Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage.

BACKGROUND: France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018 and 2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care. METHODS: Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010-14; ~7% PR), Period 1 ([P1] 2015-17; 8%-21% PR), and Period 2 ([P2] 2018-20; 100% PR). RESULTS: PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, -0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods. DISCUSSION: Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.

The Development and Effectiveness of Combining Case-Based Online Lecture and Simulation Programs to Facilitate Interprofessional Function Care Training in Nursing Homes.

The aim of this study was to (1) develop a case-based combination of online lectures and simulations for function-focused care by nursing home interdisciplinary caregivers and (2) evaluate participants' increasing shared team and task knowledge by surrogate measures of team process and team performance. The study comprised the following steps: (1) the design of a learning module using a shared understanding of function-focused care as a shared mental model; (2) the establishment of two computer programs for online lectures and simulations using cases involving older adults with disabilities; and (3) testing the educational programs using a repeated-measures design. Participants were 61 interdisciplinary caregivers from seven nursing homes in four regions. Data from participants' team process and team performance were collected pre test, post online lecture, and post simulation. Repeated-measures analysis of variance showed that the mean scores for scales of "transactive memory system," "knowledge sharing and utilization," "team outcomes," "motivation for learning transfer," "self-efficacy," "interpersonal understanding," "proactivity in problem solving," and "function-focused care knowledge" differed significantly between the time points. The results indicate that a case-based program of a combination of online lectures and simulations elicits significant improvements in participants' team process and team performance.

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.

Correction: DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.

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DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.

PURPOSE: Gross duplications are ambiguous in terms of clinical interpretation due to the limitations of the detection methods that cannot infer their context, namely, whether they occur in tandem or are duplicated and inserted elsewhere in the genome. We investigated the proportion of gross duplications occurring in tandem in breast cancer predisposition genes with the intent of informing their classifications. METHODS: The DNA breakpoint assay (DBA) is a custom, paired-end, next-generation sequencing (NGS) method designed to capture and detect deep-intronic DNA breakpoints in gross duplications in BRCA1, BRCA2, ATM, CDH1, PALB2, and CHEK2. RESULTS: DBA allowed us to ascertain breakpoints for 44 unique gross duplications from 147 probands. We determined that the duplications occurred in tandem in 114 (78%) carriers from this cohort, while the remainder have unknown tandem status. Among the tandem gross duplications that were eligible for reclassification, 95% of them were upgraded to pathogenic. CONCLUSION: DBA is a novel, high-throughput, NGS-based method that informs the tandem status, and thereby the classification of, gross duplications. This method revealed that most gross duplications in the investigated genes occurred in tandem and resulted in a pathogenic classification, which helps to secure the necessary treatment options for their carriers.

Sequential Two-Stage Network and Thematic Analysis for Exploring an Interdisciplinary Care Approach in Nursing Homes.

Since various groups of older adults with different conditions and levels of function coexist in nursing homes, it is necessary to develop integrated care strategies through collaboration among experts across related fields. The purposes of this study are to identify the regularity of information sharing in managing daily function for older adults, with a special focus on interdisciplinary cooperation, and to explore a practical care strategy for nursing home residents. The collaborative methods of network and thematic analysis were done by conducting in-depth interviews with 33 interdisciplinary experts working at seven nursing homes. This study proposed three relationships and three themes as interrelated key factors for providing interdisciplinary care to the elderly at various levels of function based on the experiences accumulated by the practitioners. First, independent sharing is required to make professional judgments about how daily function in older adults changes from reported baselines. Second, practitioners accurately judge clinical situations and supplement experts' judgments through partial sharing. Finally, all interdisciplinary consensus through complete sharing achieves the ultimate goal of maintaining remaining function in older adults. These findings can be the first step in developing practical care guidelines for interdisciplinary use, and the results can be used to develop integrated assessment and intervention strategies.

A collaborative exercise on DNA methylation based body fluid typing.

A collaborative exercise on DNA methylation based body fluid identification was conducted by seven laboratories. For this project, a multiplex methylation SNaPshot reaction composed of seven CpG markers was used for the identification of four body fluids, including blood, saliva, semen, and vaginal fluid. A total of 30 specimens were prepared and distributed to participating laboratories after thorough testing. The required experiments included four increasingly complex tasks: (1) CE of a purified single-base extension reaction product, (2) multiplex PCR and multiplex single-base extension reaction of bisulfite-modified DNA, (3) bisulfite conversion of genomic DNA, and (4) extraction of genomic DNA from body fluid samples. In tasks 2, 3 and 4, one or more mixtures were analyzed, and specimens containing both known and unknown body fluid sources were used. Six of the laboratories generated consistent body fluid typing results for specimens of bisulfite-converted DNA and genomic DNA. One laboratory failed to set up appropriate conditions for capillary analysis of reference single-base extension products. In general, variation in the values obtained for DNA methylation analysis between laboratories increased with the complexity of the required experiments. However, all laboratories concurred on the interpretation of the DNA methylation profiles produced. Although the establishment of interpretational guidelines on DNA methylation based body fluid identification has yet to be performed, this study supports the addition of DNA methylation profiling to forensic body fluid typing.

Capturing key function-focused care problems, nursing diagnoses, and interventions for nursing home patients using a web-based case management system.

PURPOSE: The aim of this study is to identify the key functional care problems, NANDA-I nursing diagnoses, and intervention plans related to function-focused care (FFC) using a web-based case management system for patients who present different cognitive status. METHODS: This study employed a retrospective descriptive research design. Data were obtained from system records on patients after the research team trained the case management system at a nursing home in Dangjin in South Chungcheong Province, South Korea. A total of 119 inpatient records were analyzed. RESULTS: The key physical, cognitive, and social functional problems, nursing diagnoses in six domains (health promotion, elimination and exchange, activity/rest, perception/cognition, coping/stress tolerance, and safety/protection), and intervention plans were identified. CONCLUSION: The identified FFC case management information of interdisciplinary caregivers will provide evidence for the implementation of effective interventions according to a patient's functional status. Additional studies related to the establishment of a large clinical database of advanced case management systems focusing on interdisciplinary caregivers' functional management are needed to support the prioritization of functional care.

The effects of sedimentation and dissolution on the cytotoxicity of Ag nanoparticles.

Nanoparticles (NPs) are being employed for various industrial purposes with increasing frequency, yet the adverse health effects associated with the prolonged exposure of humans and the environment to NPs has not been well-established. Particularly, the effects of the extrinsic (or dynamic) physicochemical properties of NPs in aqueous cell culture media (e.g., hydrodynamic size, aggregation, agglomeration, sedimentation, and dissolution of nanoparticles) on the cytotoxicities of the NPs are barely understood. In this study, to investigate the effects of two important extrinsic properties of Ag NPs, namely the sedimentation and dissolution of Ag NPs, we performed MTT cell viability tests for HeLa cells exposed to Ag NPs with varying extrinsic properties. Ag NPs with different hydrodynamic sizes, sedimentation rates, and dissolution rates were prepared via exposure to NaCl and FBS. Sedimentation of aggregated/agglomerated Ag NPs was found to contribute more significantly to the cytotoxicity of Ag NPs during early periods of exposure, whereas the cytotoxicity was more greatly enhanced later during the exposure period due to the increase in silver ions. Therefore, it is offered that any assessment of NP cytotoxicity should consider the extrinsic properties of NPs, and their time-dependent properties, because the dominant processes affecting NP cytotoxicity may change over time and lead to a misunderstanding or poor prediction of NP cytotoxicity.

NMR analysis of G-protein betagamma subunit complexes reveals a dynamic G(alpha)-Gbetagamma subunit interface and multiple protein recognition modes.

G-protein betagamma (Gbetagamma) subunits interact with a wide range of molecular partners including: G(alpha) subunits, effectors, peptides, and small molecule inhibitors. The molecular mechanisms underlying the ability to accommodate this wide range of structurally distinct binding partners are not well understood. To uncover the role of protein flexibility and alterations in protein conformation in molecular recognition by Gbetagamma, a method for site-specific (15)N-labeling of Gbeta-Trp residue backbone and indole amines in insect cells was developed. Transverse Relaxation Optimized Spectroscopy-Heteronuclear Single-Quantum Coherence Nuclear Magnetic Resonance (TROSY-HSQC NMR) analysis of (15)N-Trp Gbetagamma identified well-dispersed signals for the individual Trp residue side chain and amide positions. Surprisingly, a wide range of signal intensities was observed in the spectrum, likely representing a range of backbone and side chain mobilities. The signal for GbetaW99 indole was very intense, suggesting a high level of mobility on the protein surface and molecular dynamics simulations indicate that GbetaW99 is highly mobile on the nanosecond timescale in comparison with other Gbeta tryptophans. Binding of peptides and phosducin dramatically altered the mobility of GbetaW99 and GbetaW332 in the binding site and the chemical shifts at sites distant from the direct binding surface in distinct ways. In contrast, binding of G(alpha)(i1)-GDP to Gbetagamma had relatively little effect on the spectrum and, most surprisingly, did not significantly alter Trp mobility at the subunit interface. This suggests the inactive heterotrimer in solution adopts a conformation with an open subunit interface a large percentage of the time. Overall, these data show that Gbetagamma subunits explore a range of conformations that can be exploited during molecular recognition by diverse binding partners.

A case of Diphyllobothrium nihonkaiense infection as confirmed by mitochondrial COX1 gene sequence analysis.

Diphyllobothrium nihonkaiense has been reported in Korea as Diphyllobothrium latum because of their close morphologic resemblance. We have identified a human case of D. nihonkaiense infection using the mitochondrial cytochrome c oxidase subunit I (cox1) gene sequence analysis. On 18 February 2012, a patient who had consumed raw fish a month earlier visited our outpatient clinic with a long tapeworm parasite excreted in the feces. The body of the segmented worm was 2 m long and divided into the scolex (head) and proglottids. It was morphologically close to D. nihonkaiense and D. latum. The cox1 gene analysis showed 99.4% (340/342 bp) homology with D. nihonkaiense but only 91.8% (314/342 bp) homology with D. latum. The present study suggested that the Diphyllobothrium spp. infection in Korea should be analyzed with specific DNA sequence for an accurate species identification.

Intact Recognition Memory and Altered Hippocampal Glucocorticoid Receptor Signaling in Fkbp5-deficient Mice Following Acute Uncontrollable Stress.

The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5-knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5-knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5-knockout mice, but the levels of phosphorylated GR were lower in Fkbp5-knockout mice than in wild-type mice. Wild-type and Fkbp5-knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5-knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.

Enhanced percutaneous delivery of recombinant human epidermal growth factor employing nano-liposome system.

We encapsulated recombinant human epidermal growth factor (rhEGF) into nano-liposomes (NLs) system for topical delivery. The rhEGF-loaded NLs were prepared using a high pressure homogenization method. Morphology and overall particle distribution of NLs were investigated using transmission electron microscopy (TEM) and high resolution microscope (CytoViva™). Particle size, zeta (ζ) potential and encapsulation efficiency were measured and the percutaneous delivery of NLs was evaluated using Franz diffusion cells and immunofluorescence confocal laser scanning microscopy (CLSM). The mean particle size, zeta potential and encapsulation efficiency of the NLs were 155.57 ± 2.59 nm, -57.92 ± 4.35 mV and 9.00 ± 0.39%, respectively. TEM and microscopic analysis showed spherical, very even-sized vesicles approximately 150 nm. The skin permeation and localization of rhEGF were enhanced by NLs. CLSM image analysis provided that the NLs enhanced the permeation and localization of rhEGF in rat skin by facilitating entry through pores of skin.

Estimating binding affinities by docking/scoring methods using variable protonation states.

To investigate the effects of multiple protonation states on protein-ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK(a) of the unbound receptor and ligand and the proximity of titratable groups of the receptor to the binding site. Various ligand tautomer states were also considered. An independent docking calculation was run for each state. Several protocols were examined: using an ensemble of all generated states of ligand and receptor, using only the most probable state of the unbound ligand/receptor, and using only the state giving the most favorable docking score. The accuracies of these approaches were compared, using a set of 176 protein-ligand complexes (15 receptors) for which crystal structures and measured binding affinities are available. The best agreement with experiment was obtained when ligand poses from experimental crystal structures were used. For 9 of 15 receptors, using an ensemble of all generated protonation states of the ligand and receptor gave the best correlation between calculated and measured affinities.

Conformational flexibility and binding interactions of the G protein ßγ heterodimer.

Previous NMR experiments on unbound G protein ßγ heterodimer suggested that particular residues in the binding interface are mobile on the nanosecond timescale. In this work we performed nanosecond-timescale molecular dynamics simulations to investigate conformational changes and dynamics of Gßγ in the presence of several binding partners: a high-affinity peptide (SIGK), phosducin, and the GDP-bound α subunit. In these simulations, the high mobility of GßW99 was reduced by SIGK, and it appeared that a tyrosine might stabilize GßW99 by hydrophobic or aromatic stacking interactions in addition to hydrogen bonds. Simulations of the phosducin-Gßγ complex showed that the mobility of GßW99 was restricted, consistent with inferences from NMR. However, large-scale conformational changes of Gßγ due to binding, which were hypothesized in the NMR study, were not observed in the simulations, most likely due to their short (nanosecond) duration. A pocket consisting of hydrophobic amino acids on Gα appears to restrict GßW99 mobility in the crystal structure of the Gαßγ? heterotrimer. The simulation trajectories are consistent with this idea. However, local conformational changes of residues GßW63, GßW211, GßW297, GßW332, and GßW339 were detected during the MD simulations. As expected, the magnitude of atomic fluctuations observed in simulations was greater for α than for the ßγ subunits, suggesting that α has greater flexibility. These observations support the notion that to maintain the high mobility of GßW99 observed by solution NMR requires that the Gß-α interface must open up on time scale longer than can be observed in nanosecond scale simulations.

Adiposity and the risk of colorectal adenomatous polyps: a meta-analysis.

OBJECTIVE: The findings from epidemiological studies addressing the association between adiposity and the risk of colorectal adenomatous polyps are inconsistent. We performed a meta-analysis of epidemiological studies including cross-sectional, case-control, and cohort studies. METHODS: We searched PubMed and EMBASE in June, 2010. All searched articles were reviewed and selected independently by two evaluators according to pre-determined selection criteria. RESULTS: We included 25 studies (nine cross-sectional studies, eleven case-control studies, and five prospective cohort studies) that comprised a total of 300,671 participants and 20,903 cases in the final analysis. When all studies were pooled, the odds ratio (OR) or relative risk (RR) of adiposity and abdominal adiposity for colorectal adenomatous polyp risk was 1.43 (95% confidence interval (CI) 1.23-1.67; n = 22) and 1.42 (95% CI 1.30-1.56; n = 12), respectively. Similarly, an increased risk of colorectal adenomatous polyps was observed in most of the subgroup meta-analyses. CONCLUSIONS: Overall, we found that adiposity and abdominal adiposity significantly increased the risk of colorectal adenomatous polyps in a meta-analysis of epidemiological studies.

Disparities in health-risk behaviors, preventive health care utilizations, and chronic health conditions for people with disabilities: the Korean National Health and Nutrition Examination Survey.

OBJECTIVE: To examine how disability status is related with health disparities in South Korea. DESIGN: The study compared 3 indicators of health (health-risk behaviors, preventive health care utilizations, and chronic health conditions) according to the presence of disabilities using the Third Korean National Health and Nutrition Examination Survey, 2005 (KNHANES III). SETTING: We obtained data from the KNHANES III, which is the third nationwide representative study using a stratified, multistage probability sampling design. PARTICIPANTS: Subjects (N=5475) aged 20 years or older were included in the study; persons with disabilities (n=218) and persons without disabilities (n=5257). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nonconditional multiple logistic regression and adjusted mean were used to identify health disparities in health-risk behaviors, preventive health care utilizations, and chronic health conditions. RESULTS: Subjects with disabilities were more likely to be physically inactive (adjusted odds ratio [AOR]=3.06; 95% confidence interval [CI], 1.71-5.48 for no physical activity; AOR=1.70; 95% CI, 1.19-2.43 for insufficient physical activity) than those without disabilities. Women aged 40 years or older with disabilities were less likely to receive cervical cancer screening services (AOR=0.52; 95% CI, 0.27-0.98). Adults with disabilities had higher proportion of osteoporosis (AOR=2.41; 95% CI, 1.50-3.88), underweight (AOR=2.14; 95% CI, 1.07-4.28), suicidal thoughts (AOR=1.86; 95% CI, 1.35-2.56), and had impaired quality of life (95% CI of adjusted mean, 60.89-65.35 compared to 69.95-70.84 in adults without disabilities). CONCLUSIONS: There exists substantial disability-related health disparities in South Korea. People with disabilities may be the underserved subpopulation demonstrating health disparities. The findings in this study underscore the continued needs in order to reduce health problems and disparities for people with disabilities.

Healthcare Professionals' Perceptions of Function-Focused Care Education for Nursing Home Practitioners.

A nursing home (NH) care environment necessitates a shared cognition-based education model that maintains effective function-focused care (FFC). This study's aim was to explore healthcare professionals' perceptions of function-focused care education for the development of an education model using a shared mental model (SMM) in NHs. Semi-structured interviews with 30 interdisciplinary practitioners from four different professions (nurses, physical therapists, occupational therapists, and social workers) and focus group interviews with 12 experts were conducted. Data were analyzed using content analysis, and the education model development was guided by the shared mental models for data interpretation and formation. Our FFC interdisciplinary educational model incorporates four key learning components: learning contents, educational activities, educational goals/outcome, and environment, and four types of SMMs: team, task, team interaction, and equipment. As for educational contents, a team's competencies with FFC were found to be team knowledge (physical and psychosocial functional care), team skills to perform FFC successfully (motivation, coaching and supporting, managing discomfort), and team attitude (possessing philosophy perceptions regarding FFC). As for learning outcomes, the shared cognition-based education model suggests not only the evaluation of practitioners, but also the assessment of residents' aspects.

Concept Development of Identification of Discomfort for Nursing Home Patients With Advanced Dementia.

PURPOSE: The aim of this study is to clarify the concept of discomfort identification by concept development in the nursing home. METHODS: The Schwartz-Barcott and Kim's hybrid model was used. FINDINGS: The identification of discomfort can be explained as an interactive and confirmative process of sympathetically responding to patients with dementia's problem behavior expressions that communicate unmet needs. CONCLUSIONS: The identification of discomfort has the potential to improve the detection of multidimensional discomfort related to nursing diagnosis as a holistic and patient-centered approach. IMPLICATION FOR NURSING PRACTICE: The findings could help nursing home nurses have a better understanding of identification of discomfort and can improve nurses and interdisciplinary caregivers' knowledge for developing appropriate comfort caring activities.

Exploring a Nursing Home-Specific, Interdisciplinary, Function-Focused, Communicative Framework Based on Situation, Background, Assessment, and Recommendation.

BACKGROUND: Improved methods of communication are needed among professionals in related fields to address the increasing complexity of clinical situations and various levels of functioning experienced by older adults who live in nursing homes. PURPOSE: The purpose of this study was to explore function-focused clinical communication among nurses and providers based on the Situation, Background, Assessment, Recommendation (SBAR) approach toward interdisciplinary collaboration to maintain function among nursing home residents and to identify the characteristics of SBAR flows in nursing homes. METHODS: Detailed interviews with 28 interdisciplinary professionals working in four nursing homes were conducted. Directed qualitative content analysis was used to identify the internal attributes of SBAR-based communication. Case analysis was conducted to identify SBAR flows. RESULTS: Four themes emerged as key factors for function-focused interdisciplinary staff communication in nursing homes. Effective nursing care to maintain function among nursing home residents requires accurate awareness of abnormal circumstances. Knowledge of assessment and resident background are needed to address situations requiring intervention and identify the problems underlying a resident's current state. The optimal therapeutic environment is created by sharing roles and tasks among practitioners through referrals.Twelve generalized situations requiring function-focused communication (i.e., dislocation of body line because of joint contracture, change in walking, difficulty of moving because of pain, difficulty in eating, fever, change in sleep pattern, change in excretion pattern, change in weight, change in condition, change in problematic behavior, decrease in cognitive function, and change in relationships) and the related nurse-centered SBAR pathways were identified. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: These results represent a first prototype for developing practical communication guidelines for nursing-home-specific function-focused care and provide new insights into the interdisciplinary approach.