Search

Episodic memory (EM) and working memory (WM) are negatively affected by healthy ageing, and additional memory impairment typically occurs in clinical ageing‐related conditions such as amnestic mild cognitive impairment (aMCI). Recent studies on musical mnemonics in Alzheimer's dementia (AD) showed promising results on EM performance. However, the effects of musical mnemonics on WM performance have not yet been studied in (a)MCI or AD. Particularly in (a)MCI the use of musical mnemonics may benefit the optimisation of (working) memory performance. Therefore, in the present study, we examined the effects of musical presentation of digits consisting of pre‐recorded rhythms, sung unfamiliar pitch sequences, and their combinations, as compared to spoken presentation. Furthermore, musical expertise was assessed with two perceptual tests and the Self‐Report Inventory of the Goldsmiths Musical Sophistication Index. Thirty‐two persons with aMCI and 32 cognitively unimpaired older adults (OA) participated in this study. Confirming and extending previous findings in research on ageing, our results show a facilitating effect of rhythm in both cognitively unimpaired OA and persons with aMCI (p =.001, ηp2 =.158). Furthermore, pitch (p =.048, ηp2 =.062) and melody (p =.012, ηp2 =.098) negatively affected performance in both groups. Musical expertise increased this beneficial effect of musical mnemonics (p =.021, ηp2 =.090). Implications for the future design of music‐based memorisation strategies in (a)MCI are discussed. [ABSTRACT FROM AUTHOR]

A response is provided to the Rapporteurs' comments on Proposal 193 to amend the Shenzhen Code. If adopted, Prop. 193 would amend Div. III, Prov. 5 of the Code so as to require a simple majority to approve—as opposed to the current 60% majority to reject (and thus 40% + 1 vote to approve)—General Committee recommendations on conservation, protection, or rejection of names, suppression of works, and binding decisions. We regard the requirement of a simple majority in the affirmative to approve recommendations of the General Committee to be the fairest and most easily understood procedure available. It is also one that is consistent with the compromise worked out and published in 2016 by the Special Committee on By‐laws that reported to the Nomenclature Section at Shenzhen and would restore the procedure used at all nomenclature sections prior to the Nomenclature Section at Vienna in 2005. [ABSTRACT FROM AUTHOR]

Key Takeaways: As federal maximum contaminant level (MCL) recommendations for arsenic in drinking water are being reviewed, US utilities are preparing for more stringent regulations. If faced with reducing its treated water's arsenic concentration to 5 μg/L, the City of Alamosa, Colo., would need to increase its ferric chloride dose—raising supply, cost, and operational concerns. To avoid these issues, the city explored a new technology that generates a ferrous reagent via an in situ electrolytic process to replace bulk ferric chloride. The electrolytic ferrous reagent removed arsenic to below 5 μg/L, reduced permeate manganese levels, and improved effluent quality with a far lower coagulant dose. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disorder with a varying range of organs involved leading to adverse outcomes. However, very little is known, with conflicting results about the association between RA and atrial fibrillation (AF). We aim to evaluate the association between RA and AF, and other clinical outcomes. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until September 10, 2023. Primary clinical outcomes were AF. Secondary outcomes were acute coronary syndrome (ACS), stroke, and all-cause mortality (ACM). A total of 4 679 930 patients were included in the analysis, with 81 677 patients in the RA group and 4 493 993 patients in the nonrheumatoid arthritis (NRA) group. The mean age of the patients was 57.2 years. Pooled analysis of primary outcomes shows that RA groups of patients had a significantly higher risk of AF (odds ratios [OR], 1.53; 95% confidence interval [CI]: [1.16-2.03], p < .001) compared with NRA groups. Secondary Outcomes show that the RA group of patients had significantly higher odds of ACS (OR, 1.39; 95% CI: [1.26-1.52], p < .001), and ACM (OR, 1.19; 95% CI: [1.03-1.37], p = .02) compared with the NRA groups. However, the likelihood of stroke (OR, 1.02; 95% CI: [0.94-1.11], p = .61) was comparable between both groups of patients. Our study shows that RA groups of patients are at increased risk of having AF, ACS, and ACM. [ABSTRACT FROM AUTHOR]

Inhibitors specifically targeting the 1‐phosphatidylinositol 3‐phosphate 5‐kinase (PIKFYVE) disrupt lysosome homeostasis, thereby selectively terminating autophagy‐dependent human cancer cells in vivo as well as in vitro without harming the viability of nonmalignant cells. To elucidate the mechanism by which PIKFYVE inhibition induces cell death, autophagy‐dependent melanoma cells were compared with normal foreskin fibroblasts. RNA sequence profiling suggested that PIKFYVE inhibitors upregulated an endoplasmic reticulum (ER) stress response involving interleukin‐24 (IL24; also known as MDA7) selectively in melanoma cells. Subsequent biochemical and genetic analyses confirmed these results and extended them to tumor xenografts in which tumor formation and expansion were inhibited. IL24 expression was upregulated by the DDIT3/CHOP/CEBPz transcription factor, a component of the PERK‐dependent ER‐stress response. Ectopic expression of IL24‐induced cell death in melanoma cells, but not in foreskin fibroblasts, whereas ablation of the IL24 gene in melanoma cells prevented death. IL24 upregulation was triggered specifically by PIKFYVE inhibition. Thus, unlike thapsigargin and tunicamycin, which induce ER‐stress indiscriminately, PIKFYVE inhibitors selectively terminated PIKFYVE‐sensitive melanoma by inducing IL24‐dependent ER‐stress. Moreover, induction of cell death by a PIKFYVE inhibitor together with ectopic expression of IL24 protein was cumulative, thereby confirming the therapeutic potential of PIKFYVE inhibitors in the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is successful in patients with advanced Parkinson's disease (PD) but may worsen cognitive outcome, including facial emotion recognition (FER). Data‐analyses on 59 consecutive PD patients with complete pre‐ and postoperative assessments, using a sensitive FER test, showed no changes in FER 1 year after STN‐DBS surgery, both after group and individual analyses. These findings do however not exclude the impact of FER in and on itself on the outcome after STN‐DBS. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is characterized by a decline in episodic memory and executive functioning, hampering learning ability. Insight into outcome‐based learning capacity may be relevant for optimizing the learning potential of these patients. To date, mixed results have been found in studies in which cognitively impaired participants have to learn based on positive and negative outcomes. In this study, we investigated the role of negative and positive feedback on memory performance and participants' ability to adjust their behaviour accordingly in a sample of 23 early‐stage AD patients and 23 matched healthy controls. We administered a novel computerized object‐location memory task, in which participants were instructed to learn and memorize the locations of different everyday objects following errorless learning (EL) and trial‐and‐error learning (TEL). A separate probabilistic TEL task was employed in which participants had to learn how to adjust their behaviour based on positive and negative feedback. EL had a beneficial general effect on memory performance for object locations. However, this effect was not larger in early‐stage AD patients compared to controls and error frequency during acquisition of object locations was unrelated to later recall performance. No group differences were found on the probabilistic learning task with respect to learning performance over time and based on positive and negative feedback. Although the error monitoring system seems intact in patients with early‐stage AD, errors during learning are likely acting as a source of interference causing difficulty in storage or retrieval of object locations. [ABSTRACT FROM AUTHOR]

Understanding how to control microorganisms in source water and during treatment can help operators suppress microbial proliferation in distribution systems and prevent customer complaints. [ABSTRACT FROM AUTHOR]

Background and Objectives: Rice is a staple food for half of the world's population and plays an important role to deliver several micronutrients including B vitamins to humans. The present investigation was carried out to detect some B vitamins and estimate their concentrations in 309 traditional indica rice landraces, compared with three modern rice varieties predominantly available in the Indian market. Findings: Liquid chromatographic examination of the rice samples demonstrated that a large number of traditional rice landraces contained considerable amounts of different B vitamins. In the landraces examined, vitamin B1 (thiamine) was recorded to be present in the range of 0.01–10.55 mg/100 g, vitamin B2 (riboflavin) 0.01–2.63 mg/100 g, vitamin B3 (niacin) 0.20–4.52 mg/100 g, vitamin B5 (pantothenic acid) 0.01–18.55 mg/100 g, vitamin B6 (pyridoxine) 0.01–0.86 mg/100 g, and vitamin B7 (biotin) 0.01–5.90 mg/100 g in different rice landraces. Conclusion: Compared with traditional rice, modern rice cultivars seem to have substantially lower B vitamin levels. It appears that these vitamin‐rich traditional rice landraces if incorporated into daily diet, may serve to attain nutritional security of the poor. Significance and Novelty: Our results show that many traditional rice landraces are nutritionally superior to any modern rice cultivar, even though traditional rice landraces are normally not in priority for agronomic research and development. This study shows how native rice landraces may be leveraged to constitute novel nutritious diet that could enhance human health. [ABSTRACT FROM AUTHOR]

Introduction: Solanezumab is a monoclonal antibody that binds to the mid‐domain of soluble amyloid β peptide. This meta‐analysis evaluated the effect of low‐dose solanezumab on clinical progression in three phase 3 studies. Methods: The population comprised patients aged ≥55 years with Alzheimer's disease (AD) with mild dementia, randomized to 400 mg solanezumab or placebo every 4 weeks for 80 weeks. Frequentist mixed‐model repeated‐measures (MMRM) and Bayesian disease progression model (DPM) longitudinal analyses were conducted. Results: Pooled MMRM analyses showed a statistically significant effect of solanezumab across cognitive and functional outcome measures. DPM results were generally consistent with MMRM results, ranging from 15% to 30% slowing of clinical progression. Discussion: These analyses suggest low‐dose solanezumab slows clinical progression of AD with mild dementia. The ongoing A4 solanezumab study in participants with preclinical AD will ascertain the effect of a higher dose of solanezumab in an earlier disease stage. Highlights: Individual EXPEDITION studies were negative but suggest low‐dose solanezumab had an effect in slowing the clinical progression of Alzheimer's disease (AD) with mild dementia.At 80 weeks, mixed‐model repeated‐measures analyses showed numeric reductions in measures of clinical decline in solanezumab‐treated arms compared with placebo across almost every outcome measure, and statistical significance in multiple outcome measures in each study.Pooled analyses suggest a high probability that low‐dose solanezumab has at least some effect on slowing the clinical progression of AD with mild dementia.Across cognitive and functional outcome measures, estimates from disease progression model analyses range from 15% to 30% slowing of decline with low‐dose solanezumab in AD with mild dementia. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined differences in the timeliness of the initiation of home health care by race and the quality of home health agencies (HHA) among patients with Alzheimer's disease and related dementias (ADRD). METHODS: Medicare claims and home health assessment data were used for the study cohort: individuals aged ≥65 years with ADRD, and discharged from the hospital. Home health latency was defined as patients receiving home health care after 2 days following hospital discharge. RESULTS: Of 251,887 patients with ADRD, 57% received home health within 2 days following hospital discharge. Black patients were significantly more likely to experience home health latency (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.11–1.19) compared to White patients. Home health latency was significantly higher for Black patients in low‐rating HHA (OR = 1.29, 95% CI = 1.22–1.37) compared to White patients in high‐rating HHA. DISCUSSION: Black patients are more likely to experience a delay in home health care initiation than White patients. [ABSTRACT FROM AUTHOR]

Keywords: Rural health services EN Rural health services S20 S26 7 08/08/23 20230803 NES 230803 Inequities in the distribution of human resources in health around the world have long been a topic of concern and discussion. The concept may be explicit in a mission statement and/or seen as a moral obligation shown through service and beginning with values.The nature and content of school programs shaped social accountability, including student selection, involvement of communities in decision making and use of a curriculum that addresses the needs of underserved populations.Social accountability as a concept is not universal and should continue to be challenged and debated.Understanding of social accountability may be limited, even when enacted in school programs. The framework considers three questions: How does our school work? Future priorities: measuring impacts and outcomes of school activities THEnet's partner schools have cooperated to produce a significant collective contribution to the evidence base on approaches to education that can help build a rural and remote health workforce. [Extracted from the article]

Background: XPro1595 is a selective, brain penetrant neutralizer of soluble TNF with potent anti‐neuroinflammatory effects recently assessed for safety and pharmacological activity in a 12‐week, phase‐1b open‐label dose finding study in patients with AD (NCT03943264). An unbiased screen of imaging outcomes revealed signals for target engagement in gray matter (GM) cortices documented in the literature as regions most frequently affected by accumulation of amyloid‐beta (Aβ) in early and late phases of AD (Mattsson et al. 2019). Post‐hoc analyses were conducted to further investigate these signals. Method: Study results for patients (n = 9; MMSE range: 8‐27) with analyzable dMRIs who completed 12‐weeks of treatment with XPro1595 [0.3 mg/kg; n = 3) or (1.0 mg/kg; n = 6)] met inclusion criteria. Correlation matrices (uncorrected Pearson's r) were created to compare key secondary and exploratory imaging outcomes to clinical characteristics and CSF biomarkers of AD specific pathology (Roche Elecsys NeuroToolKit). Imaging outcomes included white matter free‐water (WM‐FW) as a prespecified proxy for neuroinflammation, and GM PerpPD+. PerpPD+ represents the diffusion components perpendicular to cortical GM minicolumns and serves as an indicator of worsening GM microarchitecture when increased in AD. Due to the small sample size, the threshold for identification of informative values was set at P<0.05. Result: At baseline, PerpPD in GM regions associated with early Aβ accumulation (insula, precuneus, isthmus and posterior cingulate, and lateral‐orbitofrontal cortices), and WM‐FW in the cingulum bundle, showed strong associations with CSF biomarkers of neurodegeneration (pTau and tTau), inflammatory gliosis (YKL‐40, GFAP and sTREM2), cognitive status (MMSE scores) and disease duration (Table1). Week‐12 results showed decreased PerpPD+ and WM‐FW in these regions, with a dose‐dependent signal concentrated in the isthmus cingulate GM and cingulum WM. Isthmus cingulate PerpPD+ ∆ (%) correlated positively with baseline Aβ42/40 and MMSE (Figure1), and negatively with duration of disease and cingulum WM‐FW, whereas cingulum WM‐FW ∆ (%) corelated with baseline pTau and tTau (Table 2). Conclusion: PerpPD+ in isthmus cingulate GM and WM‐FW in cingulum WM represent potential indicators of disease activity sensitive to early treatment effects in small, proof of concept clinical trials for AD. Additional research is warranted to further elucidate these signals. [ABSTRACT FROM AUTHOR]

Background: Recent autopsy and in vivo MRI studies supported structural integrity of the brainstem locus coeruleus (LC) as a potential indicator of initial AD‐related pathological processes. Importantly, in the earliest stages of the disease, these changes to the neuronal density of the LC are associated with changes to the somatic morphology and dendritic atrophy. Here, we aimed to examine whether LC microstructural integrity, assessed in vivo with advanced diffusion‐weighted magnetic resonance imaging (dMRI), is related to plasma AD biomarkers in a sample of cognitively unimpaired individuals. Method: Fifty‐seven cognitively unimpaired participants (mean age = 59.3±14.7y; 28 females) (Table 1) underwent a dMRI scanning session using a multi‐shell, high angular resolution acquisition protocol in a 7T scanner. LC microstructure was evaluated by applying the Neurite Orientation Dispersion and Density Imaging (NODDI) biophysical model on the dMRI data, yielding two metrics of microstructural integrity: Neurite Density Index (NDI) and Orientation Dispersion Index (ODI). Additionally, blood samples were analyzed to assess AD plasma biomarkers, including Aβ42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau phosphorylated at threonine 181 (pTau181) or threonine 231 (pTau231). Result: Higher age was associated with lower LC ODI (t = ‐2.77, p = 0.008) but not LC NDI values (t = 0.44, p = 0.658). Multiple linear regressions adjusted for age, sex, and estimated Total Intracranial Volume (eTIV) showed that lower NDI in the LC was associated with higher plasma GFAP levels (t = ‐2.08, p =.04, Figure 1). In addition, we found a negative association between ODI within the LC and Aβ42/40 (t = ‐2.79, p =.007, Figure 2). No significant relationships were found between LC NDI/ODI values and plasma NfL or pTau biomarkers. Conclusion: Consistent with animal studies, these findings suggest that microstructural changes in the LC are associated with astroglial activation in the earliest stages of the disease. Associations with Aβ42/40 were unexpected but might reflect loss of white matter compartments or changes in lipid density. In future analyses, we will further examine the biological interpretation of the NODDI metrics in subcortical regions, in particular in the context of AD‐related processes. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is a safe non‐invasive brain stimulation (NIBS) procedure which helps to stimulate a particular region of interest by modulating the neuronal firing rate, thereby modulating the cognitive functioning. The tDCS intervention is known to show improvement on memory recall and recognition in patients with mild cognitive impairment (MCI) and mild Alzheimer's Disease (mild AD) Method: We investigated the effect of anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation at the right supra‐orbital area in patients with MCI (n = 18) and mild AD (n = 20) (Refer Table 1), after due approval from Institute Ethics Committee NIMHANS. Both baseline and post‐intervention assessments for a single patient were administered by the different assessors allocated randomly using NIMHANS neuropsychological battery for elderly (NNB‐E). Two resting state functional magnetic resonance imaging (rsfMRI) acquisitions, before and after the ten sessions of tDCS, each session lasting 20 minutes. A spherical mask of 5 mm diameter was chosen a priori on the left middle frontal gyrus (LMFG) as a seed for performing seed based functional connectivity (sbFC) analysis using default preprocessing pipeline and pre‐post analysis setup in CONN 18b toolbox. Result: The combined sample of patients with MCI and mild AD showed significant improvement in word list learning trial 3 (pre tDCS 5.85 (1.59); post tDCS 6.63 (1.67); Z = 3.586, p<0.0001) and delayed recall (pre tDCS 1.50 (1.88); post tDCS 2.45 (2.33); Z = 3.656, p<0.0001) scores using NNB‐E. The sbFC analysis showed significantly reduced functional connectivity between left MFG (the region of anodal stimulation) and posterior cingulate cortex (PCC) as well as precuneus cortex (cluster‐level extent threshold p‐FDR <0.05) after tDCS. Post‐hoc tests showed that these reductions after tDCS intervention were also found to be significantly associated with attention and auditory verbal learning memory scores (Refer Figure 1 and Table 2). Conclusion: The tDCS intervention helped reducing the functional connectivity at rest, which was responsible for compensatory neuronal processes found in early AD. These findings unravel the therapeutic role of tDCS by enhancing auditory verbal memory performance and altering the functional connectivity at PCC and precuneus cortex in earlier stages of AD. [ABSTRACT FROM AUTHOR]

Background: Age is the most significant predictor of Alzheimer's disease and related dementias (ADRD). Biological age, in contrast to chronological age, is modifiable – shaped by environmental and social factors which contribute to the functional declines observed in aging. Accelerated biological aging has been observed in historically underrepresented populations in ADRD research who are at highest risk for developing ADRD. Telomere length (TL) is a marker of biological age and empirically associated with cognitive aging. However, this association has not been investigated in historically underrepresented populations such as American Indians / Alaska Natives (AI/AN). This study reports on the utility of TL to predict cognitive performance in a sample of middle‐aged and older adults from Wisconsin communities historically underrepresented in ADRD research. Method: The Wisconsin Alzheimer's Disease Research Center's (WADRC) Inclusion of Underrepresented Groups Core engages AI/AN, Blacks / African Americans (B/AA), and participants of multi‐race and ethnicity identities through community based participatory research practices. A sample (n = 188) identifying their race as AI/AN or B/AA were included if they provided whole blood and completed the Rey Auditory Verbal Learning Test (RAVLT, Trials 1‐5) and the Trails Making Test (TMT, A and B times) for verbal learning and executive functioning, respectively. DNA was extracted from whole blood and analyzed with monochrome multiplex quantitative polymerase chain reaction for TL. Multivariable linear regression analyses tested relationships between TL and cognitive test performance. Result: The participants (mean age = 60.88 ±9.06) were majority female, with 79.26% B/AA and 12.77% AI/AN (Table 1). In bivariate analyses, TL significantly correlated with all outcomes: longer telomeres correlated with better verbal learning and executive functioning performance (Figure 1A‐C). In multivariable regression models, TL significantly predicted cognitive performance for all outcomes independent of participant sex, race, age, and cognitive status (Table 2). Conclusion: These findings suggest that TL is a strong predictor of cognitive performance for historically underrepresented populations, offering potential opportunities for screening of accelerated biological aging and interventions. The community‐led research at the WADRC makes this analysis the first of its kind to include AI/AN participants. Future ADRD research should consider behavioral and socioeconomic interventions shown to modify biological aging. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with familial early‐onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole‐exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild‐type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss‐of‐function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. Highlights: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early‐onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease.TRIM25 protein studies support that the mutation exerts its effect through loss of function.TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration.The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research. [ABSTRACT FROM AUTHOR]

Translocation, often a management solution reserved for at‐risk species, is a highly time‐sensitive intervention in the face of a rapidly changing climate. The definition of abiotic and biotic habitat requirements is essential to the selection of appropriate release sites in novel environments. However, field‐based approaches to gathering this information are often too time intensive, especially in areas of complex topography where common, coarse‐scale climate models lack essential details. We apply a fine‐scale remote sensing‐based approach to study the 'akikiki (Oreomystis bairdi) and 'akeke'e (Loxops caeruleirostris), Hawaiian honeycreepers endemic to Kaua'i that are experiencing large‐scale population declines due to warming‐induced spread of invasive disease. We use habitat suitability modeling based on fine‐scale light detection and ranging (lidar)‐derived habitat structure metrics to refine coarse climate ranges for these species in candidate translocation areas on Maui. We found that canopy density was consistently the most important variable in defining habitat suitability for the two Kaua'i species. Our models also corroborated known habitat preferences and behavioral information for these species that are essential for informing translocation. We estimated a nesting habitat that will persist under future climate conditions on east Maui of 23.43 km2 for 'akikiki, compared to the current Kaua'i range of 13.09 km2. In contrast, the novel nesting range for 'akeke'e in east Maui was smaller than its current range on Kaua'i (26.29 vs. 38.48 km2, respectively). We were also able to assess detailed novel competitive interactions at a fine scale using models of three endemic Maui species of conservation concern: 'ākohekohe (Palmeria dolei), Maui 'alauahio (Paroreomyza montana), and kiwikiu (Pseudonestor xanthophrys). Weighted overlap areas between the species from both islands were moderate (<12 km2), and correlations between Maui and Kaua'i bird habitat were generally low, indicating limited potential for competition. Results indicate that translocation to east Maui could be a viable option for 'akikiki but would be more uncertain for 'akeke'e. Our novel multifaceted approach allows for the timely analysis of both climate and vegetation structure at informative scales for the effective selection of appropriate translocation sites for at‐risk species. [ABSTRACT FROM AUTHOR]

Copyright of People & Nature is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Cutaneous ulcerative skin lesions in a complex of invasive Gulf of Mexico lionfish (Red Lionfish Pterois volitans, Devil Firefish P. miles, and the hybrid Red Lionfish × Devil Firefish) became epizootic beginning in mid‐August 2017. Herein, we provide the first pathological descriptions of these lesions and summarize our analyses to elucidate the etiology of the disease. Methods: We examined ulcerated and normal fish through gross pathology and histopathology, bacterial sampling, and unbiased metagenomic next‐generation sequencing. We tracked prevalence of the disease, and we used biological health indicators (condition factor, splenosomatic and hepatosomatic index) to evaluate impacts to health, while considering sex and age as potential risk factors. Result: Typical ulcerative lesions were deep, exposing skeletal muscle, and were bordered by pale or reddened areas often with some degree of scale loss. Only incidental parasites were found in our examinations. Most fish (86%; n = 50) exhibited wound healing grossly and histologically, confirmed by the presence of granulation tissues. A primary bacterial pathogen was not evident through bacterial culture or histopathology. Metagenomic next‐generation sequencing did not reveal a viral pathogen (DNA or RNA) but did provide information about the microbiome of some ulcerated specimens. Compared with clinically healthy fish, ulcerated fish had a significantly lower condition factor and a higher splenosomatic index. Disease prevalence at monitored sites through July 2021 indicated that ulcerated fish were still present but at substantially lower prevalence than observed in 2017. Conclusion: Although some common findings in a number of specimens suggest a potential role for opportunistic bacteria, collectively our suite of diagnostics and analyses did not reveal an intralesional infectious agent, and we must consider the possibility that there was no communicable pathogen. Impact StatementAn outbreak of ulcers affected lionfish in the Gulf of Mexico. The disease occurred coincident to declines in invasive lionfish populations but could be contagious to native fish. Sick fish were examined to determine the cause. Findings were inconclusive but bacteria and environmental factors should be further investigated. [ABSTRACT FROM AUTHOR]

Background: CSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence‐based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022. Method: A Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses. Result: In the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients' age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient‐centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first‐line biomarkers according to the main clinical suspicion (i.e., FDG‐PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer's disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second‐line biomarker when results of first‐line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG‐PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid‐positive and tau‐negative CSF results) or when a diagnosis remains possible despite a negative first‐line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies). Conclusion: The task force is currently defining the second‐line biomarkers of W3 and the project it set to deliver the final algorithm by June 2022. The workflow will promote consistency in diagnosing neurocognitive disorders across countries, and rational use of resources. The initiative has an impact in preparing clinicians to work in the upcoming clinical space where etiological disease‐modifying drugs are expected to be available. [ABSTRACT FROM AUTHOR]

Water column physico‐chemical studies were conducted over the southern Central Indian Ridge between 24°44'S and 25°52'S to identify and chemically characterize seafloor hydrothermal activity. High turbidity values were observed between 2300 and 2700 m with two distinct layers, between water depths of 2320–2500 m and 2510–2650 m, at two closely spaced CTD stations at 24°48.62'S (CTD‐17‐P5) and 24°48.68'S (CTD‐17‐P8). Elevated concentrations of dissolved Mn (DMn: 19–112 nM), dissolved Fe (DFe: 33–88 nM), methane (CH4: 32–246 nM), elevated δ3He values (28%–88%), and stable carbon isotope ratios of CH4 confirm the hydrothermal origin. In plume layer‐1, the maximum concentrations were observed at 2375m at P8 and in plume layer‐2, the maximum concentrations were observed at 2570 m at P5. The stable isotope ratios of methane (δ13C‐CH4) show that heavier isotopes are enriched (−13.2‰ to −14.7‰) in the plume waters and are similar to vent fluids on the global mid‐oceanic ridges. Further, morphological and mineralogical studies of plume particles, collected from the plume layer‐2 maxima, clearly show the presence of barite, pyrite, chalcopyrite, and indicate possible venting of high‐temperature fluids in the vicinity of P5. Enrichment in methane relative to the other tracers and the general geochemical characteristics of these two plume layers, CH4/Mn (1.8–2.2); CH4/Δ3He (85–97 × 106), Mn/Δ3He (44–46 × 106), Fe/Δ3He (52–54 × 106), indicate that these plumes are formed from fluids released at the seafloor that circulated through ultramafic/gabbroic rocks. The high concentrations of dissolved gases and metals combined with the presence of sulfide particles in the water column provide evidence for a new ultramafic/gabbroic‐hosted hydrothermal vent field, at 24°49'S on the southern Central Indian Ridge. Plain Language Summary: Evidence for the seafloor hydrothermal activity was first discovered in 1970. Since then, numerous vent fields were discovered in Atlantic, Indian and Pacific Oceans. Among these three oceans, Indian Ocean is relatively less explored and most of the hydrothermal fields were discovered along the Central Indian Ridge. A multi‐disciplinary team, expertise in geophysics, geology, physical, chemical and biological oceanographers, has to work together to discover these fields. Extensive water column studies have been carried out on the southern Central Indian Ridge to identify plumes. High concentrations of manganese, iron, methane, and helium values between 2300 and 2700 m confirm the presence of hydrothermal plumes. The nature of the particles collected from these plumes shows that most of them are sulfides, sulfate and oxides of iron. The geochemical ratios in these plumes (combination of gas/metal and metal/gas) show that the fluid composition is controlled by ultramafic rocks. The chemical composition of both fluid and plume is mainly controlled by the rock type (basalt and/or ultramafic) of the sub‐seafloor. The high concentrations of gases and metals in the water column provide evidence for a new hydrothermal vent field, at 24°49'S on the southern Central Indian Ridge. Key Points: Chemical signatures in the deep waters of the southern Central Indian Ridge, at 24°49'S, provide evidence for hydrothermal plumesEnrichment of volatiles (helium and methane) over metals (manganese and iron) in plumes indicate the influence of ultramafic rocksPresence of sulfide and sulfate particles (pyrite, chalcopyrite and barite) in plumes may indicate the high‐temperature venting in the vicinity [ABSTRACT FROM AUTHOR]

Ovarian cancer ranks fifth in terms of cancer mortality in women due to lack of early diagnosis and poor clinical management. Characteristics like high cellular proliferation, EMT and metabolic alterations contribute to oncogenicity. Cancer, being a "metabolic disorder," is governed by various key regulatory factors like metabolic enzymes, oncogenes, and tumor suppressors. Sirtuins (SIRT1‐SIRT7) belong to the group of NAD+ deacetylase and ADP‐ribosylation enzymes that function as NAD+ sensors and metabolic regulators. Among sirtuin orthologs, SIRT6 emerges as an important oncogenic player, although its possible mechanistic involvement in ovarian cancer advancement is still elusive. Our data indicated a higher expression of SIRT6 in ovarian cancer tissues compared with the non‐malignant ovarian tissue. Further, we observed that overexpression of SIRT6 enhances glycolysis and oxidative phosphorylation in ovarian cancer cells. The energy derived from these processes facilitates migration and invasion through invadopodia formation by reorganization of actin fibers. Mechanistically, SIRT6 has been shown to promote ERK1/2‐driven activatory phosphorylation of DRP1 at serine‐616, which has an obligatory role in inducing mitochondrial fission. These fragmented mitochondria facilitate cell movement important for metastases. siRNA‐mediated downregulation of SIRT6 was found to decrease cellular invasion through compromised mitochondrial fragmentation and subsequent reduction in stress fiber formation in ovarian cancer cells. Thus, the present report establishes the impact of SIRT6 in the regulation of morphological and functional aspects of mitochondria that modulates invasion in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Copyright of PM & R: Journal of Injury, Function & Rehabilitation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Dance has been linked in a complex manner to pain and the physical and psychological peculiarities of this discipline could influence pain perception and chronicity of pain. Objective: To determine the differences in cognitive, emotional, and somatosensory symptoms between dancers with acute versus chronic pain. Design: A cross-sectional study of professional dancers with pain. Setting: Higher conservatory of dance. Participants: Thirty-four professional dancers experiencing pain were included. The cohort was divided into two subgroups: those with acute pain (<3 months duration) and those with chronic pain (>3 months duration). Interventions: Not applicable. Main Outcome Measures: Pain intensity (as measured by the visual analogue scale or VAS), pressure pain threshold (PPT), Pain Catastrophizing Scale (PCS), pain-related fear of movement (Tampa Scale of Kinesiophobia [TSK- 11]), fear avoidance beliefs (Fear-Avoidance Beliefs Questionnaire [FABQ]), self-efficacy (Chronic Pain Self-Efficacy Scale [CPSS]). and chronic pain severity (Chronic Pain Graded Scale [CPGS]). Results: Dancers with chronic pain reported higher levels of pain intensity in daily activities (p < .01; t = 3.42; d = 1.17) and during exercise/dance (p = .02; t = 2.82; d = 0.82), as well as lower PPT in lumbar (p = .03; t = 3.22; d = 1.1) and tibialis regions (p = .01; t = 2.51; d = 0.86). Dancers with acute pain experienced worse psychological symptoms indicated by the fear of harm subscale of TSK-11 (p = .04; t = -2.08; d = 0.72), physical activity subscale of FABQ (p = .03; t = 2.27; d = 0.78), and pain management subscale of CPSS (p = .01; t = 2.76; d = 0.94) and lower scores for CPGS scale (p = .01; t = 2.99; d = 0.7 to 1.26). Conclusions: The results showed differences in pain intensity and PPT revealing higher values in dancers with chronic pain. It is possible that the physical and psychological characteristics of dancers, as well as the sociocultural aspects of this discipline, could influence the way in which this population interprets pain. [ABSTRACT FROM AUTHOR]

In a digital economy characterized by high volumes of information and ideas, many of which could be contradictory to one another, employees high in dialectical thinking should be well poised to connect disparate ideas to generate creative solutions for business problems. Yet, it is unclear whether dialectical thinking as a creativity‐relevant skill can be realized in naturalistic workplace settings, given past mixed findings and the lack of field studies. We propose that supervisors' leadership styles are important moderators that can unlock employees' creativity potential in dialectical thinking. Additionally, we compare the activating effect of transformational leadership and the inhibiting effect of transactional leadership to investigate which leadership style is more impactful in unlocking the power of dialectical thinking on creativity. Through two multisource field studies, we find that dialectical thinking's effect on creativity is context‐sensitive, and transactional leadership's inhibiting effect on the dialectical thinking‐creativity relationship is stronger than transformational leadership's activating effect. These findings qualify the predominant view that leaders should focus on enacting activators to stimulate employee creativity; rather, avoiding inhibitors might be more effective instead. Practically, our findings suggest that leaders should ensure they engage in fewer transactional leadership behaviors. [ABSTRACT FROM AUTHOR]

Failure of colorectal cancer (CRC) treatment is due to residual disease, and its timely identification is critical for patient survival. Detecting CRC-associated mutations in patient circulating cell-free DNA is confounded by tumor mutation heterogeneity, requiring primary tumor sequencing to identify relevant mutations. In this study, we assessed BCAT1 and IKZF1 methylation levels to quantify circulating tumor DNA (ctDNA) and investigated whether this method can be used to assess tumor burden and efficacy of therapy. In 175 patients with CRC who were ctDNA-positive pretreatment, ctDNA levels were higher with advancing stage (P < 0.05) and correlated with tumor diameter (r = 0.35, P < 0.001) and volume (r = 0.58, P < 0.01). After completion of treatment (median of 70 days [IQR 49-109] after surgery, +/- radiotherapy, +/- chemotherapy), ctDNA levels were reduced in 98% (47/48) and were undetectable in 88% (42/48) of patients tested. For those with incomplete adjuvant chemotherapy after surgery, roughly half remained ctDNA-positive (11/21, 52.4%). The presence of ctDNA after treatment was associated with disease progression (HR 9.7, 95%CI 2.5-37.6) compared to no ctDNA. Assaying blood for ctDNA methylated in BCAT1/IKZF1 has the potential for identifying residual disease due to treatment failure, informing a potential need for therapy adjustment in advanced disease. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a leading cause of dementia, characterized by cognitive decline, and is more prevalent in women, possibly due to estrogen loss after menopause. Dioscorea bulbifera (DB), a medicinal plant, has been proposed as a potential treatment for AD. However, the underlying mechanism of action of DB and its neuroprotective effects in AD, particularly in the context of estrogen loss, remain unclear. Method: In this study, we employed an integrative network pharmacology approach to predict the mechanism of action of DB in AD. Using a collection of AD‐related genes and predicted DB targets, we identified putative targets, direct regulatory targets, and potential regulatory targets of DB. Pathway‐enrichment analysis was performed to elucidate the pivotal pathways involved in DB's treatment of AD. Molecular docking was conducted to verify the interactions between the core targets and the active ingredients of DB. In vivo experiments were conducted using ovariectomized rats induced with scopolamine to evaluate the neuroprotective effects of DB. Acetylcholine (Ach) and serum estradiol levels were quantified using ELISA. Result: Our results identified 132 putative targets, including 68 direct regulatory targets and 25 potential regulatory targets of DB for the treatment of AD. Pathway‐enrichment analysis revealed that neurotransmitter clearance in the synaptic cleft was a crucial pathway in the treatment of AD with DB. Molecular docking further supported the interactions between the core targets (ESR1, APP, GSK3β, BACE1, AChE, and MAOB) and the active ingredients of DB. In vivo experiments using ovariectomized rats induced with scopolamine demonstrated the neuroprotective effect of DB and validated the predicted mechanism of action. Conclusion: Our findings provide experimental support for the predicted mechanism of action of DB in AD caused by estrogen loss, and validate its neuroprotective effects using behavioral tests and ELISA in ovariectomized rats. DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment. [ABSTRACT FROM AUTHOR]

Background: Despite almost two decades of research, the physiologic role of α‐synuclein remains unclear. Mice lacking α‐syn only show mild phenotypes, and most mechanistic studies have been done either in α‐syn over‐expressing systems, or in mice lacking all three synuclein genes (α/β/γ). However, over‐expression of proteins can induce unwanted phenotypes, and 'triple‐knockout' synuclein mice have structural and physiologic changes that are not specific to α‐syn – complicating interpretations. Methods: We used CRISPR technology to systematically inactivate or activate each synuclein gene in cultured mouse hippocampal neurons, ensuring that our manipulations did not lead to compensatory changes in the non‐targeted synucleins. Gene‐editing was followed by unbiased evaluation of physiology and ultrastructure using optical synaptic vesicle (SV) recycling assays, electrophysiologic recordings, single‐molecule trafficking assays, super‐resolution imaging, and electron microscopy. Results: Neurotransmission is maintained at a range of different activity patterns, motivating us to evaluate the role of α‐syn under basal states as well as conditions involving trains of action potentials. Elimination of α‐syn led to substantial increases in basal exocytosis. Single‐molecule trafficking of SVs in these neurons indicated an increase in mobility of reserve pool vesicles when α‐syn was absent. Increasing endogenous α‐syn levels by CRISPRa had largely reciprocal effects. Recent studies in our lab found that phosphorylation of α‐syn at the Ser129‐site is a trigger for α‐syn function at the synapse. Augmenting α‐syn functionality by constitutive phosphorylation of the α‐syn Ser129‐site also triggered clustering of distal SV‐pools, consistent with a role for α‐syn in physiologic clustering of reserve pool vesicles. However, when neuronal activity was augmented by trains of action potentials, loss of α‐syn selectively attenuated endocytosis, with no effect on exocytosis. Super‐resolution imaging revealed that α‐syn was translocated to peri‐active zones upon stimulation, suggesting that the altered localization of α‐syn under these conditions resulted in facilitation of endocytosis. Finally, mass‐spectrometry data also indicate that α‐syn binds to an endocytosis‐enriched proteome under conditions that favor neuronal activity. Conclusion: Our data provide clarity of the repertoire of a‐syn specific functions under different physiologic conditions. [ABSTRACT FROM AUTHOR]

Background: The A4 Study was a 240‐week, double‐blind, placebo‐controlled Phase 3 secondary prevention trial in cognitively unimpaired adults (ages 65‐85) with elevated amyloid on PET testing solanezumab, a monoclonal antibody targeting soluble amyloid‐beta. The companion LEARN Study enrolled participants who were otherwise eligible for A4 but did not show elevated amyloid. Method: Entry criteria included CDR‐Global Scale (CDR‐GS) = 0, MMSE≥25, WMS Logical Memory = 6‐18, and elevated amyloid on florbetapir PET (for A4). The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC) with key secondary functional measures: Cognitive Function Index (CFI), Activities of Daily Living Scale (ADL), and CDR‐GS. A subset of participants underwent flortaucipir Tau PET. Result: For A4, 1169 randomized: 578 to solanezumab and 591 to placebo. Treatment groups were well matched. Solanezumab did not slow cognitive decline on the PACC (mean change (95% CI): placebo ‐1.13 (‐1.45,‐0.81); solanezumab ‐1.43 (‐1.83,‐1.03); p =.260). Secondary clinical outcomes were consistent, numerically favoring placebo. Across both arms, 36.1% progressed to symptomatic AD, defined as CDR‐GS> 0 at two consecutive visits or final visit. Higher baseline amyloid levels were strongly associated with faster cognitive decline and greater risk of progression to symptomatic AD across both groups (p<.001). Amyloid continued to accumulate in both placebo (65.9 centiloid baseline, 19.3 increase) and solanezumab (66.2 centiloid baseline, 11.6 increase) groups. Tau PET showed similar increases in placebo and solanezumab groups in medial temporal lobe and neocortical composites, that were negatively correlated with PACC decline. No serious safety signals for solanezumab were identified, with only one case of ARIA‐E. ARIA‐H rates were similar across groups. LEARN participants (N = 538, 4.2 centiloid baseline on amyloid PET) did not demonstrate cognitive decline. Conclusion: The A4 Study demonstrated the feasibility of conducting a large‐scale trial in preclinical AD, with cognitive and functional measures sensitive to decline. Solanezumab did not slow cognitive decline or clinical progression. Baseline amyloid PET was among the strongest predictors of decline across both placebo and solanezumab. LEARN participants did not demonstrate decline. These results suggest that amyloid plaque removal may be necessary even at this very early stage of AD. [ABSTRACT FROM AUTHOR]

Background: Remote, smartphone‐based cognitive assessments such as the Mobile Toolbox (MTB) can improve our ability to detect subtle, yet meaningful cognitive changes that are affected early on by Alzheimer's disease (AD) pathology. The goal of our study was to investigate which MTB tests are sensitive to subtle cognitive deficits due to early amyloid and tau deposition. Method: The MTB will be administered to N = 100 clinically normal (CN) older adults who have retrospective and prospective clinical, cognitive and AD biomarker data from three well‐characterized prospective cohort‐studies of CN older adults: the Harvard Aging Brain Study and the affiliated Subjective Cognitive Decline and Instrumental Activities of Daily Living cohorts. The MTB includes six measures of fluid cognition, including episodic memory (Picture Sequence Memory and Face‐Name Associations), executive functions (Dimensional Change Card Sort, Flanker), working memory (Memory for Sequence), processing speed (Number‐Symbol Match), and two measures of crystallized cognition (Spelling and Vocabulary). Using confirmatory factor analysis, MTB baseline data will be used to determine which MTB tests are most strongly associated with established clinical assessments (i.e., measures included in the Preclinical Alzheimer's Cognitive Composite‐5 [PACC5]) as well as amyloid and tau biomarkers on positron emission tomography (PET) imaging. Result: Preliminary MTB data was available on 15 participants (age 74.3±8.2, 63% female, 16.6±2.9 years of education, MMSE 29±1.5). Table 1 shows exploratory correlation analyses, revealing that both MTB crystallized measures were associated with education but not age or sex. As expected, worse performance on MTB memory measures were associated with lower PACC5 scores, and greater amyloid and tau burden, albeit at trend‐level. Executive function and processing speed measures were not related to amyloid but did show associations with entorhinal tau. Conclusion: While preliminary, these findings suggest that the MTB may help elucidate the subtle cognitive deficits that are associated with early AD pathology. In addition to memory measures, the MTB fluid measures capture various aspects of cognitive function that are also relevant to preclinical AD. Data collection is ongoing, and next steps include examining which (combination of) MTB measures are most sensitive for detecting emerging AD pathology and to track cognitive change over time. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to provide cut points for the automated Elecsys Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers. Methods: Cut points for Elecsys amyloid beta 42 (Aβ42), total tau (t‐tau), hyperphosphorylated tau (p‐tau), and t‐tau/Aβ42 and p‐tau/Aβ42 ratios were evaluated in Mayo Clinic Study of Aging (n = 804) and Mayo Clinic Alzheimer's Disease Research Center (n = 70) participants. Results: The t‐tau/Aβ42 and p‐tau/Aβ42 ratios had a higher percent agreement with normal/abnormal amyloid positron emission tomography (PET) than the individual CSF markers. Reciever Operating Characteristic (ROC)‐based cut points were 0.26 (0.24–0.27) for t‐tau/Aβ42 and 0.023 (0.020–0.025) for p‐tau/Aβ42. Ratio cut points derived from other cohorts performed as well in our cohort as our own did. Individual biomarkers had worse diagnostic properties and more variable results in terms of positive and negative percent agreement (PPA and NPA). Conclusion: CSF t‐tau/Aβ42 and p‐tau/Aβ42 ratios are very robust indicators of AD. For individual biomarkers, the intended use should determine which cut point is chosen. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal fusion (LSF) outcomes for workers' compensation patients are worse than for the general population. The objectives were to examine the long‐term work capacity, opioid prescription and mental health outcomes of injured workers who have undergone LSF surgery in Victoria, Australia, and to identify demographic and pre‐ and post‐operative characteristics associated with these outcomes. Methods: Retrospective study of 874 injured workers receiving elective LSF from 2008 to 2016 in the Victorian workers' compensation system. WorkSafe Victoria's claims data were used to infer outcomes for recovery. Association of demographics, pre‐surgery and surgery variables with outcomes were modelled using multivariate multinomial logistic regression analyses. Results: Twenty‐four months after LSF surgery, 282 (32.3%) of the 874 injured workers had substantial work capacity, 388 (44.4%) were prescribed opioids, and 330 (37.8%) were receiving mental health treatment. Opioid prescription and limited work capacity before surgery were independent strong predictors of opioid prescription, reduced work capacity and mental health treatment 24 months after LSF. Pre‐operative mental health treatment was associated with the use of mental health treatment at 24 months. Other predictors for poor outcomes included a greater than 12‐month duration from injury to surgery, LSF re‐operation and common law or impairment benefit lodgement before surgery. Conclusion: An association between pre‐operative factors and post‐operative outcomes after LSF in a Victorian workers' compensation population was identified, suggesting that pre‐operative status may influence outcomes and should be considered in LSF decisions. The high opioid use indicates that opioid management before and after surgery needs urgent review. [ABSTRACT FROM AUTHOR]

Purpose: To develop a disposable point‐of‐care portable perfusion phantom (DP4) and validate its clinical utility in a multi‐institutional setting for quantitative dynamic contrast‐enhanced magnetic resonance imaging (qDCE‐MRI). Methods: The DP4 phantom was designed for single‐use and imaged concurrently with a human subject so that the phantom data can be utilized as the reference to detect errors in qDCE‐MRI measurement of human tissues. The change of contrast‐agent concentration in the phantom was measured using liquid chromatography‐mass spectrometry. The repeatability of the contrast enhancement curve (CEC) was assessed with five phantoms in a single MRI scanner. Five healthy human subjects were recruited to evaluate the reproducibility of qDCE‐MRI measurements. Each subject was imaged concurrently with the DP4 phantom at two institutes using three 3T MRI scanners from three different vendors. Pharmacokinetic (PK) parameters in the regions of liver, spleen, pancreas, and paravertebral muscle were calculated based on the Tofts model (TM), extended Tofts model (ETM), and shutter speed model (SSM). The reproducibility of each PK parameter over three measurements was evaluated with the intraclass correlation coefficient (ICC) and compared before and after DP4‐based error correction. Results: The contrast‐agent concentration in the DP4 phantom was linearly increased over 10 min (0.17 mM/min, measurement accuracy: 96%) after injecting gadoteridol (100 mM) at a constant rate (0.24 ml/s, 4 ml). The repeatability of the CEC within the phantom was 0.997 when assessed by the ICC. The reproducibility of the volume transfer constant, Ktrans, was the highest of the PK parameters regardless of the PK models. The ICCs of Ktrans in the TM, ETM, and SSM before DP4‐based error correction were 0.34, 0.39, and 0.72, respectively, while those increased to 0.93, 0.98, and 0.86, respectively, after correction. Conclusions: The DP4 phantom is reliable, portable, and capable of significantly improving the reproducibility of qDCE‐MRI measurements. [ABSTRACT FROM AUTHOR]

The Tiger Barb Puntigrus tetrazona is one of the highest trade volume freshwater species in the ornamental fish industry. Culture of larval Tiger Barb is largely dependent on live feeds at first feeding and throughout early life stages, leading to increased cost relative to the use of commercially produced microparticulate diets (MDs). Potential for the successful culture of Tiger Barb by using MDs from first feeding was evaluated here, with a focus on the physiological characteristics that limit digestive capacity in larval cyprinids, as well as the hypothetical benefit of including feed attractants in formulated larval feeds. Comparable growth and survival were achieved for the first 14 d of feeding with one of three MDs when compared to feeding with brine shrimp Artemia spp. Histological preparation revealed evidence for a fully functional pharyngeal jaw structure, including pharyngeal teeth and a pharyngeal pad, from 6 d posthatch, which coincided with first feeding. The masticatory function of these structures likely facilitated the breakdown and subsequent utilization of the relatively complex macronutrients that are characteristic of MDs. Inclusion of top‐coated potential attractants (tryptophan, taurine, trimethylglycine betaine, or a mix of the three) with the most successful MD from the original trial failed to induce an increased feeding response, as evidenced by the observation of similar feeding incidence, total larval protein content, and tryptic enzyme activity relative to a negative control MD without added attractants. The results of this research suggest that the successful culture of larval Tiger Barb is possible with the use of commercially available MDs, potentially leading to cost savings and increased resilience of producers in the ornamental aquaculture industry. [ABSTRACT FROM AUTHOR]

Background: We have investigated the role of extremely‐low‐frequency magnetic field (ELF‐MF, 17.96µT, 50Hz, 2hr/day for 60 days) exposure on i.c.v. streptozotocin (STZ, 3mg/kg bw, bilaterally, single bolus) induced rat model of AD in a customized chamber. Method: Spatial memory and recognition memory was measured using Morris water maze and one trial object recognition task respectively. Further, acetylcholine, acetylchoniesterase, calcium‐calmodulin dependent protein kinase II from frontal cortex and hippocampus and serum Aß1‐42 was measured using colorimetric or ELISA technique. Result: Spatial memory in Morris water maze (MWM) showed a significant decrease both in the distance travelled before entering into goal quadrant (p=0.05) as well as in latency to the first entry into goal quadrant (p=0.05) in AD animals, upon ELF‐MF exposure. On the other hand, recognition index (p=0.003) and discrimination index (p<0.0001) in the one trial object recognition test (OTORT) on the 60th day after ELF‐MF exposure to STZ animals showed a significant increment when compared with AD induced animals. These behavioural results suggests an improvement in cognitive function in i.c.v. STZ animals, upon exposure to ELF‐MF. When we looked for serum Aß1‐42 of experimental animals, we found a significant reduction (p=0.05) of serum Aß1‐42 in AD animals after ELF‐MF exposure. Further, concentration of acetylcholine (ACh) was found to be increased (p=0.05) only in hippocampus, whereas AChE level was found to be reduced in both frontal cortex (p=0.05) as well as in hippocampus (p=0.05) after 60 day ELF‐MF treatment in i.c.v. STZ animals. Expression of CAMKII increased in frontal cortex (p=0.05) as well as in hippocampus (p0.05) after ELF‐MF treatment. These results suggests that memory retention observed in the behavioural results, may be due to the reduction of AChE in hippocampus as well as in frontal cortex, Aß1‐42 in serum, and an increase in levels of ACh, CAMKII in hippocampus as well as in the frontal cortex. Conclusion: Therefore, evidences strengthens the notion that, ELF‐MF treatment improves cognitive impairment seen in i.c.v. STZ animal model of AD through prevention of synaptic dysfunction, replenishment of ACh as well as CAMKII in hippocampus. [ABSTRACT FROM AUTHOR]

Rude and disrespectful behaviors are ubiquitous and pervasive in the workplace. The purpose of this study was to examine the effects of witnessed rudeness on dental student psychomotor performance. Using an experimental, between‐subjects design, 71 2nd (Sophomore) year dental students witnessed either an experimental (rude) or control (neutral) condition in which a confederate lab manager interacted in a rude or neutral manner with a prospective lab assistant candidate. Students then performed a mock prosthodontics psychomotor examination as part of the fixed prosthodontics preclinical course. Results indicated that those students who arrived at the experimental session cognitively depleted (+1 SD above the mean) and were exposed to the rude condition were significantly more likely to make critical errors when performing a posterior bridge preparation, compared to those students in the control group. There were no significant differences between the rude and control conditions for participants who were not cognitively depleted (−1 SD below the mean). Overall, the findings indicate that for those dental students suffering from cognitive depletion, merely witnessing rudeness can have adverse impacts on psychomotor performance and potentially, eventual patient care. [ABSTRACT FROM AUTHOR]

Lightweight insulation refractories are essential for high‐temperature performance to reduce energy consumption. This study investigates a new insulation material, that is, solid waste rice husk ash (RHA) derived lightweight refractory castable, replacing traditional insulation refractory brick. The RHA is generated after the burning of rice husk as biomass fuel. The RHA is used as an aggregate and alkali‐extracted silica sol from RHA as a binder to fabricate the insulation castable. The nanosilica containing (~30 wt%) sol is employed to synthesize the refractory castable by varying the sol amount (2.5‐12.5 wt% silica from sol). The castable specimens are cast by a vibro‐caster and fired at 900‐1200°C in a muffle furnace. The physic‐mechanical and thermal conductivity (κ) of the castable is investigated. At 1100°C with 10 wt% dry sol retaining sample shows an excellent apparent porosity (~65%), low bulk density (~ 0.8 g/cm3), and κ (0.136 W/m k) with sustainable compressive strength (6 MPa). The acquired results are a good match with the literature (other wastes‐derived insulation materials) and industrial (silica insulation brick) obtained data. These promising outcomes may inspire the refractory industries for using RHA as an aggregate and RHA extracted sol as a binder for making insulation castable. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal (AM) fungi, a group of widespread fungal symbionts of crops, could be important in driving crop yield across crop rotations through plant–soil feedbacks (PSF). However, whether preceding crops have a legacy effect on the AM fungi of the subsequent crop is poorly known. We set up an outdoor mesocosm crop rotation experiment that consisted of a first phase growing either one of four pre‐crops establishing AM and/or rhizobial symbiosis or not (spring barley, faba bean, lupine, canola), followed by an AM crop, winter barley. After the pre‐crop harvest, carbon‐rich organic substrates were applied to test whether it attenuated, accentuated or modified the effect of pre‐crops. The pre‐crop mycorrhizal status, but not its rhizobial status, affected the richness and composition of AM fungi, and this difference, in particular community composition, persisted and increased in the roots of winter barley. The effect of a pre‐crop was driven by its single symbiotic group, not its mixed symbiotic group and/or by a crop‐species‐specific effect. This demonstrates that the pre‐crop symbiotic group has lasting legacy effects on the AM fungal communities and may steer the AM fungal community succession across rotation phases. This effect was accentuated by sawdust amendment, but not wheat straw. Based on the previous observation of decreased crop yield after AM pre‐crops, our findings suggest negative PSF at the level of the plant symbiotic group driven by a legacy effect of crop rotation history on AM fungal communities, and that a focus on crop symbiotic group offers additional understanding of PSF. [ABSTRACT FROM AUTHOR]

A patent foramen ovale (PFO) is an interatrial shunt, with a prevalence of 20-34% in the general population. While most people do not have secondary manifestations of a PFO, some reported sequelae include ischaemic stroke, migraine, platypnoea-orthodeoxia syndrome and decompression illness. Furthermore, in some cases, PFO closure should be considered for patients before neurosurgery and for patients with concomitant carcinoid syndrome. Recent trials support PFO closure for ischaemic stroke patients with high risk PFOs and absence of other identified stroke mechanisms. While PFOs can be associated with migraine with auras, with some patients reporting symptomatic improvement after closure, the evidence from randomised controlled trials is less clear in supporting the use of PFO closure for migraine treatment. PFO closure for other indications such as platypnoea-orthodeoxia syndrome, decompression illness and paradoxical embolism are based largely on case series with good clinical outcomes. PFO closure can be performed as a day surgical intervention with high procedural success and low risk of complications. [ABSTRACT FROM AUTHOR]

The timing of life history events in many plants and animals depends on the seasonal fluctuations of specific environmental conditions. Climate change is altering environmental regimes and disrupting natural cycles and patterns across communities. Anadromous fishes that migrate between marine and freshwater habitats to spawn are particularly sensitive to shifting environmental conditions and thus are vulnerable to the effects of climate change. However, for many anadromous fish species the specific environmental mechanisms driving migration and spawning patterns are not well understood. In this study, we investigated the upstream spawning migrations of river herring Alosa spp. in 12 coastal Massachusetts streams. By analyzing long‐term data sets (8–28 years) of daily fish counts, we determined the local influence of environmental factors on daily migration patterns and compared seasonal run dynamics and environmental regimes among streams. Our results suggest that water temperature was the most consistent predictor of both daily river herring presence–absence and abundance during migration. We found inconsistent effects of streamflow and lunar phase, likely due to the anthropogenic manipulation of flow and connectivity in different systems. Geographic patterns in run dynamics and thermal regimes suggest that the more northerly runs in this region are relatively vulnerable to climate change due to migration occurring later in the spring season, at warmer water temperatures that approach thermal maxima, and during a narrower temporal window compared to southern runs. The phenology of river herring and their reliance on seasonal temperature patterns indicate that populations of these species may benefit from management practices that reduce within‐stream anthropogenic water temperature manipulations and maintain coolwater thermal refugia. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine social cognition and social functioning in a group of amnestic mild cognitive impairment (aMCI) and Alzheimer's dementia (AD) patients. Thirty one people with aMCI, 29 individuals with AD, and 45 healthy older adults participated in the study. Facial expressions of happiness, anger, fear, disgust, and surprise presented in different intensities had to be labelled. Mentalizing was assessed using first‐order belief theory of mind (ToM) stories and everyday social functioning by the Inventory of Interpersonal Situations (IIS), completed by an informant. aMCI patients were impaired in recognizing the emotions anger, disgust, and fear, while AD patients were impaired in recognizing the emotions anger, disgust, and surprise. More importantly, no significant differences between aMCI and AD patients were found on overall emotion recognition. Both the aMCI and AD patients were impaired on the ToM task, but no differences between the aMCI and AD patients were found. On everyday social functioning, only the AD patients showed impairments. No associations between the IIS and ToM were found, but the IIS and emotion perception were significantly correlated. Regression analysis taking all potentially confounding variables into account showed that only mood, but not the social‐cognitive task performance or any other cognitive variable, predicted social functioning. aMCI and AD patients demonstrated impairments in mentalizing and facial emotion perception, and showed decrements in everyday social functioning. Informing caregivers about these deficits may help them to understand deficits in social cognition that may be present already in the MCI stage of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Despite the utility of blood analyte evaluation as a diagnostic tool to assist in monitoring the health of marine fishes, baseline data are often lacking for many commercially important finfish species. The objective of this study was to compare hematology and plasma chemistry data for adult wild‐caught Almaco Jack Seriola rivoliana at time of capture and again following a period of acclimation to a recirculating aquaculture system and hyposalinity treatment. A total of 30 clinically healthy adult fish were caught via hook and line in the eastern Gulf of Mexico, approximately 120 mi offshore from Madeira Beach, Florida. Blood was collected from a subset of these fish (n = 13) immediately after capture and again at 16 weeks postcapture from another subset (n = 12) following a 45‐d antiparasitic hyposalinity treatment. A 19% increase in fish body weight was observed during the study period (16 weeks) and no overt health issues or mortality were noted. Compared to fish that were sampled immediately following capture, several significant differences (P < 0.05) were observed. Absolute white blood cells were lower in captive held fish, suggesting biological variation, antigenic stimulation in wild fish, and/or immunosuppression associated with stress in captive held fish. Lower sodium, chloride, and calculated osmolality indicate osmoregulatory adjustments following the hyposalinity treatment by 16 weeks postcapture. Other observed plasma biochemical differences presumptively reflect dietary and/or environmental changes, or physiological variation following acclimation to captive culture conditions. This study reports baseline blood analyte data of wild‐caught Almaco Jack and documents hematological and plasma biochemical responses to their new environment as captive broodstock. Baseline hematological and plasma biochemistry data obtained during this study are the first reported for this species. [ABSTRACT FROM AUTHOR]

Cobalt oxide nanoparticles (6 nm) supported both inside and outside of hollow carbon spheres (HCSs) were synthesized by using two different polymer templates. The oxidation of benzyl alcohol was used as a model reaction to evaluate the catalysts. PXRD studies indicated that the Co oxidation state varied for the different catalysts due to reduction of the Co by the carbon, and a metal oxidation step prior to the benzyl alcohol oxidation enhanced the catalytic activity. The metal loading influenced the catalytic efficiency, and the activity decreased with increasing metal loading, possibly due to pore filling effects. The catalysts showed similar activity and selectivity (to benzaldehyde) whether placed inside or outside the HCS (63% selectivity at 50% conversion). No poisoning was observed due to product build up in the HCS. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease of the oral cavity but the pathogenesis of the disease is still uncertain among the areca nut chewers. Every chewer does not show up with fibrotic changes that further extend to genetic basis of OSMF pathogenesis. Genetic predisposition has been now identified as a major risk factor for increasing the susceptibility toward the disease among these chewers. In this study, two single nucleotide polymorphism (SNP) of COL1A2 rs42542 (Exon 28, G1645C) and rs421587 (Intron 28, 665+15A>G) showing mRNA splice variant trait with exon 28 skipping, extended exon 28 and intron 28 retention. The polymorphisms of the COL1A2 gene was identified by polymerase chain reaction‐direct genomic DNA sequencing from 187 patients with OSMF and 188 control participants matched on age, gender, and ethnicity. COL1A2 alternative splice variants from mRNA in human oral biopsy tissues obtained from OSMF patient and controls were confirmed by using reverse transcription PCRs (RT‐PCRs). Significant genotypic associations were observed for an exon 28 SNP (GC; P < [OR‐2.35; CI {1.44‐3.83}; P <.001] and CC [OR‐6.99; CI {1.83‐31.24}; P =.001) induces Ala to Pro substitution at amino acid 459 of COL1A2 in OSMF patients. Exon skipping is significantly associated with both the SNPs. Our results confirm the role of rs42542 and rs421587 in COL1A2 alternative splicing and support a strong role in susceptibility to OSMF, and could have served as surrogate markers. [ABSTRACT FROM AUTHOR]