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1.
Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management.
Rao, SSC, Bhagatwala, J
Clinical and translational gastroenterology. 2019;(10):e00078
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Abstract
Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.
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Genetic risk factors for eating disorders: an update and insights into pathophysiology.
Himmerich, H, Bentley, J, Kan, C, Treasure, J
Therapeutic advances in psychopharmacology. 2019;:2045125318814734
Abstract
Genome-wide-association studies (GWASs), epigenetic, gene-expression and gene-gene interaction projects, nutritional genomics and investigations of the gut microbiota have increased our knowledge of the pathophysiology of eating disorders (EDs). However, compared with anorexia nervosa, genetic studies in patients with bulimia nervosa and binge-eating disorder are relatively scarce, with the exception of a few formal genetic and small-sized candidate-gene-association studies. In this article, we review important findings derived from formal and molecular genetics in order to outline a genetics-based pathophysiological model of EDs. This model takes into account environmental and nutritional factors, genetic factors related to the microbiome, the metabolic and endocrine system, the immune system, and the brain, in addition to phenotypical traits of EDs. Shortcomings and advantages of genetic research in EDs are discussed against the historical background, but also in light of potential future treatment options for patients with EDs.
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MicroRNAs and new biotechnological tools for its modulation and improving stress tolerance in plants.
Basso, MF, Ferreira, PCG, Kobayashi, AK, Harmon, FG, Nepomuceno, AL, Molinari, HBC, Grossi-de-Sa, MF
Plant biotechnology journal. 2019;(8):1482-1500
Abstract
MicroRNAs (miRNAs) modulate the abundance and spatial-temporal accumulation of target mRNAs and indirectly regulate several plant processes. Transcriptional regulation of the genes encoding miRNAs (MIR genes) can be activated by numerous transcription factors, which themselves are regulated by other miRNAs. Fine-tuning of MIR genes or miRNAs is a powerful biotechnological strategy to improve tolerance to abiotic or biotic stresses in crops of economic importance. Current approaches for miRNA fine-tuning are based on the down- or up-regulation of MIR gene transcription and the use of genetic engineering tools to manipulate the final concentration of these miRNAs in the cytoplasm. Transgenesis, cisgenesis, intragenesis, artificial MIR genes, endogenous and artificial target mimicry, MIR genes editing using Meganucleases, ZNF proteins, TALENs and CRISPR/Cas9 or CRISPR/Cpf1, CRISPR/dCas9 or dCpf1, CRISPR13a, topical delivery of miRNAs and epigenetic memory have been successfully explored to MIR gene or miRNA modulation and improve agronomic traits in several model or crop plants. However, advantages and drawbacks of each of these new biotechnological tools (NBTs) are still not well understood. In this review, we provide a brief overview of the biogenesis and role of miRNAs in response to abiotic or biotic stresses, we present critically the main NBTs used for the manipulation of MIR genes and miRNAs, we show current efforts and findings with the MIR genes and miRNAs modulation in plants, and we summarize the advantages and drawbacks of these NBTs and provide some alternatives to overcome. Finally, challenges and future perspectives to miRNA modulating in important crops are also discussed.
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The expanding roles and mechanisms of G protein-mediated presynaptic inhibition.
Zurawski, Z, Yim, YY, Alford, S, Hamm, HE
The Journal of biological chemistry. 2019;(5):1661-1670
Abstract
Throughout the past five decades, tremendous advancements have been made in our understanding of G protein signaling and presynaptic inhibition, many of which were published in the Journal of Biological Chemistry under the tenure of Herb Tabor as Editor-in-Chief. Here, we identify these critical advances, including the formulation of the ternary complex model of G protein-coupled receptor signaling and the discovery of Gβγ as a critical signaling component of the heterotrimeric G protein, along with the nature of presynaptic inhibition and its physiological role. We provide an overview for the discovery and physiological relevance of the two known Gβγ-mediated mechanisms for presynaptic inhibition: first, the action of Gβγ on voltage-gated calcium channels to inhibit calcium influx to the presynaptic active zone and, second, the direct binding of Gβγ to the SNARE complex to displace synaptotagmin downstream of calcium entry, which has been demonstrated to be important in neurons and secretory cells. These two mechanisms act in tandem with each other in a synergistic manner to provide more complete spatiotemporal control over neurotransmitter release.
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Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline.
Spinelli, M, Fusco, S, Grassi, C
Frontiers in neuroscience. 2019;:788
Abstract
In the last decade, much attention has been devoted to the effects of nutrient-related signals on brain development and cognitive functions. A turning point was the discovery that brain areas other than the hypothalamus expressed receptors for hormones related to metabolism. In particular, insulin signaling has been demonstrated to impact on molecular cascades underlying hippocampal plasticity, learning and memory. Here, we summarize the molecular evidence linking alteration of hippocampal insulin sensitivity with changes of both adult neurogenesis and synaptic plasticity. We also review the epidemiological studies and experimental models emphasizing the critical role of brain insulin resistance at the crossroad between metabolic and neurodegenerative disease. Finally, we brief novel findings suggesting how biomarkers of brain insulin resistance, involving the study of brain-derived extracellular vesicles and brain glucose metabolism, may predict the onset and/or the progression of cognitive decline.
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Pancreatitis: TIGAR-O Version 2 Risk/Etiology Checklist With Topic Reviews, Updates, and Use Primers.
Whitcomb, DC, ,
Clinical and translational gastroenterology. 2019;(6):e00027
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Abstract
The Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and severe acute pancreatitis and Obstructive (TIGAR-O) Pancreatitis Risk/Etiology Checklist (TIGAR-O_V1) is a broad classification system that lists the major risk factors and etiologies of recurrent acute pancreatitis, chronic pancreatitis, and overlapping pancreatic disorders with or without genetic, immunologic, metabolic, nutritional, neurologic, metaplastic, or other features. New discoveries and progressive concepts since the 2001 TIGAR-O list relevant to understanding and managing complex pancreatic disorders require an update to TIGAR-O_V2 with both a short (S) and long (L) form. The revised system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection. The rationale and key clinical considerations are summarized for each updated classification item. Familiarity with the structured format speeds up the completion process and supports thoroughness and consideration of complex or alternative diagnoses during evaluation and serves as a framework for communication. The structured approach also facilitates the new health information technologies that required high-quality data for accurate precision medicine. A use primer accompanies the TIGAR-O_V2 checklist with rationale and comments for health care workers and industries caring for patients with pancreatic diseases.
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Which Diet for Calcium Stone Patients: A Real-World Approach to Preventive Care.
D'Alessandro, C, Ferraro, PM, Cianchi, C, Barsotti, M, Gambaro, G, Cupisti, A
Nutrients. 2019;(5)
Abstract
Kidney stone disease should be viewed as a systemic disorder, associated with or predictive of hypertension, insulin resistance, chronic kidney disease and cardiovascular damage. Dietary and lifestyle changes represent an important strategy for the prevention of kidney stone recurrences and cardiovascular damage. A full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, yet it is rarely performed outside of stone specialist clinics. Many patients have a history of kidney stone disease while lacking a satisfactory metabolic profile. Nonetheless, in a real-world clinical practice a rational management of kidney stone patients is still possible. Different scenarios, with different types of dietary approaches based on diagnosis accuracy level can be envisaged. The aim of this review is to give patient-tailored dietary suggestions whatever the level of clinical and biochemistry evaluation. This can help to deliver a useful recommendation, while avoiding excessive dietary restrictions especially when they are not based on a specific diagnosis, and therefore potentially useless or even harmful. We focused our attention on calcium stones and the different scenarios we may find in the daily clinical practice, including the case of patients who reported renal colic episodes and/or passed stones with no information on stone composition, urinary risk factors or metabolic cardiovascular risk factors; or the case of patients with partial and incomplete information; or the case of patients with full information on stone composition, urinary risk factors and metabolic cardiovascular profile.
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An Updated List of Neuromedicinal Plants of Pakistan, Their Uses, and Phytochemistry.
Khan, AW, Khan, AU, Shah, SMM, Ullah, A, Faheem, M, Saleem, M
Evidence-based complementary and alternative medicine : eCAM. 2019;:6191505
Abstract
BACKGROUND Almost every region of Pakistan is stacked with a large number of medicinal plants. Due to high cost and unavailability of allopathic medicines for the neurological diseases, especially in rural areas, traditional healers prescribe phytotherapy for various neurological diseases like epilepsy, depression, anxiety, insomnia, Alzheimer, and migraine. Such treatments are considered to be most effective by the native people. METHODS The data was collected from articles published on medicinal plants of various districts of Pakistan, using article search engines like Medline, Pubmed, Web of Science, Science Direct, and Google Scholar. Also, information regarding various neurological uses and mode of applications of medicinal plants was obtained from traditional healers, folk medicine users, and local elderly people having knowledge of medicinal plants. RESULTS A total of 54 families were found to be used in various neurological diseases, of which the highest use was of Solanaceae (22.22%), Asteraceae (12.96%), Lamiaceae, Papaveraceae, and Poaceae, 9% each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5% each. According to districts, 15% of plants that were effective in neurological affections were found in Bahawalpur, 11% in Swat, 8% in Muzaffarabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each. According to the plant's habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33% trees, 11.65% shrubs, and 4.85% climbers. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, and flowers were found to be used 32.03%, 24.27%, 20.38%, 16.50%, 13.59%, and 11.65%, respectively. According to disease's types, 45.63% were found to be effective in insomnia, 31.06% in epilepsy 12.62% in depression, 6.80% in anxiety, 7.77% in hysteria, and 5.88% in migraine. CONCLUSION Taking into consideration this useful knowledge on medicinal properties of the plants for curing neurologic diseases, it is believed that research in areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding value to the very rich natural resources of Pakistan. This study will help all the researchers from diverse backgrounds working on plants based medicine for neurological diseases.
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Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses.
Martín-Acebes, MA, Jiménez de Oya, N, Saiz, JC
Pharmaceuticals (Basel, Switzerland). 2019;(2)
Abstract
The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force.
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10.
The impact of urbanization on risk for eating disorders.
Gorrell, S, Trainor, C, Le Grange, D
Current opinion in psychiatry. 2019;(3):242-247
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Abstract
PURPOSE OF REVIEW Urbanization has broadly been implicated in negatively impacting mental health, including risk for disordered eating and eating disorders. Understanding the specific mechanisms that contribute to risk for maladaptive eating behavior in the context of urbanization is essential to improving public health policy and guiding future clinical, research, and prevention efforts. RECENT FINDINGS This review of recent investigation related to the impact of urbanization on eating disease highlights specific risk factors for eating disorders, including acculturation to Western standards of beauty and food resources with associated body weight and body image concern. SUMMARY Recommendations for clinical and research endeavors include improved specificity in defining urbanization, as well as increased sensitivity within community-based assessment of cultural and demographic variables that may impact eating behavior and risk for eating disorders.