New Roles for Old Glue: Astrocyte Function in Synaptic Plasticity and Neurological Disorders

Previously believed to solely play a supportive role in the central nervous system, astrocytes are now considered active players in normal brain function. Evidence in recent decades extends their contributions beyond the classically held brain glue role; it’s now known that astrocytes act as a unique excitable component with functions extending into local network modulation, synaptic plasticity, and memory formation, and postinjury repair. In this review article, we highlight our growing understanding of astrocyte function and physiology, the increasing role of gliotransmitters in neuron-glia communication, and the role of astrocytes in modulating synaptic plasticity and cognitive function. Owing to the duality of both beneficial and deleterious roles attributed to astrocytes, we also discuss the implications of this new knowledge as it applies to neurological disorders including Alzheimer disease, epilepsy, and schizophrenia

Pengaturcaraan Web Hypertext Preprocessor (PHP)

Buku ini memperkenalkan kepada pembaca tentang asas pengaturcaraan web dalam Hypertext Preprocessor (PHP). Perbincangan awal dimula dengan memperkenalkan teknologi web dan perisian sumber terbuka. Kemudiannya, diikuti pengenalan kepada PHP yang merangkumi konsep, sejarah dan keperluan asas sebelum menulis atur cara PHP. Selain itu, terdapat beberapa bab yang menghuraikan pelbagai elemen bahasa pengaturcaraan. Antaranya struktur kawalan, fungsi, rentetan, dan tatasusunan. Bab akhir buku ini pula menerangkan tentang cara membangunkan aplikasi web menggunakan PHP, iaitu sistem penjanaan nombor dan variasi rawak. Buku ini juga turut menyediakan contoh atur cara dan latihan pengaturcaraan bagi memahir dan mengukuhkan lagi penguasaan pembaca dalam pengaturcaraan web. Buku ini sesuai sebagai bahan pengajaran dan pembelajaran oleh pensyarah dan pelajar, kepada pengaturcara yang ingin mempelajari bahasa penulisan skrip PHP dengan lebih mendalam, serta pembaca umum yang berminat untuk mengenali PHP dan ingin mempelajari asas pengaturcaraan web dengan mudah dan berkesan

Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [18F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer

Comparison of Correction Techniques for the Spill in Effect in Emission Tomography

In positron emission tomography (PET) imaging, accurate clinical assessment is often affected by the partial volume effect (PVE) leading to overestimation (spill-in) or underestimation (spill-out) of activity in various small regions. The spill-in correction, in particular, can be very challenging when the target region is close to a hot background region. Therefore, this study evaluates and compares the performance of various recently developed spill-in correction techniques, namely: background correction (BC), local projection (LP), and hybrid kernelized (HKEM) methods. We used a simulated digital phantom and 18F-NaF PET data of three patients with abdominal aortic aneurysms (AAA) acquired with Siemens Biograph mMRTM and mCTTM scanners respectively. Region of Interest (ROI) analysis was performed and the extracted SUVmean, SUVmax and target-to-background ratio (TBR) scores were compared. Results showed substantial spill-in effects from hot regions to targeted regions, which are more prominent in small structures. The phantom experiment demonstrated the feasibility of spill-in correction with all methods. For the patient data, large differences in SUVmean, SUVmax and TBRmax scores were observed between the ROIs drawn over the entire aneurysm and ROIs excluding some regions close to the bone. Overall, BC yielded the best performance in spill-in correction in both phantom and patient studies

3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ( blastoids ) that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day 21. We also show that the modulation of WNT signaling alters the balance between epiblast and trophoblast fates in post-implantation blastoids. This work demonstrates that 3D-cultured blastoids offer a continuous and integrated in vitro model system of human embryonic and extraembryonic development from pre-implantation to early gastrulation stages

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer