3D culture boosting fullerenol nanoparticles to induce calreticulin exposure on MCF-7 cells for enhanced macrophage-mediated cell removal.

Calreticulin (CRT) on the cell surface that acts as an "eat me" signal is vital for macrophage-mediated programmed cell removal. The polyhydroxylated fullerenol nanoparticle (FNP) has appeared as an effective inducer to cause CRT exposure on cancer cell surface, but it failed in treating some cancer cells such as MCF-7 cells based on previous findings. Here, we carried out the 3D culture of MCF-7 cells, and interestingly found that the FNP induced CRT exposure on cells in 3D spheres via re-distributing CRT from endoplasmic reticulum (ER) to cell surface. Phagocytosis experiments in vitro and in vivo illustrated the combination of FNP and anti-CD47 monoclonal antibody (mAb) further enhanced macrophage-mediated phagocytosis to cancer cells. The maximal phagocytic index in vivo was about three times higher than that of the control group. Moreover, in vivo tumorigenesis experiments in mice proved that FNP could regulate the progress of MCF-7 cancer stem-like cells (CSCs). These findings expand the application of FNP in tumor therapy of anti-CD47 mAb and 3D culture can be used as a screening tool for nanomedicine.

Impacts of lower limb flexibility exercise on aerobic gymnastics performance / Impactos do exercício de flexibilidade para membros inferiores sobre o desempenho da ginástica aeróbica / Impactos del ejercicio de flexibilidad para los miembros inferiores en el rendimiento de la gimnasia aeróbica

ABSTRACT Introduction: Aerobic gymnastics is a sport that involves a sense of beauty, rhythm and dance, with high artistic expressiveness, characteristics that have favored a strong population adherence. It is believed that the specific flexibility exercise can add a greater visual impact to their artistic movements, raising their competitive performance. Objective: Verify the impacts of lower limb flexibility exercise on the performance of aerobics athletes. Methods: Six aerobics athletes were selected to perform an 8-week experiment, adopting the PNF methodology for training. The impacts on lower limb flexibility were measured before and after the experiment, these data were analyzed and studied statistically. Results: The results of the long jump in the physical quality index of the athletes increased by 0.1209 m; the added value in the two-minute, 10-m backstroke test was 1.46. The movement performance indexes showed expressive increases: flexion increased by 2.62; right angle support increased by 0.78; split leg jump increased by 1.95; standing jump with eyes closed and the foot balance quality index was 4.63. Conclusion: Lower limb flexibility exercise can positively impact the performance of aerobic gymnastics athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A ginástica aeróbica é um esporte que envolve senso de beleza, ritmo e dança, com alta expressividade artística, características que favoreceram uma forte adesão populacional. Acredita-se que o exercício específico de flexibilidade possa adicionar um maior impacto visual aos seus movimentos artísticos, elevando o desempenho competitivo. Objetivo: Verificar os impactos do exercício de flexibilidade dos membros inferiores sobre o desempenho dos atletas de aeróbica. Métodos: Seis atletas de aeróbica foram selecionados para realizar uma experiência de 8 semanas, adotando a metodologia PNF para o treinamento. Os impactos sobre a flexibilidade dos membros inferiores foram aferidos antes e depois do experimento, esses dados foram analisados e estudados estatisticamente. Resultados: Os resultados do salto em distância no índice de qualidade física dos atletas aumentaram em 0,1209 m; o valor agregado no teste de dois minutos e 10 m de recuo foi de 1,46. Os índices de desempenho do movimento apresentaram aumentos expressivos: de flexão teve um aumento de 2,62; apoio em ângulo reto aumentou 0,78; salto de pernas divididas aumentou 1,95; salto de pé com os olhos fechados e o índice de qualidade de equilíbrio dos pés foi de 4,63. Conclusão: O exercício de flexibilidade para membros inferiores pode impactar positivamente o desempenho dos atletas de ginástica aeróbica. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La gimnasia aeróbica es un deporte que envuelve un sentido de belleza, ritmo y danza, con alta expresividad artística, características que favorecieron una fuerte adhesión de la población. Se cree que el ejercicio específico de la flexibilidad puede agregar un mayor impacto visual a sus movimientos artísticos, elevando el desempeño competitivo. Objetivo: Verificar los impactos del ejercicio de flexibilidad de los miembros inferiores en el desempeño de atletas de aeróbica. Métodos: Seis atletas de aeróbic fueron seleccionados para realizar un experimento de 8 semanas, adoptando la metodología PNF para el entrenamiento. Los impactos en la flexibilidad de los miembros inferiores fueron medidos antes y después del experimento, estos datos fueron analizados y estudiados estadísticamente. Resultados: Los resultados del salto de longitud en el índice de la calidad física de los atletas aumentaron en 0,1209 m; el valor añadido en la prueba de dos minutos y 10 m de espalda fue de 1,46. Los índices de rendimiento de movimiento mostraron aumentos expresivos: de flexión tuvo un aumento de 2,62; apoyo en ángulo recto aumentó 0,78; salto de pierna dividida aumentó 1,95; salto de pie con los ojos cerrados y el índice de calidad de equilibrio de los pies fue de 4,63. Conclusión: El ejercicio de flexibilidad de los miembros inferiores puede influir positivamente en el rendimiento de los atletas de gimnasia aeróbica. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Impacts of the pnf technique on flexibility and strength in martial arts athletes / Impactos da técnica pnf sobre flexibilidade e força em atletas de artes marciais / Impacto de la técnica pnf sobre la flexibilidad y la fuerza en atletas de artes marciales

ABSTRACT Introduction: Joint flexibility and muscle strength play a vital role in the training process of martial arts athletes. The proprioceptive neuromuscular facilitation (PNF) technique encourages the neural receptors, through the application of manual resistances, in the gain of functional range of motion and stability to its patients. It is believed that this technique can be adapted to the sports environment. Objective: Evaluate the impact of stretching using the PNF technique on martial arts athletes' flexibility and muscle strength. Methods: Through a controlled experiment, 100 martial arts athletes, without significant differences, were selected as experimental subjects, and randomly divided into two groups for a 4-week experiment. The experimental group added a protocol with PNF stretching exercises in the training, while the control group performed the usual training without interventions. Indicators of flexibility, functional activities, and strength were measured before and after the intervention, compared, and statistically analyzed. Results: Joint flexibility with the shoulder rotation test evolved from 21.88±5.71 to 19.22±5.94, and the left and right division was from 16.90±5.36 to 10.57±3.75; as for muscle strength, the flexor peak moment elevated from 210.36±51.18 to 251.37± 45.72, and flexor power had a gain from 111.76±30.63 to 135.20±2,.42. The extensor peak moment also showed expressive evolutions from 179.47±43.96 to 221.52±33.60. Conclusion: The PNF stretching exercise technique effectively optimizes martial arts athletes' joint flexibility and muscle strength. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A flexibilidade articular e a força muscular desempenham um papel vital no processo de treinamento dos atletas de artes marciais. A técnica de facilitação neuromuscular proprioceptiva (PNF) incentiva os receptores neurais, através da aplicação de resistências manuais, no ganho da amplitude de movimento funcional e da estabilidade aos seus pacientes. Acredita-se que essa técnica possa ser adaptada ao meio esportivo. Objetivo: Avaliar os impactos do alongamento utilizando a técnica de PNF sobre a flexibilidade e a força muscular dos atletas de artes marciais. Métodos: Através de um experimento controlado, 100 atletas de artes marciais, sem diferenças significativas, foram selecionados como objetos experimentais, divididos aleatoriamente em dois grupos para um experimento de 4 semanas. Ao grupo experimental foi adicionado um protocolo com exercícios de alongamento PNF no treinamento, enquanto o grupo de controle efetuou o treinamento habitual sem intervenções. Indicadores de flexibilidade, atividades funcionais e força foram aferidos antes e depois da intervenção, comparados e analisados estatisticamente. Resultados: A flexibilidade articular com o teste de giro do ombro evoluiu de 21,88±5,71 para 19,22±5,94, sendo a divisão esquerda e direita de 16,90±5,36 para 10,57±3,75; quanto a força muscular, o momento de pico do flexor elevou-se de 210,36±51,18 para 251,37± 45,72, e a potência do flexor teve um ganho de 111,76±30.63 para 135,20±2,.42. O momento de pico do extensor também demonstrou evoluções expressivas de 179,47±43,96 para 221,52±33,60. Conclusão: O exercício de alongamento com a técnica PNF demonstrou ser efetivo em otimizar a flexibilidade articular e a força muscular dos atletas de artes marciais. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La flexibilidad articular y la fuerza muscular desempeñan un papel vital en el proceso de entrenamiento de los atletas de artes marciales. La técnica de facilitación neuromuscular propioceptiva (FNP) estimula los receptores neurales, a través de la aplicación de resistencias manuales, en la ganancia de rango funcional de movimiento y estabilidad a sus pacientes. Se cree que esta técnica puede adaptarse al ámbito deportivo. Objetivo: Evaluar el impacto de los estiramientos con la técnica PNF en la flexibilidad y fuerza muscular de atletas de artes marciales. Métodos: A través de un experimento controlado, 100 atletas de artes marciales, sin diferencias significativas, fueron seleccionados como sujetos experimentales, divididos aleatoriamente en dos grupos para un experimento de 4 semanas. Al grupo experimental se le añadió un protocolo con ejercicios de estiramiento PNF en el entrenamiento, mientras que el grupo de control realizó el entrenamiento habitual sin intervenciones. Se midieron indicadores de flexibilidad, actividades funcionales y fuerza antes y después de la intervención, se compararon y se analizaron estadísticamente. Resultados: La flexibilidad articular con la prueba de rotación del hombro evolucionó de 21,88±5,71 a 19,22±5,94, siendo la división izquierda y derecha de 16,90±5,36 a 10,57±3,75; en cuanto a la fuerza muscular, el momento pico flexor se elevó de 210,36±51,18 a 251,37± 45,72, y la potencia flexora tuvo una ganancia de 111,76±30,63 a 135,20±2,, 42. El momento máximo del extensor también mostró evoluciones expresivas de 179,47±43,96 a 221,52±33,60. Conclusión: El ejercicio de estiramiento con técnica PNF demostró ser eficaz para optimizar la flexibilidad articular y la fuerza muscular de los atletas de artes marciales. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Sensors in a Flash! Oxygen Nanosensors for Microbial Metabolic Monitoring Synthesized by Flash Nanoprecipitation.

Flash nanoprecipitation (FNP) is an efficient and scalable nanoparticle synthesis method that has not previously been applied to nanosensor fabrication. Current nanosensor fabrication methods have traditionally exhibited poor replicability and consistency resulting in high batch-to-batch variability, highlighting the need for a more tunable and efficient method such as FNP. We used FNP to fabricate nanosensors to sense oxygen based on an oxygen-sensitive dye and a reference dye, as a tool for measuring microbial metabolism. We used fluorescence spectroscopy to optimize nanosensor formulations, calibrate the nanosensors for oxygen concentration determination, and measure oxygen concentrations through oxygen-sensitive dye luminescence. FNP provides an effective platform for making sensors capable of responding to oxygen concentration in gas-bubbled solutions as well as in microbial environments. The environments we tested the sensors in arePseudomonas aeruginosa biofilms andSaccharomyces cerevisiae liquid cultures─both settings where oxygen concentration is highly dependent on microbial activity. With FNP now applied to nanosensor fabrication, future nanosensor applications can take advantage of improved product quality through better replicability and consistency while maintaining the original function of the nanosensor.

Improved paclitaxel delivery with PEG-b-PLA/zein nanoparticles prepared via flash nanoprecipitation.

Polymeric micelle is a promising vehicle to improve the bioavailability and clinical outcomes of paclitaxel (PTX) which has been proven effective in the treatment of a wide range of cancers. However, conventional PTX formulation with the amphiphilic PEG-b-PLA usually suffers from insufficient PTX loading, low stability of PTX-micelles, and rapid PTX release due to low compatibility between PTX and PLA, limiting its clinical application. In this study, a novel nanoparticle platform was developed to improve the stability of PTX-loaded nanoparticles (NPs) and the delivery efficacy of PTX by integrating the flash nanoprecipitation (FNP) technique and a combination of amphiphilic PEG-PLA and super hydrophobic zein. The incorporation of zein led to the formation of distinct hydrophobic interiors of NPs which enhanced the interaction between PTX and NPs, therefore improving the encapsulation efficiency of PTX and sustained drug release compared with PEG-PLA micelles without zein. In addition, FNP allowed facile fabrication of PTX-NPs with smaller sizes and higher stability. These PTX-NPs showed superior sustained release of PTX and good cancer cell-killing in vitro. Among them, PTX-5k-16k-1Z NPs exhibited excellent biosafety and anti-tumor efficacy in a xenograft tumor model in mice, suggesting great potential in the delivery of hydrophobic drugs for cancer therapy.

Development of an In Vitro Release Assay for Low-Density Cannabidiol Nanoparticles Prepared by Flash NanoPrecipitation.

Nanoparticle encapsulation is an attractive approach to improve the oral bioavailability of hydrophobic therapeutics. The high specific surface area of nanoparticle formulations, combined with the thermodynamically driven increased solubility of an amorphous drug core, promotes rapid drug dissolution. However, the physicochemical properties of the hydrophobic therapeutic can present obstacles to in vitro characterization of nanoparticle formulations. Namely, drugs with low density and high membrane binding affinity frustrate traditional analytical methods to monitor release kinetics from nanoparticles. In this work, cannabidiol (CBD) was encapsulated into nanoparticles with low polydispersity and high drug loading via Flash NanoPrecipitation (FNP), a scalable self-assembly process. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) and lecithin were employed as amphiphilic particle stabilizers during the FNP process. However, the low density and high membrane binding affinity of the amorphous CBD nanoparticle core prevented the characterization of in vitro release kinetics by conventional methods. Released CBD could not be separated from intact nanoparticles by filtration or centrifugation. To address this challenge, an alternative approach is described to coencapsulate 6 nm hydrophobic Fe3O4 colloids with CBD during FNP. The Fe3O4 colloids were added at 33% by mass (approximately 20% by volume) to increase the density of the nanoparticles, resulting in particles with an average diameter of 160 nm (CBD-lecithin-Fe3O4) or 280 nm (CBD-HPMCAS-Fe3O4). This densification enabled the centrifugal separation of dissolved (released) CBD from unreleased CBD during the in vitro assay while avoiding the losses associated with a filtration step. The resulting nanoparticle formulations provided more rapid and complete in vitro dissolution kinetics than bulk CBD, representing a 6-fold improvement in dissolution compared to crystalline CBD. The coencapsulation of high-density Fe3O4 colloids to enable the separation of nanoparticles from release media is a novel approach to measuring in vitro release kinetics of nanoencapsulated low-density, hydrophobic drug molecules.

Small-volume in vitro lipid digestion measurements for assessing drug dissolution in lipid-based formulations using SAXS.

Lipid-based formulations improve the absorption capacity of poorly-water-soluble drugs and digestion of the formulation is a critical step in that absorption process. A recent approach to understanding the propensity for drug to dissolve in digesting lipid-based formulations couples an in vitro pH-stat lipolysis model to small-angle X-ray scattering (SAXS) by means of a flow-through capillary. However, the conventional pH-stat apparatus used to measure the extent of lipid digestion during such experiments requires digest volumes of 15-30 mL and drug doses of 50-200 mg, which is problematic for scarce compounds and can require excessive amounts of formulation reagents. This manuscript describes an approach to reduce the amount of material required for in vitro lipolysis experiments coupled to SAXS, for use in instances where the amount of drug or formulation medium is limited. Importantly, this was achieved while maintaining the pH stat conditions, which is critical for maintaining biorelevance and driving digestion to completion. The digestibility of infant formula with the poorly-water-soluble drugs halofantrine and clofazimine dispersed into it was measured as an exemplar paediatric-friendly lipid formulation. Halofantrine was incorporated in its powdered free base form and clofazimine was incorporated both as unformulated drug powder and as drug in nanoparticulate form prepared using Flash NanoPrecipitation. The fraction of triglyceride digested was found to be independent of vessel size and the incorporation of drug. The dissolution of the two forms of clofazimine during the digestion of infant formula were then measured using synchrotron SAXS, which revealed complete and partial solubilisation over 30 min of digestion for the powdered drug and nanoparticle formulations, respectively. The main challenge in reducing the volume of the measurements was in ensuring that thorough mixing was occurring in the smaller digestion vessel to provide uniform sampling of the dispersion medium.

Kabat Rehabilitation in Facial Nerve Palsy after Parotid Gland Tumor Surgery: A Case-Control Study.

Temporary facial nerve palsy after parotid tumor surgery ranges from 14 to 65%, depending on surgery, tumor type, and subsite. The study aimed to evaluate the role of Kabat physical rehabilitation in the outcomes of patients affected by severe facial nerve palsy following parotid gland surgery. The results and clinical data of two groups, Kabat and non-Kabat (control), were statistically compared. Descriptive statistics, the multiple linear regression model, difference in difference approach, and the generalized linear model were used. F-Test, Chi-square test, McFadden R-squared, and adjusted R-squared were used to assess the significance. The results showed that the House-Brackmann (HB) stage of patients who had physiotherapy performed were lower than the control group. The decrease of HB staging in the Kabat group at 3 months was -0.71 on average, thus the probability of having a high HB stage decreased by about 13% using Kabat therapy. The results are statistically significant, and indicated that when the Kabat rehabilitation protocol is performed, mainly in the cases of a high-grade HB score, the patients showed a better and faster improvement in postoperative facial nerve palsy.

Validity of Methods to Identify Individuals With Lower Extremity Amputation Using Department of Veterans Affairs Electronic Medical Records.

Objectives: To determine the positive predictive value (PPV) of algorithms to identify patients with major (at the ankle or more proximal) lower extremity amputation (LEA) using Department of Veterans Affairs electronic medical records (EMR) and to evaluate whether PPV varies by sex, age, and race. Design: We conducted a validation study comparing EMR determined LEA status to self-reported LEA (criterion standard). Setting: Veterans who receive care at the Department of Veterans Affairs. Participants: We invited a national sample of patients (N=699) with at least 1 procedure or diagnosis code for major LEA to participate. We oversampled women, Black men, and men ≤40 years of age. Interventions: Not applicable. Main Outcome Measure: We calculated PPV estimates and false negative percentages for 7 algorithms using EMR LEA procedure and diagnosis codes relative to self-reported major LEA. Results: A total of 466 veterans self-reported their LEA status (68%). PPVs for the 7 algorithms ranged from 89% to 100%. The algorithm that required a single diagnosis or procedure code had the lowest PPV (89%). The algorithm that required at least 1 procedure code had the highest PPV (100%) but also had the highest proportion of false negatives (66%). Algorithms that required at least 1 procedure code or 2 or more diagnosis codes 1 month to 1 year apart had high PPVs (98%-99%) but varied in terms of false negative percentages. PPV estimates were higher among men than women but did not differ meaningfully by age or race, after accounting for sex. Conclusion: PPVs were higher if 1 procedure or at least 2 diagnosis codes were required; the difference between algorithms was marked by sex. Investigators should consider trade-offs between PPV and false negatives to identify patients with LEA using EMRs.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration.

Tissue specificity, a key factor in the decellularized tissue matrix (DTM), has shown bioactive functionalities in tuning cell fate-e.g., the differentiation of mesenchymal stem cells. Notably, cell fate is also determined by the living microenvironment, including material composition and spatial characteristics. Herein, two neighboring tissues within intervertebral discs, the nucleus pulposus (NP) and annulus fibrosus (AF), were carefully processed into DTM hydrogels (abbreviated DNP-G and DAF-G, respectively) to determine the tissue-specific effects on stem cell fate, such as specific components and different culturing methods, as well as in vivo regeneration. Distinct differences in their protein compositions were identified by proteomic analysis. Interestingly, the fate of human bone marrow mesenchymal stem cells (hBMSCs) also responds to both culturing methods and composition. Generally, hBMSCs cultured with DNP-G (3D) differentiated into NP-like cells, while hBMSCs cultured with DAF-G (2D) underwent AF-like differentiation, indicating a close correlation with the native microenvironments of NP and AF cells, respectively. Furthermore, we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G (2D)-induced AF-specific differentiation. Additionally, the activation of YAP1 determined the tendency of NP- or AF-specific differentiation and played opposite regulatory effects. Finally, DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models, respectively. In conclusion, DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway, and this tissue specificity is both compositional and spatial, supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.

A Cost-Effective Nano-Sized Curcumin Delivery System with High Drug Loading Capacity Prepared via Flash Nanoprecipitation.

Flash nanoprecipitation (FNP) is an efficient technique for encapsulating drugs in particulate carriers assembled by amphiphilic polymers. In this study, a novel nanoparticular system of a model drug curcumin (CUR) based on FNP technique was developed by using cheap and commercially available amphiphilic poly(vinyl pyrrolidone) (PVP) as stabilizer and natural polymer chitosan (CS) as trapping agent. Using this strategy, high encapsulation efficiency (EE > 95%) and drug loading capacity (DLC > 40%) of CUR were achieved. The resulting CUR-loaded nanoparticles (NPs) showed a long-term stability (at least 2 months) and pH-responsive release behavior. This work offers a new strategy to prepare cost-effective drug-loaded NPs with high drug loading capacity and opens a unique opportunity for industrial scale-up.

Correlative Light and Electron Microscopy for Nanoparticle-Cell Interaction and Protein Localization.

Various silica-based fluorescent nanoparticles ((Si-FNP)) with magnetic or metal cores represent a standard class of nanoparticles offering new opportunities for high-resolution cellular imaging and biomedicine applications, such as drug delivery. Their high solubility, homogeneity, biocompatibility, and chemical inertness Si-FNPs make them attractive probes for correlative light and electron microscopy (CLEM) studies, offering novel insights into nanoparticle-cell interactions in detail. In the present chapter, we present a procedure for imaging silica-based fluorescent magnetic core-shell nanoparticles (Si-FMNP) at the single-particle scale in cells. Our method facilitates the acquisition of information on the extracellular and intercellular distribution of nanoparticles and their various interactions with various cellular organelles when cells are cultured and electroporated by NPs. In addition, such information could facilitate the evaluation of the efficacy of nanocarriers designed for drug delivery.

Association between Fur Animal Necrotizing Pyoderma in breeding farm mink (Neovison vison) and reduced fertility.

BACKGROUND: The disease Fur Animal Necrotizing Pyoderma (FNP) has since 2000 been reported in many fur producing countries including Canada, Finland and Denmark. Development of FNP is characterised by rapidly forming treatment-resistant wounds on paws and in the head region. Economic losses related to FNP have been associated with mortality and decreased fur quality as well as increased veterinary costs. Also it has been suggested that FNP may be associated with reduced production results for breeding mink. The aim of this study was to evaluate if there is an association between FNP lesions in breeding animals and reduced production results based on a retrospective cohort study. RESULTS: 1465 breeding animals (244 males and 1221 females) were followed during the breeding season 2019 on five Danish mink farms. Two farms were removed from the analysis since no occurrence of FNP appeared in the observation group. After exclusion, 846 breeding animals (148 males and 698 females) remained in the analysis and were divided into two groups: exposed (EXP) or non-exposed (N-EXP) depending on the disease history of the males during mating. Females exposed to FNP positive males during breeding in average produce 14% fewer kits (P = 0.032) and these females were also more than double as likely to produce small litters (N ≥ 3) than N-EXP females. Female's from the EXP group were introduced more times to males than females in the N-EXP group (P = 0.0001, 2.5 more times in average). Females in the EXP group did not have a statistically higher risk of becoming barren (P = 0.138) though the relative risk of becoming barren was 77% higher after encountering a FNP male. CONCLUSIONS: This study shows that FNP has more economic losses for the farms than direct loss of animals. Females in contact with males with FNP lesion during breeding have a higher risk of becoming barren, and produce significantly fewer kits compared to females whom haven't been in contact with a FNP positive male.

Polymeric Nanocarrier Formulations of Biologics Using Inverse Flash NanoPrecipitation.

The encapsulation of water-soluble therapeutics and biologics into nanocarriers to produce novel therapeutics has been envisioned for decades, but clinical translation has been hampered by complex synthesis strategies. The methods that have been developed are often limited by poor encapsulation efficiency/loading or complex processing to achieve therapeutic loadings high enough to be medically relevant. To address this unmet need, we introduce a solubility-driven self-assembly process to form polymeric nanocarriers comprising a biologic in a hydrophilic core, encapsulated by a poly(lactic acid) shell, and stabilized by a poly(ethylene glycol) brush. Called "inverse Flash NanoPrecipitation (iFNP)," the technique achieves biologic loadings (wt% of total formulation) that are 5-15× higher than typical values (9-27% versus < 2%). In contrast to liposomes and polymersomes, we sequentially assemble the polymer layers to form the final nanocarrier. Installation of the poly(lactic acid) shell before water exposure sequesters the biologic in the core and results in the improved loadings that are achieved. We demonstrate the broad applicability of the process and illustrate its implementation by formulating over a dozen different oligosaccharides, antibiotics, peptides, proteins, and RNA into nanocarriers with narrow size distributions, at high loadings, and with high reproducibility. Lysozyme and horseradish peroxidase are shown to retain 99% activity after processing. These results demonstrate the potential for commercial implementation of this technology, enabling the translation of novel treatments in immunology, oncology, or enzyme therapies.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles.

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer (CIJM), multi-inlet vortex mixer (MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly water-soluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

Addressing a Gap in Healthcare Access for Transition-Age Youth with Autism: A Pilot Educational Intervention for Family Nurse Practitioner Students.

A mixed-methods randomized controlled trial pilot study evaluated an educational curriculum focused on the medical needs of transition-age youth (TAY) with autism (ASD) for family nurse practitioner students. Fourteen out of a cohort of 16 (87.5%) nursing students consented to participate in the study and were randomly assigned to either a waitlist control group (WLC) (n = 8) or an intervention group (INT) (n = 6). Three measures were used to determine pre- and post-intervention levels of self-efficacy, knowledge, and attitudes. Quantitative and qualitative data provide preliminary support that participation in intervention may improve and enhance knowledge and level of self-efficacy in working with TAY with ASD.

Integrating Population Health Content into FNP Program Curriculum.

In the current healthcare environment, the healthcare industry has become increasingly focused on population health concerns. While advanced practice registered nurses (APRNs) are well prepared to contribute to population health by delivering holistic healthcare to individuals, families, groups, communities, and populations, they are not engaged in initiatives to improve population health commensurate with their numbers, education, training, experience, and role as primary care providers and essential healthcare team leaders and members. This article discusses the rationale for integrating population health into APRN curricula, one program's approach to doing so, and preliminary lessons learned from this effort. The three main lessons learned include population health content should be integrated across the curriculum for all APRN cohorts, supplementary population health content should be considered, and opportunities for integrating didactic population health content should be included across the FNP curriculum.

Enhancement of nano titanium dioxide coatings by fullerene and polyhydroxy fullerene in the photocatalytic degradation of the herbicide mesotrione.

The surface modification of commercial TiO2 Hombikat (TiO2) using nanoparticles of fullerene C60 with tetrahydrofuran (THF-nC60), as well as fullerenol C60(OH)24 nanoparticles (FNP) was investigated in this study. Characterization of THF-nC60, FNP, TiO2, TiO2/THF-nC60, and TiO2/FNP was studied by using DES, ELS, TEM, SEM, DRS and BET measurements and their photoactivity has been examined on the mesotrione degradation under simulated sunlight. It was found that FNP in self-assembled nanocomposite TiO2/FNP increased negatively charge, as well as catalytic surface of TiO2. In addition, TiO2/FNP exhibits a shift of band gap energy to lower values compared to TiO2 and TiO2/THF-nC60. BET surface area has not showed significant differences among catalysts. Furthermore, it was found that the highest photoactivity was obtained for TiO2/FNP system. Besides, influence of different concentrations of electron acceptors (H2O2 and KBrO3), as well as scavengers on the kinetics of mesotrione removal in aqueous solution with/without TiO2 and FNP under simulated sunlight was investigated. Namely, addition of mentioned electron acceptors has resulted in higher mesotrione degradation efficiency compared to O2 alone. Besides, in the first period substrate degradation probably takes place via hydroxyl radicals and after 60 min of irradiation the reaction mechanism proceeds mainly via holes. The most efficient system for mesotrione degradation and mineralization were TiO2/7 mM KBrO3 and TiO2/7 mM KBrO3/40 µl FNP, respectively.

Improving Family Nurse Practitioner Students' Confidence for Clinical Decision Making and Presenting Patient Information to the Preceptor.

BACKGROUND: Family nurse practitioner (FNP) students often lack the confidence to develop diagnostic skills and convey patient information to their clinical preceptor. Preparing FNP students for these tasks is essential to their clinical success. OBJECTIVE: To describe the adequacy of interactive case studies to increase confidence in making clinical decisions and presenting patient information to the clinical preceptor. METHODS: The authors developed three interactive case studies for student analysis during an on-campus intensive week prior to the students' first clinical rotation. Student confidence was examined pre and post to determine if the interactive cases had any effects on their diagnostic reasoning and skill in presenting patients to the preceptor. RESULTS: The pretest survey found that students were least confident in presenting a patient to the preceptor (21% not confident). After the three interactive case studies, students demonstrated a significant increase in confidence. CONCLUSION: Interactive case studies and role-playing the patient presentation prior to an initial clinical rotation is a successful educational methodology for improving FNP students' confidence for the clinical environment. IMPLICATIONS FOR NURSING: Faculty can implement interactive case studies in traditional and online courses to foster student confidence.

Survey to child/adolescent psychiatry and developmental/behavioral pediatric training directors to expand psychiatric-mental health training to nurse practitioners.

BACKGROUND: There is an ongoing shortage of child mental health professionals. Nurse practitioners (NPs) who completed behavioral and mental health training have proven that they can diagnose and manage many pediatric problems. PURPOSE: To ask the training directors of both child/adolescent psychiatry (CAP) and developmental/behavioral pediatric (DBP) programs about their receptivity and willingness to give additional training for NPs who provide care to children with behavioral and mental health issues and examine the main obstacles to the development of such programs. METHODS: A survey was sent to 151 CAP and DBP training directors in the United States. RESULTS: The return rate was 67% (N = 101). Only 12% expressed objection to the concept of additional NP training in CAP or DBP, but only 53% of training directors currently reported having sufficient faculty to do so. Some training directors reported already having advanced behavioral and mental health training programs for NPs (31%) and most (82%) would consider expanding, if funded. CONCLUSIONS: There is support for advanced training for NPs, but funding is needed to make this a reality. IMPLICATIONS FOR PRACTICE: Expansion of such programs might rapidly improve accessibility and reduce waiting time of mental health providers for children and adolescents.