Behavioral and Neural Correlates of Visual Working Memory Reveal Metacognitive Aspects of Mental Imagery.

Mental imagery (MI) is the ability to generate visual phenomena in the absence of sensory input. MI is often likened to visual working memory (VWM): the ability to maintain and manipulate visual representations. How MI is recruited during VWM is yet to be established. In a modified orientation change-discrimination task, we examined how behavioral (proportion correct) and neural (contralateral delay activity [CDA]) correlates of precision and capacity map onto subjective ratings of vividness and number of items in MI within a VWM task. During the maintenance period, 17 participants estimated the vividness of their MI or the number of items held in MI while they were instructed to focus on either precision or capacity of their representation and to retain stimuli at varying set sizes (1, 2, and 4). Vividness and number ratings varied over set sizes; however, subjective ratings and behavioral performance correlated only for vividness rating at set size 1. Although CDA responded to set size as was expected, CDA did not reflect subjective reports on high and low vividness and on nondivergent (reported the probed number of items in mind) or divergent (reported number of items diverged from probed) rating trials. Participants were more accurate in low set sizes compared with higher set sizes and in coarse (45°) orientation changes compared with fine (15°) orientation changes. We failed to find evidence for a relationship between the subjective sensory experience of precision and capacity of MI and the precision and capacity of VWM.

Do lower limb motor-evoked potentials predict walking outcomes post-stroke?

BACKGROUND: This observational study examined whether lower limb (LL) motor-evoked potentials (MEPs) 1 week post-stroke predict recovery of independent walking, use of ankle-foot orthosis (AFO) or walking aid, at 3 and 6 months post-stroke. METHODS: Non-ambulatory participants were recruited 5 days post-stroke. Transcranial magnetic stimulation was used to determine tibialis anterior MEP status and clinical assessments (age, National Institutes of Health Stroke Scale (NIHSS), ankle dorsiflexion strength, LL motricity index, Berg Balance Test) were completed 1 week post-stroke. Functional Ambulation Category (FAC), use of AFO and walking aid were assessed 3 months and 6 months post-stroke. MEP status, alone and combined with clinical measures, and walking outcomes at 3 and 6 months were analysed with Pearson χ2 and multivariate binary logistic regression. RESULTS: Ninety participants were included (median age 72 years (38-97 years)). Most participants (81%) walked independently (FAC ≥ 4), 17% used an AFO, and 49% used a walking aid 3 months post-stroke with similar findings at 6 months. Independent walking was better predicted by age, LL strength and Berg Balance Test (accuracy 92%, 95% CI 85% to 97%) than MEP status (accuracy 73%, 95% CI 63% to 83%). AFO use was better predicted by NIHSS and MEP status (accuracy 88%, 95% CI 79% to 94%) than MEP status alone (accuracy 76%, 95% CI 65% to 84%). No variables predicted use of walking aids. CONCLUSIONS: The presence of LL MEPs 1-week post-stroke predicts independent walking at 3 and 6 months post-stroke. However, the absence of MEPs does not preclude independent walking. Clinical factors, particularly age, balance and stroke severity, more strongly predict independent walking than MEP status. LL MEP status adds little value as a biomarker for walking outcomes.

Lymphedema is associated with CELSR1 in Phelan-McDermid syndrome.

Lymphedema is a troubling condition present in many disorders including the rare genetic disorder known as Phelan-McDermid syndrome (PMS). The neurobehavioral features of PMS, also known as 22q13.3 deletion syndrome, have been investigated, but little research exists on lymphedema in PMS. In this investigation, clinical and genetic data from 404 people with PMS were reviewed from the PMS-International Registry revealing a prevalence of 5% with lymphedema. Lymphedema was reported in 1 out of 47 people (2.1%) with PMS due to a SHANK3 variant and 19 out of 357 people (5.3%) with PMS due to 22q13.3 deletions. Lymphedema was more common among those in their teens or adulthood (p = 0.0011) and those with deletions >4 Mb. People with lymphedema had significantly larger deletions (mean 5.375 Mb) than those without lymphedema (mean 3.464 Mb, p = 0.00496). Association analysis identified a deletion of the CELSR1 gene to be the biggest risk factor (OR = 12.9 95% CI [2.9-56.2]). Detailed assessment of 5 subjects identified all had deletions of CELSR1, developed symptoms of lymphedema starting at age 8 or older, and typically responded well to standard therapy. In conclusion, this is the largest assessment of lymphedema in PMS to date and our results suggest that individuals with deletions >4 Mb or those with CELSR1 deletions should be assessed for lymphedema.

Applying Design-Thinking Principles to Practice-Based Pharmacy Research.

Design thinking is an approach to problem solving that focuses on a solution to a problem. This systematic approach can be applied to practice-based research or implementation projects in your practice setting. It may be useful for starting new projects as well as revisiting past projects that may not have yielded meaningful results. The design-thinking process begins with identifying a problem or knowledge gap and then the steps include: (1) understanding the problem, (2) observing the problem, (3) defining the problem, (4) brainstorming possible solutions, (5) prototyping the best solution, and (6) testing the solution.

A technical assistance program approach for pharmacist clinical services integration in primary care organizations.

BACKGROUND: Little is known about the use of technical assistance (TA) programs to facilitate the integration of pharmacist clinical services in primary care settings. OBJECTIVE: Design, implement, and evaluate a TA program to advance pharmacist integration and clinical services in primary care. PRACTICE DESCRIPTION: Structured TA program for developing new or enhancing current integrated pharmacist services was utilized in 4 primary care organizations (i.e., federally qualified health center, accountable care organization, and an academic and regional health system). PRACTICE INNOVATION: Holistic TA program with a logic model, organizational stages of pharmacist integration, project prioritization, and implementation plans. EVALUATION METHODS: A mixed-methods contextual inquiry approach for integration of pharmacist clinical services. Quantitative analysis was used for TA program activities, time spent, pilot project data, and a web-based survey for post-TA program assessment. Coincidence analysis was used to assess organizational commitment to TA services. Qualitative analysis was used for data collected through semi-structured key informant interviews and team meeting activity reports. RESULTS: TA program team spent 1872 hours over 11 months on program development, logistics, implementation, and project oversight. TA services included 88 onsite and virtual meetings, 11 onsite pharmacist coaching sessions, 6 workflow mapping sessions, and updating online learning resources. Primary care organizations that had already hired a pharmacist were more likely to uptake TA services. Most useful TA methods were webinar meetings (89%) and on-site pharmacist coaching (88%). TA project results were used for strategic planning (73%), pharmacist value/impact assessment (72%), pharmacist capacity modeling (68%), and workflow design (65%). A key learning from the TA program was the importance of a qualified pharmacist with clinical service experience in primary care settings and population health teams. CONCLUSION: TA program for the pharmacist clinical service integration has broad application to primary care organizations with diverse organizational structures, payer mixes, and practice settings.

Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models.

BACKGROUND: Each year, approximately 1.1 million children are exposed in utero to human immunodeficiency virus antiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube defect signal in infants exposed to the integrase strand transfer inhibitor (InSTI) dolutegravir from conception, suggesting that exposure during early fetal development may be detrimental. METHODS: The effects of InSTIs on 2 human embryonic stem cell (hESC) lines were characterized with respect to markers of pluripotency, early differentiation, and cellular health. In addition, fetal resorptions after exposure to InSTIs from conception were analyzed in pregnant mice. RESULTS: At subtherapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased hESC counts and pluripotency and induced dysregulation of genes involved in early differentiation. At therapeutic concentrations, bictegravir induced substantial hESC death and fetal resorptions. It is notable that first-generation InSTI raltegravir did not induce any hESC toxicity or differentiation, at any concentration tested. CONCLUSIONS: Exposure to some InSTIs, even at subtherapeutic concentrations, can induce adverse effects in hESCs and pregnant mice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of InSTIs on embryonic development, as well as their long-term safety after in utero exposure.

Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes: an overview of systematic reviews.

BACKGROUND: Reliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)]. METHODS: Medline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews. FINDINGS: The overview identified 30 systematic reviews of patient education, footwear and off-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap. INTERPRETATION: The majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.

Primary Care Pharmacist Practice Models Shape the Comprehensive Medication Management Process.

Pharmacists are well positioned to collaborate with primary care providers (PCPs) to conduct comprehensive medication management (CMM). However, depending on organizational needs and pharmacist staffing resources, different pharmacist practice models have been implemented. In this commentary, we (1) describe 2 common pharmacist practice models in primary care settings, (2) explain variations in the CMM process based on 2 practice models, and (3) outline outcomes and implications of this expanded CMM process. By tailoring the CMM process to their practice model, pharmacists can follow consistent delivery of CMM services to create a common understanding among patients, PCPs, and other care team members.

"I Spy with my Little Eye, Something that is a Face ": A Brain Network for Illusory Face Detection.

The most basic aspect of face perception is simply detecting the presence of a face, which requires the extraction of features that it has in common with other faces. Putatively, it is caused by matching high-dimensional sensory input with internal face templates, achieved through a top-down mediated coupling between prefrontal regions and brain areas in the occipito-temporal cortex ("core system of face perception"). Illusory face detection tasks can be used to study these top-down influences. In the present functional magnetic resonance imaging study, we showed that illusory face perception activated just as real faces the core system, albeit with atypical left-lateralization of the occipital face area. The core system was coupled with two distinct brain regions in the lateral prefrontal (inferior frontal gyrus, IFG) and orbitofrontal cortex (OFC). A dynamic causal modeling (DCM) analysis revealed that activity in the core system during illusory face detection was upregulated by a modulatory face-specific influence of the IFG, not as previously assumed by the OFC. Based on these findings, we were able to develop the most comprehensive neuroanatomical framework of illusory face detection until now.

Factors influencing primary care organization commitment to technical assistance for pharmacist clinical services integration.

BACKGROUND: While technical assistance (TA) has been utilized by primary care organizations (PCOs) for electronic health record installation and medical home recognition, little is known about PCOs' use of TA to optimize pharmacist clinical services and integration in team-based care or population health programs. In 2019, the Connecticut Office of Health Strategy's State Innovation Model Program funded a no-cost TA initiative for 9 PCOs to initiate and/or advance pharmacist clinical services. OBJECTIVE: To assess organizational, operational, and pharmacist factors that influenced PCO commitment to the TA program. METHODS: During the TA program, data were collected from multiple sources including PCO demographic data; discussions and meetings with PCO medical, pharmacy, and administrative leaders; on-site workflow observations; and pharmacist coaching sessions. Configurational comparative methods were applied using the data collected during the TA program. Candidate factors were identified and calibrated on the basis of the researchers' knowledge of the TA program, organizational readiness for change models, implementation science frameworks, and published literature. Each candidate factor was iteratively assessed until 13 factors were selected and calibrated by independently assigning each factor a dichotomous value across PCOs. Calibration differences between the researchers were discussed until consensus was reached. Solutions were modeled using the Coincidence Analysis (cna) package in R and RStudio (RStudio, PBC). RESULTS: Of the 9 PCOs, 4 committed to participating in the TA program. Only 1 factor, the presence of a hired pharmacist, consistently distinguished PCOs that committed from those that did not, with 100% coverage and 80% consistency. CONCLUSION: PCO commitment to participate in the TA program was best explained by the factor of already having hired a pharmacist. These results can inform future efforts to engage PCOs in TA, primary care policy initiatives, and future research to understand factors influencing PCO success with pharmacist clinical services integration.

Practical implementation insights from 2 population health pharmacist project approaches to improve blood pressure control.

BACKGROUND: Population health pharmacists (PHPs) can optimize medication regimens for blood pressure (BP) control using various approaches based on the timing of medication recommendations sent to providers. OBJECTIVE: To identify the contextual factors and implementation insights from 2 PHP approaches to consider when implementing PHP initiatives. PRACTICE DESCRIPTION: A federally qualified health center with 14 sites throughout Connecticut. PRACTICE INNOVATION: A centralized PHP performed medication reviews and sent recommendations to providers. The providers reviewed the recommendations for implementation into patients' care plans. The 2 PHP approaches used were: JUST-IN-TIME (JIT) APPROACH: A part-time, contracted PHP used weekly reports to identify 204 patients with uncontrolled hypertension (BP ≥140/90 mm Hg) and same-week provider appointments. ANYTIME (ANY) APPROACH: A full-time staff PHP used a registry report to identify 41 patients with uncontrolled hypertension (systolic BP: 140-150 mm Hg) and diabetes (glycosylated hemoglobin: 9%-10%) regardless of the next appointment date. EVALUATION METHODS: Four of the 5 Reach, Effectiveness, Adoption, Implementation, and Maintenance framework dimensions were used to assess the JIT and ANY approaches. Quantitative data were analyzed using descriptive statistics and chi-square or Fisher exact tests. RESULTS: The contextual factors that affected the reach, effectiveness, adoption, and implementation of the 2 projects included the timing of PHP recommendations, PHP employment status, and PHP's prior work experience. The PHP insights to consider when implementing these projects include the need to (1) build trusted relationships with providers/other team members; (2) demonstrate sensitivity and respect for providers' workload/workflow; (3) send concise, actionable, and timely recommendations; and (4) measure value/impact of PHP interventions with defined metrics. The organizational implementation insights to consider include clearly defining the role of the PHP, providing clinical/administrative buy-in and support, fostering a strong organizational culture for team-based care, and collaboration with the data analytics team to identify patients classified as high impact. CONCLUSION: The contextual factors and implementation insights identified can be used pragmatically by primary care clinical leaders to integrate a limited PHP resource on an existing population health team.

Glioblastoma Extracellular Vesicle-Specific Peptides Inhibit EV-Induced Neuronal Cytotoxicity.

WHO Grade 4 IDH-wild type astrocytoma (GBM) is the deadliest brain tumor with a poor prognosis. Meningioma (MMA) is a more common "benign" central nervous system tumor but with significant recurrence rates. There is an urgent need for brain tumor biomarkers for early diagnosis and effective treatment options. Extracellular vesicles (EVs) are tiny membrane-enclosed vesicles that play essential functions in cell-to-cell communications among tumor cells. We aimed to identify epitopes of brain tumor EVs by phage peptide libraries. EVs from GBM plasma, MMA plasma, or brain tumor cell lines were used to screen phage-displayed random peptide libraries to identify high-affinity peptides. We purified EVs from three GBM plasma pools (23 patients), one MMA pool (10 patients), and four brain tumor cell lines. We identified a total of 21 high-affinity phage peptides (12 unique) specific to brain tumor EVs. The peptides shared high sequence homologies among those selected by the same EVs. Dose-response ELISA demonstrated that phage peptides were specific to brain tumor EVs compared to controls. Peptide affinity purification identified unique brain tumor EV subpopulations. Significantly, GBM EV peptides inhibit brain tumor EV-induced complement-dependent cytotoxicity (necrosis) in neurons. We conclude that phage display technology could identify specific peptides to isolate and characterize tumor EVs.

Pharmacist eConsult service for primary care medication optimization and safety.

BACKGROUND: There is a critical need in primary care to proactively prevent, identify, and resolve poor medication-related outcomes. However, more than 80% of primary care practices do not have clinical pharmacists as members of expanded care teams. The emergence of eConsult services in primary care settings presents an opportunity for primary care providers (PCPs) to consult with clinical pharmacists as "on-demand" pharmacotherapy specialists. OBJECTIVES: The objectives were to (1) determine the use of a clinical pharmacist in an existing eConsult network, (2) characterize the use and type of clinical pharmacist eConsults sent by PCPs, and (3) measure the implementation percentage of pharmacist recommendations by PCPs. METHODS: The study was conducted in a federally qualified health center using an existing eConsult platform. A clinical pharmacist was contracted to receive eConsults and was expected to respond within 2 business days. PCPs were introduced to the pharmacist eConsult service through presentations that reviewed the clinical pharmacist's education/training, suitable pharmacist eConsult topics, and workflow for sending a pharmacist eConsult. RESULTS: A total of 57 eConsults containing 123 individual questions were answered. Advanced practice nurses (APRNs) sent 3 times the number of eConsults and individual questions per eConsult compared with physicians (P < 0.0001). Most eConsult questions from APRNs related to adverse drug events/drug interactions (44%), drug or dosage changes to reach therapeutic goals (18%), and renal/hepatic dosage adjustments (13%). However, physician eConsult questions were primarily targeted on patient-specific drug or dosage adjustments (62%) and comprehensive medication regimen reviews (17%). A total of 74% of the pharmacist eConsult responses had at least 50% of the recommendations implemented by PCPs. CONCLUSION: This study revealed the use of a pharmacist eConsult service for medication-related questions in an existing eConsult network for PCPs. As more practices enroll in value-based plans, pharmacist eConsults can improve the quality and safety of prescribing and chronic medication management.

Developmental changes in the processing of faces as revealed by EEG decoding.

Rapidly and accurately processing information from faces is a critical human function that is known to improve with developmental age. Understanding the underlying drivers of this improvement remains a contentious question, with debate continuing as to the presence of early vs. late maturation of face-processing mechanisms. Recent behavioural evidence suggests an important 'hallmark' of expert face processing - the face inversion effect - is present in very young children, yet neural support for this remains unclear. To address this, we conducted a detailed investigation of the neural dynamics of face processing in children spanning a range of ages (6-11 years) and adults. Uniquely, we applied multivariate pattern analysis (MVPA) to the electroencephalogram signal (EEG) to test for the presence of a distinct neural profile associated with canonical upright faces when compared both to other objects (houses) and to inverted faces. Results revealed robust discrimination profiles, at the individual level, of differentiated neural activity associated with broad face categorization and further with its expert processing, as indexed by the face inversion effect, from the youngest ages tested. This result is consistent with an early functional maturation of broad face processing mechanisms. Yet, clear quantitative differences between the response profile of children and adults is suggestive of age-related refinement of this system with developing face and general expertise. Standard ERP analysis also provides some support for qualitative differences in the neural response to inverted faces in children in contrast to adults. This neural profile is in line with recent behavioural studies that have reported impressively expert early face abilities during childhood, while also providing novel evidence of the ongoing neural specialisation between child and adulthood.

Neurochemical balance and inhibition at the subacute stage after stroke.

Stroke is a leading cause of death and disability worldwide with many people left with impaired motor function. Evidence from experimental animal models of stroke indicates that reducing motor cortex inhibition may facilitate neural plasticity and motor recovery. This study compared primary motor cortex (M1) inhibition measures over the first 12 wk after stroke with a cohort of age-similar healthy controls. The excitation-inhibition ratio and gamma-aminobutyric acid (GABA) neurotransmission within M1 were assessed using magnetic resonance spectroscopy and threshold hunting paired-pulse transcranial magnetic stimulation respectively. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Patients with a functional corticospinal pathway had motor-evoked potentials on the paretic side and exhibited better recovery from upper limb impairment and recovery of function than patients without a functional corticospinal pathway. Compared with age-similar controls, the neurochemical balance in terms of the excitation-inhibition ratio was greater within contralesional M1 in patients with a functional corticospinal pathway. There was evidence for elevated long-interval inhibition in both ipsilesional and contralesional M1 compared with controls. Short-interval inhibition measures differed between the first and second phases, with evidence for elevation of the former only in ipsilesional M1 and no evidence of disinhibition for the latter. Overall, findings from transcranial magnetic stimulation indicate an upregulation of GABA-mediated tonic inhibition in M1 early after stroke. Therapeutic approaches that aim to normalize inhibitory tone during the subacute period warrant further investigation.NEW & NOTEWORTHY Magnetic resonance spectroscopy indicated higher excitation-inhibition ratios within motor cortex during subacute recovery than age-similar healthy controls. Measures obtained from adaptive threshold hunting paired-pulse transcranial magnetic stimulation indicated greater tonic inhibition in patients compared with controls. Therapeutic approaches that aim to normalize motor cortex inhibition during the subacute stage of recovery should be explored.

Decoding the dynamic representation of facial expressions of emotion in explicit and incidental tasks.

Faces transmit a wealth of important social signals. While previous studies have elucidated the network of cortical regions important for perception of facial expression, and the associated temporal components such as the P100, N170 and EPN, it is still unclear how task constraints may shape the representation of facial expression (or other face categories) in these networks. In the present experiment, we used Multivariate Pattern Analysis (MVPA) with EEG to investigate the neural information available across time about two important face categories (expression and identity) when those categories are either perceived under explicit (e.g. decoding facial expression category from the EEG when task is on expression) or incidental task contexts (e.g. decoding facial expression category from the EEG when task is on identity). Decoding of both face categories, across both task contexts, peaked in time-windows spanning 91-170 ms (across posterior electrodes). Peak decoding of expression, however, was not affected by task context whereas peak decoding of identity was significantly reduced under incidental processing conditions. In addition, errors in EEG decoding correlated with errors in behavioral categorization under explicit processing for both expression and identity, however under incidental conditions only errors in EEG decoding of expression correlated with behavior. Furthermore, decoding time-courses and the spatial pattern of informative electrodes showed consistently better decoding of identity under explicit conditions at later-time periods, with weak evidence for similar effects for decoding of expression at isolated time-windows. Taken together, these results reveal differences and commonalities in the processing of face categories under explicit Vs incidental task contexts and suggest that facial expressions are processed to a richer degree under incidental processing conditions, consistent with prior work indicating the relative automaticity by which emotion is processed. Our work further demonstrates the utility in applying multivariate decoding analyses to EEG for revealing the dynamics of face perception.

Primary Care Pharmacist Services Align With Payment Reform and Provider "Joy of Practice".

The implementation and expansion of primary care (PC) pharmacist medication optimization and management services has been hindered mainly by the lack of a payment mechanism for PC providers to engage pharmacist services. If pharmacists expect to be included in new PC team-based payment models, we need to actively engage in ongoing PC practice transformation discussions with PC organizational leaders. In this commentary, examples of integrated PC pharmacist services and payment models are provided to (1) reinforce the feasibility of pharmacist integration into expanded PC teams and (2) share with PC leaders, payers, and policy makers.

Social and community networks influence dietary attitudes in regional New South Wales, Australia.

INTRODUCTION: Rural populations in Australia have a higher prevalence of obesity, cardiovascular disease, type II diabetes and some cancers. The purpose of the present study was to determine associations between socioeconomic characteristics (socioeconomic position, income, wealth, debt, occupation, social network diversity), dietary attitudes, and fruit and vegetable intake for people living rurally in Australia. METHOD: A community based cross-sectional survey between February and July 2018 of 326 adults (median age 57 years, range 20-90 years, 64.4% female) who attended rural shows in four rural towns in south-eastern New South Wales, supplemented with data from patients attending general practices in two additional towns. Participants completed a questionnaire that recorded self-reported daily consumption of fruit and vegetables, a dietary attitude score, and items measuring social and economic circumstances. RESULTS: Using multivariable regression analysis, the odds of meeting Australian fruit intake guidelines was 13% higher for each unit increase in dietary attitude score (odds ratio (OR)=1.13, 95% confidence interval (CI)=1.03-1.23). The odds of meeting vegetable intake guidelines were 19% higher for each unit increase in score (OR=1.19, 95%CI=1.09-1.31). Social and economic factors were not independently associated with fruit or vegetable intake. Dietary attitude score, in turn, increased on average by 0.07 points (95%CI=0.01-0.12) for each additional occupation type among the participants' social networks. For women who socialised regularly in small towns the score was 1.97 points higher (95%CI=0.93-3.00). Men in outer regional areas were more likely to meet vegetable intake guidelines than men in inner regional areas, whereas women in outer regional areas were more likely to meet fruit intake guidelines than women in inner regional areas. CONCLUSIONS: Greater fruit and vegetable intake was predicted by healthier dietary attitudes which in turn were related to social and community connections, rather than economic factors.

Effects of fusariotoxin co-exposure on THP-1 human immune cells.

Deoxynivalenol (DON), nivalenol (NIV), T-2 toxin (T2), fumonisin B1 (FB1), zearalenone (ZEA), and moniliformin (MON) mycotoxins are common food and feed contaminants produced by Fusarium spp. However, while they are usually found to co-occur in a large range of commodities, only few data are available on mycotoxin co-exposure effects and cellular response mechanisms. In this study, the individual and combined toxic effects of these fusariotoxins were evaluated on the THP-1 human immune cell line as major fusariotoxins are mostly potent immunomodulators. In particular, four relevant fusariotoxin mixtures, namely DON-MON, DON-FB1, DON-ZEA, and NIV-T2, were studied using several parameters including cell viability as well as the expression of cell surface markers and the main mitogen-activated protein kinases (MAPKs). After 48 h exposure, a reduction of cell viability in a dose-dependent manner was observed for T2, the most cytotoxic mycotoxin, followed by NIV, DON, MON, FB1, and ZEA. Regarding mycotoxin mixtures, they mainly showed antagonism on cell viability reduction. Interestingly, at concentrations inhibiting 50% of cell viability, most viable cells exhibited surface marker loss and thus became potentially non-functional. In addition, during the first 18 h of exposure, the effects of mycotoxin mixtures on early cell apoptosis and necrosis were found to be different from those induced by the toxins alone. At the molecular level, after 1 h exposure of individual and combined mycotoxins, the three main MAPK signaling pathways (p38, SAPK/JNK, and ERK1/2) were activated, highlighting a fast reaction of the exposed cells even at low cytotoxicity levels.

Primary Care Teams and Pharmacist Staffing Ratios: Is There a Magic Number?

Primary care physician (PCP) shortages are predicted for 2025, and many workforce models have recommended the expanded integration of nurse practitioners and physician assistants. However, there has been little consideration of incorporating clinical pharmacists on primary care teams to address the growing number of patient visits that involve medication optimization and management. This article summarizes various estimates of pharmacist staffing ratios based on number of PCPs, patient panel size, or annual patient encounters. Finally, some steps are offered to address the practice- and policy-based implications of expanding primary care pharmacist activities at the local and state levels.