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Background MicroRNA (miR)-214-3p is emerging as an important tumor suppressor in esophageal cancer. In this study, we examined the interaction between miR-214-3p and RAB14, a membrane trafficking protein shown to exert oncogenic functions in other malignancies, in esophageal cancer cells. Methods Studies were performed in a human esophageal epithelial cell line and a panel of esophageal cancer cell lines, as well in human specimens. MiR-214-3p expression was measured by digital PCR. Biotinylated RNA pull-down and luciferase reporter assays assessed binding. The xCELLigence RTCA system measured cell migration and invasion in real time. A lentiviral expression vector was used to create an esophageal cancer cell line stably expressing miR-214-3p. Results MiR-214-3p expression was decreased in esophageal cancer cell lines and human specimens compared to non-malignant controls. RAB14 mRNA stability and protein expression were decreased following miR-214-3p overexpression. Binding between miR-214-3p and RAB14 mRNA was observed. Either forced expression of miR-214-3p or RAB14 silencing led to a marked decrease in cellular migration and invasion. Esophageal cancer cells stably expressing miR-214-3p demonstrated decreased growth in a subcutaneous murine model. Conclusions These results further support the tumor-suppressive role of miR-214-3p in esophageal cancer cells by demonstrating its ability to regulate RAB14 expression.

BACKGROUND Practice guidelines recommend neoadjuvant chemoradiation (NCR) for locally advanced rectal cancer (LARC). We examined guideline adherence in a healthcare system serving a region with socioeconomic disparities and poor cancer outcomes. METHODS Retrospective analysis of factors associated with guideline adherence. RESULTS 63.1% of stage II/III LARC patients received NCR. Factors associated with adherence included white race (OR = 2.15, p = 0.024), private insurance (OR = 2.70, p = 0.005), employed status (OR = 2.30, p = 0.031), age at diagnosis (OR = 0.74, p = 0.032), appropriate local staging (OR = 9.17, p < 0.0001), and diagnosis later in the study period (OR per 1 year = 1.20, p = 0.006). By multivariate analysis, private insurance (OR = 2.51, p = 0.023), younger age (OR per 10 years = 0.72, p = 0.048) and appropriate local staging (OR = 6.67, p

BACKGROUND: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).OBJECTIVE: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.METHODS: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.RESULTS: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.CONCLUSION: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy.

As climate and land use increase the variability of many ecosystems, forecasts of ecological variables are needed to inform management and use of ecosystem services. In particular, forecasts of phytoplankton would be especially useful for drinking water management, as phytoplankton populations are exhibiting greater fluctuations due to human activities. While phytoplankton forecasts are increasing in number, many questions remain regarding the optimal model time step (the temporal frequency of the forecast model output), time horizon (the length of time into the future a prediction is made) for maximizing forecast performance, as well as what factors contribute to uncertainty in forecasts and their scalability among sites. To answer these questions, we developed near-term, iterative forecasts of phytoplankton 1-14 days into the future using forecast models with three different time steps (daily, weekly, fortnightly), that included a full uncertainty partitioning analysis at two drinking water reservoirs. We found that forecast accuracy varies with model time step and forecast horizon, and that forecast models can outperform null estimates under most conditions. Weekly and fortnightly forecasts consistently outperformed daily forecasts at 7-day and 14-day horizons, a trend that increased up to the 14-day forecast horizon. Importantly, our work suggests that forecast accuracy can be increased by matching the forecast model time step to the forecast horizon for which predictions are needed. We found that model process uncertainty was the primary source of uncertainty in our phytoplankton forecasts over the forecast period, but parameter uncertainty increased during phytoplankton blooms and when scaling the forecast model to a new site. Overall, our scalability analysis shows promising results that simple models can be transferred to produce forecasts at additional sites. Altogether, our study advances our understanding of how forecast model time step and forecast horizon influence the forecastability of phytoplankton dynamics in aquatic systems and adds to the growing body of work regarding the predictability of ecological systems broadly.

Background and aim To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). Methods We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. Results We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. Conclusion Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

Oxygen availability is decreasing in many lakes and reservoirs worldwide, raising the urgency for understanding how anoxia (low oxygen) affects coupled biogeochemical cycling, which has major implications for water quality, food webs, and ecosystem functioning. Although the increasing magnitude and prevalence of anoxia has been documented in freshwaters globally, the challenges of disentangling oxygen and temperature responses have hindered assessment of the effects of anoxia on carbon, nitrogen, and phosphorus concentrations, stoichiometry (chemical ratios), and retention in freshwaters. The consequences of anoxia are likely severe and may be irreversible, necessitating ecosystem-scale experimental investigation of decreasing freshwater oxygen availability. To address this gap, we devised and conducted REDOX (the Reservoir Ecosystem Dynamic Oxygenation eXperiment), an unprecedented, 7-year experiment in which we manipulated and modeled bottom-water (hypolimnetic) oxygen availability at the whole-ecosystem scale in a eutrophic reservoir. Seven years of data reveal that anoxia significantly increased hypolimnetic carbon, nitrogen, and phosphorus concentrations and altered elemental stoichiometry by factors of 2–5× relative to oxic periods. Importantly, prolonged summer anoxia increased nitrogen export from the reservoir by six-fold and changed the reservoir from a net sink to a net source of phosphorus and organic carbon downstream. While low oxygen in freshwaters is thought of as a response to land use and climate change, results from REDOX demonstrate that low oxygen can also be a driver of major changes to freshwater biogeochemical cycling, which may serve as an intensifying feedback that increases anoxia in downstream waterbodies. Consequently, as climate and land use change continue to increase the prevalence of anoxia in lakes and reservoirs globally, it is likely that anoxia will have major effects on freshwater carbon, nitrogen, and phosphorus budgets as well as water quality and ecosystem functioning. Fralin Life Sciences Institute Institute for Critical Technology and Applied Science National Science Foundation NSF: DGE-1651272 NSF: DBI-1933102 NSF: DBI-1933016 NSF: CNS-1737424 NSF: DEB-1753657 NSF: DEB-1753639 NSF: DEB-1753657 NSF: DEB-1753639 Virginia Tech Global Change Center Western Virginia Water Authority Published version

The National Institute of Health (NIH) estimates that the majority of human microbial infections are either linked to or directly caused by bacterial biofilms and these infections are immune to most currently approved FDA drugs. Hence, there is a need for the development of potent antibiotics against biofilms. We have previously shown that pentafluorosulfanyl (SF

Objective Sleep plays a critical role in children’s growth and development. This study examined the frequency and persistence of children’s sleep problems following a natural disaster, risk factors for children’s sleep problems, and the bidirectional relationship between children’s sleep problems and posttraumatic stress symptoms (PTSS) over time. Methods This study assessed 269 children (53% female, M = 8.70 years, SD = 0.95) exposed to Hurricane Ike at 8 months (Time 1) and 15 months (Time 2) post-disaster. Children completed measures of hurricane exposure and related stressors, stressful life events, sleep problems, and PTSS. Results Children’s sleep problems were significantly correlated from Time 1 to Time 2 (r = .28, p < .001). Risk factors for sleep problems at Time 2 were younger age, sleep problems at Time 1, and PTSS, not including sleep items, at Time 1. Examinations of the bidirectional relationship between sleep problems and PTSS indicated that PTSS significantly predicted later sleep problems, but sleep problems did not significantly predict later PTSS. Conclusions Findings demonstrate that PTSS may contribute to the development and course of children’s sleep problems post-disaster.

Objective The goal of this pilot study was to measure patient satisfaction, pain scores associated with injection, and patient perceptions of a pharmacist-led specialty injection clinic. Setting The Medical University of South Carolina Specialty Pharmacy. Practice description The specialty pharmacy comprises decentralized clinical pharmacy specialists who provide medication education to patients via phone. Many of the medications dispensed are self-administered injectables, but patients often request in-person assistance to learn the best way to use the drug. The investigators sought to provide an avenue for patients to receive teaching and drug administration from a pharmacist without scheduling a formal nurse visit or enrolling the patients in a manufacturer program. Practice innovation Clinical pharmacy specialists offered every patient a referral to the Assistance with Injectable Medication clinic for in-person injection teaching during the initial clinical assessment. At the first clinic visit, the patients were provided with printed injection instructions, and a demo injector from the manufacturer was available for practice before the actual drug administration. Evaluation This was a prospective pilot study conducted from January 2019 to April 2019. Patient identification occurred directly through our clinical pharmacy specialists via referrals and informational flyers. The eligible patients were aged 18 years or older and had received a qualifying subcutaneous injection via the Medical University of South Carolina Specialty Pharmacy. The outcomes included pain score and patient satisfaction. Results As of April 30, 2019, 17 patients had completed 24 clinic visits. The average reported pain and satisfaction scores (scale 0-10) were 2.5 and 9.6, respectively. The 2 most commonly administered medications in the clinic were alirocumab and adalimumab. Conclusion A clinic to assist with specialty injectable medications resulted in high patient satisfaction scores and low pain scores associated with injection.

Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456-463. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders.

The opportunity to participate in and contribute to emerging fields is increasingly prevalent in science. However, simply thinking about stepping outside of your academic silo can leave many students reeling from the uncertainty. Here, we describe 10 simple rules to successfully train yourself in an emerging field, based on our experience as students in the emerging field of ecological forecasting. Our advice begins with setting and revisiting specific goals to achieve your academic and career objectives and includes several useful rules for engaging with and contributing to an emerging field.

The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF).We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline).The microstructural components were quantified with spectral analysis using a non-negative least squares method. Linear regression was employed to investigate associations of these components with hippocampal and white matter hyperintensity (WMH) volumes. In the normal appearing white matter, a large f(int )(a proxy of ISF volume) was associated with a large WMH volume and low hippocampal volume. Likewise, a large f(int) value was associated with a lower hippocampal volume in the hippocampi.Large ISF volume (f(int)) was shown to be a prominent factor associated with both WMHs and neurodegenerative abnormalities in memory clinic patients and is argued to play a potential role in impaired glymphatic functioning. (C) 2021 The Author(s). Published by Elsevier Inc.

BACKGROUND The purpose of this study was to evaluate an unstructured and a structured program designed to increase physical activity (PA). The unstructured program increased the amount of equipment during recess, whereas the structured program introduced activities to students. METHODS PA was observed using the System for Observing Play and Leisure Activity in Youth (SOPLAY) in two school districts in Colorado. Researchers recorded baseline and follow-up observations for sedentary activity, moderate PA, and vigorous PA, as well as for available equipment for the unstructured program. Observations from schools were aggregated for data analyses at the district level. RESULTS For the program increasing equipment, moderate PA and vigorous PA increased, while sedentary behavior decreased. For the structured program, moderate PA and vigorous PA did not increase, whereas sedentary behaviors increased following the program. CONCLUSIONS Other variables are likely influencing student PA during recess, such as teachers' interaction with students or the fidelity of the program. Results indicate that funding and implementing a program aimed at increasing PA will not necessarily accomplish that goal, and additional research should be performed to determine the best practice for increasing PA.

Introduction The purpose of the current study was to examine if isometric peak force and rate of force development (RFD) were related to the ability to successfully perform a simulated casualty evacuation task in both unweighted and weighted conditions. Methods Eighteen male participants from Army Reserve Officers’ Training Corps (ROTC) completed a maximum isometric deadlift on a force plate (IRB#HE16227). Isometric peak force and RFD were calculated from ground reaction force. Two simulated casualty evacuation performance trials were then completed. The unweighted trial consisted of lifting and carrying a 75 kg dummy as quickly as possible for 50 m. The weighted trial was similar except 9 kg vests were added to both the simulation dummy and the participant to represent 18 kg of duty gear. Independent sample t-tests and Pearson correlations were performed to compare the characteristics of those who passed and failed the weighted trial. Results All of the participants (n = 18) completed the unweighted casualty evacuation trial, while 72% (n = 13) were able to complete the weighted casualty evacuation trial. The participants that successfully completed the weighted evacuation trial had significantly (p < 0.05) greater isometric peak force (1420 ± 165 vs. 1076 ± 256 N) and lean mass (74.18 ± 3.89 vs. 65.34 ± 3.89 kg) when compared to participants (n = 5) that could not complete the weighted evacuating task trial. Additionally, greater Army Physical Fitness Test scores (288 ± 13 vs. 269 ± 16 arbitrary units) and significantly faster (30.34 ± 4.41 vs. 44.92 ± 10.62 seconds) unweighted evacuation trial times were observed in participants that could complete the weighted evacuation task. Peak force was also significantly correlated with lean mass (r = 0.51, p < 0.05). There was no relationship between RFD and performance of the unweighted or weight trial. Conclusion Isometric deadlift peak force represents an important determinant for the success of a simulated casualty evacuation task and may be a useful marker to include in periodic fitness evaluations of military personnel.

Background and Purpose— Cerebral amyloid angiopathy (CAA) is a common small vessel disease that independently effects cognition in older individuals. The pathophysiology of CAA and CAA-related bleeding remains poorly understood. In this postmortem study, we explored whether blood-brain barrier leakage is associated with CAA and microvascular lesions. Methods— Eleven CAA cases (median [IQR] age=69 years [65–79 years], 8 males) and 7 cases without neurological disease or brain lesions (median [IQR] age=77 years [68–92 years], 4 males) were analyzed. Cortical sections were sampled from each lobe, and IgG and fibrin extravasation (markers of blood-brain barrier leakage) were assessed with immunohistochemistry. We hypothesized that IgG and fibrin extravasation would be increased in CAA cases compared with controls, that this would be more pronounced in parietooccipital brain regions compared with frontotemporal brain regions in parallel with the posterior predilection of CAA, and would be associated with CAA severity and number of cerebral microbleeds and cerebral microinfarcts counted on ex vivo magnetic resonance imaging of the intact brain hemisphere. Results— Our results demonstrated increased IgG positivity in the frontotemporal ( P =0.044) and parietooccipital ( P =0.001) cortex in CAA cases compared with controls. Within CAA cases, both fibrin and IgG positivity were increased in parietooccipital brain regions compared with frontotemporal brain regions ( P =0.005 and P =0.006, respectively). The percentage of positive vessels for fibrin and IgG was associated with the percentage of amyloid-β–positive vessels (Spearman ρ=0.71, P =0.015 and Spearman ρ=0.73, P =0.011, respectively). Moreover, the percentage of fibrin and IgG-positive vessels, but not amyloid-β–positive vessels, was associated with the number of cerebral microbleeds on magnetic resonance imaging (Spearman ρ=0.77, P =0.005 and Spearman ρ=0.70, P =0.017, respectively). Finally, we observed fibrin deposition in walls of vessels involved in cerebral microbleeds. Conclusions— Our results raise the possibility that blood-brain barrier leakage may be a contributory mechanism for CAA-related brain injury.

Background In the United States, patients with clinical stage II or III rectal cancer typically receive neoadjuvant chemoradiation therapy (chemo/XRT) over a 5-6 week period followed by a 6-10 week break prior to proctectomy. In the current study, we evaluate the utilization of restaging studies performed and detection of disease progression during this window. Methods A retrospective review of patients with clinical stage II/III rectal cancer was performed. Medical records were analyzed to collect clinicopathologic data and the performance and results of preoperative, early postoperative, and first surveillance CT and/or PET/CT in patients completing long course neoadjuvant chemo/XRT and undergoing proctectomy. Results Between 2005 and 2017, 176 patients with clinical stage II or III rectal adenocarcinoma completed neoadjuvant chemo/XRT and underwent proctectomy. Preoperative restaging with CT CAP and/or CT/PET was performed in 72 (40.9%) patients with no detection of disease progression. Of the 104 patients without preoperative restaging, 1 had intraoperative detection of liver metastases and 31 had early postoperative reimaging (within 30 days of proctectomy) of which 2 had detection of new pulmonary metastases. Among 72 patients with no preoperative or early postoperative reimaging, first surveillance imaging was available in 47 and detected new metastases in 8 (17%). Discussion In patients with clinical stage II/III rectal cancer who undergo long course neoadjuvant chemo/XRT, perioperative reimaging with CT CAP and/or PET/CT detects new metastases in a small percentage of patients. A multi-institutional, prospective analysis using standardized staging protocols is warranted to better determine the value of preoperative restaging in these patients.

Development of integrin-targeted cancer therapies is hindered by incomplete understanding of integrin function in tumor cells and the tumor microenvironment. Previous studies showed that mice with epidermis-specific deletion of the α3 integrin subunit fail to form skin tumors during two-step chemical tumorigenesis, indicating a pro-tumorigenic role for integrin α3β1. Here we generated mice with tamoxifen-inducible, epidermis-specific α3 knockout to determine the role of α3β1 in the maintenance of established tumor cells and/or the associated stroma. Genetic ablation of α3 in established skin tumors caused their rapid regression, indicating that α3β1 is essential to maintain tumor growth. Interestingly, while reduced proliferation and increased apoptosis were observed in α3β1-deficient tumor cells, these changes followed a robust increase in stromal apoptosis. Furthermore, macrophages and fibulin-2 levels were reduced in stroma following α3 deletion from tumor cells. Mass spectrometric analysis of conditioned medium from immortalized keratinocytes showed that α3β1 regulates a substantial fraction of the keratinocyte secretome, including fibulin-2 and macrophage colony-stimulating factor 1; RNA in situ hybridization showed that expression of these two genes was reduced in tumor keratinocytes in vivo. Our findings identify α3β1 as a regulator of the keratinocyte secretome and skin tumor microenvironment, and as a potential therapeutic target.

Highlights • CSF enhancement on post-contrast FLAIR images is a novel marker for BBB leakage. • This neuroradiological marker is frequently observed in neurological diseases. • Post-contrast FLAIR CSF enhancement is associated with higher age and brain atrophy. • There is large methodological heterogeneity between studies that use this technique. • We provide recommendations for future methodological standardization., Cerebrospinal fluid (CSF) enhancement on T2-weighted post-contrast fluid-attenuated inversion recovery (pcT2wFLAIR) images is a relatively unknown neuroradiological marker for gadolinium-based contrast agent extravasation due to blood–brain barrier (BBB) disruption. We systematically reviewed human studies reporting on CSF enhancement on pcT2wFLAIR images to provide a comprehensive overview of prevalence of this new biomarker in healthy and diseased populations as well as its etiology and optimal detection methodology. We extracted information on the prevalence of CSF enhancement, its vascular risk factor and neuroimaging correlates, and methodological attributes of each study. Forty-four eligible studies were identified. By pooling data, we found that the prevalence of CSF enhancement was 82% (95% confidence interval (CI) 80–89) in meningitis (4 studies, 65 patients), 73% (95%CI 62–81) in cases with (post-) acute intracerebral hemorrhage (2 studies, 77 cases), 64% (95% CI 54–73) in cases who underwent surgery for aneurysm treatment (2 studies, 99 patients), 40% (95% CI 30–51) in cases who underwent surgery for carotid artery disease treatment (3 studies, 76 patients), 27% (95% CI 25–30) in cases with acute ischemic stroke (9 studies, 1148 patients), 21% (95% CI 17–23) in multiple sclerosis (6 studies, 897 patients), and 13% (95% CI 7–21) in adult controls (4 studies, 112 cases). Presence of CSF enhancement was associated with higher age in eleven studies, with lobar cerebral microbleeds in one study, and with cerebral atrophy in four studies. PcT2wFLAIR imaging represents a promising method that can provide novel perspectives on BBB leakage into CSF compartments, with the potential to reveal important new insights into the pathophysiological mechanisms of varying neurological diseases.

The APOE-epsilon 4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-epsilon 4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1 beta, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau(181) and amyloid-beta(1-42) (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-epsilon 4 genotype. This suggests that APOE-epsilon 4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD. (C) 2019 The Author(s). Published by Elsevier Inc.

The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging contrast. In addition, we investigated which white matter region of interest (ROI) could predict clinical diagnosis best using diffusion metrics. One hundred three older individuals with varying cognitive impairment levels were included and underwent neuroimaging. Diffusion metrics were extracted from WMSA areas based on T1 and FLAIR contrast and from their overlapping areas, the border surrounding the WMSA and the normal-appearing white matter (NAWM). Regional diffusivity differences were calculated with linear mixed effects models. Multinomial logistic regression determined which ROI diffusion values classified individuals best into clinically defined diagnostic groups. T1-based WMSA showed lower white matter integrity compared to FLAIR WMSA-defined regions. Diffusion values of NAWM predicted diagnostic group best compared to other ROI's. To conclude, T1- or FLAIR-defined WMSA provides distinct information on the underlying white matter integrity associated with cognitive decline. Importantly, not the "diseased" but the NAWM is a potentially sensitive indicator for cognitive brain health status.

Fatigue is one of the most prevalent and impactful symptoms for people with multiple sclerosis (MS). Yet, fatigue is less understood in progressive forms of MS, and few studies have explored the extent to which MS disease course is associated with fatigue. The current study aimed to (1) describe fatigue severity and fatigue interference (the extent to which fatigue interferes with individuals' physical, mental, and social activities) in people with progressive MS (primary progressive MS and secondary progressive MS); (2) compare fatigue severity and fatigue interference in people with progressive forms of MS to people with relapsing-remitting MS (RRMS); and (3) identify factors associated with fatigue severity and fatigue interference in people with progressive forms of MS and RRMS.Secondary analysis of baseline data from participants with MS (N = 573; progressive forms of MS n = 142; RRMS n = 431) in a survey-based longitudinal study on healthy aging in people with a physical disability. Primary outcomes were average fatigue severity (0-10 Numerical Rating Scale), and fatigue interference (PROMIS Fatigue Short Form). Correlates were variables across the demographic and biopsychosocial domains, collected with validated self-reported measures. Statistical methods included t-test and chi-square analyses to compare fatigue severity and fatigue interference in people with progressive MS to those with RRMS, and multiple regression analyses to examine the association of variables with fatigue severity and fatigue interference.Participants with progressive forms of MS reported moderate to severe levels of average fatigue severity (5.9 ± 2.8) and elevated levels of fatigue interference (T-Score of 58.2 ± 7.9). There were no group differences between people with progressive MS and RRMS in average fatigue severity or fatigue interference. Common factors associated with greater fatigue severity were lower income, being unemployed, shorter disease duration, greater disability, and greater sleep disturbance. Common factors associated with fatigue interference were younger age, lower income, being unemployed, greater disability, lower alcohol consumption, being a smoker, and greater sleep disturbance. For those with progressive forms of MS, longer MS disease duration was associated with lower average fatigue severity (b = -0.08, t(532) = -3.69, p.001) and having a college degree or higher was associated with higher fatigue interference (b = 2.84, t(520) = 2.23, p = .026).In this sample, fatigue severity and fatigue interference were similar for progressive forms of MS and RRMS. Future research should consider if interventions that work for fatigue management in people with relapsing forms of MS work similarly for people with progressive forms of MS.

To describe the rate and severity of gestational hypertensive disorders (GHDs) in pregnancies complicated by trisomy 13 (T13).Retrospective cohort study of singleton deliveries in California from 2005 to 2008 using vital statistics and ICD-9 data. We were interested in gestational hypertension (gHTN), preeclampsia with and without severe features (sPREX and PREX), and gestational age at delivery. Pregnancies and maternal complications affected by prenatally diagnosed T13 were compared to unaffected pregnancies. Regression models were used to compute adjusted odds ratios for pregnancy outcomes by T13 status.Of the 2,029,004 deliveries, 142 women had prenatally diagnosed T13. A diagnosis of GHD occurred in 26.8% of the T13 pregnancies versus 6% of the non-T13 pregnancies (p .001). This remained true for gHTN (9.2% versus 3.2%, p=.001), PREX (12% versus 2.2%, p .001), and sPREX (8.5% versus 0.9%, p .001). After adjusting for confounders, T13 pregnancies were 6.3-times more likely to be affected by GHD, and 12.5-times more likely to have sPREX. Delivery37 and32 weeks in the setting of GHD was 14.1-times and 11.2-times likely among women with T13.Women with T13 pregnancies were significantly more likely to have gHTN, preeclampsia, sPREX, and to deliver32 weeks.

SUMMARY: Pericortical enhancement on postcontrast FLAIR images is a marker for subtle leptomeningeal blood-brain barrier leakage. We explored the optimal FLAIR sequence parameters for the detection of low gadolinium concentrations within the CSF. On the basis of phantom experiments and human in vivo data, we showed that detection of subtle pericortical enhancement can be facilitated by using a relatively long TE. Future studies should choose their FLAIR sequence parameters carefully when assessing pericortical enhancement due to subtle blood-brain barrier leakage.

Objective To characterize home phototherapy treatment for neonatal hyperbilirubinemia and assess the risk factors associated with the need for hospital admission during or after home phototherapy. Study design This was a retrospective study of newborn infants born at ≥35 weeks of gestation who underwent comprehensive home phototherapy (that included daily in-home lactation support and blood draws) over an 18-month period. We excluded infants who lacked a recorded birth date or time, started treatment at age >14 days, or had a conjugated serum bilirubin level of ≥2 mg/dL (≥34.2 μmol/L). The primary study outcome was any hospital admission during or within 24 hours after completion of home phototherapy. Logistic regression was used to identify risk factors for hospitalization. Results Of the cohort of 1385 infants, 1324 met the inclusion criteria. At the time home phototherapy was initiated, 376 infants (28%) were at or above the American Academy of Pediatrics phototherapy threshold. Twenty-five infants required hospitalization (1.9%; 95% CI, 1.3%-2.8%). Hospital admission was associated with a younger age at phototherapy initiation (OR, 0.63 for each day older in age; 95% CI, 0.44-0.91) and a higher total serum bilirubin level relative to the treatment threshold at phototherapy initiation (OR, 1.71 for each 1 mg/dL above the treatment threshold; 95% CI, 1.40-2.08). Conclusions Comprehensive home phototherapy successfully treated hyperbilirubinemia in the vast majority of the infants in this cohort.

The aim of this commentary is to expand upon results of previously published work on improving nutrition of cafeteria lunches in elementary schools of a high-need school district in southern Colorado, USA, between 2009 and 2015. The intent of the program was to improve the quality of school lunches by training cafeteria staff to prepare meals from scratch using fresh produce and minimally processed proteins as well as to reduce the sodium, sugar, and fat content of the food prepared. The program was successful in improving the quality and nutritional content of school lunch entrees by providing more entrees made from scratch with fresher options and decreasing the amount of processed foods served. This study shows that interventions aimed at changing the food preparation policies of school cafeterias can improve the nutrition of school lunches, and future research should expand on the benefits schools may experience by investing in similar programs.

Objective Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid beta (A beta) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood. Methods We scanned intact formalin-fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions. Results In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole-brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of A beta-positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both A beta (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but A beta was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular A beta was almost always observed at the core of the lesion (91%, p

Background. Colorado passed House Bill 11-1069 in 2011 requiring all public elementary schools to provide students with a minimum of 30 minutes of physical activity (PA) per school day (Physical Activity Expectation in Schools, 2011). The purpose of this article is to describe the results of a 3-year initiative to increase opportunities for PA and to provide recommendations for school health practitioners implementing similar programming. Intervention. In 2014, 13 school districts were funded to increase student PA during school hours and before and after school hours. Intervention activities spanned all components of the Comprehensive School Physical Activity Program framework. An evaluation was conducted to estimate the number of schools providing at least 30 minutes of PA a day. A mixed methods evaluation design was implemented that included tracking the number of minutes of PA provided before, during, and after school and semistructured interviews with school health coordinators. Results. In Year 1, an average of 48 minutes of PA were provided per day. By the end of year 3, the average minutes of PA doubled to 90 minutes per day. Teachers and staff identified professional development and administrator support as key components to incorporating more PA throughout the school day. Conclusions. Health promotion interventions in schools can increase access to PA opportunities for students. Sustainability of PA efforts in schools is dependent on funding to support professional development for teachers and staff and building administrative support for school-based PA.

The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.

Background Unplanned readmissions are costly to family satisfaction and negatively associated with quality of care. We hypothesized that patient, operative, and hospital factors would be associated with pediatric readmission. Methods All patients with an inpatient operation from 10/1/2008 to 7/28/2014 at a freestanding children's hospital were included. A retrospective cohort study using multivariable forward stepwise logistic regression determined factors associated with unplanned readmission within 30 days of discharge. Results Among 20,785 patients with an operation there were 26,978 encounters and 3,092 readmissions (11.5%). Thirteen of 33 candidate variables considered in the stepwise regression were significantly associated with readmission. Patients with an emergency department visit within 365 days of operation, American Society of Anesthesiologists class 4 or greater, Hispanic ethnicity and late-day or holiday/weekend discharges were more likely to have an unplanned readmission (odds ratio [OR] = 1.96; 95% confidence interval [CI] = 1.76 to 2.19, OR = 2.00; 95% CI = 1.58 to 2.53, OR = 1.16; 95% CI = 1.04 to 1.29, OR = 2.27; 95% CI = 1.55 to 3.63. respectively). Conclusions Patient and hospital factors may be associated with readmission. Day and time of discharge represent variability of care and are important targets for hospital initiatives to decrease unplanned readmission.

Decades of research supports the health benefits of breastfeeding. Prior studies have shown that hospital discharge bags containing free samples of infant formula are associated with decreased breastfeeding exclusivity. This study aims to determine if receiving a free sample of infant formula in the mail has an impact on breastfeeding duration and exclusivity.This was a cohort study analyzing data from the Infant Feeding Practices Study II. The main outcomes of interest were any breastfeeding through 12 months of age and exclusive breastfeeding through 6 months of age. The main predictor of interest was receipt of a free sample of infant formula in the mail around the time of the infant's birth. Logistic regression models were developed to evaluate the association between the outcomes and predictor of interest at each month.This study included 3,031 infants; mothers of 1,741 (57.4%) received a sample of infant formula in the mail. There was no difference in the likelihood of any breastfeeding at each month among those who received formula in the mail compared with those who did not. There was also no difference in exclusive breastfeeding through 5 months; however, by 6 months of age infants whose mothers received formula in the mail were less likely to be exclusively breastfed (odds ratio = 0.57; 95% confidence interval, 0.37, 0.89).Receiving infant formula in the mail decreases the likelihood of exclusive breastfeeding by 6 months of age while having no impact on the duration of any breastfeeding.

Data from solid tumor malignancies suggest that actual body weight (ABW) dosing improves overall outcomes. There is the potential to compromise efficacy when chemotherapy dosages are reduced, but the impact of dose adjustment on clinical response and toxicity in hematologic malignancies is unknown. The purpose of this study was to evaluate the outcomes of utilizing a percent of ABW for acute myeloid leukemia (AML) induction chemotherapy dosing.This retrospective, single-center study included 146 patients who received 7 + 3 induction (cytarabine and anthracycline) for treatment of AML. Study design evaluated the relationship between percentage of ABW dosing and complete response (CR) rates in patients newly diagnosed with AML.Percentage of ABW dosing did not influence CR rates in patients undergoing induction chemotherapy for AML (p = 0.83); nor did it influence rate of death at 30 days or relapse at 6 months (p = 0.94). When comparing patients dosed at 90-100 % of ABW compared to90 % ABW, CR rates were not significantly different in patients classified as poor risk (p = 0.907). All favorable risk category patients obtained CR.Preemptive dose reductions for obesity did not influence CR rates for patients with AML undergoing induction chemotherapy and did not influence the composite endpoint of death at 30 days or disease relapse at 6 months.

Medication errors are hazardous and costly. Children are at increased risk for medication errors because of weight-based dosing, limited FDA indications, and human calculation errors. The aim of this study is to determine the frequency and type of resident prescribing errors in a pediatric clinic and further compare error rates of residents in different training programs.Resident prescription error data from a pediatric clinic was collected for 5 months. Upon detection of an error, residents were notified/given feedback regarding the type of error, ways to remedy errors, and future prevention methods. Data were categorized based on medication involved, error type, and resident training program.The review included 2941 prescriptions, with the overall resident prescribing error rate being 5.88%. The pediatric resident error rate was 4%. Family medicine, internal medicine, and medicine/pediatrics had error rates of 11%, 8%, and 7%, respectively. The prescribing error rate showed a statistically significant difference with pediatrics compared with family medicine, internal medicine, and medicine/pediatrics (P0.0005, P = 0.013, and P = 0.03, respectively). The most common medication error type was overdose, followed by unclear quantity. Among the medication classes, topical agents and antimicrobials were among the top prescribed.Numerous types of medication errors occur in a pediatric clinic. Prescribing errors take place among all medical trainees; however, medication error rates in the pediatric population may vary among resident specialty. Identifying the cause of prescribing errors will allow institutions to create educational programs tailored for safe medication use in children as well as systemwide changes for error reduction.

Peer victimization that occurs via electronic media, also termed cybervictimization, is a growing area of concern for adolescents. The current study evaluated the short-term prospective relationship between cybervictimization and adolescents' symptoms of social anxiety and depression over a six-week period. Participants were 839 high-school aged adolescents (14-18 years; 58% female; 73% Hispanic White), who completed measures of traditional peer victimization, cybervictimization, depression, and social anxiety at two time points. Findings supported the distinctiveness of cybervictimization as a unique form of peer victimization. Furthermore, only cybervictimization was associated with increased levels of depressive symptoms over time, and only relational victimization was associated with increased social anxiety over time, after controlling for the comorbidity of social anxiety and depression among youth. Cybervictimization appears to be a unique form of victimization that contributes to adolescents' depressive symptoms and may be important to target in clinical and preventive interventions for adolescent depression.

Proteolytic processing of the laminin-γ2 chain is a hallmark of basement membrane maturation in the skin. Integrin α3β1, a major receptor for epidermal adhesion to laminin-332, is critical for proper basement membrane organization during skin development and wound healing. Previously, we identified a role for α3β1 in promoting the processing of laminin-γ2 in cultured keratinocytes in vitro and in wound epidermis in vivo. In the current study we identify the Bmp1 gene, which encodes variants of the mammalian tolloid/bone morphogenetic protein-1 metalloproteases, as a critical regulator of α3β1-dependent laminin-γ2 processing, thereby expanding the role of this integrin in controlling the secretion by the epidermis of factors that modulate the tissue microenvironment. Since our previous studies identified another epidermal integrin, α9β1, as a suppressive regulator of α3β1-dependent wound angiogenesis, we investigated whether α9β1 has a similar cross-suppressive effect on ability of α3β1 to promote basement membrane organization. Here, we demonstrate that, rather than a cross-suppressive role, α9β1 has an opposing role in basement membrane assembly/maturation through reduced laminin-γ2 processing via mammalian tolloid/bone morphogenetic protein-1. Indeed, while α3β1 promotes this process during wound healing, α9β1 has an inhibitory role, suggesting that regulation of basement membrane assembly requires a complex interplay between these distinct epidermal integrins.

BACKGROUND AND PURPOSE: Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment.MATERIALS AND METHODS: Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals.RESULTS: Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age (P CONCLUSIONS: Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance.

Objective Characterize the impact of a trisomy 18 (T18) fetus on maternal and obstetric outcomes in a cohort including T18-affected deliveries. Study Design Retrospective cohort study of singleton deliveries in California from 2005 to 2008 using linked vital statistics and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) data to compare deliveries affected by T18 to those without known aneuploidy. Outcomes of interest included gestational diabetes mellitus (GDM), preterm delivery (PTD), preeclampsia, cesarean delivery (CD), and intrauterine fetal demise (IUFD). The χ2 and paired t-tests were used to compare the outcomes. Multiple logistic regression was used to further characterize these risks and control potential confounders. Results Of 2,029,000 deliveries, 298 involved T18. Compared with unaffected deliveries, T18 was associated with GDM (10.7 vs. 6.5%, p = 0.003), PTD Conclusion Unlike trisomy 13 (T13), pregnancies complicated by fetal T18 did not appear to result in an increased risk of preeclampsia. However, there is an increased risk of a range of other obstetric complications.

Using a canine model of classical late-infantile neuronal ceroid lipofuscinosis (CLN2 disease), a study was conducted to evaluate the potential pharmacological activity of recombinant human tripeptidyl peptidase-1 (rhTPP1) enzyme replacement therapy administered directly to the cerebrospinal fluid (CSF). CLN2 disease is a hereditary neurodegenerative disorder resulting from mutations in CLN2, which encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Infants with mutations in both CLN2 alleles develop normally but in the late-infantile/early-childhood period undergo progressive neurological decline accompanied by pronounced brain atrophy. The disorder, a form of Batten disease, is uniformly fatal, with clinical signs starting between 2 and 4 years of age and death usually occurring by the early teenage years. Dachshunds homozygous for a null mutation in the canine ortholog of CLN2 (TPP1) exhibit a similar disorder that progresses to end stage at 10.5–11 months of age. Administration of rhTPP1 via infusion into the CSF every other week, starting at approximately 2.5 months of age, resulted in dose-dependent significant delays in disease progression, as measured by delayed onset of neurologic deficits, improved performance on a cognitive function test, reduced brain atrophy, and increased life span. Based on these findings, a clinical study evaluating the potential therapeutic value of rhTPP1 administration into the CSF of children with CLN2 disease has been initiated.

Legionella pneumophila uses the Icm/Dot type 4B secretion system (T4BSS) to deliver translocated protein substrates to the host cell, promoting replication vacuole formation. The conformational state of the translocated substrates within the bacterial cell is unknown, so we sought to determine if folded substrates could be translocated via this system. Fusions of L. pneumophila Icm/Dot-translocated substrates (IDTS) to dihydrofolate reductase (DHFR) or ubiquitin (Ub), small proteins known to fold rapidly, resulted in proteins with low translocation efficiencies. The folded moieties did not cause increased aggregation of the IDTS and did not impede interaction with the adaptor protein complex IcmS/IcmW, which is thought to form a soluble complex that promotes translocation. The translocation defect was alleviated with a Ub moiety harboring mutations known to destabilize its structure, indicating that unfolded proteins are preferred substrates. Real-time analysis of translocation, following movement during the first 30 min after bacterial contact with host cells, revealed that the folded moiety caused a kinetic defect in IDTS translocation. Expression of an IDTS fused to a folded moiety interfered with the translocation of other IDTS, consistent with it causing a blockage of the translocation channel. Furthermore, the folded protein fusions also interfered with intracellular growth, consistent with inefficient or impaired translocation of proteins critical for L. pneumophila intracellular growth. These studies indicate that substrates of the Icm/Dot T4SS are translocated to the host cytosol in an unfolded conformation and that folded proteins are stalled within the translocation channel, impairing the function of the secretion system.

Adenosis (atypical adenomatous hyperplasia) is a benign lesion that morphologically mimics prostate adenocarcinoma, although the relationship between these 2 lesions is still debated. The TMPRSS2-ERG fusion is a common chromosomal rearrangement that occurs early in the development of invasive adenocarcinoma of the prostate and results in the expression of a truncated ERG protein. This fusion is present in 50% of adenocarcinomas and in 20% of high-grade prostate intraepithelial lesions. Until recently, fluorescent in situ hybridization was the only method available to detect these rearrangements. A specific anti-ERG antibody is now available for detecting ERG protein expression and serves as a useful marker for ERG rearrangements. Formalin-fixed, paraffin-embedded tissue sections of adenosis from cases of prostate biopsies (n = 30), transurethral resections of the prostate (n = 12), and radical prostatectomies (n = 3) were analyzed via immunohistochemistry for ERG. None (0%) of the foci of adenosis were positive for ERG protein expression. Of 40 cases of Gleason score 6 adenocarcinoma on a tissue microarray, 22 (55%) were positive for ERG protein. Of the positive cases, 14 (63.6%) were moderate in intensity, with the remaining 36.4% being weak. The lack of ERG expression in adenosis supports the notion that it is not a precursor lesion of adenocarcinoma. Moreover, it suggests that immunohistochemistry for ERG expression could be a useful tool to differentiate adenosis from adenocarcinoma.

BackgroundDespite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nut allergies.MethodsPatients (n=60, aged 4-15 years), recruited for a multiple food (tree nuts, peanut, milk, egg, soy, sesame, and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFCs) to foods still eliminated.ResultsThere was significantly less evidence for eliminating tree nuts compared with other foods, as reflected by a lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20-40% for other foods, respectively P0.001) or later in life (14.5% vs. 38-75%, respectively P=0.001), and a higher rate of negative skin prick test (SPT)/specific IgE (sIgE) at initial diagnosis (25% vs.10%, P0.001). SPT/sIgE increased significantly from past initial levels to present for tree nuts (P0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive.ConclusionsTree nuts are often eliminated from the diet of multiple-food-allergic patients, despite their low probability for allergy. Sensitization and allergy to most tree nuts exist years later, suggesting that it developed during the period of elimination.

The management of recurrent soft tissue sarcoma is a challenging problem for clinicians and has a significant physical, mental, emotional, and oncologic impact for the patient. Despite excellent limb-preservation therapies, approximately one-quarter of patients may eventually develop recurrence of disease. How to most appropriately manage these patients is a matter of debate. Several treatment options exist, including surgical resection, irradiation, systemic chemotherapy, amputation, and regional therapies. This article highlights the management of recurrent extremity soft tissue sarcoma.

Objective This study aims to evaluate the perinatal and neonatal outcomes associated with prenatal diagnosis of 45,X, both with and without fetal cardiac anomalies. Study Design A retrospective cohort of singleton pregnancies in California, 2005 to 2008, using vital statistics and International Classification of Diseases, Ninth Revision data, identifying prenatally diagnosed 45,X. Outcomes included preterm delivery, preeclampsia, intrauterine fetal demise (IUFD), cesarean section, small for gestational age (SGA), neonatal death, and infant death. Bivariate and multivariate analyses were used to compare pregnancies and neonates with and without 45,X. Prenatally diagnosed cardiac anomalies were also considered. Results Of the 2,029,000 deliveries, 138 had prenatally diagnosed 45,X. Out of these 138 deliveries, 22 had a prenatally diagnosed cardiac anomaly. Compared with unaffected pregnancies, those with fetal 45,X had higher rates of preterm delivery (19.5 vs. 9.9%, p = 0.001), cesarean section (44.2 vs. 30.2%, p < 0.0001), and SGA (21.5 vs. 6.3%, p < 0.0001). The affected cohort had no IUFDs. Neonatal death was 14.5 times higher in the 45,X cohort (p < 0.0001). Of only infants with cardiac anomalies, neonatal death was significantly more likely in those with 45,X (p = 0.005). In adjusted analysis, risk of SGA (< 3rd percentile), neonatal death, and infant death remained increased for infants with 45,X while controlling for fetal cardiac anomalies. Conclusion Prenatally diagnosed 45,X was associated with increased risk of cesarean section, and adverse neonatal outcomes, including mortality.

Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants’ language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non–SRI-treated mothers with little or no depression (control), depressed but non–SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.

Stressors ranging from nutrient deprivation to immune signaling can induce the degradation of cytoplasmic material by a process known as autophagy. Increasingly, research on autophagy has begun to focus on its role in inflammation and the immune response. Autophagy acts as an immune effector that mediates pathogen clearance. The roles of autophagy bridge both the innate and adaptive immune systems and include functions in thymic selection, antigen presentation, promotion of lymphocyte homeostasis and survival, and regulation of cytokine production. In this review, we discuss the mechanisms by which autophagy is regulated, as well as the functions of autophagy and autophagy proteins in immunity and inflammation.

There is now ample documentary evidence to show that poverty—and the physical, intellectual, and emotional deprivations that go with it—can be a direct cause of mental retardation. The poor of all races are affected and—in absolute numbers—there are more whites than Negroes who suffer from it. I am, however, particularly interested in this subject because the Negro poor are victimized by this alarming situation more than others, since, in relative numbers, there are far more poor Negroes than poor whites. Too many children, and all too frequently, Negro children, thus pay a heavy price for the injustices of our society. We know today that only a few among all those who are mentally retarded suffer from an obvious organic defect with genetic cause. Genetic defects affect all levels of society in the same way, whether those afflicted are rich or poor, white or Negro. But it is quite different when damage to the brain is due not to a genetic cause but to disease before or after birth, or else to accident, infection, or poisoning. The poor, whether they are white or Negro, are more often its victims. And the mentally retarded who do not show any organic brain damage—those who are only functionally retarded—come predominantly from the poorer sections of our society. Functional retardation is very rare among those with high incomes and among well educated segments of the community. But it is very common—it can be detected in as many as 15 percent of all children—in deprived rural areas and in the chaos of the inner cities. This is now so well accepted that we have given the name of ‘‘socio-environmental retardation’’ to this kind of functional retardation prevalent among the deprived. More than half of all mentally retarded people fall into this last category. What in fact are the environmental factors in the life of the poor that stunt their intellectual development? To begin with, we are now convinced that intelligence itself is largely controlled by the kind of diet a child receives. Evidence was presented at a recent International conference that malnutrition in the first three years of life may permanently impair intelligence and it has been estimated that more than half of the 90 million babies born each year may run a risk of permanent retardation resulting from malnutrition. Moreover, experiments with several kinds of laboratory animals suggest that malnutrition at certain critical times EDITOR’S NOTE: The Whitney M. Young article was based on a presentation at the national AAMD conference in 1968 and published later in volume 7 of Mental Retardation. At the end of the decade of the 1960s the Civil Rights Movement had statutorily established equal rights and access but the dayto-day reality of the nation was a ‘‘de facto’’ segregation based on race, poverty, and privilege. Young was a social worker and civil rights activist in the 1950s, and prior to assuming the Executive Director of the Urban League, the Dean of the School of Social Work at Atlanta University. Under his leadership and vision, the Urban League moved from an organization focused on social welfare to a force for social justice. When ‘‘Poverty, intelligence and life in the inner city’’ was published, IDD was largely framed by the field in terms of the challenges of service and care, while notions of civil or even human rights were only just beginning to establish a toehold. In my earlier commentary I referred to Young’s article as ‘‘prescient.’’ In this paper, the issue of bias and overrepresentation of IDD among African Americans is the ostensible focus. But the themes addressed by Young go well beyond notions of cultural bias and engage questions about risk that is embedded in social, cultural, and economic inequities. These themes were not necessarily new in 1969 but they remain as relevant now as then. Over this past half century, the IDD field has visited and re-visited this intersection of race and poverty. And you will note their relevance throughout the goals generated across the 10 working groups of the National Goals meeting. While I implied in my commentary that Young’s appeal to the ‘‘elite of our citizenry’’ for solutions was something of a relic from another era, his call for the direct engagement of the disability field in the broader debate on income inequality still rings true.