Risk factors associated with the development of osteoradionecrosis (ORN) in Head and Neck cancer patients in Ireland: A 10-year retrospective review.

BACKGROUND AND PURPOSES: To assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN development to aid prevention. MATERIALS AND METHODS: Review of 1050 HNC patients attending the Dental Oncology Clinic, CUDSH between 2010 and 2021 identified 47 cases of ORN. Medical, dental and radiotherapy records of these forty-seven patients were retrospectively reviewed. Patient-, tumour-, and treatment-related variables were investigated in association with osteoradionecrosis development. Analysis conducted using SPSS, Pearson's Chi-square test (p < 0.05), and ordinal regression model. RESULTS: ORN incidence was 4.4 %. Median time from radiotherapy (RT) to ORN development was 9.5 months (range 1-98.5 months). ORN development within the mandibular surgical site was significant (p <.001), presenting at a higher Notani grade (p =.002), in mid-mandibular body region (p =.028), at radiation doses ≥ 60 Gy (p =.035), due to induced causes (p =.029), and without resolution (p =.019). CONCLUSION: This is the first retrospective study of ORN in HNC patients in Ireland over 10-year period. ORN incidence was extremely low (4.4%). As patients reported high smoking/alcohol use and poor dental attendance pre-diagnosis, this suggests intensive dental intervention pre/post-diagnosis contributed to low ORN rates. Mandibular surgery pre-RT increased risk of developing ORN at the surgical site. Therefore, we recommend future treatment planning should contour the surgical site, designating it an organ at risk (OAR), assigning a dose constraint, where oncologically possible, with emphasis on reducing the hot-spot to this region; findings reinforce importance of life-long expert dental care to reduce ORN incidence.

Clinical Effectiveness of Cognitively Enhanced Tai Ji Quan Training on Global Cognition and Dual-Task Performance During Walking in Older Adults With Mild Cognitive Impairment or Self-Reported Memory Concerns : A Randomized Controlled Trial.

BACKGROUND: Mild cognitive impairment (MCI) negatively impacts cognition and dual-task abilities. A physical-cognitive integrated treatment approach could mitigate this risk for dementia. OBJECTIVE: To compare the effectiveness of cognitively enhanced tai ji quan versus standard tai ji quan or stretching exercise in improving global cognition and reducing dual-task walking costs in older adults with MCI or self-reported memory concerns. DESIGN: 3-group, randomized (1:1:1), superiority trial. (ClinicalTrials.gov: NCT04070703). SETTING: Community residential homes. PARTICIPANTS: 318 older adults with self-reported memory decline or concern and a Clinical Dementia Rating (CDR) global score of 0.5 or lower at baseline. INTERVENTION: Cognitively enhanced tai ji quan (n = 105), standard tai ji quan (n = 107), or stretching (n = 106). All groups exercised at home via real-time videoconferencing, 1 hour semiweekly for 24 weeks. MEASUREMENTS: The co-primary endpoints were change in Montreal Cognitive Assessment (MoCA; range, 0 to 30) and dual-task walking costs (difference between single- and dual-task gait speed, expressed in percentage) from baseline to 24 weeks. Secondary outcomes included CDR-Sum of Boxes (CDR-SB), Trail Making Test B, Digit Span Backward (DSB), and physical performance tests. Outcomes were assessed at 16, 24 (primary endpoint), and 48 weeks (6 months after intervention). RESULTS: A total of 304 participants (96%) completed the 24-week assessment. Cognitively enhanced tai ji quan outperformed standard tai ji quan and stretching with a greater improvement in MoCA score (mean difference, 1.5 points [98.75% CI, 0.7 to 2.2 points] and 2.8 points [CI, 2.1 to 3.6 points], respectively) and in dual-task walking (mean difference, 9.9% [CI, 2.8% to 16.6%] and 22% [CI, 13% to 31%], respectively). The intervention effects persisted at 48-week follow-up. LIMITATION: There was no nonexercise control group; participants had subjective or mild cognitive impairment. CONCLUSION: Among community-dwelling older adults with MCI, cognitively enriched tai ji quan therapy was superior to standard tai ji quan and stretching exercise in improving global cognition and reducing dual-task gait interference, with outcomes sustained at 48 weeks. PRIMARY FUNDING SOURCE: National Institute on Aging.

Seating and Wheeled Mobility Clinicians Contribute to the Wound Care Team.

Many know that the wound care team consists of physicians and nurses with specialized training. Many may not know of physical therapists (PT) or occupational therapists (OT) with training in seating and wheeled mobility who address skin injuries in people who are full-time wheelchair users. PTs/OTs address the fit and use of their wheelchair to their body and look at their daily function while looking for causes of skin injury otherwise not seen and can help prevent them in the future. Therefore, this makes PTs and OTs with this expertise a valuable part of the wound care team.

A cognitively enhanced online Tai Ji Quan training intervention for community-dwelling older adults with mild cognitive impairment: A feasibility trial.

BACKGROUND: This study examines the feasibility, acceptability, and safety of a newly developed cognitive-enhancing Tai Ji Quan training intervention, delivered via remote videoconferencing, for older adults with mild cognitive impairment (MCI). METHODS: In a three-arm feasibility trial, community-dwelling older adults with MCI (N = 69; mean age = 74.6 years, 57% women) were randomized to a cognitively enhanced Tai Ji Quan (n = 23), standard Tai Ji Quan (n = 22), or stretching group (n = 24) and participated in a 60-minute online exercise session via Zoom, twice weekly for 16 weeks. Participants were recruited primarily in the state of Oregon through mass mailing and word of mouth. The primary outcomes were intervention feasibility (with respect to recruitment, online intervention delivery, fidelity and compliance, and attrition and retention rates), acceptability, and safety. We also assessed feasibility of online data collection and test-retest reliability and explored preliminary trends on secondary outcomes that included global cognitive function, dual-task cost, and domain-specific cognition function. RESULTS: The study had an average recruitment rate of 55%. Feasibility was demonstrated by the overall successful online program implementation, with good fidelity, acceptable compliance (76%), and excellent retention (94%). The cognitively enhanced Tai Ji Quan intervention was shown to be acceptable to participants as well as safe, with no major intervention-related moderate/severe events. At week 16, the group receiving cognitively enhanced Tai Ji Quan training showed a positive trend in the cognitive function and dual-task outcome measures whereas the group receiving standard Tai Ji Quan training exhibited positive trends on global and domain-specific cognitive measures. CONCLUSIONS: Preliminary findings of this pilot study indicate the feasibility, acceptability, and safety of a tailored, cognitively enhanced Tai Ji Quan training intervention delivered remotely to home settings via videoconferencing for community-dwelling older adults with MCI. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04070703.

Efficacy of exercise-based interventions in preventing falls among community-dwelling older persons with cognitive impairment: is there enough evidence? An updated systematic review and meta-analysis.

OBJECTIVE: Exercise prevents falls in the general older population, but evidence is inconclusive for older adults living with cognitive impairment. We performed an updated systematic review and meta-analysis to assess the potential effectiveness of interventions for reducing falls in older persons with cognitive impairment. METHODS: PubMed, EMBASE, CINAHL, Scopus, CENTRAL and PEDro were searched from inception to 10 November 2020. We included randomised controlled trials (RCTs) that evaluated the effects of physical training compared to a control condition (usual care, waitlist, education, placebo control) on reducing falls among community-dwelling older adults with cognitive impairment (i.e. any stage of Alzheimer's disease and related dementias, mild cognitive impairment). RESULTS: We identified and meta-analysed nine studies, published between 2013 and 2020, that included 12 comparisons (N = 1,411; mean age = 78 years; 56% women). Overall, in comparison to control, interventions produced a statistically significant reduction of approximately 30% in the rate of falls (incidence rate ratio = 0.70; 95% CI, 0.52-0.95). There was significant between-trial heterogeneity (I2 = 74%), with most trials (n = 6 studies [eight comparisons]) showing no reductions on fall rates. Subgroup analyses showed no differences in the fall rates by trial-level characteristics. Exercise-based interventions had no impact on reducing the number of fallers (relative risk = 1.01; 95% CI, 0.90-1.14). Concerns about risk of bias in these RCTs were noted, and the quality of evidence was rated as low. CONCLUSIONS: The positive statistical findings on reducing fall rate in this meta-analysis were driven by a few studies. Therefore, current evidence is insufficient to inform evidence-based recommendations or treatment decisions for clinical practice.PROSPERO Registration number: CRD42020202094.

Contrast-Enhanced Ultrasound of Muscle Perfusion May Indicate Patient Response to Left Ventricular Assist Device Therapy.

PURPOSE: Left ventricular assist device (LVAD) support is associated with peripheral vascular abnormalities beyond those associated with heart failure (HF). These abnormalities are associated with persistent functional impairments that adversely impact quality of life (QoL). Methods for measuring peripheral vascular function in this population are needed. METHODS: This pilot study investigated the use of contrast-enhanced ultrasound (CEUS) using standardized protocols to estimate changes in peripheral (quadriceps) muscle perfusion among patients with HF (INTERMACS profile 3) undergoing LVAD implantation (n = 7). Patients were then stratified by those who did ("responders", n = 4) and did not ("nonresponders", n = 3) report QoL improvement with LVAD support. RESULTS: Serial measurements obtained preoperatively and 3 months following LVAD implantation showed no significant change (P > .23) in muscle perfusion by all CEUS-based measures at rest or with an exercise stimulus for the overall population. Responders exhibited improved muscle perfusion at rest (P = .043) and decreased time to peak contrast enhancement (P = .010) at 3 months compared with baseline, suggesting improved delivery of blood to the extremities post-LVAD. Nonresponders showed unchanged resting muscle perfusion (P > .99), time to peak contrast enhancement (P = .59), and response to exercise stimulus (P > .99) following LVAD therapy. CONCLUSION: Our findings suggest that CEUS evaluation is a promising noninvasive, quantitative modality for real-time assessment of peripheral vasculature and muscle perfusion as an indication of treatment response in LVAD recipients and that this modality may capture perfusion measures important to QoL following LVAD implantation.

Opioid Disposal in Patients Undergoing Total Joint Replacement Utilizing a Carbon-Based Home Medication Disposal Pouch.

AIMS: The purpose of the pilot study was to determine if an educational program on opioid safety and disposal during a preoperative joint replacement class would increase the frequency of disposal of unused opioids with a disposal pouch at the end of the episode of care in patients undergoing joint replacement. A secondary aim was to quantify the milligrams of morphine equivalents prescribed, used, disposed, and remaining in joint replacement patients. DESIGN: The study design is quasi-experimental. METHODS: A medication disposal pouch was provided to all study subjects preoperatively. A 2-minute opioid safety and disposal instruction and demonstration of the use of the disposal pouch was performed at a weekly preoperative joint replacement class which was optional for subjects to attend. A nine-question phone survey was then administered to subjects postoperatively. RESULTS: One hundred and four patients completed the study survey. Of the subjects who attended the class and had opioids remaining, 74% disposed of their opioids compared with 36% that did not attend the class (p = .005). CONCLUSIONS: Provision of a disposal pouch in combination with a live educational program on opioid safety and disposal increased the rate of disposal of unused opioids in a postoperative population.

Conserving Africa's wildlife and wildlands through the COVID-19 crisis and beyond.

The SARS-CoV-2 virus and COVID-19 illness are driving a global crisis. Governments have responded by restricting human movement, which has reduced economic activity. These changes may benefit biodiversity conservation in some ways, but in Africa, we contend that the net conservation impacts of COVID-19 will be strongly negative. Here, we describe how the crisis creates a perfect storm of reduced funding, restrictions on the operations of conservation agencies, and elevated human threats to nature. We identify the immediate steps necessary to address these challenges and support ongoing conservation efforts. We then highlight systemic flaws in contemporary conservation and identify opportunities to restructure for greater resilience. Finally, we emphasize the critical importance of conserving habitat and regulating unsafe wildlife trade practices to reduce the risk of future pandemics.

Pericyte Bridges in Homeostasis and Hyperglycemia.

Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase in basement membrane bridges was also observed. Using cell-specific markers, we demonstrate that pericytes rather than endothelial cells colocalize with these bridges. We show that the density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and blood glucose; is rapidly reversed on a timescale of days; and is often associated with a pericyte cell body located off vessel. Cell-specific knockout of KLF4 in pericytes fully replicates this phenotype. In vivo imaging of limbal vessels demonstrates pericyte migration off vessel, with rapid pericyte filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel pericytes, we observed no pericyte loss relative to nondiabetic control retina. These findings reveal the possibility that pericyte perturbations in location and process formation may play a role in the development of pathological vascular remodeling in diabetic retinopathy.

Myh11 Lineage Corneal Endothelial Cells and ASCs Populate Corneal Endothelium.

Purpose: To establish Myh11 as a marker of a subset of corneal endothelial cells (CECs), and to demonstrate the feasibility of restoring the corneal endothelium with Myh11-lineage (Myh11-Lin[+]) adipose-derived stromal cells (ASCs). Methods: Intraperitoneal administration of tamoxifen and (Z)-4-hydroxytamoxifen eyedrops were used to trace the lineage of Myh11-expressing cells with the Myh11-Cre-ERT2-flox-tdTomato mouse model. Immunostaining and Western blot characterized marker expression and spatial distribution of Myh11-Lin(+) cells in the cornea, and administration of 5-ethynyl-2'-deoxyuridine labeled proliferating cells. ASCs were isolated from epididymal adipose Myh11+ mural cells and treated with cornea differentiation media to evaluate corneal endothelial differentiation potential. Differentiated ASCs were injected into the anterior chamber to test for incorporation into corneal endothelium following scratch injury. Results: A subset of CECs express Myh11, a marker previously thought restricted to only mural cells. Myh11-Lin(+) CECs marked a stable subpopulation of cells in the cornea endothelium. Myh11-Lin(+) ASCs undergo CEC differentiation in vitro and incorporate into injured corneal endothelium. Conclusions: Dystrophy and dysfunction of the corneal endothelium accounts for almost half of all corneal transplants, the maintenance of the cornea endothelium is poorly understood, and there are a lack of mouse models to study specific CEC populations. We establish a mouse model that can trace the cell fate of a subpopulation of CECs based on Myh11 expression. A subset of ASCs that share this Myh11 transcriptional lineage are capable of differentiating into CECs that can incorporate into injured corneal endothelium, revealing a potential cell source for creating engineered transplant material.

Effectiveness of Tai Ji Quan vs Multimodal and Stretching Exercise Interventions for Reducing Injurious Falls in Older Adults at High Risk of Falling: Follow-up Analysis of a Randomized Clinical Trial.

Importance: Exercise has been shown to reduce injurious falls in older adults. Evidence, however, is lacking regarding the types of intervention that are most effective in preventing injurious falls among older adults at high risk of falling. Objective: To determine the longer-term effectiveness of therapeutic tai ji quan intervention vs multimodal exercise and stretching exercise in decreasing injurious falls among older adults at high risk of falling. Design, Setting, and Participants: This trial involves a prespecified analysis with the data analyzed by intent-to-treat. Follow-up analysis of a single-blind randomized trial conducted in community settings of 7 urban and suburban cities in Oregon from February 20, 2015, to September 15, 2018, compared a therapeutic tai ji quan intervention with multimodal exercise and stretching exercise. Eligible participants were community-dwelling adults aged at least 70 years who were considered by a clinician to be at high risk of falling because they had fallen during the preceding year or who had impaired mobility with scores higher than 13.5 seconds on the Timed Up & Go test. Participants were randomized to 1 of the 3 interventions and were assessed monthly after randomization for 12 months, encompassing a 6-month active intervention phase and a 6-month after intervention follow-up phase. Interventions: The 3 group-based interventions were therapeutic tai ji quan (Tai Ji Quan: Moving for Better Balance [TJQMBB]), multimodal exercise, and stretching exercise, each implemented twice weekly in 60-minute sessions for 24 weeks. Main Outcomes and Measures: Primary outcomes were the incidence of moderate and serious injurious falls at 12 months, measured as incidence rate ratios (IRRs). Results: Of the 1147 persons screened, 670 (mean [SD] age, 77.7 [5.6] years; 436 women [65.1%]) were randomly assigned to 1 of 3 intervention groups: 224 persons in TJQMBB, 223 in multimodal exercise, and 223 in stretching exercise. At 12 months, the unadjusted IRR for moderate injurious falls was lower in the TJQMBB (IRR, 0.51; 95% CI, 0.35-0.74; P < .001) and multimodal exercise (IRR, 0.62; 95% CI, 0.42-0.89; P = .01) groups compared with the stretching exercise group. There was no difference between TJQMBB and multimodal exercise groups (IRR, 0.85; 95% CI, 0.58-1.25; P = .42). Both TJQMBB and multimodal exercise significantly reduced serious injurious falls (TJQMBB: IRR, 0.25 [95% CI, 0.13-0.48; P < .001]; multimodal: IRR, 0.56 [95% CI, 0.33-0.94; P = .03]) compared with stretching exercise. Use of TJQMBB was more effective than multimodal exercise (IRR, 0.47; 95% CI, 0.24-0.92; P = .03) in reducing serious injurious falls. Conclusions and Relevance: For preventing injurious falls, including those that resulted in medical treatment, TJQMBB intervention was found to be superior to multimodal and stretching exercises for older adults at high risk of falling. The findings appear to strengthen the clinical use of TJQMBB as a single exercise intervention to prevent injurious falls in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02287740.

Motivational Interviewing: Improving Confidence With Self-care Management in Postoperative Thoracolumbar Spine Patients.

Patients undergoing thoracic or lumbar spine surgery often lack confidence with self-care management of symptoms contributing to disability, such as pain, lack of sleep, depression, and immobility. The purpose of this pilot study was to examine whether a targeted motivational interview, focused on evidence-based recommendations to manage postoperative symptoms related to thoracolumbar spine surgery, would improve patient confidence with self-care management of their symptom-related disability. A quasiexperimental, 1-group, pretest-posttest design was used on a convenience sample of 15 adult surgical spine patients at a large university spine center. Level of disability was measured using the Oswestry Disability Index (ODI). Confidence with self-care management of symptom-related disability was measured using the Health Confidence Index (HCI). Paired samples t tests were completed on participants' preintervention and postintervention scores on the HCI and ODI and on each of the 10 items that the ODI questionnaire addresses. The results of the paired samples t test on participants' HCI scores showed a statistically significant improvement in participants' confidence with self-care management of symptom-related disability from pretest (mean [SD], 6.73 [2.12]) to posttest (mean [SD], 8.73 [1.43]), conditions: t14 = -3.80, P = .002. Motivational interviewing is a beneficial intervention for health professionals to incorporate into practice to encourage the implementation of various health promoting behaviors that improve confidence with self-care management of symptoms in postoperative thoracolumbar spine patients.

Cost-Effectiveness of a Therapeutic Tai Ji Quan Fall Prevention Intervention for Older Adults at High Risk of Falling.

BACKGROUND: Data on the cost-effectiveness of proven fall prevention exercise interventions are limited. We aimed to establish the cost-effectiveness of Tai Ji Quan: Moving for Better Balance (TJQMBB) compared with a conventional exercise intervention for older adults at high risk of falling. METHODS: We conducted a trial-based cost-effectiveness analysis involving 670 older adults who had a history of falling or impaired mobility. Participants received one of three interventions-TJQMBB, multimodal exercise, or stretching exercise (control)-each of which was implemented twice weekly for 24 weeks. The primary cost-effectiveness measure was the incremental cost per additional fall prevented, comparing TJQMBB and multimodal exercise to Stretching and TJQMBB to multimodal exercise, with a secondary measure of incremental cost per additional quality-adjusted life-year (QALY) gained. The intervention was conducted between February 2015 and January 2018, and cost-effectiveness was estimated from a health care system perspective over a 6-month time horizon. RESULTS: The total cost to deliver the TJQMBB intervention was $202,949 (an average of $906 per participant); for multimodal exercise, it was $223,849 ($1,004 per participant); and for Stretching, it was $210,468 ($903 per participant). Incremental cost-effectiveness ratios showed that the multimodal exercise was cost-effective ($850 per additional fall prevented; $27,614 per additional QALY gained) relative to Stretching; however, TJQMBB was the most economically dominant strategy (ie, having lower cost and being clinically more efficacious) compared with multimodal and stretching exercises with regard to cost per additional fall prevented and per additional QALY gained. TJQMBB had a 100% probability of being cost-effective, relative to Stretching, at a threshold of $500 per each additional fall prevented and $10,000 per additional QALY gained. Sensitivity analyses showed the robustness of the results when extreme cases, medical costs only, and missing data were considered. CONCLUSIONS: Among community-dwelling older adults at high risk for falls, TJQMBB is a cost-effective means of reducing falls compared with conventional exercise approaches. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02287740).

More than $1 billion needed annually to secure Africa's protected areas with lions.

Protected areas (PAs) play an important role in conserving biodiversity and providing ecosystem services, yet their effectiveness is undermined by funding shortfalls. Using lions (Panthera leo) as a proxy for PA health, we assessed available funding relative to budget requirements for PAs in Africa's savannahs. We compiled a dataset of 2015 funding for 282 state-owned PAs with lions. We applied three methods to estimate the minimum funding required for effective conservation of lions, and calculated deficits. We estimated minimum required funding as $978/km2 per year based on the cost of effectively managing lions in nine reserves by the African Parks Network; $1,271/km2 based on modeled costs of managing lions at ≥50% carrying capacity across diverse conditions in 115 PAs; and $2,030/km2 based on Packer et al.'s [Packer et al. (2013) Ecol Lett 16:635-641] cost of managing lions in 22 unfenced PAs. PAs with lions require a total of $1.2 to $2.4 billion annually, or ∼$1,000 to 2,000/km2, yet received only $381 million annually, or a median of $200/km2 Ninety-six percent of range countries had funding deficits in at least one PA, with 88 to 94% of PAs with lions funded insufficiently. In funding-deficit PAs, available funding satisfied just 10 to 20% of PA requirements on average, and deficits total $0.9 to $2.1 billion. African governments and the international community need to increase the funding available for management by three to six times if PAs are to effectively conserve lions and other species and provide vital ecological and economic benefits to neighboring communities.

Effectiveness of a Therapeutic Tai Ji Quan Intervention vs a Multimodal Exercise Intervention to Prevent Falls Among Older Adults at High Risk of Falling: A Randomized Clinical Trial.

Importance: Falls in older adults are a serious public health problem associated with irreversible health consequences and responsible for a substantial economic burden on health care systems. However, identifying optimal choices from among evidence-based fall prevention interventions is challenging as few comparative data for effectiveness are available. Objective: To determine the effectiveness of a therapeutically tailored tai ji quan intervention, Tai Ji Quan: Moving for Better Balance (TJQMBB), developed on the classic concept of tai ji (also known as tai chi), and a multimodal exercise (MME) program relative to stretching exercise in reducing falls among older adults at high risk of falling. Design, Setting, and Participants: A single-blind, 3-arm, parallel design, randomized clinical trial (February 20, 2015, to January 30, 2018), in 7 urban and suburban cities in Oregon. From 1147 community-dwelling adults 70 years or older screened for eligibility, 670 who had fallen in the preceding year or had impaired mobility consented and were enrolled. All analyses used intention-to-treat assignment. Interventions: One of 3 exercise interventions: two 60-minute classes weekly for 24 weeks of TJQMBB, entailing modified forms and therapeutic movement exercises; MME, integrating balance, aerobics, strength, and flexibility activities; or stretching exercises. Main Outcomes and Measures: The primary measure at 6 months was incidence of falls. Results: Among 670 participants randomized, mean (SD) age was 77.7 (5.6) years, 436 (65%) were women, 617 (92.1%) were white, 31 (4.6%) were African American. During the trial, there were 152 falls (85 individuals) in the TJQMBB group, 218 (112 individuals) in the MME group, and 363 (127 individuals) in the stretching exercise group. At 6 months, the incidence rate ratio (IRR) was significantly lower in the TJQMBB (IRR, 0.42; 95% CI, 0.31-0.56; P < .001) and MME groups (IRR, 0.60; 95% CI, 0.45-0.80; P = .001) compared with the stretching group. Falls were reduced by 31% for the TJQMBB group compared with the MME group (IRR, 0.69; 95% CI, 0.52-0.94; P = .01). Conclusions and Relevance: Among community-dwelling older adults at high risk for falls, a therapeutically tailored tai ji quan balance training intervention was more effective than conventional exercise approaches for reducing the incidence of falls. Trial Registration: ClinicalTrials.gov identifier: NCT02287740.

Formulation and Evaluation of Anisamide-Targeted Amphiphilic Cyclodextrin Nanoparticles To Promote Therapeutic Gene Silencing in a 3D Prostate Cancer Bone Metastases Model.

In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells). Resulting nanoparticles were less than 200 nm in size with a cationic surface charge (∼+20 mV). In sigma receptor-positive cell lines, the uptake of anisamide-targeted nanoparticles was reduced in the presence of the sigma receptor competitive ligand, haloperidol. When cells were transfected in 2D, the levels of PLK1 mRNA knockdown elicited by targeted versus untargeted nanoparticles tended to be greater but the differences were not statistically different. In contrast, when cells were grown on 3D scaffolds, recapitulating bone metastasis, targeted formulations showed significantly higher levels of PLK1 mRNA knockdown (46% for PC3 and 37% for DU145, p < 0.05). To our knowledge, this is the first time that a targeted cyclodextrin has been used to transfect prostate cancer cells in a 3D model of bone metastasis.

Implementing an Evidence-Based Fall Prevention Intervention in Community Senior Centers.

OBJECTIVES: To evaluate the impact of implementing an evidence-based fall prevention intervention in community senior centers. METHODS: We used a single-group design to evaluate the Tai Ji Quan: Moving for Better Balance (TJQMBB) program's adoption, population reach, implementation, effectiveness, and maintenance among 36 senior centers in 4 Oregon counties between 2012 and 2016. The primary outcome measure, as part of the effectiveness evaluation, was number of falls as ascertained by self-report. Trained TJQMBB instructors delivered the program to community-dwelling older adults for 48 weeks, with a 6-month postintervention follow-up. RESULTS: TJQMBB was adopted by 89% of the senior centers approached and reached 90% of the target population. The program resulted in a 49% reduction in the total number of falls and improved physical performance. Participation was well maintained after the program's completion. The average cost-effectiveness ratio for the 48-week program implementation was $917 per fall prevented and $676 per fall prevented for multiple falls. CONCLUSIONS: TJQMBB is an effective public health program that can be broadly implemented in community senior centers for primary prevention of falls among community-dwelling older adults.

Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.

siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was reduced by∼50% by day 7 in the co-culture system relative to monoculture (PC3 and LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone metastasis) was secreted into the media (1.2-4-fold increase depending on the co-culture system). A cationic cyclodextrin gene delivery vector proved significantly less toxic in the co-culture system relative to the commercially available vector Lipofectamine 2000(®). In addition, knockdown of both the GAPDH gene (minimum 15%) and RelA subunit of the NF-κB transcription factor (minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant vs the monoculture. This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development.

Functionalization of emissive conjugated polymer nanoparticles by coprecipitation: consequences for particle photophysics and colloidal properties.

The functionalization of polyfluorene (PFO) nanoparticles by coprecipitation of the conjugated polymer with an amphiphilic comb polymer, consisting of a hydrophobic polystyrene backbone with hydrophilic, carboxylic acid-terminated polyethylene oxide side-chains (PS-PEG-COOH), is investigated. The comb polymer affects the properties of the formed hybrid nanoparticles. Non-functionalized particles are typically larger (28 nm) than functionalized ones (20 nm); peak molar extinction coefficients are found to differ in a similar trend. Zeta potentials are negative, consistent with negative surface charge on PFO particles due to chemical defect formation, with additional charge on functionalized particles due to the pendant carboxylic acid groups. Emission quantum yields of functionalized particles are typically larger, consistent with lower efficiency of energy transfer to quenchers in smaller particles and weaker PFO interchain interactions due to chain dilution. The trend in per-particle fluorescence brightness values, as confirmed by single particle fluorescence imaging, reflects the nanoparticle extinction coefficients. Photostability studies on aqueous dispersions of hybrid particles indicate mild photobrightening under continuous illumination while PFO particles exhibit slow exponential emission decay. Functionalized particles are also resistant to aggregation during exposure to adenocarcinoma cells. Generally, the hybrid particles exhibit more favorable time-, pH- and medium-dependent stabilities, likely due to steric and electrostatic stabilization by PEG-carboxylic acid functionalities. Overall, the functionalized particles exhibit attractive properties: Reasonably small size, tight size distribution, high absorption cross section, radiative rate and emission quantum yield, excellent brightness and photostability, and good colloidal stability.