Glucoconjugated Dinuclear Copper(II) Complex: An Efficient Catalyst for Stereoselective Synthesis of Trisubstituted Propargylamines via Solvent-free A3 Coupling Reaction.

Development of catalytic systems using nontoxic natural precursors is the need of the era, and along this line, we have synthesized a new D-glucose derived ligand (4,6-O-ethylidene-N-(2-hydroxy-4-(octyloxy)benzylidene)-ß-D-glucopyranosylamine) and its dinuclear copper(II) complex. The molecular structure of the complex has been established by single-crystal X-ray diffraction studies and detailed noncovalent intermolecular interactions present in it has been explored by Hirshfeld surface analysis. Further, the complex has been used as catalyst in the enantioselective (87-99% ee) synthesis of propargylamines in good to excellent yield (82-95%) via aldehyde-amines-alkynes (A3) coupling reaction under solvent-free condition. The formation of aminal intermediate during the reaction has been confirmed by 1H-NMR and single-crystal X-ray diffraction studies. The catalytic system is reusable without any appreciable loss in the enantioselectivity or product yield.

Comparative analysis of parametric B-spline and Hermite cubic spline based methods for accurate ECG signal modeling.

Analyzing Electrocardiogram (ECG) signals is imperative for diagnosing cardiovascular diseases. However, evaluating ECG analysis techniques faces challenges due to noise and artifacts in actual signals. Machine learning for automatic diagnosis encounters data acquisition hurdles due to medical data privacy constraints. Addressing these issues, ECG modeling assumes a crucial role in biomedical and parametric spline-based methods have garnered significant attention for their ability to accurately represent the complex temporal dynamics of ECG signals. This study conducts a comparative analysis of two parametric spline-based methods-B-spline and Hermite cubic spline-for ECG modeling, aiming to identify the most effective approach for accurate and reliable ECG representation. The Hermite cubic spline serves as one of the most effective interpolation methods, while B-spline is an approximation method. The comparative analysis includes both qualitative and quantitative evaluations. Qualitative assessment involves visually inspecting the generated spline-based models, comparing their resemblance to the original ECG signals, and employing power spectrum analysis. Quantitative analysis incorporates metrics such as root mean square error (RMSE), Percentage Root Mean Square Difference (PRD) and cross correlation, offering a more objective measure of the model's performance. Preliminary results indicate promising capabilities for both spline-based methods in representing ECG signals. However, the analysis unveils specific strengths and weaknesses for each method. The B-spline method offers greater flexibility and smoothness, while the cubic spline method demonstrates superior waveform capturing abilities with the preservation of control points, a critical aspect in the medical field. Presented research provides valuable insights for researchers and practitioners in selecting the most appropriate method for their specific ECG modeling requirements. Adjustments to control points and parameterization enable the generation of diverse ECG waveforms, enhancing the versatility of this modeling technique. This approach has the potential to extend its utility to other medical signals, presenting a promising avenue for advancing biomedical research.

Exploring a new frontier in cardiac diagnosis: ECG analysis enhanced by machine learning and parametric quartic spline modeling.

The heart's study holds paramount importance in human physiology, driving valuable research in cardiovascular health. However, assessing Electrocardiogram (ECG) analysis techniques poses challenges due to noise and artifacts in authentic recordings. The advent of machine learning systems for automated diagnosis has heightened the demand for extensive data, yet accessing medical data is hindered by privacy concerns. Consequently, generating artificial ECG signals faithful to real ones is a formidable task in biomedical signal processing. This paper introduces a method for ECG signal modeling using parametric quartic splines and generating a new dataset based on the modeled signals. Additionally, it explores ECG classification using three machine learning techniques facilitated by Orange software, addressing both normal and abnormal sinus rhythms. The classification enables early detection and prediction of heart-related ailments, facilitating timely clinical interventions and improving patient outcomes. The assessment of synthetic signal quality is conducted through power spectrum analysis and cross-correlation analysis, power spectrum analysis of both real and synthetic ECG waves provides a quantitative assessment of their frequency content, aiding in the validation and evaluation of synthetic ECG signal generation techniques. Cross-correlation analysis revealing a robust correlation coefficient of 0.974 and precise alignment with a negligible time lag of 0.000 s between the synthetic and real ECG signals. Overall, the adoption of quartic spline interpolation in ECG modeling enhances the precision, smoothness, and fidelity of signal representation, thereby improving the effectiveness of diagnostic and analytical tasks in cardiology. Three prominent machine learning algorithms, namely Decision Tree, Logistic Regression, and Gradient Boosting, effectively classify the modeled ECG signals with classification accuracies of 0.98620, 0.98965, and 0.99137, respectively. Notably, all models exhibit robust performance, characterized by high AUC values and classification accuracy. While Gradient Boosting and Logistic Regression demonstrate marginally superior performance compared to the Decision Tree model across most metrics, all models showcase commendable efficacy in ECG signal classification. The study underscores the significance of accurate ECG modeling in health sciences and biomedical technology, offering enhanced accuracy and flexibility for improved cardiovascular health understanding and diagnostic tools.

Increased Systemic Levels of Centrally Acting B-Type Natriuretic Peptide Are Associated with Chronic Itch of Different Types.

B-type natriuretic peptide (BNP) is an itch-selective neuropeptide that was shown to play a role in both histaminergic and nonhistaminergic itch in mice. It was also shown that elevated serum BNP is linked to increased pruritus in nondiabetic hemodialysis patients. This study examined plasma BNP levels of 77 patients and N-terminal pro-BNP levels of 33 patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity. Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale and in particular for patients with chronic pruritus of unknown origin. On the basis of this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, pharmacological and ablation strategies determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord. These data support that BNP and N-terminal pro-BNP levels are associated with chronic itch and may be used in clinical setting.

Phage for drug delivery vehicles.

Viruses being the natural carriers of gene have been widely used as drug delivery systems. However, the commonly used eukaryotic viruses such as adenoviruses, retroviruses, and lentiviruses, besides efficiently targeting the cells, can also stimulate immunological response or disrupt tumour suppressor genes leading to cancer. Consequently, there has been an increase interest in the scientific fraternity towards exploring other alternatives, which are safer and equally efficient for drug delivery. Bacteriophages, in this context have been at the forefront as an efficient, reliable, and safer choice. Novel phage dependent technologies led the foundation of peptide libraries and provides way to recognising abilities and targeting of specific ligands. Hybridisation of phage with inorganic complexes could be an appropriate strategy for the construction of carrying bioinorganic carriers. In this chapter, we have tried to cover major advances in the phage species that can be used as drug delivery vehicles.

Acute radiotherapy-associated oral pain may promote tumor growth at distant sites.

Introduction: Patients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site. Methods: Mice underwent single fraction tongue irradiation (27 Gy, or 0 Gy "sham" control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics. Results: Tongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once). Discussion: This research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.

Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.

Psoriasis is characterized by intense pruritus, with a subset of individuals with psoriasis experiencing thermal hypersensitivity. However, the pathophysiology of thermal hypersensitivity in psoriasis and other skin conditions remains enigmatic. Linoleic acid is an omega-6 fatty acid that is concentrated in the skin, and oxidation of linoleic acid into metabolites with multiple hydroxyl and epoxide functional groups has been shown to play a role in skin barrier function. Previously, we identified several linoleic acid‒derived mediators that were more concentrated in psoriatic lesions, but the role of these lipids in psoriasis remains unknown. In this study, we report that two such compounds-9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate-are present as free fatty acids and induce nociceptive behavior in mice but not in rats. By chemically stabilizing 9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate through the addition of methyl groups, we observed pain and hypersensitization in mice. The nociceptive responses suggest an involvement of the TRPA1 channel, whereas hypersensitive responses induced by these mediators may require both TRPA1 and TRPV1 channels. Furthermore, we showed that 9,10,13-trihydroxy-octadecenoate‒induced calcium transients in sensory neurons are mediated through the Gßγ subunit of an unidentified G-protein coupled receptor (GPCR). Overall, mechanistic insights from this study will guide the development of potential therapeutic targets for the treatment of pain and hypersensitivity.

Multidrug Resistance among Patients with Surgical Site Infection in a Tertiary Care Centre.

Introduction: Infections at surgical sites are a major problem all over the world. Pathogens linked to postoperative infections are becoming increasingly resistant to antibiotics, which presents a significant therapeutic challenge for surgeons and raises the financial burden placed on patients. The study aimed to find the prevalence of multidrug resistance among patients with surgical site infections in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted from 3 November 2022 to 2 May 2023 among post-operative patients with surgical site infection after receiving ethical approval from the Institutional Review Committee. Swab samples were sent for antimicrobial susceptibility testing. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 147 patients with surgical site infection, the prevalence of multi-drug resistance was 95 (64.63%) (56.90-72.36, 95% Confidence Interval). Among them, 51 (53.68%) patients were in the 21-40 years age group and most of them were male 53 (55.79%). Conclusions: The prevalence of multidrug-resistant cases was similar to other studies done in similar settings. Keywords: antimicrobial drug resistance; multidrug resistance; Staphylococcus aureus; surgical site infection.

Chain length effect of spiro-ring N-alkylation on photophysical signalling parameters in Fe(III) selective rhodamine probes.

Manifestation of photophysical signalling parameters in rhodamine derivatives exhibiting complexation induced spiro-ring opening is crucial for the realization of selective metal ion detection at trace levels. Substitution of various functional groups, such as alkylation to the core architecture, modulates the physico-chemical properties of such molecular probes. Despite a few studies, relationships between the extent of photophysical signal modulations and the chain lengths of n-alkyl substituents are still elusive. In this investigation, a few molecular probes based on the rhodamine B (1-5) and rhodamine 6G (6-10) platform were synthesized by their derivatization with n-alkyl substituents of varying chain lengths at the amino-donor of their spiro-ring end, which exhibited Fe(III)-selective absorption and fluorescence 'off-on' signal transduction along with colorization of solution. The Fe(III)-selectivity in these probes remained the same despite their structural distinctions through varied n-alkyl chain lengths of the substituents; however, the quantifiable signalling parameters such as spectroscopic enhancement factors, sensitivity, the kinetics of spiro-ring opening and effectiveness of probe-Fe(III) interactions were analyzed. These parameters were also correlated in terms of the influence of different chain lengths of n-alkyl substituents that efficiently contributed to their inter-componential interactive stereo-electronic environment.

Current status and applications of genus Geobacillus in the production of industrially important products-a review.

The genus Geobacillus is one of the most important genera which mainly comprises gram-positive thermophilic bacterial strains including obligate aerobes, denitrifiers and facultative anaerobes having capability of endospore formation as well. The genus Geobacillus is widely distributed in nature and mostly abundant in extreme locations such as cool soils, hot springs, hydrothermal vents, marine trenches, hay composts and dairy plants. Due to plasticity towards environmental adaptation, the Geobacillus sp. shows remarkable genome diversification and acquired many beneficial properties, which facilitates their exploitation for many biotechnological applications. Many thermophiles are of biotechnological importance and having considerable interest in commercial applications for the production of industrially important products. Recently, due to catabolic versatility especially in the degradation of hemicellulose and starch containing agricultural waste and rapid growth rates, these microorganisms show potential for the production of biofuels, thermostable enzymes and bioremediation. This review mainly summarizes the status of Geobacillus sp. including its notable properties, biotechnological studies and its potential application in the production of industrially important products.

Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain.

Osteoarthritis (OA) associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Therapeutic options are limited, and the available options are often associated with adverse effects. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. Here, we use multiple approaches, including cellular, mouse genetic, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. We found the monoiodoacetate (MIA)-induced OA-pain in mice is associated with decreased limb use and hypersensitivity. Exogenous artemin induces mechanical, heat, and cold hypersensitivity, and systemic intraperitoneal anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA-pain. An artemin receptor GFRα3 expression is increased in sensory neurons in the MIA model. Our results provide a molecular basis of arthritis pain linked with artemin/GFRα3 signaling and indicate that further work is warranted to investigate the neuronal plasticity and the pathways that drive pain in OA.

A Calcium Imaging Approach to Measure Functional Sensitivity of Neurons.

Pain associated with chemotherapy and radiation therapy is one of the most common reasons for discontinuation of these treatments and has a dramatic effect on the quality of life in cancer patients. However, the mechanisms underlying chemotherapy and radiation therapy associated with pain are not well understood. Pain sensations are mediated through sensory neurons whose cell bodies are located in the dorsal root ganglia (DRG). Pain mediators activate these sensory neurons causing an influx of ions, including calcium. One common technique to study pain is to use primary cell culturing mouse DRG to study this calcium influx in vitro. This protocol details from an isolation to culture and maintenance of DRG neurons and functional recording using calcium imaging caused by either pain mediators or neuronal sensitization that are induced by drugs that are often used in the treatment of cancer.

Role of TRP ion channels in pruritus.

The transient receptor potential (TRP) channel superfamily responds to various physical, chemical, and environmental stimuli including the detection of sensations both harmful and non-harmful. Among these sensations is pruritus, or itch. There are at least 27 different TRP channels and about six of them are involved in pruriception. The function of these six receptors is primarily seen in the skin and the dorsal root ganglia. Identification and biological insights provided by these receptors in pruriception is important for human health as mutations and activations of many of these channels cause discomfort and disease. This review will focus on involvement of TRP channels in pruriception that may render these channels as the targets of many antagonistic topical medications, which may help patients' better cope with the pruritus that results from various cutaneous and systemic diseases.

The emerging role of neuroimmune interactions in atopic dermatitis and itch.

Millions of people globally suffer from allergic diseases, and the cases have been rising in the past decades. One of the major manifestations of allergic diseases is itch, which is an unpleasant symptom that triggers the urge to scratch and greatly affects the quality of life. Thus, research on how sensation of itch is detected/transmitted from the contact of the allergen to the nervous system is crucial in mitigating itch. Recent studies have attempted to elucidate the mechanisms of itch in allergic diseases. Here, we aim to review the endogenous mediators released from immune/nonimmune skin cells (that are indirectly involved in the propagation of itch) and the sensory neurons that express receptors for these itch mediators that are associated with direct transmission of itch in cutaneous allergic diseases. As the mechanisms for allergic itch become clearer, new therapeutic approaches to relieve itch are likely to be developed. Recent clinical trials are testing numerous compounds that target the endogenous mediators and their receptors. These studies provide the possibility of more effective itch treatment for allergic diseases.

Is enucleation followed by peripheral ostectomy and Carnoy's solution application an adequate treatment for Odontogenic keratocyst? A case series with up to five years of follow up / A enucleação seguida da osteotomia periférica e a aplicação de solução de Carnoy é um tratamento adequado para o ceratocisto odontogênico? Uma série de casos com acompanhamento de até cinco anos

Objective: To evaluate the treatment outcome of enucleation and peripheral ostectomy with the use of Carnoy's solution for management of Odontogenic keratocyst. Material and Methods: 17 patients with OKC who reported from 2011 to 2015 were included. All the cases were treated by enucleation and peripheral ostectomy of 0.5mm followed by Carnoy's solution cauterization for 4 minutes. All patients were followed up for 4-5 years. Results: All the cases were followed-up by using serial panoramic radiography and clinical evaluation at regular intervals. No recurrence was reported in any of the cases. Conclusion: Treatment of Odontogenic keratocyst by enucleation and 0.5mm of peripheral ostectomy, followed by Carnoy's solution cauterization for 4 minutes is an effective treatment with zero recurrence rates for five years of follow-up (AU)

Objetivo: Avaliar o resultado do tratamento de enucleação e osteotomia periférica com o uso de solução de Carnoy para o manejo do ceratocisto odontogênico (OKC). Material e Métodos: 17 pacientes com OKC com acompanhamento de 2011 a 2015 foram incluídos. Todos os casos foram tratados através da enucleação e osteotomia periférica de 0,5 mm, seguido da cauterização com solução de Carnoy por 4 minutos. Todos os pacientes foram acompanhados por 4-5 anos. Resultados: Todos os casos foram acompanhados por meio de séries de radiografias panorâmicas e avaliação clínica em intervalos regulares. Nenhuma recorrência foi reportada em nenhum dos casos. Conclusão: O tratamento de ceratocisto odontogênico por meio da enucleação e osteotomia periférica de 0,5mm, seguido da cauterização com solução de Carnoy por 4 minutos é um tratamento efetivo com zero taxa de recorrência em um acompanhamento de 5 anos. (AU)

Management of patients with allergy to local anesthetics: two case reports.

Lidocaine is the most commonly used local anesthetic (LA) agent in various dental as well as oral and maxillofacial procedures. Although rare, adverse effects and allergic reactions to lidocaine have been reported. In patients with suspected allergy to LA or a history of such reaction, careful history-taking and allergy testing should be performed to choose an alternative LA agent to avoid any adverse effects. Here, we present two cases of delayed hypersensitivity reaction to lidocaine, wherein the patients presented with erythema, edema, and itching. Intradermal testing confirmed allergic reaction to lidocaine, and the patients underwent successful dental treatment using an alternative LA agent. This report highlights the importance of allergy testing prior to LA use considering the serious consequences of allergy to these agents and describes the management of such patients using an alternative LA agent.