Blood volume reduction due to rapid plasma loss after birth in preterm piglets.

BACKGROUND: Understanding changes in blood volume after preterm birth is critical to preventing cardiovascular deterioration in preterm infants. The aims were to determine if blood volume is higher in preterm than term piglets and if blood volume changes in the hours after birth. METHODS: Paired blood volume measurements were conducted in preterm piglets (98/115d gestation, ~28wk gestation infant) at 0.5-5 h (n = 12), 0.5-9 h (n = 44) and 5-11 h (n = 7) after birth, and in a term cohort at 0.5-9 h (n = 40) while under intensive care. RESULTS: At 30 min after birth, blood volume was significantly lower in preterm piglets compared to term piglets. By 9 h after birth, blood volume had reduced by 18% in preterm piglets and 13% in term piglets. By 5-9 h after birth, preterm piglets had significantly lower blood volumes than at term (61 ± 10 vs. 76 ± 11 mL/kg). CONCLUSIONS: In contrast to clinical resources, preterm piglets have a lower blood volume than at term. Substantial reductions in blood volume after birth leave some preterm piglets hypovolemic. If this also occurs in preterm infants, this may have important clinical consequences. Modern studies of blood volume changes after birth are essential for improving preterm outcomes. IMPACT: Preterm piglets do not have a higher blood volume than their term counterparts, in contrast to current clinical estimates. Rapid reduction in blood volume after birth leads to hypovolemia in some preterm piglets. There is a critical need to understand blood volume changes after birth in preterm infants in order to improve clinical management of blood volume.

A test of Conserving Nature's Stage: protecting a diversity of geophysical traits can also support a diversity of species at a landscape scale.

Conserving Nature's Stage (CNS) is a concept from conservation planning that promotes the protection of areas encompassing a broad range of enduring geophysical traits to provide long-term habitat for diverse species. The efficacy of using enduring geophysical characteristics as surrogates for biodiversity, independent of non-geophysical features and when considering finer resolution area selections, has yet to be investigated. Here, we evaluated CNS using 33 fine-scale inventories of vascular plant, non-vascular plant, invertebrate or vertebrate species from 13 areas across three continents. For each inventory, we estimated a continuous multidimensional surrogate defined from topographic and soil estimates of the surveyed plots. We assessed surrogate effectiveness by comparing the species representation of surrogate selected plots to the representation from plots picked randomly and using species information. We then used correlation coefficients to assess the link between the performance and qualities of the inventories, surroundings and surrogates. The CNS surrogate showed positive performance for 24 of the 33 inventories, and among these tests, represented 28 more species than random and 83% of the total number of species on average. We also found a small number of weak correlations between performance and environmental variability, as well as qualities of the surrogate. Our study demonstrates that prioritizing areas for a variety of geophysical characteristics will, in most cases, promote the representation of species. Our findings also point to areas for future research that might enhance CNS surrogacy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

The status and future of essential geodiversity variables.

Rapid environmental change, natural resource overconsumption and increasing concerns about ecological sustainability have led to the development of 'Essential Variables' (EVs). EVs are harmonized data products to inform policy and to enable effective management of natural resources by monitoring global changes. Recent years have seen the instigation of new EVs beyond those established for climate, oceans and biodiversity (ECVs, EOVs and EBVs), including Essential Geodiversity Variables (EGVs). EGVs aim to consistently quantify and monitor heterogeneity of Earth-surface and subsurface abiotic features, including geology, geomorphology, hydrology and pedology. Here we assess the status and future development of EGVs to better incorporate geodiversity into policy and sustainable management of natural resources. Getting EGVs operational requires better consensus on defining geodiversity, investments into a governance structure and open platform for curating the development of EGVs, advances in harmonizing in situ measurements and linking heterogeneous databases, and development of open and accessible computational workflows for global digital mapping using machine-learning techniques. Cross-disciplinary collaboration and partnerships with governmental and private organizations are needed to ensure the successful development and uptake of EGVs across science and policy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

Evaluating clinical reasoning in first year DPT students using a script concordance test.

BACKGROUND: A script concordance test (SCT) provides a series of clinical vignettes to assess clinical reasoning in uncertainty. Appraised throughout health education literature, SCTs are cognitive assessments of clinical reasoning, though their use in Doctor of Physical Therapy (DPT) entry-level education has not been investigated. The purpose of this study was to develop and explore the reliability and validity of a SCT for first year DPT students. METHODS: The SCT was developed and implemented over four phases. During phases one and two, DPT program faculty consulted on course content from the first-year curriculum. Thirty clinical vignettes with three follow-up questions each were constructed. The SCT was pilot tested with five clinicians in phase three to assess question clarity. During phase four, the SCT was administered to students and a reference panel via Qualtrics. First year DPT students (n = 44) and reference panel physical therapists with at least two years of experience and advanced certification (n = 15) completed the SCT. Internal consistency was analyzed using Cronbach's Alpha. Differences between student and reference panel percent-correct scores were analyzed with a t-test. Relationships between student SCT scores and academic records were explored with Spearman's Rho. RESULTS: The SCT had an internal consistency of 0.74. A significant difference in scores was found between the students [mean 58.5 (+/-5.31)] and reference panel [65.8 (+/-4.88), p < .01]. No significant correlations between student SCT scores and academic records were found. CONCLUSIONS: The developed SCT was reliable and demonstrated satisfactory internal consistency among test items. The SCT successfully differentiated between groups, with the reference panel demonstrating statistically significant higher percent-correct scores compared to students. SCTs may provide means to measure clinical reasoning in DPT students and lead to novel pedagogical approaches to enhance clinical reasoning.

Five-Year Prospective Observational Study of African-American Men on Active Surveillance for Prostate Cancer Demonstrates Race Is Not Predictive of Oncologic Outcomes.

INTRODUCTION: This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period. PATIENTS AND METHODS: All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05. RESULTS: A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P > .05 for all). CONCLUSIONS: Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.

Functional Degeneracy in Paracoccus denitrificans Pd1222 Is Coordinated via RamB, Which Links Expression of the Glyoxylate Cycle to Activity of the Ethylmalonyl-CoA Pathway.

Metabolic degeneracy describes the phenomenon that cells can use one substrate through different metabolic routes, while metabolic plasticity, refers to the ability of an organism to dynamically rewire its metabolism in response to changing physiological needs. A prime example for both phenomena is the dynamic switch between two alternative and seemingly degenerate acetyl-CoA assimilation routes in the alphaproteobacterium Paracoccus denitrificans Pd1222: the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). The EMCP and the GC each tightly control the balance between catabolism and anabolism by shifting flux away from the oxidation of acetyl-CoA in the tricarboxylic acid (TCA) cycle toward biomass formation. However, the simultaneous presence of both the EMCP and GC in P. denitrificans Pd1222 raises the question of how this apparent functional degeneracy is globally coordinated during growth. Here, we show that RamB, a transcription factor of the ScfR family, controls expression of the GC in P. denitrificans Pd1222. Combining genetic, molecular biological and biochemical approaches, we identify the binding motif of RamB and demonstrate that CoA-thioester intermediates of the EMCP directly bind to the protein. Overall, our study shows that the EMCP and the GC are metabolically and genetically linked with each other, demonstrating a thus far undescribed bacterial strategy to achieve metabolic plasticity, in which one seemingly degenerate metabolic pathway directly drives expression of the other. IMPORTANCE Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. Understanding the underlying mechanisms of metabolic control in bacteria is of importance for applications in health (e.g., targeting of metabolic pathways with new antibiotics, development of resistances) and biotechnology (e.g., metabolic engineering, introduction of new-to-nature pathways). In this study, we use the alphaproteobacterium P. denitrificans as model organism to study functional degeneracy, a well-known phenomenon of bacteria to use the same carbon source through two different (competing) metabolic routes. We demonstrate that two seemingly degenerate central carbon metabolic pathways are metabolically and genetically linked with each other, which allows the organism to control the switch between them in a coordinated manner during growth. Our study elucidates the molecular basis of metabolic plasticity in central carbon metabolism, which improves our understanding of how bacterial metabolism is able to partition fluxes between anabolism and catabolism.

Cryptic Diversity of Black Band Disease Cyanobacteria in Siderastrea siderea Corals Revealed by Chemical Ecology and Comparative Genome-Resolved Metagenomics.

Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the cyanobacterial species Roseofilum reptotaenium, other filamentous cyanobacterial strains and bacterial heterotrophs are readily detected. Through chemical ecology and metagenomic sequencing, we uncovered cryptic strains of Roseofilum species from Siderastrea siderea corals that differ from those on other corals in the Caribbean and Pacific. Isolation of metabolites from Siderastrea-derived Roseofilum revealed the prevalence of unique forms of looekeyolides, distinct from previously characterized Roseofilum reptotaenium strains. In addition, comparative genomics of Roseofilum strains showed that only Siderastrea-based Roseofilum strains have the genetic capacity to produce lasso peptides, a family of compounds with diverse biological activity. All nine Roseofilum strains examined here shared the genetic capacity to produce looekeyolides and malyngamides, suggesting these compounds support the ecology of this genus. Similar biosynthetic gene clusters are not found in other cyanobacterial genera associated with black band disease, which may suggest that looekeyolides and malyngamides contribute to disease etiology through yet unknown mechanisms.

Exploring Delay to Follow-Up in a Rural Multidisciplinary Cleft Clinic.

BACKGROUND: Oral clefts require longitudinal multidisciplinary care with follow-up visits at regular intervals throughout a patient's childhood, and delayed care can be detrimental. Although loss to follow-up is commonly studied, this metric does not account for patients that do return to care, but months or years later than recommended. The aim of this study was to explore and determine risk factors for delay to follow-up (DTFU) in a cleft clinic at a rural academic center. METHODS: Medical records from the multidisciplinary cleft clinic at a single rural tertiary care institution between January 1, 2010, and December 31, 2019, were reviewed. The primary outcome was DTFU, measured as the difference in days between recommended and actual follow-up dates for a given visit. RESULTS: A cohort of 282 patients was analyzed, with a total of 953 visits. A total of 71% of patients experienced at least 1 delay in follow-up of 30 days or longer, and 50% had at least 1 delay of 90 days or longer. Out of all visits, the mean DTFU was 73 days (around 2.5 months). For 23% of patients, at least half their visits were delayed by more than 90 days, whereas 11% experienced a delay of more than 90 days with every visit. Patients who failed to show up to at least 1 appointment had significantly higher risk of DTFU ( P < 0.0001). Driving distance, driving time, SES, stage of cleft care, and cleft phenotype were not correlated with DTFU. For canceled appointments, 50.5% of recorded cancellation reasons were patient driven. CONCLUSIONS: Delay to follow-up in a multidisciplinary cleft clinic was prevalent in this rural cohort, with half of patients experiencing delays of 3 months or longer, and about 1 in 9 experiencing this delay with every visit. Delay to follow-up identifies patients with consistently high rates of delay in care, which could eventually lead to targeted interventions to increase compliance. Delay to follow-up may be a new and valuable measure of cleft care compliance that can be easily implemented by other institutions. Further investigation is needed to determine the relationship between delay and clinical outcomes in cleft patients.

Firefighter Suicide: A Theoretical Model for a Population Specific Behavioral Autopsy Program.

Some research suggests that firefighters are possibly at greater risk than other at-risk first responder/public service populations for suicidality (e.g., police, Veterans, active duty military non-deployed males; Martin et al., 2017; Stanley et al., 2015; Stanley et al., 2016). Behavioral autopsies have been utilized to elucidate the clinical picture of other at-risk populations; however, to date there is no proposed or applied model for a suicide behavior autopsy in fire personnel. Developing a standardized suicide behavior autopsy will allow for a comprehensive understanding of firefighters who die by suicide and highlight potential areas for intervention. The aim of this paper is to integrate best practices for autopsy procedures from other high-risk populations into a comprehensive theoretical model for a proposed behavioral health autopsy for firefighters. Our recommended protocol is presented along with relevant limitations, clinical implications, and recommendations for future research.

Role of Blood Pressure Responses to Exercise and Vascular Insulin Sensitivity with Nocturnal Blood Pressure Dipping in Metabolic Syndrome.

INTRODUCTION: Nocturnal systolic blood pressure (SBP) dipping is independently related to cardiovascular disease risk, but it is unclear if vascular insulin sensitivity associates with SBP dipping in patients with metabolic syndrome (MetS). METHODS: Eighteen adults with MetS (ATP III criteria 3.3 ± 0.6; 53.2 ± 6.5 years; body mass index 35.8 ± 4.5 kg/m2) were categorized as "dippers" (≥10% change in SBP; n = 4 F/3 M) or "non-dippers" (<10%; n = 9 F/2 M). Twenty-four-hour ambulatory blood pressure was recorded to assess SBP dipping. A euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) with ultrasound (flow mediated dilation) was performed to test vascular insulin sensitivity. A graded, incremental exercise test was conducted to estimate sympathetic activity. Heart rate (HR) recovery after exercise was then used to determine parasympathetic activity. Metabolic panels and body composition (DXA) were also tested. RESULTS: Dippers had greater drops in SBP (16.63 ± 5.2 vs. 1.83 ± 5.6%, p < 0.01) and experienced an attenuated rise in both SBPslope (4.7 ± 2.3 vs. 7.2 ± 2.5 mm Hg/min, p = 0.05) and HRslope to the incremental exercise test compared to non-dippers (6.5 ± 0.9 vs. 8.2 ± 1.7 bpm/min, p = 0.03). SBP dipping correlated with higher insulin-stimulated flow-mediated dilation (r = 0.52, p = 0.03), although the relationship was no longer significant after covarying for HRslope (r = 0.42, p = 0.09). CONCLUSION: Attenuated rises in blood pressure and HR to exercise appear to play a larger role than vascular insulin sensitivity in SBP dipping in adults with MetS.

The still-face paradigm in Latin American mother-child dyads at 2 and 3 years: Effects of socioeconomic status and temperament.

The still-face paradigm (SFP) is a common method in infancy used to assess emotion regulation and interactions when an adult (typically the caregiver) abruptly stops a positive interaction with a child and switches to a more neutral affect. The effect of this paradigm has been studied in different countries and age ranges, but research in Latin America and with toddlers (e.g., 2-3 years old) of different socioeconomic backgrounds is scarce. The current study analyzed caregiver-child interactions in this novel sample, to analyze the possibility of generalization of the typical response of this paradigm (i.e., less positive affect, reduced gaze, and more negative affect in children when parent affect changes). The sample consisted of 114 caregiver-child dyads from low to middle socioeconomic status (SES) (children's Mage = 26.61 months, SD = 6.73, range = 18-36; 61 girls). The SFP modified version (i.e., on the floor and with a series of standardized toys), the temperament Early Childhood Behavior Questionnaire adapted for Argentina, and an SES scale were used. The typical SFP response was observed in Latin American children. In addition, older children and children with higher SES exhibited better general regulation, and there were weak associations with temperament. For gender differences, boys demonstrated more aggressive behaviors at Phase II. Results from this study suggest that children's response to this paradigm is an unconditional response to the lack of social reinforcers and is only partially associated with social and individual variables.

Factors Influencing Maternal Antepartum Tdap Vaccination.

INTRODUCTION: Antepartum Tdap remains low despite national recommendations. This prospective observational study aims to identify factors associated with lower antepartum Tdap rates. METHODS: Maternal demographics, personal health beliefs, Tdap vaccination status, and recall of in-office obstetric provider actions were collected from a convenience sample of postpartum women in a New York metropolitan hospital. Bivariate and multivariable logistic regression were used to identify significant factors and adjusted odds ratios (OR) for recorded Tdap; OR > 1 reflects elements with increased odds of not receiving antepartum Tdap, while OR < 1 demonstrates increased odds of receipt. RESULTS: Surveys were collected (n = 1682) from a study population demographically similar to New York City and more diverse in race/ethnicity than the national population. Demographic analysis showed Hispanic women less likely than white, non-Hispanic women to vaccinate (OR 2.44, CI 1.54-3.88). Health beliefs associated with non-receipt of antepartum Tdap included "It is dangerous for pregnant women to get vaccines" (OR 1.68, CI 1.01-2.77), and "I worry about the safety of the Tdap vaccine" (OR 1.59, CI 1.12-2.24). Obstetric provider actions associated with vaccination included receiving an OB recommendation (OR 0.39, CI 0.23-0.65), getting written information about Tdap (OR 0.44, CI 0.30-0.64), and having Tdap offered in office (OR 0.24, CI 0.15-0.37). Health beliefs associated with antepartum Tdap included "I generally do what my OB/GYN provider recommends" (OR 0.49, CI 0.30-0.80), and "Pregnant women should get the Tdap (pertussis) vaccine" (OR 0.17, CI 0.09-0.33). DISCUSSION: Maternal race/ethnicity, personal health beliefs, and obstetric provider actions predict antepartum Tdap.

Increasing Parent Satisfaction With Discharge Planning: An Improvement Project Using Technology in a Level 3 NICU.

BACKGROUND: Neonatal intensive care unit (NICU) families are often overwhelmed by the discharge process. Their anxiety can inhibit learning and contribute to poor infant outcomes and increased healthcare utilization after discharge. Quality of the discharge teaching is the strongest predictor of discharge readiness, so NICUs must develop excellent discharge preparation programs. PURPOSE: This improvement project enhances NICU discharge preparedness by providing consistent, early discharge teaching using technology as a supplemental resource and raises parental satisfaction with the process. METHODS: Neonatal intensive care unit staff and former NICU parents developed a task force to create technology-based discharge education content. The content was originally uploaded to an e-book and later transferred to the electronic health record inpatient portal. Families were able to view discharge teaching content at their own convenience and pace and review topics as needed with the NICU staff. Postdischarge follow-up phone calls provided insight into parental reaction to the new education format. RESULTS: Parent satisfaction top-box scores, reflecting the highest rating in the "Prepared for Discharge" category of the patient satisfaction survey, improved from a baseline of 47% in 2017 to 70% in 2019. Overwhelmingly, 92% of families highly rated the tablet-based discharge teaching during postdischarge phone calls. IMPLICATIONS FOR PRACTICE: A comprehensive, consistent, and early discharge program using technology can lead to more effective and efficient NICU discharge education and improved parent satisfaction. IMPLICATIONS FOR RESEARCH: Further studies are needed to generalize hospital-based inpatient portal teaching as an additional resource for parental education in the NICU.

Insulin stimulation reduces aortic wave reflection in adults with metabolic syndrome.

Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness and altered central hemodynamics that contribute, partly, to increased cardiovascular disease (CVD) risk. Although insulin affects aortic wave reflections in healthy adults, the effects in individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of pressure waveforms and hemodynamics in people with MetS. Thirty-five adults with obesity (27 women; 54.2 ± 6.0 yr; 37.1 ± 4.8 kg/m2) were selected for MetS (ATP III criteria) following an overnight fast. Pulse wave analysis was assessed using applanation tonometry before and after a 2-h euglycemic-hyperinsulinemic clamp (90 mg/dL, 40 mU/m2/min). Deconvolution analysis was used to decompose the aortic waveform [augmentation index corrected to heart rate of 75 beats/min (AIx@75); augmentation pressure (AP)] into backward and forward pressure components. Aerobic fitness (V̇o2max), body composition (DXA), and blood biochemistries were also assessed. Insulin significantly reduced augmentation index (AIx@75, 28.0 ± 9.6 vs. 23.0 ± 9.9%, P < 0.01), augmentation pressure (14.8 ± 6.4 vs. 12.0 ± 5.7 mmHg, P < 0.01), pulse pressure amplification (1.26 ± 0.01 vs. 0.03 ± 0.01, P = 0.01), and inflammation [high-sensitivity C-reactive protein (hsCRP): P = 0.02; matrix metallopeptidase 7 (MMP-7): P = 0.03] compared to fasting. In subgroup analyses to understand HTN influence, there were no insulin stimulation differences on any outcome. V̇o2max, visceral fat, and blood potassium correlated with fasting AIx@75 (r = -0.39, P = 0.02; r = 0.41, P = 0.03; r = -0.53, P = 0.002). Potassium levels were also associated with insulin-mediated reductions in AP (r = 0.52, P = 0.002). Our results suggest insulin stimulation improves indices of aortic reflection in adults with MetS.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on central and peripheral hemodynamics in adults with metabolic syndrome. We provide evidence that insulin infusion reduces aortic wave reflection, potentially through a reduction in inflammation and/or via a potassium-mediated vascular response.

Epigenetic regulation of the miR142-3p/interleukin-6 circuit in glioblastoma.

Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target.

Emerging coherence and relations to communication among executive function tasks in toddlers: Evidence from a Latin American sample.

Recent work within early executive function (EF) seems to suggest that toddlers show distinct patterns of development, involving poorly correlated performance across EF tasks and significant improvements over relatively short periods of time. The present study sought to extend these findings by investigating evidence for these patterns in toddlers and the existence of more traditional patterns of EF (e.g., correlations between tasks, links to language) when using the same tasks in a novel Latin American sample. Eighty toddlers (18-24 months) and sixty young preschoolers (30-36) months completed a battery of EF tasks, early social communication, and receptive and expressive language measures. Results indicated that toddlers showed similar distinct patterns of development (i.e., few relations between tasks and links to responding to joint attention), but by early preschool a more cohesive EF and links to language were present. Further, work demonstrated significant age (older children outperformed younger children), gender (girls outperformed boys), and socioeconomic differences (satisfied basic needs outperformed unsatisfied basic needs, but only on the snack delay). This work provides evidence for patterns of emerging EF development within this novel cultural sample (and evidence for group differences) that may be supported by communicative and representational development.

Does a Sway-Based Mobile Application Predict Future Falls in People With Parkinson Disease?

OBJECTIVE: To determine whether Sway, a sway-based mobile application, predicts falls and to evaluate its discriminatory sensitivity and specificity relative to other clinical measures in identifying fallers in individuals with Parkinson disease (PD). DESIGN: Observational cross-sectional study. SETTING: Community. PARTICIPANTS: A convenience sample of subjects with idiopathic PD in Hoehn and Yahr levels I-III (N=59). INTERVENTIONS: Participants completed a balance assessment using Sway, the Movement Disorders Systems-Unified PD Rating Scale motor examination, Mini-BESTest, Activities-specific Balance Confidence (ABC) Scale, and reported 6-month fall history. Participants also reported falls for each of the following 6 months. Binomial logistic regression was used to identify significant predictors of future fall status. Cutoff scores, sensitivity, and specificity were based on receiver operating characteristic plots. MAIN OUTCOME MEASURES: Sway score. RESULTS: The most predictive logistic regression model included fall history, ABC Scale, and Sway (P<.001). This model explained 61% (Nagelkerke R2) of the variance in fall prediction and correctly classified 85% of fallers. However, only fall history and ABC Scale were statistically significant (P<.02). Participants were 32 times more likely to fall in the future if they fell in the past. The ABC Scale and Mini Balance Evaluation Systems Test (Mini-BESTest) demonstrated greater accuracy than Sway (area under the curve=0.76, 0.72, and 0.65, respectively). Cutoff scores to identify fallers were 85% for the ABC Scale and 21 of 28 for the Mini-BESTest. CONCLUSION: Sway did not improve the accuracy of predicting future fallers beyond common clinical measures and fall history.

Suicidal Ideation among Veterans Living with Cancer Referred to Mental Health.

Objectives: Eliminating Veteran suicide is a top priority for the Department of Veterans' Affairs (VA). This study identified factors associated with suicidal ideation (SI) among a rarely studied subgroup of Veterans: those with cancer.Methods: Veterans (age M = 61.83) with cancer (N= 175) referred for psychological evaluation completed measures of pain, sleep, depressive, anxiety, and PTSD symptoms. SI was defined by endorsing on paper-and-pencil questionnaire thoughts of killing oneself in the past 2 weeks or during clinical interview.Results: 25.1% reported SI. Compared to those without SI, Veterans with SI had higher ratings on measures of depression, anxiety, and PTSD symptoms. History of suicide attempt(s) was included in the model due to clinical significance. Logistic regression was performed with these variables as predictors of SI. The omnibus model was significant (p< .001). However, only anhedonia and depressed mood had a statistically significant contribution to the model (ß = 0.540, p= .001).Conclusions: Anhedonia and depressed mood predicted SI among Veterans with cancer above and beyond other risk factors.Clinical Implications: This study's findings highlight the importance of incorporating suicide risk screenings in oncology clinics across VA medical centers.

Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition.

Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation. Here, we show that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination. Deposition of misfolded cytosolic proteins at INQ involves chaperone-assisted nuclear import via nuclear pores. The compartment-specific aggregases, Btn2 (nuclear) and Hsp42 (cytosolic), direct protein deposition to nuclear INQ and cytosolic (CytoQ) sites, respectively. Intriguingly, Btn2 is transiently induced by both protein folding stress and DNA replication stress, with DNA surveillance proteins accumulating at INQ. Our data therefore reveal a bipartite, inter-compartmental protein quality control system linked to DNA surveillance via INQ and Btn2.