A Case Report of Treatment-Resistant Agitation in Dementia With Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics.

Palliative care teams are often consulted to assist in treating persistent dementia-related behavioral issues. Delta-9-tetrahydrocannabinol (THC) offers an alternative to traditional antipsychotic drugs in the long-term management of dementia with behavioral change. We present the case of an 85-year-old man with dementia with Lewy bodies with worsening aggression refractory to antipsychotic management. Multiple regimens of antipsychotics failed both in the outpatient and inpatient settings. After exhausting other options and in the setting of worsening agitation, a tincture of THC was prescribed. After starting THC tincture, the patient's behavior rapidly improved, and he was discharged home to the care of his spouse. The challenges of prescribing and obtaining THC are discussed.

Health Conditions, Substance Use, Physical Activity, and Quality of Life in Current and Former Baseball Players.

BACKGROUND: A comprehensive understanding of lifestyle (health conditions and substance use), health-related quality of life (HRQoL), flourishing (holistic representation of health), and physical activity can inform stakeholders (players, coaches, and clinicians) and help improve long-term health across the life span. PURPOSE: To describe health conditions (comorbidities or diagnoses), substance use, physical activity, HRQoL, and flourishing in current and former collegiate and professional baseball players and to assess the relationship between playing position and HRQoL/flourishing in former baseball players. STUDY DESIGN: Descriptive epidemiology study. METHODS: Eligible participants were those ≥18 years old with ≥1 season of collegiate or professional baseball experience. Participants completed a survey on health conditions (asthma, diabetes, hypertension, hypercholesterolemia, and depression), substance use (tobacco, alcohol, and energy drinks), physical activity (International Physical Activity Questionnaire-Short Form), HRQoL (Veterans Rand 12-Item Health Survey [VR-12] physical and mental component scores), and flourishing (Flourishing Scale). Adjusted multivariable regressions were performed for HRQoL and flourishing. RESULTS: Overall, 260 baseball players opened the survey, and 214 (current players, 97; former players, 117) participated for an 82% response rate. Of the former players, 32% had hypertension or hypercholesterolemia. In addition, 26% of current players had used smokeless tobacco (median, 3 years; interquartile range [IQR], 1-5 years) as compared with 34% of former players (median, 15 years; IQR, 5-25 years). In addition, 14% of current players had used electronic cigarettes (median, 2 years; IQR, 0-4 years) as opposed to 3% of former (median, 3 years; IQR, 2-4 years). Energy drinks were consumed by 31% and 14%, respectively, of current and former players on at least a weekly basis. Current baseball players performed 8667 metabolic equivalents per week of physical activity as opposed to 3931 in former players. Pitching was associated with worse VR-12 Mental Component Scores (-5.0; 95% confidence interval, -9.0 to -1.0). Playing position was not related to VR-12 Physical Component Scores or flourishing in former baseball players. CONCLUSION: The similar smokeless tobacco prevalence between current and former baseball players suggests that they may start using tobacco products during baseball participation and continue after retirement. Similar reported HRQoL as compared with the general US population and high flourishing and physical activity levels suggest that baseball players may present with good musculoskeletal and psychological health.

Psychophysiologic symptom relief therapy for chronic back pain: a pilot randomized controlled trial.

INTRODUCTION: Chronic back pain is the leading cause of disability in the United States. Based on the hypothesis that nonspecific back pain may be rooted in a psychophysiologic etiology, we propose a new approach to chronic back pain. OBJECTIVES: A pilot study was conducted to assess whether psychophysiologic symptom relief therapy (PSRT) can reduce disability and back pain bothersomeness for patients with chronic back pain. METHODS: This was a three-armed, randomized trial for adults with nonspecific chronic back pain that compared PSRT with usual care and an active comparator (mindfulness-based stress reduction [MBSR]). Psychophysiologic symptom relief therapy-randomized participants received a 12-week (36 hours) course based on the psychophysiological model of pain. All groups were administered validated questionnaires at baseline and at 4, 8, 13, and 26 weeks. The primary outcome was the reduction in pain disability measured by the Roland-Morris Disability Questionnaire. RESULTS: The mean Roland-Morris Disability Questionnaire score for the PSRT group (n = 11) decreased from 9.5 (±4.3 SDs) to 3.3 (±5.1) after 26 weeks which was statistically significant compared with both MBSR (n = 12) (P = 0.04) and usual care (n = 12) (P = 0.03). Pain bothersomeness scores and pain-related anxiety decreased significantly over 26 weeks in PSRT compared with MBSR and usual care (data in manuscript). At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively. Psychophysiologic symptom relief therapy attendance was 76%, and there was 100% follow-up of all groups. CONCLUSION: Psychophysiologic symptom relief therapy is a feasible and potentially highly beneficial treatment for patients with nonspecific back pain.

Health-related quality of life and flourishing in current and former recreational and elite cricketers.

BACKGROUND: Health related quality of life (HRQoL) and flourishing are constructs that encompasses a holistic representation of physical, psychological, and social health. The underlying psychological factors that can affect HRQoL and flourishing in sports participants is poorly understood. The purpose of this study was to i) evaluate HRQoL (physical and mental-components) and flourishing in recreational and elite and current and former cricketers; ii) determine the effect of resilience, playing-standard, and playing status on HRQoL and flourishing in cricketers. METHODS: The Cricket Health and Wellbeing Study (n = 2598 current and former cricketers, aged ≥18 years) collected cross-sectional questionnaire data including the Flourishing Scale, Short Form-8 (physical (PCS) and mental (MCS) component scores), resilience (European Social Survey), highest standard-of-play, and playing status. Multivariable linear regressions with fractional polynomials were utilised, adjusted for age, gender, total cricket-seasons, comorbidity, ≥ 4-week time-loss injury, and orthopaedic surgery. RESULTS: Two thousand two hundred eighty individuals (aged (mean (SD)) 51.7(14.7) years, 61% played recreationally, 37% former cricketers) were included in analyses. The median (IQR) PCS was 51.4(46.9-55.9), MCS was 54.3(50.0-58.6), and Flourishing Scale score was 48 [ (1-7)] .Greater resilience was associated with better PCS (effect (95% CI) 1.41(0.70-2.11)), MCS (4.78(4.09-5.48)), and flourishing (2.07(2.55-3.59)) compared to less resilience. Playing standard was not associated with HRQoL. Playing at an elite standard was associated with greater flourishing (1.21(0.68, 1.73)), compared with playing recreationally. Current cricket participation was associated with better PCS (3.61(2.92-4.30)) and flourishing scores (0.53(0.02-1.04)), compared to former cricket participation. CONCLUSION: Cricketers reported high levels of mental-components of HRQoL and flourishing, and this was similar in recreational, elite, current and former cricketers. Current cricket participation and a higher standard-of-play was associated with greater flourishing. Current cricket participation was also associated with better PCS, however playing-status was not related to MCS. Further research is needed to understand if cricket participation may have psychological benefits that persist beyond cricket retirement.

Brodifacoum Inhalation and its Clinical Manifestations in a 21-Year-Old Caucasian Man.

Exposure to brodifacoum, a superwarfarin substance, can lead to severe coagulopathic manifestations. Brodifacoum is a lipophilic, vitamin K antagonist with a long half-life. Clinical manifestations are challenging to diagnose if the patient cannot provide information regarding exposure. Herein, we report the first case in the literature, to our knowledge, of a patient who had intentionally inhaled brodifacoum. We performed coagulation studies such as prothrombin time (PT) and international normalized ratio (INR) to monitor vitamin K dependent coagulation factors in the patient, a 21-year-old Caucasian man. On admission to the hospital, the INR of the patient was 12.9; a computed tomography (CT) angiogram detected a mediastinal hemorrhage. In the absence of 4-factor PCC, the patient received 30 plasma transfusions during a 4-day period due to persistent left pleural effusions, along with vitamin K therapy to normalize his coagulation factors. His high-performance liquid chromatography (HPLC) results on hospital day 3 and day 26 confirmed the presence of brodifacoum in his body. We believe that inhalation led the poison to bypass the initial metabolism process of the liver, resulting in rapid anticoagulation and subsequent bleeding diathesis. Management of brodifacoum poisoning is case dependent on the amount of exposure and INR status. Constant INR monitoring, large dose vitamin K therapy and initial plasma transfusions (in the absence of PCC) were able to prevent severe internal bleeding in the patient.

The immortalized UROtsa cell line as a potential cell culture model of human urothelium.

The UROtsa cell line was isolated from a primary culture of normal human urothelium through immortalization with a construct containing the SV40 large T antigen. It proliferates in serum-containing growth medium as a cell monolayer with little evidence of uroepithelial differentiation. The working hypothesis in the present study was that this cell line could be induced to differentiate and express known features of in situ urothelium if the original serum-containing growth medium was changed to a serum-free formulation. We demonstrated that the UROtsa cells could be successfully placed into a serum-free growth medium consisting of a 1:1 mixture of Dulbeco's modified Eagle's medium and Ham's F-12 supplemented with selenium (5 ng/mL), insulin (5 microg/mL), transferrin (5 microg/mL), hydrocortisone (36 ng/mL), triiodothyronine (4 pg/mL), and epidermal growth factor (10 ng/mL). Under serum-free growth conditions, confluent UROtsa cells were shown by light microscopy to produce raised, three-dimensional structures. Routine ultrastructural examination disclosed these three-dimensional areas to consist of a stratified layer of cells that strongly resembled in situ urothelium. The cells displayed numerous desmosomal connections, complex interactions of the lateral membranes, and abundant intermediate filaments within the cytoplasm. Freeze fracture analysis demonstrated that the cells possessed tight-junction sealing strands and gap junctions. The overall morphology was most consistent with that found in the intermediate layers of in situ urothelium. The basal expression patterns of the metallothionein (MT) and heat shock proteins 27, 60, and 70 were determined in these cells, and expression was in agreement with that known to occur for in situ urothelium. The cells were also successfully tested for their ability to be stably transfected using expression vectors containing the MT-3 or MT-2A genes. The findings suggest that the UROtsa cells grown with a serum-free medium could be a valuable adjunct for studying environmental insult to the human urothelium in general and for the stress response in particular.

Validation of a novel estrogen receptor-based microtitration plate assay for the determination of phytoestrogens in soy-based foods.

A novel, nonisotopic microtitration plate assay based on the human estrogen receptor has been used to screen soy-based and soy-containing foods for their phytoestrogen content (measured as genistein equivalents). The validation of the assay for use with food extracts has been demonstrated by investigation of recoveries after acidic and enzymic hydrolysis, by investigation of matrix effects, and by comparison of results with HPLC analysis. Phytoestrogen levels in soy products analyzed ranged between 520 and 1872 microgram of genistein equiv/g of soy flour, 5-282 microgram/g of soy concentrates, 503-1292 microgram/g of soy-protein isolates, and 108-226 microgram/g of soy-based infant formulas. Samples of textured vegetable protein and bread containing soy and linseed gave values of 1114 and 68 microgram/g, respectively. Comparison of results for 12 samples analyzed both by the receptor assay and by HPLC showed good correlation (r(2) = 0.905). The assay, which is rapid and simple to perform, is suitable for screening phytoestrogen-containing foods in order to assess human exposure to these bioactive compounds. The assay sensitivity is 3.4 microgram/g, and 14 samples/plate can be analyzed in 4 h following hydrolysis.

The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, Cataract, and Age-related Maculopathy Study.

PURPOSES: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence. METHODS: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye. RESULTS: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation. CONCLUSIONS: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.

The role of past intake of vitamin E in early cataract changes.

PURPOSE: We examined the association between prior supplementation of vitamin E and early cataract changes in volunteers currently enrolled in the cross-sectional VECAT study. The Vitamin E and Cataract Prevention Study (VECAT) is a clinical trial currently in progress, designed to assess the affect of vitamin E supplementation on the development and progression of cataract and age-related macular degeneration. METHODS: A history of vitamin E supplementation was ascertained through a self-administered questionnaire that was mailed to each of the 1,111 participants who were enrolled at the time in the prospective VECAT Study. RESULTS: With a 99% response rate, we found that 26% of participants reported prior supplementation of vitamin E. Only 8.8% of these participants took supplementation greater than the recommended daily intake (RDI) of 10 mg/day. Of these 26%, 57% took supplementation in the form of multivitamins as opposed to a vitamin E supplement on its own. The range of supplement intake ranged from as little as 0.1 mg/day to a maximum of 55 mg/day. A statistically significant association was found between prior supplementation and the absence of cortical opacity (OR = 0.47, 95%CI = 0.28-0.83), after adjusting for age. The levels of nuclear opacity (NO) were not statistically different between those who reported intake and those with no prior vitamin E supplementation. CONCLUSION: Prior vitamin E supplementation may protect VECAT participants from developing at least early cortical cataracts. No apparent protective role in terms of nuclear opacities and nuclear color was found regardless of the level, regularity or duration of intake.

Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast Saccharomyces cerevisiae.

The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated second-site suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16delta deletion strain, and a cdc1delta cos16delta double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.

cAMP inhibits bud growth in a yeast strain compromised for Ca2+ influx into the Golgi.

Biochemical and physiological studies have implicated cAMP and cAMP-dependent protein kinase (PKA) in a plethora of essential cellular processes. Here we show that yeast cells partially depleted of PKA activity (due to a tpkw mutation) and bearing a lesion in a Golgi-localized Ca2+ pump (Pmr1), arrest division with a small bud. The bud morphology of the arrested tpk1w pmr1 mutant cells is characteristic of cells in S phase; however, the terminal phenotype of processes such as DNA replication and nuclear division suggests arrest at the G2/M boundary. This small bud, G2-arrest phenotype is similar to that of strains with a defect in cell wall biosynthesis (pkc1) or membrane biogenesis (och1); however, the biochemical defect may be different since the tpk1w pmr1 double mutants retain viability. The growth defect of the tpk1w pmr1 mutant can be alleviated by preventing the increase in cellular cAMP levels that is known to be associated with a decrease in PKA activity, or by supplementing the medium with millimolar amounts of Ca2+. Although the biochemical consequences of this increase in cAMP concentration are not known, the small-bud phenotype of the double mutant and the known protein processing defect of the pmr1 lesion suggest that the localization or function of some membrane component might be compromised and susceptible to perturbations in cellular cAMP levels. One candidate for such a protein is the cAMP-binding membrane ectoprotein recently described in yeast.