Perceived responsibility for developing and maintaining home–school partnerships: the experiences of parents and practitioners

Encouraging partnerships between parents of children with special educational needs and disabilities (SEND) and educational practitioners is a key theme in educational policy in England. However, there are unanswered questions regarding whether parents and teachers are mutually responsible for developing and maintaining these partnerships, as well as a paucity of literature eliciting the views of educational practitioners from a SEND context. This article draws on a study which explored parent and teacher experiences of partnership, specifically focusing on perceptions of responsibility regarding the development and maintenance of these partnerships. In-depth interviews were conducted with 22 parents of children with a wide range of SENDs, and 15 educational practitioners. Findings highlighted that although there appeared to be perceived mutual responsibility regarding home–school communication, educational practitioners were overall held accountable for developing and maintaining partnerships, and were required to be trustworthy and approachable in order for positive home–school relationships to flourish. © 2018 NASE

Surgical therapy of primary hepatic angiosarcoma

Abstract Background Primary hepatic angiosarcoma (PHA) is a rare tumor entity. Radical surgical resection is currently considered the best treatment choice. The aim of this analysis is to report our experience with surgery for PHA. Methods All resections of PHA from 01/2002 until 06/2017 were identified from our prospective institutional database. All cases were re-confirmed by a second pathologist. We analyzed completeness of resection, overall (OS) and disease-free survival (DFS). Results Nine patients with PHA underwent hepatic resection. Median follow-up after surgery was 15.5 months (range: 3–144). At last follow-up 4/9 patients were alive, three of them without recurrence 15, 21 and 144 months after surgery. Five patients developed PHA recurrence. Four of these died 3 to 17 months after surgery. One patient with PHA recurrence is alive 15 months after surgery. Another patient without PHA recurrence died 59 months after surgery from pancreatic cancer. Median OS and DFS after resection was 18 months (range: 3–144 months) and 10 months (range: 2–144 months), respectively. After R-0 resection (n = 8), the median OS and DFS was 59 and 11 months. Conclusions Resection of PHA is the only approach to achieve complete tumor removal and offers a chance for long-term survival and should be evaluated in cases of PHA

The NSL complex maintains nuclear architecture stability via lamin A/C acetylation

While nuclear lamina abnormalities are hallmarks of human diseases, their interplay with epigenetic regulators and precise epigenetic landscape remain poorly understood. Here, we show that loss of the lysine acetyltransferase MOF or its associated NSL-complex members KANSL2 or KANSL3 leads to a stochastic accumulation of nuclear abnormalities with genomic instability patterns including chromothripsis. SILAC-based MOF and KANSL2 acetylomes identified lamin A/C as an acetylation target of MOF. HDAC inhibition or acetylation-mimicking lamin A derivatives rescue nuclear abnormalities observed in MOF-deficient cells. Mechanistically, loss of lamin A/C acetylation resulted in its increased solubility, defective phosphorylation dynamics and impaired nuclear mechanostability. We found that nuclear abnormalities include EZH2-dependent histone H3 Lys 27 trimethylation and loss of nascent transcription. We term this altered epigenetic landscape "heterochromatin enrichment in nuclear abnormalities" (HENA). Collectively, the NSL-complex-dependent lamin A/C acetylation provides a mechanism that maintains nuclear architecture and genome integrity

Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure.

BackgroundA hallmark of heart failure is impaired cytoplasmic Ca(2+) handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca(2+) handling via altered excitation-transcription coupling contribute to the development and progression of heart failure.Methods and resultsUsing tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca(2+) pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca(2+) transporters. These changes were associated with altered nucleoplasmic Ca(2+) handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca(2+) levels with diminished and prolonged nuclear Ca(2+) transients and slowed intranuclear Ca(2+) diffusion. Altered nucleoplasmic Ca(2+) levels were translated to higher activation of nuclear Ca(2+)/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca(2+) alterations occurred early during hypertrophy and preceded the cytoplasmic Ca(2+) changes that are typical of heart failure.ConclusionsDuring cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca(2+) signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca(2+) regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling

CD137-mediated immunotherapy for allergic asthma

The prevalence of asthma continues to increase. Asthma is caused by a Th2 cell–driven immune response. Its optimal treatment remains a challenge, and a sufficient immunotherapeutic approach to treating asthma has yet to be found. Using a murine asthma model, we show that a single injection of an anti-CD137 (4-1BB) mAb prevents the development of airway hyperreactivity, eosinophilic airway inflammation, excessive mucus production, and elevated IgE during the observation period of 7 weeks. Most importantly, even established disease is completely reversed by anti-CD137 mAb administration. The protection is associated with markedly reduced Th2 cytokine production and increased secretion of the Th1 cytokine IFN-γ. While B lymphocytes are partly depleted, the number of CD8(+) T cells is increased. Blockade of IFN-γ and depletion of CD8(+) T cells during treatment with anti-CD137 mAb reduces in part but does not abrogate the protective effect of CD137 mAb. In contrast, CD137 mAb–mediated CD4(+) T cell anergy is critical for the observed effects, since transfer of CD4(+) T cells from CD137 mAb–treated mice conveyed protection. These data demonstrate, for the first time to our knowledge, the capacity of anti-CD137 mAb to ameliorate allergic asthma, and they indicate CD137 as a possible target for therapeutic intervention in this disease

Early Remodeling of Perinuclear Ca2+ Stores and Nucleoplasmic Ca2+ Signaling During the Development of Hypertrophy and Heart Failure

Background—A hallmark of heart failure is impaired cytoplasmic Ca2+ handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca2+ handling via altered excitation-transcription coupling contribute to the development and progression of heart failure. Methods and Results—Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca2+ handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca2+ pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca2+ transporters. These changes were associated with altered nucleoplasmic Ca2+ handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca2+ levels with diminished and prolonged nuclear Ca2+ transients and slowed intranuclear Ca2+ diffusion. Altered nucleoplasmic Ca2+ levels were translated to higher activation of nuclear Ca2+/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca2+ alterations occurred early during hypertrophy and preceded the cytoplasmic Ca2+ changes that are typical of heart failure. Conclusions-During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca2+ signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca2+ regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling

A Palaeopathological Assessment of the Late 19th and Early 20th Century Khoesan

Since the arrival of Dutch colonists in the Cape of Good Hope, South Africa, Khoesan populations were subjectedto severe political and economic marginalisation and often fell prey to racial conflict. These circumstancespersisted until the early 20th century, during which an astonishing number of Khoesan skeletons weretransported from South Africa to various locations in Europe, as at the time, different institutions competed toobtain these remains. The purpose of this study was to assess the health status of the late 19th and early 20thcentury Khoesan. Skeletal remains housed in two different European institutions were studied. The samplecomprised 140 specimens from the Rudolf Pöch Skeletal Collection in Vienna, Austria, and 15 specimens fromthe Musée de l’Homme in Paris, France. These individuals represent both sexes and were aged betweennewborn and 75 years, with 54 being younger than 20 years of age. Results indicated high levels of typicaldisease conditions associated with groups under stress, such as periostitis, cribra orbitalia and porotichyperostosis. Treponemal disease, rickets, osteoarthritis and trauma were also encountered amongst other morespecific indicators of health and disease. This study provided additional knowledge on the health status and livesof the Khoesan people during this turbulent period and created new awareness regarding a group of severelymistreated individualsSANPAD and the research of M. Steyn is funded by the National Research Foundation (NRF) of South Africa.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-12122017-03-31hb2017Anatom