Preparation and assessment of agar/TEMPO-oxidized bacterial cellulose cryogels for hemostatic applications.

In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material.

The novel HLA-C*06:372 allele, identified in a stem cell donor of an old order mennonite ethnicity.

HLA-C*06:372 differs from HLA-C*06:02:01:01 by a single substitution in exon 4.

Holmium Laser Enucleation of Prostate: Is novel En Bloc Enucleation Technique Better Than the Traditional 2-Lobe Technique-A Prospective Randomized Study.

OBJECTIVE: To compare the safety and efficacy of the en bloc technique with the standard 2-lobe technique for holmium laser enucleation of the prostate (HoLEP). METHODS: This prospective study included patients with benign prostatic hyperplasia (BPH) who underwent HoLEP from September 2020 to March 2022, by en bloc or 2-lobe technique. Patient demographics, prostate volume, enucleation, morcellation and operative time, and incidence of postoperative incontinence were compared between the 2 groups. RESULTS: We included 64 patients (30 en bloc and 34 2-lobe techniques) who underwent HoLEP in this study. The mean age, prostate volume, creatinine, and PSA of patients were comparable in both groups [(68.53 vs. 67.55 years; P=.62), (79.43 vs. 79.88 g, P=.92), (1.08 mg/dL vs. 1.20 mg/dL, P=.35), (3.78 vs. 4.63 ng/mL; P=.376), respectively]. The enucleation time was significantly shorter in the en bloc group than in the 2-lobe group (54.2 vs. 61.67; P=.03). Additionally, the mean operative time was also comparatively shorter in the en bloc group than the 2-lobe group (72.36 vs. 80.50; P=.057). The improvement in the quality-of-life (QoL) score was significantly better with en bloc than the 2-lobe group (3.80 vs. 2.11; P=.01). There was a significant difference in stress urinary incontinence on days 1, 7, and 30 (P .001) with en bloc compared to the two-lobe technique. CONCLUSION: Although the outcomes of en bloc and 2-lobe endoscopic enucleation of prostate techniques were comparable, the en bloc technique seems to be a better option in most patients undergoing HoLEP due to less enucleation and operative time and lowered stress urinary incontinence incidence.

The CRTC-1 transcriptional domain is required for COMPASS complex-mediated longevity in C. elegans.

Loss of function during aging is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy aging.

Exploring the Impact of Head Group Modifications on the Anticancer Activities of Fatty-Acid-like Platinum(IV) Prodrugs: A Structure-Activity Relationship Study.

We conducted the first comprehensive investigation on the impact of head group modifications on the anticancer activities of fatty-acid-like Pt(IV) prodrugs (FALPs), which are a class of platinum-based metallodrugs that target mitochondria. We created a small library of FALPs (1-9) with diverse head group modifications. The outcomes of our study demonstrate that hydrophilic modifications exclusively enhance the potency of these metallodrugs, whereas hydrophobic modifications significantly decrease their cytotoxicity. To further understand this interesting structure-activity relationship, we chose two representative FALPs (compounds 2 and 7) as model compounds: one (2) with a hydrophilic polyethylene glycol (PEG) head group, and the other (7) with a hydrophobic hydrocarbon modification of the same molecular weight. Using these FALPs, we conducted a targeted investigation on the mechanism of action. Our study revealed that compound 2, with hydrophilic modifications, exhibited remarkable penetration into cancer cells and mitochondria, leading to subsequent mitochondrial and DNA damage, and effectively eradicating cancer cells. In contrast, compound 7, with hydrophobic modifications, displayed a significantly lower uptake and weaker cellular responses. The collective results present a different perspective, indicating that increased hydrophobicity may not necessarily enhance cellular uptake as is conventionally believed. These findings provide valuable new insights into the fundamental principles of developing metallodrugs.

Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction in C. elegans.

mTORC1 (mechanistic target of rapamycin complex 1) is a metabolic sensor that promotes growth when nutrients are abundant. Ubiquitous inhibition of mTORC1 extends lifespan in multiple organisms but also disrupts several anabolic processes resulting in stunted growth, slowed development, reduced fertility, and disrupted metabolism. However, it is unclear if these pleiotropic effects of mTORC1 inhibition can be uncoupled from longevity. Here, we utilize the auxin-inducible degradation (AID) system to restrict mTORC1 inhibition to C. elegans neurons. We find that neuron-specific degradation of RAGA-1, an upstream activator of mTORC1, or LET-363, the ortholog of mammalian mTOR, is sufficient to extend lifespan in C. elegans. Unlike raga-1 loss of function genetic mutations or somatic AID of RAGA-1, neuronal AID of RAGA-1 robustly extends lifespan without impairing body size, developmental rate, brood size, or neuronal function. Moreover, while degradation of RAGA-1 in all somatic tissues alters the expression of thousands of genes, demonstrating the widespread effects of mTORC1 inhibition, degradation of RAGA-1 in neurons only results in around 200 differentially expressed genes with a specific enrichment in metabolism and stress response. Notably, our work demonstrates that targeting mTORC1 specifically in the nervous system in C. elegans uncouples longevity from growth and reproductive impairments, and that many canonical effects of low mTORC1 activity are not required to promote healthy aging. These data challenge previously held ideas about the mechanisms of mTORC1 lifespan extension and underscore the potential of promoting longevity by neuron-specific mTORC1 modulation.

Li iontronics in single-crystalline T-Nb2O5 thin films with vertical ionic transport channels.

The niobium oxide polymorph T-Nb2O5 has been extensively investigated in its bulk form especially for applications in fast-charging batteries and electrochemical (pseudo)capacitors. Its crystal structure, which has two-dimensional (2D) layers with very low steric hindrance, allows for fast Li-ion migration. However, since its discovery in 1941, the growth of single-crystalline thin films and its electronic applications have not yet been realized, probably due to its large orthorhombic unit cell along with the existence of many polymorphs. Here we demonstrate the epitaxial growth of single-crystalline T-Nb2O5 thin films, critically with the ionic transport channels oriented perpendicular to the film's surface. These vertical 2D channels enable fast Li-ion migration, which we show gives rise to a colossal insulator-metal transition, where the resistivity drops by 11 orders of magnitude due to the population of the initially empty Nb 4d0 states by electrons. Moreover, we reveal multiple unexplored phase transitions with distinct crystal and electronic structures over a wide range of Li-ion concentrations by comprehensive in situ experiments and theoretical calculations, which allow for the reversible and repeatable manipulation of these phases and their distinct electronic properties. This work paves the way for the exploration of novel thin films with ionic channels and their potential applications.

Evaluation of Anti-plaque and Anti-gingivitis Efficacy of Two Commercially Available Herbal and Non-herbal Toothpastes.

BACKGROUND:  Plaque-associated oral disease affects a considerable portion of the population and is considered one of the major causes of tooth loss. The presence of plaque may be the reason for dental caries, gingivitis, periodontal problems, and halitosis. Many mechanical aids are used to control plaque, including toothbrushes, dental floss, mouth rinses, and dentifrices, and the most effective method of controlling gingivitis is supragingival plaque control. AIM AND OBJECTIVE: To evaluate and compare the anti-plaque and anti-gingivitis efficacy of commercially available herbal toothpaste (Meswak) and non-herbal toothpaste (Pepsodent). MATERIALS AND METHOD: 50 subjects aged between 10 and 15 years with a full complement of dentition were included in the study. The two toothpastes were provided to the subjects in plain white tubes by the investigator. Subjects were instructed to brush their teeth twice daily using the given toothpaste for 21 days. Plaque and gingival scores on days 0, 7, and 21 were recorded, and the data were subjected to statistical analysis. RESULT: At the end of the 21-day study, there was a statistically significant difference between the groups for plaque and gingival scores. CONCLUSION: The plaque and gingival scores were significantly reduced throughout the study in both groups. In comparison, the herbal dentifrices show more effectiveness in reducing plaque and gingival scores, but no statistically significant difference was seen between the two groups.

Marginal Bone Level Measurements of Unsplinted Implants Used for Mandibular Overdentures: A Six-Month Randomized Prospective Clinical Study Comparing Early and Delayed Loading Protocols.

Background and purpose Implant-supported mandibular overdentures are a good alternative for patients having poor retention of mandibular conventional dentures. The aim of this prospective study was to evaluate and compare the results between early loading and delayed loading of mandibular overdentures on two unsplinted implants. Materials and methods  A total of 14 completely edentulous male patients in the age group of 50-60 years were selected for the study. Two 3.5×13 mm implants were placed in the mandibular interforaminal region. The patients were divided into two groups: (i) the test group in which the overdenture was connected after one week of surgery, and (ii) the control group, in which the overdenture was connected three months after surgery. Marginal bone levels were evaluated at baseline (during loading), three months, and six months post loading. Unpaired 't' test was used for the comparison of intergroup measurements.  Results No implants were lost. Marginal bone resorptions showed no statistically significant differences between the two groups over six months period after loading. Conclusion The results of this prospective clinical study suggested that there was no significant difference in the clinical and radiographic state of patients treated with implant-supported mandibular overdentures loaded either one week or three months after implant surgery.

Reversal of Anomalous Hall Effect and Octahedral Tilting in SrRuO3 Thin Films via Hydrogen Spillover.

The perovskite SrRuO3 (SRO) is a strongly correlated oxide whose physical and structural properties are strongly intertwined. Notably, SRO is an itinerant ferromagnet that exhibits a large anomalous Hall effect (AHE) whose sign can be readily modified. Here, a hydrogen spillover method is used to tailor the properties of SRO thin films via hydrogen incorporation. It is found that the magnetization and Curie temperature of the films are strongly reduced and, at the same time, the structure evolves from an orthorhombic to a tetragonal phase as the hydrogen content is increased up to ≈0.9 H per SRO formula unit. The structural phase transition is shown, via in situ crystal truncation rod measurements, to be related to tilting of the RuO6 octahedral units. The significant changes observed in magnetization are shown, via density functional theory (DFT), to be a consequence of shifts in the Fermi level. The reported findings provide new insights into the physical properties of SRO via tailoring its lattice symmetry and emergent physical phenomena via the hydrogen spillover technique.

Curcumin coated 3D biocomposite scaffolds based on chitosan and cellulose for diabetic wound healing.

The objective of present work is to fabricate porous three-dimensional biocomposite scaffolds with interconnected pore networks and mechanical strength for wound healing. Variable concentrations of chitosan and methylcellulose hydrogels were blended in the presence of calcium cations to prepare scaffolds by freeze-drying method. Curcumin-aerosol was deposited over the scaffold surface to improve antimicrobial efficacy. Scaffold stability and curcumin interaction were evaluated by Differential Scanning Calorimeter, Thermal Gravimetric Analyzer and Fourier Transform Infrared Spectrophotometer. Scanning Electron Microscopy indicate multi-layered porosity, mesh-like structure and pore-size ranging from 50 to 500 µm. Erythrocyte interaction with chitosan and methylcellulose using Surface Plasmon Resonance assay in the presence of curcumin depicted high binding affinity of chitosan alone than curcumin. The antibacterial activity of SCF-4C against Escherichia coli and Staphylococcus aureus and the instant haemostasis in erythrocyte-agglutination assay by SCF-7 indicate good material properties for wound treatment. Bleeding time and wound healing efficacy conducted on Sprague Dawley rats depict minimum clotting time of SCF-4 (∼32 ± 2 s) compared to SCF-4C (∼45 ± 2 s), while highest ∼85 ± 5 s was observed in curcumin alone. SCF-4C exhibit complete wound healing on day14 in diabetic animals. In-vivo studies confirmed that high concentration of chitosan in presence of curcumin enhances diabetic wound healing process.

Successful management of recalcitrant fungal keratitis with topical caspofungin.

Objective: To report a case of recalcitrant fungal keratitis successfully managed with topical caspofungin acetate in North India. Methods: Case report and literature review. Results: An 18-year-old male patient presented with complaints of redness, watering, pain and diminution of vision in the right eye and was referred to our centre as a case of corneal ulcer. The patient was examined and found to have a near total epithelial defect, with corneal infiltrates approximately 8x8 mm. A provisional diagnosis of polymicrobial keratitis was made based on corneal scraping suggestive of S tap h ylococcus aureus and confocal scan revealing fungal hyphae. The patient failed to respond to topical voriconazole 1%, natamycin 5% and moxifloxacin hydrochloride 0.5% with oral voriconazole. In view of the poor response to these drugs, the patient was subsequently administered topical caspofungin 0.5% in place of natamycin and continued on topical and oral voriconazole, in addition to topical moxifloxacin and cycloplegics, which finally led to healing with minimal scarring. The patient attained a best corrected visual acuity (BCVA) of 6/12. Conclusion: Topical caspofungin may be used as a useful and effective alternative in cases of recalcitrant fungal keratitis. It may result in healing with minimal scarring.

Uroflowmetric analysis and derivation of nomograms for normal paediatric Indian population between 5 to 15 years of age.

Objective: We aimed to established normal uroflowmetric values and subsequently derived nomograms of maximum flow rate (Qmax) and average flow rate (Qavg) against voided volume (VV) in children aged 5-15 years at our institute. Methods: A total of 440 children underwent uroflowmetric evaluation with no history of urological, renal, psychiatric, or neurological disorder between 5 and 15 years of age. Each subject data regarding Qmax, Qavg, VV, time to Qmax, and flow time, as well as age, sex, height, and weight were recorded. Of the 440 children, around 300 (68.18%) children could produce a normal flow rate at VV of more than 50 mL. Of the remaining 140 (31.82%) children, 50.00% voided less than 50 mL, and remaining 50.00% had abnormal voiding pattern, staccato or interrupted (21.43% each) and plateau or tower shaped (3.57% each). Cases were divided into two age groups (5-9 years and 10-15 years), and uroflowmetric analysis was done between boys and girls in both age groups to derive nomograms of Qavg and Qmax. Results: Qmax and Qavg flow nomograms were plotted for boys and girls. Mean Qmax for boys was 16.68 mL/s and for girls 20.69 mL/s. The mean Qavg values were 11.04 mL/s and 8.60 mL/s for girls and boys, respectively. The Qmax and Qavg values were higher in girls. There were significant increases in flow rates with increasing age, body surface area, and VV in both sexes. Conclusions: Nomograms for Qmax and Qavg may be a useful tool in evaluation of lower urinary tract disturbances in children.

Control of Oxygen Vacancy Ordering in Brownmillerite Thin Films via Ionic Liquid Gating.

Oxygen defects and their atomic arrangements play a significant role in the physical properties of many transition metal oxides. The exemplary perovskite SrCoO3-δ (P-SCO) is metallic and ferromagnetic. However, its daughter phase, the brownmillerite SrCoO2.5 (BM-SCO), is insulating and an antiferromagnet. Moreover, BM-SCO exhibits oxygen vacancy channels (OVCs) that in thin films can be oriented either horizontally (H-SCO) or vertically (V-SCO) to the film's surface. To date, the orientation of these OVCs has been manipulated by control of the thin film deposition parameters or by using a substrate-induced strain. Here, we present a method to electrically control the OVC ordering in thin layers via ionic liquid gating (ILG). We show that H-SCO (antiferromagnetic insulator, AFI) can be converted to P-SCO (ferromagnetic metal, FM) and subsequently to V-SCO (AFI) by the insertion and subtraction of oxygen throughout thick films via ILG. Moreover, these processes are independent of substrate-induced strain which favors formation of H-SCO in the as-deposited film. The electric-field control of the OVC channels is a path toward the creation of oxitronic devices.

Enhanced Watershed Segmentation Algorithm-Based Modified ResNet50 Model for Brain Tumor Detection.

This work delivers a novel technique to detect brain tumor with the help of enhanced watershed modeling integrated with a modified ResNet50 architecture. It also involves stochastic approaches to help in developing enhanced watershed modeling. Cancer diseases, primarily the brain tumor, have been exponentially raised which has alarmed researchers from academia and industry. Nowadays, researchers need to attain a more effective, accurate, and trustworthy brain tumor tissue detection and classification approach. Different from traditional machine learning methods that are just targeting to enhance classification efficiency, this work highlights the process to extract several deep features to diagnose brain tumor effectively. This paper explains the modeling of a novel technique by integrating the modified ResNet50 with the Enhanced Watershed Segmentation (EWS) algorithm for brain tumor classification and deep feature extraction. The proposed model uses the ResNet50 model with a modified layer architecture including five convolutional layers and three fully connected layers. The proposed method can retain the optimal computational efficiency with high-dimensional deep features. This work obtains a comprised feature set by retrieving the diverse deep features from the ResNet50 deep learning model and feeds them as input to the classifier. The good performing capability of the proposed model is achieved by using hybrid features of ResNet50. The brain tumor tissue images were extracted by the suggested hybrid deep feature-based modified ResNet50 model and the EWS-based modified ResNet50 model with a high classification accuracy of 92% and 90%, respectively.

Efficacy of Trabeculectomy Combined With Limited Deep Sclerectomy Versus Trabeculectomy Alone: A Randomized-controlled Trial.

PRCIS: The addition of limited deep sclerectomy (LDS) to conventional trabeculectomy increases the success rate, especially in pseudophakic eyes. PURPOSE: This study aimed to evaluate the efficacy of LDS in enhancing the intraocular pressure (IOP)-lowering outcomes of trabeculectomy. DESIGN: This was a parallel-arm, single-masked, randomized-controlled trial. METHODS: A total of 68 patients (68 eyes) with moderate to advanced primary open-angle glaucoma or primary angle-closure glaucoma with pseudophakia were recruited at a tertiary eye care center in Northern India and randomized into 2 groups. Thirty-five eyes in group 1 were subjected to trabeculectomy alone and 33 eyes in group 2 were subjected to trabeculectomy with LDS. All cases were supplemented with low-dose subconjunctival mitomycin-C (0.1 mg/mL for 1 min) in both groups. The primary outcome measure was IOP, and success rates were calculated for IOP ≤18/15/12 and ≥5 mm Hg. The secondary outcome measures included evaluation of bleb morphology, presence of an intrascleral aqueous lake, and supraciliary flow on ultrasound biomicroscopy. RESULTS: The mean postoperative IOP at 12 months was 13.4±1.83 mm Hg in group 1 and 12.5±1.67 mm Hg in group 2 (P=0.04). For IOP cutoff ≤15 mm Hg, absolute success was noted in 11 (31.4%) and 22 eyes (66.6%) in groups 1 and 2, respectively (P=0.004). At 12 months, the intrascleral lake was detected in 2 (6%) eyes in group 1 and in 9 (29%) eyes in group 2 (P=0.02). Supraciliary flow was detected in 2 eyes (6.2%) in group 2 and none in group 1 at 12 months (P=0.02). In the Cox proportional hazard model, trabeculectomy with LDS was associated with a lower rate of failure (hazard ratio: 0.32, 95% confidence interval: 0.13-0.75, P=0.009). CONCLUSION: The addition of LDS to trabeculectomy led to lower mean IOP and higher success rates at 12 months, compared with trabeculectomy alone.

Fabrication of Three-Dimensional Bioactive Composite Scaffolds for Hemostasis and Wound Healing.

Fabrication of 3D composite scaffolds was carried out by lyophilization of variable concentrations of collagen and chitosan gel solutions. Fibrinogen and thrombin aerosol were deposited over the surface of scaffolds to enhance hemostasis and wound healing. Composite scaffolds were characterized using differential scanning calorimetry, thermogravimetric analysis, and Fourier-transform infrared spectrophotometer to ascertain the aerosol deposition and stability. Scanning electron microscope showed multilayered porosity with pore size of ~30 µm and mushroom-like fibril growth of aerosol. A detailed investigation by surface plasmon resonance confirmed higher binding affinity of collagen toward the human blood platelets and erythrocytes in comparison to chitosan and was found to increase with the increase in blood cell concentration from 480.8 to 886.4 RU for erythrocytes. Scaffolds showed higher binding response for platelets than erythrocytes, while fibrinogen and thrombin showed no or limited interaction. Highest blood sorption of 83 ± 4% was observed in case of aerosol deposited scaffolds. Aerosol deposited scaffolds showed minimum clotting time of 20 ± 3 s and bleeding time of 38 ± 4 s, which was significantly lower compared to the scaffolds without aerosol treatment. Aerosol deposited composite scaffolds with 2:1 concentration of chitosan/collagen showed complete wound contraction by day 14, while 50% was observed in case of the control group. In vivo studies revealed that chitosan had a crucial role in the inflammatory phase, while collagen played an important role in the proliferation and maturation phase. The present study suggests that the fabricated 3D composite scaffolds with bioactive moieties may be a potential candidate for enhanced hemostasis and wound healing applications.