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Tibayrenc M,Ayala FJ
Relevant units of analysis for applied and basic research dealing with neglected transmissible diseases: The predominant clonal evolution model of pathogenic microorganisms.
PLoS Negl Trop Dis. 2017 Apr;11(4):e0005293
The predominant clonal evolution (PCE) model seeks to formulate a common population genetics framework for all micropathogens (namely, parasitic protozoa, fungi and yeasts, bacteria, and viruses). It relies on a definition of clonality that is only based on population structure features (namely, strongly restrained genetic recombination). Its clear-cut properties make it of strong interest for applied and basic research, since it permits the definition of stable, clearly delimited units of analysis below the species level: clonal genotypes and discrete genetic subdivisions ("near-clades"). These units of analysis can be used for clinical and epidemiological studies, vaccine and drug design, species description, and evolutionary studies on natural and experimental populations. In this review, the evolutionary and population genetics background of the model will be only briefly mentioned, while considerable emphasis will be given to its practical significance for the study and control of neglected tropical diseases. The goal of the paper is to make this practical usefulness accessible to a broad audience of readers, including scientists who are not evolution specialists, such as epidemiologists, field scientists, and clinicians. For extensive developments about the evolutionary background of the model, see our previous papers [1-9]. Citations of these former articles lead to the many references quoted in them, which cannot be listed again here.
PMID: 28448491

Garson LM
Pocket Anesthesia.
Anesth Analg. 2017 Apr 24;
PMID: 28448391

Gautschi O,Milia J,Filleron T,Wolf J,Carbone DP,Owen D,Camidge R,Narayanan V,Doebele RC,Besse B,Remon-Masip J,Janne PA,Awad MM,Peled N,Byoung CC,Karp DD,Van Den Heuvel M,Wakelee HA,Neal JW,Mok TSK,Yang JCH,Ou SI,Pall G,Froesch P,Zalcman G,Gandara DR,Riess JW,Velcheti V,Zeidler K,Diebold J,Früh M,Michels S,Monnet I,Popat S,Rosell R,Karachaliou N,Rothschild SI,Shih JY,Warth A,Muley T,Cabillic F,Mazières J,Drilon A
Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry.
J Clin Oncol. 2017 May 01;35(13):1403-1410
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.
PMID: 28447912

Kang YJ,Tian G,Bazrafkan A,Farahabadi MH,Azadian M,Abbasi H,Shamaoun B,Steward O,Akbari Y
Recovery from coma post-cardiac arrest is dependent on the orexin pathway.
J Neurotrauma. 2017 Apr 27;
Cardiac arrest affects >550,000 people annually in the USA while 80-90% of survivors suffer from a comatose state. Arousal from coma is critical for recovery but mechanisms of arousal are undefined. Orexin-A, a hypothalamic excitatory neuropeptide, has been linked to arousal deficits in various brain injuries. We investigated the orexinergic system's role in recovery from cardiac arrest-related neurological impairments, including arousal deficits. Using an asphyxial cardiac arrest and resuscitation model in rats, we examine neurological recovery post-resuscitation in conjunction with changes in orexin-A levels in cerebrospinal fluid and orexin-expressing neurons. We show that recovery from neurological deficits begins between 4 hours and 24 hours post-resuscitation, with additional recovery by 72 hours post-resuscitation. Orexin-A levels in the cerebrospinal fluid are lowest during periods of poorest arousal post-resuscitation (4 hours) and recover to control levels by 24 hours. Immunostaining revealed that the number of orexin-A immunoreactive neurons declined at 4 hours post-resuscitation but increased to near normal levels by 24 hours. There were no significant changes in the number of neurons expressing melanin-concentrating hormone, another neuropeptide localized in similar hypothalamus regions. Lastly, administration of the dual orexin receptor antagonist, suvorexant, during the initial 24 hours post-resuscitation, led to sustained neurological deficits. These results indicate that the orexin pathway is critical during early phases of neurological recovery following cardiac arrest. Blocking this early action leads to persistent neurological deficits. This is of considerable clinical interest given that suvorexant recently received FDA-approval for insomnia treatment. Key words: cardiac arrest, coma, orexin, arousal, neurological recovery.
PMID: 28447885

Samtani SR,Thomas GS
Assessment of left ventricular ejection fraction reserve in an era of decreasing frequency of myocardial ischemia during myocardial perfusion imaging.
J Nucl Cardiol. 2017 Apr 26;
PMID: 28447281

Cavanagh C,Cauffman E
The Longitudinal Association of Relationship Quality and Reoffending Among First-Time Juvenile Offenders and Their Mothers.
J Youth Adolesc. 2017 Apr 26;
To understand how youth desist from crime after their first arrest, it is necessary to investigate their primary support system: their parents. As such, this study examined the reciprocal effects of justice system contact on the mother-child dyad. Interviews with 317 mothers and their sons from Orange County, CA, Jefferson Parish, LA, and Philadelphia, PA were conducted semiannually over two and a half years. At the beginning of the study, the sons were first-time offenders aged 13-17 and mostly non-White (i.e., 19.2 White, 56.5 Latino, 21.5 Black, and 2.8% another race/ethnicity). The results revealed that a high quality initial mother-son relationship reduces youths' re-offending over time. Furthermore, as mothers perceived that their sons were offending more, they reported less warmth in their relationships with their sons two and a half years later. Interestingly, youth's age emerged as a moderator. First, older youth were less likely to engage in reoffending if they had a warm maternal relationship. Second, decreases in relationship warmth associated with re-offending were steeper for younger youth. The findings have implications for juvenile justice policy in terms of improving probationary outcomes for youth offenders, and alleviating the financial and emotional burden on justice system-involved families.
PMID: 28447243

Chui PW,Parzynski CS,Nallamothu BK,Masoudi FA,Krumholz HM,Curtis JP
Hospital Performance on Percutaneous Coronary Intervention Process and Outcomes Measures.
J Am Heart Assoc. 2017 Apr 26;6(5)
The Physician Consortium for Performance Improvement recently proposed percutaneous coronary intervention (PCI)-specific process measures. However, information about hospital performance on these measures and the association of PCI process and outcomes measures are not available.
PMID: 28446493

Hu Z,Chen M,Zhang P,Liu J,Abbott GW
Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.
Cardiovasc Diabetol. 2017 Apr 26;16(1):57
Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9).
PMID: 28446231

McLaren CE,Chen WP,O'Sullivan TD,Gillen DL,Su MY,Chen JH,Tromberg BJ
Sample size and power determination when limited preliminary information is available.
BMC Med Res Methodol. 2017 Apr 26;17(1):75
We describe a novel strategy for power and sample size determination developed for studies utilizing investigational technologies with limited available preliminary data, specifically of imaging biomarkers. We evaluated diffuse optical spectroscopic imaging (DOSI), an experimental noninvasive imaging technique that may be capable of assessing changes in mammographic density. Because there is significant evidence that tamoxifen treatment is more effective at reducing breast cancer risk when accompanied by a reduction of breast density, we designed a study to assess the changes from baseline in DOSI imaging biomarkers that may reflect fluctuations in breast density in premenopausal women receiving tamoxifen.
PMID: 28446127

Klein RH,Lin Z,Hopkin AS,Gordon W,Tsoi LC,Liang Y,Gudjonsson JE,Andersen B
GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states.
PLoS Genet. 2017 Apr 26;13(4):e1006745
Transcription factor binding, chromatin modifications and large scale chromatin re-organization underlie progressive, irreversible cell lineage commitments and differentiation. We know little, however, about chromatin changes as cells enter transient, reversible states such as migration. Here we demonstrate that when human progenitor keratinocytes either differentiate or migrate they form complements of typical enhancers and super-enhancers that are unique for each state. Unique super-enhancers for each cellular state link to gene expression that confers functions associated with the respective cell state. These super-enhancers are also enriched for skin disease sequence variants. GRHL3, a transcription factor that promotes both differentiation and migration, binds preferentially to super-enhancers in differentiating keratinocytes, while during migration, it binds preferentially to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Furthermore, GRHL3 represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Hence, chromatin relocates GRHL3 binding and enhancers to regulate both the irreversible commitment of progenitor keratinocytes to differentiation and their reversible transition to migration.
PMID: 28445475

Gong C,Li L,Li Z,Ji H,Stern A,Xia Y,Cao T,Bao W,Wang C,Wang Y,Qiu ZQ,Cava RJ,Louie SG,Xia J,Zhang X
Discovery of intrinsic ferromagnetism in two-dimensional van der Waals crystals.
Nature. 2017 Apr 26;
The realization of long-range ferromagnetic order in two-dimensional van der Waals crystals, combined with their rich electronic and optical properties, could lead to new magnetic, magnetoelectric and magneto-optic applications. In two-dimensional systems, the long-range magnetic order is strongly suppressed by thermal fluctuations, according to the Mermin-Wagner theorem; however, these thermal fluctuations can be counteracted by magnetic anisotropy. Previous efforts, based on defect and composition engineering, or the proximity effect, introduced magnetic responses only locally or extrinsically. Here we report intrinsic long-range ferromagnetic order in pristine Cr2Ge2Te6 atomic layers, as revealed by scanning magneto-optic Kerr microscopy. In this magnetically soft, two-dimensional van der Waals ferromagnet, we achieve unprecedented control of the transition temperature (between ferromagnetic and paramagnetic states) using very small fields (smaller than 0.3 tesla). This result is in contrast to the insensitivity of the transition temperature to magnetic fields in the three-dimensional regime. We found that the small applied field leads to an effective anisotropy that is much greater than the near-zero magnetocrystalline anisotropy, opening up a large spin-wave excitation gap. We explain the observed phenomenon using renormalized spin-wave theory and conclude that the unusual field dependence of the transition temperature is a hallmark of soft, two-dimensional ferromagnetic van der Waals crystals. Cr2Ge2Te6 is a nearly ideal two-dimensional Heisenberg ferromagnet and so will be useful for studying fundamental spin behaviours, opening the door to exploring new applications such as ultra-compact spintronics.
PMID: 28445468

Chou JA,Streja E,Nguyen DV,Rhee CM,Obi Y,Inrig JK,Amin A,Kovesdy CP,Sim JJ,Kalantar-Zadeh K
Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients.
Nephrol Dial Transplant. 2017 Apr 21;
Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (?) and IDH frequency are incrementally associated with all-cause mortality.
PMID: 28444336

Roskamp KW,Montelongo DM,Anorma CD,Bandak DN,Chua JA,Malecha KT,Martin RW
Multiple Aggregation Pathways in Human γS-Crystallin and Its Aggregation-Prone G18V Variant.
Invest Ophthalmol Vis Sci. 2017 Apr 01;58(4):2397-2405
Cataract results from the formation of light-scattering precipitates due to point mutations or accumulated damage in the structural crystallins of the eye lens. Although excised cataracts are predominantly amorphous, in vitro studies show that crystallins are capable of adopting a variety of morphologies depending on the preparation method. Here we characterize thermal, pH-dependent, and UV-irradiated aggregates from wild-type human γS-crystallin (γS-WT) and its aggregation-prone variant, γS-G18V.
PMID: 28444328

Vang YS,Xie X
HLA class I binding prediction via convolutional neural networks.
Bioinformatics. 2017 Apr 21;
Many biological processes are governed by protein-ligand interactions. One such example is the recognition of self and nonself cells by the immune system. This immune response process is regulated by the major histocompatibility complex (MHC) protein which is encoded by the human leukocyte antigen (HLA) complex. Understanding the binding potential between MHC and peptides can lead to the design of more potent, peptide-based vaccines and immunotherapies for infectious autoimmune diseases.
PMID: 28444127

Prince RC,Potma EO
Crossing the arterial wall with CARS.
Proc Natl Acad Sci U S A. 2017 Apr 25;
PMID: 28442563

Mizoguchi S,Iwanishi H,Kokado M,Sumioka T,Parfitt GJ,Xie Y,Arita R,Shirakawa R,Yamanaka O,Okada Y,Jester JV,Saika S
Ocular surface alkali injury damages meibomian glands in mice.
Ocul Surf. 2017 Apr 22;
To examine effects of alkali injury of the ocular surface on meibomian gland pathology in mice.
PMID: 28442381

Papa M,Foladori P,Guglielmi L,Bertanza G
How far are we from closing the loop of sewage resource recovery? A real picture of municipal wastewater treatment plants in Italy.
J Environ Manage. 2017 Apr 22;198(Pt 1):9-15
This paper presents the results of a broad-scale survey of resource recovery implementation in Italian wastewater treatment plants (WWTPs). To the best of our knowledge, this is the first survey comprising a large number of WWTPs done in Europe: more than 600 plants were investigated, representing a treated load of around 20 million population equivalent (??25% of the total in Italy). Conventional and innovative options for both material and energy recovery along the water and sludge line were surveyed, in order to i) offer a real and complete picture of the current state of resource recovery in WWTPs, and ii) underline key aspects and potential areas for improvements, as a baseline for future developments in the direction of more sustainable plants. Survey outcomes showed that resource recovery is just in its infancy in sewage treatment: only 40% of plants perform at least one option for material/energy recovery. The action most often implemented is recovery of material from surplus sludge for agricultural purposes and the internal reuse of treated effluent as water for various types of plant maintenance. The production of energy from biogas also occurs frequently but only in large plants. On the other hand, some well-known options, such as external reuse of treated effluent or nutrients recovery, were implemented only in a minority of plants: this is likely due to limitations resulting either from strict regulation or difficulty placing recovered products on the market. In conclusion, an overall explanation of these driving forces within the system is explored.
PMID: 28441554

Mahboubi H,Sahyouni R,Moshtaghi O,Tadokoro K,Ghavami Y,Ziai K,Lin HW,Djalilian HR
CyberKnife for Treatment of Vestibular Schwannoma: A Meta-analysis.
Otolaryngol Head Neck Surg. 2017 Apr 01;:194599817695805
Objectives (1) Perform a meta-analysis of the available data on the outcomes of CyberKnife radiosurgery for treatment of vestibular schwannomas (VSs) in the published English-language literature and (2) evaluate the collective outcomes of CyberKnife treatment with respect to tumor control and hearing preservation. Data Sources A thorough literature search of published English-language articles was performed in the PubMed, Ovid, and Cochrane databases. Review Methods A database search was conducted with the keywords "CyberKnife" and "vestibular schwannoma" or "acoustic neuroma." A total of 25 papers were found and reviewed. Data were extracted for patient demographics, number of patients with neurofibromatosis type 2, pretreatment hearing status, tumor size, margin dose, and follow-up duration. The primary outcome variables evaluated were tumor control and hearing preservation. Results After careful review of the published articles, 11 papers reported data on outcomes of CyberKnife treatment for VS and were included in the analysis, comprising 800 patients studied during 1998 to 2012. The reported mean tumor volume ranged from 0.02 to 19.8 cm(3), and the follow-up duration ranged from 6 to 120 months. Margin dose varied from 14 to 25 Gy. The collective mean tumor control rate was 96.3% (95% CI: 94.0%-98.5%). The collective hearing preservation rate was 79.1% (95% CI: 71.0%-87.3%) in 427 patients with measurable hearing. Conclusion Clinical data on outcomes of CyberKnife radiosurgery for treatment of VSs are sparse and primarily limited to single-institution analyses, with considerable variation in tumor volume and follow-up time. This meta-analysis not only provides an in-depth analysis of available data in the literature but also reviews reported outcomes and complications.
PMID: 28441508

Liu K,Marple GR,Allard J,Li S,Veerapaneni S,Lowengrub J
Dynamics of a multicomponent vesicle in shear flow.
Soft Matter. 2017 Apr 25;
We study the fully nonlinear, nonlocal dynamics of two-dimensional multicomponent vesicles in a shear flow with matched viscosity of the inner and outer fluids. Using a nonstiff, pseudo-spectral boundary integral method, we investigate dynamical patterns induced by inhomogeneous bending for a two phase system. Numerical results reveal that there exist novel phase-treading and tumbling mechanisms that cannot be observed for a homogeneous vesicle. In particular, unlike the well-known steady tank-treading dynamics characterized by a fixed inclination angle, here the phase-treading mechanism leads to unsteady periodic dynamics with an oscillatory inclination angle. When the average phase concentration is around 1/2, we observe tumbling dynamics even for very low shear rate, and the excess length required for tumbling is significantly smaller than the value for the single phase case. We summarize our results in phase diagrams in terms of the excess length, shear rate, and concentration of the soft phase. These findings go beyond the well known dynamical regimes of a homogeneous vesicle and highlight the level of complexity of vesicle dynamics in a fluid due to heterogeneous material properties.
PMID: 28440378

Daskivich TJ,Dru CJ,Skarecky D,Ahlering T,Freedland SJ
Association of comorbid disease burden at diagnosis with higher tumor grade in men with non-metastatic prostate cancer.
Prostate Cancer Prostatic Dis. 2017 Apr 25;
While older age is associated with higher tumor grade, it is unknown whether comorbid disease burden has a similar, independent association. We sought to evaluate the impact of comorbid disease burden on tumor grade at diagnosis as indicated by biopsy Gleason score.
PMID: 28440321

Kim DK,Parihar JS,Kwon YS,Kim S,Shinder B,Lee N,Farber N,Ahlering T,Skarecky D,Yuh B,Ruel N,Kim WJ,Rha KH,Kim IY
Risk of complications and urinary incontinence following cytoreductive prostatectomy: a multi-institutional study.
Asian J Androl. 2017 Apr 25;
Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.
PMID: 28440262

Cho HM,Ding H,Kumar N,Sennung D,Molloi S
Calibration phantoms for accurate water and lipid density quantification using dual energy mammography.
Phys Med Biol. 2017 Apr 25;
The aim of this study is to investigate the feasibility of water and lipid as calibration phantoms for accurate dual energy breast density quantification. Dual energy calibration was performed on a mammography system based on scanning multi-slit Si strip photon-counting detectors using plastic water and adipose-equivalent phantoms as the basis materials. Two different methods were used to convert the dual energy decomposition measurements in plastic phantom thicknesses into the true water and lipid basis materials. The first method was based entirely on the theoretically calculated effective attenuation coefficients of the investigated materials in the mammographic energy range. The conversion matrix was determined through the linear least-squares fitting of the target material using the calculated effective attenuation coefficients of water and lipid. The second method was based on experimental calibration with plastic water phantom, adipose-equivalent phantom, and its correlation to known water and lipid thicknesses. These two methods were then validated by using an independent measurement of water and lipid mixture phantoms and postmortem breasts. The correlation between the dual energy decomposition measurements and the known values was evaluated using linear regression analysis. The averaged root-mean-square (RMS) errors for water density quantification derived from the theoretical and experimental conversions were 8.6% and 1.6%, respectively. The postmortem breast tissue study also indicates that the experimentally acquired conversion coefficient improved the accuracy in water density quantification, in comparison with that from the theoretical conversion. The results show that conversion of the dual energy measurements into water and lipid thicknesses improves the accuracy in breast tissue decomposition.
PMID: 28440226

Filiault DL,Seymour DK,Maruthachalam R,Maloof JN
The Generation of Doubled Haploid Lines for QTL Mapping.
Methods Mol Biol. 2017;1610:39-57
Recombinant inbred lines (RILs) are an essential tool for quantitative trait locus (QTL) mapping in Arabidopsis thaliana. Conventionally, the development of these lines is a time-consuming and tedious process requiring six to eight generations of selfing. Here, we describe an alternative approach: the rapid generation of RILs in A. thaliana via the creation of doubled haploids. In this method, F1 plants are crossed to an engineered haploid inducer to produce haploid plants. The chromosomes of these haploids then spontaneously double, generating immortalized homozygous F2 lines called doubled haploid RILs (DH RILs). Finally, DH RILs are genotyped using low-coverage whole-genome sequencing and are ready to be used for QTL mapping.
PMID: 28439856

Kil YS,Pham ST,Seo EK,Jafari M
Angelica keiskei, an emerging medicinal herb with various bioactive constituents and biological activities.
Arch Pharm Res. 2017 Apr 24;
Angelica keiskei (Miq.) Koidz. (Umbelliferae) has traditionally been used to treat dysuria, dyschezia, and dysgalactia as well as to restore vitality. Recently, the aerial parts of A. keiskei have been consumed as a health food. Various flavonoids, coumarins, phenolics, acetylenes, sesquiterpene, diterpene, and triterpenes were identified as the constituents of A. keiskei. The crude extracts and pure constituents were proven to inhibit tumor growth and ameliorate inflammation, obesity, diabetics, hypertension, and ulcer. The extract also showed anti-thrombotic, anti-oxidative, anti-hyperlipidemic, anti-viral, and anti-bacterial activities. This valuable herb needs to be further studied and developed not only to treat these human diseases but also to improve human health. Currently A. keiskei is commercialized as a health food and additives in health drinks. This article presents a comprehensive review of A. keiskei and its potential place in the improvement of human health.
PMID: 28439780

Kalantar-Zadeh K,Rhee CM,Chou J,Ahmadi SF,Park J,Chen JL,Amin AN
The Obesity Paradox in Kidney Disease: How to Reconcile it with Obesity Management.
Kidney Int Rep. 2017 Mar;2(2):271-281
Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in the elderly. These are populations in whom protein-energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, i.e., overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help discover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.
PMID: 28439569

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