The Shift: COVID-19-Associated Deaths are Now Trending Lower Among Blacks and Hispanics Compared to Whites.

BACKGROUND: Throughout the coronavirus (COVID-19) pandemic, research revealed people of color were more likely to be infected, have severe illness, and die due to the virus. However, some areas in the USA are now reporting a new shift; lower Black and Hispanic COVID-19 mortality rates compared to their White counterparts. Research indicates that this shift is the result of COVID-19's impact on disparities by race. In this paper, we analyze death data to determine if the new shift has occurred locally. Specifically, we examined COVID-19 prevalence and related death data in Connecticut by comparing race/ethnicity through two periods of time: one before and one after the first case of the Omicron variant of COVID-19. METHODS: This cross-sectional epidemiological analysis to examine cases and deaths by racial/ethnic status utilizes Connecticut data from March 2020 to February 2022. The following assumption is applied: expected pre-Omicron cases and deaths from March 5, 2020 to November 27, 2021 are equal to the number of cases and deaths during Omicron cases and deaths from November 28, 2021 to February 17, 2022. Race/ethnicity are operationalized as non-Hispanic White, non-Hispanic Black, and Hispanic. RESULTS: Pre-Omicron (March 5, 2020 to November 27, 2021) compared to the monthly aged adjusted COVID-19 case rate for Whites (394/10,000 populations), Blacks had a higher rate (501/10,000 populations), and Hispanics had the highest (585/10,000 populations). During the Omicron period (November 28 to February 17, 2022), significant changes in COVID-19 case rates were observed in all three ethnic groups, but the biggest changes were observed in Hispanics, followed by Blacks, and then Whites. The rate ratios further showed a remarkable reduction of 47% in case rates (from 1.0 pre-Omicron and from 1.47 during Omicron, p < 0.0001) for Hispanics, when compared to that of Whites. While Blacks showed a significant, smaller reduction of 5% in case rates (from 1.27 pre-Omicron and from 1.22 during the Omicron, p < 0.001) when compared to Whites. Regarding COVID-19-related mortality, the racial differences were similar. CONCLUSIONS AND RELEVANCE: By examining Connecticut's COVID-19 death and case data, this study identified the new shift that occurred locally. The current shift may be anchored in the evolution of the COVID-19 virus, public health guidelines/policies, and the degree to which populations have complied with public health recommendations.

Effects of Longitudinal Changes in Neuroticism and Stress on Cognitive Decline.

OBJECTIVE: The relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: The authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MEASUREMENTS: The authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. RESULTS: In multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = -0.080[95%CL: -0.145 to -0.015], T = -2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. CONCLUSION: Our findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Genipin does not reduce the initiation or propagation of microcracks in collagen networks of cartilage.

Objective: We recently initiated microcracks, i.e. micron-scale cracks in the collagen networks of cartilage, using both single low-energy impacts and unconfined, cyclic compressions. We also tracked the propagation of microcracks after cyclic compressions simulating 12,000 walking strides. In this study, we aimed to determine the effect of one or more genipin treatments on: (1) the initiation of microcracks under mechanical impacts and (2) the subsequent propagation of microcracks under cyclic, unconfined compression. We hypothesized that treatments with genipin would improve the resistance of cartilage to microdamage, specifically reducing both the initiation of microcracks under impact loading and the propagation of microcracks under cyclic compression. Design: We tested 49 full-thickness, cylindrical osteochondral specimens. We incorporated one or two doses of genipin in between mechanical treatments, i.e. single low-energy mechanical impacts to initiate microcracks and unconfined, cyclic compressions to propagate microcracks. We also imaged specimens using second harmonic generation confocal microscopy, and analyzed the resulting images to quantify changes in morphologies (length, width, and depth) and orientations of microcracks. Finally, we used separate mixed-regression modeling to evaluate the effects of genipin treatments on mechanically induced microcracks. Results: Specimens treated with genipin presented significantly longer and marginally deeper microcracks after mechanical impacts. Two doses of genipin caused significantly longer and wider microcracks under propagation verses one dose. Conclusions: Our results do not support our hypothesis: unfortunately treatments with genipin, and the resulting mechanisms of cross-linking, do not provide resistance to microdamage, quantified as the initiation and propagation of microcracks.

Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults.

Older adults represent a vulnerable population with elevated risk for numerous morbidities. To explore the association of the microbiome with aging and age-related susceptibilities including frailty and infectious disease risk, we conducted a longitudinal study of the skin, oral, and gut microbiota in 47 community- or skilled nursing facility-dwelling older adults vs. younger adults. We found that microbiome changes were not associated with chronological age so much as frailty: we identified prominent changes in microbiome features associated with susceptibility to pathogen colonization and disease risk, including diversity, stability, heterogeneity, and biogeographic determinism, which were moreover associated with a loss of Cutibacterium (C.) acnes in the skin microbiome. Strikingly, the skin microbiota were also the primary reservoir for antimicrobial resistance, clinically important pathobionts, and nosocomial strains, suggesting a potential role particularly for the skin microbiome in disease risk and dissemination of multidrug resistant pathogens.

Association of 1-year change in neuroticism and 3-year change in cognitive performance among older depressed adults.

OBJECTIVES: The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism. MEASUREMENTS: We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates. RESULTS: We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score. CONCLUSIONS: Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Changes in COVID-19-Associated Deaths During a Year Among Blacks and Hispanics Compared to Whites in the State of Connecticut.

BACKGROUND: With recent COVID-19 vaccination rates relatively high in the USA, the USA still maintains the most documented cases globally,[1] even though COVID-19 cases, hospitalization, and mortality have been declining. However, the health burden has been largely felt in communities involving racial and ethnic minorities. Thus, in order to provide a clearer picture of what is happening in Black, Indigenous, and people of color communities, we examined the racial/ethnic differences of monthly COVID-19 deaths in Connecticut. METHODS: This is an epidemiological study analyzing mortality data from March 1, 2020, to February 28, 2021, obtained from the Connecticut State Department of Public Health. The data include cause of death (COVID-19 death identified by ICD-10 code U071), race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic), sex, and age. Both crude and age-adjusted rates were reported by racial/ethnic groups. To compare age-adjusted rates between racial groups, with estimated age-adjusted death counts as outcomes, between-racial group rate ratios, 95% confidence intervals, and p values significant at < 0.05 were derived from the Poisson regression model. RESULTS: From March 2020 to May 2020 (wave 1) of COVID-19 cases, the COVID-19-related mortality rates were the highest for all three race groups (Whites, Blacks, and Hispanics) with statistical group differences (p < 0.05). Blacks had the highest rates of deaths followed by Hispanics and then Whites. Further, more Whites died in a nursing home when compared to Blacks and Hispanics. From June 2010 to October 2020 (wave 2), COVID-19 mortality declined significantly for all three race groups with no statistical differences between groups. COVID-19 deaths in nursing homes declined for all three racial/ethnic groups. From November 2020 to February 2021 (wave 3), COVID-19 mortality rates were significantly higher compared to wave 2 but lower than wave 1 for all three race groups. The mortality rates for Blacks and Hispanics were higher than Whites. Hispanics had the highest rates of deaths, followed by Blacks, and then Whites (p < 0.05). Whites showed the lowest mortality rates among all three racial/ethnic groups. CONCLUSIONS: In summary, COVID-19 health disparities among Black and Hispanic populations were evident in this study. Blacks and Hispanics had significantly higher mortality rates when compared to Whites. Blacks had the highest mortality rates during wave 1, and in wave 3, Hispanics has the highest mortality rates. Our data are important because they show monthly COVID-19 deaths data by race. Data reported this way gives a better and more accurate understanding of what is really happening in Black, Indigenous, and people of color populations.

Fentanyl, Heroin, and Cocaine Overdose Fatalities are Shifting to the Black Community: An Analysis of the State of Connecticut.

BACKGROUND: Historically, Blacks and Hispanics have had lower opioid-involved overdose death rates in Connecticut (CT). We examined if a shift has taken place where rates of Black fatal overdoses have now surpassed Whites in the state. METHODS: Drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2012 to 2019 in Connecticut. Measures were by race (White, Hispanic, Black, and Asian or Pacific Islander), age groups, and types of drugs, including fentanyl, heroin, cocaine, and other opioids. Poisson regression was used to test the interactions (race × age); joinpoint regression analysis was used to evaluate trend lines of fatality rate by racial/ethnic group within each age group with a significance level of p < 0.05. RESULTS: Drug overdose fatality rates in CT from 2012 to 2019 showed a significant increase for all races combined, estimated 3.6 deaths per 100,000 population per year. For Whites, overdose deaths were 4.6 per year from 2012 to 2017 with no change from 2017 to 2019. The overdose fatality rate for Hispanics was 3.0 and for Asian or Pacific Islanders 0.6 per year from 2012 to 2019. For Blacks, the death rates were statistically flat between 2012 and 2014; however, from 2015 to 2019, this group saw the largest average increase of 6.0 overdose deaths per 100,000 population each year. By 2019, the overdose fatality rate was higher in Blacks than in Whites, (39 vs. 38 per 100,000, respectively). Further, Blacks ages 50 years and over reported the highest overdose fatality rates among all race/age groups, an increase of 8.5 deaths per 100,000 population since 2014. CONCLUSIONS AND RELEVANCE: Connecticut is a microcosm of the opioid overdose trend in the New England region of our country. The majority of overdose deaths in CT involved illicit drugs, fentanyl, heroin, and cocaine, rather than prescription drugs. Blacks 50-years-old and over showed the fastest growing overdose death rates. Opioid deaths are now shifting to the Black community, creating an urgent public health crisis.

Excess Deaths Among Blacks and Latinx Compared to Whites During Covid-19.

IMPORTANCE: Blacks and Latinx are disproportionately affected by Coronavirus disease 2019 (Covid-19) and experience higher mortality rates than Whites and Asians in the USA. Such racial disparities, in Covid-19 testing, cases, and mortality are visible in Connecticut too. Recently, excess deaths have become an important consideration in news reports and academic research. However, data on racial differences in excess death is limited. OBJECTIVE: This study examines racial/ethnic differences in excess deaths in the state of Connecticut during the Covid-19 pandemic. DESIGN: This is a cross-sectional epidemiological study to estimate excess deaths by racial/ethnic status utilizing mortality data during the peak months of Covid-19 infections from March 1 to June 30, 2020, in Connecticut. The following assumption is applied: expected non-Covid-19 deaths from March 1 to June 30, 2020, are equal to the number of deaths occurring during the period of March 1 to June 30, 2019. Race/ethnicity are defined as Non-Hispanic White, Non-Hispanic Black, and Latinx. Descriptive statistics and rates with 95% confidence intervals are presented. Chi-square analyses are performed where applicable. SETTING: Connecticut PARTICIPANTS: All deaths in Connecticut from March 1 to June 30, 2020. EXPOSURE: Covid-19 and race/ethnicity RESULTS: From March 1 to June 30, 2020, a total of 14,226 all-cause deaths occurred including 1514 Blacks (10.6%), 1095 Latinx (7.7%), and 11,617 Whites (81.7%). This represented a 74% increase in mortality for Blacks; 63% for Latinx, and 30% for Whites. In addition, 42.70% of the deaths in Blacks were attributed to Covid-19; 38.5% for Latinx, and 23.0% for Whites (p<0.001). Covid-19 deaths accounted for over 90% of the excess deaths in Blacks and Hispanics. In contrast, in Whites, Covid-19 deaths exceeded the number of excess deaths by 353 cases (113.2%), indicating that some Whites may have died from other underlined health conditions with a positive Covid-19 diagnosis. Furthermore, there was an increase in undetermined deaths in 2020, which accounted for 10.8% of deaths in Blacks, 13% in Latinx, and 6.2% of deaths in Whites. CONCLUSIONS AND RELEVANCE: Excess deaths in Blacks and Latinx were found above the numbers of deaths determined to have occurred due to Covid-19. The fact that a large number of undetermined deaths were found for Blacks and Latinx individuals, and testing rates for Blacks and Latinx individuals (as determined by positivity rates) were lacking during this period strongly suggests, these excess deaths were Covid-19-related deaths. The study findings indicate that Black and Latinx COVID-19-related deaths may be underreported in this pandemic. We advocate for targeted strategies that increase testing capacity, treatment, and vaccine availability in Black and Latinx communities.

A New Stage of the Caregiving Career: Informal Caregiving After Long-term Institutionalization.

BACKGROUND AND OBJECTIVES: The "unexpected career" of caregiving has previously been conceptualized in stages: community care through institutional placement/residence, ending with death of the care recipient. Transition programs such as Money Follows the Person (MFP) created a new stage of the caregiving career, caring for someone post-long-term institutionalization, about which little is known. Using Pearlin's Caregiver Stress Process Model, this study explores effects on caregivers from the return of their loved ones to the community after a long-term institutional stay. RESEARCH DESIGN AND METHODS: Cross-sectional surveys of 656 caregivers of persons transitioned through Connecticut's MFP program 2014-2018, completed 6 months posttransition. RESULTS: Regardless of the age/disability of the care recipient, and despite experiencing high caregiving intensity, caregivers experienced less burden, anxiety, and depression, and higher benefits of caregiving than demonstrated in literature for the general caregiving population. Most felt less stressed than before and during the participant's institutional stay. Factors associated with worse outcomes included worry about safety, strained finances, missing work, and desiring additional services. Black and Hispanic caregivers experienced lower burden and anxiety and higher benefits of caregiving than White caregivers. DISCUSSION AND IMPLICATIONS: By providing community supports to participants, transition programs can have broad ancillary benefits for caregivers and improve outcomes in the Pearlin model, lessening potentially deleterious effects of an unexpected return to intensive caregiving duties after institutional placement. Positive results for Black and Hispanic caregivers may reflect cultural expectations in caring for family that buffer the adverse effects of caregiving.

GRK2 enforces androgen receptor dependence in the prostate and prostate tumors.

Metastatic tumors that have become resistant to androgen deprivation therapy represent the major challenge in treating prostate cancer. Although these recurrent tumors typically remain dependent on the androgen receptor (AR), non-AR-driven tumors that also emerge are particularly deadly and becoming more prevalent. Here, we present a new genetically engineered mouse model for non-AR-driven prostate cancer that centers on a negative regulator of G protein-coupled receptors that is downregulated in aggressive human prostate tumors. Thus, prostate-specific expression of a dominant-negative G protein-coupled receptor kinase 2 (GRK2-DN) transgene diminishes AR and AR target gene expression in the prostate, and confers resistance to castration-induced involution. Further, the GRK2-DN transgene dramatically accelerates oncogene-initiated prostate tumorigenesis by increasing primary tumor size, potentiating visceral organ metastasis, suppressing AR, and inducing neuroendocrine marker mRNAs. In summary, GRK2 enforces AR-dependence in the prostate, and the loss of GRK2 function in prostate tumors accelerates disease progression toward the deadliest stage.

Treadmill Exercise Reverses Depression Model-Induced Alteration of Dendritic Spines in the Brain Areas of Mood Circuit.

Depression is one of the most prevalent psychiatric disorders. Exercise has been shown to be effective in the amelioration of depression, but the underlying mechanism remains largely unknown. Alterations in the density and morphology of dendritic spines are associated with psychiatric diseases. Chronic unpredictable mild stress (CUMS) is an established animal model of depression. The aim of this study was to determine whether treadmill exercise reverses CUMS-induced both depression-like behaviors and alterations in spine density and morphology of the principal neurons in the brain areas of the mood circuits including the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and basolateral amygdala (BLA). Male rats were randomly divided into four groups: control, CUMS, exercise, and CUMS+exercise. CUMS-induced depression-like behaviors were evaluated by the sucrose preference test (SPT). Golgi staining was used to visualize dendritic spines. Our results showed that CUMS-induced depression-like behaviors characterized by a decrease in sucrose consumption were accompanied by a decrease in spine density and a change in spine morphology in the pyramidal neurons of both the hippocampal CA3 area and the mPFC, and an increase in spine density and an alteration in spine shape in both the NAc medium spiny neurons (MSNs) and the BLA neurons; exercise reversed both CUMS-induced depression-like behaviors and alterations in dendritic spines. This study provides important information for understanding the mechanism through which exercise ameliorates CUMS-induced depression-like behaviors.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience.

BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis. OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut. METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review. RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female. CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.

Advertising Content, Platform Characteristics and the Appeal of Beer Advertising on a Social Networking Site.

AIMS: The current study was conducted to investigate how changes in the content of a social media ad, user engagement values associated with the ad and user-generated comments (UGCs) associated with the ad can influence the appeal (i.e. source appeal, informational appeal and emotional appeal) of a social media ad. SHORT SUMMARY: Facebook beer ads that violated the guidelines of a relevant marketing code were rated as more emotionally appealing compared to Facebook beer ads that did not violated the guidelines. Increased emotional appeal in beer advertising increases the probability that the ad will be remembered and influence future drinking occasions. METHODS: A 2 (ad regulatory compliance: compliant vs. non-compliant) × 2 (user engagement: low vs. high) × 2 (UGC congruence: pro- vs anti-alcohol) mixed factorial experiment was conducted with 120 young adults, 21-24 years old. Each participant viewed four Facebook beer ads that were previously evaluated for thematic content and regulatory compliance. Participants were randomized to view either high or low user engagement values and either pro- or anti-drinking user-generated comments. After each ad exposure, ad appeal was assessed. Statistical analysis was conducted using hierarchical linear modeling. Models were adjusted for demographics, Alcohol Use Disorders Identification Test (AUDIT) scores and Facebook involvement. RESULTS: Source appeal (P = 0.034) and informational appeal (P < 0.001) were significantly higher among ads that were compliant with existing advertising regulations. Emotional appeal was significantly higher among ads that were non-compliant (P = 0.004). The effect of user engagement and UGCs were non-significant (p's > 0.05). Additionally, AUDIT scores (p's < 0.01) and Facebook involvement scores (p's < 0.01) were positively associated with all forms of ad appeal. CONCLUSION: The appeal of Facebook beer ads may be primarily determined by ad content. Increased emotional appeal in advertising caused by non-compliant advertising may increase the probability that the ad will be remembered and influence future drinking occasions.

Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia.

PURPOSE: Clinicians use tamsulosin, an α1-adrenoceptor antagonist, to manage symptomatic benign prostatic hyperplasia (BPH). Because α1-adrenoceptors are also present in the brain, the potential exists for adverse effects on cognitive functions. We explored the association between tamsulosin use and dementia risk. METHODS: We used Medicare data (2006-2012) to conduct a cohort study among patients aged ≥65 years and diagnosed with BPH. Men taking tamsulosin (n = 253 136) were matched at a 1:1 ratio using propensity-scores to each of 6 comparison cohorts: patients who used no BPH-medication (n = 180 926), and patients who used the following alternative-BPH-medications: doxazosin (n = 28 581), terazosin (n = 23 858), alfuzosin (n = 17 934), dutasteride (n = 34 027), and finasteride (n = 38 767). Assessment began following the first fill of BPH-medication to identify incident dementia by ICD-9 diagnosis codes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for dementia using Cox proportional hazard regression for each of the 6 propensity-score-matched cohort-pairs. RESULTS: The median follow-up period for all cohorts was 19.8 months. After propensity-score matching, the tamsulosin cohort had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years in the no-BPH-medication cohort. The risk of dementia was significantly higher in the tamsulosin cohort, when compared with the no-BPH-medication cohort (HR [95% CI]: 1.17 [1.14, 1.21]) and each of the alternative-BPH-medication cohorts: doxazosin (1.20 [1.12, 1.28]), terazosin (1.11 [1.04, 1.19]), alfuzosin (1.12 [1.03, 1.22]), dutasteride (1.26 [1.19, 1.34]), and finasteride (1.13 [1.07, 1.19]). The significance of these findings persisted in sensitivity analyses. CONCLUSION: Tamsulosin may increase the risk of dementia in older men with BPH.

Presence of neuroticism and antidepressant remission rates in late-life depression: results from the Neurobiology of Late-Life Depression (NBOLD) study.

ABSTRACTNeuroticism in older adults is common yet understudied, particularly its effects on depression treatment outcomes. We hypothesized that presence of high neuroticism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. In this longitudinal cohort study, 43 depressed older adults completed the Revised NEO Personality Inventory (NEO PI-R). A study psychiatrist administered the Montgomery Ǻsberg Depression Rating Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of medical burden) at baseline, and the MADRS at each clinical visit. All subjects began open-label sertraline treatment and were followed over 12 weeks with clinically indicated flexible dosing and an option to switch antidepressants. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score < 8) and final MADRS score. We found that higher total neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000) and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728-0.983), were associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers. Findings remained significant after controlling for baseline MADRS and CIRS score. In conclusion, assessment of personality, particularly features of neuroticism, may be important in management of late-life depression. Future studies should determine if depressed patients high in neuroticism may benefit from psychotherapy focusing on emotional regulation and stress management.

A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

Proximal Aberrant Crypt Foci Associate with Synchronous Neoplasia and Are Primed for Neoplastic Progression.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas.Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy.Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR.

Metformin Use in Practice: Compliance With Guidelines for Patients With Diabetes and Preserved Renal Function.

IN BRIEF Several contraindications limit the use of metformin, most notably the risk of lactic acidosis. This article reports on an examination of a population of patients with diabetes with preserved renal function to evaluate provider compliance with guidelines on metformin use and to identify factors that contributed when practice diverged from recommendations. It found that metformin was withheld from approximately one-third of these patients because of 1) an existent contraindication to metformin, 2) patient behavior or preference, or 3) provider preference or bias based on patient or personal factors. Although providers generally follow current recommendations for the use of metformin, deviations from guidelines in practice are common.

Acute Effects of Moderate Alcohol Consumption on Postural Stability in Older Adults.

This study involved healthy community-living older adults in an investigation of the association between moderate alcohol consumption (AC) and acute changes in postural stability and whether the association differed according to pre-AC balance skills. Thirty-nine moderate drinkers aged ≥ 65 years (62% women; mean age: 73.9 ± 6.1 years) consumed a moderate dose of alcohol (0.4 g/kg; administered as two drinks). Breath alcohol concentration and postural stability were measured at five time points (pre-AC and 40, 80, 120, and 160 minutes post-AC) using unipedal stance time (UPST) and center of pressure (CoP) displacement. Pre-AC UPST was used to categorize participants into good-balance (≥30 seconds) and poor-balance (<30 seconds) groups. Peak breath alcohol concentration was 30 mg/dL at 40 minutes post-AC. For all participants, postural stability declined significantly at 80 minutes post-AC (UPST, p = .005; anterior-posterior CoP displacement, p = .029). While the poor-balance group did not show a significant decrease in UPST duration over the course of the study, the good-balance group experienced significant decline at 80 minutes compared with baseline ( p < .001) and remained above the 30-second UPST cutoff. Both groups experienced similar worsening in anterior-posterior CoP displacement at 80 minutes post-AC. Thus, moderate AC was associated with acute decline in postural stability in older adults. The worsened anterior-posterior CoP displacement post-AC in the poor-balance group was of particular concern because these participants were already at lower balance functioning pre-AC. Larger, more representative studies of varying groups of participants are needed to further explore how this change relates to fall incidents and fall risk.