Experiences of Adult Play.

IMPORTANCE: Play has been viewed as a critical occupation supporting health since the founding of occupational therapy, but the complexity of play presents challenges to scholars who study adults. Researchers in occupational science and occupational therapy often address experiential qualities of occupations, including those considered to be play. However, the literature lacks clear descriptions of what constitutes adult play as well as the experiences of adults during preferred activities. OBJECTIVE: To contribute to the body of knowledge on the wide range of preferred activities adults in the United States pursue and may perceive as play experiences. We refer to these activities as adult play because they contain experiential qualities of play described in key play literature. DESIGN: Cross-sectional survey study. SETTING: A 31-item survey, the Daily Occupational Experience Survey-revised (DOESr), was uploaded to Qualtrics for data collection using snowball sampling. The online survey link was distributed to participants aged 18-64 years. PARTICIPANTS: The survey was completed by 491 participants. Exploratory factor analysis was used to extract the most prevalent patterns of play experiences reported. Internal consistency and content validity were also examined. RESULTS: The factor analysis yielded an optimal solution of five factors representing distinct patterns of adult play experiences: Creativity-Adventure, Restoration, Deep Engagement, Ludos, and Mastery. CONCLUSIONS AND RELEVANCE: The five factors identified by the DOESr represent distinct patterns of adult play experiences. The DOESr demonstrated acceptable internal consistency for three of the five factors as well as for the overall tool. Plain-Language Summary: Previous research on adult occupations has not addressed the array of experiences that adults seek or enjoy while engaging in play. This study identified five patterns of adult play experiences. Understanding these patterns may assist occupational therapy practitioners when tailoring clients' play experiences to promote optimal health and well-being.

Plan-do-study-act (PDSA) interventions to improve real-world endoscopy unit productivity.

Background and study aims The Plan-Do-Study Act (PDSA) ramp is a framework that uses initial small changes to build consensus and momentum for subsequent, iterative process improvement. Our aim was to study its impact on endoscopy unit efficiency and throughput. Methods Following a granular time-and-motion analysis to evaluate baseline performance (phase 1) we instituted successive interventions and measured their impact on core efficiency metrics including procedure volume and turnover time (phases 2-3). Results We identified that inefficiency in turnover of anesthesia-supported endoscopy was the most crucial issue. Implementation of a pre-procedure anesthesia visit in phase 2 reduced turnover time by 15.5 minutes (95% confidence interval 3.9-27.1 minutes). Subsequent changes (phase 3) including front-loaded procedure scheduling and parallel in-room preparation resulted in an 18% increase in procedure volume. Conclusions The PDSA ramp model is an effective means of assessing operational processes, developing novel interventions, and building consensus to improve the real-world productivity in a resource-conscious manner.

Single-tube four-target lateral flow assay detects human papillomavirus types associated with majority of cervical cancers.

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after 30 min of amplification the LOD was 100, 10, and 10 copies/reaction of HPV16, HPV18, and HPV45, respectively, and 0.1 ng/reaction of human genomic DNA (gDNA). Next, we implemented the assay on lateral flow strips, and the LOD was maintained for HPV16 and HPV18, but increased to 100 copies/reaction for HPV45 and to 1 ng/reaction for gDNA. Lastly, we used the LAMP test to evaluate total nucleic acid extracted from 38 clinical samples; compared to qPCR, the LAMP test had 89% sensitivity and 95% specificity. When integrated with sample preparation, this multiplexed LAMP assay could be useful for point-of-care testing.

Pediatric produce prescription initiatives in the U.S.: a scoping review.

BACKGROUND: To describe pediatric Produce Prescription (PRx) interventions and their study designs, outcomes, and opportunities for future research. METHODS: A scoping review framework was used to describe PRx interventions published between January 2000 and September 2023. Articles from online databases were uploaded into Covidence. Data on study characteristics, outcomes of interest (health, food insecurity (FI), nutritional and culinary efficacy, and fruit and vegetable (F/V) consumption), and feasibility were extracted. The Mixed Methods Appraisal Tool (MMAT) was used for quality assessment. RESULTS: 19 articles met inclusion criteria. Ten studies were quantitative, five were qualitative, and four used mixed-methods. Interventions included food vouchers (n = 14) or food box/pantries (n = 5). Four studies allowed food items in addition to F/Vs. Six studies measured changes in FI and five reported a statistically significant decrease. Seven studies measured changes in F/V consumption and five reported a statistically significant increase. One study reported a statistically significant reduction in child BMI z-score. Most studies reported high feasibility. Few studies used high-quality methods. CONCLUSIONS: Pediatric PRx interventions show promising potential to reduce FI and improve diet quality and health-related outcomes. Future studies should utilize rigorous study designs and validated assessment tools to understand the impact of pediatric PRx on health. IMPACT: This work offers a summary of programmatic outcomes including retention, redemption, incentives, nutrition education, study design and quality limitations to help inform future work. We found positive impacts of pediatric produce prescriptions (PRx) on FI, F/V consumption, and nutritional knowledge and culinary skills. More high-quality, rigorous studies are needed to understand the best delivery and design of PRx and their impact on child behavior and health outcomes. This work provides support for the need for rigorous studies and the potential for PRx to play a role in multi-pronged strategies that address pediatric FI and diet-related disease.

A novel tailed primer nucleic acid test for detection of HPV 16, 18 and 45 DNA at the point of care.

Cervical cancer is a leading cause of death for women in low-resource settings despite being preventable through human papillomavirus (HPV) vaccination, early detection, and treatment of precancerous lesions. The World Health Organization recommends high-risk HPV (hrHPV) as the preferred cervical cancer screening strategy, which is difficult to implement in low-resource settings due to high costs, reliance on centralized laboratory infrastructure, and long sample-to-answer times. To help meet the need for rapid, low-cost, and decentralized cervical cancer screening, we developed tailed primer isothermal amplification and lateral flow detection assays for HPV16, HPV18, and HPV45 DNA. We translated these assays into a self-contained cartridge to achieve multiplexed detection of three hrHPV genotypes in a disposable cartridge. The developed test achieves clinically relevant limits of detection of 50-500 copies per reaction with extracted genomic DNA from HPV-positive cells. Finally, we performed sample-to-answer testing with direct lysates of HPV-negative and HPV-positive cell lines and demonstrated consistent detection of HPV16, HPV18, and HPV45 with 5000-50,000 cells/mL in < 35 min. With additional optimization to improve cartridge reliability, incorporation of additional hrHPV types, and validation with clinical samples, the assay could serve as a point-of-care HPV DNA test that improves access to cervical cancer screening in low-resource settings.

An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.

A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings.

Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ("Xpert"), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

Sugar is not always sweet: exploring the relationship between hyperglycemia and COVID-19 in a predominantly African American population.

INTRODUCTION: The purpose of this study is to examine the effect of admission glucose in patients hospitalized with COVID-19 with and without diabetes mellitus in a largely African American cohort. DESIGN AND METHODS: This study included 708 adults (89% non-Hispanic Black) admitted with COVID-19 to an urban hospital between 1 March and 15 May 2020. Patients with diabetes were compared with those without and were stratified based on admission glucose of 140 and 180 mg/dL. Adjusted ORs were calculated for outcomes of mortality, intubation, intensive care unit (ICU) admission, acute kidney injury (AKI), and length of stay based on admission glucose levels. RESULTS: Patients with diabetes with admission glucose >140 mg/dL (vs <140 g/dL) had 2.4-fold increased odds of intubation (95% CI 1.2 to 4.6) and 2.1-fold increased odds of ICU admission (95% CI 1.0 to 4.3). Patients with diabetes with admission glucose >180 mg/dL (vs <180 g/dL) had a 1.9-fold increased mortality (95% CI 1.2 to 3.1). Patients without diabetes with admission glucose >140 mg/dL had a 2.3-fold increased mortality (95% CI 1.3 to 4.3), 2.7-fold increased odds of ICU admission (95% CI 1.3 to 5.4), 1.9-fold increased odds of intubation (95% CI 1.0 to 3.7) and 2.2-fold odds of AKI (95% CI 1.1 to 3.8). Patients without diabetes with glucose >180 mg/dL had 4.4-fold increased odds of mortality (95% CI 1.9 to 10.4), 2.7-fold increased odds of intubation (95% CI 1.2 to 5.8) and 3-fold increased odds of ICU admission (95% CI 1.3 to 6.6). CONCLUSION: Our results show hyperglycemia portends worse outcomes in patients with COVID-19 with and without diabetes. While our study was limited by its retrospective design, our findings suggest that patients presenting with hyperglycemia require closer observation and more aggressive therapies.

Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.

RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to protect against cell death in a range of preclinical cellular and animal models of diseases. SAR443060 (previously DNL747) is a selective, orally bioavailable, central nervous system (CNS)-penetrant, small-molecule, reversible inhibitor of RIPK1. In three early-stage clinical trials in healthy subjects and patients with AD or ALS (NCT03757325 and NCT03757351), SAR443060 distributed into the cerebrospinal fluid (CSF) after oral administration and demonstrated robust peripheral target engagement as measured by a reduction in phosphorylation of RIPK1 at serine 166 (pRIPK1) in human peripheral blood mononuclear cells compared to baseline. RIPK1 inhibition was generally safe and well-tolerated in healthy volunteers and patients with AD or ALS. Taken together, the distribution into the CSF after oral administration, the peripheral proof-of-mechanism, and the safety profile of RIPK1 inhibition to date, suggest that therapeutic modulation of RIPK1 in the CNS is possible, conferring potential therapeutic promise for AD and ALS, as well as other neurodegenerative conditions. However, SAR443060 development was discontinued due to long-term nonclinical toxicology findings, although these nonclinical toxicology signals were not observed in the short duration dosing in any of the three early-stage clinical trials. The dose-limiting toxicities observed for SAR443060 preclinically have not been reported for other RIPK1-inhibitors, suggesting that these toxicities are compound-specific (related to SAR443060) rather than RIPK1 pathway-specific.

Characterization of wax valving and µPIV analysis of microscale flow in paper-fluidic devices for improved modeling and design.

Paper-fluidic devices are a popular platform for point-of-care diagnostics due to their low cost, ease of use, and equipment-free detection of target molecules. They are limited, however, by their lack of sensitivity and inability to incorporate more complex processes, such as nucleic acid amplification or enzymatic signal enhancement. To address these limitations, various valves have previously been implemented in paper-fluidic devices to control fluid obstruction and release. However, incorporation of valves into new devices is a highly iterative, time-intensive process due to limited experimental data describing the microscale flow that drives the biophysical reactions in the assay. In this paper, we tested and modeled different geometries of thermally actuated valves to investigate how they can be more easily implemented in an LFIA with precise control of actuation time, flow rate, and flow pattern. We demonstrate that bulk flow measurements alone cannot estimate the highly variable microscale properties and effects on LFIA signal development. To further quantify the microfluidic properties of paper-fluidic devices, micro-particle image velocimetry was used to quantify fluorescent nanoparticle flow through the membranes and demonstrated divergent properties from bulk flow that may explain additional variability in LFIA signal generation. Altogether, we demonstrate that a more robust characterization of paper-fluidic devices can permit fine-tuning of parameters for precise automation of multi-step assays and inform analytical models for more efficient design.

Sample-to-answer, extraction-free, real-time RT-LAMP test for SARS-CoV-2 in nasopharyngeal, nasal, and saliva samples: Implications and use for surveillance testing.

The global COVID-19 pandemic has highlighted the need for rapid, accurate and accessible nucleic acid tests to enable timely identification of infected individuals. We optimized a sample-to-answer nucleic acid test for SARS-CoV-2 that provides results in <1 hour using inexpensive and readily available reagents. The test workflow includes a simple lysis and viral inactivation protocol followed by direct isothermal amplification of viral RNA using RT-LAMP. The assay was validated using two different instruments, a portable isothermal fluorimeter and a standard thermocycler. Results of the RT-LAMP assay were compared to traditional RT-qPCR for nasopharyngeal swabs, nasal swabs, and saliva collected from a cohort of patients hospitalized due to COVID-19. For all three sample types, positive agreement with RT-LAMP performed using the isothermal fluorimeter was 100% for samples with Ct <30 and 69-91% for samples with Ct <40. Following validation, the test was successfully scaled to test the saliva of up to 400 asymptomatic individuals per day as part of the campus surveillance program at Rice University. Successful development, validation, and scaling of this sample-to-answer, extraction-free real-time RT-LAMP test for SARS-CoV-2 adds a highly adaptable tool to efforts to control the COVID-19 pandemic, and can inform test development strategies for future infectious disease threats.

Understanding factors relevant to poor sleep and coping methods in people with schizophrenia.

BACKGROUND: Sleep disruption is pervasive in people with schizophrenia, but few studies have explored their sleep experiences. This study aims to identify factors relevant to sleep problems and explore coping methods used by community-dwelling people with schizophrenia. METHODS: Eighteen participants with schizophrenia were recruited from three mental health centers in Taiwan. They completed a semi-structured interview and the Pittsburgh Sleep Quality Index (PSQI) assessment. The Person-Environment-Occupation model offered a framework to assess factors related to sleep. Thematic analysis was used for the qualitative data analysis. RESULTS: Factors related to sleep were classified under person, environment, and occupation domains. The person domain included three subthemes: psychiatric symptoms, unpleasant emotions, and frustration about sleep. The environment domain included three subthemes: sensory intrusions from the environment, quality of bedding, and roommates. The occupation domain included sleep interruption and sleep preparation. There were notable discrepancies in sleep quality between the participants' narratives and their PSQI global scores. Regarding coping methods for poor sleep, sleep medication was the primary strategy while some participants also used other strategies, such as modifying the environment, adjusting routines, or engaging in activities that improve sleep quality. CONCLUSIONS: Psychiatric symptoms and nightmares were identified as unique sleep disruptions in people with schizophrenia, and poor economic status was also found to impact their sleep. The sleep quality of people with schizophrenia tends to be poor, as identified by the PSQI, even though they may have positive perceptions of their sleep quality. Our participants appeared to prefer to take hypnotics to address their sleep problems, which may be due to limited knowledge about alternatives. Mental health professionals are encouraged to receive training in the application of non-pharmacological approaches to support their clients' issues related to sleep.

KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability.

We have performed 280 µs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise analysis of the Kelch domain points to stability as a possible target of cancer in KEAP1. Interestingly, structural analysis of the R470C ANCHOR mutant, the most prevalent missense mutation in KEAP1, revealed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating an covalent modification as this mutant's mode of action.

Association of COVID-19 transmission with high levels of ambient pollutants: Initiation and impact of the inflammatory response on cardiopulmonary disease.

Ambient air pollution contributes to 7 million premature deaths annually. Concurrently, the ongoing coronavirus disease 2019 (COVID-19) pandemic, complicated with S-protein mutations and other variants, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in over 2.5 million deaths globally. Chronic air pollution-mediated cardiopulmonary diseases have been associated with an increased incidence of hospitalization and mechanical ventilation following COVID-19 transmission. While the underlying mechanisms responsible for this association remain elusive, air pollutant-induced vascular oxidative stress and inflammatory responses have been implicated in amplifying COVID-19-mediated cytokine release and vascular thrombosis. In addition, prolonged exposure to certain types of particulate matter (PM2.5, d < 2.5 µm) has also been correlated with increased lung epithelial and vascular endothelial expression of the angiotensin-converting enzyme-2 (ACE2) receptors to which the SARS-CoV-2 spike glycoproteins (S) bind for fusion and internalization into host cells. Emerging literature has linked high rates of SARS-CoV-2 infection to regions with elevated levels of PM2.5, suggesting that COVID-19 lockdowns have been implicated in regional reductions in air pollutant-mediated cardiopulmonary effects. Taken together, an increased incidence of SARS-CoV-2-mediated cardiopulmonary diseases seems to overlap with highly polluted regions. To this end, we will review the redox-active components of air pollutants, the pathophysiology of SARS-CoV-2 transmission, and the key oxidative mechanisms and ACE2 overexpression underlying air pollution-exacerbated SARS-CoV-2 transmission.

Exploring the Conformational Landscape of the Neh4 and Neh5 Domains of Nrf2 Using Two Different Force Fields and Circular Dichroism.

The nuclear factor erythroid 2-related factor 2 (Nrf2)-ARE transcriptional response pathway plays a critical role in protecting the cell from oxidative stresses via the upregulation of cytoprotective genes. Aberrant activation of Nrf2 in cancer cells can confer this cytoprotectivity, thereby reducing the efficacy of both chemotherapeutics and radiotherapies. Key to this antioxidant pathway is the interaction between Nrf2 and CREB binding protein (CBP), mediated by the Neh4 and Neh5 domains of Nrf2. Disruption of this interaction via small-molecule therapeutics could negate the effects of aberrant Nrf2 upregulation. Due to the disordered nature of these domains, there remains no three-dimensional structure of Neh4 or Neh5, making structure-based drug design a challenge. Here, we performed 48 µs of unbiased molecular dynamics (MD) simulations with the Amber99SB*-ILDNP and CHARMM36m force fields and circular dichroism (CD) spectropolarimetry experiments to elucidate the free-state structures of these domains; no previous data regarding their conformational landscapes exists. There are two main findings: First, we find Neh5 to be markedly more disordered than Neh4, which has nine residues in the middle of the domain showing α-helical propensity, thus pointing to Neh4 and Neh5 having different binding mechanisms. Second, the two force fields show strong differences for the glutamic acid-rich Neh5 peptide but are in reasonable agreement for Neh4, which has no glutamic acid. The CHARMM36m force field agrees more closely with the CD results.

Allele-Specific Recombinase Polymerase Amplification to Detect Sickle Cell Disease in Low-Resource Settings.

Sickle cell disease (SCD) is a group of common, life-threatening disorders caused by a point mutation in the ß globin gene. Early diagnosis through newborn and early childhood screening, parental education, and preventive treatments are known to reduce mortality. However, the cost and complexity of conventional diagnostic methods limit the feasibility of early diagnosis for SCD in resource-limited areas worldwide. Although several point-of-care tests are commercially available, most are antibody-based tests, which cannot be used in patients who have recently received a blood transfusion. Here, we describe the development of a rapid, low-cost nucleic acid test that uses real-time fluorescence to detect the point mutation encoding hemoglobin S (HbS) in one round of isothermal recombinase polymerase amplification (RPA). When tested with a set of clinical samples from SCD patients and healthy volunteers, our assay demonstrated 100% sensitivity for both the ßA globin and ßS globin alleles and 94.7 and 97.1% specificities for the ßA globin allele and ßS globin allele, respectively (n = 91). Finally, we demonstrate proof-of-concept sample-to-answer genotyping of genomic DNA from capillary blood using an alkaline lysis procedure and direct input of diluted lysate into RPA. The workflow is performed in <30 min at a cost of <$5 USD on a commercially available benchtop fluorimeter and an open-source miniature fluorimeter. This study demonstrates the potential utility of a rapid, sample-to-answer nucleic acid test for SCD that may be implemented near the point of care and could be adapted to other disease-causing point mutations in genomic DNA.

Improving Performance of a SARS-CoV-2 RT-LAMP Assay for Use With a Portable Isothermal Fluorimeter: Towards a Point-of-Care Molecular Testing Strategy.

Frequent and accessible testing is a critical tool to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To develop low-cost rapid tests, many researchers have used reverse transcription loop-mediated isothermal amplification (RT-LAMP) with fluorescent readout. Fluorescent LAMP-based assays can be performed using cost-effective, portable, isothermal instruments that are simpler to use and more rugged than polymerase chain reaction (PCR) instruments. However, false-positive results due to nonspecific priming and amplification have been reported for a number of LAMP-based assays. In this report, we implemented a RT-LAMP assay for SARS-CoV-2 on a portable isothermal fluorimeter and a traditional thermocycler; nonspecific amplification was not observed using the thermocycler but did occur frequently with the isothermal fluorimeter. We explored 4 strategies to optimize the SARS-CoV-2 RT-LAMP assay for use with an isothermal fluorimeter and found that overlaying the reaction with mineral oil and including the enzyme Tte UvrD helicase in the reaction eliminated the problem. We anticipate these results and strategies will be relevant for use with a wide range of portable isothermal instruments.

Interventions Within the Scope of Occupational Therapy Practice to Improve Performance of Daily Activities for Older Adults With Low Vision: A Systematic Review.

IMPORTANCE: The prevalence of low vision increases with age. Low vision has detrimental effects on older adults' independence. OBJECTIVE: To identify the effectiveness of interventions within the scope of occupational therapy practice to maintain, restore, and improve performance in daily activities for older adults with low vision. DATA SOURCES: Literature published between 2010 and 2017 was searched in CINAHL, Cochrane Databases, MEDLINE, OTseeker, and PsycINFO. STUDY SELECTION AND DATA COLLECTION: The authors screened and appraised studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Studies were eligible if the participants' mean age was 55 yr or older, the level of evidence was Level III or higher, the intervention was within the scope of occupational therapy practice, and the outcome measures assessed the performance of daily activities. FINDINGS: Fourteen studies met the review criteria. Three intervention themes were identified: low vision rehabilitation services (n = 6), self-management approach (n = 6), and tango (n = 2). Moderate evidence was found for low vision rehabilitation services. Low evidence was found for using the self-management approach or adding the self-management approach to existing low vision rehabilitation services. Low evidence was found for tango. CONCLUSION AND RELEVANCE: This systematic review supports the use of low vision rehabilitation services as an effective approach. Occupational therapy practitioners are encouraged to be part of multidisciplinary teams that offer comprehensive low vision evaluations and multicomponent services. WHAT THIS ARTICLE ADDS: Low vision rehabilitation that offers multidisciplinary services, including occupational therapy, is effective in promoting independence among older adults with low vision.