Noble Gas Analyses to Distinguish Between Surface and Subsurface Brine Releases at a Legacy Oil Site.

Attributing the sources of legacy contamination, including brines, is important to determine remediation options and to allocate responsibility. To make sound remediation decisions, it is necessary to distinguish subsurface sources, such as leaking oil and gas ("O&G") wells or natural upward fluid migrations, from surface releases. While chemical signatures of surface and subsurface releases may be similar, they are expected to imprint specific dissolved noble gas signatures, caused by the accumulation of terrigenic noble gases in subsurface leaks or re-equilibration of noble gases following surface releases. We demonstrate that only a historic surface release influenced the dissolved noble gas signature of groundwater in monitoring wells contaminated with brine near an abandoned O&G well, rather than subsurface leakage from the well. Elevated brine concentrations were associated with lower terrigenic helium concentrations, indicating re-equilibration with atmospheric helium at the surface during the release. Geophysical surveying indicating elevated salinity in surficial soils upgradient of the wells further supported the interpretation of the noble gas data. Eliminating the possibility that subsurface leakage was the source of the plume was critical to selecting the proper remedial action at the site, which otherwise may have included an unnecessary and costly well re-abandonment. This study demonstrates the use of noble gas analysis to compare potential sources of brine contamination in groundwater and to exclude subsurface leakage as a potential source in an oilfield.

Altered Grooming Cycles in Transgenic Drosophila.

Head grooming in Drosophila consists of repeated sweeps of the legs across the head, comprising regular cycles. We used the GAL4-UAS system to study the effects of overexpressing shibirets1 and of Adar knockdown via RNA interference, on the period of head-grooming cycles in Drosophila. Overexpressing shibirets1 interferes with synaptic vesicle recycling and thus with cell communication, while Adar knockdown reduces RNA editing of neuronal transcripts for a large number of genes. All transgenic flies and their controls were tested at 22° to avoid temperature effects; in wild type, cycle frequency varied with temperature with a Q10 of 1.3. Two experiments were performed with transgenic shibirets1: (1) each fly was heat-shocked for 10 min at 30° immediately before testing at 22° and (2) flies were not heat shocked. In both experiments, cycle period was increased when shibirets1 was overexpressed in all neurons, but was not increased when shibirets1 was overexpressed in motoneurons alone. We hypothesize that grooming cycles in flies overexpressing shibirets1 are lengthened because of synaptic impairment in neural circuits that control head-grooming cycles. In flies with constitutive, pan-neuronal Adar knockdown, cycle period was more variable within individuals, but mean cycle period was not significantly altered. We conclude that RNA editing is essential for the maintenance of within-individual stereotypy of head-grooming cycles.

The von Hippel-Lindau protein forms fibrillar amyloid assemblies that are mitigated by the anti-amyloid molecule Purpurin.

The von Hippel-Lindau protein (pVHL) is a tumor suppressor involved in oxygen regulation via dynamic nucleocytoplasmic shuttling. It plays a crucial role in cell survival by degrading hypoxia-inducible factors (HIFs). Mutations in the VHL gene cause angiogenic tumors, characterized as VHL syndrome. However, aggressive tumors involving wild-type pVHL have also been described but the underlying mechanism remains to be revealed. We have previously shown that pVHL possesses several short amyloid-forming motifs, making it aggregation-prone. In this study, using a series of biophysical assays, we demonstrated that a pVHL-derived fragment (pVHL104-140) that harbors the nuclear export motif and HIF binding site, forms amyloid-like fibrillar structures in vitro by following secondary-nucleation-based kinetics. The peptide also formed amyloids at acidic pH that mimics the tumor microenvironment. We, subsequently, validated the amyloid formation by pVHL in vitro. Using the Curli-dependent amyloid generator (C-DAG) expression system, we confirmed the amyloidogenesis of pVHL in bacterial cells. The pVHL amyloids are an attractive target for therapeutics of the VHL syndrome. Accordingly, we demonstrated in vitro that Purpurin is a potent inhibitor of pVHL fibrillation. The amyloidogenic behavior of wild-type pVHL and its inhibition provide novel insights into the molecular underpinning of the VHL syndrome and its possible treatment.

Personality disorders in older adults: Differences in self-informant ratings.

Previous research on self-informant reports in assessing personality disorders (PDs) has been mainly focused on adults, leaving older adults under-studied. We examined self-informant agreement in PD screening among older adults (≥60 years) using the Gerontological Personality disorders Scale (GPS). Potential differences such as who reports more personality pathology on a PD screener (i.e., GPS), item accessibility and the effect of relational aspects were studied as well. Data of 326 older adult-informant dyads, of which the older adults were sampled from five general practices in the Netherlands, were used. Results indicate that self-informant agreement ranged from r = 0.26-0.73, with lower concordance on the GPS-subscale measuring intrapersonal aspects of personality pathology. Informants were more sensitive to habitual pathological personality features than older adults. Two GPS items showed differential item functioning across self- and informant-report. Of relational aspects, only congeniality affected the GPS-iv scores; lower ratings on congeniality were associated with higher GPS-iv scores (i.e., higher reporting of personality problems).

Relationships Between Diverse Forms of Anxiety With Intrapersonal Functioning Among Older Adults.

This study assessed how clinical anxiety, anxiety about aging, and death anxiety related to one another and to intrapersonal functioning. Older adults completed the Geriatric Anxiety Scale, Anxiety About Aging Scale, Death Anxiety Scale-Extended, and Intrapersonal Problems Rating Scale. Clinical anxiety was strongly correlated with anxiety about aging (r = .50) and death anxiety (r = .59), and anxiety about aging and death anxiety were strongly positively correlated with each other (r = .51). Intrapersonal problems were significantly and strongly positively correlated with clinical anxiety (r = .79), anxiety about aging (r = .50), and death anxiety (r = .56). Multiple regression results showed that the three types of anxiety accounted for a large amount of variance in intrapersonal problems. Findings suggest strong comorbidities between diverse forms of anxiety with some unique features. Intrapersonal deficits may be prominent in the presence of diverse forms of anxiety. Screening should consider these relationships.

Esophageal adenocarcinoma with metastasis to the prostatic urethra and bladder.

Metastatic esophageal adenocarcinoma to the urinary bladder is extremely rare and aggressive. We discuss here the case of an 83-year-old male with history of esophageal adenocarcinoma treated with chemoradiation therapy and esophagectomy who presented with gross hematuria and lower urinary tract symptoms. Pathology of the bladder tumor after transurethral resection demonstrated invasive adenocarcinoma of both the bladder and the prostatic urethra consistent with metastatic esophageal adenocarcinoma.

Relationship between anxiety and quality of life among older adults with self-reported polypharmacy in long-term care: A cross-sectional study.

AIMS: To investigate the relationship between anxiety and quality of life among older adults with self-reported polypharmacy living in the long-term care setting. DESIGN: A cross-sectional design was used. METHODS: Between July 2021 and August 2022, 92 older adults living in long-term care completed an anonymous one-time questionnaire packet. Polypharmacy was measured as self-reported five or more medications daily. Anxiety was measured using the Geriatric Anxiety Scale-Long Term Care tool. Quality of life was measured as health-related quality of life using two global questions from the RAND-36 and as medication-related quality of life using the Medication-Related Quality of Life Scale. RESULTS: The prevalence of polypharmacy was 89%. Among participants with polypharmacy, average age was 80.1 ± 7.9 years. The majority were female (70%) and white (85%). There was a moderate-to-strong correlation between anxiety and quality of life. Specifically, anxiety was negatively related to current health-related quality of life, perceived change in health-related quality of life and medication-related quality of life. Overall, anxiety explained 27-31% of the variance in both health-related and medication-related quality of life. CONCLUSION: The results of this study indicate that as anxiety increases, health-related and medication-related quality of life decreases in older adults living in long-term care who report consuming five or more medications daily. Advanced practice nurses can use these findings to guide practice, tailor interventions and improve care for these long-term care residents. IMPLICATIONS: Multiple medications are increasingly prescribed to treat multiple comorbidities in older adults. As a result, the prevalence of polypharmacy (≥5 medications per day) is rising and problematic. The main findings of this study highlight the negative relationship between anxiety and quality of life in this population and the need for adequate assessment of anxiety by advanced practice nurses in order to personalize care. REPORTING METHOD: In preparing the manuscript, the authors have adhered to relevant EQUATOR guidelines and the STROBE checklist for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution outside of participation in the actual study for purposes of data collection.

Assessment of Personality Disorders in Older Adults. A Practice Guide.

Assessment of personality disorders (PDs) in older adults is a nuanced trade of its own. The aim of this practice guide is to illustrate gerontological assessment challenges using 3 case vignettes. We argue that it is important to pay extra attention to the influence of cognitive and medical (somatic) disorders on personality functioning in older adults during personality assessment. We also note that information provided by informants contributes added value to personality assessment. Personality assessment should be sufficiently age-specific to prevent overdiagnosis or underdiagnosis in older adults. Furthermore, given the reduced psychological or somatic capacity of some older adults, phased or sequential personality assessment is recommended. This should be focused on the assessment questions to be answered, for example starting with short general screening of personality functioning, followed by more in-depth exploration. Personality assessment should be kept as brief and simple as possible in terms of formulation of the items.

Assessing late-life anxiety in Japanese older adults: psychometric evaluation of the Japanese version of the Geriatric Anxiety Scale.

BACKGROUND: This study developed a Japanese version of the Geriatric Anxiety Scale (GAS-J) and its short form (GAS-10-J) to evaluate anxiety in Japanese older adults and assess its psychometric properties using a cross-sectional design. METHODS: A total of 331 community-dwelling older adult participants (208 men, 116 women, seven unknowns; mean age = 73.47 ± 5.17 years, range = 60-88 years) recruited from two Silver Human Resources Centres in the Kanto region, Japan, answered a set of self-report questionnaires. Of these respondents, 120 participated in a follow-up survey to evaluate test-retest reliability. RESULTS: Confirmatory factor analysis suggested that, as with the original GAS, the GAS-J had a three-factor structure and the GAS-10-J had a unifactor structure with high standardised factor loadings. Test-retest correlations and internal consistency analyses indicated that these scales were reliable. Correlations between the GAS-J/GAS-10-J with the Geriatric Anxiety Inventory, Generalised Anxiety Disorder-7, Geriatric Depression Scale-15, World Health Organization-Five Well-Being Index, and Kihon Checklist were mostly consistent with our hypotheses, thereby supporting the construct validity of the GAS-J/GAS-10-J. CONCLUSIONS: The findings indicate that the GAS-J and GAS-10-J have robust psychometric properties for assessing late-life anxiety in Japanese older adults. Further GAS-J studies are required for clinical groups.

Associations between physical health and the alternative model of personality disorders: A cross-sectional age study.

The Alternative Model of Personality Disorders (AMPD) is a relatively new dimensional model of personality disorders (PDs) that assesses two diagnostic constructs: personality functioning and pathological personality traits. Thus far, research on the AMPD among older adults has been limited, but the research that does exist suggests limited generalizability to the unique biopsychosocial context of later life. To further examine the applicability of the AMPD to older adults, the purpose of this study was to examine relationships between the AMPD's two constructs with perceived physical health status among younger and older adult samples. Older adults (n = 222) and younger adults (n = 215) completed the Short Form-36 (SF-36), Levels of Personality Functioning Scale-Self-Report (LPFS-SR), and Personality Inventory for DSM-5-Brief Form (PID-5-BF). Correlations and Fisher's z-tests revealed significantly stronger relationships between the SF-36 with the LPFS-SR and PID-5-BF domains for older adults than younger adults. Additionally, age group significantly moderated the relationships between personality functioning and pathological personality traits and health. The stronger relationships between health and the AMPD's constructs for older adults suggest meaningful overlap between negative health outcomes and PD pathology. Future research should further investigate specific mechanisms in which personality pathology negatively impacts health in older adults.

Personality, Interpersonal Problems, and Anxiety Among Older Adults.

INTRODUCTION: This study examined relationships between personality disorder (PD) features, Big Five personality traits, and interpersonal problems with anxiety. METHOD: Older adults (N = 130) completed the Geriatric Anxiety Scale, Coolidge Axis Two Inventory, Big Five Inventory-2, and Circumplex Scales of Interpersonal Problems. Pearson correlation analyses were used to assess simple relationships between anxiety with PD features (CATI scales), Big Five personality domains (BFI-2 scales), and interpersonal problems (CSIP scales). Multiple linear regression analyses were performed to determine the extent to which the PD scales of the CATI, the personality scales of the BFI-2, and the scales of the CSIP explained variance in anxiety. RESULTS: Anxiety was positively correlated with 13 of 14 PD scales, ranging from .23 (Narcissistic) to .61 (Depressive). Regarding Big Five personality traits, anxiety was negatively associated with Agreeableness (-.23), Conscientiousness (-.30), and Extraversion (-.31) but was positively associated with Negative Emotionality (.56). Regarding interpersonal problems, anxiety was positively related to all eight CSIP scales, ranging from Self-sacrificing (.30) to Distant/Cold (.62). Regression analyses indicated that PD features accounted for the most variance in anxiety symptoms (53%), followed by interpersonal problems (46%), and Big Five personality traits (33%). DISCUSSION: Anxiety appears to be meaningfully associated with PD features, several aspects of Big Five personality traits, and interpersonal problems, suggesting that these variables may play important roles in the development and maintenance of anxiety, or vice versa. Our findings especially speak to the growing awareness of the deleterious impact of PD features on clinical syndromes in later life, as evidenced by strong comorbidities with anxiety.

Impact of self-reported cognitive dysfunction on the alternative model of personality disorders among older adults.

METHOD: Older adults (N = 202) completed the Levels of Personality Functioning Scale-Self-Report, Personality Inventory for DSM-5, and Coolidge Axis II Inventory with its six self-report cognitive dysfunction scales. RESULTS: Results suggested high correlational overlap between subjective cognitive problems with personality functioning and pathological personality, as measured by the AMPD. Hierarchical regressions revealed that subjective measures of executive functions, perceptual motor, and language difficulties were most strongly related to the AMPD's constructs. Results are discussed in the context of prior research on objective cognitive impairment among individuals with PDs. CONCLUSION: The degree of overlap found within the current older adult sample suggested an age-related problem or potential age-bias, with older adults being at-risk of (a) having their subjective cognitive problems being incorrectly interpreted as personality pathology under the AMPD or (b) having personality pathology being overlooked under the AMPD, with symptoms instead attributed to subjective cognitive issues. This study suggested that subjective cognitive dysfunction may be one mechanism that contributes to differential performance of the AMPD among older adults.

Development and Validation of a Short Form of the Geriatric Anxiety Scale (GAS-12) among Italian Older Adults.

OBJECTIVES: We developed a new Italian short version of the Geriatric Anxiety Scale (GAS-12) and evaluated its psychometric properties. The GAS-12 specifically screens for anxiety symptoms in the Italian older adult population by identifying items that best discriminate anxiety in this population. METHODS: In Study 1, we administered the full-length Italian translation of the GAS to 517 older adults and used item response theory to identify the most discriminating items and to develop the short form used in Study 2. In Study 2, we evaluated the functioning of the new short form of the questionnaire in a new sample of 427 older adults using Confirmatory factor analysis. RESULTS: Analyses indicated 12 items that discriminated well between anxious and non-anxious participants and distributed along the latent continuum of each trait. The GAS-12 fits a three-factor structure. There was also evidence for convergent and divergent validity. CONCLUSIONS: The Italian GAS-12 appears to be a useful instrument for the quantitative screening of anxiety in Italian older adults. CLINICAL IMPLICATIONS: Anxiety imposes significant impairment thus making imperative the screening and assessment of anxiety symptoms. The GAS-12 is particularly indicated with limited time and many scales in a clinical assessment or research protocols.

Self-sustaining smouldering combustion for the treatment of industrial oily waste.

Significant onsite handling and offsite management costs are incurred by oilfield operators annually to properly manage hydrocarbon waste streams such as tank bottoms or other oily sludge or oil impacted soil generated during oil and gas production processes. The current study reports for the first-time technical results of a field trial on use of a smouldering combustion technology performed in an active oilfield. Two treatment batches with oily sludges, stabilized through blending with soil, resulted in permanent hydrocarbon removal (98-99.9% reduction) to create treated soil that met standards for reuse as clean backfill onsite. Emissions profile data collected pre- and post-thermal oxidizer indicated effective removal of volatile organic compounds, CO and SO2, but had increased NO and CO2 due to combustion of propane to affect the thermal oxidation. Regulatory, financial, environmental and safety considerations are discussed in context of future full-scale smouldering technology deployment. The technology has the potential to lower overall unit costs for management of hydrocarbon impacted waste and reduce waste sent to landfills, which can benefit more remote sites.

Functionalized nanoparticles targeting biomarkers for prostate cancer imaging and therapy.

Nanomedicine is an evolving field of scientific research with unique advantages and challenges for the detection and treatment of medical diseases. Since 1995, the FDA has approved the administration of nanoparticle-based therapies. The initial generation of nanoparticles relied on an enhanced permeability and retention effect, associated with an increased penetrability of tumor related blood vessels. With increasing knowledge of biomarkers and molecular targets, active targeting of circulating tumor cells by nanoparticles provides an exciting area for application. The selective targeting of prostate cancer cells using a nanotechnology-based mechanism has the potential to optimize the delivery of therapeutic payloads directly to prostate cancer cells while minimizing systemic toxicities. The molecular targets that have been studied include prostate specific membrane antigen, gastrin-releasing peptide protein, glucose related protein, CD44, claudin, C-X-C chemokine receptor type 4 (CXCR-4), and adenosine. The clinical potential for nanoparticle-based therapies is supported by several studies that have progressed past the preclinical stage into clinical trials. In this review, we present the molecular biomarkers that have been targeted by ligands conjugated to the surface of nanoparticles for prostate cancer imaging and therapy.

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions.

Controlling the infectivity of respiratory RNA viruses is critical, especially during the current SARS-CoV-2 pandemic. There is an unmet need for therapeutic agents that can reduce viral replication, preferably independent of the accumulation of viral mutations. Zinc ions have an apparent activity as modulators of intracellular viral RNA replication and thus, appear attractive in reducing viral RNA load and infectivity. However, the intracellular concentration of zinc is usually too low for achieving an optimal inhibitory effect. Various herbal polyphenols serve as excellent zinc ionophores with known antiviral properties. Here, we combined zinc picolinate with a collection of flavonoids, representing commonly used polyphenols. Copper was added to avoid ionic imbalance during treatment and to improve efficacy. Each component separately, as well as their combinations, did not interfere with the viability of cultured A549, H1299, or Vero cells in vitro as determined by MTT assay. The safe combinations were further evaluated to determine antiviral activity. Fluorescence-activated cell sorting and quantitative polymerase chain reaction were used to evaluate antiviral activity of the combinations. They revealed a remarkable (50-95%) decrease, in genome replication levels of a diverse group of respiratory RNA viruses, including the human coronavirus OC43 (HCoV-OC43; a betacoronavirus that causes the common cold), influenza A virus (IAV, strain A/Puerto Rico/8/34 H1N1), and human metapneumovirus (hMPV). Collectively, our results offer an orally bioavailable therapeutic approach that is non-toxic, naturally sourced, applicable to numerous RNA viruses, and potentially insensitive to new mutations and variants.

The contribution of individual residues of an aggregative hexapeptide derived from the human γD-crystallin to its amyloidogenicity.

Human γD-crystallin protein is abundant in the lens and is essential for preserving lens transparency. With age the protein may lose its native structure resulting in the formation of cataract. We recently reported an aggregative peptide, 41Gly-Cys-Trp-Met-Leu-Tyr46 from the human γD-crystallin, termed GDC6, exhibiting amyloidogenic properties in vitro. Here, we aimed to determine the contribution of each residue of the GDC6 to its amyloidogenicity. Molecular dynamic (MD) simulations revealed that the residues Trp, Leu, and Tyr played an important role in the amyloidogenicity of GDC6 by facilitating inter-peptide main-chain hydrogen bonds, and π-π interactions. MD predictions were further validated using single-, double- and triple-alanine-substituted GDC6 peptides in which their amyloidogenic propensity was individually evaluated using complementary biophysical techniques including Thioflavin T assay, turbidity assay, CD spectroscopy, and TEM imaging. Results revealed that the substitution of Trp, Leu, and Tyr together by Ala completely abolished aggregation of GDC6 in vitro, highlighting their importance in the amyloidogenicity of GDC6.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

Distinctions between depression and anxiety with fear of being a burden in late life.

Objectives: The perception of being a burden is a well-known risk factor for dying by suicide. Research on factors that precede the state of perceived burdensomeness, such as fearing being a burden, is necessary. We investigated the extent to which health status, elevated depressive symptoms, and elevated anxiety symptoms are associated with fear of being a burden in late life.Method: Older adult participants (N = 155) completed the Geriatric Anxiety Scale (GAS), Patient Health Questionnaire (PHQ-8), and demographic and health questions. Fear of being a burden, assessed with a supplemental item on the GAS, was categorically grouped as 'no fear' or 'some fear'. Using logistic regression, we examined predictors of fear of being a burden.Results: In the first step, elevated depression was associated with fear of being a burden (OR = 2.30, 95% CI: 1.09, 4.89, p = .03), but health status was not significant. In the second step, elevated anxiety was significant (OR = 2.63, 95% CI: 1.15, 5.99, p = .02); depression was no longer significant.Conclusion: Contrary to expectations, anxiety more strongly predicted fear of being a burden than depression. Future research should further investigate the role of anxiety in fear of being a burden and ways of intervening.

Inhibitor-Mediated Structural Transition in a Minimal Amyloid Model.

Despite the fundamental clinical importance of amyloid fibril formation, its mechanism is still enigmatic. Crystallography of minimal amyloid models was a milestone in the understanding of the architecture and biological activities of amyloid fibers. However, the crystal structure of ultimate dipeptide-based amyloids is not yet reported. Herein, we present the crystal structure of a typical amyloid-forming minimal dipeptide, Ac-Phe-Phe-NH2 (Ac-FF-NH2 ), showing a canonical ß-sheet structure at the atomic level. The simplicity of the structure helped in investigating amyloid-inhibition using crystallography, never previously reported for larger peptide models. Interestingly, in the presence of an inhibitor, the supramolecular packing of Ac-FF-NH2 molecules rearranged into a supramolecular 2-fold helix (21 helix). This study promotes our understanding of the mechanism of amyloid formation and of the structural transitions that occur during the inhibition process in a most fundamental model.