Label Free Particle-by-Particle Quantification of DNA Loading on Sorted Gold Nanostars.

This paper describes a label free technique for determining ligand loading on metal nanoparticles using a variant of secondary ion mass spectrometry. Au4004+ clusters bombard DNA-functionalized anisotropic gold nanostars and isotropic nanospheres with similar surface areas to determine ligand density. For each projectile impact, co-localized molecules within the emission area of a single impact (diameter of 10-15 nm) were examined for each particle. Individual nanoparticle analysis allows for determination of the relationship between particle geometry and DNA loading. We found that branched particles exhibited increased ligand density versus nanospheres and determined that positive and neutral curvature could facilitate additional loading. This methodology can be applied to optimize loading for any ligand-core interaction independent of nanoparticle core, ligand, or attachment chemistry.

Detecting and Visualizing Reaction Intermediates of Anisotropic Nanoparticle Growth.

This paper describes a correlative approach to detect, visualize, and characterize intermediate species during a seedless, anisotropic nanoparticle synthesis. Changes in radical concentration as a function of time were correlated in situ to the optical properties and morphology of the particles. Depending on type and concentration of reaction precursors, either one or two increases in radical production occurred, corresponding to initial particle formation and increased branch length, respectively. Thus, changes in radical intensity can be considered as an indicator of nanoparticle structure and properties.

Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars.

This paper reports an in vivo evaluation of toxicology and biodistribution of a highly anisotropic Au nanoconstruct composed of a gold nanostar (AuNS) core and a ligand shell of a G-quadruplex DNA aptamer AS1411 (Apt) supporting both targeting and therapy capabilities. We examined the toxicity of the nanoconstructs (Apt-AuNS) at four different injected concentrations. At the highest dose tested (48 mg/kg), maximal tolerated dose was not reached. Clinical pathology showed no apparent signs of acute toxicity. Interestingly, the nanoconstructs circulated longer in female rats compared to male rats. In two different tumor models, the biodistribution of Apt-AuNS, especially tumor accumulation, was different. Accumulation of Apt-AuNS was 5 times higher in invasive breast cancer tumors compared to fibrosarcoma tumors. These results provide insight on identifying a tumor model and nanoconstruct for in vivo studies, especially when an in vitro therapeutic response is observed in multiple cancer cell lines. From the clinical editor: This study investigated the toxicity and distribution of aptamer loaded gold nanostars in a rodent model of invasive breast cancer and fibrosarcoma. Acute toxicity was not identified even in the highest studied doses. Fivefold accumulation was demonstrated in the breast cancer model compared to the fibrosarcoma model. Studies like this are critically important in further clarifying the potential therapeutic use of these nanoconstructs, especially when ex vivo effects are clearly demonstrated.

Need for operational simplicity and timely disbursal of benefits-a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India.

BACKGROUND: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. METHODS: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. RESULTS: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. CONCLUSION: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Sodium chloride or plasmalyte-148 for patients presenting to emergency departments with diabetic ketoacidosis: A nested cohort study within a multicentre, cluster, crossover, randomised, controlled trial.

OBJECTIVE: To test the hypothesis that fluid resuscitation in the ED with plasmalyte-148 (PL) compared with 0.9% sodium chloride (SC) would result in a lower proportion of patients with diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission. METHODS: We performed a prespecified nested cohort study at two hospitals within a cluster, crossover, open label, randomised, controlled trial comparing the effects of PL versus SC as fluid therapy for patients who presented to the ED with DKA. All patients presenting within a fixed recruitment period were included. The primary outcome was the proportion of patients admitted to ICU. RESULTS: Eighty-four patients were enrolled (SC n = 38, PL n = 46). The SC group had a lower median pH on admission (SC: 7.09 [interquartile range (IQR) 7.01-7.21], PL: 7.17 [IQR 6.99-7.26]). The median volume of intravenous fluids administered in ED was 2150 mL (IQR 2000-3200 mL; SC) and 2200 mL (IQR 2000-3450; PL); respectively. A higher proportion of patients in the SC group, 19 (50%), was admitted to ICU compared with PL group, 18 (39.1%); however, after adjustment for pH at presentation and diabetes type in a multivariable logistic regression model, the PL group did not have a significantly different rate of ICU admission compared with the SC group (odds ratio for ICU admission 0.73, 95% confidence interval 0.13-3.97, P = 0.71). CONCLUSION: Patients with DKA treated with PL compared with SC in the EDs had similar rates of requiring ICU admission.

Separation of Stabilized MOPS Gold Nanostars by Density Gradient Centrifugation.

This article describes the stabilization and postsynthetic separation of gold nanostars (AuNS) synthesized with a morpholine-based Good's buffer, 3-(N-morpholino)propanesulfonic acid. Resuspension of AuNS in ultrapure water improved the shape stability of the particles over 30 days. We demonstrated the sorting of nanostars via rate-zonal centrifugation through a linear sucrose gradient based on branch length and number. We determined that one round of centrifugation was sufficient for separation. Also, we improved the structural homogeneity and stability of the nanoparticles through the optimization of the storage conditions and established a robust method to sort AuNS based on size and shape.

Shape-Dependent Nonlinear Optical Properties of Anisotropic Gold Nanoparticles.

This Letter reports the shape-dependent third-order nonlinear optical properties of anisotropic gold nanoparticles. We characterized the nonlinear absorption coefficients of nanorods, nanostars, and nanoshells using femtosecond Z-scan measurements. By comparing nanoparticle solutions with a similar linear extinction at the laser excitation wavelength, we separated shape effects from that of the localized surface plasmon wavelength. We found that the nonlinear response depended on particle shape. Using pump-probe spectroscopy, we measured the ultrafast transient response of nanoparticles, which supported the strong saturable absorption observed in nanorods and weak nonlinear response in nanoshells. We found that the magnitude of saturable absorption as well as the ultrafast spectral responses of nanoparticles were affected by the linear absorption of the nanoparticles.