 24 h at 6 days post-fertilization (dpf), followed by exposure to 15 mM of PTZ for 30 min. Behavioral assessments were conducted to observe changes in locomotor activity. Additionally, c-Fos expression was measured as an indicator of neuronal activation and analyzed mRNA levels of the astrocyte activation marker (GFAP) along with various inflammatory cytokines. Western blot analysis was conducted to evaluate GABA A receptor expression. Pretreatment with Nec-1 restored normal behavior and reversed the expression of c-Fos in zebrafish larvae induced by PTZ. Additionally, Nec-1 reduced the elevated mRNA expression of inflammatory cytokines and significantly suppressed TNF/TNFR1 signaling, thereby inhibiting the enhanced internalization of GABA A receptors. Our findings indicate that Nec-1 reduced the severity of PTZ-induced seizures in zebrafish by regulating behavior changes, suppressing inflammatory mediators, and enhancing the expression of GABA A receptors, suggesting potential anticonvulsant properties., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The nanocellulosic pellicle derived from the symbiotic culture of bacteria and yeast (Kombucha SCOBY) is an important biomaterial for 3D bioprinting in tissue engineering. However, this nanocellulosic hydrogel has a highly entangled gel network. This needs to be partially modified to improve its processability and extrusion ability for its applications in the 3D bioprinting area. To control its mechanical and biological properties for direct 3D bioprinting applications, uniform reinforcement of nanocellulose-interacting polymers and nanoparticles in such a prefabricated gel network is essential. In this study, the hydrogel network is partially hydrolyzed with organic acid and subsequently transformed into a 3D bioprintable polyelectrolyte complex with chitosan and kaolin nanoparticles without any chemical crosslinker using a handheld 3D bioprinter. This handheld bioprinter ensures homogeneity in both biomixing and bioprinting of chitosan and kaolin within the modified nanocellulose network for multi-layered bioprinted scaffolds through an extensional shear mechanism. The biomixing simulation, mechanical (static, dynamic, and cyclic), 3D bioprinting, and cellular studies confirm the homogeneous biomixing of kaolin nanoparticles and live cells in this nanocellulose-chitosan polyelectrolyte hydrogel. The combination of SCOBY-derived nanocellulose-chitosan bioink with kaolin nanoparticles and a screw-driven handheld extrusion bioprinter demonstrates a promising platform for layer-by-layer regeneration of complex tissues with homogeneous cell/particle distribution with high cell viability., 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 © 2024. Published by Elsevier B.V.)

Emotions play a vital role in recognizing a person's thoughts and vary significantly with stress levels. Emotion and stress classification have gained considerable attention in robotics and artificial intelligence applications. While numerous methods based on machine learning techniques provide average classification performance, recent deep learning approaches offer enhanced results. This research presents a hybrid deep learning model that extracts features using AlexNet and DenseNet models, followed by feature fusion and dimensionality reduction via Principal Component Analysis (PCA). The reduced features are then classified using a multi-class Support Vector Machine (SVM) to categorize different types of emotions. The proposed model was evaluated using the DEAP and EEG Brainwave datasets, both well-suited for emotion analysis due to their comprehensive EEG signal recordings and diverse emotional stimuli. The DEAP dataset includes EEG signals from 32 participants who watched 40 one-minute music videos, while the EEG Brainwave dataset categorizes emotions into positive, negative, and neutral based on EEG recordings from participants exposed to six different film clips. The proposed model achieved an accuracy of 95.54% and 97.26% for valence and arousal categories in the DEAP dataset, respectively, and 98.42% for the EEG Brainwave dataset. These results significantly outperform existing methods, demonstrating the model's superior performance in terms of precision, recall, F1-score, specificity, and Mathew correlation coefficient. The integration of AlexNet and DenseNet, combined with PCA and multi-class SVM, makes this approach particularly effective for capturing the intricate patterns in EEG data, highlighting its potential for applications in human-computer interaction and mental health monitoring, marking a significant advancement over traditional methods., (© 2024. The Author(s).)

In this work we developed a hydrothermal method for synthesizing amorphous Ni-Co hydroxide (NC(OH)) and in the subsequent step crystalline NiCo 2 O 4 (NCO) has been produced using water as the solvent. For nickel-zinc batteries, NC(OH) was found to have superior performance to its NCO prepared by two-step process. The thermal stability analysis exhibited the optimum temperature to obtain the NC(OH), and NCO electrode materials. The XRD pattern showed mixed phases containing both Ni and Co hydroxides (during the initial step) and in the subsequent step (calcined) the formation of cubic spinel structure was noticed. For NC(OH), aggregated particles with irregular morphology were observed while clustered nanorod-like shapes were noticed for NCO samples. To be noted, that the nanorod morphology was obtained through a facile approach without employing any structure-directing agent. Both NC(OH) and NCO were employed as cathodes for Ni-Zn battery studies against Zn foil anode with a polyamide-based separator soaked in 6 M KOH saturated with ZnO additive was used as electrolyte. The Ni-Zn cell was fabricated in CR2032 coin cell configuration. The electrochemical studies such as cyclic voltammetry (CV) showed the characteristic redox peaks for NC(OH) sample exhibiting high peak current compared to its NCO counterpart. The NC(OH) had a capacity of 268 mAh g -1 against 120 mAh g -1 for NCO at a current density of 1 Ag -1 . The cell was able to retain 85 % of the capacity at the end of 500 cycles and showed remarkable rate capability. The Ni-Zn battery presents energy and power densities of 428.8 Wh Kg -1 and 2.68 kW Kg -1 , respectively surpassing the normal values reported for aqueous rechargeable batteries. Owing to the presence of Ni and Co in hydroxide form (reduced crystallinity) the NC(OH) sample showed improved electrochemical activity. This work provides a facile approach and effective strategy for developing bimetallic hydroxides for optimal energy storage performance., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Sarcopenia is a common musculoskeletal disorder characterized by degenerative processes and is strongly linked to an increased susceptibility to falls, fractures, physical limitations, and mortality. Several models have been used to explore therapeutic and preventative measures as well as to gain insight into the molecular mechanisms behind sarcopenia. With novel experimental methodologies emerging to design foods or novel versions of conventional foods, understanding the impact of nutrition on the prevention and management of sarcopenia has become important. This review provides a thorough assessment of the use of rodent models of sarcopenia for understanding the aging process, focusing the effects of nutrients, plant extracts, exercise, and combined interventions on skeletal muscle health. According to empirical research, nutraceuticals and functional foods have demonstrated potential benefits in enhancing physical performance. In preclinical investigations, the administration of herbal extracts and naturally occurring bioactive compounds yielded advantageous outcomes such as augmented muscle mass and strength generation. Furthermore, herbal treatments exhibited inhibitory effects on muscle atrophy and sarcopenia. A substantial body of information establishes a connection between diet and the muscle mass, strength, and functionality of older individuals. This suggests that nutrition has a major impact in both the prevention and treatment of sarcopenia., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Choon Young Kim reports financial support was provided by National Research Foundation of Korea., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: By 2023, COVID-19 had caused 6.8 million deaths in the United States. COVID-19 presents more severely in leukemia compared to solid tumors (OR 1.6, p<0.05). However, data on Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are limited. We investigated the mortality in AML and MDS patients with COVID-19., Methods: Data from the 2020-2021 National Inpatient Sample was used to conduct a cross-sectional analysis. We identified AML and MDS patients with COVID-19 hospitalizations through ICD-10 codes. Analysis was done by propensity matching and multivariate regression with a p-value of ≤0.05., Results: Of 28,028 AML admissions, 336 (1.2%) were admitted for COVID-19. AML-COVID-19 cohort had a lower hospitalization risk (aOR 0.3, p=0.000) and higher mortality (21.7% vs 8.7%; aOR 1.6, p=0.023) than AML patients admitted for other causes. AML patients post-HSCT (Hematopoietic Stem Cell Transplantation) had a higher risk of COVID-19 (20.2% vs 9.8%; aOR 2.6, p=0.000) and increased mortality (19.1% vs 6.7%; aOR 4.1, p=0.000) compared to other causes. Similarly, of 28,148 MDS patients, 769 (2.7%) were admitted for COVID-19. The MDS-COVID-19 cohort had a lower hospitalization risk (aOR 0.59, p=0.000) and higher mortality (19.6% vs 6.6%; aOR 2.2, p=0.000) compared to other causes. In MDS, HSCT did not alter the risk of COVID-19 hospitalizations (3% vs 3.9%; aOR 0.9, p=0.662), but these patients had higher mortality (17.4% vs 5.1%; aOR 4.0, p=0.032)., Conclusion: COVID-19 hospitalization was low in AML and MDS but carried a high mortality risk. Post-HSCT, the mortality is high, warranting research into understanding the underlying factors., 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 Sivasubramanian, Joshi, Ravkumar, Madhumithaa Jagannathan, Babu, Sripathi, Javvaji, Jain, Kumar Shanmugam, Swami Kannan, Tirupathi and Dalal.)

Objective: To investigate the prevalence of problematic internet use (PIU) among adolescents and determine the associated factors contributing to PIU., Methods: In April/May 2023, a cross-sectional study was conducted among adolescents studying in grades 9 to 12 in government and private non-residential schools in Western Tamil Nadu, India. Participants completed a semi-structured questionnaire assessing demographic characteristics, behavioral patterns, and internet usage. The Problematic and Risky Internet Use Screening Scale (PRIUSS) was employed to quantify PIU., Results: Out of 1795 participants, 398 (24.5%) were identified with PIU. Prevalence rates of PIU were similar between adolescents studying in English (n = 189; 25.4%) and Tamil medium (n = 209; 23.7%), with no significant differences based on gender [boys (n = 270, 25.4%) and girls (n = 121, 22.2%)]. Students possessing personal gadgets showed higher PIU [n = 287 (27%) Vs. n = 111 (20%)]. Specific risk factors for PIU identified students in English medium and scoring below 80% [OR (95%CI) 1.5 (1.1, 2.3); P = 0.029 ] and those with multiple gadgets at home [1.3 (1.01, 1.7); P = 0.04]., Conclusion: Adolescents have a high prevalence of PIU. Implementing school-based educational programs will mitigate excessive internet usage.

Objectives: A quality indicator (QI) for the treatment of systemic lupus erythematosus (SLE) during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a QI for SLE associated with pregnancy and childbirth., Methods: To identify candidate QIs, we conducted a systematic literature review on the development of QIs for SLE related to pregnancy and childbirth and on clinical practice guidelines. Candidate QI items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as QIs. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related SLE QIs., Results: Four articles on SLE QI development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate QIs were extracted that were limited to items related to pregnancy and childbirth and 41 items were selected on which all panel members agreed., Conclusion: We developed pregnancy-related SLE QIs using the RAND/UCLA method and selected 41 items, which could be used clinically., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

The γ-lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ-lactams, 2-oxopyrrolidine-3-carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3-cyano-2-pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition. The process demonstrated excellent diastereoselectivity and showed good tolerance to a range of isonitriles and carbonyl compounds., (© 2024 Wiley‐VCH GmbH.)

Maximum dose bioassays were conducted to assess the efficacy of multiple registered active ingredients for diamondback moth (DBM), Plutella xylostella (L.), control in Georgia and Florida from 2021 to 2023 as a follow-up to an earlier study. Low efficacy (<40% mortality) was recorded for the highest labeled rate of Bacillus thuringiensis var. kurstaki strain ATBS-351 in Georgia, as well as chlorantraniliprole, cyantraniliprole, and cyclaniliprole in Georgia and Florida. The active ingredients with the highest efficacy (>80% mortality) in both states were naled, emamectin benzoate, and spinetoram. Independent analysis of data by state indicated that the efficacy of bifenthrin, chlorantraniliprole, cyantraniliprole, tolfenpyrad, and methomyl was higher in Florida populations than in Georgia populations. In addition, a comparison of these data to a recent DBM maximum dose survey in the same region suggested that these DBM populations have rapidly developed high levels of resistance to cyantraniliprole and cyclaniliprole. This work provides growers in the region with a recent ranking of insecticide efficacy that documents the loss of control for certain active ingredients, which assists pest managers in the planning of ongoing insecticide rotations for DBM resistance management., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)