Inhibition of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations and Ca2+ Dysregulation in Aged Rats

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4–6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca2+ channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling

Kualitas Hidup Pasien Diabetes Melitus Tipe 2 di Puskesmas Se Kota Kupang

Diabetes Mellitus is well known as a chronic disease which can lead to a decrease in quality of life in all domains. The study aims to explore the diabetic type 2 patient\u27s quality of life and find out the factors affecting in type 2 diabetic mellitus patients. The cross-sectional study design is used that included 65 patient with type 2 diabetes mellitus, in 11 public health centers of Kupang City. Data were collected by using Short Form Survey (SF-36) that assessed 8-scale health profile. Independent sample t-test is used to analyze the correlation between the factors affecting and the quality of life. the study showed that the QoL of DM patients decreased in all 8- health profile including physical functioning, social functioning, mental health, general health, pain, change in the role due to physical problems and emotional problems. The Study also showed there was a relationship between gender, duration of suffering from Diabetes mellitus, and complications to the quality of life. Male perceived a better quality of life than female

Post-doctoral research fellowship as a health policy and systems research capacity development intervention: a case of the CHESAI initiative

BACKGROUND: Building capacity in health policy and systems research (HPSR), especially in low- and middle-income countries, remains a challenge. Various approaches have been suggested and implemented by scholars and institutions using various forms of capacity building to address challenges regarding HPSR development. The Collaboration for Health Systems Analysis and Innovation (CHESAI) – a collaborative effort between the Universities of Cape Town and the Western Cape Schools of Public Health – has employed a non-research based post-doctoral research fellowship (PDRF) as a way of building African capacity in the field of HPSR by recruiting four post-docs. In this paper, we (the four post-docs) explore whether a PDRF is a useful approach for capacity building for the field of HPSR using our CHESAI PDRF experiences. METHODS: We used personal reflections of our written narratives providing detailed information regarding our engagement with CHESAI. The narratives were based on a question guide around our experiences through various activities and their impacts on our professional development. The data analysis process was highly iterative in nature, involving repeated meetings among the four post-docs to reflect, discuss and create themes that evolved from the discussions. RESULTS: The CHESAI PDRF provided multiple spaces for our engagement and capacity development in the field of HPSR. These spaces provided us with a wide range of learning experiences, including teaching and research, policy networking, skills for academic writing, engaging practitioners, co-production and community dialogue. Our reflections suggest that institutions providing PDRF such as this are valuable if they provide environments endowed with adequate resources, good leadership and spaces for innovation. Further, the PDRFs need to be grounded in a community of HPSR practice, and provide opportunities for the post-docs to gain an in-depth understanding of the broader theoretical and methodological underpinnings of the field. CONCLUSION: The study concludes that PDRF is a useful approach to capacity building in HPSR, but it needs be embedded in a community of practice for fellows to benefit. More academic institutions in Africa need to adopt innovative and flexible support for emerging leaders, researchers and practitioners to strengthen our health systemsIS

Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma

Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either because of outgrowth of an intrinsically resistant sub-clone or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers, we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6; PEA1 and PEA2; and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and single nucleotide polymorphism (SNP) array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different time points in the same individual. This implies that platinum-sensitive and -resistant disease was not linearly related, but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells