Substance Use Screening in Geriatric Primary Care: Cultural Issues and Alcohol Consumption in the Deep South.

OBJECTIVES: To investigate indicators of potentially hazardous alcohol use among older adults living in a region with high substance use stigma. METHODS: Patients at a university-affiliated geriatrics clinic in the Deep South of theUS completed behavioral health screenings including self-reported alcohol use, symptoms of depression or anxiety, and cognitive functioning between 2018 and 2022. RESULTS: Participants (N = 278) averaged 76.04 years of age (SD = 9.25), were predominantly female (70.9%), and non-Hispanic white (84.5%), with an averageof 6.08 comorbid diagnoses (SD = 2.86). Race/ethnicity, age, and symptoms of anxiety were associated with alcohol use and hazardous alcohol use, with non-Hispanic whites, younger individuals, and those with more anxiety symptoms reporting more alcohol use. Notably, alcohol use and hazardous alcohol use were associated with cognitive functioning in the dementia range. CONCLUSION: Self-reported alcohol use is low in geriatric primary care in the Deep South, US, differs by race/ethnicity, and is predictive of cognitive impairment when alcohol use is hazardous. Issues of trust and stigma may play a role in self-report ofstigmatized behaviors. CLINICAL IMPLICATIONS: Self-reported alcohol intake must be considered within the cultural context of regional stigma. Recommendations to address this are provided.

Over-expression of the molecular chaperone Hsp104 in Saccharomyces cerevisiae results in the malpartition of [PSI+ ] propagons.

The ability of a yeast cell to propagate [PSI+ ], the prion form of the Sup35 protein, is dependent on the molecular chaperone Hsp104. Inhibition of Hsp104 function in yeast cells leads to a failure to generate new propagons, the molecular entities necessary for [PSI+ ] propagation in dividing cells and they get diluted out as cells multiply. Over-expression of Hsp104 also leads to [PSI+ ] prion loss and this has been assumed to arise from the complete disaggregation of the Sup35 prion polymers. However, in conditions of Hsp104 over-expression in [PSI+ ] cells we find no release of monomers from Sup35 polymers, no monomerization of aggregated Sup35 which is not accounted for by the proportion of prion-free [psi- ] cells present, no change in the molecular weight of Sup35-containing SDS-resistant polymers and no significant decrease in average propagon numbers in the population as a whole. Furthermore, they show that over-expression of Hsp104 does not interfere with the incorporation of newly synthesised Sup35 into polymers, nor with the multiplication of propagons following their depletion in numbers while growing in the presence of guanidine hydrochloride. Rather, they present evidence that over-expression of Hsp104 causes malpartition of [PSI+ ] propagons between mother and daughter cells in a sub-population of cells during cell division thereby generating prion-free [psi- ] cells.

Global Versus Momentary Osteoarthritis Pain and Emotional Distress: Emotional Intelligence as Moderator.

Background: Pain and emotional well-being are complexly associated both globally and in the moment. Emotional regulation strategies may contribute to that complexity by shaping the pain-well-being association. Purpose: Using emotional intelligence (EI) as an integrative conceptual framework, this study probed the role of emotional regulation in the associations of osteoarthritis pain with emotional well-being in varying time frames. Perceived attention to, clarity, and regulation of emotions were examined as predictors of well-being, and as moderators of the well-being-pain association, at global and momentary (within-day) levels. Methods: In a microlongitudinal study, 218 older adults with physician-diagnosed knee osteoarthritis self-reported global pain, depressive symptoms, and EI (mood attention, clarity, and repair). Momentary pain and positive and negative affect were then assessed four times daily for 7 days. EI subscales were examined as moderators of the pain-well-being association at global and momentary levels, controlling demographics and general health. Results: Global and momentary pain were positively associated with mood clarity and negatively with attention, but not with repair. Clarity and repair negatively predicted depression, and buffered effects of pain on depression. Momentary negative affect was negatively predicted by mood clarity and repair; again, clarity and mood repair buffered effects of momentary pain on negative affect. Only mood repair predicted positive affect, with no interactions emerging. Conclusions: Attention to mood states exacerbates the experience of pain in both short and long terms. In contrast, both mood clarity and ability to repair moods appear important to both momentary and longer-term emotional well-being.

Church Leaders Share and Implement Solution-Focused Health Strategies During the COVID-19 Pandemic in Rural Alabama.

Bridging the healthcare access gap and addressing COVID-19 vaccine hesitancy among rural-dwelling Black American adults residing in the Deep South require involvement of faith-based leaders in the community. This study explored perceived barriers and resources to meeting community needs, including vaccination, during the COVID-19 pandemic as reported by 17 Black American church leaders in the rural West Alabama Black Belt geographic region in May 2022. The main themes that emerged included (1) attending to community impact of COVID-19 illness and death; (2) maximizing health literacy and diminishing vaccine hesitancy through engaging in preventive health practices and sharing public health information; (3) addressing challenges created or exacerbated by COVID-19, including reduction in in-person attendance (particularly among adolescents and young adults), limited access to and literacy with technology, and political perceptions influencing engagement in preventive health behaviors; (4) maximizing technological solutions to increase attendance in the church; and (5) engaging in solution-focused and innovative initiatives to meet the identified needs in the congregation and community. Church leaders in West Alabama rural areas facing economic, health, and technological disparities identified "silver linings" as well as challenges created or exacerbated during the pandemic. As the need for COVID-19 vaccination and booster vaccination continues, Black American church leaders play pivotal roles in meeting rural community needs.

Momentary Associations of Osteoarthritis Pain and Affect: Depression as Moderator.

OBJECTIVES: This research examined main and moderating effects of global depressive symptoms upon in-the-moment associations of pain and affect among individuals with knee osteoarthritis (OA). Effects of depression on short-term change in pain and affect were also examined. METHOD: Older adults with physician-confirmed OA (N = 325) completed a baseline interview tapping global depressive symptoms, followed by an experience sampling protocol that captured momentary pain and affect 4 times daily for 7 days. Multilevel models controlling demographics and health conditions examined main and moderating effects of depression on momentary associations of pain with positive affect (PA) and negative affect (NA). Similar methods addressed short-term change in pain and affect. Auxiliary analyses explored broad associations of depressive symptoms with person-level averages and variability in pain and affect. RESULTS: Global depression predicted current pain, PA, and NA, as well as change in pain and affect over a 3- to 8-h period. Furthermore, both in the moment and over short periods, the association of pain and NA was stronger among persons higher in depressive symptoms. No moderating effect for the PA-pain association was found. Depressive symptoms were also associated with variability in pain and affect, particularly NA. DISCUSSION: Results confirm previous work on the relation of chronic pain with both global depressive symptoms and short-term affect. This research further demonstrates a unique moderating role of depression on the association of momentary pain with NA and suggests that the causal path may be stronger from pain to affect than vice versa.

Adult attention-deficit/hyperactivity disorder and driving: why and how to manage it.

Driving is a complex task that can be a significant challenge for individuals with attention-deficit/hyperactivity disorder (ADHD). A slight lapse in attention or inhibition while driving (not uncommon in individuals with ADHD) can result in hazardous consequences for these individuals and their families. This is also an interesting clinical scenario for the treating physician, who is always trying to optimize the various treatment options for the patient. Despite such potentially perilous consequences for society, this subject only recently has received researchers' attention. This review paper highlights the psychological differences between drivers with and without ADHD and examines differences between these groups in various driving simulation models. Research updates involving pharmacologic and nonpharmacologic interventions are discussed at length. Although the long-term effects of such interventions may not be clearly defined, there is enough evidence to suggest the public health significance of such interventions for optimally managing adult symptoms of ADHD.

Dissection and design of yeast prions.

Many proteins can misfold into beta-sheet-rich, self-seeding polymers (amyloids). Prions are exceptional among such aggregates in that they are also infectious. In fungi, prions are not pathogenic but rather act as epigenetic regulators of cell physiology, providing a powerful model for studying the mechanism of prion replication. We used prion-forming domains from two budding yeast proteins (Sup35p and New1p) to examine the requirements for prion formation and inheritance. In both proteins, a glutamine/asparagine-rich (Q/N-rich) tract mediates sequence-specific aggregation, while an adjacent motif, the oligopeptide repeat, is required for the replication and stable inheritance of these aggregates. Our findings help to explain why although Q/N-rich proteins are relatively common, few form heritable aggregates: prion inheritance requires both an aggregation sequence responsible for self-seeded growth and an element that permits chaperone-dependent replication of the aggregate. Using this knowledge, we have designed novel artificial prions by fusing the replication element of Sup35p to aggregation-prone sequences from other proteins, including pathogenically expanded polyglutamine.

Guanidine hydrochloride inhibits the generation of prion "seeds" but not prion protein aggregation in yeast.

[PSI(+)] strains of the yeast Saccharomyces cerevisiae replicate and transmit the prion form of the Sup35p protein but can be permanently cured of this property when grown in millimolar concentrations of guanidine hydrochloride (GdnHCl). GdnHCl treatment leads to the inhibition of the replication of the [PSI(+)] seeds necessary for continued [PSI(+)] propagation. Here we demonstrate that the rate of incorporation of newly synthesized Sup35p into the high-molecular-weight aggregates, diagnostic of [PSI(+)] strains, is proportional to the number of seeds in the cell, with seed number declining (and the levels of soluble Sup35p increasing) in the presence of GdnHCl. GdnHCl does not cause breakdown of preexisting Sup35p aggregates in [PSI(+)] cells. Transfer of GdnHCl-treated cells to GdnHCl-free medium reverses GdnHCl inhibition of [PSI(+)] seed replication and allows new prion seeds to be generated exponentially in the absence of ongoing protein synthesis. Following such release the [PSI(+)] seed numbers double every 20 to 22 min. Recent evidence (P. C. Ferreira, F. Ness, S. R. Edwards, B. S. Cox, and M. F. Tuite, Mol. Microbiol. 40:1357-1369, 2001; G. Jung and D. C. Masison, Curr. Microbiol. 43:7-10, 2001), together with data presented here, suggests that curing yeast prions by GdnHCl is a consequence of GdnHCl inhibition of the activity of molecular chaperone Hsp104, which in turn is essential for [PSI(+)] propagation. The kinetics of elimination of [PSI(+)] by coexpression of a dominant, ATPase-negative allele of HSP104 were similar to those observed for GdnHCl-induced elimination. Based on these and other data, we propose a two-cycle model for "prionization" of Sup35p in [PSI(+)] cells: cycle A is the GdnHCl-sensitive (Hsp104-dependent) replication of the prion seeds, while cycle B is a GdnHCl-insensitive (Hsp104-independent) process that converts these seeds to pelletable aggregates.

Racial/ethnic differences in sleep quality among older adults with osteoarthritis.

OBJECTIVE: To examine racial/ethnic differences in sleep quality and the pain-sleep association among older adults with osteoarthritis of the knee. DESIGN: Baseline interview followed by a 7-day microlongitudinal study using accelerometry and self-reports. SETTING: Participants were community residents in western Alabama and Long Island, NY. PARTICIPANTS: Ninety-six African Americans (AAs) and 128 non-Hispanic whites (NHWs) with physician-diagnosed knee osteoarthritis, recruited from a variety of clinical and community settings. MEASUREMENTS: Self-reports yielded demographics, body mass index, physical health problems, and depressive symptoms. Sleep quality was measured for 3 to 7 nights using wrist-worn accelerometers; pain was self-reported daily over the same period. RESULTS: With demographics and health controlled, AAs displayed poorer sleep efficiency, greater time awake after sleep onset and sleep fragmentation, and marginally more awakenings during the night, but no differences in total sleep time. AAs also showed greater night-to-night variability in number of awakenings and sleep fragmentation, and marginally greater variability in total sleep time and sleep efficiency. Sleep quality was not associated with pain either the day before sleep or the day after. Average daily pain interacted with race, whereas AAs displayed no effect of pain on sleep efficiency, NHWs exhibited better sleep efficiency at higher levels of average pain. CONCLUSIONS: These data corroborate previous studies documenting poorer sleep among AAs vs NHWs. The findings of greater night-to-night variability in sleep among AAs, as well as a negative association of pain with sleep quality among NHWs, are unique. Further study is needed to elucidate these findings.

Long-term benefits of prompts to use safety belts among drivers exiting senior communities.

Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using a repeated baseline design (AAB), we previously reported that motivating signs boosted safety belt usage by drivers exiting senior communities from baseline (72% and 68% usage), to postinstallation of signs (94%), to 6 months follow-up (80%). The current study was a 4-year follow-up in which six senior communities, with seat belt signs, were compared to six matched control senior communities with no signs. Safety belt usage was stable, across 4 years, at approximately 80% for both male and female drivers and front seat passengers for the six communities with signs, and was approximately 55% for control sites. These finding suggest that the simple and low-cost intervention of erecting signs to prompt safety belt use has persistent benefits that affect driver and passenger behavior alike.

[PSI(+)] turns 50.

The year 2015 sees the fiftieth anniversary of the publication of a research paper that underpins much of our understanding of fungal prion biology, namely "ψ, a cytoplasmic suppressor of super-suppressor in yeast" by Brian Cox. Here we show how our understanding of the molecular nature of the [PSI(+)] determinant evolved from an 'occult' determinant to a transmissible amyloid form of a translation termination factor. We also consider the impact studies on [PSI] have had--and continue to have--on prion research. To demonstrate this, leading investigators in the yeast prion field who have made extensive use of the [PSI(+)] trait in their research, provide their own commentaries on the discovery and significance of [PSI].

Quantifying the relationship between perceived consequences of ADHD medication and its usage.

OBJECTIVE: To address a major barrier of medication noncompliance for individuals with ADHD, the authors present the ADHD Medication Attitude Scale (AMAS) with initial psychometric analyses and discriminant validity data. METHOD: The AMAS was posted on ADHD websites, along with questions about demographics and medication usage over a 6-month period. A total of 356 ADHD respondents qualified for data analysis (160 males, 196 females, mean age = 18.58, years range = 13-62 years, SD = 6.07). RESULTS: Factor analysis revealed two factors: one indicating positive and the other indicating negative attitude toward medication. The final refined 22-item scale demonstrated good reliability (α =.83). More positive and less negative attitude factor scores, as well as age (older than 19 years), independently predicted respondents' self-report of taking medication, χ(2) (1, N = 248) = 38.95, p < .001. CONCLUSION: The AMAS is a psychometrically sound means of assessing attitudes toward ADHD medication, which significantly relate to self-reported medication usage.

Prions remodel gene expression in yeast.

Epigenetic mechanisms participate in the regulation of gene transcription in eukaryotes. Two studies in yeast have revealed an additional mechanism for controlling global gene transcription that is based on an inherited self-perpetuating change in the conformation of two different components of key transcriptional regulatory complexes.

The number and transmission of [PSI] prion seeds (Propagons) in the yeast Saccharomyces cerevisiae.

BACKGROUND: Yeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division. PRINCIPAL FINDINGS: Analysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division. CONCLUSIONS: While propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n(0), the number of propagons per cell (500-1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI+] and the spontaneous formation of prion-free cells.

The genetic control of the formation and propagation of the [PSI+] prion of yeast.

It is over 40 years since it was first reported that the yeast Saccahromyces cerevisiae contains two unusual cytoplasmic 'genetic' elements: [PSI(+)] and [URE3]. Remarkably the underlying determinants are protein-based rather than nucleic acid-based, i.e., that they are prions, and we have already learnt much about their inheritance and phenotypic effects from the application of 'classical' genetic studies alongside the more modern molecular, cellular and biochemical approaches. Of particular value has been the exploitation of chemical mutagens and 'antagonistic' mutants which directly affect the replication and/or transmission of yeast prions. In this Chapter we describe what has emerged from the application of classical and molecular genetic studies, to the most intensively studied of the three native yeast prions, the [PSI(+)] prion.

Prion stability.

The rate of spontaneous change from psi(-) to the psi(+) condition, determined in yeast by states of the Sup35p protein, is briefly discussed together with the conditions necessary for such change to occur. Conditions that promote and which affect the rate of induction of psi(+) in Sup35p and of other prion-forming proteins to their respective prion forms are also discussed. These include the influence of the amount of non-prion protein, the presence of other prions, the activity of chaperones, and brief descriptions of the role of native sequences in the proteins and how alteration of sequences in prion-forming proteins influences the rate of induction of [prion(+)] and amyloid forms. The second part of this article discusses the conditions which affect the reversion of psi(+) to psi-, including factors which affect the copy-number of prion "seeds" or propagons and their partition. The principal factor discussed is the activity of the chaperone Hsp104, but the existence of other factors, such protein sequence and of other, less well-studied agents is touched upon and comparisons are made, as appropriate, with studies with other yeast prions. We conclude with a discussion of models of maintenance, in particular that of Tanaka et al. published in Nature (2006), which provides much insight into the phenotypic and genetic parameters of the numerous "variants" of prions increasingly being described in the literature.

Cell division is essential for elimination of the yeast [PSI+] prion by guanidine hydrochloride.

Guanidine hydrochloride (Gdn.HCl) blocks the propagation of yeast prions by inhibiting Hsp104, a molecular chaperone that is absolutely required for yeast prion propagation. We had previously proposed that ongoing cell division is required for Gdn.HCl-induced loss of the [PSI+] prion. Subsequently, Wu et al.[Wu Y, Greene LE, Masison DC, Eisenberg E (2005) Proc Natl Acad Sci USA 102:12789-12794] claimed to show that Gdn.HCl can eliminate the [PSI+] prion from alpha-factor-arrested cells leading them to propose that in Gdn.HCl-treated cells the prion aggregates are degraded by an Hsp104-independent mechanism. Here we demonstrate that the results of Wu et al. can be explained by an unusually high rate of alpha-factor-induced cell death in the [PSI+] strain (780-1D) used in their studies. What appeared to be no growth in their experiments was actually no increase in total cell number in a dividing culture through a counterbalancing level of cell death. Using media-exchange experiments, we provide further support for our original proposal that elimination of the [PSI+] prion by Gdn.HCl requires ongoing cell division and that prions are not destroyed during or after the evident curing phase.

The [PSI+] prion of yeast: a problem of inheritance.

The [PSI(+)] prion of the yeast Saccharomyces cerevisiae was first identified by Brian Cox some 40 years ago as a non-Mendelian genetic element that modulated the efficiency of nonsense suppression. Following the suggestion by Reed Wickner in 1994 that such elements might be accounted for by invoking a prion-based model, it was subsequently established that the [PSI(+)] determinant was the prion form of the Sup35p protein. In this article, we review how a combination of classical genetic approaches and modern molecular and biochemical methods has provided conclusive evidence of the prion basis of the [PSI(+)] determinant. In so doing we have tried to provide a historical context, but also describe the results of more recent experiments aimed at elucidating the mechanism by which the [PSI(+)] (and other yeast prions) are efficiently propagated in dividing cells. While understanding of the [PSI(+)] prion and its mode of propagation has, and will continue to have, an impact on mammalian prion biology nevertheless the very existence of a protein-based mechanism that can have a beneficial impact on a cell's fitness provides equally sound justification to fully explore yeast prions.

Nitrate reduction and the isolation of Nit- mutants in Hansenula polymorpha.

Hansenula polymorpha (syn. Pichia angusta) is able to grow on nitrate as sole nitrogen source. Nitrate reductase (NR) assays, optimized in crude extracts from nitrate-grown cells, revealed that NR preferentially used NADPH, but also used NADH, as electron donor and required FAD for maximum activity. NR activity was present in nitrate-grown and nitrite-grown cells, and was absent in cells grown in ammonium, glutamate and methylamine. Addition of reduced nitrogen compounds to nitrate-grown cells led to loss of NR activity, even if added with nitrate. Under nitrogen starvation, NR activity was not observed; however, following growth on nitrate, NR activity is maintained in the absence of nitrate. Increases but not decreases in NR activity were dependent on protein synthesis. Conditions for chlorate selection were optimized, and Nit- (nitrate-) mutants were isolated. Some of these mutants showed reduced or absent NR activity. Sixty-one NR- mutants revealed the monogenic recessive nature of their lesions and were grouped in 10 complementation classes. These mutants will be used in gene cloning experiments aimed at identifying structural and regulatory elements involved in the first step of nitrate reduction.