Quantification of monodisperse and biocompatible gold nanoparticles by single-particle ICP-MS.

Bioanalytical and biomedical applications often require nanoparticles that exhibit narrow size distributions and biocompatibility. Here, we demonstrate how different synthesis methods affect gold nanoparticle (AuNPs) monodispersity and cytotoxicity. Using single particle inductively coupled plasma mass spectrometry (SP-ICP-MS), we found that the size distribution of AuNPs synthesized with a cetyltrimethylammonium chloride (CTAC) cap was significantly improved compared to AuNPs synthesized with citrate capping agents. We determined an up to 4× decrease in the full width at half maximum (FWHM) value of the normal distributions of AuNP diameter and up to a 12% decrease in relative standard deviation (RSD). While the CTAC-capped AuNPs exhibit narrow nanoparticle size distributions, they are cytotoxic, which limits safe and effective bioanalytical and biomedical applications. We sought to impart biocompatibility to CTAC-capped AuNPs through a PEGylation-based surface ligand exchange. We developed a unique ligand exchange method driven by physical force. We demonstrated the successful PEGylation using various PEG derivatives and used these PEGylated nanoparticles to further bioconjugate nucleic acids and peptides. Using cell viability quantification, we confirmed that the monodisperse PEGylated AuNPs were biocompatible. Our monodisperse and biocompatible nanoparticles may advance safe and effective bioanalytical and biomedical applications of nanomaterials.

Controlling Nanoparticle Uptake in Innate Immune Cells with Heparosan Polysaccharides.

We used heparosan (HEP) polysaccharides for controlling nanoparticle delivery to innate immune cells. Our results show that HEP-coated nanoparticles were endocytosed in a time-dependent manner by innate immune cells via both clathrin-mediated and macropinocytosis pathways. Upon endocytosis, we observed HEP-coated nanoparticles in intracellular vesicles and the cytoplasm, demonstrating the potential for nanoparticle escape from intracellular vesicles. Competition with other glycosaminoglycan types inhibited the endocytosis of HEP-coated nanoparticles only partially. We further found that nanoparticle uptake into innate immune cells can be controlled by more than 3 orders of magnitude via systematically varying the HEP surface density. Our results suggest a substantial potential for HEP-coated nanoparticles to target innate immune cells for efficient intracellular delivery, including into the cytoplasm. This HEP nanoparticle surface engineering technology may be broadly used to develop efficient nanoscale devices for drug and gene delivery as well as possibly for gene editing and immuno-engineering applications.

Prevalence and Risk Factors of Dental Trauma in Ha'il, Saudi Arabia.

AIM: This study will aid in determining the prevalence and risk factors for dental trauma. This will assist in developing a treatment budget plan, thereby, fend off complications. MATERIALS AND METHODS: This study was an observational study, having a cross-sectional design, in which information was obtained from 555 participants. Data were obtained using a non-probability convenient sampling technique. A validated questionnaire was used as a study tool. Data were analyzed using the statistical package for the social sciences (SPSS, version 20). Descriptive and inferential statistics were used. Data were displayed as numbers and percentages, and the Chi-squared test was used to measure the association. RESULTS: Dental trauma was found to be 44% prevalent. Most of the injuries occurred in the 6-9-years age-group (19.1%) and were more common in boys (54.13%) than in girls. The majority of respondents (61%) identified "falls" as the most common cause of dental trauma, and the frequent location for the occurrence of dental injuries was found to be "home" (64.44%). Only 18% of parents reported that their kid's experienced nail-biting concerns, with the majority claimed that their kids never developed oral habits. Most dental injuries occurred during the summer season (48%). CONCLUSION: Young aged group and male gender group were more prone to dental injuries; dental injuries along with fall were found as the most common cause of dental trauma, whereas most of the dental traumas were reported to have occurred at home. CLINICAL SIGNIFICANCE: The study evaluated risk factors and the prevalence of dental trauma in the population of Ha'il, Saudi Arabia. It will be an effective tool for determining the need for treatment facilities.

First report of Tsukamurella endocarditis in an immunocompromised patient receiving chemotherapy.

Tsukamurella spp. are gram-positive rods that can be isolated from the environment in soil and moist areas. In rare instances, they are known to cause infections in immunocompromised hosts. We present the first reported case of Tsukamurella endocarditis in an immunocompromised patient who was successfully treated with a 6-week course of imipenem and trimethoprim-sulfamethoxazole.

Caries risk assessment by Caries Management by Risk Assessment (CAMBRA) Protocol among the general population of Pakistan-a multicenter analytical study.

Background: Caries risk (CR) assessment tools are used to properly identify individuals with caries risk and to improve preventive procedures and programs. A tool such as CAMBRA determines the precise protective factors of caries and identifies an individual's specific therapeutic intervention. The purpose of this study was to assess the caries risk using the CAMBRA protocol among the general population of Pakistan. Methods: This multicentre analytical study was conducted in ten dental hospitals in different provinces of Pakistan and the caries risk assessment was carried out using a questionnaire that was designed using the Caries Management by Risk Assessment (CAMBRA) protocol. All 521 participants were intra-orally examined to assess oral hygiene status and the presence of disease. Multiple logistic regression test was performed for analysis. Results: A higher number of participants (61.2%) were found to be in the moderate risk category of caries risk assessment. The males are 51% less likely to have caries compared to the females (AOR = 0.49, P = 0.081). The majority of participants (71.3%) had one or more disease indicators, with white spots and visible cavities. Those with visible, heavy plaque were 13.9 times more likely to have caries compared to those without (AOR = 13.92, P < 0.001). Those using calcium and phosphate during the last 6 months were 90% less likely to have caries compared to those not using them (AOR = 0.10, P < 0.001). There was no significant interaction between all eight risk factors retained in the final model (P > 0.05), the Hosmer and Lemeshow Test P < 0.001, classification accuracy = 87.1%, and AUC = 91.2%. Conclusion: The caries risk among the general population of Pakistan is moderate, with significant variation among age groups, education levels, and socioeconomic status.

Perception, attitude, and preference of trainees towards workplace-based assessment in dental education at a tertiary care institute in Multan, Pakistan.

BACKGROUND: Modern medical education has flourished with an emergent interest in a variety of assessment approaches that entails direct observation of performance and provision of feedback. Workplace-based assessment (WPBA) has been embraced into specialty training in the United Kingdom (UK) within National Health Service (NHS). In Pakistan, this educational framework is incorporated to gauge the clinical proficiency of trainees at the postgraduate and undergraduate levels. The present study was done to identify how WPBA is perceived by dental field postgraduate trainees in Pakistan. OBJECTIVE: The study explored and ascertained trainees' perceptions, attitudes, and preferences considering their experiences with the systematic organization and execution of WPBA in dental educational settings. METHODS: This cross-sectional study design involved the clinical trainees of various cadres in a tertiary care hospital in Multan. A structured and validated questionnaire previously used for another analysis was administered among 90 trainees at the institute. The results were analyzed and tabulated using SPSS-21. Influential statistics (Pearson's Chi-Square Test) was performed and the confidence interval was set at 95% (P≤0.05). RESULTS: The response rate was 88%. Opinions were more positive compared to the former surveys. The majority of the respondents (65.8%) have shown a positive attitude towards WPBA and preferred it to be a valuable assessment system as it fosters reflective practices in educational settings. In addition, it was shown that WPBA has the potential to improve clinical training (72.2%) and aid in the effective implementation of clinical practice (68.4%). As the system of digital education has been introduced ever since the pandemic, the highest percentage of participants (56%) preferred a combination of on-paper and online assessment systems. CONCLUSION: The study reported that WPBA proposes the opportunity to associate teaching, learning, and assessment. The faculty training program is a significant input to upholding the quality of WPBA. Empirical research on WPBA is essential to be carried out to overcome the inadequacies thus endorsing its application universally.

The intracellular uptake of CD95 modified paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles.

The CD95/CD95L receptor-ligand system is mainly recognised in the induction of apoptosis. However, it has also been shown that CD95L is over-expressed in many cancer types where it modulates immune-evasion and together with its receptor CD95 promotes tumour growth. Here, we show that CD95 surface modification of relatively large microparticles >0.5 µm in diameter, including those made from biodegradable polylactic-co-glycolic acid (PLGA), enhances intracellular uptake by a range of CD95L expressing cells in a process akin to phagocytosis. Using this approach we describe the intracellular uptake of microparticles and agent delivery in neurons, medulloblastoma, breast and ovarian cancer cells in vitro. CD95 modified paclitaxel-loaded PLGA microparticles are shown to be significantly more effective compared to conventional paclitaxel therapy (Taxol) at the same dose in subcutaneous medulloblastoma (∗∗∗P < 0.0001) and orthotopic ovarian cancer xenograft models where a >65-fold reduction in tumour bioluminescence was measured after treatment (∗P = 0.012). This drug delivery platform represents a new way of manipulating the normally advantageous tumour CD95L over-expression towards a therapeutic strategy. CD95 functionalised drug carriers could contribute to the improved function of cytotoxics in cancer, potentially increasing drug targeting and efficacy whilst reducing toxicity.