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1.
Article in English | MEDLINE | ID: mdl-39052020

ABSTRACT

Laser-induced graphene (LIG) has been emerging as a promising electrode material for supercapacitors due to its cost-effective and straightforward fabrication approach. However, LIG-based supercapacitors still face challenges with limited capacitance and stability. To overcome these limitations, in this work, we present a novel, cost-effective, and facile fabrication approach by integrating LIG materials with candle-soot nanoparticles. The composite electrode is fabricated by laser irradiation on a Kapton sheet to generate LIG material, followed by spray-coating with candle-soot nanoparticles and annealing. Materials characterization reveals that the annealing process enables a robust connection between the nanoparticles and the LIG materials and enhances nanoparticle graphitization. The prepared supercapacitor yields a maximum specific capacitance of 15.1 mF/cm2 at 0.1 mA/cm2, with a maximum energy density of 2.1 µWh/cm2 and a power density of 50 µW/cm2. Notably, the synergistic activity of candle soot and LIG surpasses the performances of previously reported LIG-based supercapacitors. Furthermore, the cyclic stability of the device demonstrates excellent capacitance retention of 80% and Coulombic efficiency of 100% over 10000 cycles.

2.
Indian J Tuberc ; 71 Suppl 1: S37-S43, 2024.
Article in English | MEDLINE | ID: mdl-39067953

ABSTRACT

BACKGROUND & OBJECTIVES: The purpose of present study is to analyse the distribution and pattern of genetic mutations in PRE-XDR-TB and extensive drug resistant Mycobacterium tuberculosis (XDR-TB) using second-line line probe assay and to compare them with different parameters. METHOD: Sputum, Lymph node aspirate and cold accesses from patients with rifampicin resistant Tuberculosis were subjected to first line and second line Probe Assay (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluroquinolones (Levofloxacin & Moxifloxacin) and Aminoglycosides (Amikacin, Ofloxacin and Kanamycin). The genetic mutation pattern was analysed and compared with demographic, clinical and other parameters. RESULTS: The final study population included 123 fluoroquinolone resistant isolates including 14 isolates with additional second line aminoglycosides drug resistance. The most frequent mutation observed among Gyr A drug resistance mutation was D94G (Gyr A MUT3C, 50/123,40%) corresponding to high level resistance to levofloxacin and moxifloxacin. The most frequent wild type mutant among Gyr A gene locus was WT 3 (85/123,69%). The most common mutation among second line aminoglycoside resistant isolates was at eis WT2 (7/14,50%) followed by rrs MUT 2 (4/14,29%). CONCLUSIONS: GyrA MUT3C (Asp94Gly) was the most common mutation in Gyr A gene locus in M. tuberculosis causing high level levofloxacin and moxifloxacin resistance. Patients with Asp94Gly mutation was significantly associated with underweight body mass index (p = 0.026). This study also observed that history of anti-tuberculosis therapy is a risk factor for FQ drug resistance mutations (p < 0.001).


Subject(s)
Antitubercular Agents , Mutation , Mycobacterium tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Male , Female , Adult , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Middle Aged , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Microbial Sensitivity Tests , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Moxifloxacin/therapeutic use , Moxifloxacin/pharmacology , Young Adult
4.
Fed Pract ; 41(3): 84-87, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38835675

ABSTRACT

Background: Nonadherence to medications is a common clinical issue. We describe a case in which weekly visits to assess medication adherence achieved euthyroidism in a patient with persistent primary hypothyroidism and suspected nonadherence to levothyroxine. The patient, however, did not report nonadherence. Case Presentation: A male aged 67 years with multinodular goiter underwent total thyroidectomy for abnormal thyroid nodule biopsy. Surgical pathology revealed papillary thyroid cancer with lymph node metastasis for which he received radioactive iodine treatment. His plasma thyrotropin (TSH) was noted to be 0.28 uIU/mL (reference range 0.35-4.00 uIU/mL) 7 months postsurgery while taking 224 mcg levothyroxine tablets daily. His plasma TSH remained elevated for about 5 years despite titrations of the levothyroxine dosage, counseling, and multiple follow-up visits. A home care nurse was involved in monitoring the patient taking levothyroxine daily and correctly but was unsuccessful. The patient and his son reported taking levothyroxine daily and correctly. The patient was asked to visit the primary care clinic every week for 6 weeks with all his medications. Repeat plasma TSH normalized to 1.01 uIU/mL. The suspected etiology of previously high plasma TSH was nonadherence to levothyroxine, which was discussed in detail with the patient. The patient verbalized understanding, was willing to follow recommendations and ended the weekly clinic visits. Repeat plasma TSH was again high and the patient claimed adherence, but weekly visits to primary care clinic were resumed, and life-threatening consequences of hypothyroidism were discussed with the patient and his son. After 9 weeks of visits, he was noted to have low plasma TSH (0.23 uIU/mL). Conclusions: Weekly visits seem impractical but may help in cases of persistent hypothyroidism in which the patient admits to being or is suspected to be nonadherent to levothyroxine. Knowing their medication use will be checked at weekly clinic visits may motivate the patient to be adherent.

5.
Transpl Int ; 37: 12536, 2024.
Article in English | MEDLINE | ID: mdl-38835886

ABSTRACT

Living donor liver transplantation (LDLT) needs "Mercedes Benz" or "J-shaped" incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT.


Subject(s)
Liver Transplantation , Living Donors , Postoperative Complications , Humans , Liver Transplantation/methods , Liver Transplantation/adverse effects , Female , Male , Middle Aged , Retrospective Studies , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Length of Stay , Treatment Outcome
6.
Ann Otol Rhinol Laryngol ; 133(8): 741-749, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38822732

ABSTRACT

OBJECTIVE: This study aimed to evaluate the prevalence, incidence, and associated demographic factors of chronic suppurative otitis media (CSOM), utilizing a nationwide healthcare claims database. METHODS: This retrospective study utilized outpatient administrative claims data from the IBM MarketScan Research Database from 2007 to 2021. The database (11 246 909 584 claims with 148 147 615 unique patients) includes health data from the private-sector, Medicare/Medicaid, managed care providers, and EMR providers. Included patients had a diagnosis of CSOM based on ICD-9-CM and ICD-10-CM codes. Prevalence and health utilization were estimated by age, gender, and geographic region. RESULTS: In the United States, the estimated CSOM prevalence and incidence was 0.46% and 0.03%, respectively. Among CSOM patients (n = 679 906), mean age (SD) was 8.1 (15.4) years, and 52.8% were male. Most patients (81.1%) were aged 0 to 10 years. CSOM prevalence was lower in females (OR = 0.64, 95% CI 0.64-0.65, P < .001), less common in older age (OR = 0.94, 95% CI 0.94-0.94, P < .001), and highest in the South region (OR = 2.08, 95% CI 2.06-2.09, P < .001). CONCLUSION: Our results show CSOM prevalence (0.46%) is similar to other developed countries. CSOM prevalence was highest in those aged 0 to 10 years, in males and in the South region. Of note, prevalence and cost are likely significantly underestimated given limitations in accurate ICD-CM coding and the exclusion of uninsured patients. Further epidemiological studies are warranted to characterize the impact of CSOM on the US healthcare system.


Subject(s)
Otitis Media, Suppurative , Humans , Otitis Media, Suppurative/epidemiology , United States/epidemiology , Male , Female , Chronic Disease/epidemiology , Retrospective Studies , Child, Preschool , Infant , Prevalence , Child , Adolescent , Adult , Middle Aged , Incidence , Young Adult , Aged , Infant, Newborn , Databases, Factual
7.
Proc Natl Acad Sci U S A ; 121(22): e2401656121, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38787880

ABSTRACT

Understanding the dynamics of electric-double-layer (EDL) charging in porous media is essential for advancements in next-generation energy storage devices. Due to the high computational demands of direct numerical simulations and a lack of interfacial boundary conditions for reduced-order models, the current understanding of EDL charging is limited to simple geometries. Here, we present a network model to predict EDL charging in arbitrary networks of long pores in the Debye-Hückel limit without restrictions on EDL thickness and pore radii. We demonstrate that electrolyte transport is described by Kirchhoff's laws in terms of the electrochemical potential of charge (the valence-weighted average of the ion electrochemical potentials) instead of the electric potential. By employing the equivalent circuit representation suggested by these modified Kirchhoff's laws, our methodology accurately captures the spatial and temporal dependencies of charge density and electric potential, matching results obtained from computationally intensive direct numerical simulations. Our network model provides results up to six orders of magnitude faster, enabling the efficient simulation of a triangular lattice of five thousand pores in 6 min. We employ the framework to study the impact of pore connectivity and polydispersity on electrode charging dynamics for pore networks and discuss how these factors affect the time scale, energy density, and power density of capacitive charging. The scalability and versatility of our methodology make it a rational tool for designing 3D-printed electrodes and for interpreting geometric effects on electrode impedance spectroscopy measurements.

8.
Am J Ophthalmol ; 265: 296-302, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38701875

ABSTRACT

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by 3 uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering) and UWFFA (Optos Plc) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA compared with Set 1. RESULTS: The mean age of the patients was 46.9 ± 22.4 years (range, 7-96), and 91 (57.6%) were female. With Set 1 alone, 138 eyes (55.2%) were found to have active disease; localization was anterior in 58 eyes (42.0%), posterior in 53 eyes (38.4%), and anterior + posterior in 27 eyes (19.6%). With Set 2, 169 eyes of 107 patients had active anterior, posterior, or panuveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 eyes (18.3%) with active disease (P = .006) and an additional 31 eyes (18.3%) having disease in both anterior + posterior segments (P < .001). Regarding the primary outcome, management was changed in 68 eyes (27.4%) in Set 2 compared with Set 1. CONCLUSIONS: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared with clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of patients with uveitis at the baseline visit.

9.
Nanotechnology ; 35(33)2024 May 30.
Article in English | MEDLINE | ID: mdl-38759631

ABSTRACT

In this paper, the piezoresistive sensitivity is enhanced by applying uniform mechanical stress (MS) on the multi-nanosheet (NS) channels of sub-5 nm junctionless field-effect transistors. The piezoresistivity of the sensing device is boosted by narrowing channel conductivity using low gate biasing and reducing physical channel width, resulting in the maximum (∼6 times higher) sensitivity observed in the subthreshold regime compared to the ON-state condition. In addition, the sensitivity is extensively increased by ∼30.3% near the threshold voltage with horizontally multi-NS stacking due to the uniform MS distribution on the multi-NS channels, which can sense slight deflection of pressure on the circular diaphragm. These results show that the tunable sensitivity of junctionless multi-channel devices is superior to the inversion mode, a consequence of the less scattering effect, better thermal stability, and low electronic noise.

10.
J Assoc Physicians India ; 72(3): 79-81, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38736122

ABSTRACT

Blood pressure (BP) measurement is affected by multiple variables which influence clinical management decisions and patient outcomes. Around 24-hour ambulatory blood pressure monitoring (ABPM) avoids incorrect diagnosis of hypertension (HT), and unnecessary treatment and provides the best prediction of cardiovascular (CV) risk. Clinically important phenotypes of HT such as masked HT (masked HT), white coat HT (white coat HT), and nocturnal HT (nocturnal HT) may be missed by not incorporating ambulatory BP monitoring in practice. However, lack of device availability, operational difficulties, and cost remain barriers to its widespread acceptance in India. In this review, we discuss the when, what, who, why, and where (5Ws) relevant to ABPM measurement.


Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Humans , Blood Pressure Monitoring, Ambulatory/methods , Hypertension/diagnosis , Masked Hypertension/diagnosis , White Coat Hypertension/diagnosis , Blood Pressure/physiology , India
12.
J Phys Chem B ; 128(20): 4975-4985, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38743687

ABSTRACT

The primary event in chemical neurotransmission involves the fusion of a membrane-limited vesicle at the plasma membrane and the subsequent release of its chemical neurotransmitter cargo. The cargo itself is not known to have any effect on the fusion event. However, amphiphilic monoamine neurotransmitters (e.g., serotonin and dopamine) are known to strongly interact with lipid bilayers and to affect their mechanical properties, which can in principle impact membrane-mediated processes. Here, we probe whether serotonin can enhance the association and fusion of artificial lipid vesicles in vitro. We employ fluorescence correlation spectroscopy and total internal reflection fluorescence microscopy to measure the attachment and fusion of vesicles whose lipid compositions mimic the major lipid components of synaptic vesicles. We find that the association between vesicles and supported lipid bilayers is strongly enhanced in a serotonin dose-dependent manner, and this drives an increase in the rate of spontaneous fusion. Molecular dynamics simulations and fluorescence spectroscopy data show that serotonin insertion increases the water content of the hydrophobic part of the bilayer. This suggests that the enhanced membrane association is likely driven by an energetically favorable drying transition. Other monoamines, such as dopamine and norepinephrine, but not other related species, such as tryptophan, show similar effects on membrane association. Our results reveal a lipid bilayer-mediated mechanism by which monoamines can themselves modulate vesicle fusion, potentially adding to the control toolbox for the tightly regulated process of neurotransmission in vivo.


Subject(s)
Lipid Bilayers , Molecular Dynamics Simulation , Serotonin , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Serotonin/chemistry , Serotonin/metabolism , Membrane Fusion , Synaptic Vesicles/metabolism , Synaptic Vesicles/chemistry , Spectrometry, Fluorescence , Hydrophobic and Hydrophilic Interactions
13.
Ann Hematol ; 103(6): 2133-2144, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634917

ABSTRACT

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.


Subject(s)
Anticoagulants , Cytochrome P-450 CYP2C9 , Economics, Pharmaceutical , International Normalized Ratio , Vitamin K Epoxide Reductases , Warfarin , Humans , Warfarin/economics , Warfarin/administration & dosage , Warfarin/therapeutic use , Female , Male , Middle Aged , Cytochrome P-450 CYP2C9/genetics , Aged , Vitamin K Epoxide Reductases/genetics , Anticoagulants/administration & dosage , Anticoagulants/economics , Anticoagulants/therapeutic use , Pharmacogenomic Testing/economics , Adult , Pharmacogenetics/economics , Cost-Benefit Analysis
14.
ACS Appl Mater Interfaces ; 16(14): 17339-17346, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38531044

ABSTRACT

Living organisms inspire the design of microrobots, but their functionality is unmatched. Next-generation microrobots aim to leverage the sensing and communication abilities of organisms through magnetic hybridization, attaching magnetic particles to them for external control. However, the protocols used for magnetic hybridization are morphology specific and are not generalizable. We propose an alternative approach that leverages the principles of negative magnetostatics and magnetophoresis to control nonmagnetic organisms with external magnetic fields. To do this, we disperse model organisms in dispersions of Fe3O4 nanoparticles and expose them to either uniform or gradient magnetic fields. In uniform magnetic fields, living organisms align with the field due to external torque, while gradient magnetic fields generate a negative magnetophoretic force, pushing objects away from external magnets. The magnetic fields enable controlling the position and orientation of Caenorhabditis elegans larvae and flagellated bacteria through directional interactions and magnitude. This control is diminished in live spermatozoa and adult C. elegans due to stronger internal biological activity, i.e., force/torque. Our study presents a method for spatiotemporal organization of living organisms without requiring magnetic hybridization, opening the way for the development of controllable living microbiorobots.


Subject(s)
Caenorhabditis elegans , Nanoparticles , Animals , Magnetics , Magnets , Magnetic Fields
15.
BMJ Open ; 14(3): e080620, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38508619

ABSTRACT

INTRODUCTION: Satisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia. METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app. ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.


Subject(s)
Acute Pain , Ketoprofen/analogs & derivatives , Tramadol , Tromethamine , Humans , Male , Female , Tramadol/therapeutic use , Acute Pain/drug therapy , Prospective Studies , Pain, Postoperative/drug therapy , Double-Blind Method , Registries , Thailand , Observational Studies as Topic , Drug Combinations
16.
J Chem Theory Comput ; 20(7): 2774-2785, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38530869

ABSTRACT

The complexity and size of large molecular systems, such as protein-ligand complexes, pose computational challenges for accurate post-Hartree-Fock calculations. This study delivers a thorough benchmarking of the Molecules-in-Molecules (MIM) method, presenting a clear and accessible strategy for layer/theory selections in post-Hartree-Fock computations on substantial molecular systems, notably protein-ligand complexes. An approach is articulated, enabling augmented computational efficiency by strategically canceling out common subsystem energy terms between complexes and proteins within the supermolecular equation. Employing DLPNO-based post-Hartree-Fock methods in conjunction with the three-layer MIM method (MIM3), this study demonstrates the achievement of protein-ligand binding energies with remarkable accuracy (errors <1 kcal mol-1), while significantly reducing computational costs. Furthermore, noteworthy correlations between theoretically computed interaction energies and their experimental equivalents were observed, with R2 values of approximately 0.90 and 0.78 for CDK2 and BZT-ITK sets, respectively, thus validating the efficacy of the MIM method in calculating binding energies. By highlighting the crucial role of diffuse or small Pople-style basis sets in the middle layer for reducing energy errors, this work provides valuable insights and practical methodologies for interaction energy computations in large molecular complexes and opens avenues for their application across a diverse range of molecular systems.


Subject(s)
Proteins , Quantum Theory , Ligands , Thermodynamics , Proteins/chemistry , Protein Binding
17.
Nano Lett ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38437028

ABSTRACT

Nanopore-based sensing platforms have transformed single-molecule detection and analysis. The foundation of nanopore translocation experiments lies in conductance measurements, yet existing models, which are largely phenomenological, are inaccurate in critical experimental conditions such as thin and tightly fitting pores. Of the two components of the conductance blockade, channel and access resistance, the access resistance is poorly modeled. We present a comprehensive investigation of the access resistance and associated conductance blockade in thin nanopore membranes. By combining a first-principles approach, multiscale modeling, and experimental validation, we propose a unified theoretical modeling framework. The analytical model derived as a result surpasses current approaches across a broad parameter range. Beyond advancing our theoretical understanding, our framework's versatility enables analyte size inference and predictive insights into conductance blockade behavior. Our results will facilitate the design and optimization of nanopore devices for diverse applications, including nanopore base calling and data storage.

18.
Int J Womens Health ; 16: 1-7, 2024.
Article in English | MEDLINE | ID: mdl-38193139

ABSTRACT

We evaluated the potential relevance of our multi-cancer detection test, OncoVeryx-F, for ovarian cancer screening. For this, we compared its accuracy with that of CA125-based screening. We demonstrate here that, in contrast to CA125-based detection, OncoVeryx-F detected ovarian cancer with very high sensitivity and specificity. Importantly here, Stage I cancers too could be detected with an accuracy of >98%. Furthermore, again unlike CA 125, the detection accuracy of OncoVeryx-F remained comparable in both Caucasian and South Asian/Indian women. Thus, the robustness and accuracy of OncoVeryx-F, particularly for early-stage detection, underscores its potential utility for ovarian cancer screening.

19.
Can J Ophthalmol ; 59(2): e155-e160, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36803933

ABSTRACT

OBJECTIVE: To identify risk factors for surgical failure after scleral buckling (SB) for primary rhegmatogenous retinal detachment (RRD) repair. DESIGN: Single-centre retrospective consecutive case series. PARTICIPANTS: All patients who underwent SB for repair of primary RRD at Wills Eye Hospital between January 1, 2015, and December 31, 2018, were included. METHODS: Single-surgery anatomic success (SSAS) rate and risk factors associated with surgical failure were evaluated. A multivariable logistic regression model was completed to assess the effect of demographic, clinical, and operative variables on SSAS rate. RESULTS: A total of 499 eyes of 499 patients were included. Overall SSAS rate was 86% (n = 430 of 499). Using multivariate analysis, surgical failure was more likely in males (adjusted odds ratio [adjusted OR] = 2.98; 95% CI, 1.58-5.62; p = 0.0007) with a macula-off status on preoperative examination (adjusted OR = 2.15; 95% CI, 1.10-4.20; p = 0.03) and preoperative proliferative vitreoretinopathy (adjusted OR = 4.26; 95% CI, 1.10-16.5; p = 0.04). Time interval between initial examination and surgery (p = 0.26), distribution of buckle or band material used (p = 0.88), and distribution of tamponade used (p = 0.74) were not significantly different between eyes with and without surgical failure. CONCLUSION: Male sex, macula-off status, and preoperative proliferative vitreoretinopathy were factors with increased odds of surgical failure after SB for primary RRD repair. Operative characteristics, such as type of band or use of tamponade, were not associated with surgical failure.


Subject(s)
Retinal Detachment , Vitreoretinopathy, Proliferative , Humans , Male , Scleral Buckling/adverse effects , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retinal Detachment/surgery , Retrospective Studies , Vitreoretinopathy, Proliferative/complications , Vitreoretinopathy, Proliferative/surgery , Treatment Outcome , Vitrectomy/adverse effects , Visual Acuity , Risk Factors
20.
Nephrology (Carlton) ; 29(2): 93-99, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37794611

ABSTRACT

AIM: End-stage kidney disease (ESKD) is increasingly becoming a healthcare concern in New Zealand and haemodialysis remains the most common modality of treatment. Frailty and health-related quality of life (HRQOL) are established predictors of prognosis and have already been shown to be poor in the dialyzing population. Existing data show correlation between these measures in the ESKD population, however there is little evidence for those on haemodialysis specifically. Our study aimed to assess for a correlation between frailty and HRQOL in the haemodialysis population at Palmerston North Hospital, and to assess for any differences in frailty and HRQOL scores between indigenous Maori and non-Maori subgroups. METHODS: A cross-sectional study was conducted involving 93 in-centre haemodialysis patients from Palmerston North Hospital, New Zealand. Baseline demographic data was measured alongside frailty and HRQOL scores, which were measured using the Kidney Disease Quality of Life tool (KDQOL-36) and the Edmonton Frail Scale. RESULTS: A statistically significant negative correlation was observed between frailty and all aspects of HRQOL (p < .05), with the strongest correlation observed between frailty and the physical component (r = -.64, p = <.001). Independent samples t-test showed no statistically significant difference between scores for Maori and non-Maori in frailty (M = 7.4, SD = 3.3 vs. M = 6.8, SD = 3.2; t (91) = -0.92, p = .80), or HRQOL (p values > .05 in all components). CONCLUSION: A negative correlation was observed between frailty and HRQOL. This information can be beneficial in guiding discussions around treatment modality and for future patients and useful in enabling better predictions of prognosis. No statistically significant differences in frailty and HRQOL scores were observed between Maori and non-Maori groups, however the generalizability of this finding is limited due to the insufficient size of the study population.


Subject(s)
Frailty , Kidney Failure, Chronic , Humans , Quality of Life , Frailty/diagnosis , Frailty/epidemiology , Maori People , New Zealand/epidemiology , Cross-Sectional Studies , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Hospitals
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