The Effect of Sensory Level Versus Motor Level Electrical Stimulation of Pharyngeal Muscles in Acute Stroke Patients with Dysphagia: A Randomized Trial.

Dysphagia is a serious cause of morbidity and mortality in stroke survivors. Electrical stimulation is often included as part of the treatment plan for dysphagia and can be applied at a sensory or motor level intensity. However, evidence to support these different modes of stimulation is lacking. This study compared the effectiveness of sensory and motor level stimulation on post-stroke dysphagia. This is a randomized trial conducted in an inpatient rehabilitation facility. Thirty-one participants who had dysphagia caused by stroke within 6 months prior to enrolment were included. Participants were excluded if they had a contraindication for electrical stimulation, previous stroke, psychiatric disorder, contraindications for modified barium swallow study (MBSS), or pre-morbid dysphagia. Each patient received ten sessions that included 45 min of anterior neck sensory or motor level electrical stimulation in addition to traditional dysphagia therapy. Motor stimulation was administered at an intensity sufficient to produce muscle contractions. Sensory stimulation was defined as the threshold at which the patient feels a tingling sensation on their skin. Swallow functional assessment measure (FAM), dysphagia outcome severity scale (DOSS), national outcome measurement system (NOMS), penetration aspiration scale (PAS), diet change, and the swallowing quality of life questionnaire (SWAL-QOL). Clinical outcomes were analyzed using a Wilcoxon signed-rank test, Mann-Whitney U test, RM ANOVA, or chi-square analysis. There was no significant difference in age, length of stay, or initial swallow FAM between groups. Patients in the sensory group showed significant improvement on swallow FAM, DOSS, and NOMS, while those in the motor group did not (Sensory: Swallow FAM (S = 48, p = 0.01), DOSS (S = 49.5, p = 0.001), NOMS (S = 52.5, p = 0.006); Motor: Swallow FAM (S = 20.5, p = 0.2), DOSS (S = 21, p = 0.05), NOMS (S = 29.5, p = 0.2)). When the groups were combined, there was statistically significant improvement on all measures except the PAS (Swallow FAM (S = 138.5, p = 0.003), DOSS (S = 134.5, p < 0.001), NOMS (S = 164, p = 0.0004)). When comparing motor to sensory NMES, there was no significant difference between groups for Swallow FAM (p = .12), DOSS (p = 0.52), or NOMS (p = 0.41). There was no significant difference in diet change for solid food or liquids among the groups, although 50% more participants in the sensory group saw improvement in diet. This study supports the use of electrical stimulation as part of the treatment plan for post-stroke dysphagia. Sensory-level stimulation was associated with greater improvement on outcome measures compared to motor level stimulation.

Developing a Public Health Maternal and Child Health Training Program: Lessons Learned from Five Schools of Public Health.

Maternal and child health (MCH), as a core sub-field of public health, continues to be an essential area in which additional workforce development and investment are needed. Recent public health workforce assessments in the United States reveal there will be a significant number of vacancies in MCH public health positions in the near future, creating the need for a well-trained and skilled public health MCH workforce. In order to address this potential critical workforce gap, the U.S. Department of Health and Human Services, Health Resources and Services Administration's Maternal and Child Health Bureau initiated the Maternal and Child Health Public Health Catalyst Program in 2015 to support the creation of MCH training programs in accredited schools of public health that previously did not have a MCH concentration. This article details the accomplishments and lessons learned from the first five MCH Catalyst Program grantees: Drexel University; Florida International University; Rutgers, The State University of New Jersey; Texas A&M University; and the University at Albany.

Virtual town halls addressing vaccine hesitancy among racial/ethnic minorities: Preliminary findings.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains a public health priority, and vaccination is important for ending the pandemic. Racial and ethnic minorities are disproportionally affected by COVID-19 yet report high levels of vaccination hesitancy. OBJECTIVE: We conducted virtual town halls to address vaccine hesitancy among racial and ethnic minorities in South Florida. METHODS: Our approach used social influence and persuasion models. In a formative phase, we gathered meeting preferences from our communities and developed and tested our approach. In an implementation phase, we conducted 6 virtual town halls in partnership with minority community-based organizations. RESULTS: The town halls reached 383 participants (mean age 37.5 years; 63.4% female, 33.9% male, 2.7% nonbinary; 59% racial/ethnic minority) who completed pre- and postmeeting assessments. Among nonvaccinated participants, at the prepoll, 58% reported a high likelihood of seeking vaccination, rising to 63% at the postassessment. Unvaccinated non-hesitant and hesitant groups were compared on trusted information sources and reasons and barriers for vaccination. Nonhesitant participants reported significantly greater trust in the COVID-19 Task Force (97.3% vs. 83.3%) as a source of vaccine information than did hesitant participants. Nonhesitant participants were significantly more likely to endorse family safety (82.5% vs. 63.2%), community safety (72.5% vs. 26.3%), personal safety (85% vs. 36.8%), and wanting to return to a normal life (70% vs. 31.6%) as reasons for vaccination than were hesitant participants. Hesitant participants were significantly more likely to endorse concerns about vaccine safety doubts (63.2% vs. 17.5%) and not believing the pandemic is as bad as people say it is (21.1% vs. 5%) as barriers to vaccination than were nonhesitant participants. Qualitative data revealed high consumer satisfaction with the town halls. CONCLUSION: This study supports the feasibility, acceptability, and potential impact of virtual town halls for addressing vaccine hesitancy among racial/ethnic minorities; however, our approach was resource intensive, required an extensive community-university collaborative infrastructure, and yielded a small effect.

Getting Their Feet in the Door: Communication Cues to Action for HIV Testing and Condom Use Behaviors Among Hispanic/Latinx College Students.

Hispanic/Latinx youth in the U.S. are disproportionately affected by HIV, and are in need of culturally, linguistically, and developmentally tailored HIV prevention programs focused on expanding routine screening and environmental prevention efforts. With SAMHSA support, we implemented an HIV prevention campaign targeting 18- to 24-year-old Hispanic/Latinx college students. Based on formative feedback, both traditional communication and social media channels were employed to motivate students to seek free-of-charge on-campus HIV testing. Participants' attitudes regarding the benefits of and confidence in condom use were also examined. From 2015 to 2018, 1406 Hispanic 18-24 year olds received an on-campus HIV test; for nearly half, this was their first HIV test ever. Among first time testers, the reasons for not getting tested sooner included that over 70% thought they were unlikely to have an HIV infection, over 20% said they did not know where to get tested, and 10% reported being afraid to find out their status. Moreover, participants reported a variety of cues to seeking testing: just under half reported printed flyers, on-campus lawn signs, and word-of-mouth, and almost 15% reported social media. Repeat testers (n = 717) were significantly more likely than first time testers to report hearing about HIV testing through social media. There were significant gains from baseline to the 1-month follow-up in both perceived advantages of condom use and confidence in condom use. Our study showed that messages conveyed through traditional communication channels remain important and serve as cues to seek HIV testing for Hispanic/Latinx college students, especially those who have never before been tested.

Early Mobilization Rehabilitation Program for Children With Cerebral Palsy Undergoing Single-Event Multilevel Surgery.

PURPOSE: This study investigates functional and technical outcomes to support an early mobilization approach to rehabilitation after single-event multilevel surgery (SEMLS) for children with cerebral palsy (CP), and disseminates innovative guidelines emphasizing early walking. METHODS: Twenty-three participants with spastic diplegic CP ages 7 through 17 years, Gross Motor Function Classification System levels I to III, who underwent an early mobilization program after SEMLS were reviewed. Outcomes were examined from motion analysis data and clinical documentation. RESULTS: All participants were able to return to school walking at discharge. At 1-year postoperatively, participants had returned to their prior walking level or better. Change in Gait Deviation Index and Pediatric Outcomes Data Collection Instrument indicated improvements in functional mobility and gait consistent with or greater than the literature. CONCLUSION: This intensive early mobilization program restores participation in daily activities, walking, and school within the first month postoperatively.

Hispanic Students' Perceptions About HIV/STI Testing and Prevention: A Mixed-Methods Study in a Hispanic-Serving University.

Hispanic young adults in the United States are disproportionately affected by HIV and should be considered a priority for prevention efforts. The purpose of this study was to explore perceptions and beliefs of English-speaking students (aged 18-24 years) at a Hispanic-serving university about HIV/sexually transmitted infection (STI) testing and prevention to increase acceptance and adoption of services. Four major themes emerged from four qualitative focus groups (n = 30 students) and were corroborated by an optional anonymous survey (n = 24 surveys): (a) preferences for HIV/STI testing services, (b) essential HIV/STI testing information, (c) preferred delivery method of HIV/STI testing information, and (d) culturally appropriate message design with Hispanic young adults. Findings suggest that Hispanic young adults perceive accessible testing to be important to their community and view normalization of these services as a necessary component of successful adoption and adherence. Although flyers were reported as a practical means for distributing on-campus testing and service information, social media was endorsed as one of the most effective ways to reach young adults. Among participants, there was less consensus regarding the need for cultural tailoring. Results provide practical insights into the development and application of health promotion strategies with an ethnic minority group and demonstrate how a mixed-methods approach can be employed to inform health promotional efforts.

Nanocarriers for vascular delivery of anti-inflammatory agents.

There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation.

Advanced drug delivery systems for antithrombotic agents.

Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena.

Targeting to endothelial cells augments the protective effect of novel dual bioactive antioxidant/anti-inflammatory nanoparticles.

Oxidative stress and inflammation are intertwined contributors to numerous acute vascular pathologies. A novel dual bioactive nanoparticle with antioxidant/anti-inflammatory properties was developed based on the interactions of tocopherol phosphate and the manganese porphyrin SOD mimetic, MnTMPyP. The size and drug incorporation efficiency were shown to be dependent on the amount of MnTMPyP added as well as the choice of surfactant. MnTMPyP was shown to retain its SOD-like activity while in intact particles and to release in a slow and controlled manner. Conjugation of anti-PECAM antibody to the nanoparticles provided endothelial targeting and potentiated nanoparticle-mediated suppression of inflammatory activation of these cells manifested by expression of VCAM, E-selectin, and IL-8. This nanoparticle technology may find applicability with drug combinations relevant for other pathologies.

Being Pregnant during COVID-19: Exploring the COVID-19 Related Beliefs, Behaviors, and Birth Outcome among Users of a Pregnancy App.

Being pregnant during COVID-19 increases the risk of experiencing severe COVID-19 symptoms, which in turn increases the risk of complications. This study aimed to examine COVID-19-related beliefs, behaviors, and birth outcomes among users of Count the Kicks (CTK), a fetal movement tracking app. This study used the End of Pregnancy Survey data from 1037 CTK users. We used descriptive analyses to analyze COVID-19-related beliefs and behaviors and used the chi-square statistic and Z statistic to examine factors associated with vaccination and birth outcome. Nearly half of the survey respondents reported not being concerned that in-person prenatal visits might lead to COVID-19 exposure. Most respondents (65.9%) had already received the COVID-19 vaccine at the time of the survey. The vaccination rate was statistically significantly lower among African Americans than the remaining race/ethnicity groups (mostly white). The healthy birth rate is lower among respondents with high-risk pregnancies, while the stillbirth rate is highest among Hispanics. Vaccination status was not associated with the likelihood of a healthy birth. Our findings confirmed that vaccination does not compromise birth outcomes, further contributing to the existing evidence of COVID vaccine safety during pregnancy. This study also demonstrates an example of using data from a pregnancy app to facilitate research on app users in real-time.

aBnormal motION capture In aCute Stroke (BIONICS): A Low-Cost Tele-Evaluation Tool for Automated Assessment of Upper Extremity Function in Stroke Patients.

BACKGROUND: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility. METHODS: In this study we want to develop an automated method for evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale describing upper extremity motor function. We pair this technology with a series of machine learning models, including different neural network structures and an eXtreme Gradient Boosting model, to score 16 of 33 (49%) Fugl-Meyer item activities. RESULTS: In this observational study, 45 acute stroke patients completed at least 1 recorded Fugl-Meyer assessment for the training of the auto-scorers, which yielded average accuracies ranging from 78.1% to 82.7% item-wise. CONCLUSION: In this study, an automated method was developed for the evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale describing upper extremity motor function. This novel method is demonstrated with potential to conduct telehealth rehabilitation evaluations and assessments with accuracy and availability.

Consensus-Based Evaluation of Outcome Measures in Pediatric Stroke Care: A Toolkit.

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, validity, feasibility, and predictive utility. A total of 48 outcome measures were included and were rated by experts based on the available evidence within the literature supporting the strengths of their psychometric properties and practical use. Only three measures were found to be validated for use in pediatric stroke: the Pediatric Stroke Outcome Measure, the Pediatric Stroke Recurrence and Recovery Questionnaire, and the Pediatric Stroke Quality of Life Measure. However, multiple additional measures were deemed to have good psychometric properties and acceptable utility for assessing pediatric stroke outcomes. Strengths and weaknesses of commonly used measures including feasibility are highlighted to guide evidence-based and practicable outcome measure selection. Improving the coherence of outcome assessment will facilitate comparison of studies and enhance research and clinical care in children with stroke. Further work is urgently needed to close the gap and validate measures across all clinically significant domains in the pediatric stroke population.

Carboxylesterase-triggered hydrolysis of nanoparticle PEGylating agents.

Despite the importance of PEGylation in achieving long nanoparticle circulation times, many nanoparticles are coated with PEGylating agents susceptible to enzymatic degradation. In this study, solid lipid nanoparticles (SLNs) prepared with ester-containing compounds were evaluated for their stability in the presence of carboxylesterase. SLN suspensions became turbid within 30 min of enzymatic exposure, indicating possible disassociation of a portion of the nanoparticles. The particle size of SLNs incubated with the enzyme was smaller than the size of controls, although their morphologies appeared similar in transmission electron microscopy images. Although SLNs offered some protection over micelles, PEG6000 monostearate was rapidly degraded within 15 min. Hydrolysis of polysorbate 60 was much slower, reaching only 36% in 2 h. These studies reveal the importance of confirming the stability of PEG surface coatings prior to undertaking in vivo experiments in small animal models, which can have considerably higher plasma esterase activity than humans.

CRTH2 antagonist MK-7246: a synthetic evolution from discovery through development.

In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules.

Optimization of the lyophilization process for long-term stability of solid-lipid nanoparticles.

OBJECTIVES: To optimize a lyophilization protocol for solid-lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions. MATERIALS AND METHODS: The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH). RESULTS AND DISCUSSION: Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results. CONCLUSIONS: A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.

Stress and Anxiety Among Parents of Transition-Aged Children with Autism Spectrum Disorder: a Systematic Review of Interventions and Scales.

The period between adolescence to young adulthood can be stressful for parents of transition-aged children (14 to 22 years old) with autism spectrum disorder. A systematic review was undertaken to examine if existing interventions address the unique parental stressors of this phase and if the scales used to measure parental stress and anxiety are suitable for this group. Of the 9813 studies screened, only 13 studies met the inclusion criteria. Findings indicated that interventions focused on mindfulness, social functioning, or multiple components, of which only two addressed the transition period and only three specifically targeted parents of this age group. Moreover, of the six scales which assessed stress or anxiety, none were designed for these parents. Findings highlight the urgent need for more suitable scales and targeted interventions.

Physicochemical characterization of nanotemplate engineered solid lipid nanoparticles.

As the physicochemical characteristics of solid lipid nanoparticles (SLNs) play a critical role in their success, it is important to understand how the materials and process used in their preparation affect these properties. In this study, two stearyl alcohol-based formulations were prepared using nanotemplate engineering technology and characterized. Both formulations were of a small particle size (<100 nm), ellipsoidal shape, and low polydispersity. (1)H NMR spectroscopy confirmed that the SLNs have the expected solid core structure and PEGylated surface. Analysis of the bulk materials indicated that a number of complex interactions are present among the SLN components, including a eutectic between stearyl alcohol and Brij 78. The decreased crystallinity resulting from these interactions may allow for enhanced drug loading. Physiological stability was identified and confirmed as a potential problem due to the low melting point of the eutectic. However, it is expected that with appropriate formulation modifications nanotemplate engineered SLNs will possess the properties necessary for a successful drug delivery system.

Polymer micelles with hydrazone-ester dual linkers for tunable release of dexamethasone.

PURPOSE: To develop polymer micelles for the tunable release of Dexamethasone (DEX) in tumors. METHODS: DEX was conjugated to poly(ethylene glycol)-poly(aspartate) block copolymers using hydrazone, ester, or hydrazone-ester dual linkers. Ketonic acids containing 3, 4, and 5 methylene groups were used as spacers to separate the dual linkers. Polymer micelles from the DEX-conjugated polymers were tested for drug release at different pH values and carboxylesterase activity levels. RESULTS: DLS measurements and (1)H-NMR analysis confirmed all DEX-loaded micelles were <100 nm with core-shell structure. Single linker micelles appeared unsuitable to release DEX preferentially in acidic tumor tissues. Hydrazone linkages between DEX and polymers were non-degradable at both pH 7.4 and 5.0. Ester linkages stable at pH 5.0 were unstable at pH 7.4. Hydrazone-ester dual linkers suppressed DEX release at pH 7.4 while accelerating drug release at pH 5.0. DEX release decreased at pH 5.0 as the length of ketonic acid increased but was independent of spacer length at pH 7.4. Dual linker micelles were stable in the presence of carboxylesterases, suggesting DEX release was primarily due to pH-dependent hydrolysis. CONCLUSION: Tunable release of DEX was achieved using pH-sensitive polymer micelles with hydrazone-ester dual linkers.

U.S. Medicare policy change in catheter guidelines Improves patient care in home and hospice setting.

This spring marks the one-year anniversary of an historic change in Medicare policy. This change is positively impacting quality of care for more than a million people with chronic diseases and conditions that are yet still little known. In April 2008, the Centers for Medicare and Medicaid Services (CMS) of the Department of Health and Human Services eliminated the mandatory reuse of intermittent catheters for outpatients who receive such prescriptions from doctors. In short, no more cleaning and reusing catheters at home for people who self-catheterize.

Use of Textured Thin Liquids in Patients With Dysphagia.

Purpose: The goals of this article are to explore the use of textured thin liquids for dysphagic patients who require thickened liquids and to illustrate their impact on hydration and patient satisfaction. Method: A retrospective evaluation of textured thin liquids was completed using patient data looking at laboratory values relevant to the detection of dehydration (blood urea nitrogen, creatinine, sodium) and patient satisfaction (using a clinician-generated questionnaire) on different modified liquid textures. In addition, the viscosity for all liquids was tested using a rheometer. Results: Measurements show that the viscosity of the textured thin liquids examined in this pilot study are significantly lower than the viscosity of nectar-thick liquids and fall within the "thin" category as defined by the National Dysphagia Diet guidelines. Patients on honey- and nectar-thick liquids had laboratory values signifying dehydration, whereas those receiving the textured thin liquid consistency were within the normal range for all laboratory values. Importantly, when consuming textured thin liquids, patients reported significant improvement in their satisfaction related to their thirst. Conclusion: The results of this pilot study highlight the consequences of common thickened liquid dietary recommendations and of the potentially beneficial clinical application of textured thin liquids for patients with dysphagia as well as the need for future prospective research.