Signatures of a surface spin-orbital chiral metal.

The relation between crystal symmetries, electron correlations and electronic structure steers the formation of a large array of unconventional phases of matter, including magneto-electric loop currents and chiral magnetism1-6. The detection of such hidden orders is an important goal in condensed-matter physics. However, until now, non-standard forms of magnetism with chiral electronic ordering have been difficult to detect experimentally7. Here we develop a theory for symmetry-broken chiral ground states and propose a methodology based on circularly polarized, spin-selective, angular-resolved photoelectron spectroscopy to study them. We use the archetypal quantum material Sr2RuO4 and reveal spectroscopic signatures that, despite being subtle, can be reconciled with the formation of spin-orbital chiral currents at the surface of the material8-10. As we shed light on these chiral regimes, our findings pave the way for a deeper understanding of ordering phenomena and unconventional magnetism.

Uncovering the Lowest Thickness Limit for Room-Temperature Ferromagnetism of Cr1.6Te2.

Metallic ferromagnetic transition metal dichalcogenides have emerged as important building blocks for scalable magnetic and memory applications. Downscaling such systems to the ultrathin limit is critical to integrate them into technology. Here, we achieved layer-by-layer control over the transition metal dichalcogenide Cr1.6Te2 by using pulsed laser deposition, and we uncovered the minimum critical thickness above which room-temperature magnetic order is maintained. The electronic and magnetic structures are explored experimentally and theoretically, and it is shown that the films exhibit strong in-plane magnetic anisotropy as a consequence of large spin-orbit effects. Our study elucidates both magnetic and electronic properties of Cr1.6Te2 and corroborates the importance of intercalation to tune the magnetic properties of nanoscale materials' architectures.

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial.

BACKGROUND & AIMS: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC. METHODS: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. RESULTS: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 µg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia. CONCLUSIONS: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827).

Not all T cell epitopes are equally desired: a review of in silico tools for the prediction of cytokine-inducing potential of T-cell epitopes.

Assessment of protective or harmful T cell response induced by any antigenic epitope is important in designing any immunotherapeutic molecule. The understanding of cytokine induction potential also helps us to monitor antigen-specific cellular immune responses and rational vaccine design. The classical immunoinformatics tools served well for prediction of B cell and T cell epitopes. However, in the last decade, the prediction algorithms for T cell epitope inducing specific cytokines have also been developed and appreciated in the scientific community. This review summarizes the current status of such tools, their applications, background algorithms, their use in experimental setup and functionalities available in the tools/web servers.

Transmembrane pH gradient imaging in rodent glioma models.

A unique feature of the tumor microenvironment is extracellular acidosis in relation to intracellular milieu. Metabolic reprogramming in tumors results in overproduction of H+ ions (and lactate), which are extruded from the cells to support tumor survival and progression. As a result, the transmembrane pH gradient (ΔpH), representing the difference between intracellular pH (pHi) and extracellular pH (pHe), is posited to be larger in tumors compared with normal tissue. Controlling the transmembrane pH difference has promise as a potential therapeutic target in cancer as it plays an important role in regulating drug delivery into cells. The current study shows successful development of an MRI/MRSI-based technique that provides ΔpH imaging at submillimeter resolution. We applied this technique to image ΔpH in rat brains with RG2 and U87 gliomas, as well as in mouse brains with GL261 gliomas. pHi was measured with Amine and Amide Concentration-Independent Detection (AACID), while pHe was measured with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). The results indicate that pHi was slightly higher in tumors (7.40-7.43 in rats, 7.39-7.47 in mice) compared with normal brain (7.30-7.38 in rats, 7.32-7.36 in mice), while pHe was significantly lower in tumors (6.62-6.76 in rats, 6.74-6.84 in mice) compared with normal tissue (7.17-7.22 in rats, 7.20-7.21 in mice). As a result, ΔpH was higher in tumors (0.64-0.81 in rats, 0.62-0.65 in mice) compared with normal brain (0.13-0.16 in rats, 0.13-0.16 in mice). This work establishes an MRI/MRSI-based platform for ΔpH imaging at submillimeter resolution in gliomas.

Genetic diversity, spatial connectivity, and population structure of Asian silurid catfish Wallago attu (Bloch and Schneider, 1801) in the Ganga River System: insights from mitochondrial DNA analysis.

BACKGROUND: The Ganga River System (GRS) is a biodiversity hotspot, its ecological richness is shaped by a complex geological history. In this study, we examined the genetic diversity, spatial connectivity, and population structure of the Asian Silurid catfish, Wallago attu, across seven tributaries of the GRS. METHODS AND RESULTS: We employed three mitochondrial DNA (mtDNA) regions: cytochrome c oxidase subunit I (COXI), cytochrome b (Cyt b), and control region (CR). Our comprehensive dataset encompassed 2420 bp of mtDNA, derived from 176 W. attu individuals across 19 sampling sites within the seven rivers of GRS. Our findings revealed high gene diversity (Hd:0.99) within W. attu populations. Analysis of Molecular Variance (AMOVA) highlighted that maximum genetic variations were attributed within the populations, and the observed genetic differentiation among the seven populations of W. attu ranged from low to moderate. Network analysis uncovered the presence of three distinct genetic clades, showing no specific association with seven studied rivers. Bayesian skyline plots provided insights into the demographic history of W. attu, suggesting a recent population expansion estimated to have occurred approximately 0.04 million years ago (mya) during the Pleistocene epoch. CONCLUSIONS: These results significantly enhance our understanding of the genetic diversity and spatial connectivity of W. attu, serving as a vital foundation for developing informed conservation strategies and the sustainable management of this economically valuable resource within the Ganga River System.

Interfacial-interaction induced modifications in segmental dynamics and free volume of the poly(ethyleneimine) canopy in nanoparticle-organic hybrid materials: an investigation by temperature dependent broadband dielectric and positron annihilation spectroscopy.

Broadband dielectric spectroscopy, positron annihilation lifetime spectroscopy and differential scanning calorimetry are used to investigate the molecular dynamics, free volume and thermal behaviour of a poly(ethyleneimine), PEI, canopy in liquid-like nanoparticle-organic hybrid materials (NOHMs) consisting of alumina nanoparticles and nanorods as inorganic nanocores. It is confirmed that the highly branched PEI canopy in liquid-like NOHMs possesses an ordered structure having less entanglements of the side chains as compared to neat PEI. The size of the free volumes associated with the PEI canopy for nanoparticle- and nanorod-based NOHMs is larger and smaller, respectively, as compared to neat PEI. The time scales characterizing the segmental dynamics and side chain relaxations of the canopy in the nanorod-based NOHM are slowed down drastically as compared to the nanoparticle-based NOHM and neat PEI. These results confirm that the shape of the inorganic cores plays a deterministic role toward the structural arrangement (free volume) and segmental dynamics of the canopy polymer in liquid-like NOHMs.

Wide-angle camouflage detectors by manipulating emissivity using a non-reciprocal metasurface array.

Camouflage detectors that can detect incoming radiation from any angle without being detected are extremely important in stealth, guided missile, and heat-seeking missile industries. In order to accomplish this, the absorption and emission processes must be manipulated simultaneously. However, Kirchhoff's fundamental law suggests that absorption and emission are always in the same direction α(θ) = ε(θ), i.e., absorption and emission are reciprocal. This means that the emission from the detector always points back to the source, for example towards a laser source in a guided missile. Thus, detector emission serves as a complementary measure to hide an object. Here, we present a novel camouflage detector that uses a nonreciprocal metasurface array to independently detect the direction of the incoming radiation as well as manipulate its emissivity response. This is accomplished by using a magneto-optical material called indium arsenide (InAs), which breaks Lorentz reciprocity and Kirchhoff's fundamental law such that α(θ) ≠ ε(θ). This design results in the following absorption and emission: α(θ) = ε(-θ). Nine metasurfaces were designed, optimized, and operated at different incident angles from +50° to -50° at a wavelength of 13 µm. Furthermore, by keeping all metasurfaces in a pixilated array form, one could make a device that works over the full ±50° range. Potentially, this array of nonreciprocal metasurfaces can be used to fabricate thermal emitters or solar-harvesting systems.

Tetrahydrobenzothiophene derivatives ameliorate Mia PaCa-2 cell progression and induces apoptosis via inhibiting EGFR2 tyrosine kinase signal.

A series of new thiophene analogues with acarbonitrile-basedmoiety were designed and synthesized via structural optimization. The conjugates were assessed for their in-vitro cytotoxic activity against a human pancreatic cancer cell line (Mia PaCa-2) and among them compound 5b showed IC50 value of 13.37 ± 2.37 µM. The compounds 5b (20 µM & 25 µM) and 7c (30 & 35 µM) also showed reduced clonogenicity, enhanced ROS and decreased mitochondrial membrane potential in Mia PaCa-2 cells. Treatment with these compounds also increased apoptotic population as evident with the double staining assay. Among the evaluated series, compounds 5b, 5g, 7c, and 9a attained a greater inhibitory potency than first generation's reversible EGFR inhibitor, Gefitinib. EGFR2 enzyme inhibitory studies revealed that 5b efficiently and arbitrarily suppressed the development of EGFR2 dependent cells and inhibited the enzymatic activity with an IC50 value of 0.68 µM; interestingly, the most effective molecule 5b with N-methyl piperazine substitution, has 1.29-fold greater potency than well-known EGFR inhibitor Gefitinib and increased Gefitinib's anti-growth impact with 2.04 folds greater against Mia PaCa-2. The in-vitro studies were validated with in-silico docking studies wherein compounds 5b and 7c exhibited binding energies of -8.2 and -7.4 Kcal/mol respectively. The present study reveals that tetrahydrobenzothiophene based analogues could be a promising lead for the evolution of potent chemo preventives over pancreatic cancer.

Multimodal Biomedical Image Segmentation using Multi-Dimensional U-Convolutional Neural Network.

Deep learning recently achieved advancement in the segmentation of medical images. In this regard, U-Net is the most predominant deep neural network, and its architecture is the most prevalent in the medical imaging society. Experiments conducted on difficult datasets directed us to the conclusion that the traditional U-Net framework appears to be deficient in certain respects, despite its overall excellence in segmenting multimodal medical images. Therefore, we propose several modifications to the existing cutting-edge U-Net model. The technical approach involves applying a Multi-Dimensional U-Convolutional Neural Network to achieve accurate segmentation of multimodal biomedical images, enhancing precision and comprehensiveness in identifying and analyzing structures across diverse imaging modalities. As a result of the enhancements, we propose a novel framework called Multi-Dimensional U-Convolutional Neural Network (MDU-CNN) as a potential successor to the U-Net framework. On a large set of multimodal medical images, we compared our proposed framework, MDU-CNN, to the classical U-Net. There have been small changes in the case of perfect images, and a huge improvement is obtained in the case of difficult images. We tested our model on five distinct datasets, each of which presented unique challenges, and found that it has obtained a better performance of 1.32%, 5.19%, 4.50%, 10.23% and 0.87%, respectively.

Robust brain tumor classification by fusion of deep learning and channel-wise attention mode approach.

Diagnosing brain tumors is a complex and time-consuming process that relies heavily on radiologists' expertise and interpretive skills. However, the advent of deep learning methodologies has revolutionized the field, offering more accurate and efficient assessments. Attention-based models have emerged as promising tools, focusing on salient features within complex medical imaging data. However, the precise impact of different attention mechanisms, such as channel-wise, spatial, or combined attention within the Channel-wise Attention Mode (CWAM), for brain tumor classification remains relatively unexplored. This study aims to address this gap by leveraging the power of ResNet101 coupled with CWAM (ResNet101-CWAM) for brain tumor classification. The results show that ResNet101-CWAM surpassed conventional deep learning classification methods like ConvNet, achieving exceptional performance metrics of 99.83% accuracy, 99.21% recall, 99.01% precision, 99.27% F1-score and 99.16% AUC on the same dataset. This enhanced capability holds significant implications for clinical decision-making, as accurate and efficient brain tumor classification is crucial for guiding treatment strategies and improving patient outcomes. Integrating ResNet101-CWAM into existing brain classification software platforms is a crucial step towards enhancing diagnostic accuracy and streamlining clinical workflows for physicians.

A hybrid deep CNN model for brain tumor image multi-classification.

The current approach to diagnosing and classifying brain tumors relies on the histological evaluation of biopsy samples, which is invasive, time-consuming, and susceptible to manual errors. These limitations underscore the pressing need for a fully automated, deep-learning-based multi-classification system for brain malignancies. This article aims to leverage a deep convolutional neural network (CNN) to enhance early detection and presents three distinct CNN models designed for different types of classification tasks. The first CNN model achieves an impressive detection accuracy of 99.53% for brain tumors. The second CNN model, with an accuracy of 93.81%, proficiently categorizes brain tumors into five distinct types: normal, glioma, meningioma, pituitary, and metastatic. Furthermore, the third CNN model demonstrates an accuracy of 98.56% in accurately classifying brain tumors into their different grades. To ensure optimal performance, a grid search optimization approach is employed to automatically fine-tune all the relevant hyperparameters of the CNN models. The utilization of large, publicly accessible clinical datasets results in robust and reliable classification outcomes. This article conducts a comprehensive comparison of the proposed models against classical models, such as AlexNet, DenseNet121, ResNet-101, VGG-19, and GoogleNet, reaffirming the superiority of the deep CNN-based approach in advancing the field of brain tumor classification and early detection.

INF2 and ROBO2 gene mutation in an Indian family with end stage renal failure and follow-up of renal transplantation.

BACKGROUND: Accurate genetic diagnosis of end-stage renal disease patients with a family history of renal dysfunction is very essential. It not only helps in proper prognosis, but becomes crucial in designating donor for live related renal transplant. We here present a case of family with deleterious mutations in INF2 and ROBO2 and its importance of genetic testing before preparing for kidney transplantation. CASE PRESENTATION: We report the case of a 29-year-female with end-stage renal disease and rapidly progressive renal failure. Mutational analysis revealed an Autosomal Dominant inheritance pattern and mutation in exon 4 of the INF2 gene (p. Thr215Ser) and exon 26 of the ROBO2 gene (p. Arg1371Cys). Her mother was diagnosed for CKD stage 4 with creatinine level of 4.3 mg/dL. Genetic variants (INF2 and ROBO2) identified in proband were tested in her sisters and mother. Her elder sister was positive for both heterozygous variants (INF2 and ROBO2). Her mother was positive for mutation in INF2 gene, and her donor elder sister did not showed mutation in INF2 gene and had mutation in ROBO2 gene without any clinical symptoms. CONCLUSION: This case report emphasize that familial genetic screening has allowed us in allocating the donor selection in family where family member had history of genetic defect of Chronic Kidney Disease. Information of the causative renal disorder is extremely valuable for risk-assessment and planning of kidney transplantation.

Enhancing Immunological Memory: Unveiling Booster Doses to Bolster Vaccine Efficacy Against Evolving SARS-CoV-2 Mutant Variants.

A growing number of re-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals has sparked discussions about the potential need for a booster vaccine dosage to counteract declining antibody levels and new strains. The protective immunity produced by vaccinations, and past illnesses relies on immunological memory. CD4 + T cells, CD8 + T cells, B cells, and long-lasting antibody responses are all components of the adaptive immune system that can generate and maintain this immunological memory. Since novel mutant variants have emerged one after the other, the world has been hit by repeated waves. Various vaccine formulations against SARS-CoV-2 have been administered across the globe. Thus, estimating the efficacy of those vaccines against gradually developed mutant stains is the essential parameter regarding the fate of those vaccine formulations and the necessity of booster doses and their frequency. In this review, focus has also been given to how vaccination stacks up against moderate and severe acute infections in terms of the longevity of the immune cells, neutralizing antibody responses, etc. However, hybrid immunity shows a greater accuracy of re-infection of variants of concern (VOCs) of SARS-CoV-2 than infection and immunization. The review conveys knowledge of detailed information about several marketed vaccines and the status of their efficacy against specific mutant strains of SARS-CoV-2. Furthermore, this review discusses the status of immunological memory after infection, mixed infection, and vaccination.

Comparison of preformed microcuff and preformed uncuffed endotracheal tubes in pediatric cleft palate surgery-A randomized controlled trial.

BACKGROUND AND AIMS: Airway management in children with oral cleft surgery carries unique challenges, concerning the proximity of the surgical site and the tracheal tube. We hypothesized that using a Microcuff oral RAE tube would reduce tube exchange and migration rate. We aimed to compare the performance of Microsoft and uncuffed oral performed tracheal tubes in children undergoing cleft palate surgeries regarding the rate of tracheal tube exchange, endobronchial intubation, and ventilatory parameters. METHODS: One hundred children scheduled for cleft palate surgery were randomized into two groups. In the uncuffed group (n = 50), the tracheal tube was selected using the Modified Coles formula, and in the Microcuff (n = 50) group, the manufacturer's recommendations were followed. Intraoperatively, we compared the primary outcome of tube exchange using the chi-square test. The leak pressure and ventilatory parameters after head extension and mouth gag application were measured in both groups. RESULTS: The tracheal tube exchange rate was significantly lower in the Microcuff group (0/50) than in uncuffed (19/50) preformed tubes (0 vs. 38% respectively; p <.001). The uncuffed and Microcuff tracheal tube were comparable concerning ventilation parameters and leak pressure of finally placed tubes (17.78 ± 3.95 vs. 19.26 ± 3.81 cm H2 O respectively, with a mean difference (95% CI) of -1.48 (-0.01-2.98); p-value =0.059. Cuff pressure did not vary significantly during the initial hour, and the incidence of postoperative airway morbidity between uncuffed and Microcuff tube was comparable, 5/50 (10%) versus 7/50 (14%) with risk ratio (95% CI) of 0.71(0.24-2.1), p value .49. CONCLUSION: Microcuff oral preformed tubes performed better than uncuffed tubes regarding tube exchange during cleft palate surgery.

Low diversity, high dominance, and high host prevalence of parasitic isopods of the family Cymothoidae in Chilika lagoon, India: a comparative study between a semi-enclosed ecosystem and its adjoining open region.

Patterns in parasite diversity are shaped by their environmental and ecological settings, and to better understand their interactions with hosts and the corresponding biology, it is crucial to understand these context-dependent patterns. To achieve this, we use cymothoid isopods, an important group of fish parasites, to test a long-standing hypothesis about parasite diversity and prevalence pattern: whether semi-enclosed water bodies allow low diversity and high prevalence of parasitic isopods. Specifically, we compare these patterns between Chilika lagoon (Odisha, India), a semi-enclosed water body, and the adjoining Odisha coast (India). Our finding reveals that the semi-enclosed Chilika lagoon has a considerably lower diversity of parasitic isopods than its adjoining open sea along the Odisha coast. Additionally, the parasitic isopod infection levels in Chilika lagoon are noticeably higher, and isopod assemblage is less even than those in coastal waters along the Odisha coast. Our results support the hypothesised association between enclosed water bodies, parasite diversity, and host prevalence and contribute to an enhanced comprehension of the ecology of parasitic isopods in distinct marine environments.

Thoracic organ transplantation and pregnancy outcomes: systematic review and meta-analysis.

PURPOSE: Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose them to increased risk of adverse feto-maternal outcomes. The study aimed to systematically analyze and assess the risk of adverse pregnancy outcomes in women with thoracic organ transplant. METHODS: MEDLINE, EMBASE, and Cochrane library were searched for publication between January 1990 and June 2020. Risk of bias was assessed using Joanna Briggs critical appraisal tool for case series. The primary outcomes included maternal mortality and pregnancy loss. The secondary outcomes were maternal complications, neonatal complications, and adverse birth outcomes. The analysis was performed using the DerSimonian-Laird random effects model. RESULTS: Eleven studies captured data from 275 parturient with thoracic organ transplant describing 400 pregnancies. The primary outcomes included maternal mortality {pooled incidence (95% confidence interval) 4.2 (2.5-7.1) at 1 year and 19.5 (15.3-24.5) during follow-up}. Pooled estimates yielded 10.1% (5.6-17.5) and 21.8% (10.9-38.8) risk of rejection and graft dysfunction during and after pregnancy, respectively. Although 67% (60.2-73.2) of pregnancies resulted in live birth, total pregnancy loss and neonatal death occurred in 33.5% (26.7-40.9) and 2.8% (1.4-5.6), respectively. Prematurity and low birth weight were reported in 45.1% (38.5-51.9) and 42.7% (32.8-53.2), respectively. CONCLUSIONS: Despite pregnancies resulting in nearly 2/3rd of live births, high incidence of pregnancy loss, prematurity and low birth weight remain a cause of concern. Focused pre-conceptual counseling to avoid unplanned pregnancy, especially in women with transplant-related organ dysfunctions and complications, is vital to improve pregnancy outcomes. PROSPERO NUMBER: CRD42020164020.

Relationship between difference of preoperative and cardiopulmonary bypass mean arterial pressure, and acute kidney injury in cardiac surgical patients undergoing valve surgery.

BACKGROUND: Modifiable and non-modifiable factors contribute to development and progression of acute kidney injury (AKI) during cardiac surgery. We hypothesized that, the difference between preoperative mean arterial pressure (MAP) and the average mean arterial pressure maintained on cardiopulmonary bypass (CPB) would be strongly predictive of AKI. We also measured plasma Neutrophil gelatinase-associated lipocalin (NGAL), to establish its association with cardiac surgery associated-AKI (CSA-AKI). METHODS: One hundred and twelve high-risk patients undergoing valve, and valve plus coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB) were included in this study. Delta mean arterial pressure (MAP) was calculated as the difference between the average of pre-operative and on-bypass MAP, and blood was sampled for NGAL levels, at baseline, and 6-h after CPB. Detailed data collection was done, tabulating most of the factors which might influence development of post-operative cardiac surgery associated-AKI (CSA-AKI). To define CSA-AKI within the first 24-h post-operatively, the Kidney Disease Improving Global Outcomes (KDIGO) classification was used. RESULTS: Out of 112 patients, 44 (39.3%) developed CSA-AKI postoperatively. With an ROC analysis cut-off of delta MAP of more than 25.67 mmHg, 46.4% patients developed post-operative AKI, and the average CPB flows which were 1.8 ± 0.2 were not contributory to the development of early CSA-AKI. In our study, ELISA test for human NGAL was performed on serum samples, and the estimated cut-off value of 1661 ng/mL was found to be significantly associated with early CSA-AKI. CONCLUSIONS: Delta MAP and CPB flows are not related to early post-surgical CSA-AKI in cases with prior high-risk elements. However, baseline serum NGAL, as well as its percent change during the early post-surgical period independently predicted the development of CSA-AKI. This implies that, there may be patients with a higher pre-operative preponderance to develop this complication, which could actually be delineated by the use of serum NGAL estimations at baseline.

Outcomes of lateral femoral sliding osteotomy in primary total knee arthroplasty for type two fixed valgus deformity.

PURPOSE: The aim of our study was to determine the surgical outcomes of patients who underwent lateral femoral sliding osteotomy (LFSO) with total knee arthroplasty (TKA) for Ranawat's type 2 fixed valgus deformity. METHODS: The consecutive patients who underwent primary TKA with posterior-stabilized implant and LFSO for fixed valgus deformity were reviewed. The radiological parameters analyzed were pre- and postoperative hip-knee-ankle (HKA) angle and tibio-femoral angle in varus-valgus stress views. The clinical outcome was measured by Oxford knee score (OKS), knee society score (KSS), and functional score (KSS-F). The complications and any reoperation were noted in the follow-up. RESULTS: There were total 28 patients included with an average follow-up time of 47.2 ± 24.9 months. The average arc of motion was 101.3 ± 23.8° preoperatively and 102.7 ± 11.8° postoperatively (p > 0.05). The average deformity in varus and valgus stress views was 196.6 ± 4.8 and 207.8 ± 7.4°, respectively. There was significant improvement in HKA from 205.2 ± 8.3° preoperatively to 181.9 ± 3.7° postoperatively (p < 0.05). At the final follow-up, bony union of the osteotomy fragment was noted in all the patients. There was significant improvement in OKS, KSS, and KSS-F score from a preoperative 15.1 ± 3.9, 35.1 ± 10.6, and 26.6 ± 12.6 to 40.3 ± 2.9, 85.6 ± 4.8, and 89.4 ± 7.7, postoperatively (p < 0.05), respectively. One patient had acute periprosthetic joint infection that was managed with debridement and polyethylene insert exchange. CONCLUSION: Lateral femoral sliding osteotomy is an effective technique for optimal soft tissue balance in fixed valgus deformity. It provides satisfactory clinical outcome with restoration of knee alignment without using the constrained implants.

Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.

Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells. All of these inhibitors, however, are either ineffective, very toxic, or have yet to be subjected to rigorous testing on their effectiveness. Although various drug-like compounds targeting ALDH have been reported in the literature, none have made it to routine use in the oncology clinic. As a result, new potent, non-toxic, bioavailable, and therapeutically effective ALDH inhibitors are still needed. In this study, we designed and synthesized potent multi-ALDH isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500 nM. Compound 3 was also the most cytotoxic to cancer cells, with an IC50 in the range of 2.1 to 3.8 µM for ovarian, colon, and pancreatic cancer cells, compared to normal and embryonic kidney cells (IC50 7.1 to 8.7 µM). Mechanistically, compound 3 increased ROS activity due to potent multi-ALDH isoform inhibition, which increased apoptosis. Taken together, this study identified a potent multi-isoform ALDH inhibitor that could be further developed as a cancer therapeutic.