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Curing breast cancer and killing the heart: A novel model to explain elevated cardiovascular disease and mortality risk among women with early stage breast cancer.
Kirkham, AA, Beaudry, RI, Paterson, DI, Mackey, JR, Haykowsky, MJ
Progress in cardiovascular diseases. 2019;(2):116-126
Abstract
Due to advances in prevention, early detection and treatment, early breast cancer mortality has decreased by nearly 40% during the last four decades. Yet, the risk of cardiovascular disease (CVD) mortality is significantly elevated following a breast cancer diagnosis, and it is a leading cause of death in this population. This review will discuss the most recent evidence for risks, pathology, mechanisms, and prevention of CVD morbidity and mortality in women with breast cancer. This evidence will be synthesized into a new model 'the compounding risk and protection model.' This model proposes that the balance between risk factors (i.e., older age, pre-existing traditional CVD risk factors and shared biologic pathways for CVD and cancer such as inflammation, as well as treatment-related and lifestyle toxicity) and potential protection factors (i.e., lifelong non-smoking, regular physical activity, a healthy diet rich in fruits and vegetables, and management of body weight and stress, heart failure therapy) determine the individual risk of CVD morbidity and mortality after diagnosis of early breast cancer.
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2.
Choosing among second-generation antidepressant treatments for depressed patients with cardiac diseases.
Kasper, S
International journal of psychiatry in clinical practice. 2019;(2):134-148
Abstract
Objectives: The present paper aimed to assist physicians in the accurate choice among second-generation agents (SGAs) for patients with cardiovascular disease (CVD). Methods: We reviewed the published pharmacokinetic (PK) and pharmacodynamic (PD) clinical data that report potential -or absence of- drug interactions between second-generation agents (SGAs) and CVD drugs most commonly used in cardiology, including antiplatelet drugs and anticoagulants, statins, beta-blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics and the antiarrhythmic drugs amiodarone and digoxin. We also reviewed the cardiovascular safety profile that has been published for each class of SGAs and side effects reported by patients with CVD. Results: Most relevant PK/PD data about SGAs and CVD drugs are based on small studies or detailed case reports. In many cases, the drug interactions are at most assessed in healthy volunteers so that the clinical relevance of findings needs further investigation in patients with CVD. Case reports of serious, sometimes fatal reactions due to concomitant administration of certain drugs require careful consideration. The major cardiac side effects of SGAs include HR increase, postural hypotension and slight prolongation of the intraventricular conduction time and QT interval. On normal dosage of antidepressants, both advanced heart block and ventricular arrhythmias could occur in patients with severe heart disease, together with clinically important loss of myocardial contractile force. Conclusions: Data reported in the present review should help physicians about their decision-making processes that govern SGAs use in CVD patients.
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3.
Oral adjuvant therapy for colorectal cancer: recent developments and future targets.
Shahiwala, A, Qawoogha, SS, Tambuwala, MM
Therapeutic delivery. 2019;(10):659-669
Abstract
Colorectal cancer is considered the third most frequent malignant neoplasm occurring in both men and women worldwide. Most approaches that have been used to fight and treat this type of malignancy are either invasive or nonselective. Noninvasive therapy using oral route can increase patient compliance and reduce treatment costs. Innovative measures such as use of nanotechnology and theranostic systems have been initiated in the oral therapy, which has been proven to be greatly advantageous in decreasing side effects, improving detection and diagnoses. This manuscript investigates recent innovative and novel therapeutic approaches through oral route and potential targets in the treatment of colorectal cancer.
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4.
The Current Situation of the Tyrolean Iceman.
Zink, AR, Maixner, F
Gerontology. 2019;(6):699-706
Abstract
The Tyrolean Iceman, commonly known as Ötzi, is the world's oldest glacier mummy and one of the best investigated ancient human remains in the world. Since the discovery of the 5,300-year-old Copper Age individual in 1991, in a glacier in the Eastern Italian Alps, a variety of morphological, biochemical, and molecular analyses have been performed that revealed important insights into his origin, his life habits, and the circumstances surrounding his demise. In more recent research, the mummy was subjected to cutting-edge modern research methodologies currently focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still preserved in the mummified tissues. This application of innovative "-omics" technologies revealed novel insights on the ancestry, disease predisposition, diet, and the presence of pathogens in the glacier mummy. In this review, the most important and actual results of the molecular studies will be highlighted.
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5.
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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Far-red light acclimation in diverse oxygenic photosynthetic organisms.
Wolf, BM, Blankenship, RE
Photosynthesis research. 2019;(3):349-359
Abstract
Oxygenic photosynthesis has historically been considered limited to be driven by the wavelengths of visible light. However, in the last few decades, various adaptations have been discovered that allow algae, cyanobacteria, and even plants to utilize longer wavelength light in the far-red spectral range. These adaptations provide distinct advantages to the species possessing them, allowing the effective utilization of shade light under highly filtered light environments. In prokaryotes, these adaptations include the production of far-red-absorbing chlorophylls d and f and the remodeling of phycobilisome antennas and reaction centers. Eukaryotes express specialized light-harvesting pigment-protein complexes that use interactions between pigments and their protein environment to spectrally tune the absorption of chlorophyll a. If these adaptations could be applied to crop plants, a potentially significant increase in photon utilization in lower shaded leaves could be realized, improving crop yields.
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Maternal Implications of Breastfeeding: A Review for the Internist.
Sattari, M, Serwint, JR, Levine, DM
The American journal of medicine. 2019;(8):912-920
Abstract
Breastfeeding seems to be a low-cost intervention that provides both short- and long-term health benefits for the breastfeeding woman. Interventions to support breastfeeding can increase its rate, exclusivity, and duration. Internists often have a longitudinal relationship with their patients and can be important partners with obstetricians and pediatricians in advocating for breastfeeding. To play their unique and critical role in breastfeeding promotion, internists need to be knowledgeable about breastfeeding and its maternal health benefits. In this paper, we review the short- and long-term maternal health benefits of breastfeeding. We also discuss special considerations in the care of breastfeeding women for the internist.
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8.
Human Chitinases: Structure, Function, and Inhibitor Discovery.
Kumar, A, Zhang, KYJ
Advances in experimental medicine and biology. 2019;:221-251
Abstract
Chitinases are glycosyl hydrolases that hydrolyze the β-(1-4)-linkage of N-acetyl-D-glucosamine units present in chitin polymers. Chitinases are widely distributed enzymes and are present in a wide range of organisms including insects, plants, bacteria, fungi, and mammals. These enzymes play key roles in immunity, nutrition, pathogenicity, and arthropod molting. Humans express two chitinases, chitotriosidase 1 (CHIT1) and acid mammalian chitinase (AMCase) along with several chitinase-like proteins (CLPs). Human chitinases are reported to play a protective role against chitin-containing pathogens through their capability to degrade chitin present in the cell wall of pathogens. Now, human chitinases are gaining attention as the key players in innate immune response. Although the exact mechanism of their role in immune response is not known, studies in recent years begin to relate chitin recognition and degradation with the activation of signaling pathways involved in inflammation. The roles of both CHIT1 and AMCase in the development of various diseases have been revealed and several classes of inhibitors have been developed. However, a clear understanding could not be established due to complexities in the design of the right experiment for studying the role of human chitinase in various diseases. In this chapter, we will first outline the structural features of CHIT1 and AMcase. We will then review the progress in understanding the role of human chitinases in the development of various diseases. Finally, we will summarize the inhibitor discovery efforts targeting both CHIT1 and AMCase.
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9.
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.