A sustainable strategic approach for N-alkylation of amines with activation of alcohols triggered via a hydrogen auto-transfer reaction using a Pd(II) complex: evidence for metal-ligand cooperativity.

This work describes a new well-defined, air-stable, phosphine free palladium(II) [Pd(L)Cl] (1) catalyst. This catalyst was utilized for N-alkylation of amines and indole synthesis where H2O was found to be the by-product. A broad range of aromatic amines were alkylated using this homogeneous catalyst with a catalyst loading of 0.1 mol%. Greener aromatic and aliphatic primary alcohols were utilized and a hydrogen auto-transfer strategy via a metal-ligand cooperative approach was investigated. The precursor of the antihistamine-containing drug molecule tripelennamine was synthesized on a gram scale for large-scale applicability of the current synthetic methodology. A number of control experiments were performed to investigate the possible reaction pathway and the outcomes of these experiments indicated the azo-chromophore as a hydrogen reservoir during the catalytic cycle.

Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry.

BACKGROUND: Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators. METHODS: The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA. RESULTS: The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3 years after enrollment. CONCLUSIONS: There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap.

Synthetic and Clinical Perspectives of Evotaz: An Overview.

Viruses cause a variety of diseases in the human body. Antiviral agents are used to prevent the production of disease-causing viruses. These agents obstruct and kill the virus's translation and replication. Because viruses share the metabolic processes of the majority of host cells, finding targeted medicines for the virus is difficult. In the ongoing search for better antiviral agents, the USFDA approved EVOTAZ, a new drug discovered for the treatment of Human Immunodeficiency Virus (HIV). It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor. The combination drug was created in such a way that it can inhibit both CYP enzymes and proteases at the same time, resulting in the virus's death. The drug is not effective in children under the age of 18; however, it is still being studied for various parameters. This review article focuses on EVOTAZ's preclinical and clinical aspects, as well as its efficacy and safety profiles.

Artificial Intelligence for the Management of Breast Cancer: An Overview.

Breast cancer is a severe global health problem, and early detection, accurate diagnosis, and personalized treatment is the key to improving patient outcomes. Artificial intelligence (AI) and machine learning (ML) have emerged as promising breast cancer research and clinical practice tools in recent years. Various projects are underway in early detection, diagnosis, prognosis, drug discovery, advanced image analysis, precision medicine, predictive modeling, and personalized treatment planning using artificial intelligence and machine learning. These projects use different algorithms, including convolutional neural networks (CNNs), support vector machines (SVMs), decision trees, and deep learning methods, to analyze and improve different types of data, such as clinical, genomic, and imaging data for breast cancer management. The success of these projects has the potential to transform breast cancer care, and continued research and development in this area is likely to lead to more accurate and personalized breast cancer diagnosis, treatment, and outcomes.

Surgical Correction of Post-traumatic Residual Deformity of the Mandible: A Case Report.

Mandibular fractures are the most common trauma cases that we often come across in our day-to-day practice of oral and maxillofacial surgery. Various factors can lead to deformities and make those cases more challenging, which includes a delay in surgical treatment, resulting in non-union or malunion of the fracture site causing occlusal disturbances and functional abnormalities in the temporomandibular joint.

Absence of Superconductivity in LK-99 at Ambient Conditions.

The report of the synthesis of modified lead apatite (LK-99), with evidence of superconductivity at more than boiling water temperature, has steered the scientific community. There have been several failures to reproduce superconductivity in LK-99, despite partial successes. Here, we have continued our efforts to synthesize phase-pure LK-99 with improved precursors. The synthesis process being followed is the same as suggested by Sukbae Lee et al. The phase purity of each precursor is evidenced by powder X-ray diffraction (PXRD) and is well-fitted by Rietveld refinement. The PXRD confirms the synthesis of phase-pure polycrystalline LK-99 with a lead apatite structure. The sample is highly resistive, showing insulator-like behavior in resistivity measurement in the temperature range from 215 to 325 K, which confirms the absence of superconductivity in synthesized LK-99 at room temperature. The magnetization measurements of LK-99 on the SQUID magnetometer resemble the behavior of a resistive diamagnetic material at 280 K. Moreover, we have also performed first principle calculations to investigate the electronic band structure of LK-99 in the vicinity of the Fermi level. Our study verifies that the copper (Cu)-doped lead apatite (LK-99) exhibits band crossing at the Fermi level, indicating the generation of strong correlation in the presently studied system. Our experimental results do not approve the appearance of superconductivity in LK-99, i.e., Pb9CuP6O25.

A Highly Selective Pyrene Appended Oxacalixarene Receptor for MNA and 4-NP Detection: an Experimental and Computational Study.

A novel pyrene-substituted oxacalixarene was designed and synthesized as a selective probe for the simultaneous detection of MNA and 4-NP. Utilizing 1H-NMR, 13C-NMR, and FT-IR analysis techniques, its structure was characterized. The binding property of BPOC to a variety of NACs, including 1,3-DNB, 2,3-DNT, 2,4-DNT, 2,6-DNT, 4-NP, 4-NT, and PA, revealed that the sensor binds to MNA and 4-NP with remarkable selectivity. Binding constant reveals lower detection limits of MNA is 0.2 µM and 0.3 µM for 4-NP. Using docking and density functional theory (DFT), computational insights were provided for investigating the stability and spectroscopic analysis of the inclusion complex. From molecular docking study, we observed the best docking score of BPOC with 4-NT and MNA complex. The calculations supplement the findings significantly and clarify the structural geometry and mode of interactions in supramolecular complexation. In an MTT experiment on human PBMC to check for cytotoxicity, this chemical was found to influence 1 × 105 cell viability dose-dependently.

Stochastic modeling and parameter estimation of turbogenerator unit of a thermal power plant under classical and Bayesian inferential framework.

The work reported in present study deals with the development of a novel stochastic model and estimation of parameters to assess reliability characteristics for a turbogenerator unit of thermal power plant under classical and Bayesian frameworks. Turbogenerator unit consists of five components namely turbine lubrication, turbine governing, generator oil system, generator gas system and generator excitation system. The concepts of cold standby redundancy and Weibull distributed random variables are used in development of stochastic model. The shape parameter for all the random variables is same while scale parameter is different. Regenerative point technique and semi-Markov approach are used for evaluation of reliability characteristics. Sufficient repair facility always remains available in plant as well as repair done by the repairman is considered perfect. As the life testing experiments are time consuming, so to highlight the importance of proposed model Monte Carlo simulation study is carried out. A comparative analysis is done between true, classical and Bayesian results of MTSF, availability and profit function.

Reduced metal nanocatalysts for selective electrochemical hydrogenation of biomass-derived 5-(hydroxymethyl)furfural to 2,5-bis(hydroxymethyl)furan in ambient conditions.

Selective electrochemical hydrogenation (ECH) of biomass-derived unsaturated organic molecules has enormous potential for sustainable chemical production. However, an efficient catalyst is essential to perform an ECH reaction consisting of superior product selectivity and a higher conversion rate. Here, we examined the ECH performance of reduced metal nanostructures, i.e., reduced Ag (rAg) and reduced copper (rCu) prepared via electrochemical or thermal oxidation and electrochemical reduction process, respectively. Surface morphological analysis suggests the formation of nanocoral and entangled nanowire structure formation for rAg and rCu catalysts. rCu exhibits a slight enhancement in ECH reaction performance in comparison to the pristine Cu. However, the rAg exhibits more than two times higher ECH performance without compromising the selectivity for 5-(HydroxyMethyl) Furfural (HMF) to 2,5-bis(HydroxyMethyl)-Furan (BHMF) formation in comparison to the Ag film. Moreover, a similar ECH current density was recorded at a reduced working potential of 220 mV for rAg. This high performance of rAg is attributed to the formation of new catalytically active sites during the Ag oxidation and reduction processes. This study demonstrates that rAg can potentially be used for the ECH process with minimum energy consumption and a higher production rate.

Takotsubo Cardiomyopathy: A Possible Rare Complication of Guillain-Barré Syndrome.

Dysautonomia is a common and severe complication of Guillain-Barré syndrome (GBS), which may manifest as cardiac arrhythmias, labile blood pressure, diaphoresis, and changes in gastrointestinal motility. Takotsubo cardiomyopathy (TCM) is a life-threatening manifestation of dysautonomia in patients with GBS, which is not widely underlined in the literature. The association between GBS and TCM has been well-documented in previous studies; however, there are few reported cases with GBS who developed TCM following their diagnosis with GBS. In this case report, we will discuss our experience treating a 59-year-old female patient who became hemodynamically unstable while recovering from an acute GBS infection. She was diagnosed with TCM after undergoing an echocardiogram and coronary angiogram ruling out thrombotic or obstructive coronary disease and myocarditis.

Atrial Myxoma: An Unusual Etiology of Ischemic Stroke in an Adult Patient.

Atrial myxoma is the most frequent primary cardiac tumor; however, it is a rare, substantial cause of cardiogenic emboli causing a stroke, especially in young adults. A cardiac myxoma has no specific clinical presentation, ranging from constitutional symptoms to non-cardiac symptoms and emboli, which leads to a diagnostic challenge in the clinical process. We report a case of a left atrial myxoma in an adult female who presented with sudden onset of right-sided weakness, headache, and numbness. Imaging confirmed cardiogenic emboli from the cardiac myxoma, which was reflected in an ischemic stroke.

Highly Responsive Near-Infrared Si/Sb2Se3 Photodetector via Surface Engineering of Silicon.

The development of imaging technology and optical communication demands a photodetector with high responsiveness. As demonstrated by microfabrication and nanofabrication technology advancements, recent progress in plasmonic sensor technologies can address this need. However, these photodetectors have low optical absorption and ineffective charge carrier transport efficiency. Sb2Se3 is light-sensitive material with a high absorption coefficient, making it suitable for photodetector applications. We developed an efficient, scalable, low-cost near-infrared (NIR) photodetector based on a nanostructured Sb2Se3 film deposited on p-type micropyramidal Si (made via the wet chemical etching process), working on photoconductive phenomena. Our results proved that, at the optimized thickness of the Sb2Se3 layer, the proposed Si micropyramidal substrate enhanced the responsivity nearly two times, compared with that of the Sb2Se3 deposited on a flat Si reference sample and a glass/Sb2Se3 sample at 1064 nm (power density = 15 mW/cm2). More interestingly, the micropyramidal silicon-based device worked at 0 V bias, paving a path for self-bias devices. The highest specific detectivity of 2.25 × 1015 Jones was achieved at 15 mW/cm2 power density at a bias voltage of 0.5 V. It is demonstrated that the enhanced responsivity was closely linked with field enhancement due to the Kretschmann configuration of Si pyramids, which acts as hot spots for Si/Sb2Se3 junction. A high responsivity of 47.8 A W-1 proved it suitable for scalable and cost-effective plasmonic-based NIR photodetectors.

Restoration of the joint geometry after stemless shoulder arthroplasty.

Aim: This study aims to evaluate restoration of anatomy following Total Shoulder Arthroplasty (TSA) with the Mathys Affinis Short prosthesis. Background: Over the last decade stemless shoulder arthroplasty has increased in popularity. One of the reported advantages of the stemless designs is the ability to restore anatomy following surgery. However, very few studies have evaluated restoration of anatomy following stemless shoulder arthroplasty. Methods: The study included all patients who had undergone TSA using the Affinis Short (Mathys Ltd, Bettlach, Switzerland) prosthesis for primary osteoarthritis between 2010 and 2016. The mean follow up was 42.8 months (range 9.4 to 83.4 months). Pre and post-operative radiographs were assessed for Centre of Rotation (COR), Humeral Head Height (HHH), Humeral Head Diameter (HHD), Humeral Height (HH) and, Neck Shaft Angle (NSA) using the best fit circle method on PACS software. Measurements were scored and compared to assess the accuracy of the implant in restoring the native geometry, including the intraobserver variability. The same data was collected by another experienced observer to measure the interobserver variability. Results: The deviation of COR of the prosthesis from the anatomical centre was less than 3 mm in 58 cases (85%). Humeral head height and humeral head diameter showed a variation of less than 3 mm in 66 cases (97%) and 43 cases (63%) respectively. Humeral height followed a similar trend, with 62 cases (91.2%) showing a difference of less than 5 mm. The neck shaft angle showed a variation of more than 8 degrees in 38 cases (55%), and 29 cases (42.6%) had a postoperative angle of less than 130 degrees. Conclusion: Overall, stemless total shoulder arthroplasty with the Affinis Short prosthesis allows excellent restoration of anatomy confirmed by most of the measured radiographic parameters. The variability in neck shaft angle might be due to differing surgical techniques, with some surgeons preferring a slightly vertical neck cut to protect the rotator cuff insertion.

Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect.

Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36-3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Factors Affecting Quality of Life of Cancer Patients in North India.

INTRODUCTION: Cancer is the second leading reason of death in many countries, and its burden and prognosis are highly dependent on disease stage at diagnosis. Lack of perception of the population about cancer and its related risk factors usually sequel in defer/delayed presentation and increased treatment morbidity and decrease survival chances. Quality of life (QOL) is defined as Individual view of life, merits, intentions, standards and interests in the framework of culture. AIMS AND OBJECTIVES: To study the socio-demographic profile and factors affecting quality of life of cancer patients. MATERIAL AND METHOD: Using a cross-sectional study, between 1 January 2021 to 31 December 2021, 192 cancer confirmed patients at cancer registry centre at District civil hospital, Ambala cantt. were interviewed using a pre tested semi-structured questionnaire along with EORTC QLQ-C30 (version 3) questionnaire scale for QOL. The data was entered into an excel sheet and was analysed using IBM SPSS version 28. RESULTS: Out of 192 patients, 95 were male and 97 were female. Results shows that female (60.05±19.167) had better mean score of QL2 than male (58.68±18.906) with P value=0.619. Overweight (BMI25.0-29.9) had better mean QL2 score (65.50±18.147) than obese (BMI>30.0) mean QL2 score (61.67±14.803), normal weight (BMI 18.0-24.9) mean QL2 score (59.57±18.575) and underweight (BMI<18.0) mean QL2 score (49.46±19.595) with P value of 0.004. CONCLUSION: Present study found that QOL had significant association with BMI, type of cancer, history of smoking, lost income after cancer diagnosis and stage of cancer at the time of diagnosis. While gender, occupation, age group, religion, residence, marital status, type of family, income, tobacco alcohol and physical activity showed no significance association with QOL.

In-Silico Prediction of Novel Fused Quinazoline Based Topoisomerase Inhibitors as Anticancer Agents.

BACKGROUND: The prospective uses of tryptanthrin and its analogues in cancer chemotherapy are well known, and they are also predicated on their capacity to reverse drug resistance in cancer therapy. OBJECTIVE: The current project entails developing a novel hybrid analogue that includes modifying the tryptanthrin molecule at the C-6 carbonyl position and is expected to exhibit substantial anticancer action. METHODS: In the ATPase domain of human topoisomerase II, a series of 162 substituted Schiff base analogues of tryptanthrin were developed, and molecular docking experiments were done using Gold 5.1 software interfaced with Hermes 1.6.2. (PDB ID: 1ZXM). RESULTS: Most of the compounds were found to have Goldscore above 100 and formed interactions with the residues like ASN91, ALA92, ASN95, ARG98, ASN120, ILE125, ILE141, PHE142, SER149, THR215, and ILE217. Compound RK-149 had highest Goldscore of 132.59, forming an interaction with ASN91 but had a lesser Goldscore as compared to the standard drug etoposide and had a better score than tryptanthrin. CONCLUSION: The nitrogen in the imine bond of the proposed compounds is responsible for significant interactions, demonstrating their anticancer potential.

Outcomes of different stem sizes in shoulder arthroplasty.

Background: The successive refinement in implant design and operative technique alongwith improved understanding has resulted in increased incidence of total shoulder arthroplasty (TSA). Simultaneously, the indications of TSA have widened and include a range of shoulder pathologies. Methods: Using the keywords and relevant literature, we have described an overview of the different stem sizes used in shoulder arthroplasty. Relevant description of clinical and radiological outcome is done with regards to different stem sizes. Discussion: There are plethora of shoulder replacement systems, based on unique philosophy and having their own advantages and disadvantages. Additionally, the rise in ageing population had increased the need for revision TSA, thereby necessitating the judicious choice of implant at primary TSA. We further present the role of cemented and uncemented humeral stems and discuss the findings of finite element analysis. The choice of humeral stem size and use of cemented or uncemented stems have been reported to affect the clinical and radiological outcomes.

Evaluation of oxindole derivatives as a potential anticancer agent against breast carcinoma cells: In vitro, in silico, and molecular docking study.

In this study we have performed the in vitro anticancer activity of spiro oxindole derivatives against MCF-7 (human Adreno carcinoma) and MDA-MB-231 (triple negative breast cancer) cell lines to propose a possible role of these derivatives in the treatment of cancer. Compound 6, which has an N-benzyl substitution with a chloro group on the indolin-2-one scaffold, had the most potent activity against MCF-7 (3.55 ± 0.49 µM) and MDA-MB-231 (4.40 ± 0.468 µM) of all the synthesized molecules. A normal mouse embryonic fibroblast (NIH/3 T3) cell line was used to test the cellular toxicity of these derivatives. The results showed that none of the compounds were cytotoxic to normal cells. In addition, pharmacokinetic (ADME) and toxicity study profiles were predicted in silico. All the synthesized derivatives (1 to 7) demonstrated the necessary physicochemical properties for bioavailability. Finally, in vitro results of promising compound 6 were validated using molecular docking and dynamic simulation studies, which revealed their binding affinities and conformational stability in the binding cavity. Thus, these derivatives may serve as lead structures for a new generation of anticancer agents.

Synthetic and Medicinal Perspective of 1,2,4-Triazole as Anticancer Agents.

Cancer is still one of the leading causes of death worldwide. Many researchers are working to design and develop heterocyclic-based drugs with the potential to treat cancer at various stages. There is always an unmet need to discover new anticancer drugs to treat different types of cancer. Based on literature reports, it was evident that hybrid 1,2,4-triazoles exhibit a wide spectrum of biological potential (particularly potent anticancer activity), as compared to the corresponding monocyclic compounds. In this review, we summarized fused/hybrid 1,2,4-triazole and poly-functionalized 1,2,4-triazoles as anticancer agents. Triazole may be fused with other heterocyclic scaffolds like pyrimidine, pyridine, piperidine, quinoxaline, quinazoline, thiadiazine, indole, phthalazine etc. A clear explanation of the method of synthesis, structure-activity relationship, and in vitro results plus the inhibitory concentration of new molecules are focused on in this review article.

Assessment of prevalence and characteristics of asthma-COPD overlap among patients with chronic airflow obstruction.

Given the paucity of research on asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) and the high prevalence of co-morbidities and healthcare utilization associated with it, the current study looked at the prevalence of ACO and its clinico-radiological phenotype in patients with chronic airflow obstruction. The study was conducted at a tertiary care hospital in North India. Patients over 40 with COPD or asthma were screened for inclusion in the ACO, asthma, and COPD groups. The ACO and COPD groups were further investigated. The clinical characteristics, lung functions, health-related quality of life, and radiological features of both groups were investigated and compared. ACO was discovered in 16.3% of patients with chronic airflow obstruction (asthma and COPD). The most commonly observed symptoms at presentation in the evaluated ACO patients (n=77) were shortness of breath, wheezing, cough, and expectoration (mean age at presentation: 57.9; mean duration of illness: 8.62 years). Exacerbation rates in ACO patients were significantly higher than in COPD patients (p<0.001). The ACO group had a significantly greater mean change in FEV1 post-bronchodilator in millilitres (ml) and percentage (379.61 ml and 37.72%) than the COPD group (p<0.001). The proportion of patients with emphysema was lower in the ACO group than in the COPD group (p<0.001). The ACO and COPD groups did not differ significantly in major airway wall thickness (p=0.3), but the COPD group had a significantly higher proportion of patients with vascular attenuation and distortion (p<0.001). Patients with COPD had a higher degree of hyperinflation, according to high resolution computed tomography (HRCT) indices. This study found that patients with ACO have a distinct phenotype in terms of clinical presentation and HRCT features. More research on the radiological features of ACO is required to identify the anatomical abnormalities involved in the disease's pathogenesis and to validate the radiological features of ACO.