1,054 research outputs found

    Childhood Obesity and Obstructive Sleep Apnea

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    The global epidemic of childhood and adolescent obesity and its immediate as well as long-term consequences for obese individuals and society as a whole cannot be overemphasized. Obesity in childhood and adolescence is associated with an increased risk of adult obesity and clinically significant consequences affecting the cardiovascular and metabolic systems. Importantly, obesity is additionally complicated by obstructive sleep apnea (OSA), occurring in up to 60% of obese children. OSA, which is diagnosed using the gold standard polysomnogram (PSG), is characterised by snoring, recurrent partial (hypopneas) or complete (apneas) obstruction of the upper airway. OSA is frequently associated with intermittent oxyhemoglobin desaturations, sleep disruption, and sleep fragmentation. There is emerging data that OSA is associated with cardiovascular burden including systemic hypertension, changes in ventricular structure and function, arterial stiffness, and metabolic syndromes. Thus, OSA in the context of obesity may independently or synergistically magnify the underlying cardiovascular and metabolic burden. This is of importance as early recognition and treatment of OSA in obese children are likely to result in the reduction of cardiometabolic burden in obese children. This paper summarizes the current state of understanding of obesity-related OSA. Specifically, this paper will discuss epidemiology, pathophysiology, cardiometabolic burden, and management of obese children and adolescents with OSA

    On-line bibliographic databases: relevant information retrieval on demand

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    Relevant and selective information can de readily sought by the users if they have sccess to on-line bibliographic databases. The right information is retrieved 'instantly' out of the computer-held bibliographic records from an extensive and comprehensive range of indexes and databases spread all over the world this technique

    Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS.

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    Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair

    Birth data accessibility via primary care health records to classify health status in a multi-ethnic population of children: an observational study

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/license/by/4.0

    PENDAMPINGAN PEMBENTUKAN KESADARAN BELAJAR MELALUI SOSIALISASI PRIMER DAN SEKUNDER BAGI SISWA SEKOLAH DASAR DI DESA OENAK

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    Masalah terkait kesadaran belajar siswa dalam dunia pendidikan merupakan masalah yang sangat serius untuk diperhatikan. Selain minimnya fasilatas yang menjamin proses belajar, kesadaran belajar siswa sangat diperlukan sebagai landasan dasar untuk memperoleh dan mengasah pengetahuan baik dalam pendidikan formal maupun non formal. Masalah kesadaran belajar siswa ini terjadi karena minimnya sosialisasi primer dan sekunder yang ada dalam keluarga dan masyarakat sebagai bentuk kepedulian terhadap dunia pendidikan anak. Oleh karena itu, untuk mengatasi masalah kesadaran belajar siswa tersrebut, Mahasiswa KKN Universitas Katolik Widya Mandira Kupang melakukan observasi dan analisis terkait pendampingan belajar anak dalam keluarga dan program pendampingan belajar siswa secara personal dalam kelompok dengan metode face to face di Desa Oenak. Berdasarkan hasil observasi dan metode yang dilakukan oleh mahasiswa Universitas Katolik Widya Mandira Kupang, program pendampingan belajar bagi siswa Sekolah Dasar sangat efektif dalam pembentukan kesadaran belajar siswa sekolah dasar di desa Oenak. Tentunya pendampingan ini tidak terlepas dari kreatifitas mahasiwa dalam proses mengajar

    Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early Onset Pancreatic Cancer: Clinical Outcomes and Toxicity

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    Purpose/Objective(s): Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age \u3c55 years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). Materials/Methods: This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens. Results: From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (\u3e 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (\u3c 34 vs \u3e 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in KRAS (10/15, 66.7%), TP53 (7/15, 46.7%), NOTCH 1/2 (3/15, 20%), CDK2NA (2/15, 13.3%), and SMAD4(1/15, 6.7%). Conclusion: Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration \u3e 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques

    MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men

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    The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle

    Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

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    The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant
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