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ObjectiveThe presence of diabetes before or during pregnancy can increase perinatal mortality and morbidities. It is well known an infant of a diabetic mother (IDM) may experience complications such as macrosomia, hypoglycemia, respiratory distress syndrome, cardiac anomalies, and other abnormalities of organogenesis. Medical providers including physicians, nurses, and speech therapists have experienced challenges with helping IDMs orally feed. Challenges with oral feeding can lead to prolonged hospital stays and placement of supplemental feeding devices. The etiology of an IDM's oral feeding delays is not well understood and does not necessarily affect all infants.Study designThis descriptive review explores what is known about potential contributing factors to feeding difficulty in IDMs, including differences in infant behavior and swallowing mechanics.ResultsSome IDMs are unable to maintain active alert states and have decreased autonomic regulation and motor control. Studies of sucking and swallowing demonstrate reduced sucking pressure, fewer sucking bursts, and slowing of esophageal sphincter function.ConclusionThe increasing prevalence of diabetes during pregnancy makes further investigations into the characteristics and trajectories of state, behavior, and oral feeding of IDMs imperative.

BackgroundIn a large pedigree with an unusual phenotype of spastic paraplegia or dystonia and autosomal dominant inheritance, linkage analysis previously mapped the disease to chromosome 2q24-2q31.ObjectiveThe aim of this study is to identify the genetic cause and molecular basis of an unusual autosomal dominant spastic paraplegia and dystonia.MethodsWhole exome sequencing following linkage analysis was used to identify the genetic cause in a large family. Cosegregation analysis was also performed. An additional 384 individuals with spastic paraplegia or dystonia were screened for pathogenic sequence variants in the adenosine triphosphate (ATP) synthase membrane subunit C locus 3 gene (ATP5MC3). The identified variant was submitted to the "GeneMatcher" program for recruitment of additional subjects. Mitochondrial functions were analyzed in patient-derived fibroblast cell lines. Transgenic Drosophila carrying mutants were studied for movement behavior and mitochondrial function.ResultsExome analysis revealed a variant (c.318C > G; p.Asn106Lys) (NM_001689.4) in ATP5MC3 in a large family with autosomal dominant spastic paraplegia and dystonia that cosegregated with affected individuals. No variants were identified in an additional 384 individuals with spastic paraplegia or dystonia. GeneMatcher identified an individual with the same genetic change, acquired de novo, who manifested upper-limb dystonia. Patient fibroblast studies showed impaired complex V activity, ATP generation, and oxygen consumption. Drosophila carrying orthologous mutations also exhibited impaired mitochondrial function and displayed reduced mobility.ConclusionA unique form of familial spastic paraplegia and dystonia is associated with a heterozygous ATP5MC3 variant that also reduces mitochondrial complex V activity.

PurposeTo understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care.MethodsThirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments.ResultsMedical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities.ConclusionBy direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

The remote instruction context presents many challenges for teachers, including managing student behavior. The practice of defining and teaching expectations is considered a high-leverage practice in special education, and should be applied to the remote setting to support the learning of students with and without disabilities. We present four recommended steps for adapting this practice for the remote setting and use a fictional vignette with example materials to demonstrate the process. Additionally, we provide other useful online resources for providing effective online instruction for students with disabilities.

Purpose: This study aimed at examining differences in satisfaction with the employment situation between employed and unemployed Latinx with multiple sclerosis (MS) in the United States (N = 148). Method: Participants in this study responded to a national survey of the employment and community living concerns of people with MS. Multivariate analysis of variance and a follow-up univariate analysis of variance were conducted to compare the group differences. Results: The analyses revealed statistically significant between-group differences in satisfaction ratings on items pertaining to personal and environmental resources and fair treatment, but no significant between-group differences in response to items related to legal rights. Conclusion: The findings in this study confirmed our a priori expectation that satisfaction ratings regarding the overall employment situation among Latinx Americans with MS would vary as a function of their workforce participation status. Implications for future research and clinical practice in vocational rehabilitation in the COVID-19 era are discussed.

The FaceBase Consortium was established by the National Institute of Dental and Craniofacial Research in 2009 as a 'big data' resource for the craniofacial research community. Over the past decade, researchers have deposited hundreds of annotated and curated datasets on both normal and disordered craniofacial development in FaceBase, all freely available to the research community on the FaceBase Hub website. The Hub has developed numerous visualization and analysis tools designed to promote integration of multidisciplinary data while remaining dedicated to the FAIR principles of data management (findability, accessibility, interoperability and reusability) and providing a faceted search infrastructure for locating desired data efficiently. Summaries of the datasets generated by the FaceBase projects from 2014 to 2019 are provided here. FaceBase 3 now welcomes contributions of data on craniofacial and dental development in humans, model organisms and cell lines. Collectively, the FaceBase Consortium, along with other NIH-supported data resources, provide a continuously growing, dynamic and current resource for the scientific community while improving data reproducibility and fulfilling data sharing requirements.

Background: In exploring the matter of sensory loss and job discrimination, the National EEOC ADA Research Project (NEARP) seeks to answer a singular question. Objective: How do persons with hearing loss (HL) vs. visual loss (VL) experience the nature and scope of workplace discrimination differently, if at all? Methods: The NEARP team uses an ex post facto, causal comparative quantitative design that includes descriptive and inferential, nonparametric statistics. Closed EEOC files involving ADA allegations of workplace discrimination filed by Americans with Hearing Loss (HL, N = 21,847) and Vision Loss (VL, N = 16,136) were compared in terms of demographics, issues, and investigatory outcomes. Results: HL and VL groups show Demographic differences to one another and to population statistics of sensory impairment in the areas of Gender and Race/Ethnicity. Regarding Issues, HL and VL groups are different from one another with respect to several prevalent matters (i.e., Discharge, Reasonable Accommodation) and small-scale matters (i.e., Hiring and Terms/Conditions). With respect to the Merit of allegations following EEOC investigation, HL and VL are very similar. Conclusion: Workplace discrimination is experienced differently for Charging Parties who experience HL vs. VL. Moreover, important differences exist Charging Parties from both sensory impairments vs. those from a General Disability Population.

Purpose: The profession of rehabilitation counseling has long been responsive to emerging disabilities. To date, however, the profession's attention and response to the ongoing opioid crisis in the United States has been incommensurate with the scope and detriment of opioids and opioid use disorder (OUD) on Americans with disabilities. The opioid crisis, including the overuse, abuse, and overdose rates associated with prescription and illegal opioids, affects people of all ages and backgrounds. However, people with disabilities are at increased risk for developing OUDs, and they experience greater barriers to OUD treatment than people without disabilities. Method: This article describes the origins and development of this crisis, the relationship between disability and increased risk for OUD, and the barriers to treatment that exist. We then evaluate the role of rehabilitation counseling, including the need for further action in advocacy, research, education, and policy. Results and Conclusions: Throughout this article, we encourage a more urgent and concerted response than seems to be the case presently.

Live cell RNA imaging using genetically encoded fluorescent labels is an important tool for monitoring RNA activities. A recently reported RNA aptamer-fluorogen system, the Spinach, in which an RNA aptamer binds and induces the fluorescence of a GFP-like 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI) ligand, can be readily tagged to the RNA of interest. Although the aptamer-fluorogen system is sufficient for imaging highly abundant non-coding RNAs (tRNAs, rRNAs, etc.), it performs poorly for mRNA imaging due to low brightness. In addition, whether the aptamer-fluorogen system may perturb the native RNA characteristics has not been systematically characterized at the levels of RNA transcription, translation and degradation. To increase the brightness of these aptamer-fluorogen systems, we constructed and tested tandem arrays containing multiple Spinach aptamers (8-64 aptamer repeats). Such arrays enhanced the brightness of the tagged mRNA molecules by up to ~17 fold in living cells. Strong laser excitation with pulsed illumination further increased the imaging sensitivity of Spinach array-tagged RNAs. Moreover, transcriptional fusion to the Spinach array did not affect mRNA transcription, translation or degradation, indicating that aptamer arrays might be a generalizable labeling method for high-performance and low-perturbation live cell RNA imaging.

Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13); adjusted p= 2.2 x 10(-3)). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

The importance of Emotional Intelligence (EI) in daily life has received extensive attention over the past decade (Goleman, 1998). EI has been defined as the ability to observe the emotions of oneself and others while utilizing these observations in the direction of one's behavior and thinking (Salovey & Mayer, 1989). It has been suggested that, not only can EI be taught, but the level of awareness an individual possesses about his or her own emotions can be increased by instruction in EI (Bagshaw, 2000). Brackett and Katulak (2007) found EI training for school children resulted in better academic performance and interpersonal interactions. If an increase in the ability to perceive and regulate one's emotions while also recognizing the emotional states of others can occur as a result of training in EI, then, it is not contradictory to propose that this ability would be greater in those who engage in experiential related degree programs. This study assessed whether undergraduate students in experiential learning programs would exhibit higher levels of emotional intelligence than students in didactic learning programs.

Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb-29.3 Mb; p(raw )= 4.64 × 10(-15)). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans.

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.

Infections, readmissions, and mortalities after total joint arthroplasty (TJA) are serious complications, and transfusions have been associated with increased complication rates following TJA. Certain populations, including women, Black patients, patients who have public insurance and older adults have higher risks of transfusion. Recently, there has been a decline in transfusion rates and a greater emphasis on equity in medicine. This study examined whether disparities in transfusion rates still exist and what variables influence rates over time. We used a health care system database to identify 5,435 total knee arthroplasty (TKA) and 2,105 total hip arthroplasty (THA) patients from 2013 to 2021. Transfusion rates were 2.9 and 3.1% in the TKA and THA arthroplasty groups, respectively. White race represented 67.1 and 69.8% of the TKA and THA groups, respectively. Fisher exact and Wilcoxon rank sum tests were used to compare categorical and continuous variables. Multivariable logistic regressions were performed to predict transfusion rates within 5 days of surgery and adjust for potential confounders. Transfusion rates declined over time. However, Black patients had a higher rate of transfusion than White patients despite similar hemoglobin levels, 5.1 versus 1.8% (P <.001) in the TKA group and 4.1 versus 2.7% (P =.103) in the THA group. Following adjustment, the biggest factor associated with a higher transfusion risk in the TKA group was being Black (adjusted odds ratio = 2.2, 95% confidence interval = 1.55 to 3.13). Transfusion rates for TJA patients are declining; however, Black patients continued to receive transfusions at higher rates in patients receiving TKA. [ABSTRACT FROM AUTHOR]

BackgroundEven in the era of digital technology, several hospitals still rely on paper-based forms for data entry for patient admission, triage, drug prescriptions, and procedures. Paper-based forms can be quick and convenient to complete but often at the expense of data quality, completeness, sustainability, and automated data analytics. Digital forms can improve data quality by assisting the user when deciding on the appropriate response to certain data inputs (eg, classifying symptoms). Greater data quality via digital form completion not only helps with auditing, service improvement, and patient record keeping but also helps with novel data science and machine learning research. Although digital forms are becoming more prevalent in health care, there is a lack of empirical best practices and guidelines for their design. The study-based hospital had a definite plan to abolish the paper form; hence, it was not necessary to compare the digital forms with the paper form. ObjectiveThis study aims to assess the usability of three different interactive forms: a single-page digital form (in which all data input is required on one web page), a multipage digital form, and a conversational digital form (a chatbot). MethodsThe three digital forms were developed as candidates to replace the current paper-based form used to record patient referrals to an interventional cardiology department (Cath-Lab) at Altnagelvin Hospital. We recorded usability data in a counterbalanced usability test (60 usability tests: 20 subjects×3 form usability tests). The usability data included task completion times, System Usability Scale (SUS) scores, User Experience Questionnaire data, and data from a postexperiment questionnaire. ResultsWe found that the single-page form outperformed the other two digital forms in almost all usability metrics. The mean SUS score for the single-page form was 76 (SD 15.8; P=.01) when compared with the multipage form, which had a mean score of 67 (SD 17), and the conversational form attained the lowest scores in usability testing and was the least preferred choice of users, with a mean score of 57 (SD 24). An SUS score of >68 was considered above average. The single-page form achieved the least task completion time compared with the other two digital form styles. ConclusionsIn conclusion, the digital single-page form outperformed the other two forms in almost all usability metrics; it had the least task completion time compared with those of the other two digital forms. Moreover, on answering the open-ended question from the final customized postexperiment questionnaire, the single-page form was the preferred choice.

BackgroundWhen a patient is suspected of having an acute myocardial infarction, they are accepted or declined for primary percutaneous coronary intervention partly based on clinical assessment of their 12-lead electrocardiogram (ECG) and ST-elevation myocardial infarction criteria. ObjectiveWe retrospectively determined the agreement rate between human (specialists called activator nurses) and computer interpretations of ECGs of patients who were declined for primary percutaneous coronary intervention. MethodsVarious features of patients who were referred for primary percutaneous coronary intervention were analyzed. Both the human and computer ECG interpretations were simplified to either “suggesting” or “not suggesting” acute myocardial infarction to avoid analysis of complex heterogeneous and synonymous diagnostic terms. Analyses, to measure agreement, and logistic regression, to determine if these ECG interpretations (and other variables such as patient age, chest pain) could predict patient mortality, were carried out. ResultsOf a total of 1464 patients referred to and declined for primary percutaneous coronary intervention, 722 (49.3%) computer diagnoses suggested acute myocardial infarction, whereas 634 (43.3%) of the human interpretations suggested acute myocardial infarction (P

Student engagement is vital in enhancing the student experience and encouraging deeper learning. Involving students in the design of assessment criteria is one way in which to increase student engagement. In 2011, a marking matrix was used at Aston University (UK) for logbook assessment (Group One) in a project-based learning module. The next cohort of students in 2012 (Group Two) were asked to collaboratively redesign the matrix and were given a questionnaire about the exercise. Group Two initially scored a lower average logbook mark than Group One. However, Group Two showed the greatest improvement between assessments, and the quality of, and commitment to, logbooks was noticeably improved. Student input resulted in a more defined, tougher mark scheme. However, this provided an improved feedback system that gave more scope for self-improvement. The majority of students found the exercise incorporated their ideas, enhanced their understanding, and was useful in itself.

Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.

Discusses the unique factors that online electronic resources pose in school library settings. Topics include the appropriateness of online electronic resources; strategic planning for Internet access, including acceptable use policies; administrative issues; selection and acquisition; organization; and intellectual access, including library instruction to meet information and technology literacy standards. (Author/LRW)