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We report the case of a 57-year-old man who presented overnight to a district general hospital as a primary percutaneous coronary intervention alert for an inferior ST elevation myocardial infarction. On presentation to cardiac catheterisation lab, he had ongoing chest pain but began to complain of left-sided limb weakness and pain in his right leg. He was found to have dense hemiparesis on examination with an National Institute of Health Stroke Scale of 8 and an absent right femoral pulse. During the procedure, his common iliac arteries were imaged showing a complete occlusion of his right common iliac. After stenting the culprit lesion in his right coronary artery, he was transferred to a different hospital within the trust where he could receive thrombolysis for his stroke. Unfortunately, after thrombolysis, he went on to develop haemorrhagic transformation of his stroke and an upper gastrointestinal bleed with prolonged recovery of his neurological symptoms after a 27-day hospital stay; but CT arterial imaging showed resolution of right common iliac occlusion predischarge. Here, we discuss the best possible approach to management with simultaneous thrombotic events.

Background Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. Objectives To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. Methods MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. Results We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06-0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. Conclusions Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Objective Determine if online training for child care providers increases knowledge and awareness of and adherence to California's Healthy Beverages in Child Care Act (AB2084) policy. Design Cluster, randomized controlled trial with 2 intervention groups and 1 control group. Setting Licensed child care centers and family child care homes. Participants Child care providers in 3 California regions. Intervention Thirty-minute, self-paced online training in English or Spanish, with or without 6-months of ongoing technical assistance. Main outcomes measured Providers’ self-reported knowledge and awareness of and adherence to AB2084 at baseline, after 1 and 6 months. Analysis Generalized estimating equations and generalized linear models, adjusted for the percentage of children on child care subsidies and region. Results Outcomes were similar between groups receiving and not receiving technical assistance. Providers receiving training (both intervention groups combined) experienced larger increases in knowledge (P = 0.002 and P = 0.003) and awareness (P = 0.004 and P = 0.001) of AB2084 compared with the control group after 1 and 6 months. All groups reported pre-post increases in adherence to AB2084. Conclusions and Implications A brief online training supports increased knowledge and awareness of healthy beverage policy among child care providers. The training is available online and is free for California child care providers.

Renal artery stenosis (RAS) typically involves varying degrees of calcification, and treatment can be fraught with risk and suboptimal results. Intravascular lithotripsy (IVL) uses shockwaves to fragment calcium to facilitate angioplasty. We present a case of severe bilateral RAS successfully treated with IVL and stenting after conventional methods had failed. (Level of Difficulty: Intermediate.), Graphical abstract

Objective To compare food/beverage provisions between child care sites participating and not participating in the Child and Adult Care Food Program (CACFP). Design Cross-sectional survey administered in 2016. Setting Licensed child care centers and homes. Participants Child care providers (n = 2,400) randomly selected from California databases (30% responded). Respondents (n = 680) were primarily site directors (89%) at child care centers (83%) participating in CACFP (70%). Main Outcome Measures Meals/snacks served, and food/beverage provisions provided to children of age 1–5 years on the day before the survey. Analysis Odds ratios unadjusted and adjusted for the number of meals/snacks using logistic regression. Results Compared with CACFP sites, non-CACFP sites provided fewer meals/snacks; had lower odds of providing vegetables, meats/poultry/fish, eggs, whole grains, and milk; and had higher odds of providing candy, salty snacks, and sugary drinks. After adjusting for the number of meals/snacks, differences were attenuated but remained significant for meats/poultry/fish, milk, candy, salty snacks (centers only), and sugary drinks. Differences emerged in favor of CACFP for flavored/sugar-added yogurt, sweet cereals, frozen treats, and white grains. Conclusions and Implications Child care sites participating in CACFP are more likely to provide nutritious foods/beverages compared with non-CACFP sites. Child care sites are encouraged to participate in or follow CACFP program guidelines.

Infant nutrition can influence development, eating behaviors and obesity risk. Nearly half of infants in the U.S. are in non-parental care where they consume much of their daily nutrition. Because little is known about the quality of infant nutrition in childcare, the study objective was to characterize the foods and beverages provided to infants in childcare in California. From a randomly selected sample of 2,400 licensed childcare in California, 736 responded to a 2016 survey; a subset of 297 cared for infants. Differences in 26 foods and 7 beverages provided between centers and homes, and by CACFP participation, were assessed using logistic regression models adjusted for CACFP participation and whether the site was a center or home, respectively. Several differences between centers and homes were identified. One the day prior to the survey, more centers than homes ever provided cow’s milk (25.1% vs 13.0%, p = 0.02) and whole grains (76.7% vs 62.9%, p = 0.03), and fewer centers than homes provided frozen treats (1.4% vs 10.3%, p = 0.003). When comparing difference by CACFP participation, fewer CACFP than non-CACFP sites usually provided breastmilk (32.6% vs 54.2%, p = 0.0004) and ever provided cow’s milk (14.2% vs 37.1%, p

Arrhythmic fluctuations in neural activity occur at many levels of the nervous system. Such activity does not have a characteristic temporal periodicity but can exhibit statistical similarities, most commonly power-law scaling behavior, which is indicative of scale-free dynamics. The recurrence of scaling laws across many different systems and its manifestation in behavior has prompted a search for unifying principles in human brain function. With this in mind, a focused search for abnormities in scale-free dynamics is of considerable clinical relevance to migraine and other clinical pain disorders. Here, we examined the scale-free properties of the resting-state functional magnetic resonance imaging (fMRI) signal in the broadband frequency range known to be related to spontaneous neural activity (0.01-0.1 Hz). In a large cohort of episodic migraine patients (N = 40), we observed that the strength of long-range temporal correlations in the fMRI signal (captured by the scaling exponent α) was significantly higher in the sensorimotor network compared with healthy controls. Increases in the scaling exponent were positively correlated with fMRI signal variance and negatively correlated with the patient's self-reported headache intensity. These changes in the fMRI signal suggest that the temporal structure of amplitude fluctuations carries valuable information about the dynamic state of the underlying neuronal networks and ensuing sensory impairments in migraine. The demonstrated scaling laws pose a novel quantitative approach for examining clinically relevant interindividual variability in migraine and other pain disorders.

Objective To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane Library searched up to 13 May 2021. Eligibility criteria for selecting studies Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. Outcome and measures The primary outcome was glycated haemoglobin (HbA 1c ). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. Results 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA 1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P2 =75%, P1c and for absolute dietary GI and SBP (P1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. Conclusions This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. Study registration ClinicalTrials.gov NCT04045938 .

Background Children’s consumption of sugar-sweetened beverages is associated with obesity, diabetes, and dental decay. California’s Healthy Beverages in Child Care Act (AB 2084) requires all licensed child care centers and family child care homes to comply with healthy beverages standards, however many licensed providers in California are unaware of the law and few are fully compliant with the law’s requirements. The aim of the current project is to describe the development of a self-paced online training on best practices and implementation of AB 2084 in English and Spanish for family child care home and child care center providers; and to evaluate the feasibility, defined as being accessible, acceptable, and satisfactory to providers, of this new online course. Methods The project was broken into two main stages: (1) development of the online course; and (2) evaluation of the final online course. The first stage was completed in five phases: (1) identify relevant course content and develop narration script; (2) conduct in-person focus groups with child care providers to review and edit the content; (3) adapt course content and translate for Spanish-speaking providers; (4) build the online course and resources; and (5) pilot online course and evaluate accessibility. The second stage, evaluation of the acceptability and satisfaction of the final course was rated on a Likert scale from 1 to 4; the evaluation was completed as part of a larger randomized control trial with 43 child care providers. The course features four key requirements of AB 2084 as the main sections of the course (milk, sweetened beverages, juice, and water), plus background information about beverages and children’s health, special topics including caring for children with special needs, family engagement, written policies, and child engagement. Results The child care providers who completed the evaluation found the online training was easily understandable (median(Q1,Q3,IQR) = 4 (4,4,0)), included new information (3 (1, 3, 4)), provided useful resources (4(4,4,0)), and was rated with high overall satisfaction (3 (1, 3, 4)). Conclusion Online training in English and Spanish designed for child care providers is a feasible medium to deliver important health messages to child care providers in an accessible, acceptable, and satisfactory manner.

Deep brain stimulation (DBS) in Parkinson's disease (PD) alters neuronal function and network communication to improve motor symptoms. The subthalamic nucleus (STN) is the most common DBS target for PD, but some patients experience adverse effects on memory and cognition. Previously, we reported that DBS of the ventral anterior (VA) and ventrolateral (VL) nuclei of the thalamus and at the interface between the two (VA|VL), collectively VA-VL, relieved forelimb akinesia in the hemiparkinsonian 6-hydroxydopamine (6-OHDA) rat model. To determine the mechanism(s) underlying VA-VL DBS efficacy, we examined how motor cortical neurons respond to VA-VL DBS using single-unit recording electrodes in anesthetized 6-OHDA lesioned rats. VA-VL DBS increased spike frequencies of primary (M1) and secondary (M2) motor cortical pyramidal cells and M2, but not M1, interneurons. To explore the translational merits of VA-VL DBS, we compared the therapeutic window, rate of stimulation-induced dyskinesia onset, and effects on memory between VA-VL and STN DBS. VA-VL and STN DBS had comparable therapeutic windows, induced dyskinesia at similar rates in hemiparkinsonian rats, and adversely affected performance in the novel object recognition (NOR) test in cognitively normal and mildly impaired sham animals. Interestingly, a subset of sham rats with VA-VL implants showed severe cognitive deficits with DBS off. VA-VL DBS improved NOR test performance in these animals. We conclude that VA-VL DBS may exert its therapeutic effects by increasing pyramidal cell activity in the motor cortex and interneuron activity in the M2, with plausible potential to improve memory in PD.

Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by autoantibodies against the glomerular basement membrane. Atypical anti-GBM nephritis is clinically less aggressive and characterized by the absence of circulating autoantibodies to the basement membrane. A previously healthy 53-year-old white woman presented with a rising creatinine over a short observation period. Renal biopsy, urinary sediment, and laboratory testing confirmed the diagnosis of atypical anti-GBM disease. She received plasmapheresis, steroids, and cyclophosphamide. She developed hemorrhagic cystitis early in the treatment from oral cyclophosphamide and mycophenolate mofetil was substituted as a first-line drug. She responded favorably and continued on mycophenolate mofetil without evidence of relapse. Despite the absence of circulating autoantibodies, a diagnosis of atypical anti-GBM nephritis should not be excluded if a high index of clinical suspicion exists. Early renal biopsy should be considered. Mycophenolate mofetil may be a reasonable replacement for oral cyclophosphamide in the treatment of atypical anti-GBM disease when cyclophosphamide is contraindicated.

OBJECTIVES: Sugar-sweetened beverages (SSBs) have been linked to weight gain, and it is unclear if other food sources of fructose-containing sugars behave similarily. We conducted a systematic review and meta-analysis of controlled feeding trials to assess the effect of different food sources of fructose-containing sugars on body weight. METHODS: MEDLINE, EMBASE, and The Cochrane library were searched through January 2019. We included controlled feeding trials of ≥2 weeks investigating the effect of different food sources of sugars. Four levels of energy control were prespecified: substitution (energy-matched comparisons); addition (energy from sugars added to diet); subtraction (energy from sugars subtracted from diet); or ad libitum (energy from sugars freely replaced). The primary outcome was body weight. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). GRADE assessed the certainty of evidence. RESULTS: We identified 110 controlled trials (N = 5133) assessing the effect of 7 different food sources of fructose-containing sugars (SSBs, fruit, fruit juice, dried fruit; baked goods, sweets, & desserts; mixed sources; added caloric sweeteners). No effect on body weight was observed in substitution trials, whereas there was an increasing effect in addition trials (MD, 0.23 kg [95% CI, 0.06 to 0.40]) and ad libitum trials (1.43 kg [0.78 to 2.16]), and a decreasing effect in subtraction trials (–0.52 kg [–1.02 to −0.02]). There was evidence of interaction by food source with fruit showing weight loss in substitution trials and SSBs showing weight gain in addition trials. The certainty of evidence was moderate for the effects in the addition and subtraction trials and high for the effects in the substitution and ad libitum trials. CONCLUSIONS: Energy control and food source appear to mediate the effect of fructose-containing sugars on body weight. Food sources of fructose-containing sugars adding excess energy to diets (especially sugars-sweetened beverages) appear to lead to weight gain. There is low to moderate likelihood that more research will substantially alter our estimates (ClinicalTrials.gov Identifier, NCT02558920) FUNDING SOURCES: American Society for Nutrition Foundation (commissioned and funded), Diabetes Canada.

INTRODUCTION Since 2012, licensed California child care centers and homes, per state policy, are required to serve only unflavored low-fat or nonfat milk to children aged 2 years or older, no more than one serving of 100% juice daily, and no beverages with added sweeteners, and they are required to ensure that drinking water is readily accessible throughout the day. We evaluated adherence to the policy after 4 years in comparison to the adherence evaluation conducted shortly after the policy went into effect. METHODS Licensed California child care sites were randomly selected in 2012 and 2016 and surveyed about beverage practices and provisions to children aged 1-5 years. We used logistic regression to analyze between-year differences for all sites combined and within-year differences by site type and participation in the federal Child and Adult Care Food Program (CACFP) in self-reported policy adherence and beverage provisions. RESULTS Respondents in 2016 (n = 680), compared with those in 2012 (n = 435), were more adherent to California's 2010 Healthy Beverages in Child Care Act overall (45.1% vs 27.2%, P < .001) and with individual provisions for milk (65.0% vs 41.4%, P < .001), 100% juice (91.2% vs 81.5%, P < .001), and sugar-sweetened beverages (97.4% vs 93.4%, P = .006). In 2016, centers compared with homes (48.5% vs 28.0%, P = .001) and CACFP sites compared with non-CACFP sites (51.6% vs 27.9%, P < .001) were more adherent to AB2084 overall. DISCUSSION Beverage policy adherence in California child care has improved since 2012 and is higher in CACFP sites and centers. Additional policy promotion and implementation support is encouraged for non-CACFP sites and homes. Other states should consider adopting such policies.

Child care has broad reach to young children. Yet, not all child care settings have nutrition standards for what and how foods and beverages should be served to infants as they transition to toddlerhood. The purpose of this paper is to describe the development of nutrition recommendations to guide feeding young children in licensed child care settings in the USA, a process that could be adapted in other countries. Nutrition standards were designed by nutrition and child care experts to address what and how to feed young children, also including the transition from infants to toddlers. Nutrition standards are important for health and can be feasibly implemented in child care settings. Feasibility considerations focused on family child care homes, which typically have fewer resources than child care centers or preschools. Infant standards include recommendations for vegetables, fruits, proteins, grains, and breast milk and other beverages. Also included are recommendations for supporting breastfeeding, introducing complementary foods, and promoting self-regulation in response to hunger and satiety. Toddler standards are expanded to address the frequency as well as types of food groups, and recommendations on beverages, sugar, sodium, and fat. Feeding practice recommendations include meal and snack frequency and style, as well as the promotion of self-regulation among older children.

OBJECTIVES: Excess calories as fructose may initiate pathways increasing biomarkers of inflammation. Whether this effect is mediated by the food matrix at different energy levels is unknown. We conducted a systematic review and meta-analysis of controlled feeding trials of the effect of food sources of fructose-containing sugars at different energy control levels on biomarkers of inflammation (NCT02716870). METHODS: We searched MEDLINE, Embase, and the Cochrane Library through January 15 2020 for controlled trials ≥7d. Trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugar in the diet); addition (excess energy from sugar added to diets); subtraction (energy from sugar subtracted from diets); ad libitum (energy from sugar freely replaced in the diet). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Independent reviewers extracted data and assessed the risk of bias. Certainty of evidence was assessed by GRADE. RESULTS: We included 48 trials (109 trial comparisons, n = 2108) assessing the effect of 10 food sources (SSBs, sweetened dairy, sweetened dairy alternatives (soy), fruit, 100% fruit juice, dried fruit, sweetened cereal grains/bars, sweets, added nutritive sweetener, and mixed sources) across the 4 levels of energy control. Total fructose-containing sugars had no effect on any outcome in any level of energy control. There was evidence of interaction by food source; in substitution trials, sweetened dairy alternative (soy) decreased CRP. In addition trials, fruit decreased while added nutritive sweetener increased TNF-α. The certainty of evidence was low for the effect of sweetened dairy alternative (soy) on CRP in substitution trials, and generally moderate for all other comparisons. CONCLUSIONS: Food source more than energy control appears to mediate the effect of fructose-containing sugars on inflammation. The evidence provides some indication that sweetened dairy alternatives (soy) and fruit decrease and added nutritive sweeteners increase biomarkers of inflammation. More high-quality randomized trials of different fructose containing food sources are needed to improve our estimates. FUNDING SOURCES: Diabetes Canada.

OBJECTIVES: Overconsumption of fructose-containing sugars may increase blood pressure. Whether this effect is mediated by the food matrix is unclear. We conducted a systematic review and meta-analysis of controlled feeding trials of the effect of food sources of fructose-containing sugars at different levels of energy control on blood pressure (NCT02716870). METHODS: We searched MEDLINE, Embase and the Cochrane Library through January, 2020 for controlled trials ≥7d. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars in the diet); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in the diet) trials. Outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP). Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed by GRADE. RESULTS: We included 76 trials (121 trial comparisons, N = 4 302) assessing 9 food sources (sugar-sweetened beverages [SSBs], sweetened dairy alternatives, 100% fruit juice, fruit, dried fruit, sweets, added nutritive sweetener, sweetened cereal grains/bars, and mixed sources) across the 4 levels of energy control. Total fructose-containing sugars decreased SBP (mean difference, −2.76 mmHg [95% CI, −4.36, −1.16], P = 0.001) and DBP (−1.26 mmHg [−2.29, −0.23], P = 0.016) in addition trials and the removal of these sugars decreased SBP (−1.79 mmHg [−3.36, −0.21], P = 0.026) in subtraction trials. There was evidence of interaction by food source with fruit decreasing and sweets and mixed sources increasing SBP and DBP in addition trials and the removal of SSBs decreased SBP in subtraction trials. The certainty of evidence was generally moderate to low for all food source-outcome relationships, except for the decreasing-effect of fruit on DBP in addition trials (high). CONCLUSIONS: Food source and energy control appear to mediate the effect of fructose-containing sugars on blood pressure. The evidence provides a good indication that fruit decreases while excess calories from SSBs, sweets and mixed sources increase blood pressure. More high-quality trials of different food sources are needed to improve our estimates. FUNDING SOURCES: Diabetes Canada.

OBJECTIVES: Fructose as a source of excess calories increases non-alcoholic fatty liver disease (NAFLD) markers. Whether this effect is mediated by the food matrix is unknown. We thus conducted a systematic review and meta-analysis of controlled feeding trials assessing the effect of important food sources of fructose-containing sugars at different energy control levels on NAFLD markers. METHODS: MEDLINE, Embase, and Cochrane Library were searched through January 18, 2021 for controlled trials ≥7-days. Four trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed by GRADE. RESULTS: We included 44 trials (65 trial comparisons, n = 1941) assessing the effect of 8 food sources (sugar-sweetened beverages [SSBs]; sweetened dairy alternative [soy]; fruit juice; fruit; dried fruit; baked goods, desserts and sweets; added nutritive sweetener; and mixed sources) across 4 energy levels. Total fructose-containing sugars increased IHCL in addition trials (standardized mean difference = 1.69 [95% CI, 1.00–2.37], P

Standardisation of practice within surgical pathology begins with standardisation of procedures and processes and results in standardisation of practice by all professionals within the surgical pathology department, including pathologists’ assistants (PAs). Healthcare in today’s world is constantly evolving, and surgical pathology is no exception. Testing that was unavailable just years ago can now be considered standard practice that defines a patient’s prognosis and treatment, such is the case with breast cancer biomarkers.1 These tests sometimes emerge into practice faster than their quality control and quality assurance practices can be universally implemented, leading to issues such as those defined by the Cameron Inquiry in Canada2 and the Barne’s Report in the UK.3 These investigations and resulting recommendations call for standardisation of practice in the department directly performing these tests via reproducible, objective, strict quality assurance and control measures, and of all preanalytical and postanalytical steps involved in handling the specimens destined for testing, including standardisation of the professionals involved in these steps. Standardisation in regards to surgical pathology applies to all tasks, beginning with specimen acceptance and accessioning and continues to specimen preparation for fixation, decalcification, ancillary testing, gross descriptions and dissections including specimen sampling, and extends to successive histology techniques such as tissue processing, staining, stain interpretation and immunohistochemistry. Most of these tasks are easily standardised, such as standardisation fixation solutions, fixation times, ischaemic times, programming tissue processors and other automated and easily reproducible tasks. However, standardising a task as interpretive and unique as gross description and dissection of a complex specimen proves more of a challenge. Traditionally, these complex, difficult to standardise functions were performed by the diagnosing pathologist themselves, and their own preferences were sometimes evident in their practice. However, over the span of years, these tasks were slowly undertaken by a new profession that began to …

OBJECTIVES: Healthy default beverage policies for restaurant kids’ meals have been identified as a top strategy to improve beverage intake in young children and reduce obesity and diabetes risk. California passed a statewide policy (SB1192), effective January 2019, specifying kids’ meal default beverages as water, unflavored milk, or a nondairy alternative. Although other localities have adopted similar policies, there have been no studies on their effectiveness. The aim of this study was to assess changes in beverages offered with kids’ meals before and after a healthy default beverage policy took effect and to quantify policy adherence in menus and cashier orders in quick service restaurants (QSR). METHODS: The study employed a pre-post policy design. Baseline data on beverages offered as part of kids’ meals were collected from 111 QSR in low-income areas in California in late 2018, prior to policy implementation. Follow-up data were collected from the same restaurants one year later. Data were collected by menu observation and purchase of kids’ meals. Both walk-in and drive-through settings were assessed where available. Full policy adherence was defined as offering only SB1192-compliant beverages, and was assessed 3 ways: menu board, cashier order, and a combined metric. RESULTS: At baseline, prior to any legislative requirement, 6 (6.3%) restaurant menu boards, 5 (4.5%) cashier orders, and 0 restaurants overall were already fully adherent. At follow-up, 64 (66.0%) restaurant menu boards, 1 (0.9%) cashier order, and 0 restaurants overall were fully adherent. Generalized estimating equations, clustered by restaurant chain, were used to test pre-post policy changes. Adherence in menu boards increased (59.7%, p = < .0001). There were no changes in adherence in cashier orders or overall adherence. CONCLUSIONS: California's healthy default beverage policy for restaurant kids’ meals was effective in changing QSR menu board offerings but did not impact cashier order processes. Additional staff training may improve policy implementation. Studies are underway to assess the impact of staff training and customer behavior change. FUNDING SOURCES: University of California Division of Agriculture and Natural Resources, Robert Wood Johnson Foundation Healthy Eating Research, CA Department of Public Health/USDA.

Highlights • Increased fMRI activation of bilateral pulvinar nuclei with symptomatic light. • Pulvinar nuclei are associated with melanopsin visual pathway and migraine. • First demonstration of fMRI activation of melanopsin pathway during photophobia., Numerous pathologies can contribute to photophobia. When considering light transduction alone, photophobia may be triggered through melanopsin pathways (non-image forming), rod and cone pathways (image-forming), or some combination of the two. We evaluated a 39 year old female patient with longstanding idiopathic photophobia that was exacerbated by blue light, and tested her by presenting visual stimuli in an event-related fMRI experiment. Analysis showed significantly greater activation in bilateral pulvinar nuclei, associated with the melanopsin intrinsically photosensitive retinal ganglion cell (ipRGC) visual pathway, and their activation is consistent with the patient's report that blue light differentially evoked photophobia. This appears to be the first demonstration of functional activation of the ipRGC pathway during photophobia in a patient.

Background: Nationally, child care providers serve nutritious food to over 4.5 million children each day as part of the federal Child and Adult Care Food Program (CACFP). As implementation of the first major revisions to the CACFP standards occurs in 2017, understanding how to support compliance is critical. Methods: In 2016, surveys were sent to a randomly selected sample of 2400 licensed California child care centers and homes. Compliance with the new CACFP standards and best practices for infants under 1 year and children 1–5 years of age was assessed. Also, compliance was compared by CACFP participation, and between centers and homes. Interviews were conducted with 16 CACFP stakeholders to further understand barriers to and facilitators of compliance. Results: Analysis of 680 survey responses revealed that compliance with most individual CACFP standards and best practices examined was high (>60% of sites). However, compliance with all new standards was low (

Migraineurs show hypersensitivity to sensory stimuli at various stages throughout the migraine cycle. A number of putative processes have been implicated including a dysfunction in the descending pain modulatory system in which the periaqueductal gray (PAG) is considered to play a crucial role. Recurring migraine attacks could progressively perturb this system, lowering the threshold for future attacks, and contribute to disease chronification. Here, we investigated PAG connectivity with other brain regions during a noxious thermal stimulus to determine changes in migraineurs, and associations with migraine frequency. 21 episodic migraine patients and 22 matched controls were included in the study. During functional MRI, a thermode was placed on the subjects' temple delivering noxious and non-noxious heat stimuli. A psychophysiological interaction (PPI) analysis was carried out to examine pain-induced connectivity of the PAG with other brain regions. The PPI analysis showed increased PAG connectivity with the S1 face representation area and the supplementary motor area, an area involved with pain expectancy, in patients with higher frequency of migraine attacks. PAG connectivity with regions involved with the descending pain modulatory system (i.e., prefrontal cortex) was decreased in the migraineurs versus healthy individuals. Our results suggest that high frequency migraineurs may have diminished resistance to cephalic pain and a less efficient inhibitory pain modulatory response to external stressor (i.e., noxious heat). The findings support the notion that in migraine there is less effective pain modulation (viz., decreased pain inhibition or increased pain facilitation), potentially contributing to increased occurrence of attacks/chronification of migraine.

Background Essential tremor (ET) is heterogeneous in nature and cases may be subdivided based on clinical features. ET patients may thus be subdivided by age of onset, family history of tremor, and presence of head tremor. We recently described climbing fiber-Purkinje cell (CF-PC) synaptic abnormalities in ET; however, these CF pathological features have not been studied across different ET subtypes. Objectives To explore whether these CF-PC synaptic abnormalities differ across ET subtypes. Methods We studied two climbing fiber (CF-PC) synaptic pathologies (CF synaptic density and percentage of CFs in the parallel fiber [PF] territory) in the cerebella of 60 ET cases with a range of clinical presentations and 30 age-matched controls. Results Compared to controls, ET cases had lower CF synaptic density and a higher percentage of CFs in the PF territory. ET cases with tremor onset ≥ 50 years did not differ significantly with respect to CF synaptic density and percentage of CFs in the PF territory. Similar results were found when comparing familial vs. sporadic ET cases, and ET cases with head tremor vs. those without head tremor. Among all ET cases, lower CF synaptic density was associated with lower PC counts and higher torpedo counts. In addition, higher percentage of CFs in the PF territory was associated with lower PC counts and higher torpedo counts. Conclusions These findings support the notion that changes in the distribution of CF-PC synapses are broadly part of the neurodegenerative process in the ET cerebellum.

Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson's disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls. We observed differences in terms of CF pathological features across these disorders. Specifically, PD cases and ET cases both had more CFs extending into the parallel fiber (PF) territory, but ET cases had more complex branching and increased length of CFs in the PF territory along with decreased CF synaptic density compared to PD cases. MSA cases and SCA1 cases had the most severely reduced CF synaptic density and a marked paucity of CFs extending into the PF territory. Furthermore, CFs in a subset of MSA cases formed collateral branches parallel to the PC layer, a feature not seen in other diagnostic groups. Using unsupervised cluster analysis, the cases and controls could all be categorized into four clusters based on the CF pathology and features of PC pathology, including counts of PCs and their axonal torpedoes. ET cases and PD cases co-segregated into two clusters, whereas SCA1 cases and MSA cases formed another cluster, separate from the control cluster. Interestingly, the presence of resting tremor seemed to be the clinical feature that separated the cases into the two ET-PD clusters. In conclusion, our study demonstrates that these degenerative movement disorders seem to differ with respect to the pattern of CF synaptic pathology they exhibit. It remains to be determined how these differences contribute to the clinical presentations of these diseases.

Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH.This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined.Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P0.001) and a 1.22 mmHg decrease in CPP (P0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased.Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

Increasing silver nanoparticle (AgNP) use in sprays, consumer products and medical devices has raised concerns about potential health effects. While previous studies have investigated AgNPs, most were limited to a single particle size or surface coating. In this study, we investigated the effect of size, surface coating and dose on the persistence of silver in the lung following exposure to AgNP. Adult male rats were intratracheally instilled with four different AgNPs: 20 or 110nm in size and coated with either citrate or polyvinylpyrrolidone (PVP) at 0.5 or 1.0mg/kg doses. Silver retention was assessed in the lung at 1, 7 and 21 days post exposure. ICP-MS quantification demonstrated that citrate coated AgNPs persisted in the lung to 21 days with greater than 90% retention, while PVP coated AgNP had less than 30% retention. Localization of silver in lung tissue at one day post exposure demonstrated decreased silver in proximal airways exposed to 110nm particles compared with 20nm AgNPs. In terminal bronchioles one day post exposure, silver was localized to surface epithelium but was more prominent in the basement membrane at 7 days. Silver positive macrophages in bronchoalveolar lavage fluid decreased more quickly after exposure to particles coated with PVP. We conclude that PVP coated AgNPs had less retention in the lung tissue over time and larger particles were more rapidly cleared from large airways than smaller particles. The 20nm citrate particles the greatest effect; increasing lung macrophages even 21days after exposure and resulted in the greatest silver retention in lung tissue.