An Innovative Approach to Deliver Student-Directed Livestream Simulations During a Pandemic.

ABSTRACT: University and facility closures because of COVID-19 required nursing programs to develop innovative ways to ensure students met clinical hour requirements, standards, and expectations. One rural university utilized student-directed livestream virtual simulation sessions that included synchronous prebriefing, student-directed simulation activity, and immediate debriefing. Students were anonymously surveyed for feedback and evaluation of the activities. Students reported the sessions were helpful for learning and required use of prioritization, clinical judgment, and communication/collaboration skills. Other responses included communication issues, audiovisual issues, and low realism, which prompted future recommendations.

Evaluation and Student Perceptions of an OB Boot Camp Simulation for Undergraduate Nursing Students: A Mixed-Method Approach.

Obstetrical nursing offers unique challenges as a specialty clinical area as the process of birth and the nature of the setting are unpredictable. Traditional undergraduate baccalaureate nursing students may not have experience with maternal/newborn care. An eight-hour OB Boot Camp was developed to prepare students for their first obstetrical clinical rotation. An explanatory sequential mixed-method research study was used to explore student perceptions and evaluate the experience. On the basis of the results of this research study, the OB Boot Camp was a valuable instructional method to prepare students for obstetrical clinical rotations and coursework.

Clinical and genetic analyses of familial and sporadic frontotemporal dementia patients in Southern Italy.

INTRODUCTION: We investigated the clinical differences between familial and sporadic frontotemporal dementia (FTD), screening for mutations in known FTD genes. METHODS: We diagnosed 22 affected individuals belonging to eight families and 43 sporadic cases with FTD in Apulia, Southern Italy, in 2 years. Mutations in common causative FTD genes (GRN, MAPT, VCP, and TARDBP) and C9ORF72 expansions were screened. RESULTS: Behavioral variant of FTD was the most common clinical subtype (50% and 69% in familial and sporadic cases, respectively). Social conduct impairment/disinhibition, loss of insight, and inflexibility were the most frequent clinical features observed at onset. One new mutation was identified in GRN in family A. DISCUSSION: Disease onset in sporadic FTD was more frequently characterized by a clustering of behavioral symptoms with apathy and loss of personal hygiene. Mutations in common causative FTD genes are not a major cause of familial and sporadic FTD in the Southern Italian population.

A Novel Splice-Acceptor Site Mutation in GRN (c.709-2 A>T) Causes Frontotemporal Dementia Spectrum in a Large Family from Southern Italy.

Heterozygous loss of function mutations in granulin represent a significant cause of frontotemporal lobar degeneration with ubiquitin and TDP-43 inclusions (FTLD-TDP). We report a novel GRN splice site mutation (c.709-2 A>T), segregating with frontotemporal dementia spectrum in a large family from southern Italy. The GRN c.709-2 A>T is predicted to result in the skipping of exon 8, leading to non-sense mediated mRNA decay. Moreover, the PGRN plasma levels in the GRN c.709-2 A>T carriers were significantly lower (24 ng/ml) compared to controls (142.7 ng/ml) or family members non-carriers (82.0 ng/ml) (p-value = 0.005, Kruskal Wallis), suggesting progranulin haploinsufficiency. We do not report any potential pathogenic GRN mutation in a follow-up cohort composed of 6 FTD families and 43 sporadic FTD cases, from the same geographic area. Our study suggests that GRN (c.709-2 A>T) is a novel and likely very rare cause of FTD in this Italian cohort. Finally, in line with previous studies, we show that GRN haploinsufficiency leads to a heterogeneous clinical picture, and plasma progranulin levels may be a reliable tool to identify GRN loss of function mutations. However, given that a) genetic and environmental factors, gender, and age may regulate PGRN plasma levels and b) plasma progranulin levels may not reflect PGRN levels in the central nervous system, we suggest that the measurement of progranulin in the plasma should always be coupled with genetic screening of GRN for mutations.

A case of dementia with PRNP D178Ncis-129M and no insomnia.

OBJECTIVE: To describe a dementia case clinically diagnosed as Alzheimer disease with a PRNP genotype usually associated with familial fatal insomnia. METHODS: Polymerase chain reaction amplification and subsequent direct sequencing of PGRN, MAPT, PSEN1, PSEN2, APP, and PRNP genes. RESULTS: A point mutation (D178N) was found in the PRNP gene. CONCLUSIONS: The mutation D178N in the PRNP gene associated with the M129 genotype is usually associated with familial fatal insomnia. However, a few cases have been reported with different clinical phenotypes. Here, we describe one of these cases and stress the importance of genetic screening of PRNP in early onset dementia cases.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

Analysis of Nigerians with apparently sporadic Parkinson disease for mutations in LRRK2, PRKN and ATXN3.

Several genetic variations have been associated with Parkinson disease in different populations over the past few years. Although a considerable number of worldwide populations have been screened for these variants, results from Sub-Saharan populations are very scarce in the literature. In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3. No pathogenic mutations were found in any of the genes. Hence, common pathogenic mutations in these genes, observed in several different populations, are not a frequent cause of Parkinson disease in Nigeria.

TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis.

BACKGROUND: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. METHODOLOGY/PRINCIPAL FINDINGS: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus. CONCLUSIONS: Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American.

Structural genomic variation in ischemic stroke.

Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions; 3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study.

Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation.

BACKGROUND: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. OBJECTIVE: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. METHODS: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. RESULTS: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. CONCLUSIONS: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.

A genome-wide genotyping study in patients with ischaemic stroke: initial analysis and data release.

BACKGROUND: Despite evidence of a genetic role in stroke, the identification of common genetic risk factors for this devastating disorder remains problematic. We aimed to identify any common genetic variability exerting a moderate to large effect on risk of ischaemic stroke, and to generate publicly available genome-wide genotype data to facilitate others doing the same. METHODS: We applied a genome-wide high-density single-nucleotide-polymorphism (SNP) genotyping approach to a cohort of samples with and without ischaemic stroke (n=278 and 275, respectively), and did an association analysis adjusted for known confounders in a final cohort of 249 cases and 268 controls. More than 400,000 unique SNPs were assayed. FINDINGS: We produced more than 200 million genotypes in 553 unique participants. The raw genotypes of all the controls have been posted publicly in a previous study of Parkinson's disease. From this effort, results of genotype and allele association tests have been publicly posted for 88% of stroke patients who provided proper consent for public release. Preliminary analysis of these data did not reveal any single locus conferring a large effect on risk for ischaemic stroke. INTERPRETATION: The data generated here comprise the first phase of a genome-wide association analysis in patients with stroke. Release of phase I results generated in these publicly available samples from each consenting individual makes this dataset a valuable resource for data-mining and augmentation.

Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data.

BACKGROUND: The cause of sporadic ALS is currently unknown. Despite evidence for a role for genetics, no common genetic variants have been unequivocally linked to sporadic ALS. We sought to identify genetic variants associated with an increased or decreased risk for developing ALS in a cohort of American sporadic cases. METHODS: We undertook a genome-wide association study using publicly available samples from 276 patients with sporadic ALS and 271 neurologically normal controls. 555 352 unique SNPs were assayed in each sample using the Illumina Infinium II HumanHap550 SNP chip. FINDINGS: More than 300 million genotypes were produced in 547 participants. These raw genotype data are freely available on the internet and represent the first publicly accessible SNP data for ALS cases. 34 SNPs with a p value less than 0.0001 (two degrees of freedom) were found, although none of these reached significance after Bonferroni correction. INTERPRETATION: We generated publicly available genotype data for sporadic ALS patients and controls. No single locus was definitively associated with increased risk of developing disease, although potentially associated candidate SNPs were identified.

Bulimia: medical complications.

Bulimia nervosa is a common eating disorder that predominantly affects young women. There are three main models of purging in bulimia. Resulting medical complications are related to the particular mode and frequency of purging. Commonly, there are oral and gastrointestinal complications along with serious electrolyte and endocrine complications. The majority of the medical complications of bulimia nervosa are treatable if diagnosed in a timely fashion. Some of these patients require inpatient hospitalization, and others can be managed along a continuum of outpatient care. The American Psychiatric Association has comprehensive treatment guidelines for the management of bulimia. Primary care physicians and gynecologists need to be familiar with this disorder and its medical implications.

Podiatric problems are associated with worse health status in persons with severe mental illness.

The objective of this study was to determine the prevalence of self-reported podiatric impairments and their effect on health status in persons with severe mental illness. A sample of psychiatric outpatients (N=309) underwent interviews assessing medical conditions and health status with the Medical Outcomes Study Short Form-36 (SF-36). Podiatric health was assessed using nine items from the National Health Interview Survey (NHIS). Eighty percent of patients reported at least one podiatric problem. The most common problems were foot pain (48%), nail disorders (35%) and corns/calluses (28%). Prevalence rates were 4-11 times higher than those reported by the general population in the 1990 NHIS. The total number of podiatric problems was inversely related to eight self-reported health status domains and both summary SF-36 scores (all P<==.0001). After controlling for sociodemographic factors, psychiatric illness and medical conditions, the total number of podiatric limitations remained significantly associated with lower patient ratings in four of the eight SF-36 domains and both summary scores. We concluded that persons with severe and persistent mental illness have markedly elevated rates of podiatric problems when compared to the general population group. These problems are associated with worsened self-perceived health status. Addressing podiatric health may be a successful way to improve the overall health of this population.

A survey of herbal product use in a dialysis population in Northwest Ohio.

OBJECTIVE: To identify herbal product use in a dialysis population. DESIGN AND SETTING: Cross-sectional survey conducted at 2 freestanding dialysis centers in Northwest Ohio. PATIENTS: Two hundred and sixteen hemodialysis and peritoneal dialysis patients who provided informed consent. INTERVENTION: All patients were surveyed by personal interview regarding use of herbal products. Patients identified as current users were asked questions about specific agents. Respondents reporting past but not current use were questioned about specific agents and reasons for discontinuation. RESULTS: Thirty-one patients reported taking herbal therapies. Twenty-six patients discontinued use before the survey. Sixteen different herbal products were reported being used in our study population. Those who reported ever using an herbal product were more likely to be employed or disabled and have higher education when compared with nonusers. CONCLUSION: Our data suggest a lower frequency of herbal product use in the dialysis population as compared with the general population and other chronically ill populations. Education and employment are factors associated with use. Many of the herbal therapies used potentially could have significant adverse effects in dialysis patients. These include effects on blood pressure, blood glucose, coagulation parameters, and electrolyte disturbances. Dialysis patients currently taking herbal products may not be reevaluating their need for continuation and may not be informing members of the nephrology care team about their use.