Intersectionality and Social Security Age-18 Redetermination: Reducing the Stress and Trauma of Transition for Black Transition-Age Youth with Disabilities.

Greater attention is being paid to the transition to adulthood for youth with disabilities. We are also at a period of reckoning with the vestiges of slavery, Jim Crow, and a lack of constitutional protections for Black-identifying persons. The contemporary impact of inequitable access to opportunities, services, and supports that would improve the quality of life of racialized Black individuals has added consequences for Black youth with disabilities. A sub-population of youth with disabilities receives monthly support in the form of Supplemental Security Income (SSI), with a disproportionate number of Black-identifying youth qualifying for SSI. Such youth are impacted by the intersectionality of racism, disability, and poverty. The outcome of an SSI age-18 redetermination can be precarious and occurs in the backdrop of these intersectional forces, impacting the life course of racialized Black youth and their families on a scale that is concerning. The authors describe the time frames of pre age-18 redetermination, age-18 redetermination and post age-18 redetermination in the contexts of intersectionality and transition, and articulate what type of services and supports can reduce the experience of chronic stress in the lives of racialized Black youth facing an SSI age-18 redetermination, and thereby improve the outcomes of these youth as they transition to adulthood.

Hospitalization and Mortality for Insured Patients in the United States with COVID-19 with and without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neuropsychiatric condition that may be associated with negative health outcomes. This retrospective cohort study reveals the odds of hospitalization and mortality based on ASD for a population of insured patients with COVID-19. The odds of hospitalization and mortality for people with ASD were found to be greater than individuals without ASD when adjusted for sociodemographic characteristics. Hospitalization and mortality was associated with a dose-response increase to comorbidity counts (1 to 5+). Odds of mortality remained greater for those with ASD when adjusting for comorbid health conditions. ASD is a risk factor for COVID-19 mortality. Comorbid health conditions play a particular role in increasing the odds of COVID-19 related hospitalization and death for ASD patients.

Electrospinning Drug-Loaded Alginate-Based Nanofibers towards Developing a Drug Release Rate Catalog.

Electrospinning natural polymers represents a developing interest in the field of biomaterials. Electrospun nanofibers have been shown to facilitate tissue regeneration and emulate body tissue, making them ideal for modern biomedical applications. These water-soluble natural polymers including alginate, have also shown promise as drug delivery vehicles. However, many biopolymers including alginate are inherently charged, making the formation of nanofibers difficult. To better understand the potential of natural polymer-based fibers in drug delivery applications, fiber formulations and drug loading concentrations of alginate-based scaffolds were investigated. It was found electrospinning poly(vinyl alcohol) with alginate facilitated fiber formation while the co-polymer agarose showed minor improvement in terms of alginate electrospinnability. Once uniform fibers were formed, the antibiotic ciprofloxacin was added into the polymer electrospinning solution to yield drug-loaded nanofibers. These optimized parameters coupled with small molecule release rate data from the drug-loaded, alginate-based fibers have been used to establish a catalog of small molecule release profiles. In the future, this catalog will be further expanded to include drug release rate data from other innately charged natural polymer-based fibers such as chitosan. It is anticipated that the cataloged profiles can be applied in the further development of biomaterials used in drug delivery.

Crystal structure of a hypothetical protein from Giardia lamblia. Corrigendum.

The name of one of the authors in Beard et al. [(2022), Acta Cryst. F78, 59-65] is corrected.

Crystal structure of a hypothetical protein from Giardia lamblia.

Giardiasis is the most prevalent diarrheal disease globally and affects humans and animals. It is a significant problem in developing countries, the number one cause of travelers' diarrhea and affects children and immunocompromised individuals, especially HIV-infected individuals. Giardiasis is treated with antibiotics (tinidazole and metronidazole) that are also used for other infections such as trichomoniasis. The ongoing search for new therapeutics for giardiasis includes characterizing the structure and function of proteins from the causative protozoan Giardia lamblia. These proteins include hypothetical proteins that share 30% sequence identity or less with proteins of known structure. Here, the atomic resolution structure of a 15.6 kDa protein was determined by molecular replacement. The structure has the two-layer αß-sandwich topology observed in the prototypical endoribonucleases L-PSPs (liver perchloric acid-soluble proteins) with conserved allosteric active sites containing small molecules from the crystallization solution. This article is an educational collaboration between Hampton University and the Seattle Structural Genomics Center for Infectious Disease.

Characteristics, treatment, and outcomes of Myasthenia Gravis in COVID-19 patients: A systematic review.

OBJECTIVE: Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19. METHODS: We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics. RESULTS: Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%). CONCLUSION: This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.

Examination of Race and Autism Intersectionality Among African American/Black Young Adults.

Background: African American/Black (AA/B) young adults with diagnoses of autism spectrum disorders rarely are studied in a way that acknowledges both their racial identity and their autism diagnosis. Little is known about intersectional oppression in the lives of these young adults. Early adulthood is a time when a young people of color may come to terms with a society that may not treat them fairly and equally due to their race. Autistic AA/B young adults may be even more vulnerable to stress and psychological disempowerment due to the added impact of negative experiences of being Black and having an autism diagnosis. Methods: Thirty-two autistic and 30 non-autistic AA/B young adults took part in an online survey examining risk factors of everyday discrimination, perceived stress and potential protective factors of psychological empowerment, and Black identity. Differences in score measures for the autistic and non-autistic samples were examined along with the predictors of perceived stress assessed. Frequencies of intersectional discrimination experiences were also examined. Results: Autistic AA/B participants reported significantly less everyday discriminatory experiences than non-autistic AA/B participants, whereas perceived stress was not significantly different between the two groups. The majority of non-autistic AA/B participants endorsed race as their prime source of experiences of discrimination, whereas autistic AA/B participants also cited being autistic as a major contributor to reports of discrimination. Although the autistic group had significantly lower reports of self-determination, they reported higher on the Black identity, private regard scale, pertaining to feelings about group membership, which can be considered a protective factor. There is heterogeneity in reasons for discriminatory experiences for autistic AA/B young adults whereby some of the participants (12%-30%) endorsed race + disability as dual reasons for experiencing regular discrimination. Conclusions: Mental health clinicians and other direct service providers working with autistic AA/B young adults should understand that intersecting identities of race and disability may be at play when they are working with these individuals, and that treatment should consider these factors.

Why is this an important issue?: The experiences of autistic African American/Black adults need more attention. There is not much research looking at intersecting identities of race and disability. What was the purpose of this study?: The purpose of this study was to examine race + disability intersectionality in discrimination experiences and to examine how risk factors and protective factors vary between autistic and non-autistic African American/Black young adults. What did the researchers do?: The researchers conducted an online study comparing the experiences of autistic and non-autistic young adults who identified as African American/Black. Thirty-two autistic and 30 non-autistic African American/Black young adults took part in the study looking at experiences of discrimination, stress, Black identity, and self-determination. What were the results of the study?: Autistic African American/Black participants reported fewer everyday discriminatory experiences than non-autistic African American/Black participants, but perceived stress was not different between the two groups. Most of the non-autistic African American/Black participants listed race as their prime source of discrimination experiences, whereas autistic African American/Black participants also cited being autistic as a major contributor to reports of discrimination. Reasons for discriminatory experiences for autistic African American/Black young adults are varied, with up to 30% relating to experiences of discrimination being dual issues of race and disability. What do these findings add to what was already known?: There is a lot of research on the experiences of African African/Black people facing social adversities due to race. This study adds to what is known by shedding light on discrimination experiences of autistic African American/Black young adults. The findings show the need for both societal change and trauma-informed practices with autistic individuals who are negatively impacted by a society that views them through a racialized lens. What are potential weaknesses in the study?: This study is not reflective of all autistic African American/Black people. Individuals who took part in the study may have self-selected due to interest in the topic. In addition, gender was not taken into account for this study. How will these findings help autistic adults now or in the future?: Knowing more about autistic African American/Black young adults' experiences can help inform advocacy to reduce discrimination and interventions to promote resiliency. The results of this study also highlight the importance of studying intersectionality in disability research. More research is needed about the experiences of autistic African American/Black young adults.

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. METHODS: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. RESULTS: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. CONCLUSION: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads to mortality. Outcomes of patients with COVID-19-related ARDS compared to ARDS unrelated to COVID-19 is not well characterized. AREAS COVERED: We performed a systematic review of PubMed, Scopus, and MedRxiv 11/1/2019 to 3/1/2021, including studies comparing outcomes in COVID-19-related ARDS (COVID-19 group) and ARDS unrelated to COVID-19 (ARDS group). Outcomes investigated were duration of mechanical ventilation-free days, intensive care unit (ICU) length-of-stay (LOS), hospital LOS, and mortality. Random effects models were fit for each outcome measure. Effect sizes were reported as pooled median differences of medians (MDMs), mean differences (MDs), or odds ratios (ORs). EXPERT OPINION: Ten studies with 2,281 patients met inclusion criteria (COVID-19: 861 [37.7%], ARDS: 1420 [62.3%]). There were no significant differences between the COVID-19 and ARDS groups for median number of mechanical ventilator-free days (MDM: -7.0 [95% CI: -14.8; 0.7], p = 0.075), ICU LOS (MD: 3.1 [95% CI: -5.9; 12.1], p = 0.501), hospital LOS (MD: 2.5 [95% CI: -5.6; 10.7], p = 0.542), or all-cause mortality (OR: 1.25 [95% CI: 0.78; 1.99], p = 0.361). Compared to the general ARDS population, results did not suggest worse outcomes in COVID-19-related ARDS.

Efficacy of convalescent plasma therapy for COVID-19: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID-19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID-19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full-text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta-analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = -0.49 days [95% CI = -3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID-19.

Remdesivir therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials that examined remdesivir treatment for COVID-19. MATERIALS AND METHODS: A systematic literature search was performed using Pubmed, Embase, and ClinicalTrials.gov to identify studies published up to October 25, 2020 that examined COVID-19 treatment with remdesivir. A total of 3 randomized controlled trials that consisted of 1691 patients were included in the meta-analysis. RESULTS: The odds for mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) following treatment was significantly lower in the remdesivir group compared to the control group (OR = 0.48 [95% CI: 0.34; 0.69], p < 0.001). The odds of early (at day 14/15; OR = 1.42 [95% CI: 1.16; 1.74], p < 0.001) and late (at day 28/29; OR = 1.44 [95% CI: 1.16; 1.79], p = 0.001) hospital discharge were significantly higher in the remdesivir group compared to the control group. There was no difference in the odds for mortality in patients treated with remdesivir (OR = 0.77 [95% CI: 0.56; 1.06], p = 0.108). CONCLUSIONS: Remdesivir attenuates disease progression, leading to lower odds of MV/ECMO and greater odds of hospital discharge for COVID-19 patients. However, remdesivir does not affect odds of mortality.

Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.

A Systematic Review of Intracranial Aneurysms in the Pregnant Patient - A Clinical Conundrum.

Hemodynamic and hormonal changes during pregnancy can increase rates of formation, growth, and rupture of intracranial aneurysms (IA), and the increased incidence of subarachnoid hemorrhage (SA) in pregnant patients represents a risk to both mother and fetus. Despite this, management and treatment guidelines have not been defined for this patient population. In most instances, treatment decisions are made on a case-by-case basis with varying degrees of input from subspecialists. Important considerations, such as aneurysm location, morphology, size, growth pattern, and patient characteristics have not been presented in a management algorithm in the context of the pregnant patient. Given limited and controversial literature describing management of IAs in pregnant patients, we performed a systematic literature review. We then describe our multidisciplinary team approach and provide analysis of existing literature to provide guidelines for the management of the pregnant patient with an IA. A systematic review was undertaken to identify studies describing the management of IAs in the pregnant patient using the PubMed database. Overall maternal and fetal morbidity and mortality rates were determined. Data was analyzed for 1537 patients, including 1115 (73%) pregnant with ruptured intracranial aneurysms. In most cases, these aneurysms were managed conservatively (77%; 781/1013); however, when treatment was provided, surgical clipping was the most common modality (15%; 149/1013). Overall maternal outcomes were reported for 934 cases with morbidity and mortality rates of 5% (42/934) and 21% (194/934), respectively. Overall fetal outcomes were reported for 114 cases with morbidity and mortality rates of 10% (12/119) and 8% (9/119), respectively. Pregnancy-associated physiological changes likely elevate the risk of intracranial aneurysm formation, growth, and rupture. Treatment for aneurysms and SAs is safe and effective during pregnancy when risks are properly mitigated. Due to the complexity of care, such patients should be treated using a collaborative, interdisciplinary approach by a multidisciplinary team.

Inequities in Family Quality of Life for African-American Families Raising Children with Disabilities.

Over time, groundbreaking changes in societies' views and treatment of persons with disabilities, along with significant legislative and policy changes, have impacted the quality of life of African-American families raising children with disabilities. This article presents some of the challenges and inequities faced by African-American families that impact their quality of life using critical race theory (CRT). Also, it reviews results obtained by a study of 123 African-American families raising children with disabilities. The article offers implications for policy and practice and discusses the role for social workers in addressing disparities in healthcare and other areas.

Establishment of the Alabama Hereditary Cancer Cohort - strategies for the inclusion of underrepresented populations in cancer genetics research.

BACKGROUND: Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies. METHODS: Two approaches, hospital and community-based recruitment (CBR), were developed and implemented over 36 months to study the genetics of hereditary breast cancer and associated cancers in Alabama, a medically underserved state with double the national percentage of self-identifying African Americans, establishing the Alabama Hereditary Cancer Cohort. RESULTS: Overall, 242 individuals enrolled. This included 84 cancer probands through hospital recruitment, as well as 76 probands and 82 family members through CBR. Eighty-one percent of the study participants' counties of residence are completely medically underserved. Furthermore, African Americans represent 26% of the hospital probands compared to 49% and 70% of the probands and family members who, respectively, enrolled through CBR. CONCLUSION: Although both recruitment mechanisms were instrumental, the unique trust building, educational, and traveling components of CBR facilitated the enrollment of African Americans resulting in large families for genetic analyses. The ultimate goal is to gain insight from these rudimentary efforts in order to expand recruitment and accrue a unique resource for cancer genetics research.

Sequence selectivity of macrolide-induced translational attenuation.

The prevailing "plug-in-the-bottle" model suggests that macrolide antibiotics inhibit translation by binding inside the ribosome tunnel and indiscriminately arresting the elongation of every nascent polypeptide after the synthesis of six to eight amino acids. To test this model, we performed a genome-wide analysis of translation in azithromycin-treated Staphylococcus aureus. In contrast to earlier predictions, we found that the macrolide does not preferentially induce ribosome stalling near the 5' end of mRNAs, but rather acts at specific stalling sites that are scattered throughout the entire coding region. These sites are highly enriched in prolines and charged residues and are strikingly similar to other ligand-independent ribosome stalling motifs. Interestingly, the addition of structurally related macrolides had dramatically different effects on stalling efficiency. Our data suggest that ribosome stalling can occur at a surprisingly large number of low-complexity motifs in a fashion that depends only on a few arrest-inducing residues and the presence of a small molecule inducer.

Near-infrared surface-enhanced Raman spectroscopy (NIR-SERS) for the identification of eosin Y: theoretical calculations and evaluation of two different nanoplasmonic substrates.

This work demonstrates the development of near-infrared surface-enhanced Raman spectroscopy (NIR-SERS) for the identification of eosin Y, an important historical dye. NIR-SERS benefits from the absence of some common sources of SERS signal loss including photobleaching and plasmonic heating, as well as an advantageous reduction in fluorescence, which is beneficial for art applications. This work also represents the first rigorous comparison of the enhancement factors and the relative merits of two plasmonic substrates utilized in art applications; namely, citrate-reduced silver colloids and metal film over nanosphere (FON) substrates. Experimental spectra are correlated in detail with theoretical absorption and Raman spectra calculated using time-dependent density functional theory (TDDFT) in order to elucidate molecular structural information and avoid relying on pigment spectral libraries for dye identification.

RNA CoSSMos: Characterization of Secondary Structure Motifs--a searchable database of secondary structure motifs in RNA three-dimensional structures.

RNA secondary structure is important for designing therapeutics, understanding protein-RNA binding and predicting tertiary structure of RNA. Several databases and downloadable programs exist that specialize in the three-dimensional (3D) structure of RNA, but none focus specifically on secondary structural motifs such as internal, bulge and hairpin loops. The RNA Characterization of Secondary Structure Motifs (RNA CoSSMos) database is a freely accessible and searchable online database and website of 3D characteristics of secondary structure motifs. To create the RNA CoSSMos database, 2156 Protein Data Bank (PDB) files were searched for internal, bulge and hairpin loops, and each loop's structural information, including sugar pucker, glycosidic linkage, hydrogen bonding patterns and stacking interactions, was included in the database. False positives were defined, identified and reclassified or omitted from the database to ensure the most accurate results possible. Users can search via general PDB information, experimental parameters, sequence and specific motif and by specific structural parameters in the subquery page after the initial search. Returned results for each search can be viewed individually or a complete set can be downloaded into a spreadsheet to allow for easy comparison. The RNA CoSSMos database is automatically updated weekly and is available at http://cossmos.slu.edu.

Structural characterization of naturally occurring RNA single mismatches.

RNA is known to be involved in several cellular processes; however, it is only active when it is folded into its correct 3D conformation. The folding, bending and twisting of an RNA molecule is dependent upon the multitude of canonical and non-canonical secondary structure motifs. These motifs contribute to the structural complexity of RNA but also serve important integral biological functions, such as serving as recognition and binding sites for other biomolecules or small ligands. One of the most prevalent types of RNA secondary structure motifs are single mismatches, which occur when two canonical pairs are separated by a single non-canonical pair. To determine sequence-structure relationships and to identify structural patterns, we have systematically located, annotated and compared all available occurrences of the 30 most frequently occurring single mismatch-nearest neighbor sequence combinations found in experimentally determined 3D structures of RNA-containing molecules deposited into the Protein Data Bank. Hydrogen bonding, stacking and interaction of nucleotide edges for the mismatched and nearest neighbor base pairs are described and compared, allowing for the identification of several structural patterns. Such a database and comparison will allow researchers to gain insight into the structural features of unstudied sequences and to quickly look-up studied sequences.

Positional and neighboring base pair effects on the thermodynamic stability of RNA single mismatches.

Many naturally occurring RNA structures contain single mismatches, many of which occur near the ends of helices. However, previous thermodynamic studies have focused their efforts on thermodynamically characterizing centrally placed single mismatches. Additionally, algorithms currently used to predict secondary structure from sequence are based on two assumptions for predicting the stability of RNA duplexes containing this motif. It has been assumed that the thermodynamic contribution of small RNA motifs is independent of both its position in the duplex and the identity of the non-nearest neighbors. Thermodynamically characterizing single mismatches three nucleotides from both the 3' and 5' ends (i.e., off-center) of an RNA duplex and comparing these results to those of the same single mismatch-nearest neighbor combination centrally located have allowed for the investigation of these effects. The thermodynamic contributions of 13 single mismatch-nearest neighbor combinations are reported, but only nine combinations are studied at all three duplex positions and are used to determine trends and patterns. In general, the 5'- and 3'-shifted single mismatches are relatively similar, on average, and more favorable in free energy than centrally placed single mismatches. However, close examination and comparison shows there are several associated idiosyncrasies with these identified general trends. These peculiarities may be due, in part, to the identities of the single mismatch, the nearest neighbors, and the non-nearest neighbors, along with the effects of the single mismatch position in the duplex. The prediction algorithm recently proposed by Davis and Znosko [Davis, A. R., and Znosko, B. M. (2008) Biochemistry 47, 10178-10187] is used to predict the thermodynamic parameters of single mismatch contribution, and those values are compared to the measured values presented here. This comparison suggests the proposed model is a good approximation but could be improved by the addition of parameters that account for positional and/or non-nearest neighbor effects. However, more data are required to improve our understanding of these effects and to accurately account for them.