Percutaneous femoral access: Stuck guide wire, decannulation difficulty due to unravelling and knotting.

Percutaneous techniques for femoral arterial access are increasingly being performed due to advances in endovascular cerebral procedures, as they provide a less morbid and minimally invasive approach than open procedures. Common complications associated with this peripheral puncture include hematoma, bleeding, pseudoaneurysm, arteriovenous fistula, retroperitoneal bleeding, inadvertent venous puncture, dissection, etc. The retrograde femoral access is currently the most frequently used arterial access as it is technically straightforward, allows for the use of larger size sheaths and catheters, allows repeated attempts, etc. Although being technically less challenging, grave complications can occur due to hardware failure. Here, we present a case of unruptured posterior inferior cerebellar artery (PICA) aneurysm, who underwent uneventful diagnostic cerebral digital substraction angiography (DSA) via right femoral artery route on first attempt, but on second attempt for therapeutic intervention, landed up with stuck guide wire and faced decannulation difficulty due to unravelling of guide wire and multiple knot formation, which was finally removed after multiple attempts at pulling and improvised manoeuvres. Such cannulation and decannulation difficulties have been reported multiple times for central venous access, but extremely rarely for femoral routes, making this case a rarity and worth reporting.

Visualization and characterisation of microplastics in aquatic environment using a home-built micro-Raman spectroscopic set up.

Microplastics (MP) which are tiny plastic particles of sizes range from 1 µm (µm) to 5 mm (mm), have become a growing cause of concern due to their widespread presence in the environment and their potential impacts on ecosystems and human health. Marine organisms have the potential to consume microplastics, which could lead to physical injuries, blockages, or the transfer of harmful substances up the food chain. Humans may indirectly consume microplastics through contaminated seafood and water, although the complete scope of health risks is currently under investigation. An essential step in gaining a comprehensive understanding of microplastic pollution in waterbodies is the identification of microplastics, which is also crucial for further development of effective environmental regulations to address its adverse impacts. Majority of the researchers are accomplishing it globally using commercial platforms based on Raman spectroscopy. However, the development of indigenous Raman systems, which can enable microplastic identification, particularly in developing nations, is the need of the hour due to the outrageous cost of commercial platforms. In the current study, a custom-designed micro-Raman spectroscopy system was developed to detect and characterize microplastics from waterbodies. The developed system enabled visualization, size measurement and characterization of microplastics. Experimental parameters were fine-tuned, and a standardized Raman database was established for each type of plastic. This system exhibited high resolution which was capable of analysing microparticles of size up to 5 µm. Principal component analysis was carried out on the experimental Raman data, demonstrating good classification amongst different kinds of plastics. The performance of the developed system in analysing real samples was evaluated through experiments conducted on water samples obtained from the shore of Malpe Beach in Udupi district. The results revealed the presence of polyethylene and polyethylene terephthalate in the samples, along with the detection of pigments like copper phthalocyanine and indigo blue.

Midvastus Versus Medial Parapatellar Approach in Simultaneous Bilateral Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to compare the postoperative outcomes over a period of 3 years in patients who underwent bilateral total knee arthroplasty (TKA) using midvastus (MV) versus medial parapatellar (MPP) approaches. METHODS: In this retrospective study, 2 propensity-matched cohorts of patients who underwent simultaneous bilateral TKA via MV (n = 100) and MPP (n = 100) approaches from January 2017 to December 2018 were compared. Surgical parameters compared were surgery time and the incidence of lateral retinacular release (LRR). Clinical parameters including the visual analog score for pain, time for straight leg raise (SLR), range of motion, the Knee Society Score, and the Feller patellar score were assessed in the early postoperative and follow-up periods up to 3 years. Radiographs were evaluated for alignment, patellar tilt, and displacement. RESULTS: LRR was performed on 17 knees (8.5%) in the MPP group and 4 knees (2%) in the MV group which was significant (P = .03). The time to SLR was significantly lower in the MV group. There was no statistically significant difference in the length of hospital stay between the groups. The visual analog score, range of motion, and Knee Society Score were better in the MV group within 1 month (P < .05), but no statistically significant differences were found later. Patellar scores, radiographic patellar tilt, and displacements were similar at all follow-up periods. CONCLUSION: In our study, the MV approach had faster SLR, less LRR, and better pain and function scores in the first few weeks after TKA. However, its effect on different patient outcomes has not been sustained at 1 month and further follow-up points. We recommend that surgeons use the surgical approach with which they are most familiar.

Methods for Ex Vivo AAV Transduction in Rodent and Human Retinal Explants.

Translational research is heavily dependent on animal models, and reliable disease models are essential for the development of novel therapies. Here, we outline the methods for culturing mouse and human retinal explants. In addition, we show efficient adeno-associated virus (AAV) transduction of the mouse retinal explants to aid the study and development of AAV-based therapeutics against ocular diseases.

RNA-targeting strategies as a platform for ocular gene therapy.

Genetic medicine is offering hope as new therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of Leber Congenital Amaurosis (LCA), an inherited blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval. Numerous gene therapy clinical trials are ongoing for other eye diseases, and novel delivery systems, discovery of new drug targets and emerging technologies are currently driving the field forward. Targeting RNA, in particular, is an attractive therapeutic strategy for genetic disease that may have safety advantages over alternative approaches by avoiding permanent changes in the genome. In this regard, antisense oligonucleotides (ASO) and RNA interference (RNAi) are the currently popular strategies for developing RNA-targeted therapeutics. Enthusiasm has been further fuelled by the emergence of clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems that allow targeted manipulation of nucleic acids. RNA-targeting CRISPR-Cas systems now provide a novel way to develop RNA-targeted therapeutics and may provide superior efficiency and specificity to existing technologies. In addition, RNA base editing technologies using CRISPR-Cas and other modalities also enable precise alteration of single nucleotides. In this review, we showcase advances made by RNA-targeting systems for ocular disease, discuss applications of ASO and RNAi technologies, highlight emerging CRISPR-Cas systems and consider the implications of RNA-targeting therapeutics in the development of future drugs to treat eye disease.

Bio-physical and computational studies on serum albumin / target protein binding of a potential anti-cancer agent.

The successful evolution of an effective drug depends on its pharmacokinetics, efficiency and safety and these in turn depend on the drug-target/drug-carrier protein binding. This work, deals with the interaction of a pyridine derivative, 2-hydroxy-5-(4-methoxyphenyl)-6-phenylpyridine 3-carbonitrile (HDN) with serum albumins at physiological conditions utilizing the steady state and time-resolved fluorescence techniques by probing the emission behavior of Trp in BSA and HSA. In-silico studies revealed a combined static and dynamic quenching mechanism for the interactions. The binding studies suggests a spontaneous binding between HDN and the albumins with a moderate binding affinity (Kb ∼ 10-5 M-1) with a single class of binding site. The FRET mediated emission from HDN indicates preferential binding of HDN in subdomain IIA of the albumins with Trp residue in close proximity. Circular dichroism results indicate HDN induced conformational changes for BSA and HSA, but the α-helical secondary structure was well preserved even up to a concentration of 10 µM HDN. Moderate binding affinity of HDN with BSA and HSA and the unaltered secondary structure of proteins on binding propose the potential application of HDN as an efficient drug. The application of docking method on the affinity of HDN towards the proposed target/receptor is discussed.

Transplantation of 3D adipose-derived stem cell/hepatocyte spheroids alleviates chronic hepatic damage in a rat model of thioacetamide-induced liver cirrhosis.

Cirrhosis refers to irreversible liver damage where healthy tissue is replaced by scar tissue, resulting in impaired liver function. There is no cure and current treatments only prevent further liver damage; thus, novel therapeutic options are urgently needed. Here, we report a new approach that enables the formation of self-assembled 3D spheroids of adipose-derived stem cells (ADSCs) and murine hepatocytes (AML12) via reconstituted collagen fibers. Compared with the spheroids formed in the commercially available EZSHERE dish, the collagen fiber-based ADSC/hepatocyte spheroids offer a notable benefit in structure formation and paracrine factor secretion. To test the regenerative capability of the collagen fiber-based 3D ADSC/hepatocyte spheroids, a rat model of thioacetamide (TAA)-induced liver cirrhosis was employed. The transplantation of the collagen fiber-based 3D ADSC/hepatocyte spheroids show an improvement in liver function and ameliorates pathological liver cirrhosis in TAA-treated rats. In summary, our data show collagen fiber-based self-assembled 3D ADSC/hepatocyte spheroids to possess the excellent regenerative capacity in response to TAA-induced liver injury, promising an alternative therapeutic strategy for liver cirrhosis.

Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization.

Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV. Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model. Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea. Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.

Topologically directed confocal Raman imaging (TD-CRI): Advanced Raman imaging towards compositional and micromeritic profiling of a commercial tablet components.

Particle size distribution (PSD), spatial location and particle cluster size of ingredients, polymorphism, compositional distribution of a pharmaceutical product are few of the most important attributes in establishing the drug release-controlling microstructural and solid state properties that would be used to (re)design or reproduce similar products. There are numerous solid-state techniques available for PSD analysis. Laser diffraction (LD) is mostly used to study PSD of raw materials. However, a constraint of LD is the interference between the active pharmaceutical ingredients (API) and excipients, where it is very challenging to measure API size in a tablet. X-ray powder diffraction (XRPD) is widely employed in establishing the polymorphism of API and excipients. This research examined a commercial osmotic tablet in terms of extracting solid state properties of API and functional excipient by Raman Imaging. Establishing repeatability, reproducibility, and sample representativeness when the samples are non-uniform and inhomogeneous necessitates multiple measurements. In such scenarios, when employing imaging-based techniques, it can be time-consuming and tedious. Advanced statistical methodologies are used to overcome these disadvantages and expedite the characterization process. Overall, this study demonstrates that Raman imaging can be employed as a non-invasive and effective offline method for assessing the solid-state characteristics of API and functional excipients in complex dosage forms like osmotic tablets.

Bulk Gene Expression Deconvolution Reveals Infiltration of M2 Macrophages in Retinal Neovascularization.

Purpose: This study interrogated the transcriptional features and immune cellular landscape of the retinae of rats subjected to oxygen-induced retinopathy (OIR). Methods: Bulk RNA sequencing was performed with retinal RNA isolated from control and OIR rats. Gene set enrichment analysis (GSEA) was undertaken to identify gene sets associated with immune responses in retinal neovascularization. Bulk gene expression deconvolution analysis by CIBERSORTx was performed to identify immune cell types involved in retinal neovascularization, followed by functional enrichment analysis of differentially expressed genes (DEGs). Protein-protein interaction analysis was performed to predict the hub genes relevant to identified immune cell types. CIBERSORTx was applied to profile immune cell types in the macula of patients with both proliferative diabetic retinopathy (PDR) and diabetic macular edema using a public RNA-seq dataset. Results: Transcriptome analysis by GSEA revealed that the retina of OIR rats and patients with PDR is characterized by increased immunoregulatory interactions and complement cascade. Deconvolution analysis demonstrated that M2 macrophages infiltrate the retinae of OIR rats and patients with PDR. Functional enrichment analysis of DEGs in OIR rats showed that the dysregulated genes are related to leukocyte-mediated immunity and myeloid leukocyte activation. Downstream protein-protein interaction analysis revealed that several potential hub genes, including Ccl2, Itgam, and Tlr2, contribute to M2 macrophage infiltration in the ischemic retina. Conclusions: This study highlights application of the gene expression deconvolution tool to identify immune cell types in inflammatory ocular diseases with transcriptomes, providing a new approach to assess changes in immune cell types in diseased ocular tissues.

Methods for in vitro CRISPR/CasRx-Mediated RNA Editing.

Specific changes in the genome have been accomplished by the revolutionary gene-editing tool known as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system. The advent of programmable RNA editing CRISPR/Cas nucleases has made this gene-editing tool safer and more precise. Specifically, CasRx, a family member of the Cas13d family, has shown great therapeutic potential. Here, we describe the in vitro methods of utilizing this powerful RNA editing platform and determine the RNA editing efficiencies for CasRx with different forms of guide RNAs (also known as gRNA or sgRNA).

ACRBP (Sp32) is involved in priming sperm for the acrosome reaction and the binding of sperm to the zona pellucida in a porcine model.

In boar sperm, we have previously shown that capacitation is associated with the appearance of the p32 tyrosine phosphoprotein complex. The principal tyrosine phosphoprotein involved in this complex is the acrosin-binding protein (ACRBP), which regulates the autoconversion of proacrosin to intermediate forms of acrosin in both boar and mouse sperm. However, the complete biological role of ACRBP has not yet been elucidated. In this study, we tested the hypothesis that tyrosine phophorylation and the presence of the ACRBP in the sperm head are largely necessary to induce capacitation, the acrosome reaction (AR) and sperm-zona pellucida (ZP) binding, all of which are necessary steps for fertilization. In vitro fertilization (IVF) was performed using matured porcine oocytes and pre-capacitated boar sperm cultured with anti-phosphotyrosine antibodies or antibodies against ACRBP. Anti-ACRBP antibodies reduced capacitation and spontaneous AR (P<0.05). Sperm-ZP binding declined in the presence of anti-phosphotyrosine or anti-ACRBP antibodies. The localisation of anti-ACRBP antibodies on the sperm head, reduced the ability of the sperm to undergo the AR in response to solubilized ZP or by inhibiting the sarco/endoplasmic reticulum Ca2+-ATPase. These results support our hypothesis that tyrosine phosphorylated proteins and ACRBP are present upon the sperm surface in order to participate in sperm-ZP binding, and that ACRBP upon the surface of the sperm head facilitates capacitation and the AR in the porcine.

GlycoGAIT: A web database to browse glycogenes and lectins under gastric inflammatory diseases.

The perplexing nature of dynamic glycosylation modification plays imperative role in determining the regulatory role of key glycoconjugates involved in immune system. Systematic analysis of change in expression pattern of glycogenes and lectins can bring in a comprehensive understanding of genetic basis of the glycobiological changes occurring in pathological condition. Advancement in the field of glycobiology has capacitated the process of linking gene expression changes of glycogenes with its biological function. This instigated us to systematically analyze changes in expression patterns focusing on glycome genomics under diverse gastrointestinal immune dysfunction background. To necessitate this, as a pilot project, we carefully integrated several publically available databases to construct a glycosylation process associated gene set as well as public expression microarray data associated with gastrointestinal infections into an online database called Glycosylation and Gut Associated Immune Tolerance (GlycoGAIT). Currently the database comprises of 548 well characterized genes belonging to glycogenes and lectins along with gene expression data obtained from human biopsy samples under both H. pylori infection and inflammatory bowel disease (IBD) condition. The user-friendly interface enables the users to quickly compare and interpret changes in expression patterns of glycome genomics under different gut associated inflammatory conditions. The database is available online at: https://apps.connexios.com/glycogait/.

Barotrauma: Tooth Under Pressure.

With the growing number of air passengers, flight attendants, leisure pilots, as well as military and airline pilots, dentists may encounter physiological and pathological phenomena precipitated by high altitude. With the introduction of the self-contained breathing apparatus (SCUBA), many of these manifestations caused by changes in atmospheric pressure were reported in association with diving as well. Limited literature exists on this subject. Hence, this article aims to review literature concerning the classification, etiology and manifestations of barodontalgia, as well as important clinical considerations for its management.

Barotrauma: Tooth under Pressure.

With the growing number of air passengers, flight attendants, leisure pilots, as well as military and airline pilots, dentists may encounter physiological and pathological phenomena precipitated by high altitude. With the introduction of the self-contained breathing apparatus (SCUBA), many of these manifestations caused by changes in atmospheric pressure were reported in association with diving as well. Limited literature exists on this subject. Hence, this article aims to review literature concerning the classification, etiology and manifestations of barodontalgia, as well as important clinical considerations for its management.

Prevalence of Behavioural and Psychological Symptoms of Dementia in Individuals with Learning Disabilities.

A review of 23 studies investigating the prevalence of Behavioural and psychological symptoms of dementia (BPSD) in the general and learning disability population and measures used to assess BPSD was carried out. BPSD are non-cognitive symptoms, which constitute as a major component of dementia regardless of its subtype Research has indicated that there is a high prevalence of BPSD in the general dementia population. There are limited studies, which investigate the prevalence of BPSD within individuals who have learning disabilities and dementia. Findings suggest BPSDs are present within individuals with learning disabilities and dementia. Future research should use updated tools for investigating the prevalence of BPSD within individuals with learning disabilities and dementia.

A perspective on toxicology ofConusvenom peptides

The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery. The focus of this investigation is to summarize the worldwide distribution ofConus and their species diversity with special reference to the Indian coast. In addition, this study will contribute to understanding the structural properties of conotoxin and therapeutic application ofConus venom peptides. Cone snails can inject a mix of various conotoxins and these venoms are their major weapon for prey capture, and may also have other biological purposes, and some of these conotoxins fatal to humans.Conusvenoms contain a remarkable diversity of pharmacologically active small peptides; their targets are an iron channel and receptors in the neuromuscular system. Interspecific divergence is pronounced in venom peptide genes, which is generally attributed to their species specific biotic interactions. There is a notable interspecific divergence observed in venom peptide genes, which can be justified as of biotic interactions that stipulate species peculiar habitat and ecology of cone snails. There are several conopeptides used in clinical trials and one peptide (Ziconotide) has received FDA approval for treatment of pain. This perspective provides a comprehensive overview of the distribution of cone shells and focus on the molecular approach in documenting their taxonomy and diversity with special reference to geographic distribution of Indian cone snails, structure and properties of conopeptide and their pharmacological targets and future directions.

Comparison of the frictional resistance between archwire and different bracket system: An in vitro study.

BACKGROUND AND OBJECTIVES: The purpose of this study is to evaluate the frictional resistance generated by conventional stainless steel, radiance ceramic bracket, self-ligating and composite brackets using a 0.019 × 0.025 stainless steel straight length wires in a 022 slot and to select brackets based on their frictional characteristic. METHODOLOGY: In order to conduct this study, four different types of bracket system were selected of the mclaughlin-bennet-trevesi (MBT) discipline. They are Group 1 - stainless steel, Group 2 - composite bracket Group 3 - (American Orthodontics) radiance ceramic bracket Group 4 - self-ligating bracket (SLB) (Empower). In this study, five maxillary brackets of an arch of each type were used. All brackets are 0.022 × 0.028 in preadjusted edgewise appliance which simulates the dental arch. Five brackets were bonded to a stainless steel bar of dimension 150 mm × 25 mm × 3 mm. The bracket-arch wire units were submitted to mechanical test with an Instron universal testing machine 3365. A testing apparatus or holding jig was designed to hold the bracket during the mechanical test. Each sample was pulled at a speed of 6 mm for 1 min. Descriptive statistical information including mean and standard deviation of maximum friction force was calculated for each bracket wire combination. INTERPRETATION AND CONCLUSION: The SLB has the least friction among the four groups. The ceramic bracket showed the highest friction followed by stainless steel bracket, composite bracket, and SLB.