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Medulloblastoma is the most common malignant brain tumor in childhood. Initial treatment generally includes surgery, irradiation, and chemotherapy. Approximately 20–30% of patients will experience a recurrence, which portends a very poor prognosis. The current standard of care for evaluation for relapse includes radiographic surveillance with magnetic resonance imaging at regular intervals. The presence of circulating tumor DNA in the cerebrospinal fluid has been demonstrated to be a predictor of a higher risk of progression in a research setting for patients with medulloblastoma treated on a prospective single institution clinical trial. We have previously published and clinically validated a liquid-biopsy-based genetic assay utilizing low-pass whole genome sequencing to detect copy number alterations in circulating tumor DNA. Here, we present two teenage patients with posterior fossa medulloblastoma with recurrent disease who have been monitored with serial liquid biopsies showing tumor evolution over time, demonstrating the clinical utility of these approaches. [ABSTRACT FROM AUTHOR]

Social determinants of health (SDH) have been found to be important contributors to postoperative outcomes, especially those related to procedures that require significant postoperative resources. The association between short-term gastrostomy tube (GT) outcomes and SDH in the pediatric population is unknown. A retrospective review was performed of all patients less than 18 y old who received a GT between January 2018 and December 2020 at a single institution. Data including demographics, area deprivation index (ADI), and perioperative information were collected. Patient characteristics were compared in those that did and did not have an unexpected emergency department (ED) visit within 6 wk of discharge from GT placement. Statistical analysis was performed using Wilcoxon sum-rank, Chi-squared test, and Fisher's exact test where applicable, and univariable and multivariable logistic regression. Of the 541 children who underwent GT placement, 112 (20.7%) returned to the ED within 6 wk postdischarge. In univariable analysis, Black children had 1.64 the odds of an unexpected ED visit compared to White children (95% confidence interval [CI] 1.04-2.60, P = 0.03). When controlling for ethnicity, primary language, insurance, ADI and comorbidities, Black children had 1.80 the odds of an unexpected ED visit compared to White children (95% CI 1.10-2.97, P = 0.02). Final model fit which added a race by ADI interaction term revealed Black children had 2.52 the odds of an unexpected ED visit compared to White children in the low (1-6) ADI group (95% CI 1.41-4.60, P = 0.002). Within advantaged neighborhoods (ADI 1-6), the probability of unplanned ED visits for White children was 17.3% (95%CI 8.9% - 31.1%), which was significantly lower than that for Black children (34.6%, 95% CI 18.8% - 54.7%; P value = 0.006). Race and neighborhood disadvantage can be associated with unexpected ED visits within 6 wk of discharge from GT placement in the pediatric population. For procedures that require significant postdischarge resources it is important to study the effect of SDH on return to the healthcare system as they can be an important driver of disparities in outcomes. [ABSTRACT FROM AUTHOR]

Objective: To understand the mechanisms of mindfulness' impact on migraine. Background: Promising mindfulness research demonstrates potential benefit in migraine, but no data‐driven model exists from the lived experiences of patients that explains the mechanisms of mindfulness in migraine. Methods: Semi‐structured qualitative interviews were conducted with adults with migraine who participated in two mindfulness‐based stress reduction (MBSR) clinical trials (n = 43). Interviews were audio‐recorded, transcribed, and summarized into a framework matrix with development of a master codebook. Constructivist grounded theory approach was used to identify themes/subthemes. Results: Participants who learned mindfulness techniques through MBSR experienced altered pain perception, altered response to migraine attacks and disease, increased awareness of external and internal experiences, improved overall well‐being, and group benefits. Mindfulness resulted in earlier stress‐body awareness and increased interoceptive awareness resulting in earlier attack recognition, leading to earlier and more effective management. Interictal factors of self‐blame, guilt, and stigma decreased while migraine acceptance, hope, empowerment, self‐efficacy, and self‐compassion increased. Improved emotion regulation resulted in decreased fear of migraine, pain catastrophizing, anticipatory anxiety, and pain reactivity. Although taught as prevention, mindfulness was used both acutely and prophylactically. We created a conceptual model hypothesizing that MBSR skills led to an infusion of mindfulness in daily life, resulting in altered pain perception and experience, ultimately leading to improvement in overall well‐being, which may positively feed back to the infusion of mindfulness in daily life. The therapeutic benefit of learning mindfulness in a group setting may moderate these effects. Conclusions: This study identified several new potential mechanisms of mindfulness' effect on migraine. After learning MBSR skills, participants reported altered pain and migraine perception and experiences. Increased stress‐body and interoceptive awareness resulted in earlier migraine awareness and treatment. Mindfulness may target important interictal factors that affect disease burden such as fear of migraine, pain catastrophizing, and anticipatory anxiety. This is the first data‐driven study to help elucidate the mechanisms of mindfulness on migraine from patient voices and can help direct future research endeavors. [ABSTRACT FROM AUTHOR]

Dispersal is well recognized as a major driver of evolutionary processes in local populations. Nevertheless, dispersal abilities should also be perceived as a life‐history trait, being subject to evolutionary changes in response to various drivers. Empirical studies investigating these drivers rarely consider that they may influence male and female dispersal differently. The purpose of our study was to document intersexual differences in density‐dependent emigration from local habitat patches. As a model system, we used a metapopulation of Maculinea (Phengaris) teleius butterfly, in which densities of both sexes vary greatly throughout the flying season. Following intensive mark–release–recapture surveys, the parameters and predictors of dispersal were analysed with the Virtual Migration model and the multi‐state recapture model. The emigration rate in males was substantially higher in the early season, especially at smaller habitat patches. With the proportion of females increasing with the season progression, males became reluctant to emigrate from their natal patches. In turn, higher female emigration in the later part of the season was most strongly associated with female tendency to reduce intraspecific competition experienced by their offspring. Our findings provide evidence for the impact of reproductive strategies on dispersal in both sexes. The difference in reproductive strategies of males and females explains sex‐biased dispersal in different parts of the season, which carries important implications for metapopulation functioning. [ABSTRACT FROM AUTHOR]

Objective: To assess the overall readability of five currently available hyperacusis questionnaires and to assess the variability of single items within each questionnaire. Design: Comparative study of self-report hyperacusis questionnaires: (1) Geräuschüberempfindlichkeits-Fragebogen (GUF), (2) Noise Avoidance Questionnaire (NAQ), (3) Hyperacusis Questionnaire (HQ), (4) Sound Sensitive-Tinnitus Index (SSTI), and (5) Inventory of Hyperacusis Symptoms (IHS). Well-established readability formulas Flesh-Kincaid Grade Level (FKGL), Flesch Reading Ease (FRE), Simple Measure of Gobbledygook (SMOG) and FORCAST and a computerised readability calculation software were used. Study sample: Five questionnaires. Results: Reading levels calculated by each formula varied for every questionnaire. Readability scores ranged from 7.7th to 12.7th grade for overall readability depending on the questionnaire. This exceeded the grade reading levels of 5th–6th grade (10–12 years old) as recommended by the American Medical Association or 7th–8th grade (12–14 years old) as recommended by the US National Institutes of Health. Single item readability analysis based on FKGL revealed that 32%–70% of single items are written above the recommended grade levels. Conclusion: All five questionnaires are written at close to or exceeding the recommended grade levels. This requires attention from developers but also when interpreting the questionnaire scores obtained in clinic. [ABSTRACT FROM AUTHOR]

Large panel sizes are often held responsible for worse access to appointments in primary care. We evaluated the relationship between appointment backlog, panel size, and primary care clinician time in clinic, using Spearman correlation and multiple regression in a retrospective analysis. We found no independent association between panel size and days until third next available appointment, but larger panel size adjusted for clinician time in clinic was associated with worse access. Less clinician time in clinic was independently associated with longer backlogs for appointments. Our findings suggest that patients of part-time clinicians may be less likely to obtain timely appointments than patients of fulltime clinicians, regardless of panel size. [ABSTRACT FROM AUTHOR]

This study develops a framework for analyzing the judgments handed down by courts in malpractice cases. We analyzed 215 cases that included awards for damages caused by medical negligence, handled by Israeli courts from 2005 to 2011. The Pareto principle coupled with the mean square error criterion supports the selection of the vital hospital departments and the vital causes of claims. A quality function deployment matrix is used to translate the desired improvement in malpractice costs into relevant medical decisions and diagnostic tests. Based on the analysis, we can conclude that the essential part of all malpractice claims submitted to and found legitimate by the courts was related to the obstetrics field. We reveal that most claims have elements in common. When we based the analysis on the malpractice compensation, covering costs of corrective treatment, suffering, future medical treatment, and associated legal fees, based on court data, we found that the group of vital causes decreased. In this study, we analyze claims related to the obstetrics department. Other departments where errors are frequently made should be addressed in turn, with the objective of continuously improving the medical system. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Malignant rhabdoid tumor (MRT) can occur in the kidney, central nervous system, or extracranial/extrarenal locations and is characterized by alterations in the SMARCB1 gene. The tumors occur in infants and young children and confer a poor prognosis requiring aggressive therapeutic interventions to improve the chances for survival. MRTs pose a diagnostic challenge, as they display heterogeneous histopathologic features and differentiate along multiple lineages. The identification of alterations in the SMARCB1 gene in MRT using immunohistochemical (IHC) staining has lead to improved diagnosis of MRT as well as the discovery of the loss of SMARCB1 expression in some non-MRTs. Whether loss of SMARCB1 plays a pathogenic role in nonrhabdoid tumors remains to be determined; however, most of these tumors lack the clinical and other molecular features of MRT. We review the histopathologic features of MRT and the importance and significance of loss of expression of SMARCB1 in both MRT and nonrhabdoid tumors. [ABSTRACT FROM AUTHOR]

We report a comparative analysis of three-layered poly(ethylene terephthalate) films. The first set of three-layered films was prepared entirely from virgin poly(ethylene terephthalate). The second set of films was prepared from a recycled poly(ethylene terephthalate) core layer and virgin poly(ethylene terephthalate) skin layers. The resistance of the films to impact was tested using the free falling drop dart method. The selected strength properties of various thicknesses of these films were also tested. It was shown that the poly(ethylene terephthalate) film containing a layer of recycled polymer has properties similar to the film obtained from virgin polymer and can thus be successfully used in the manufacturing of packaging materials. [ABSTRACT FROM AUTHOR]

Purpose: Enhanced recovery protocols [ERPs] standardize care and have been demonstrated to improve surgical quality in adults. We retrospectively compared outcomes before and after implementation of ERPs in children undergoing elective laparoscopic cholecystectomy [ELC] surgery.Methods: A pediatric-specific ERP was implemented for children undergoing ELC at one [C1] of the two Pediatric Surgical Centers in July 2016. We retrospectively reviewed 606 patients undergoing ELC between July 2014 and December 2019. Of these, 206 patients underwent ELC prior to ERP implementation [Pre-ERP] were compared to 400 patients undergoing ELC managed in the post-ERP implementation period (between January 2017 and December 2019), 21 of which were managed by enhanced recovery protocol. Primary Outcomes included immediate peri-operative and post-operative narcotic use in mean morphine equivalents [MME], narcotics at discharge, complications, nurse calls and returns to system [RTS].Results: There was a significant decrease in opioid use both post-operatively and at time of discharge in the ERP managed cohort. The MME use during the post-operative period was 0.85 in the in ERP-compliant patients compared to 6.40 in the non-compliant group (p < 0.027). Eighty-six percent of ERP-compliant patients in the study required no narcotics at discharge, which was statistically significant when compared to ERP non-compliant cohort (p < 0.0001). There was also no change in RTS, nurse calls or complications. In addition, in the post-ERP period (2017-2019), a dominant proportion of patients at C1 partially complied with the ERP, resulting in a statistically significantly decrease of opioid use between sites in the post-op period (6.54 vs 10.57 MME) post-ERP (p < 0.001). Similar effects were noted in discharge narcotics.Conclusion: The use of pediatric-specific ERP in children undergoing ELC is safe, effective, and provides compassionate pain control while leading to a reduction in opioid use peri-operatively and at discharge. This improvement occurred without changes in RTS, nursing calls or complications.Level Of Evidence: Level III; Retrospective study. [ABSTRACT FROM AUTHOR]

Background Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy. [ABSTRACT FROM AUTHOR]

Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif. [ABSTRACT FROM AUTHOR]

Objective: To better characterize the ways that migraine affects multiple domains of life. Background: Further understanding of migraine burden is needed. Methods: Adults with migraine randomized to mindfulness‐based stress reduction or headache education arms (n = 81) in two separate randomized clinical trials participated in semistructured in‐person qualitative interviews conducted after the interventions. Interviews queried participants on migraine impact on life and were audio‐recorded, transcribed, and summarized into a framework matrix. A master codebook was created until meaning saturation was reached and magnitude coding established code frequency. Themes and subthemes were identified using a constructivist grounded theory approach. Results: Despite most participants being treated with acute and/or prophylactic medications, 90% (73/81) reported migraine had a negative impact on overall life, with 68% (55/81) endorsing specific domains of life impacted and 52% (42/81) describing impact on emotional health. Six main themes of migraine impact emerged: (1) global negative impact on overall life; (2) impact on emotional health; (3) impact on cognitive function; (4) impact on specific domains of life (work/career, family, social); (5) fear and avoidance (pain catastrophizing and anticipatory anxiety); and (6) internalized and externalized stigma. Participants reported how migraine (a) controls life, (b) makes life difficult, and (c) causes disability during attacks, with participants (d) experiencing a lack of control and/or (e) attempting to push through despite migraine. Emotional health was affected through (a) isolation, (b) anxiety, (c) frustration/anger, (d) guilt, (e) mood changes/irritability, and (f) depression/hopelessness. Cognitive function was affected through concentration and communication difficulties. Conclusions: Migraine has a global negative impact on overall life, cognitive and emotional health, work, family, and social life. Migraine contributes to isolation, frustration, guilt, fear, avoidance behavior, and stigma. A greater understanding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine. [ABSTRACT FROM AUTHOR]

Outcome analysis showed overall survival in patients with infratentorial IDH-mutant astrocytomas to be longer than those with diffuse midline gliomas, but shorter than patients with supratentorial IDH-mutant astrocytomas, specifically those classified as "low grade" by methylation subclass. Keywords: brain biopsy; brainstem glioma; IDH; isocitrate dehydrogenase; low grade glioma; young adult EN brain biopsy brainstem glioma IDH isocitrate dehydrogenase low grade glioma young adult 1 5 5 07/05/21 20210701 NES 210701 Isocitrate dehydrogenase (IDH) mutations are rare in pediatric and adolescent gliomas. Brainstem gliomas are very rare in adults, but approximately 10% of pediatric CNS tumors occur in this location, with diffuse midline glioma, K27M-mutant representing most cases. Brain biopsy, brainstem glioma, IDH, isocitrate dehydrogenase, low grade glioma, young adult. [Extracted from the article]

Primary diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare tumors, recently recognized as a unique entity based on their unique pathologic and clinical characteristics. We report three cases of DLGNT and compare their clinical characteristics and presentation with other reported cases, and with primary leptomeningeal gliomatosis. Because their prognosis is better than that of diffuse leptomeningeal gliomatosis, and pathologic diagnosis may be difficult, clinicians should consider this diagnosis in patients who present with new neurological symptoms, hydrocephalus and diffuse leptomeningeal enhancement on MRI. Further studies are required to better understand the unique biological characteristics of these tumors and to improve therapy. [ABSTRACT FROM AUTHOR]

Objectives: 1. Roll out telemedicine tools to adults using any cochlear implant device in the UK 2. Commission a formal evaluation to establish whether the new care model improves: • patient empowerment • equity of access • patient and staff experience • clinic efficiency Methods We will introduce a remote care pathway choice to adults using cochlear implants in participating centres in the UK. Benefits will be available to users of any device. This is a complex intervention comprising four components successfully trialled together previously: • personalised responsive web app (hearing rehabilitation, music, advice, troubleshooting, training, ordering spares, goal setting, questionnaires, reminders, monitoring of implant site photos) • home hearing test • self device adjustment at home (with appropriate device) • upgrading of sound processors at home Clinicians will access an online dashboard to monitor their patients, and will receive alerts if patients are not interacting with the tools or other indicators are achieved. Conclusions : We previously completed an RCT of remote care tools. We examined patient preference using conjoint analysis; the main outcome evaluated was patient empowerment. The remote care group had a significant increase in empowerment after using the telemedicine tools. Their hearing improved, suggesting better ability to take action to keep hearing stable. Patients and clinicians were very positive about remote care and wanted to continue. We need high quality evidence that a remote care pathway delivers our aims. An independent evaluation will be done to establish if the new care model improves: 1. patients' confidence to self-manage 2. stability of hearing as a result of self-initiated monitoring and action 3. equity of access to follow-up care 4. patients' experience of care 5. staff experience 6. use of resources [ABSTRACT FROM AUTHOR]

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA ( n = 72) and EPN_PFB tumors ( n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts ( n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Atypical teratoid rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) tumors that occur mostly in young children and have historically carried a very poor prognosis. While recent clinical trial results show that this tumor is curable, outcomes are still poor compared to other central nervous system embryonal tumors. We here review prior AT/RT clinical trials and highlight promising pre-clinical results that may inform novel clinical approaches to this aggressive cancer. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were: to evaluate the prevalence of abdominal wall defects in the Polish population, to analyze temporal trends in the prevalence, to identify areas (clusters) of high risk of abdominal wall defects, and to characterize, with respect to epidemiology, children with abdominal wall defects and their mothers in the area defined as a cluster.Material and Methods: We used isolated congenital malformations (gastroschisis Q79.3 and omphalocele Q79.2 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10, the extended version)) data reported to the Polish Registry of Congenital Malformations (PRCM) over the years 1998- 2008 based on the population of 2 362 502 live births. We analyzed 11 administrative regions of Poland with complete epidemiologic data.Results: Of 11 regions, 2 had a significantly higher standardized prevalence of isolated gastroschisis: Dolnośląskie (1.7/10 000 live births, p = 0.0052) and Śląskie (1.9/10 000 live births, p < 0.0001). Furthermore, within the region of Dolnośląskie, we defined a clear prevalence of the isolated gastroschisis cluster (p = 0.023). We comprehensively examined demographic and socio-economic risk factors for abdominal wall defects in this area, and we found that these factors failed to account for the cluster.Conclusions: We identified a distinct prevalence cluster for isolated gastroschisis, although a precise reason for the disease clustering in this region remains unknown. Cluster identification enables more focused research aimed at identification of specific factors with teratogenic effects. [ABSTRACT FROM AUTHOR]

Genetic analysis of familial forms of Alzheimer's disease (AD) causally links the proteolytic processing of the amyloid precursor protein (APP) and AD. However, the specific type of amyloid and mechanisms of amyloid pathogenesis remain unclear. We conducted a detailed analysis of intracellular amyloid with an aggregation specific conformation dependent monoclonal antibody, M78, raised against fibrillar Aß42. M78 immunoreactivity colocalizes with Aß and the carboxyl terminus of APP (APP-CTF) immunoreactivities in perinuclear compartments at intermediate times in 10 month 3XTg-AD mice, indicating that this represents misfolded and aggregated protein rather than normally folded APP. At 12 months, M78 immunoreactivity also accumulates in the nucleus. Neuritic plaques at 12 months display the same spatial organization of centrally colocalized M78, diffuse chromatin and neuronal nuclear NeuN staining surrounded by peripheral M78 and APP-CTF immunoreactivity as observed in neurons, indicating that neuritic plaques arise from degenerating neurons with intracellular amyloid immunoreactivity. The same staining pattern was observed in neuritic plaques in human AD brains, showing elevated intracellular M78 immunoreactivity at intermediate stages of amyloid pathology (Braak A and B) compared to no amyloid pathology and late stage amyloid pathology (Braak 0 and C, respectively). These results indicate that intraneuronal protein aggregation and amyloid accumulation is an early event in AD and that neuritic plaques are initiated by the degeneration and death of neurons by a mechanism that may be related to the formation of extracellular traps by neutrophils. [ABSTRACT FROM AUTHOR]

Abstract: Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Current therapies are toxic and not always curative that necessitates development of targeted immunotherapy. However, little is known about immunobiology of this tumor. In this study, we show that MB cells in 9 of 20 primary tumors express CD1d, an antigen-presenting molecule for Natural Killer T cells (NKTs). Quantitative RT-PCR analysis of 61 primary tumors revealed an elevated level of CD1d mRNA expression in a molecular subgroup characterized by an overactivation of Sonic Hedgehog (SHH) oncogene compared with Group 4. CD1d-positive MB cells cross-presented glycolipid antigens to activate NKT-cell cytotoxicity. Intracranial injection of NKTs resulted in regression of orthotopic MB xenografts in NOD/SCID mice. Importantly, the numbers and function of peripheral blood type-I NKTs were preserved in MB patients. Therefore, CD1d is expressed on tumor cells in a subset of MB patients and represents a novel target for immunotherapy. [Copyright &y& Elsevier]

Coalitions are often the means through which communities plan and coordinate services for individuals and address larger environmental issues associated with social problems. Since 2003, the Centers for Disease Control and Prevention (CDC) has supported local coordinated community response coalitions (CCRs) in 14 states to prevent intimate partner violence (IPV) through its Domestic Violence Prevention Enhancements and Leadership Through Alliances (DELTA) Program. Utilizing quantitative and qualitative evaluation data from 2003 and 2006 from DELTA-funded CCRs (N = 59), this article reports on improvements in internal CCR capacity and external supports that can affect the ability of CCRs to prevent IPV. Data are examined through the Interactive Systems Framework for Dissemination and Implementation (ISF) to convey how CCR internal capacity and external supports contribute to the substantial infrastructure needed to effectively address IPV. Family social workers will gain an understanding of the capacities needed by CCRs to prevent IPV, the multiple organizations and systems that support the work of these CCRs, and how they themselves can work to strengthen the capacities of local coalitions that address IPV. [ABSTRACT FROM AUTHOR]

Background: Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Aβ and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results: We immunized rabbits with a morphologically homogeneous population of Aβ42 fibrils. The resulting immune serum (OC) specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 x G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type II diabetes, demonstrating its generic specificity for amyloid fibrils. Conclusion: Since the fibril specific antibodies are conformation dependent, sequence-independent, and recognize epitopes that are distinct from those present in prefibrillar oligomers, they may have broad utility for detecting and characterizing the accumulation of amyloid fibrils and fibrillar type oligomers in degenerative diseases. [ABSTRACT FROM AUTHOR]