Infant Sitting and Multi-Directional Reaching Skill.

We tested twenty-one 6- to 10-month-old infants with a wide range of sitting experience in forward and rightward reaching during unsupported sitting on the floor. Sessions were video-recorded for further behavioral and machine learning-based kinematic analyses. All infants, including novice sitters, successfully touched and grasped toys in both directions. Infant falls, hand support, and base of support changes were rare. Infants with more sitting experience showed better upright posture than novice sitters. However, we found no differences in trunk displacement or reaching kinematics between directions or across sitting experience. Thus, multi-directional reaching is functional in both novice and experienced infant sitters. We suggest that trunk and arm stability in sagittal and frontal planes is integral to learning to sit.

Cost-effectiveness of an urinary biomarker panel in combination with MRI for prostate cancer diagnosis.

PURPOSE: The health impact and cost-effectiveness of the biomarker test SelectMDx were evaluated when used in combination with MRI, in two US populations: biopsy naïve men and men with a previous negative biopsy. METHODS: Using a decision model, the current MRI strategy was compared with two SelectMDx strategies: SelectMDx used before MRI to select men for MRI and SelectMDx used after a negative MRI to select men for biopsy. Parameters were informed by the literature most relevant for both populations. Differences in quality-adjusted life years (QALYs) and costs between the current strategy and the SelectMDx strategies were calculated using two different assumptions regarding PCa-specific mortality (SPCG-4 and PIVOT). RESULTS: In biopsy naïve men, the use of SelectMDx before MRI results in a gain of 0.004 QALY per patient under the SPCG-4 scenario, and a gain of 0.030 QALY under the PIVOT scenario. The cost savings are $1650 per patient. When used after MRI, SelectMDx results in a QALY gain per patient of 0.004 (SPCG-4), and 0.006 (PIVOT) with $262 in cost savings. In the previous negative population, SelectMDx before MRI results in a QALY gain of 0.006 (SPCG-4) and 0.022 (PIVOT), with $1281 in cost savings per patient. SelectMDx after MRI results in a QALY gain of 0.003 (SPCG-4) and 0.004 (PIVOT) with $193 in cost savings. CONCLUSION: Application of SelectMDx results in better health outcomes and cost savings. The value of SelectMDx was highest when used before MRI to select patients for MRI and subsequent biopsy.

Promoting Nurse-Led Mobility Protocols for Hospitalized Older Adults: A Systematic Review.

Hospitalized older adults (aged ≥65 years) are at risk for functional decline and negative outcomes associated with immobility, such as pressure injuries and falls. There is a paucity of research that examines impacts of mobility interventions in older adults in medical surgical units. The current systematic review examines the impact of mobility-related interventions in this population. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided this review. Eligibility determination and data extraction, synthesis, and evaluation were independently performed by the authors. Findings revealed that older adult patients who participated in mobility protocols or early mobility programs were mobilized significantly more and were more mobile after discharge. Several studies also showed reduced hospital length of stay (LOS). The literature supports mobility programs as interventions that can have significant impacts on mobilization for medical surgical patients and reduce hospital LOS. [Journal of Gerontological Nursing, 48(7), 24-30.].

Initial Findings from a High Genetic Risk Prostate Cancer Clinic.

OBJECTIVE: To improve prostate cancer screening for high-risk men, we developed an early detection clinic for patients at high genetic risk of developing prostate cancer. Despite the rapidly growing understanding of germline variants in driving aggressive prostate cancer and the increased availability of genetic testing, there is little evidence surrounding how best to screen these men. METHODS: We are reporting on the first 45 patients enrolled, men between the ages of 35-75, primarily with known pathogenic germline variants in prostate cancer susceptibility genes. Screening consists of an intake lifestyle survey, PSA, DRE, and SelectMDx urine assay. A biopsy was recommended for any of the following indications: 1) abnormal DRE, 2) PSA above threshold, or 3) SelectMDx above threshold. The primary outcomes were number needed to screen, and number needed to biopsy to diagnose a patient with prostate cancer. RESULTS: Patients enrolled in the clinic included those with BRCA1 (n=7), BRCA2 (n=16), Lynch Syndrome (n=6), and CHEK2 (n = 4) known pathogenic germline variants. The median age and PSA were 58 (range 35-71) and 1.4 ng/ml (range 0.1-11.4 ng/ml), respectively. 12 patients underwent a prostate needle biopsy and there were 4positive biopsies for prostate cancer. CONCLUSION: These early data support the feasibility of opening a dedicated clinic for men at high genetic risk of prostate cancer. This early report on the initial enrollment of our long-term study will help optimize early detection protocols and provide evidence for personalized prostate cancer screening in men with key pathogenic germline variants.

Design of Polymeric and Biocompatible Delivery Systems by Dissolving Mesoporous Silica Templates.

There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.

Titanate Nanowires as One-Dimensional Hot Spot Generators for Broadband Au-TiO2 Photocatalysis.

Metal-semiconductor nanocomposites have become interesting materials for the development of new photocatalytic hybrids. Along these lines, plasmonic nanoparticles have proven to be particularly efficient photosensitizers due to their ability to transfer plasmonic hot electrons onto large bandgap semiconductors such as TiO2, thus extending the activity of the latter into a broader range of the electromagnetic spectrum. The extent of this photosensitization process can be substantially enhanced in those geometries in which high electromagnetic fields are created at the metal-semiconductor interface. In this manner, the formation of plasmonic hot spots can be used as a versatile tool to engineer the photosensitization process in this family of hybrid materials. Herein, we introduce the use of titanate nanowires as ideal substrates for the assembly of Au nanorods and TiO2 nanoparticles, leading to the formation of robust hybrids with improved photocatalytic properties. Our approach shows that the correct choice of the individual units together with their rational assembly are of paramount importance in the development of complex nanostructures with advanced functionalities.

Tobacco Mosaic Virus-Functionalized Mesoporous Silica Nanoparticles, a Wool-Ball-like Nanostructure for Drug Delivery.

The design of versatile tools to improve cell targeting and drug delivery in medicine has become increasingly pertinent to nanobiotechnology. Biological and inorganic nanocarrier drug delivery systems are being explored, showing advantages and disadvantages in terms of cell targeting and specificity, cell internalization, efficient payload delivery, and safety profiles. Combining the properties of a biological coating on top of an inorganic nanocarrier, we hypothesize that this hybrid system would improve nanoparticle-cell interactions, resulting in enhanced cell targeting and uptake properties compared to the bare inorganic nanocarrier. Toward this goal, we engineered a hierarchical assembly featuring the functionalization of cargo-loaded mesoporous silica nanoparticles (MSNPs) with tobacco mosaic virus (TMV) as a biological coating. The MSNP functions as a delivery system because the porous structure enables high therapeutic payload capacity, and TMV serves as a biocompatible coating to enhance cell interactions. The resulting MSNP@TMV nanohybrids have a wool-ball-like appearance and demonstrate enhanced cell uptake, hence cargo delivery properties. The MSNP@TMV have potential for medical applications such as drug delivery, contrast agent imaging, and immunotherapy.

Cost-Effectiveness of Urinary Biomarker Panel in Prostate Cancer Risk Assessment.

PURPOSE: SelectMDx (MDxHealth®) is a panel of urinary biomarkers used in conjunction with traditional risk factors to individualize risk prediction for clinically significant prostate cancer. In this study we sought to characterize the effectiveness of SelectMDx in a population of American men with elevated prostate specific antigen. MATERIALS AND METHODS: We developed a Markov decision analytical model to simulate the chain of events and downstream outcomes associated with ultrasound guided prostate biopsy and a strategy in which the biomarker panel is implemented prior to biopsy. The primary outcome was health outcomes, measured in QALYs (quality-adjusted life years). The secondary outcome was health care costs from the Medicare payer perspective. Multiple 1-way sensitivity analyses were performed to characterize model robustness. RESULTS: The expected mean QALYs per patient under the current standard was 10.796 at a cost of $11,060 during an 18-year horizon. Incorporating the urinary biomarker panel resulted in an expected mean of 10.841 QALYs per patient and a mean cost of $9,366, representing an average of 0.045 QALYs gained at a cost savings of $1,694 per patient. When extrapolating these data to a conservative estimate of 311,879 men per year undergoing biopsy, one would expect that the biomarker panel would result in an incremental 14,035 QALYs gained at a cost savings of $528,323,026 in each yearly cohort. The biomarker panel strategy dominated the current standard across a wide range of sensitivity analyses. CONCLUSIONS: Routine use of the SelectMDx urinary biomarker panel to guide biopsy decision making improved health outcomes and lowered costs in American men at risk for prostate cancer. This strategy may optimize the value of prostate cancer risk assessment in an era of increasing financial accountability.

Optimal Trial Design for Studying Urinary Markers in Bladder Cancer: A Collaborative Review.

CONTEXT: Urine-based tumor markers are not routinely used in the diagnosis and surveillance of bladder cancer. The main limitation of urinary markers has been a lack of clarity regarding clinical benefit. OBJECTIVE: To review the indications for urinary marker use, barriers to marker utilization, and clinical trial designs for markers available for detection (hematuria populations) and surveillance (bladder cancer populations). The study aim was to facilitate an optimal trial design that could change clinical practice. EVIDENCE ACQUISITION: A PubMed search was conducted on February 17, 2018, using the MeSH search terms "Urinary Bladder Neoplasms" [Mesh] AND "Biomarkers" [Mesh] AND "Urine" [Mesh] yielded 127 articles, of which only two also fulfilled the search term "Randomized Controlled Trial" [Publication Type]. Neither of these two articles examined clinical outcomes for patients but rather focused on the performance characteristics of the urinary marker. For the search terms "Hematuria" [Mesh] AND "Randomized Controlled Trial" [Publication Type] AND "Urinary Bladder Neoplasms" [Mesh] yielded 12 articles, none of which used randomization with the outcome of interest being a clinical endpoint. EVIDENCE SYNTHESIS: Several potential designs for urinary marker trials were developed for detection and surveillance of bladder cancer. A marker-based approach compared to usual care for evaluation of hematuria in a primary care setting could reduce unnecessary cystoscopy in patients with low risk and expedite care in patients with higher risk. For bladder cancer surveillance, marker-based approaches could reduce cystoscopy for patients with low-grade disease and potentially improve detection for patients with high risk. CONCLUSIONS: Urinary markers are not currently routinely used owing to the absence of level 1 evidence supporting incorporation of urinary markers into protocols for detection or surveillance of bladder cancer. This review provides practical designs for studies that could demonstrate superiority of marker-based approaches over current clinical care. The sample sizes required for these studies are no greater than many of those accrued for previous urinary marker studies, but the proposed trial concepts require planning and a willingness to risk failure of the marker to demonstrate the desired benefits. PATIENT SUMMARY: In this review we discuss current limitations in the use of urinary markers for detection and surveillance of bladder cancer. We identify potential studies that could demonstrate a clinical benefit of the use of markers in improving detection of bladder cancer by reducing evaluation of patients unlikely to have cancer or expediting identification of cancer. For surveillance, a marker trial could improve identification of bladder cancer or reduce cystoscopy in patients with low risk.

A Biomimetic Escape Strategy for Cytoplasm Invasion by Synthetic Particles.

The translocation of nanomaterials or complex delivery systems into the cytosol is a major challenge in nanobiotechnology. After receptor-mediated endocytosis, most nanomaterials are sequestered and undergo degradation, therapy inactivation, or exocytosis. Herein we explore a novel surface particle coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell-invasive mechanisms, namely, receptor-mediated endocytosis, endolysosomal escape, and cytosolic particle release preserving cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical, or catalytic functionalities, thus opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting new developments in the biotechnological, pharmaceutical, and biomedical industries.