Gold nanoclusters as prospective carriers and detectors of pramipexole

Pramipexole (PPX) is known in the treatment of Parkinson''s disease and restless legs syndrome. We carried out a theoretical investigation on pramipexole–Au cluster interactions for the applications of drug delivery and detection. Three Au_N clusters with sizes N = 6, 8 and 20 were used as reactant models to simulate the metallic nanostructured surfaces. Quantum chemical computations were performed in both gas phase and aqueous environments using density functional theory (DFT) with the PBE functional and the cc-pVDZ-PP/cc-pVTZ basis set. The PPX drug is mainly adsorbed on gold clusters via its nitrogen atom of the thiazole ring with binding energies of ca. −22 to −28 kcal mol⁻¹ in vacuum and ca. −18 to −24 kcal mol⁻¹ in aqueous solution. In addition to such Au–N covalent bonding, the metal–drug interactions are further stabilized by electrostatic effects, namely hydrogen-bond NH⋯Au contributions. Surface-enhanced Raman scattering (SERS) of PPX adsorbed on the Au surfaces and its desorption process were also examined. In comparison to Au₈, both Au₆ and Au₂₀ clusters undergo a shorter recovery time and a larger change of energy gap, being possibly conducive to electrical conversion, thus signaling for detection of the drug. A chemical enhancement mechanism for SERS procedure was again established in view of the formation of nonconventional hydrogen interactions Au⋯H–N. The binding of PPX to a gold cluster is expected to be reversible and triggered by the presence of cysteine residues in protein matrices or lower-shifted alteration of environment pH. These findings would encourage either further theoretical probes to reach more accurate views on the efficiency of pramipexole–Au interactions, or experimental attempts to build appropriate gold nanostructures for practical trials, harnessing their potentiality for applications.

Gold clusters as prospective carriers and detectors of pramipexole.     

Evaluation of Targeted Next-Generation Sequencing for the Management of Patients Diagnosed with a Cancer of Unknown Primary

BackgroundCancer of unknown primary (CUP) comprises a heterogeneous collection of malignancies that are typically associated with a poor prognosis and a lack of effective treatment options. We retrospectively evaluated the clinical utility of targeted next-generation sequencing (NGS) among CUP patients to assist with diagnosis and identify opportunities for molecularly guided therapy.Patients and MethodsPatients with a CUP at Moffitt Cancer Center who underwent NGS between January 1, 2014 and December 31, 2019, were eligible for study inclusion. Next-generation sequencing results were assessed to determine the frequency of clinically actionable molecular alterations, and chart reviews were performed to ascertain the number of patients receiving molecularly guided therapy.ResultsNinety-five CUP patients were identified for analysis. Next-generation sequencing testing identified options for molecularly guided therapy for 55% (n = 52) of patients. Among patients with molecularly guided therapy options, 33% (n = 17) were prescribed a molecularly guided therapy. The median overall survival for those receiving molecularly guided therapy was 23.6 months. Among the evaluable patients, the median duration of treatment for CUP patients (n = 7) receiving molecular-guided therapy as a first-line therapy was 39 weeks. The median duration of treatment for CUP patients (n = 8) treated with molecularly guided therapy in the second- or later-line setting was 13 weeks. Next-generation sequencing results were found to be suggestive of a likely primary tumor type for 15% (n = 14) of patients.ConclusionNext-generation sequencing results enabled the identification of treatment options in a majority of patients and assisted with the identification of a likely primary tumor type in a clinically meaningful subset of patients.     

Impact of Infectious Disease after Lactococcus lactis Strain Plasma Intake in Vietnamese Schoolchildren: A Randomized,Placebo-Controlled,Double-Blind Study

Lactococcus lactis strain Plasma (LC-Plasma) is reported to have anti-viral effects via direct activation of plasmacytoid dendritic cells, which upregulate the production of type I and III interferons. A randomized, placebo-controlled, double-blind, parallel group study was designed for elementary schoolchildren, grades 1 to 3, in Vietnam. LC-Plasma or a control were administered to schoolchildren as a beverage (1.0 × 10¹¹ count LC-Plasma/day/person). The primary endpoint was to determine the efficacy of LC-Plasma in reducing the cumulative days absent from school due to upper respiratory disease (URID) and gastrointestinal disease (GID), and the secondary endpoint was to evaluate the potency of LC-Plasma on URID/GID symptoms and general well-being scores. LC-Plasma intake significantly reduced the cumulative days absent from school due to URID/GID (Odds ratio (OR) = 0.57, p = 0.004) and URID alone (OR = 0.56, p = 0.005); LC-Plasma also significantly reduced the number of cumulative fever positive days during the first 4 weeks of intervention (OR = 0.58, p = 0.001) and cumulative days with diarrhea during the last 4 weeks of the intervention period (OR = 0.78, p = 0.01). The number of positive general wellbeing days was significantly improved in the LC-Plasma group compared with the control throughout the intervention period (OR = 0.93, 0.93, p = 0.03, 0.04 in the first and last 4 weeks of the intervention, respectively). These data suggest that LC-Plasma seems to improve the health condition of elementary schoolchildren and reduces school absenteeism due to infectious disease, especially URID.     

Gold nanoparticle-based optical nanosensors for food and health safety monitoring: recent advances and future perspectives

Modern society has been facing serious health-related problems including food safety, diseases and illness. Hence, it is urgent to develop analysis methods for the detection and control of food contaminants, disease biomarkers and pathogens. As the traditional instrumental methods have several disadvantages, including being time consuming, and having high cost and laborious procedures, optical nanosensors have emerged as promising alternative or complementary approaches to those traditional ones. With the advantages of simple preparation, high surface-to-volume ratio, excellent biocompatibility, and especially, unique optical properties, gold nanoparticles (AuNPs) have been demonstrated as excellent transducers for optical sensing systems. Herein, we provide an overview of the synthesis of AuNPs and their excellent optical properties that are ideal for the development of optical nanosensors based on local surface plasmon resonance (LSPR), colorimetry, fluorescence resonance energy transfer (FRET), and surface-enhanced Raman scattering (SERS) phenomena. We also review the sensing strategies and their mechanisms, as well as summarizing the recent advances in the monitoring of food contaminants, disease biomarkers and pathogens using developed AuNP-based optical nanosensors in the past seven years (2015–now). Furthermore, trends and challenges in the application of these nanosensors in the determination of those analytes are discussed to suggest possible directions for future developments.

We provide an overview of the synthesis of AuNPs and their excellent optical properties for the development of optical nanosensors including colorimetric, fluorescence resonance energy transfer, and surface-enhanced Raman scattering sensors.     

Enhanced power conversion efficiency of an n-Si/PEDOT:PSS hybrid solar cell using nanostructured silicon and gold nanoparticles

Herein, the effect of nanostructured silicon and gold nanoparticles (AuNPs) on the power conversion efficiency (PCE) of an n-type silicon/poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (n-Si/PEDOT:PSS) hybrid solar cell was investigated. The Si surface modified with different nanostructures including Si nanopyramids (SiNPs), Si nanoholes (SiNHs) and Si nanowires (SiNWs) was utilized to improve light trapping and photo-carrier collection. The highest power conversion efficiency (PCE) of 8.15% was obtained with the hybrid solar cell employing SiNWs, which is about 8%, 20% and 40% higher compared to the devices using SiNHs, SiNPs and planar Si, respectively. The enhancement is attributed to the low reflectance of the SiNW structures and large PEDOT:PSS/Si interfacial area. In addition, the influence of AuNPs on the hybrid solar cell''s performance was examined. The PCE of the SiNW/PEDOT:PSS hybrid solar cell with 0.5 wt% AuNP is 8.89%, which is ca. 9% higher than that of the device without AuNPs (8.15%). This is attributed to the increase in the electrical conductivity and localized surface plasmon resonance of the AuNP-incorporated PEDOT:PSS coating layer.

n-Si/PEDOT:PSS hybrid solar cells using nanostructured silicon and AuNPs were prepared and investigated.     

An analysis of reflective writing early in the medical curriculum: The relationship between reflective capacity and academic achievement

Objective: To examine the relationship between reflection, gender, residency choice, word count, and academic achievement among medical students.

Methods: A modified version of the Reflection Evaluation for Learners’ Enhanced Competencies Tool (REFLECT) was developed and used for this study (Cronbach’s alpha of 0.86 with an intraclass correlation coefficient [ICC] of 0.68). This was applied to writing samples about professionalism in gross anatomy from first-year medical students between 2005 and 2011. Four analysts reviewed and scored written reflections independently. Composite reflection scores were compared with gender, residency choice, length of written reflection, NBME® Gross Anatomy and Embryology Subject Examination scores, and final gross anatomy course.

Results: Total of 319 written reflections were evaluated. Female students who pursued medicine specialties had the highest composite reflection scores (87 [27.2%]). Word count frequently correlated with reflection score (p?<?0.0001). Students who performed well on the NBME® Gross Anatomy and Embryology Subject Examination tended to achieve high anatomy course grades (p?<?0.0001). There was no statistically significant relationship between composite reflection scores and NBME® Gross Anatomy and Embryology Subject Examination scores (p?=?0.16) or anatomy course grades (p?=?0.90).

Conclusions: This study suggests there are likely no correlations between reflective capacity and academic performance on tests of medical knowledge administered early in the medical curriculum.     

Warming and Salt Intrusion Affect Microcystin Production in Tropical Bloom-Forming Microcystis

The Vietnamese Mekong Delta is predicted to be one of the regions most impacted by climate change, causing increased temperature and salinity in inland waters. We hypothesized that the increase in temperature and salinity may impact the microcystin (MC) production of two Microcystis strains isolated in this region from a freshwater pond (strain MBC) and a brackish water pond (strain MTV). The Microcystis strains were grown at low (27 °C), medium (31 °C), high (35 °C) and extremely high (37 °C) temperature in flat photobioreactors (Algaemist). At each temperature, when cultures reached a stable state, sea salt was added to increase salinity to 4‰, 8‰, 12‰ and 16‰. MC concentrations and cell quota were reduced at high and extremely high temperatures. Salinity, in general, had comparable effects on MC concentrations and quota. At a salinity of 4‰ and 8‰, concentrations of MC per mL of culture and MC cell quota (based on chlorophyll, dry-weight and particle counts) were higher than at 0.5‰, while at the highest salinities (12‰ and 16‰) these were strongly reduced. Strain MBC produced five MC variants of which MC-RR and MC-LR were most abundant, followed by MC-YR and relatively low amounts of demethylated variants dmMC-RR and dmMC-LR. In strain MTV, MC-RR was most abundant, with traces of MC-YR and dmMC-RR only in cultures grown at 16‰ salinity. Overall, higher temperature led to lower MC concentrations and cell quota, low salinity seemed to promote MC production and high salinity reduced MC production. Hence, increased temperature and higher salinity could lead to less toxic Microcystis, but since these conditions might favour Microcystis over other competitors, the overall biomass gain could offset a lower toxicity.     

The diagnosis of infection in chronic leg ulcers: A narrative review on clinical practice

This literature review aimed to provide a narrative review of evidence on validity of clinical and microbial indicators of infection and to gain insights into the diagnosis of infection in chronic leg ulcers (CLUs). A search was conducted in Cinahl, Medline, the Cochrane Library databases, Embase, Web of Science, ScienceDirect, Pubmed, PsycINFO, ProQuest dissertations, and Google Scholar from January 1990 to July 2017. The inclusion criteria were original studies, systematic reviews, and consensus documents focused on “infection” in CLUs, English language, clinical and community settings, and human. The reviewed studies were inconsistent in criteria for infection between investigated wound types and lack of specificity regarding wound types. There were few studies investigating the criteria for diagnosis of infection in leg ulcers. The identification of leg ulcer infection still remains problematic and relies on out‐of‐date and not uniform evidence. Literature in this area was mostly limited to level III and IV evidence based on The Australian National Health and Medical Research Council Levels of Evidence, or expert opinion. This literature review showed seven clinical signs and symptoms that could be diagnostic for infection in CLUs, including: new, increased, or altered ulcer pain; malodour; increased ulcer area; wound breakdown, delayed or non‐healing; and erythema and increased local temperature, whilst the microbial indicators used to diagnose infected leg ulcers were varied and regarded as less important.