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Thyrotoxicosis has been associated with several cardiac conditions including atrial fibrillation, congestive heart failure due to left ventricular dysfunction, and cardiomyopathy. However, few cases of ventricular fibrillation as a complication of thyrotoxicosis have been reported. Our case described a 45-year-old male with a history of hypertension and Graves' disease, who presented with 1 week of left-sided chest pain associated with shortness of breath on exertion and occasional palpitations. His workup revealed acute diastolic congestive heart failure secondary to thyrotoxicosis, causing pulmonary hypertension, which led to ventricular fibrillation and cardiac arrest. After being treated with methimazole and metoprolol, the patient's symptoms improved. This case underscores the significance of assertive medical interventions alongside both invasive and non-invasive cardiac procedures. Addressing thyrotoxicosis and ventricular arrhythmia in hyperthyroid patients is crucial to prevent potentially life-threatening complications., Competing Interests: The authors declare that they have no competing interests., (Copyright 2024, Rajagopal Nair et al.)

Mycobacterium marinum is a non-tuberculous mycobacterium which can be found in naturally occurring, non-chlorinated water sources and is a known pathogen that affects fish. In humans, M. marinum typically results in cutaneous lesions, it can occasionally lead to more invasive disorders. We discuss four cases of M. marinum-related cutaneous infections examined in a tertiary care facility. We want to draw attention to the challenges of accurately diagnosing this infection, stress the significance of having a high level of clinical suspicion in order to identify it, and discuss the available treatment choices., (© 2024 John Wiley & Sons Ltd.)

Although difluoromethyl ketones are used as tools in chemical biology and leads in drug discovery, the metabolic stability of these compounds is generally uncharacterized and must be inferred from in vivo pharmacological assays. In order to address this gap which impedes their wider use, we have synthesized and performed metabolic stability studies for thirty-nine β-amino and β-hydroxy difluoromethyl ketones. These investigations provide structure-stability relationships of the difluoromethyl ketones following incubation with rodent serum and liver microsomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David A. Colby reports funding was provided by National Institute of General Medical Sciences. David A. colby reports financial support was provided by National Institute on Drug Abuse. David A. Colby reports a relationship with Fluoriq LLC that includes: equity or stocks. If there are other authors, they 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 Ltd. All rights reserved.)

An excellent technique for producing pharmaceuticals called "molecular farming" enables the industrial mass production of useful recombinant proteins in genetically modified organisms. Protein-based pharmaceuticals are rising in significance because of a variety of factors, including their bioreactivity, precision, safety, and efficacy rate. Heterologous expression methods for the manufacturing of pharmaceutical products have been previously employed using yeast, bacteria, and animal cells. However, the high cost of mammalian cell system, and production, the chance for product complexity, and contamination, and the hurdles of scaling up to commercial production are the limitations of these traditional expression methods. Plants have been raised as a hopeful replacement system for the expression of biopharmaceutical products due to their potential benefits, which include low production costs, simplicity in scaling up to commercial manufacturing levels, and a lower threat of mammalian toxin contaminations and virus infections. Since plants are widely utilized as a source of therapeutic chemicals, molecular farming offers a unique way to produce molecular medicines such as recombinant antibodies, enzymes, growth factors, plasma proteins, and vaccines whose molecular basis for use in therapy is well established. Biopharming provides more economical and extensive pharmaceutical drug supplies, including vaccines for contagious diseases and pharmaceutical proteins for the treatment of conditions like heart disease and cancer. To assess its technical viability and the efficacy resulting from the adoption of molecular farming products, the following review explores the various methods and methodologies that are currently employed to create commercially valuable molecules in plant systems., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

The focus of this case study is the delayed diagnosis of a perinatal HIV transmission, which was identified when the infant reached 4 months of age, and the social conditions and structural determinants that contributed to the increased transmission risk. Despite adhering to the diagnostic testing protocols and neonatal antiretroviral (ARV) guidelines of the New York State Department of Health, this transmission still occurred. This transmission event prompted strategies to address criminalization of substance use during pregnancy and a reevaluation of the HIV testing and treatment protocols, including the timing of testing. Obtaining a diagnostic specimen at birth before initiating prophylactic or presumptive therapy, without causing delays in therapy, and incorporating HIV-1 DNA or RNA testing 2 to 6 weeks after discontinuing ARV therapy might have facilitated earlier detection and a quicker resumption of ARV therapy for this high-risk infant. Subsequently, the New York State HIV perinatal testing guidelines were updated. These changes included the recommendation to obtain a diagnostic specimen at birth before initiating ARV medications, whenever feasible, without causing delays in ARV initiation. Additionally, an extra virologic diagnostic test is recommended at 2 to 6 weeks after discontinuing ARVs for infants at high risk of perinatal HIV transmission, especially those with possible DNA or RNA suppression due to ARV prophylaxis or presumptive HIV therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Interleaflet coupling-the influence of one leaflet on the properties of the opposing leaflet-is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by clustering transmembrane receptors for immunoglobulin E (IgE), FcεRI. This transmembrane signaling depends on the stabilization of ordered regions in the inner leaflet for sorting of intracellular signaling components. The resting inner leaflet has a lipid composition that is generally less ordered than the outer leaflet and that does not spontaneously phase separate in model membranes. We propose that interleaflet coupling can mediate ordering and disordering of the inner leaflet, which is poised in resting cells to reorganize upon stimulation. To test this in live cells, we first established a straightforward approach to evaluate induced changes in membrane order by measuring inner leaflet diffusion of lipid probes by imaging fluorescence correlation spectroscopy, by imaging fluorescence correlation spectroscopy (ImFCS), before and after methyl-α-cyclodexrin (mαCD)-catalyzed exchange of outer leaflet lipids (LEX) with exogenous order- or disorder-promoting phospholipids. We examined the functional impact of LEX by monitoring two Ag-stimulated responses: recruitment of cytoplasmic Syk kinase to the inner leaflet and exocytosis of secretory granules (degranulation). Based on the ImFCS data in resting cells, we observed global increase or decrease of inner leaflet order when outer leaflet is exchanged with order- or disorder-promoting lipids, respectively. We find that the degree of both stimulated Syk recruitment and degranulation correlates positively with LEX-mediated changes of inner leaflet order in resting cells. Overall, our results show that resting-state lipid ordering of the outer leaflet influences the ordering of the inner leaflet, likely via interleaflet coupling. This imposed lipid reorganization modulates transmembrane signaling stimulated by Ag clustering of IgE-FcεRI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. All rights reserved.)

Objective: We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5 mg and intravenous (IV) paracetamol 1 gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia., Methods: This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1-3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery., Results: There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: -1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from -0.8 cm to -1.6 cm., Discussion: The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Little is known about the effect of a multi-drug weight loss strategy in obesity treatment, particularly combining bupropion/naltrexone and glucagon-like peptide 1 (GLP-1) analogue. The purpose of this study was to evaluate if there are any additive effects of prescribing bupropion/naltrexone on top of GLP-1 analogue as weight loss therapy., Methods: This was a retrospective cohort study of adult patients with a body mass index (BMI) ≥ 30 kg/m 2 prescribed GLP-1 analogue therapy at an obesity specialist clinic in Vancouver, Canada. We compared a 6 and 12-month change in total body weight loss (TBWL) for those receiving monotherapy from the initiation of GLP-1 analogue therapy with those receiving combination therapy from the initiation of bupropion/naltrexone added-on therapy. Patients prescribed combination therapy were stratified into responder (loss of ≥ 5% TBWL) and non-responder (TBWL < 5%) subgroups based on initial response to the GLP-1 analogue alone for any amount of time., Results: The mean weight loss among patients prescribed GLP-1 analogue monotherapy at 12 months was 11.42 kg, SD 9.95 (9.6% TBWL). There was no significant difference between these two treatment strategies overall (HR 0.88, 95% CI 0.68 to 1.14, p = 0.35). However, when stratified by response to initial GLP analogue therapy, the addition of bupropion/naltrexone was associated with a statistically significant reduction in weight in both the responder (4.3% TBWL (p < 0.01)) and non-responder groups (4.0% TBWL (p < 0.01))., Conclusions: GLP-1 analogues are an effective treatment for weight loss, and the addition of bupropion/naltrexone is associated with greater weight loss including in patients who are initially non-responsive to GLP-1 analogues., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In India, fish roes are generally considered worthless garbage and disposed of without recovering the valuable molecules, creating environmental and disposal problems. The present investigation aimed to optimize the extraction conditions, partial purification, and characterization of sialoglycoproteins (RRSGP) from Labeo rohita (rohu) roes. RSM generated optimum conditions for maximum RRSGP (70.49 %) extraction, which were 1.25 M NaCl, 1:32.5(w/v) solid-to-liquid ratio, 47.5 °C temperature, and 3 h time. Further, sialoglycoproteins from RRSGPs were partially purified, and result revealed that obtained peak-1 (PRRSGP) using QFF anion exchange chromatography exhibited higher glycoprotein and sialic acid content (p < 0.05). SDS-PAGE pattern of PRRSGP presented dominant bands of 97 kDa and 27 kDa glycoproteins. FTIR spectrum of PRRSGP confirmed the presence of glycated proteins. HPLC analysis revealed that PRRSGP consists of Neu5Ac. Furthermore, β-elimination reaction elucidated that PRRSGP contained N-glycosidic linkage. PRRSGP exhibited tyrosine and glutamate as primary amino acids. Glycan part of PRRSGP presented mannose and N-acetyl galactosamine as dominant neutral and amino sugar, respectively. Furthermore, PRRSGP exhibited antioxidant activity with EC 50 value for DPPH (8.79 mg/ml) and ABTS (2.21 mg/ml). Besides, RRSGP displayed better protein solubility, foaming, and emulsion properties. Therefore, rohu roes are potential source of sialoglycoproteins that can be recovered and used as bio-functional ingredients in food and nutraceutical applications., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Several farmed fish species, including carps, tilapia, salmon, and catfish, have experienced significant economic losses in aquaculture due to motile Aeromonas septicemia caused by Aeromonas hydrophila. In the present study, a novel lytic bacteriophage infecting hypervirulent Aeromonas hydrophila (vAh) was isolated and characterized. This is the first report of a phage against vAh. Phage AhFM11 demonstrated lytic activity against both vAh strains and the A. hydrophila reference strain ATCC 35654. The AhFM11 genome was sequenced and assembled, comprising 168,243 bp with an average G + C content of 41.5%. The genome did not harbor any antibiotic resistance genes. Genomic information along with transmission electron microscopy revealed that phage AhFM11 belongs to the Straboviridae family. Therapeutic application of monophage AhFM11 in fish showed 100% survival in injection, 95% in immersion and 93% in oral feeding of phage top-coated feed. Fish and chicken meat spiked with A. hydrophila and phage showed significant reduction of A. hydrophila. These findings support that phage AhFM11 can be used as a biocontrol agent against vAh as an alternative to antibiotics., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Globally, lung cancer contributes significantly to the public health burden-associated mortality. As this form of cancer is insidious in nature, there is an inevitable diagnostic delay leading to chronic tumor development. Non-small cell lung cancer (NSCLC) constitutes 80-85% of all lung cancer cases, making this neoplasia form a prevalent subset of lung carcinoma. One of the most vital aspects for proper diagnosis, prognosis, and adequate therapy is the precise classification of non-small cell lung cancer based on biomarker expression profiling. This form of biomarker profiling has provided opportunities for improvements in patient stratification, mechanistic insights, and probable druggable targets. However, numerous patients have exhibited numerous toxic side effects, tumor relapse, and development of therapy-based chemoresistance. As a result of these exacting situations, there is a dire need for efficient and effective new cancer therapeutics. De novo drug development approach is a costly and tedious endeavor, with an increased attrition rate, attributed, in part, to toxicity-related issues. Drug repurposing, on the other hand, when combined with computer-assisted systems biology approach, provides alternatives to the discovery of new, efficacious, and safe drugs. Therefore, in this review, we focus on a comparison of the conventional therapy-based chemoresistance mechanisms with the repurposed anti-cancer drugs from three different classes-anti-parasitic, anti-depressants, and anti-psychotics for cancer treatment with a primary focus on NSCLC therapeutics. Certainly, amalgamating these novel therapeutic approaches with that of the conventional drug regimen in NSCLC-affected patients will possibly complement/synergize the existing therapeutic modalities. This approach has tremendous translational significance, since it can combat drug resistance and cytotoxicity-based side effects and provides a relatively new strategy for possible application in therapy of individuals with NSCLC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 (TLR4) signals via the Myddosome when triggered by lipopolysaccharide (LPS) or amyloid-beta (Aβ) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here, we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aβ 1-42 fibrils (80 vs 372 s). The mean lifetimes of the Myddosomes were also shorter when triggered by LPS compared to sonicated Aβ fibrils (170 and 220 s), respectively. In both cases, a range of Myddosome of different sizes (50-500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively, our data suggest that compared to LPS the multivalency of Aβ fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aβ fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates., Competing Interests: BL, PS, JB, SK, CB, DK No competing interests declared, (© 2024, Li, Suresh et al.)

An efficient and straightforward one-pot tandem synthesis of 3-arylindan-1-ones was consummated through silver nitrate-promoted C-C coupling of simple indane-1,3-dione with arylboronic acid via 1,3-indanedione monotosylhydrazone under microwave conditions. The resulting series of 3-arylindan-1-ones exhibited impressive yields, surpassing those achievable with traditional methods and requiring a shorter time frame. This innovative approach significantly accelerated the synthesis of biologically active compounds such as (+)-indatraline (Lu 19-005) and several other industrially relevant substances.

In response to the critical demand for advancements in coronary artery stents, this study addresses the challenges associated with arterial recoil and restenosis post-angioplasty and the imperative to encourage rapid re-endothelialization for minimizing thrombosis risks. We employed an innovative approach inspired by mussel adhesion, incorporating placental anticoagulant protein (AnnexinV) on stent design. The introduction of a post-translationally modified catecholic amino acid L-3,4-dihydroxyphenylalanine (L-Dopa), mimicking mussel characteristics, allowed for effective surface modification of Stainless steel stents through genetic code engineering in AnnexinV (AnxDopa). The efficacy of AnxDopa was analyzed through microscale thermophoresis and flow cytometry, confirming AnxDopa's exceptional binding with phosphatidylserine and activated platelets. AnxDopa coated stainless steel demonstrates remarkable bio-, hemo-, and immuno-compatibility, preventing smooth muscle cell proliferation, platelet adhesion, and fibrin formation. It acts as an interface between the stent and biological fluid, which facilitates the anticoagulation and rapid endothelialization. Surface modification of SS verified through XPS analysis and contact angle measurement attests to the efficacy of AnxDopa mediated surface modification. The hydrophilic nature of the AnxDopa-coated surface enhanced the endothelialization through increased protein absorption. This approach represents a significant stride in developing coronary stents with improved biocompatibility and reduced restenosis risks, offering valuable contributions to scientific and clinical realms alike., 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 Elsevier B.V. All rights reserved.)

Objectives: This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive cycling in 20 male and female cyclists. A multi-omics approach was used that included untargeted proteomics and a targeted oxylipin panel., Methods: A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 2.25 h cycling bout at close to 70%VO 2max . The BEET supplement provided 212 mg of nitrates per day, 200 mg caffeine from green tea extract, 44 mg vitamin C from Camu Camu berry, B-vitamins from quinoa sprouts (40% Daily Value for thiamin, riboflavin, niacin, and vitamin B6), and 2.5 g of a mushroom blend containing Cordyceps sinensis and Inonotus obliquus. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5 h-, 3 h-, and 24 h-post-exercise., Results: The 2.25 h cycling bout increased plasma levels of 41 of 67 oxylipins detected. BEET supplementation significantly increased plasma nitrate (NO 3 - ) and nitrite (NO 2 - ) (sum, NO 3 -  + NO 2 - ) concentrations (interaction effect, p  < 0.001) and two anti-inflammatory oxylipins [18-hydroxyeicosapentaenoic acid (18-HEPE) and 4-hydroxy-docosahexanoic acid (4-HDoHE)]. The untargeted proteomics analysis identified 616 proteins (458 across all times points), and 2-way ANOVA revealed a cluster of 45 proteins that were decreased and a cluster of 21 that were increased in the BEET versus PL trials. Functional enrichment supported significant BEET-related reductions in inflammation-related proteins including several proteins related to complement activation, the acute phase response, and immune cell adhesion, migration, and differentiation., Discussion: Intake of a BEET-based supplement during a 2-week period was linked to higher plasma levels of NO 3 -  + NO 2 - , elevated post-exercise levels of two anti-inflammatory oxylipins, and a significant decrease in a cluster of proteins involved in complement activation and inflammation. These data support that 2-weeks intake of nitrate from a mixed beet-based supplement moderated protein biomarkers of exercise-induced inflammation in athletes., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nieman, Sakaguchi, Williams, Mulani, Shivprasad Suresh, Omar and Zhang.)

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability. The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog., 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.)

The rising prevalence of drug-resistant Mycobacterium tuberculosis (MTB) strains poses a significant challenge to global tuberculosis (TB) control efforts. This study aimed to analyze drug resistance patterns and investigate the molecular characteristics of 193 MTB clinical isolates to shed light on the mechanisms of drug resistance. Of the 193 MTB clinical isolates, 28.5% (n = 53) exhibited mono-drug or multidrug resistance. Pyrazinamide mono-drug resistance (PZAr) was the most prevalent (17%, n = 33), followed by isoniazid mono-drug resistance (3.6%, n = 7). Rifampicin resistance was associated with mutations in the rpoB gene (D435Y, D435V, S450L, L452P). Isoniazid resistance mutations were found in the katG (S315T), inhA (C[-15] T), and ndh (R268H) genes, whereas ethambutol resistance mutations were observed in the embB gene (M306V, M306I, M306L, G406S, Q497R). Surprisingly, 94% of PZAr isolates (n = 31) showed no mutations in the pncA or rpsA genes. The presence of the R268H mutation in the ndh gene, not previously linked to PZAr, was detected in 15% of PZAr isolates (n = 5), suggesting its potential contribution to PZAr in specific cases but not as a predominant mechanism. The specific molecular mechanisms underlying PZAr in the majority of the isolates remain unknown, emphasizing the need for further research to uncover the contributing factors. These findings contribute to the understanding of drug resistance patterns and can guide future efforts in TB control and management.

Anxiety and depression in children and adolescents warrant special attention as a public health concern given their devastating and long-term effects on development and mental health. Multiple factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study aimed to understand how environmental factors and genomics affect children and adolescents anxiety and depression across three cohorts: Adolescent Brain and Cognitive Development Study (US, age of 9-10; N=11,875), Consortium on Vulnerability to Externalizing Disorders and Addictions (INDIA, age of 6-17; N=4,326) and IMAGEN (EUROPE, age of 14; N=1888). We performed data harmonization and identified the environmental impact on anxiety/depression using a linear mixed-effect model, recursive feature elimination regression, and the LASSO regression model. Subsequently, genome-wide association analyses with consideration of significant environmental factors were performed for all three cohorts by mega-analysis and meta-analysis, followed by functional annotations. The results showed that multiple environmental factors contributed to the risk of anxiety and depression during development, where early life stress and school support index had the most significant and consistent impact across all three cohorts. In both meta, and mega-analysis, SNP rs79878474 in chr11p15 emerged as a particularly promising candidate associated with anxiety and depression, despite not reaching genomic significance. Gene set analysis on the common genes mapped from top promising SNPs of both meta and mega analyses found significant enrichment in regions of chr11p15 and chr3q26, in the function of potassium channels and insulin secretion, in particular Kv3, Kir-6.2, SUR potassium channels encoded by the KCNC1, KCNJ11, and ABCCC8 genes respectively, in chr11p15. Tissue enrichment analysis showed significant enrichment in the small intestine, and a trend of enrichment in the cerebellum. Our findings provide evidences of consistent environmental impact from early life stress and school support index on anxiety and depression during development and also highlight the genetic association between mutations in potassium channels, which support the stress-depression connection via hypothalamic-pituitary-adrenal axis, along with the potential modulating role of potassium channels., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Thapaliya, Ray, Farahdel, Suresh, Sapkota, Holla, Mahadevan, Chen, Vaidya, Perrone-Bizzozero, Benegal, Schumann, Calhoun and Liu.)

Water can be sustainably and ecologically converted by electrocatalysts into hydrogen and oxygen, which, in turn, can be converted into energy. However, the advancement of using water as green energy is hampered by limitations in the study of high-performance catalysts. The purpose of this study was to construct an electrocatalyst by anchoring well-dispersed multiwalled carbon nanotubes (MWCNTs) on nickel-copper (NiCu-MOF) nanoblocks through a simple solvothermal method. The synthesis of NiCu-MOF@MWCNTs demonstrated exceptional electrocatalytic performance for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline medium. At 10 mA cm -2 in 1.0 M KOH, the OER and HER performance of the catalyst displays a relatively low overpotential, with only 220 and 78 mV, respectively. Furthermore, the catalytic activity remained unchanged for 24 h in 1.0 M KOH. This performance was superior to the majority of electrocatalysts that have been reported. This was achieved by utilizing the strong synergy that exists between MWCNTs and bimetallic (Ni-Cu) nano blocks present in the metal-organic framework. The enhanced electrocatalytic activity of the nanocomposite can be attributed to the synergistic impact caused by its various components.

To circumvent the synthesis and isolation of imines, a method was devised to construct α,α-difluoro-β-amino ketones from N -Boc-α-amidosulfones. The reactive nucleophiles, difluoroenolates, are generated in situ from the pentafluoro- gem -diols using cesium fluoride in pyridine. NMR studies confirm the role of the α-amidosulfones in this process. Incubation of the α,α-difluoro-β-amino ketones in rat serum demonstrates the relative stability of this structure as well as its value as a chemical probe or lead.

Formulating agrochemical products involves combining several chemical components, including the active ingredient(s), to obtain a final product with desirable efficacy. A formulated product incorporates additional components to modulate properties that enhance the efficacy of the active(s) by modifying physical properties such as viscosity, hydrophobicity, miscibility, and others. In plants, understanding the formulation's ability to spread on tissues and penetrate through the outer layer is critical in evaluating the efficacy of the final product. We have previously demonstrated the use of mass spectrometry imaging to determine spreadability. In this study, we show that laser ablation electrospray mass spectrometry (LAESI-MS) can be a valuable tool to assess the penetrability of formulations into the leaf tissues by selectively sampling various layers of leaf tissue by manipulating the laser intensity and analyzing the ablated material using a mass spectrometer. Using this technique, we were able to identify a formulation composition that can improve the penetration and uptake of active ingredients.

Malaria is one of the serious health concerns worldwide as it remains a clinical challenge due to the complex life cycle of the malaria parasite and the morphological changes it undergoes during infection. The malaria parasite multiplies rapidly and spreads in the population by changing its alternative hosts. These various morphological stages of the parasite in the human host cause clinical symptoms (anemia, fever, and coma). These symptoms arise due to the preprogrammed biology of the parasite in response to the human pathophysiological response. Thus, complete elimination becomes one of the major health challenges. Although malaria vaccine(s) are available in the market, they still contain to cause high morbidity and mortality. Therefore, an approach for eradication is needed through the exploration of novel molecular targets by tracking the epidemiological changes the parasite adopts. This review focuses on the various novel molecular targets., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background Health care is a significant contributor to climate change. Global pressure for a change towards a more sustainable way of providing dental health care has resulted in the creation of the Green Impact Toolkit, which is comprised of a list of suggested changes that dental practices can make to become more sustainable in a number of categories, such as procurement, waste and water.Aims To compare the effectiveness of changes suggested by the Green Impact Toolkit.Materials and methods A comparative life cycle assessment (LCA) was conducted using the Ecoinvent database v3.8 and these data were processed using OpenLCA v1.10.3 software.Results The carbon footprint per patient was significantly reduced after the recommendations were implemented. For instance, using water from a rainwater collection tank instead of the mains supply saved 30 g CO2eq (carbon dioxide equivalents) per patient, a 90% reduction in carbon footprint.Discussion This comparative LCA identified some effective changes which can be easily made by a dental practice. Nevertheless, some actions require some initial financial investment and may be difficult to implement in a busy modern dental practice setting.Conclusion The findings from this study can be used to guide dental practices to making choices which are more sustainable and eco-friendly in the future., (© 2024. The Author(s).)

Antimicrobial peptides (AMPs) with potent anti-listerial activity were characterized from a novel marine Bacillus velezensis FTL7. A Box-Behnken statistical experimental design was used to study the combined impact of culture conditions on the production of AMPs by B. velezensis FTL7. The conditions optimized by statistical experimental design were 34.5 °C incubation temperature, 23 h incubation time, and 7.6 initial pH of the medium. AMP purification was performed by ammonium sulphate fractionation and butanol extraction followed by reversed-phase C 18 solid-phase extraction. Tricine-SDS-PAGE analysis revealed a peptide with a molecular mass of ~ 6.5 kDa in an active AMPs fraction, whereas the mass spectrometry (MS) analysis showed the presence of AMPs in the mass range of 1-1.6 kDa, along with a 6.5 kDa peptide. Both MS and MS/MS analysis confirmed the AMPs as lipopeptides including surfactin, fengycins and iturin A and a circular bacteriocin amylocyclicin. The minimum inhibitory concentration of these AMPs against L. monocytogenes Scott A was 2.5 µg/mL. Further, the in-silico docking studies showed that the AMPs from B. velezensis FTL7 have high binding energy and stable binding patterns towards L. monocytogenes target proteins. Thus, this new combination of AMPs can serve as an effective food bio-preservative., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03944-5., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Leukaemic optic neuropathy is an uncommon cause of visual loss which represents a neuro-oncological emergency with the potential of irreversible blindness if untreated. It can be difficult to diagnose, often presenting with normal neuroradiological and cerebrospinal fluid findings. We present the case of a 26-year-old woman with T-cell acute lymphoblastic leukaemia with optic neuropathy secondary to leukaemic infiltration, who demonstrated features on optical coherence tomography that aided the diagnosis of this condition. This included the presence of numerous, small, hyperreflective opacities erupting from the optic nerve head, which improved following treatment with radiotherapy and chemotherapy, and later recurred when the condition relapsed. This finding may help clinicians differentiate between other causes of optic neuropathy as well as assessing response to treatment and monitoring for recurrence., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 Taylor & Francis Group, LLC.)

Signaling receptors on the plasma membrane, such as insulin receptor, can have their activity modulated to some extent by their surrounding lipids. Studying the contribution of membrane lipid properties such as presence of ordered lipid domains or bilayer thickness on the activity of receptors has been a challenging objective in living cells. Using methyl-alpha cyclodextrin-mediated lipid exchange, we are able to alter the lipids of the outer leaflet plasma membrane of mammalian cells to investigate the effect of the properties of the exchanged lipid upon receptor function in live cells. In this article, we describe the technique of lipid exchange in detail and how it can be applied to better understand lipid-mediated regulation of insulin receptor activity in cells., (Copyright © 2024. Published by Elsevier Inc.)

Smartphone accelerometry has potential to provide clinicians with specialized gait analysis not available in most clinical settings. The Gait&Balance Application (G&B App) uses smartphone accelerometry to assess spatiotemporal gait parameters under two conditions: walking looking straight ahead and walking with horizontal head turns. This study investigated the validity of G&B App gait parameters compared with the GAITRite® pressure-sensitive walkway. Healthy young and older adults (age range 21-85 years) attended a single session where a smartphone was secured over the lumbosacral junction. Data were collected concurrently with the app and GAITRite® systems as participants completed the two walking conditions. Spatiotemporal gait parameters for 54 participants were determined from both systems and agreement evaluated with partial Pearson's correlation coefficients and limits of agreement. The results demonstrated moderate to excellent validity for G&B App measures of step time (r p 0.97, 95 % CI [0.96, 0.98]), walking speed (r p 0.83 [0.78, 0.87]), and step length (r p 0.74, [0.66, 0.80]) when walking looking straight ahead, and results were comparable with head turns. The validity of walking speed and step length measures was influenced by sex and height. G&B App measures of step length variability, step time variability, step length asymmetry, and step time asymmetry had poor validity. The G&B App has potential to provide valid measures of unilateral and bilateral step time, unilateral and bilateral step length, and walking speed, under two walking conditions in healthy young and older adults. Further research should validate this tool in clinical conditions and optimise the algorithm for demographic characteristics., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Defatted Lagenaria siceraria seed flour (DLSSF) was obtained from defatted seed cake, dried, and ground through a sieve of 500 μm and characterized. A 2 × 4 factorial design (two flour hydration rates and four fat substitution rates) was used to produce a low-fat beef patty by replacing fat with DLSSF. Beef kidney fat was used to formulate the control sample. Chemical, physical, technological, sensory, and nutritional characteristics of low-fat beef patties manufactured were evaluated. DLSSF contains mainly protein. As fat replacers, DLSSF induces a significant increase in the pH of the raw and cooked patty, the moisture and protein contents, the cooking yield, the cohesion, chewiness, springiness, and lightness of the cooked beef patty with fat substitution rate. There is a decrease in fat content, total calories, water retention capacity, hardness, and redness of the cooked patty with a fat substitution rate. From the sensory analysis, the substitution of fat improves the acceptability of samples. Based on the overall parameters analyzed, DLSSF containing 60% water can be used to produce low-fat beef patty by replacing fat at 100%. From these results, hydrated DLSSF could be an effective method to solve the problems of noncommunicable diseases related to animal fat consumption., (© 2024 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Dicliptera cuneata Nees is a traditional medicinal plant but its extract or phytochemicals are less known. Therefore, it is of interest to investigate the anti-inflammatory and antioxidant effects of aerial part hydroalcoholic extract of Dicliptera cuneata Nees. Hence, we used protein denaturation assay, FRAP assay, Nitric oxide and peroxide scavenging assays methods following standard developed techniques. The hydro-alcoholic extract exhibited dose-dependent effectiveness in all the assays and showed maximum efficacy in the assays at higher doses selected. Data shows that hydroalcholic extract of Dicliptera cuneata Nees showed anti-inflammatory and antioxidant properties in in vitro settings. It should be noted that more data is needed to further develop the extract into suitable formulations., (© 2023 Biomedical Informatics.)

High-content imaging for compound and genetic profiling is popular for drug discovery but limited to endpoint images of fixed cells. Conversely, electronic-based devices offer label-free, live cell functional information but suffer from limited spatial resolution or throughput. Here, we introduce a semiconductor 96-microplate platform for high-resolution, real-time impedance imaging. Each well features 4096 electrodes at 25 µm spatial resolution and a miniaturized data interface allows 8× parallel plate operation (768 total wells) for increased throughput. Electric field impedance measurements capture >20 parameter images including cell barrier, attachment, flatness, and motility every 15 min during experiments. We apply this technology to characterize 16 cell types, from primary epithelial to suspension cells, and quantify heterogeneity in mixed co-cultures. Screening 904 compounds across 13 semiconductor microplates reveals 25 distinct responses, demonstrating the platform's potential for mechanism of action profiling. The scalability and translatability of this semiconductor platform expands high-throughput mechanism of action profiling and phenotypic drug discovery applications., (© 2023. The Author(s).)

Various polymeric materials have been investigated to produce unique modes of delivery for drug modules to achieve either temporal or spatial control of bioactives delivery. However, after intravenous administration, phagocytic cells quickly remove these nanostructures from the systemic circulation via the reticuloendothelial system (RES). To overcome these concerns, ecofriendly block copolymers are increasingly being investigated as innovative carriers for the delivery of bioactives. In this review, we discuss the design, fabrication techniques, and recent advances in the development of block copolymers and their applications as drug carrier systems to improve the physicochemical and pharmacological attributes of bioactives., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to a lack of ancestry-matched, functional, and segregation data, Asians have a higher rate of receiving a variant of uncertain significance (VUS) result following panel testing. Managing VUS results presents challenges, as it often leads to increased anxiety and distress among cancer patients undergoing genetic testing. This exploratory study aims to investigate the experience of Asian cancer patients upon receiving a VUS result. A qualitative, semi-structured interview study was conducted, involving cancer patients who had received a VUS result through the Cancer Genetics Service of the National Cancer Centre Singapore. Twenty participants were interviewed, and their responses were transcribed and analyzed using thematic analysis to identify key themes. Thematic analysis revealed five major themes: (1) VUS results are interpreted as uncertain outcomes; (2) a VUS result provides relief and prompts positive behavioral adjustments; (3) patients employ fatalism and religion as coping mechanisms to navigate uncertainty; (4) genetic counselors, family, and the community offer reassurance and support; (5) patients value updates on variant classifications for future management. While this novel study provides unique insights into the perspectives of Asian patients who receive VUS results, it also highlights patients' effective management of VUS results and uncertainty, which has implications for improving counseling practices in Asia. Emphasis must be placed on accurate interpretation and clear communication of VUS results to dispel the possibility of misconceptions, misdiagnosis, and mismanagement in cancer care., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Background: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS., Methods: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths. Image quality was evaluated qualitatively by a radiologist and quantitatively using a semi-automated pipeline to quantify common artefacts and image quality issues. The intra- and inter-rater repeatability of qualitative and quantitative scoring was also assessed., Results: Qualitative radiological scoring found that the image quality was generally good, with 94% of examinations rated as good or excellent and only one examination rated as non-diagnostic. There was a significant correlation between radiological and quantitative scoring for most measures, and intra- and inter-rater repeatability were generally good. When the quality of an overall examination was low, this was often due to low quality diffusion-weighted imaging (DWI), where signal to noise ratio (SNR), anterior thoracic signal loss and brain geometric distortion were found as significant predictors of examination quality., Conclusions: It is possible to successfully deliver a multi-centre WB-MRI study using the MY-RADS protocol involving scanners with a range of manufacturers, models and field strengths. Quantitative measures of image quality were developed and shown to be significantly correlated with radiological assessment. The SNR of DW images was identified as a significant factor affecting overall examination quality., Trial Registration: ClinicalTrials.gov, NCT03188172 , Registered on 15 June 2017., Critical Relevance Statement: Good overall image quality, assessed both qualitatively and quantitatively, can be achieved in a multi-centre whole-body MRI study using the MY-RADS guidelines., Key Points: • A prospective multi-centre WB-MRI study using MY-RADS can be successfully delivered. • Quantitative image quality metrics were developed and correlated with radiological assessment. • SNR in DWI was identified as a significant predictor of quality, allowing for rapid quality adjustment., (© 2023. European Society of Radiology (ESR).)

Maxillary midline diastema is a self-correcting anomaly which in few conditions may get retained in adolescence stage due to various aetiological factors and correction of which is usually done at permanent dentition stage. The persistence of midline diastema can be predicted in mixed dentition period and necessary management could be provided at the mixed dentition period. This case report is on a novel technique using 'M' spring to correct the midline diastema in mixed dentition period., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This numerical research presents a simple hybrid structure comprised of TiO 2 -Cu-BaTiO 3 for a modified Kretschmann configuration that exhibits high sensitivity and high resolution for biosensing applications through an angular interrogation method. Recently, copper (Cu) emerged as an exceptional choice as a plasmonic metal for developing surface plasmon sensors (SPR) with high resolution as it yields finer, thinner SPR curves than Ag and Au. As copper is prone to oxidation, especially in ambient conditions, the proposed structure involves the utilization of barium titanate (BaTiO 3 ) film as a protection layer that not only preserves Cu film from oxidizing but enhances the performance of the sensor to a great extent. Numerical results also show that the utilization of a thin adhesive layer of titanium dioxide (TiO 2 ) between the prism base and Cu film not only induces strong interaction between them but also enhances the performance of the sensor. Such a configuration, upon suitable optimization of the thickness of each layer, is found to enhance sensitivity as high as 552°/RIU with a figure of merit (FOM) of 136.97 RIU -1 . This suggested biosensor design with enhanced sensitivity is expected to enable long-term detection with greater accuracy and sensitivity even when using Cu as a plasmonic metal.

The present study is mainly concerned with the development of cost-efficient composite material utilized to produce one-dimensional manganese oxide (α-MnO 2 ) nanoparticles coated on two-dimensional graphitic carbon nitrides (HT-GCN) as nanocomposite (α-MnO 2 /HT-GCN) for highly efficient CIP degradation. The α-MnO 2 nanoparticles (NPs) were prepared by a simple hydrothermal technique before being decorated on HT-GCN (H denotes protonation and T represents thermal-decomposition-graphitic carbon nitride). Tauc plots were used to calculate the band gap values of the photocatalysts α-MnO 2 (1.74 eV), GCN (2.84 eV), HT-GCN (2.63 eV), and α-MnO 2 /HT-GCN (2.31 eV). The mechanism was investigated by various scavengers, particularly isopropanol ( • OH) makes a significant role in the photodegradation process. The degradation percentage for ciprofloxacin was 89.2% and the rate of reaction R 2  = 0.9913. This study demonstrates a unique method for developing a heterojunction-based nanocomposite of α-MnO 2 /HT-GCN, which exhibit better light absorption performance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The packaging of antimicrobials/chemotherapeutics into nanoliposomes can enhance their activity while minimizing toxicity. However, their use is still limited owing to inefficient/inadequate loading strategies. Several bioactive(s) which are non ionizable, and poorly aqueous soluble cannot be easily encapsulated into aqueous core of liposomes by using conventional means. Such bioactive(s) however could be encapsulated in the liposomes by forming their water soluble molecular inclusion complex with cyclodextrins. In this study, we developed Rifampicin (RIF) - 2-hydroxylpropyl-β-cyclodextrin (HP-β-CD) molecular inclusion complex. The HP-β-CD-RIF complex interaction was assessed by using computational analysis (molecular modeling). The HP-β-CD-RIF complex and Isoniazid were co-loaded in the small unilamellar vesicles (SUVs). Further, the developed system was functionalized with transferrin, a targeting moiety. Transferrin functionalized SUVs (Tf-SUVs) could preferentially deliver their payload intracellularly in the endosomal compartment of macrophages. In in vitro study on infected Raw 264.7 macrophage cells revealed that the encapsulated bioactive(s) could eradicate the pathogen more efficiently than free bioactive(s). In vivo studies further revealed that the Tf-SUVs could accumulate and maintain intracellular bioactive(s) concentrations in macrophages. The study suggests Tf-SUVs as a promising module for targeted delivery of a drug combination with improved/optimal therapeutic index and effective clinical outcomes., 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 B.V. All rights reserved.)

Understanding the molecular mechanisms of environmental salinity stress tolerance and acclimation strategies by photosynthetic organisms facilitates accelerating the genetic improvement of tolerant economically important crops. In this study, we have chosen the marine algae Dunaliella (D.) salina , a high-potential and unique organism that shows superior tolerance against abiotic stresses, especially hypersaline conditions. We have grown the cells in three different salt concentrations 1.5M NaCl (control), 2M NaCl, and 3M NaCl (hypersaline). Fast chlorophyll fluorescence analysis showed increased initial fluorescence (Fo) and decreased photosynthetic efficiency, indicating hampered photosystem II utilization capacity under hypersaline conditions. Also, the reactive oxygen species (ROS) localization studies and quantification revealed elevated accumulation of ROS was observed in the chloroplast in the 3M condition. Pigment analysis shows a deficit in chlorophyll content and increased carotenoid accumulation, especially lutein and zeaxanthin content. This study majorly explored the chloroplast transcripts of the D. salina cell as it is the major environmental sensor. Even though most of the photosystem transcripts showed moderate upregulation in hypersaline conditions in the transcriptome study, the western blot analysis showed degradation of the core as well as antenna proteins of both the photosystems. Among the upregulated chloroplast transcripts, chloroplast Tidi, flavodoxin IsiB, and carotenoid biosynthesis-related protein transcripts strongly proposed photosynthetic apparatus remodeling. Also, the transcriptomic study revealed the upregulation of the tetrapyrrole biosynthesis pathway (TPB) and identified the presence of a negative regulator of this pathway, called the s-FLP splicing variant. These observations point towards the accumulation of TPB pathway intermediates PROTO-IX, Mg-PROTO-IX, and P-Chlide, those earlier reported as retrograde signaling molecules. Our comparative transcriptomic approach along with biophysical and biochemical studies in D. salina grown under control (1.5 M NaCl) and hypersaline (3M NaCl) conditions, unveil an efficient retrograde signaling mechanism mediated remodeling of photosynthetic apparatus., Competing Interests: Authors NP and AK were employed by Novelgene Technologies Pvt, Ltd. The remaining 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 Ramachandran, Pandey, Yadav, Suresh, Kumar and Subramanyam.)

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

Background: Knowledge of anatomy and morphometry of the patella and patellar tendon is crucial for the selection of bone-patellar tendon-bone (BTB) graft for anterior cruciate ligament reconstruction. Graft tunnel mismatch in BTB graft especially in patients with patella alta or baja can result in compromised fixation for the bone-to-bone healing. This complication can be avoided by proper templating of graft using parameters measured from magnetic resonance imaging (MRI). The study aimed to derive morphometric data from MRI and predict the suitability of BTB graft preoperatively., Methods: MRI of 1,002 knees was chosen from database after applying the eligibility criteria, which included individuals in the age group of 18-50 years (both sexes) with the intact patella and patellar tendon. Individuals with pathologies of the knee joint and associated structures such as patellar fracture/dislocations, fractures of the distal femur and proximal tibia, and avulsion of the quadriceps tendon or patellar tendon were excluded. For analysis, 1.5 Tesla, proton density, and fat-suppressed sequences of sagittal and axial sections of T2-weighted MRI images were used., Results: Mean age of the 1,002 patients was 35.45 years and there were 290 women and 712 men. Respective measurements were as follows: patella length, width, and thickness, 40.3 mm, 40.2 mm, and 18.6 mm, respectively; patellar tendon length, width, and insertional thickness, 45.2 mm, 27.2 mm, and 5.7 mm, respectively; Insall-Salvati ratio, 1.13; overall graft length, 90.2 mm; and effective tendon length, 26.1 mm., Conclusions: A simple MRI analysis can give us valuable inputs on BTB graft morphometry. The values can also help us with the near-perfect graft harvest. The intraoperative complication of graft tunnel mismatch can be avoided by predicting the overall graft length, effective tendon length, tibial tunnel length, and patellar position using the measured parameters on MRI., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

There is an urgent unmet medical need to develop therapeutic options for the ~50% of depression patients suffering from treatment-resistant depression, which is difficult to treat with existing psycho- and pharmaco-therapeutic options. Classical psychedelics, such as the 5HT 2A agonists, have re-emerged as a treatment paradigm for depression. Recent clinical trials highlight the potential effectiveness of 5HT 2A agonists to improve mood and psychotherapeutic growth in treatment-resistant depression patients, even in those who have failed a median of four previous medications in their lifetime. Moreover, microdosing could be a promising way to achieve long-term alleviation of depression symptoms without a hallucinogenic experience. However, there are a gamut of practical barriers that stymie further investigation of microdosing 5HT 2A agonists, including: low compliance with the complicated dosing regimen, high risk of diversion of controlled substances, and difficulty and cost administering the long-term treatment regimens in controlled settings. Here, we developed a drug delivery system composed of multilayered cellulose acetate phthalate (CAP)/Pluronic F-127 (P) films for the encapsulation and interval delivery of 5HT 2A agonists from a fully biodegradable and biocompatible implant. CAPP film composition, thickness, and layering strategies were optimized, and we demonstrated three distinct pulses from the multilayered CAPP films in vitro. Additionally, the pharmacokinetics and biodistribution of the 5HT 2A agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) were quantified following the subcutaneous implantation of DOI-loaded single and multilayered CAPP films. Our results demonstrate, for the first time, the interval delivery of psychedelics from an implantable drug delivery system and open the door to future studies into the therapeutic potential of psychedelic delivery., (© 2023 Wiley Periodicals LLC.)

Aims/hypothesis: Beta cells control glucose homeostasis via regulated production and secretion of insulin. This function arises from a highly specialised gene expression programme that is established during development and then sustained, with limited flexibility, in terminally differentiated cells. Dysregulation of this programme is seen in type 2 diabetes but mechanisms that preserve gene expression or underlie its dysregulation in mature cells are not well resolved. This study investigated whether methylation of histone H3 lysine 4 (H3K4), a marker of gene promoters with unresolved functional importance, is necessary for the maintenance of mature beta cell function., Methods: Beta cell function, gene expression and chromatin modifications were analysed in conditional Dpy30 knockout mice, in which H3K4 methyltransferase activity is impaired, and in a mouse model of diabetes., Results: H3K4 methylation maintains expression of genes that are important for insulin biosynthesis and glucose responsiveness. Deficient methylation of H3K4 leads to a less active and more repressed epigenome profile that locally correlates with gene expression deficits but does not globally reduce gene expression. Instead, developmentally regulated genes and genes in weakly active or suppressed states particularly rely on H3K4 methylation. We further show that H3K4 trimethylation (H3K4me3) is reorganised in islets from the Lepr db/db mouse model of diabetes in favour of weakly active and disallowed genes at the expense of terminal beta cell markers with broad H3K4me3 peaks., Conclusions/interpretation: Sustained methylation of H3K4 is critical for the maintenance of beta cell function. Redistribution of H3K4me3 is linked to gene expression changes that are implicated in diabetes pathology., (© 2023. The Author(s).)