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Objective The purpose of this study is to examine the utilization of kyphoplasty/vertebroplasty procedures in the management of compression fractures. With the growing elderly population and the associated increase in rates of osteoporosis, vertebral compression fractures have become a daily encounter for spine surgeons. However, there remains a lack of consensus on the optimal management of this patient population. Methods A retrospective analysis of 91 million longitudinally followed patients from 2016 to 2019 was performed using the PearlDiver Patient Claims Database. Patients with compression fractures were identified using International Classification of Disease, 10th Revision codes, and a subset of patients who received kyphoplasty/vertebroplasty were identified using Common Procedural Terminology codes. Baseline demographic and clinical data between groups were acquired. Multivariable regression analysis was performed to determine predictors of receiving kyphoplasty/vertebroplasty. Results A total of 348,457 patients with compression fractures were identified with 9.2% of patients receiving kyphoplasty/vertebroplasty as their initial treatment. Of these patients, 43.5% underwent additional kyphoplasty/vertebroplasty 30 days after initial intervention. Patients receiving kyphoplasty/vertebroplasty were significantly older (72.2 vs. 67.9, p < 0.05), female, obese, had active smoking status and had higher Elixhauser Comorbidity Index scores. Multivariable analysis demonstrated that female sex, smoking status, and obesity were the 3 strongest predictors of receiving kyphoplasty/vertebroplasty (odds ratio, 1.27, 1.24, and 1.14, respectively). The annual rate of kyphoplasty/vertebroplasty did not change significantly (range, 8%–11%). Conclusion The majority of vertebral compression fractures are managed nonoperatively. However, certain patient factors such as smoking status, obesity, female sex, older age, osteoporosis, and greater comorbidities are predictors of undergoing kyphoplasty/vertebroplasty.

This study employed a critical inquiry paradigm to explore the significance of equity and social justice in teaching qualitative methodologies and methods to graduate students. Graduate students of multiple minoritized identities and a faculty member conducted a two-year inquiry into the research apprenticeship experience, including the stages of student-led conceptualization, data collection, analysis, international conference presentation, and publication. The study investigated the experiences of the faculty and students as well as the responsibilities of the institution against the backdrop of historical and contemporary pandemics. Consequently, we problematized hidden curriculum and unconscious assumptions to suggest research course design sequencing improvements. The findings emphasize the impact of these experiences on qualitative research teaching and learning practices and institutional responsibility to graduate student research apprenticeships. The Graduate Research Apprenticeship Nested Design Pathway is presented as a tool that institutions worldwide can adapt and implement to serve the complex needs of their students.

Background:. Type-II dens fractures have long been described in the literature as occurring in a bimodal distribution, peaking in young adulthood as well as in older adulthood; however, the origin of this claim is unclear. The primary goal of this study was to examine the incidence of type-II dens fractures and assess for bimodality. Methods:. This is a retrospective cross-sectional review of the National Trauma Data Bank (NTDB) records on traumatic type-II dens fractures between October 2015 and December 2016. Rates were obtained from the NTDB, and the incidence per 100,000 was ascertained by utilizing U.S. Census data from 2016. Subgroupings by gender and Black or White race were also examined. Results:. Dens fractures occur unimodally, peaking around 89 years of age overall, skewed left by high rates in older White adults. The Black subgroup demonstrated trimodality, with the fracture incidence peaking at 25, 62, and 82 years of age. Rates among Black and White patients were similar until age 65, after which dens fractures occurred disproportionately in White patients. Fractures prior to age 75 occurred predominantly in men. Conclusions:. The evidence derived in this study challenges the common belief that type-II dens fractures occur bimodally across the entire population. However, there remains utility in considering younger and older patients as distinct groups for the purposes of management.

Background: In patients with concomitant hip and lumbar spine disease, the question of which surgery—total hip arthroplasty (THA) or lumbar spine fusion (LSF)—to address first has not been adequately answered. We aimed to evaluate the risk of dislocation after THA in patients with LSF first or after THA. Methods: Retrospective review utilizing the PearlDiver database querying Current Procedural Terminology codes for LSF in the year prior (LSF first) or in the year after primary or revision THA (THA first). International Classification of Disease codes identified postoperative hip dislocation as our primary outcome variable. Demographic data collected included age, sex, and obesity. Dislocation rates were described as a proportion of the cohort and compared with chi-square tests. Results: We identified 280,857 primary THA and 42,314 revision THA cases from 2012-2019. Of these, 2090 underwent primary THA and LSF, and 283 underwent revision THA and LSF within a year of each procedure. No differences in age, sex, or obesity between groups were noted. No difference in rate of all-time dislocation for primary THA was noted for the LSF first 51/1429 (3.6%) compared to the THA first 30/661 (4.0%) groups (P = .34), or for revision THA with LSF first 48/204 (23.5%) compared to THA first 27/117 (23.1%) groups (P = 1.0). Conclusions: There was no difference in the risk of dislocation after primary or revision THA if LSF occurred prior to or after the THA. These findings can help surgeons as they counsel patients with concomitant lumbar spine and hip degeneration.

The evolution of prosthetic limbs continues to develop, with novel manufacturing techniques being evaluated, including additive manufacturing. Additive manufacturing (AM), or 3D-printing, holds promise for enabling personalized and tailored medical device options. The requirements for personalized medicine, coupled with the limitations of small-batch manufacturing, have made the technique viable for exploration. In this manuscript, an approach is presented for incorporating additive manufacturing for prostheses, both as a final part and in applications as an intermediate manufacturing step. As a result, through the use of these methods a multi-gesture capable electromyographic prosthesis was designed and manufactured, currently being evaluated in clinical trials for pediatric patients. This paper explored the results of this unique method of applying additive manufacturing techniques, and assessed how the blend of different manufacturing techniques improved performance and reduced device weight. Creating unique and aesthetic cosmetic coverings for the device was achieved through using additive manufacturing as an intermediate manufacturing component and, then, applying thermoforming. Cosmesis components saw a 33% reduction in weight from this change in manufacturing. The approach is explored to blend multiple manufacturing techniques to create cosmesis components and structural components for the prosthesis. The techniques serve the design intent to reduce reported challenges with upper limb prosthesis devices and to encourage device retention. Recommendations for manufacturing strategies are discussed, including the limitations.

Background: Vitamin D has been shown to play important roles in both calcium homeostasis and bone healing. Only three studies have directly examined the relationship between vitamin D deficiency and hardware failure, nonunion, and/or revision surgery. Results are contradictory and none were large enough to provide the statistical power necessary to make definitive conclusions. Methods: A retrospective analysis was performed utilizing the PearlDiver national insurance claims database consisting of 91 million individual patient records. Patients aged 30 and over who underwent a non-segmental posterior lumbar fusion procedure (CPT-22840) in 2012-2019 were included. Data collected included, hardware failure, revision surgery occurrence, and vitamin D deficiency. Hardware failure and revision rates were compared between vitamin D deficient and non-deficient groups. We ran a logistic regression analysis using the following variables: age, Charlson Comorbidity Index (CCI), gender, vitamin D deficiency, obesity, tobacco use, diabetes, osteoporosis, rheumatoid arthritis, and Crohn's disease. Results: 108,137 patients matching inclusion criteria were identified, with an overall hardware failure rate of 2.7% and revision rate of 4.1%. Failure rates were significantly higher for patients diagnosed with vitamin D deficiency during the full queried period (3.3% vs. 2.6%, OR = 1.26; p < 0.0001), as were revision rates (4.3% vs 3.5%, OR = 1.25; p < 0.0001). Patients diagnosed with deficiency pre-surgery, higher failure (3.1% vs 2.6%, OR = 1.19; p < 0.01) and rates of revision (4.4% vs 3.5%, OR = 1.27; p < 0.0001) were increased compared to the non-deficient group. In the logistic regression analysis, vitamin D deficiency remains a significant contributor to hardware failure and revision surgery. Conclusions: These results demonstrate that pre- and/or post-operative vitamin D deficiency is independently correlated with risk for hardware failure and revision surgery in single-level lumbar fusion patients.

Abstract Background It is common practice to use a combination approach of computed tomography (CT) scan followed by upright radiographs when assessing traumatic thoracolumbar (TL) vertebral fractures. The purpose of this study was to determine the clinical utility of upright spine radiographs in the setting of traumatic TL fracture management. Our null hypothesis is that upright TL radiographs rarely change management of acute vertebral fractures. Methods A retrospective study was performed on patients with an initial plan of non-operative management for a TL fracture between January 2014 and June 2020 at a single Level 1 trauma center. Patients were followed from time of initial consult to either conversion to surgery (operative) or last available outpatient follow up imaging (non-operative). Lateral kyphotic angle of the fractured vertebra and anterior vertebral body height% loss on initial CT, first upright radiograph, and endpoint upright radiograph imaging were measured. Measurements were compared between and within operative and non-operative groups using t-tests and Mann-Whitney U tests when appropriate. P-values ≤ 0.05 were considered statistically significant. Results The study included 70 patients with an average age of 54 years and 37 (52.9%) were women. Six (8.6%) of 70 patients had a change from non-operative to operative management based on upright radiographs. The mean (standard deviation) change in degrees of kyphosis from CT scan to first X-ray was 4.6 (7.0) in the non-operative group and 11.5 (8.1) in the operative group (P = 0.03). Delta degrees of kyphosis from CT scan to endpoint X-ray was 6.4 (9.0) and 16.2 (6.2) in the non-operative and operative groups, respectively (P = 0.01). In the operative group, mean degrees of kyphosis increased from 1.6 (7.6) in initial CT to 13.1 (8.9) in first X-ray (P = 0.02). First X-ray mean anterior body height% loss was 37.5 (17.6) and 53.2 (16.1) in the non-operative and operative groups, respectively (P = 0.04). Conclusions Upright radiographs are useful in guiding traumatic vertebral fracture management decisions. Larger studies are needed to determine the degree of change in kyphosis between CT and first standing radiograph that is suggestive of operative management. Trial registration number and date of registration Not applicable.

Speech frequency following responses (sFFRs) are increasingly used in translational auditory research. Statistically-based automated sFFR detection could aid response identification and provide a basis for stopping rules when recording responses in clinical and/or research applications. In this brief report, sFFRs were measured from 18 normal hearing adult listeners in quiet and speech-shaped noise. Two statistically-based automated response detection methods, the F-test and Hotelling’s T2 (HT2) test, were compared based on detection accuracy and test time. Similar detection accuracy across statistical tests and conditions was observed, although the HT2 test time was less variable. These findings suggest that automated sFFR detection is robust for responses recorded in quiet and speech-shaped noise using either the F-test or HT2 test. Future studies evaluating test performance with different stimuli and maskers are warranted to determine if the interchangeability of test performance extends to these conditions.

The hippocampus consists of a stereotyped neuronal circuit repeated along the septal-temporal axis. This transverse circuit contains distinct subfields with stereotyped connectivity that support crucial cognitive processes, including episodic and spatial memory. However, comprehensive measurements across the transverse hippocampal circuit in vivo are intractable with existing techniques. Here, we developed an approach for two-photon imaging of the transverse hippocampal plane in awake mice via implanted glass microperiscopes, allowing optical access to the major hippocampal subfields and to the dendritic arbor of pyramidal neurons. Using this approach, we tracked dendritic morphological dynamics on CA1 apical dendrites and characterized spine turnover. We then used calcium imaging to quantify the prevalence of place and speed cells across subfields. Finally, we measured the anatomical distribution of spatial information, finding a non-uniform distribution of spatial selectivity along the DG-to-CA1 axis. This approach extends the existing toolbox for structural and functional measurements of hippocampal circuitry.

The efferent auditory nervous system may be a potent force in shaping how the brain responds to behaviorally significant sounds. Previous human experiments using the frequency following response (FFR) have shown efferent-induced modulation of subcortical auditory function online and over short- and long-term time scales; however, a contemporary understanding of FFR generation presents new questions about whether previous effects were constrained solely to the auditory subcortex. The present experiment used sine-wave speech (SWS), an acoustically-sparse stimulus in which dynamic pure tones represent speech formant contours, to evoke FFRSWS. Due to the higher stimulus frequencies used in SWS, this approach biased neural responses toward brainstem generators and allowed for three stimuli (/bɔ/, /bu/, and /bo/) to be used to evoke FFRSWSbefore and after listeners in a training group were made aware that they were hearing a degraded speech stimulus. All SWS stimuli were rapidly perceived as speech when presented with a SWS carrier phrase, and average token identification reached ceiling performance during a perceptual training phase. Compared to a control group which remained naïve throughout the experiment, training group FFRSWS amplitudes were enhanced post-training for each stimulus. Further, linear support vector machine classification of training group FFRSWS significantly improved post-training compared to the control group, indicating that training-induced neural enhancements were sufficient to bolster machine learning classification accuracy. These results suggest that the efferent auditory system may rapidly modulate auditory brainstem representation of sounds depending on their context and perception as non-speech or speech.

Abstract Yarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the production of renewable chemicals and enzymes for fuel, feed, oleochemical, nutraceutical and pharmaceutical applications. Metabolic engineering of this non-conventional yeast started through conventional molecular genetic engineering tools; however, recent advances in gene/genome editing systems, such as CRISPR–Cas9, transposons, and TALENs, has greatly expanded the applications of synthetic biology, metabolic engineering and functional genomics of Y. lipolytica. In this review we summarize the work to develop these tools and their demonstrated uses in engineering Y. lipolytica, discuss important subtleties and challenges to using these tools, and give our perspective on important gaps in gene/genome editing tools in Y. lipolytica.

Several cues are used to convey musical emotion, the two primary being musical mode and musical tempo. Specifically, major and minor modes tend to be associated with positive and negative valence, respectively, and songs at fast tempi have been associated with more positive valence compared to songs at slow tempi (Balkwill and Thompson, 1999; Webster and Weir, 2005). In Experiment I, we examined the relative weighting of musical tempo and musical mode among adult cochlear implant (CI) users combining electric and contralateral acoustic stimulation, or “bimodal” hearing. Our primary hypothesis was that bimodal listeners would utilize both tempo and mode cues in their musical emotion judgments in a manner similar to normal-hearing listeners. Our secondary hypothesis was that low-frequency (LF) spectral resolution in the non-implanted ear, as quantified via psychophysical tuning curves (PTCs) at 262 and 440 Hz, would be significantly correlated with degree of bimodal benefit for musical emotion perception. In Experiment II, we investigated across-channel spectral resolution using a spectral modulation detection (SMD) task and neural representation of temporal fine structure via the frequency following response (FFR) for a 170-ms /da/ stimulus. Results indicate that CI-alone performance was driven almost exclusively by tempo cues, whereas bimodal listening demonstrated use of both tempo and mode. Additionally, bimodal benefit for musical emotion perception may be correlated with spectral resolution in the non-implanted ear via SMD, as well as neural representation of F0 amplitude via FFR – though further study with a larger sample size is warranted. Thus, contralateral acoustic hearing can offer significant benefit for musical emotion perception, and the degree of benefit may be dependent upon spectral resolution of the non-implanted ear.

The purposes of this study were to determine if there are any differences in awareness and utilization of available home- and community-based long-term care (HCBLTC) between rural American Indian and white elderly with co-morbid diabetes, and to examine how they learned about HCBLTC programs. Survey data were analyzed from 62 American Indians and 64 whites aged 65 years or older living in the community. The American Indian respondents were more likely to be aware of and to have used HCBLTC programs compared to their white counterparts. The most common way that the American Indian participants learned about HCBLTC programs was through health care referrals, while the most common way for whites was through friends. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids are associated with higher risk of dependence and more intense withdrawal symptoms than plant-derived Δ9-tetrahydrocannabinol (THC). Avoidance of withdrawal symptoms, including anxiogenic effects, can contribute to continued cannabinoid use. Adult male and female Long-Evans rats were given escalating doses of WIN 55,212-2 (WIN) via twice daily intrajugular infusions. Precipitated withdrawal was elicited with SR 141716 (rimonabant) 4 h after the final infusion. Global withdrawal scores (GWS) were compiled by summing z-scores of observed somatic behaviors over a 30-min period with locomotor activity simultaneously collected via beam breaks. Rimonabant precipitated withdrawal in female and male rats at 3 or 10 mg/kg, respectively, but the individual behaviors contributing to GWS were not identical. 3 mg/kg rimonabant did not impact locomotor behavior in females, but 10 mg/kg decreased locomotion in male controls. Spontaneous withdrawal observed between 6 and 96 h after the final infusion was quantifiable up to 24 h following WIN administration. Individual behaviors contributing to GWS varied by sex and time point. Males undergoing spontaneous withdrawal engaged in more locomotion than females undergoing withdrawal. Separate groups of rats were subjected to a battery of anxiety-like behavioral tests (elevated plus maze, open field test, and marble burying test) one or two weeks after WIN or vehicle infusions. At one week abstinence, sex-related effects were noted in marble burying and the open field test but were unrelated to drug treatment. At two weeks abstinence, females undergoing withdrawal spent more time grooming during marble burying and performed more marble manipulations than their male counterparts. WIN infusions did not impact estrous cycling, and GWS scores were not correlated with estrous at withdrawal. Collectively, these results show qualitative sex differences in behaviors contributing to the behavioral experience of cannabinoid withdrawal supporting clinical findings from THC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The incidence of secondary malignancies associated with busulfan exposure is considered low, but has been poorly characterized. Because this alkylating agent is increasingly utilized as conditioning prior to gene therapy in nonmalignant hematologic and related disorders, more precise characterization of busulfan's potential contribution to subsequent malignant risk is warranted., Procedure: We conducted a literature-based assessment of busulfan and subsequent late effects, with emphasis on secondary malignancies, identifying publications via PubMed searches, and selecting those reporting at least 3 years of follow-up., Results: We identified eight pediatric and 13 adult publications describing long-term follow-up in 570 pediatric and 2076 adult hematopoietic cell transplant (HCT) recipients. Secondary malignancies were reported in 0.5% of pediatric HCT recipients, with no cases of myelodysplastic syndrome (MDS) or acute myelocytic leukemia (AML). Fatal secondary malignancies were reported in 0.8% of 1887 evaluable adult HCT recipients, and an overall incidence of secondary malignancies of 4.8% was reported in a subset of 389 evaluable adult patients. We also reviewed long-term results from eight publications evaluating lentiviral- and human promotor-based HSC-targeted gene therapy in 215 patients with nonmalignant conditions, in which busulfan/treosulfan monotherapy or busulfan/fludarabine was the only conditioning. Two malignancies were reported in patients with sickle cell disease (SCD), one of which was potentially busulfan-related. No additional malignancies were reported in 173 patients with follow-up of 5-12 years., Conclusion: The incidence of busulfan-related secondary malignancies is low, and likely to be substantially less than 1% in pediatric transplant recipients, especially those receiving busulfan monotherapy for nonmalignant conditions other than SCD., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously, it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats., (© 2022 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Major depressive disorder is the most common neuropsychiatric comorbidity of human immunodeficiency virus (HIV), and women are more frequently affected in the general population and among those with HIV. The rate of depression in HIV is three times higher than the general population. Differences in biomarkers in neuroendocrine and inflammatory pathways are one possible explanation for the increased prevalence of depression in individuals with HIV, especially biological women. Therefore, we aimed to perform a systematic review identifying differences in neuroendocrine factors leading to depression in men versus women with HIV., Methods: A comprehensive search of 8 databases was performed, followed by title and abstract screening and later full-text screening by two independent researchers. A risk of bias assessment was completed., Results: Twenty-six full-text articles were included in the review. Significant correlations between depression and neuroendocrine marker levels were found for cortisol (both sexes), testosterone (only in men), oxytocin (only tested in women), and estradiol (only in women). No significant correlation between depression and hormone level was found for prolactin, dehydroepiandrosterone (DHEAS), or sex hormone binding globulin (SHBG). Nearly all studies included only men or women and did not directly compare neuroendocrine markers between the two sexes. One study found that the correlation between cortisol levels and depression scores was stronger in women than men., Conclusion: Neuroendocrine systems are highly active in the brain and important in the development and persistence of mental illness. Given that HIV can, directly and indirectly, impact hormone signaling, it is likely contributing to the high rate of depression in individuals with HIV. However, few studies explore neuroactive hormones in depression and HIV, nor how this connection may differ between the sexes. More high-quality research is needed in this area to explore the link further and inform possible avenues of treatment., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Glutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self-administration. We used intravenous self-administration of two constituents of cannabis, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) to examine how contingent cannabis use and cue-induced cannabinoid-seeking alters glutamatergic neurotransmission and synaptic plasticity in NAcore. NMDA receptor (NMDAR)-dependent long-term depression (LTD) in the NAcore was lost after cannabinoid, but not sucrose self-administration. Surprisingly, when rats underwent cue-induced cannabinoid seeking, LTD was restored. Loss of LTD was accompanied by desensitization of cannabinoid receptor 1 (CB1R). CB1R are positioned to regulate synaptic plasticity by being expressed on glutamatergic terminals and negatively regulating presynaptic excitability and glutamate release. Supporting this possibility, LTD was restored by promoting CB1R signaling with the CB1 positive allosteric modulator GAT211. These data implicate NAcore CB1R as critical regulators of metaplasticity induced by cannabis self-administration and the cues predicting cannabis availability., (© 2019 Society for the Study of Addiction.)

Nicotine self-administration is associated with decreased expression of the glial glutamate transporter (GLT-1) and the cystine-glutamate exchange protein xCT within the nucleus accumbens core (NAcore). N-acetylcysteine (NAC) has been shown to restore these proteins in a rodent model of drug addiction and relapse. However, the specific molecular mechanisms driving its inhibitory effects on cue-induced nicotine reinstatement are unknown. Here, we confirm that extinction of nicotine-seeking behavior is associated with impaired NAcore GLT-1 function and expression and demonstrates that reinstatement of nicotine seeking rapidly enhances membrane fraction GLT-1 expression. Extinction and cue-induced reinstatement of nicotine seeking was also associated with increased tumor necrosis factor alpha (TNFα) and decreased glial fibrillary acidic protein (GFAP) expression in the NAcore. NAC treatment (100 mg/kg/day, i.p., for 5 d) inhibited cue-induced nicotine seeking and suppressed AMPA to NMDA current ratios, suggesting that NAC reduces NAcore postsynaptic excitability. In separate experiments, rats received NAC and an antisense vivo-morpholino to selectively suppress GLT-1 expression in the NAcore during extinction and were subsequently tested for cue-induced reinstatement of nicotine seeking. NAC treatment rescued NAcore GLT-1 expression and attenuated cue-induced nicotine seeking, which was blocked by GLT-1 antisense. NAC also reduced TNFα expression in the NAcore. Viral manipulation of the NF-κB pathway, which is downstream of TNFα, revealed that cue-induced nicotine seeking is regulated by NF-κB pathway signaling in the NAcore independent of GLT-1 expression. Ultimately, these results are the first to show that immunomodulatory mechanisms may regulate known nicotine-induced alterations in glutamatergic plasticity that mediate cue-induced nicotine-seeking behavior., (© 2019 Society for the Study of Addiction.)

Repeated exposure to drug-associated cues without reward (extinction) leads to refraining from drug seeking in rodents. We determined if refraining is associated with transient synaptic plasticity (t-SP) in nucleus accumbens shell (NAshell), akin to the t-SP measured in the NAcore during cue-induced reinstatement of drug seeking. Using whole cell patch electrophysiology, we found that medium spiny neurons (MSNs) in NAshell expressed increased ratio of AMPA to NMDA glutamate receptor currents during refraining, which normalized to baseline levels by the end of the 2-hour extinction session. Unlike t-SP observed in NAcore during reinstated drug seeking, neither dendrite spine head enlargement nor activation of matrix metalloproteases (MMP2/9) accompanied the increased AMPA:NMDA in NAshell during refraining. Refraining was also not associated with changes in paired pulse ratio, NMDA receptor current decay time, or AMPA receptor rectification index in NAshell MSNs. Our preliminary data in transgenic mice suggest that t-SP may increase D2-MSN inputs relative to D1-MSN inputs., (© 2019 Society for the Study of Addiction.)

With the increase in our older adult population, there is a need for dementia training for informal and formal dementia caregivers. The objective of this scoping study is to assess dementia knowledge instruments utilized in educational programs and interventions intended for formal and informal dementia caregivers. Scoping review methodology was used to search PubMed, PsycInfo, CINAHL and Web of Science with tailored database search terms. The search yielded 8101 results, with 35 studies meeting inclusion. Studies were conducted in eight countries, had varying study designs (randomized controlled trials [RCTs] = 9, non-RCTs = 6, one-group study design = 20) and utilized previously published (19) and author developed (16) instruments. Furthermore, the studies were internationally diverse, conducted in the United States (n = 18), Australia (n = 7), UK (n = 3), China (n = 2), Canada (n = 2), Taiwan (n = 1), Brazil (n = 1) and multi-country (n = 1). Only two studies focused on minority populations. While author-developed instruments may be more relevant and timesaving, studies should strive to validate instruments or use previously published instruments to help standardize findings across studies and understand better the effects of educational programs on caregiver knowledge. Geriatr Gerontol Int 2020; 20: 397-413., (© 2020 Japan Geriatrics Society.)

Background: Lumbar spine range of motion (ROM) is a key component of injury prevention and normative data has not currently been determined for an elite gymnastics population. In current clinical practice, it is commonplace to measure sagittal spinal alignment, during 'high-load, low-dynamic' control tasks, subjectively, while also only considering the lumbar spine as a single segment., Purpose: To develop normative data for total lumbar spine ROM and ROM during a simulated landing task (SLT) in an elite gymnastics population, evaluating findings in the context of the existing biomechanical literature., Study Design: Repeated measures, cross sectional design., Methods: Lumbar spine and low lumbar spine (LLS) ROM during a SLT were measured, using the Dorsa Vi: Vi Perform™ system in asymptomatic male and female elite gymnasts. Values for maximal ROM and LLS angle during the SLT were collated and descriptively analyzed. Lumbar ROM and posture was evaluated in relation to the current biomechanical literature and a proposed Conceptual Compressive Lumbar Load Distribution Model (CCLLDM)., Results: Thirty elite gymnasts (15 male, 15 female), participated. Participants were members of the British Artistic Gymnastics elite senior and junior training program and were between the ages of 16 to 30 years. Mean (SD) maximal lumbar spinal movements were 64.23˚ (6.34 °) for flexion and 25.89˚ (11.14 °) for extension. During the SLT, participants performed lumbar spine flexion of 15.96˚ (8.80 °), when considered as a single segment. When considering the lumbar spine as a two segment model the LLS position during the SLT was towards end range anterior pelvic tilt, suggesting LLS extension., Conclusion: These data provide a baseline for asymptomatic lumbar spine movements in an elite gymnastics population and provides insight into upper and lower lumbar spine movement during a SLT. The data and newly developed CCLLDM provide clinicians with a potential framework to identify sporting skills that may be associated with increased spinal tissue load., Levels of Evidence: 3b.

This research examined factors influencing older women's post-fall decision making. We surveyed 130 independent older women from continuing care retirement communities and non-institutional homes. We categorized women's post-fall decisions as medical, corrective, and social decisions, and examined the associations between post-fall decision categories, decisional conflict, number of post-fall changes, self-rated health, frequency of falls, severity of falls, health literacy, awareness and openness to long-term care institutional options, and demographics. Older women experienced greater decisional conflict when making medical decisions versus social ( p = .012) and corrective ( p = .047) decisions. Significant predictors of post-fall decisional conflict were awareness of institutional care options ( p = .001) and health literacy ( p = .001). Future educational interventions should address knowledge deficits and provide resources to enhance collaborative efforts to lower women's post-fall decisional conflict and increase satisfaction in the decisions they make after a fall.

Context: Because of persistent effects of early childhood caries and impacts of dental health professional shortages areas, the integration of oral health in primary care settings is a public health priority. In this study, we explored oral health interprofessional practice (OHIP) as an integrative pathway to reduce oral health disparities. OHIP can include performing oral health risk assessments, describing the importance of fluoride in the drinking water, implementing fluoride varnish application, and referring patients to a dental home., Objective: To conduct a formative evaluation of how 15 pediatric primary care practices implemented the adoption of OHIP in their clinical settings., Design: Using an ecological framework, we conducted a qualitative process evaluation to measure the factors that inhibited and facilitated OHIP adoption into pediatric settings. Document review analysis and qualitative interviews were conducted with pediatric practices to contextualize challenges and facilitators to OHIP adoption., Setting and Participants: A total of 15 Children's Health Insurance Program Reauthorization Act pediatric practices located in 13 South Carolina counties participated in this study., Main Outcome Measures: Outcomes of interest were the facilitators and challenges of OHIP adoption into pediatric primary care practices., Results: Thematic analysis revealed challenges for OHIP adoption including limited resources and capacity, role delineation for clinical and administrative staff, communication, and family receptiveness. OHIP training for clinical practitioners and staff and responsiveness from clinical staff and local dentists were facilitators of OHIP adoption. Twelve key recommendations emerged on the basis of participant experiences within OHIP, with developing an active dental referral network and encouraging buy-in from clinical staff for OHIP adoption as primary recommendations., Conclusion: We demonstrated the effectiveness of a learning collaborative meeting among pediatric primary care providers to adopt OHIPs. This work reveals an actionable pathway to support oral health equity advancement for children through an additional access point of preventive oral care, reinforcement of positive oral health behaviors, and interaction between parent and child for overall health and wellness of the family.

This exploratory, descriptive study examined involvement of family members and professionals in older women's post-fall decision making. We conducted semistructured interviews with 17 older women who had recently fallen and 11 individuals these women identified as being engaged in their post-fall decision-making processes. Qualitative data analysis involved open and axial coding and development of themes. After experiencing a fall, these older women's openness to others' opinions and advice; their assessments of types and credibility of potential information sources; and the communication practices they established with these sources influenced how they accessed, accepted, or rejected information from family members and professionals. Increased awareness of the involvement of others in post-fall decision making could enhance communication with older women who fall. Developing and implementing practical strategies to help family members and professionals initiate and engage in conversations about falls and their consequences could lead to more open decision making and improved post-fall quality of life among older women.

Background: Recent observational studies in the United States indicated live attenuated influenza vaccine (LAIV) was less effective in children against clinical influenza infection caused by A(H1N1)pdm09 relative to inactivated influenza vaccine (IIV). During the 2013-2014 influenza season, we conducted an observational study among children aged 5-17 years to compare serologic responses to LAIV and IIV and explore factors associated with vaccine failure., Methods: One hundred and sixty-one children received one dose of trivalent IIV or quadrivalent LAIV according to parental preference. Baseline and postvaccination serum samples were tested with hemagglutination inhibition (HI) assays against vaccine reference strains. Geometric mean titers (GMT), geometric mean fold rise (GMFR), seroconversion, and seroprotection (HI titer ≥ 40) were used to assess response to vaccine. Active surveillance for acute respiratory illness was conducted during the influenza season and influenza cases were confirmed by reverse transcription polymerase chain reaction (RT-PCR). Logistic regression was used to examine the association between vaccine type and vaccine failure., Results: LAIV and IIV recipients were similar with respect to demographics and baseline GMT for each vaccine strain. RT-PCR confirmed influenza (vaccine failure) occurred in 8 (13%) of 62 LAIV recipients and 3 (3%) of 99 IIV recipients (p = .02). Postvaccination GMFR for A(H1N1)pdm09 was higher for IIV vs LAIV receipt (GMFR 3.3 vs. 0.8, p < .0001). Postvaccination titers against A(H1N1)pdm09 were ≥40 for 91% and 44% of IIV and LAIV recipients, respectively (p < .0001). Among 13 IIV and 18 LAIV recipients with seronegative baseline titer against A(H1N1pdm09), 54% and 0% seroconverted, respectively. LAIV receipt was the only factor associated with A(H1N1)pdm09 vaccine failure in the age-adjusted multivariable model (odds ratio 4.5, 95% CI 1.1-18.2)., Conclusion: Receipt of LAIV generated minimal HI antibody response in children, including among those seronegative at baseline. LAIV recipients had significant increased risk of A(H1N1)pdm09 infection compared to IIV recipients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The Society of Vascular Surgery (SVS) guidelines currently suggest thoracic endovascular aortic repair (TEVAR) for grade II-IV and nonoperative management (NOM) for grade I blunt traumatic aortic injury (BTAI). However, there is increasing evidence that grade II may also be observed safely. The purpose of this study was to compare the outcome of TEVAR and NOM for grade I-IV BTAI and determine if grade II can be safely observed with NOM., Methods: The records of patients with BTAI from 2004 to 2015 at a Level I trauma center were retrospectively reviewed. Patients were separated into two groups: TEVAR versus NOM. All BTAIs were graded according to the SVS guidelines. Minimal aortic injury (MAI) was defined as BTAI grade I and II. Failure of NOM was defined as aortic rupture after admission or progression on subsequent computed tomography (CT) imaging requiring TEVAR or open thoracotomy repair (OTR). Statistical analysis was performed using Mann-Whitney U and χ tests., Results: A total of 105 adult patients (≥16 years) with BTAI were identified over the 11-year period. Of these, 17 patients who died soon after arrival and 17 who underwent OTR were excluded. Of the remaining 71 patients, 30 had MAI (14 TEVAR vs. 16 NOM). There were no failures in either group. No patients with MAI in either group died from complications of aortic lesions. Follow-up CT imaging was performed on all MAI patients. Follow-up CT scans for all TEVAR patients showed stable stents with no leak. Follow-up CT in the NOM group showed progression in two patients neither required subsequent OTR or TEVAR., Conclusions: Although the SVS guidelines suggest TEVAR for grade II-IV and NOM for grade I BTAI, NOM may be safely used in grade II BTAI., Level of Evidence: Therapeutic study, level IV.

Background: Alcohol is a possible risk factor for abdominal aortic aneurysm (AAA), but evidence from individual studies is weak and inconsistent. Existing narrative reviews suggest the possibility of non-linear associations. The aim here was to quantify any association using a systematic literature review, followed by dose-response meta-analysis of prospective studies., Methods: MEDLINE, Embase and Web of Science were searched systematically to January 2017 for relevant prospective studies of alcohol consumption and AAA risk. Summary estimates of highest versus lowest levels of consumption, and linear and non-linear dose-response curves were quantified using random-effects models., Results: Eleven relevant cohorts were identified describing results from 3580 individuals with among 473 092 participants. Data were extracted from ten cohorts for meta-analyses of high versus low levels of alcohol consumption (risk ratio for AAA 0·93, 95 per cent c.i. 0·78 to 1·11; P = 0·4, I 2  = 47 per cent). The linear dose-response risk ratio for AAA, derived from 11 cohorts, was 1·00 (0·97 to 1·04) per 8 g alcohol per day (P = 0·9, I 2  = 73 per cent). Non-linear dose-response results showed a tick-shaped curve with lower risk up to 2 units/day, but increasing risk beyond that (P = 0·05). The increase in risk beyond 2 units/day was stronger in men than in women., Conclusion: Although the linear dose-response analysis revealed little evidence of an association between alcohol consumption and AAA risk, a tick-shaped trend in the association was observed. This non-linear dose-response analysis revealed reduced risks for alcohol consumption below 2 units/day, masking increased risks for 2 or more units/day., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression. Upregulated RAD6 enhances DNA damage tolerance and repair efficiency of OC cells and promotes their survival. Increased RAD6 levels cause histone 2B ubiquitination-mediated epigenetic changes that stimulate transcription of stem cell genes, including ALDH1A1 and SOX2, leading to a cancer stem cell phenotype, which is implicated in disease recurrence and metastasis. Downregulation of RAD6 or its inhibition using a small molecule inhibitor attenuated DNA repair signaling and expression of cancer stem cells markers and sensitized chemoresistant OC cells to carboplatin. Together, these results suggest that RAD6 could be a therapeutic target to prevent and treat acquired chemoresistance and disease recurrence in OC and enhance the efficacy of standard chemotherapy.

The Sexual Health in Faith Traditions Study evaluated the relationships between religiosity, spirituality, internalized homonegativity, and sexual risk behaviors among a sample of African American men who have sex with men living in the Deep South. Participants were recruited primarily from Black Gay Pride celebrations to complete a self-administered, paper-and-pencil survey. Structural equation modeling was used to determine relationships between key constructs and condom use for insertive ( n = 285) and receptive ( n = 263) anal intercourse in the past 3 months. Almost half of respondents reported using condoms "every time" when engaging in insertive (48.3%) or receptive (45.1%) anal intercourse. Religiosity and spirituality were differentially associated with dimensions of internalized homonegativity. While no significant direct relationships were reported between either religiosity or spirituality and condom use, dimensions of internalized homonegativity mediated significant indirect relationships. Findings suggest that religiosity and spirituality influence African American men who have sex with men's internalized homonegativity and, subsequently, engagement in safer sex behaviors.

This study examined the psychometric properties of the Internalized Homonegativity Inventory (IHNI) among African American men who have sex with men (AAMSM) in the southeastern United States. Data from 261 AAMSM were analyzed using exploratory factor analysis. Results showed evidence of a two-factor solution: personal and moral homonegativity and gay affirmation. Internal consistencies were greater than .80, and correlations with other variables (e.g., sociodemographics, religiosity, masculinity) provided evidence of validity. Findings suggesting a two-factor instead of a three-factor solution may indicate that the IHNI manifests differently for AAMSM in the Deep South than for predominantly White MSM. Further research should examine how incorporating new conceptions of internalized homonegativity into culturally specific health-promotion interventions for AAMSM might enhance effectiveness.

In this descriptive qualitative research, we examined older women's responses and decisions after experiencing a fall. Falls were unexpected, sudden events that heightened these women's awareness of their physical, emotional, spiritual, and social independence. Interviewees reported assessing personal, physical, and emotional needs; feeling burdened by the extra work; trying to get back to normal; seeking and obtaining assistance and spiritual support; avoiding specific people, objects, and places; planning ahead; and putting the fall out of mind. Consideration of older women's post-fall responses and decisions should be incorporated into fall prevention and management programs, services, and clinical recommendations.

Background: Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection., Methods: Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains., Results: 2010-2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010-2011) H3N2 component. Prior vaccination enhanced CD8 + T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009-2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ-secreting CD4 + CD69 + T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009-2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α-secreting CD8 + CD69 + T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010-2011 season than those who were not previously vaccinated., Conclusions: Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

This study is among the first to examine how health risks are communicated through traditional and social media during a public health crisis. Using an innovative research approach, the study combined a content analysis with in-depth interviews to examine and understand how stakeholders involved in crisis response perceived media coverage after a chemical spill contaminated the drinking water of 300,000 West Virginia residents. A content analysis of print, television, and online media stories and tweets revealed that health risk information was largely absent from crisis coverage. Although traditional media stories were significantly more likely to include health information compared to tweets, public health sources were underutilized in traditional media coverage. Instead, traditional media favored the use of government sources outside the public health field, which stakeholders suggested was problematic because of a public distrust of officials and official information during the crisis. Results also indicated that Twitter was not a common or reliable source for health information but was important in the spread of other types of information. Ultimately, the study highlights a need for more deliberate media coverage of health risks and provides insight into how Twitter is used to spread crisis information.

Unlabelled: High-dose (HD) influenza vaccine shows improved relative efficacy against influenza disease compared to standard-dose (SD) vaccine in individuals ⩾65years. This has been partially credited to superior serological responses, but a comprehensive understanding of cell-mediated immunity (CMI) of HD vaccine remains lacking. In the current study, a total of 105 participants were randomly administered HD or SD vaccine and were evaluated for serological responses. Subsets of the group (n=12-26 per group) were evaluated for B and T cell responses at days 0, 7, 14 and 28 post-vaccination by flow cytometry or ELISPOT assay. HD vaccine elicited significantly higher hemagglutination inhibition (HI) titers than SD vaccine at d28, but comparable titers at d365 post-vaccination. HD vaccine also elicited higher vaccine-specific plasmablast responses at d7 post-vaccination than SD vaccine. However, long-lived memory B cell induction, cytokine-secreting T cell responses and persistence of serological memory were comparable regardless of vaccine dose. More strategies other than increased Ag amount may be needed to improve CMI in older adults., Trial Registration: ClinicalTrials.gov NCT 01189123., Competing Interests: H Keipp Talbot received research support from Sanofi-Pasteur, Gilead and MedImmune. She currently serves as an advisor for Novartis and VaxInnate; Marie R Griffin received grant support from MedImmune and Pfizer (formerly Wyeth). All the remaining authors disclosed no potential conflicts of interest., (Published by Elsevier Ltd.)

The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1α-OHase, 1,25D3-MARRS, TREM-1, cathelicidin, RIG-I, and interferon-β by qRT-PCR. Mean serum 25(OH)D was 30 ± 4 ng/mL and was not associated with age. Baseline expression of VDR, 1α-OHase, 1,25D3-MARRS, TREM-1, and RIG-I also did not differ by age; IFN-β expression, however, was higher in the 70+ year old group. 25(OH)D3- and 1,25(OH)2D3-induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1α-OHase. Ligand-induced 1,25D3-MARRS expression was higher in subjects ≥ 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults ≥ 50 years, the expression and functionality of the VDR, 1α-OHase and key vitamin D pathway genes were not consistently associated with age., Competing Interests: The authors, MM, MT, SMS, AJR, WGD, P-YC, EAB, DKS and SS declare no conflict of interest. HKT has received research funding from Sanofi Pasteur, MedImmune, and Gilead; and she serves on Advisory Boards for Teva Pharmaceuticals and MedImmune. MES has received research funding from MedImmune. MRG receives research funding from MedImmune. LAC is an employee of Abbott Nutrition.

Spiritual framing of breast cancer communication may provide a useful strategy for addressing disparate rates of breast cancer mortality among African American women. The efficacy of a spiritually framed breast cancer screening (BCS) message was compared with that of a traditional BCS message. Specifically, 200 African American women were randomly assigned to review either a spiritually framed or traditional BCS message and complete a self-administered survey, including a thought-listing form. Message efficacy was measured by number of thoughts generated (elaboration), ratio of positive to negative thoughts (polarity), and intention to obtain and/or recommend a mammogram. Multiple linear regression and structural equation modeling were used to assess direct and indirect (mediated) associations among variables. Spiritual framing was positively associated with greater elaboration (β = .265, SE = .36, p < .001) and more positive polarity (β = .237, SE = .04, p < .001) . Spiritual framing also had a significant indirect effect on mammography intentions through polarity (standardized indirect effect = .057, 95% confidence interval [.024, .106], p < .001). These results indicate that spiritual framing may improve the efficacy of BCS messages among African American women by eliciting more positive thoughts about screening. Interventions targeting African American women might consider the role of spirituality when tailoring messages to encourage regular mammography use.

Aim: To determine the scaling factors required for inclusion of renal drug glucuronidation clearance in the prediction of total clearance via glucuronidation (CLUGT )., Methods: Microsomal protein per gram of kidney (MPPGK) was determined for human 'mixed' kidney (n = 5) microsomes (MKM). The glucuronidation activities of deferiprone (DEF), propofol (PRO) and zidovudine (AZT) by MKM and paired cortical (KCM) and medullary (KMM) microsomes were measured, along with the UGT 1A6, 1A9 and 2B7 protein contents of each enzyme source. Unbound intrinsic clearances (CLint,u,UGT ) for PRO and morphine (MOR; 3- and 6-) glucuronidation by MKM, human liver microsomes (HLM) and recombinant UGT1A9 and 2B7 were additionally determined. Data were scaled using in vitro-in vivo extrapolation (IV-IVE) approaches to assess the influence of renal CLint,u,UGT on the prediction accuracy of the calculated CLUGT values of PRO and MOR., Results: MPPGK was 9.3 ± 2.0 mg g(-1) (mean ± SD). The respective rates of DEF (UGT1A6), PRO (UGT1A9) and AZT (UGT2B7) glucuronidation by KCM were 1.4-, 5.2- and 10.5-fold higher than those for KMM. UGT 1A6, 1A9 and 2B7 were the only enzymes expressed in kidney. Consistent with the activity data, the abundance of each of these enzymes was greater in KCM than in KMM. The abundance of UGT1A9 in MKM (61.3 pmol mg(-1) ) was 2.7 fold higher than that reported for HLM., Conclusions: Scaled renal PRO glucuronidation CLint,u,UGT was double that of liver. Renal CLint,u,UGT should be accounted for in the IV-IVE of UGT1A9 and considered for UGT1A6 and 2B7 substrates., (© 2016 The British Pharmacological Society.)

Research suggests that workplace discrimination plays a role in absenteeism, productivity, and turnover. A link among workplace discrimination, mental health, and health disparities may also exist. The purpose of this study was to determine whether self-reported workplace discrimination is associated with alcohol abuse among hospital workers. Cross-sectional analysis of baseline data collected from a prospective cohort study of workers in two healthcare institutions (n = 664) was conducted. Workplace discrimination in the previous 12 months was reported by 14% (n = 91) of participants who were four times more likely to score higher on likely alcohol abuse than their peers. White participants who reported any discrimination were more likely to score higher on likely alcohol abuse than racial/ethnic minority participants who reported any discrimination. Given a diversifying workforce, further research is needed on how workplace discrimination contributes to stress and maladaptive coping, and ultimately health disparities., (© 2016 The Author(s).)

Series of 4-amino-6-(arylamino)-1,3,5-triazine-2-carbohydrazides (3a-e) and N'-phenyl-4,6-bis(arylamino)-1,3,5-triazine-2-carbohydrazides (6a-e), for ease of readership, we will abbreviate our compound names as 'new triazines', have been synthesized, based on the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ9 and 4-amino-N'-phenyl-6-(arylamino)-1,3,5-triazine-2-carbohydrazides. Synthesis of the target compounds was readily accomplished in two steps from either bis-aryl/aryl biguanides via reaction of phenylhydrazine or hydrazinehydrate with key 4-amino-6-bis(arylamino)/(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were evaluated for their abilities to inhibit Rad6B ubiquitin conjugation and in vitro anticancer activity against several human cancer cell lines: ovarian (OV90 and A2780), lung (H1299 and A549), breast (MCF-7 and MDA-MB231) and colon (HT29) cancer cells by MTS assays. All the 10 new triazines exhibited superior Rad6B inhibitory activities in comparison to selective Rad6 inhibitor TZ9 that was reported previously. Similarly, new triazines also showed better IC50 values in survival assays of various tumor cell lines. Particularly, new triazines 6a-c, exhibited lower IC50 (3.3-22 μM) values compared to TZ9., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity., Methods: We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼ 30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥ 40 and>100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site., Results: Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567]=9.97, p<.0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio=6.8, 95% CI=3.1 - 15.3)., Conclusion: Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees., Competing Interests: 4. Conflicts of Interest M. G. has received research funding from MedImmune and Novartis, and A. N. has received research funding from GlaxoSmithKline. All other authors report no potential conflicts. Supported by the Centers for Disease Control and Prevention (contract 200-2010-F-33132 to Abt Associates Inc.)., (Published by Elsevier Ltd.)

Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize β-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder.

Background: During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States., Methods: Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 - adjusted odds ratio)] for vaccination in cases versus test-negative controls., Results: Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier., Conclusions: The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)