Position of Beta-blockers in the Treatment of Hypertension Today: An Indian Consensus.

BACKGROUND: Management of essential hypertension (HTN) remains challenging, with contemporary control being achieved in <1/10 of the cases, especially when aligned with the recently updated guidelines of American College of Cardiology (ACC) or International Society of Hypertension (ISH). The place and positioning of beta-blockers have been evolving, with recent focused updates, such as the European Society of Hypertension (ESH) 2023 guidelines, that may hold relevance for the Indian phenotypic traits of premature cardiovascular disease (CVD), fragile coronary architecture, and/or high resting heart rate. To further develop consensus on the clinical role and relevance of beta-blockers, including nebivolol, an Indian consensus was evolved with graded recommendations on their clinical role in HTN, HTN with additional cardiovascular (CV) risk, or type 2 diabetes mellitus (T2DM). METHODOLOGY: An expert review panel was constituted, comprising interventional and clinical cardiologists as experts, to synthesize the literature for the development of a validated knowledge, attitude, and practice (KAP) survey questionnaire. Research databases, including Cochrane Systematic Reviews, PubMed, and Google Scholar, were accessed for contemporary information and guidelines on beta-blockers updated until Dec 2023. Delphi rounds were conducted to develop graded recommendations based on the strength, quality of evidence, and the agreement among the panelists (n = 9). Consensus was achieved on the graded recommendations, with ≥70% of national panelists in agreement. RESULTS: Ninety-six percent of respondents opined that the new ESH HTN guidelines (2023) help gain confidence in using beta-blockers, which are considered first-line drugs for the treatment of HTN. Beta-blockers, including nebivolol, can be recommended in patients with HTN with high resting heart rates, including young hypertensive patients under 40 years of age. For people under 60 years old with HTN, regardless of whether they have comorbid diseases, beta-blockers are the recommended drug choice. Ninety-five percent of respondents opined that nebivolol is the preferred beta-blocker in hypertensive patients with T2DM, followed by bisoprolol and metoprolol. More than 90% of respondents opined that the three most commonly preferred beta-blockers by experts in patients with angina were nebivolol, metoprolol, and bisoprolol. CONCLUSION: Beta-blockers, including nebivolol, can be considered initial-line therapy for HTN management in real-life settings in India and nebivolol is preferred because of its two important properties: highest beta-1 selectivity and endothelial-dependent vasodilation.

Efficient removal of succinic acid by continuous hydrodynamic cavitation combined with ozone and side influent injection.

Micropollutants (MPs) encompass a range of human-made pollutants present in trace amounts in environmental systems. MPs include pharmaceuticals, personal care products, pesticides, persistent organic pollutants, micro- and nano-plastics, and artificial sweeteners, all posing ecological risks. Conventional municipal wastewater treatment methods often face challenges in completely removing MPs due to their chemical characteristics, stability, and resistance to biodegradation. In this research, an Advanced Oxidation Process, combining hydrodynamic cavitation (HC) with dissolved ozone (O3) and side injection, was employed to efficiently degrade succinic acid (SA), an ozone-resistant compound and common byproduct. The HC/O3 process was run to treat different synthetic effluents, focusing on evaluating the influence of O3-to-total organic carbon (TOC) ratio, cavitation number (Cv) and O3 dosage. Notably, the results from a series of 14 experiments highlighted the critical significance of a low O3-to-TOC ratio value of 0.08 mg/mg and Cv value of 0.056 in HC for achieving efficient SA removal of 41.2% from an initial SA solution (106.3 mg/L). Regarding a series of four proof-of-concept experiments and their replications, the average TOC removal reached 62% when treating wastewater treatment plant effluent spiked with SA. This significant removal rate was achieved under initial conditions: Cv of 0.02, O3-to-TOC ratio set at 0.77 mg/mg, TOC concentration of 47.7 mg/L, 106 mg/L of SA, and a temperature of 25 °C. Notably, the electrical energy per order required for the 62% reduction in TOC was a modest 12.5 kWh/m3/order, indicating the potential of the continuous HC/O3 process as a promising approach for degrading a wide range of MPs.

Molecular detection and phylogenetic analysis of ovine herpesvirus-2 in subclinical infections of cattle and sheep.

Ovine herpesvirus-2 (OvHV-2) is the causative agent of malignant catarrhal fever (MCF), a serious and often fatal disease that affects cattle and other ruminants. This study aimed to investigate the molecular epidemiology and genetic diversity of OvHV-2 strains circulating in sheep and cattle populations in the Jammu and Kashmir region of India. Screening of 150 sheep and 57 cattle blood samples revealed the presence of the OvHV-2 polymerase (pol) gene in 8.6% of sheep, 10% of apparently healthy cattle, and 29.7% of cattle exhibiting MCF-like symptoms. The full-length glycoprotein B (gB) gene (2800 bp) and an 875 bp internal fragment were successfully amplified, cloned, and sequenced from pol-positive samples. Comparative sequence analysis of the deduced gB amino acid sequences identified seven substitutions at positions 278, 341, 390, 440, 468, 539, and 566 compared to reference strains. Phylogenetic analysis based on the gB nucleotide sequences clustered the OvHV-2 strains from this study within the Indian clade, distinct from strains reported in the UK and US. These findings provide insights into the genetic diversity of OvHV-2 strains circulating in Jammu and Kashmir, with the identified mutations potentially influencing virus-host interactions. Further investigations into the functional implications of these mutations are warranted to understand their role in viral pathogenesis and tropism.

Measurement of fast neutron induced (n,γ) reaction cross-section of 68Zn, 96Zr, 121Sb and 123Sb in the energy range of 1 to 2 MeV.

The (n,γ) reaction cross-section for the elements 68Zn, 96Zr, 121Sb and 123Sb, present in the reactor structural/shielding materials, was measured by neutron activation technique in the neutron energy region of 1-2 MeV as very limited data is available in this energy range. Further, the neutron spectrum peaks in this energy region for the fast breeder reactors and proposed accelerator driven sub-critical systems. The natural strontium (natSr) element was used as a neutron flux monitor by considering effective combined reaction cross-section for 86Sr(n,γ)87Srm and 87Sr(n,n')87Srm reactions. The pellets of mixture of sample and monitor were irradiated by a quasi-mono energetic fast neutron beam, generated by 7Li(p,n)7Be reaction at FOTIA, Bhabha Atomic Research Centre, Mumbai, India. The activity of activation products was measured by off-line gamma-ray spectrometry using High Purity Germanium Detector (HPGe). The present data with improved uncertainty and covariance analysis enhance the cross-section data base for better constraining the evaluated data and theoretical models. The theoretical (n,γ) reaction cross-sections were calculated using TALYS 1.96, which could reasonably explain the present data with the Fermi gas level density prescription.

Targeting SARS-CoV2 spike glycoprotein: molecular insights into phytocompounds binding interactions - in-silico molecular docking.

This study utilized small molecular characterization and docking study to evaluate the binding affinity of seven antiviral phytocompounds with the SARS CoV-2 variants (SARS-CoV-2 Spike Glycoprotein, SARS-CoV-2 Spike Protein Variant in 1-RBD, Alpha Variant SARS-CoV2- Spike Protein). The results revealed that five of seven compounds, possesses excellent drug lead property reveled through in-silico ADMET analysis. In addition, six of seven except D-Glucosamine, exhibited excellent binding affinity. Six ligands possess significant binding affinity towards SARS-CoV-2 variants 6VXX, 7LWV and 7R13, which is certainly greater than Remdesivir. Fagaronine found to be the best drug candidate against SARS-CoV-2 variants, It was found that -7.4, -5.6 and -6.3 is the docking score respectively. Aranotin, Beta aescin, Gliotoxin, and Fagaronine formed hydrogen bonds with specific amino acids and exhibited significant binding interactions. These findings suggest that these phytocompounds could be promising candidates for developing antiviral therapies against SARS-CoV-2. Moreover, the study underscores the importance of molecular docking in understanding protein-ligand interactions and its role in drug discovery. The documented pharmacological properties of these compounds in the literature further support their potential therapeutic relevance in various diseases.

Advancements in breast cancer therapy: The promise of copper nanoparticles.

BACKGROUND: Breast cancer (BC) is the most prevalent cancer among women worldwide and poses significant treatment challenges. Traditional therapies often lead to adverse side effects and resistance, necessitating innovative approaches for effective management. OBJECTIVE: This review aims to explore the potential of copper nanoparticles (CuNPs) in enhancing breast cancer therapy through targeted drug delivery, improved imaging, and their antiangiogenic properties. METHODS: The review synthesizes existing literature on the efficacy of CuNPs in breast cancer treatment, addressing common challenges in nanotechnology, such as nanoparticle toxicity, scalability, and regulatory hurdles. It proposes a novel hybrid method that combines CuNPs with existing therapeutic modalities to optimize treatment outcomes. RESULTS: CuNPs demonstrate the ability to selectively target cancer cells while sparing healthy tissues, leading to improved therapeutic efficacy. Their unique physicochemical properties facilitate efficient biodistribution and enhanced imaging capabilities. Additionally, CuNPs exhibit antiangiogenic activity, which can inhibit tumor growth by preventing the formation of new blood vessels. CONCLUSION: The findings suggest that CuNPs represent a promising avenue for advancing breast cancer treatment. By addressing the limitations of current therapies and proposing innovative solutions, this review contributes valuable insights into the future of nanotechnology in oncology.

Green synthesis of silver and copper nanoparticles and their composites using Ocimum sanctum leaf extract displayed enhanced antibacterial, antioxidant and anticancer potentials.

Green-synthesized silver and copper nanoparticles (NPs), along with their composites, exhibit various biological activities. Ocimum sanctum (Holy basil), traditionally used as medicine in South Asia, treats respiratory disorders, digestive issues, skin diseases and inflammatory conditions. Modern scientific studies support these bioactivities; however, no studies have investigated their bioactivity in combination with NPs. In this study, silver and copper NPs were synthesized using AgNO3 and CuSO4·5H2O solutions, respectively, with Ocimum sanctum leaf extract, and their antibacterial, antioxidant and anticancer properties were examined. Spectroscopic analyses, including Fourier transform infra-red (FTIR), transmission electron microscopy (TEM) and X-ray diffraction (XRD), elucidated the physicochemical characteristics of the green-synthesized nanoparticles (Os-AgNPs and Os-CuNPs), revealing sizes of 11.7 and 13.1 nm, respectively. The Os-AgNPs:Os-CuNPs nano-composite with a 1:2 ratio exhibited a zone of inhibition ranging from 8 to 12 mm against tested bacterial pathogens. Additionally, the NPs and their composites demonstrated potent antioxidant activity, with notable 2-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity observed in composites with ratios of 2:1 and 1:2. Furthermore, they displayed potential anticancer activity against human leukaemia (Jurkat) cancer cells. Although no distinct difference in anticancer property was observed among the NPs and their composites, our study highlights their well-defined nanostructure and significant biological activity, suggesting their potential as therapeutic agents in the pharmaceutical industry.

Efficacy and Safety Profile of Gamma Knife Radiosurgery in Classic and Idiopathic Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia is a debilitating disease, with severe recurrent paroxysms of shock-like facial pain. Although pharmacotherapy may suffice in the majority of cases, a proportion of patients require surgical treatment. Gamma knife radiosurgery (GKRS) represents a potential non-invasive alternative to surgery in these patients. METHODS: We retrospectively analysed all patients that underwent GKRS for classic/idiopathic TN between 2013 and 2023. Pain prior to GKRS was graded per the Barrow Neurological Institute (BNI) pain score, which was also used to define outcomes. "Complete pain relief (CPR)" was defined as a BNI pain score of I or II, while "Adequate pain relief (APR)" was defined as a BNI pain score of III, and "Failure" as a BNI score of IV or V. RESULTS: The mean age of 70 patients (50 females and 20 males) was 47.4 ± 12.4 years. The mean follow-up was 51.3 ± 16.2 months. Although initial pain relief was achieved in 64 patients (91.4%), recurrence of pain at the latest follow-up occurred in 10 patients (14.3%). Overall, 41 patients (58.6%) achieved CPR, while 13 patients (18.6%) achieved APR. Multivariate analysis revealed that multiple prior failed procedures for TN predicted failure of pain relief. CONCLUSION: GKRS is effective among patients with classic/idiopathic TN, with complete pain relief in 58.6% of patients, and adequate pain relief in 18.6% of patients. The most frequent complication is facial hypesthesia, affecting 38.6% of patients. Multiple prior failed procedures for TN significantly predict failure of pain relief at latest follow-up.

Improving safety: Neuraxial blockade guided by thromboelastography for patients with uncertain coagulation profile.

ABSTRACT: Neuraxial blockade procedures are essential for anesthesia and pain management but pose risks in patients with uncertain coagulation profiles. Traditional coagulation tests often fail to predict bleeding risks associated with neuraxial blockade. Thromboelastography (TEG) offers real-time insights into coagulation status, potentially improving safety outcomes. In this case series, six patients underwent neuraxial blockade guided by TEG analysis. An individualized anesthetic plan was formulated based on TEG findings to mitigate bleeding risks while ensuring pain management. Tailoring anesthetic techniques to real-time TEG data improved safety outcomes with minimized bleeding complications and satisfactory pain control. In conclusion, neuraxial blockade guided by TEG enhances safety in patients with uncertain coagulation profiles. Further studies are needed to validate benefits in broader clinical settings.

Phase and frequency-resolved microscopy of operating spin Hall nano-oscillator arrays.

Coherent optical detection is a powerful technique for characterizing a wide range of physical excitations. Here, we use two optical approaches (fundamental and parametric pumping) to microscopically characterize the high-frequency auto-oscillations of single and multiple nano-constriction spin Hall nano-oscillators (SHNOs). To validate the technique and demonstrate its robustness, we study SHNOs made from two different material stacks, NiFe/Pt and W/CoFeB/MgO, and investigate the influence of both the RF injection power and the laser power on the measurements, comparing the optical results to conventional electrical measurements. To demonstrate the key features of direct, non-invasive, submicron, spatial, and phase-resolved characterization of the SHNO magnetodynamics, we map out the auto-oscillation magnitude and phase of two phase-binarized SHNOs used in Ising machines. This proof-of-concept platform establishes a strong foundation for further extensions, contributing to the ongoing development of crucial characterization techniques for emerging computing technologies based on spintronics devices.

Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence.

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution's experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10-6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10-6, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p < 10-7). Patients who were MRD positive and had not yet relapsed had a higher clonal diversity than those patients who were MRD positive and had relapsed. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. Clonal Diversity could complement MRD assessment in the prediction of outcomes in MM.

Evaluation of alveolar bone width alterations around dental implants.

Teeth that are lost can be replaced with dental implants. A sufficient width of bone surrounding the implant is beneficial to its success. Therefore, it is of interest to examine alterations in width of alveolar bone surrounding dental implants at natural and rebuilt bone locations [alveolar ridge preservation (ARP) /Guided Bone Regeneration (GBR)] using CTBT. A CBCT examination of the implant recipient site was performed on sixty patients (both male and female), who had undergone dental implants. All conventional surgical procedures were followed for inserting dental implants. All participants had their horizontal alveolar bone widths around implants assessed at 3 positions: subcrestal width 1 mm (CW1 (crestal level-CW1), subcrestal width 4 mm (CW4), and subcrestal width 7 mm (CW7). There were 32 male patients and 28 female patients out of 60 totals. The mean bone width was 7.02 mm at CW1 prior to surgery and 6.91 mm afterward; it was 8.52 mm at CW4 and 8.13 mm afterward; and it was 10.21 mm at CW7 prior to surgery and 10.08 mm afterward. There was a substantial difference (P<0.05). At CW1, the bone width was 0.38 mm at local bone and -0.02 mm at ARP/GBR; at CW4, the bone width was 0.46 mm at local bone and 0.23 mm at ARP/GBR; and at CW7, the bone width was 0.22 mm at local bone and 0.02 mm at ARP/GBR. There was no discernible difference (P>0.05). Resorption of the alveolar bone width was only noticeable at the middle third of the sites. Long-term alterations in the alveolar bone width surrounding dental implants at local and rebuilt bone sites can be observed using CBCT images.

Optimising essential oil yields and quality from Pimenta dioica (L.) merr. Leaf: impact of NaCl concentrations, pH media and sequential separation of essential oil components during hydrodistillation.

The study examined the effects of herb drying, salt concentration, pH, and sampling approach on essential oil yield and composition in Pimenta dioica (L.) Merr. Fresh samples yielded higher essential oil (EO) (1.25%) than shade-dried ones. Increasing NaCl concentration correlated with higher EO yields, while a basic pH favoured superior yields. Gas Chromatography identified Eugenol and ß-myrcene as primary constituents. Eugenol content peaked at 10% NaCl (56.429%) and was lowest at pH 4 (42.850%). ß-myrcene content was highest at pH 4 (31.476%). Hydro distillation with systematic sampling evaluated the effects of 14 fractions in different time frames. Phenylpropanoids (mainly eugenol) and acyclic monoterpene (mainly ß-myrcene) dominated all fractions, with cyclic monoterpene (mainly limonene) enriched in the first four fractions. Fractions 10 to 14 showed significant increases in eugenol compared to the control. These findings provide insights for meeting market demands, enhancing the commercial potential of P. dioica EO.

Enhancing handwritten text recognition accuracy with gated mechanisms.

Handwritten Text Recognition (HTR) is a challenging task due to the complex structures and variations present in handwritten text. In recent years, the application of gated mechanisms, such as Long Short-Term Memory (LSTM) networks, has brought significant advancements to HTR systems. This paper presents an overview of HTR using a gated mechanism and highlights its novelty and advantages. The gated mechanism enables the model to capture long-term dependencies, retain relevant context, handle variable length sequences, mitigate error propagation, and adapt to contextual variations. The pipeline involves preprocessing the handwritten text images, extracting features, modeling the sequential dependencies using the gated mechanism, and decoding the output into readable text. The training process utilizes annotated datasets and optimization techniques to minimize transcription discrepancies. HTR using a gated mechanism has found applications in digitizing historical documents, automatic form processing, and real-time transcription. The results show improved accuracy and robustness compared to traditional HTR approaches. The advancements in HTR using a gated mechanism open up new possibilities for effectively recognizing and transcribing handwritten text in various domains. This research does a better job than the most recent iteration of the HTR system when compared to five different handwritten datasets (Washington, Saint Gall, RIMES, Bentham and IAM). Smartphones and robots are examples of low-cost computing devices that can benefit from this research.

Association of Pharmacist Interventions With Adverse Drug Events and Potential Adverse Drug Events.

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs). METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs. RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33. CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.

Cardiac arrhythmia detection using artificial neural network.

This paper outlines the development of the 'Cardiac Abnormality Monitoring' wearable medical device, aimed at creating a compact safety monitor integrating advanced Artificial Neural Network (ANN) algorithms. Given power consumption constraints and cost-effectiveness, a strategy combining sophisticated instruments with neural network algorithms is proposed to enhance performance. This approach aims to compete with high-end wearable devices, utilizing innovative manufacturing techniques. The paper evaluates the feasibility of employing the Levenberg-Marquardt (LM) ANN algorithm in power-conscious wearable devices, considering its potential for offline embedded systems or IoT gadgets capable of cloud-based data uploading. The Levenberg-Marquardt ANN is chosen primarily for its practicality in prototype development, with other neural network algorithms also explored to identify potential alternatives. We have compared the six neural network models and determined the model that has the potential to replace the primary neural network model. We found that the 'Kernelized SVC with PCA' can test accuracy. To be specific, in this paper, we will evaluate the performance of the ANN model and also check its feasibility and practicality by integrating it with a constructed prototypical working model.

Comparison of TL characteristics of natural quartz and zircon.

The dosimetry of different minerals is carried out to investigate the dose received by the population in case of a nuclear accident. Retrospective dosimetry is a field where there is a continuous search to find new materials. Beach sand minerals, namely quartz and zircon, were exposed to beta and gamma radiation and studied separately. A comparison of the thermoluminescence (TL) output of different peaks of quartz for beta and gamma was studied. Comparison of quartz peaks with the TL output of zircon peaks was carried out. TL output for a constant dose of gamma is always higher compared to the TL output received due to beta.

Dynamic task offloading edge-aware optimization framework for enhanced UAV operations on edge computing platform.

Resource optimization, timely data capture, and efficient unmanned aerial vehicle (UAV) operations are of utmost importance for mission success. Latency, bandwidth constraints, and scalability problems are the problems that conventional centralized processing architectures encounter. In addition, optimizing for robust communication between ground stations and UAVs while protecting data privacy and security is a daunting task in and of itself. Employing edge computing infrastructure, artificial intelligence-driven decision-making, and dynamic task offloading mechanisms, this research proposes the dynamic task offloading edge-aware optimization framework (DTOE-AOF) for UAV operations optimization. Edge computing and artificial intelligence (AI) algorithms integrate to decrease latency, increase mission efficiency, and conserve onboard resources. This system dynamically assigns computing duties to edge nodes and UAVs according to proximity, available resources, and the urgency of the tasks. Reduced latency, increased mission efficiency, and onboard resource conservation result from dynamic task offloading edge-aware implementation framework (DTOE-AIF)'s integration of AI algorithms with edge computing. DTOE-AOF is useful in many fields, such as precision agriculture, emergency management, infrastructure inspection, and monitoring. UAVs powered by AI and outfitted with DTOE-AOF can swiftly survey the damage, find survivors, and launch rescue missions. By comparing DTOE-AOF to conventional centralized methods, thorough simulation research confirms that it improves mission efficiency, response time, and resource utilization.

Field tuning Kitaev systems for spin fractionalization and topological order.

The honeycomb Kitaev model describes aZ2spin liquid with topological order and fractionalized excitations consisting of gappedπ-fluxes and free Majorana fermions. Competing interactions, even when not very strong, are known to destabilize the Kitaev spin liquid. Magnetic fields are a convenient parameter for tuning between different phases of the Kitaev systems, and have even been investigated for potentially counteracting the effects of other destabilizing interactions leading to a revival of the topological phase. Here we review the progress in understanding the effects of magnetic fields on some of the perturbed Kitaev systems, particularly on fractionalization and topological order.