Pharmacogenomics, Ahead of Print.
http://ift.tt/2zWGDTr
Παρασκευή 1 Δεκεμβρίου 2017
Polymorphisms associated with adalimumab and infliximab response in moderate-to-severe plaque psoriasis
Population pharmacogenomics: impact on public health and drug development
Pharmacogenomics, Ahead of Print.
http://ift.tt/2iC9aGx
The future of pharmacogenetics in Parkinson's disease treatment
Pharmacogenomics, Ahead of Print.
http://ift.tt/2zWGwY1
What is the role of mitochondrial dysfunction in skin photoageing?
Abstract
Skin ageing is a complex process involving both internal and external factors, which leads to a progressive loss of cutaneous function and structure. Solar radiation is the primary environmental factor implicated in the development of skin ageing and the term photoageing describes the distinct clinical, histological and structural features of chronically sun-exposed skin. The changes that accompany photoageing are undesirable for aesthetic reasons and can compromise the skin and make it more susceptible to a number of dermatological disorders. As a result, skin ageing is a topic that is of growing interest and concern to the general population, illustrated by the increased demand for effective interventions that can prevent or ameliorate the clinical changes associated with aged skin. In this viewpoint essay we explore the role that mitochondria play in the process of skin photoageing. There is continuing evidence supporting the proposal that mitochondria dysfunction and oxidative stress are important contributing factors in the development of skin photoageing. Further skin-directed mitochondrial research is warranted to fully understand the impact of mitochondrial status and function in skin health. A greater understanding of the ageing process and the regulatory mechanisms involved could lead to the development of novel preventative interventions for skin ageing.
This article is protected by copyright. All rights reserved.
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Small animal PET imaging analysis with [18F]FHBG in a mouse model of HSV1-tk gene expression in melanoma
Abstract
The purpose of this study was to establish a small animal model for molecular imaging and to acquire basic data on assessing the efficacy of candidate melanoma drugs using small-animal PET imaging analysis with [18F]FHBG for herpes simplex virus 1-thymidine kinase (HSV1-tk) gene expression in a melanoma mouse model. The B16 melanoma cell line was transduced with a recombinant lentiviral vector containing the HSV1-tk gene and inoculated into the back skin of C57BL/6J mice. [18F]FHBG PET imaging showed better contrast for HSV1-tk(+) melanomas compared to brain, heart, gall bladder, intestine, and kidney than did [18F]FDG PET imaging.
This article is protected by copyright. All rights reserved.
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A heart of stone: an autopsy case of massive myocardial calcification
Abstract
A case of massive calcification of the myocardium is presented that was diagnosed by postmortem computed tomography (PMCT) and confirmed by conventional autopsy. There are two types of pathologic calcification, dystrophic and metastatic. Massive calcification of the myocardium is associated with variable clinical outcomes, including sudden unexpected death. A 53-year-old man was found after he collapsed beside a walkway. He was transferred to hospital and died approximately two months later. To investigate the cause of death, PMCT and conventional autopsy were performed, which revealed massive calcification of the myocardium, a very rare finding at autopsy. Massive myocardial calcification was one of the possible causes of his collapse. PMCT may be a useful diagnostic tool for detecting massive calcification of the myocardium following sudden cardiac death.
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Injury potential of thrown sharp kitchen and household utensils
Abstract
We examined the possibility of inflicting serious injuries with sharp objects in an experimental setting by throwing four sharp objects from different distances and with different throwing techniques. Using an overarm-handle (OA/H), overarm-blade (OA/B), underarm-handle (UA/H), underarm-blade (UA/B) and thrust (T/H) throwing technique, 10 adults (sex ratio 1:1) threw a chef's knife, a skinning knife, a paring knife and office scissors from 4 m and 2 m distance at synthetic abdomen models made of 10% gelatin covered with synthetic skin. The amount of hits and penetrations of the target and their penetration depth were noted, as was the rotation of the blade tip towards the target along its flight trajectory. The chef's knife injury/hit ratio was 0.167/4 m and 0.160/2 m; the skinning knife recorded an injury/hit ratio of 0.087/4 m and 0.153/2 m; the paring knife of 0.087/4 m and 0.113/2 m; and the scissors 0.087/4 m and 0.067/2 m. Mean penetration depths were as follows: the chef's knife: 4 m, 4.42 cm, 2 m, 3.41 cm; the skinning knife: 4 m, 4.19 cm, 2 m, 4.11 cm; the paring knife: 4 m, 1.62 cm, 2 m, 1.55 cm; and the scissors: 4 m, 2.08 cm, 2 m, 0.95 cm. Handle-throw penetration-depths were: 4 m: 3.77 cm and 2 m: 2.86 cm; blade-throw depths were: 4 m: 3.14 cm and 2 m: 2.69 cm. Overarm-throw penetration-depths were: 4 m: 3.62 cm and 2 m: 3.25 cm; and underarm-throw penetration-depths were 4 m: 3.30 cm and 2 m: 2.30 cm. No thrust-throws with the paring knife and scissors could pierce the target. The tips pointed toward the target at angles of 60°-120°, earlier in handle-throws than blade-throws, especially with the paring knife and the scissors. When thrown, especially with a handle-held technique, heavier objects pierced more often and more deeply. Thrust-throws at short distances are unlikely to pierce a human.
http://ift.tt/2zWQlW1
Study protocol for statin web-based investigation of side effects (StatinWISE): a series of randomised controlled N-of-1 trials comparing atorvastatin and placebo in UK primary care
Introduction
Statins are effective at preventing cardiovascular disease, widely prescribed and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals.
Methods and analysisThis series of 200 randomised, double-blinded N-of-1 trials in primary care will determine (1) the effect of statins on all muscle symptoms and (2) the effect of statins on muscle pain that is perceived to be statin related. Patients who are considering discontinuing statin use due to muscle symptoms and those who have discontinued in the last 3 years due to such symptoms will be recruited. Participants will be randomised to a sequence of six 2-month treatment periods during which they will receive atorvastatin 20 mg per day or matched placebo. On each of the last 7 days of each treatment period, participants will rate their muscle symptoms on a Visual Analogue Scale (VAS).
At the end of their trial, participants will be shown numerical and graphical summaries of their own symptom data during statin and placebo periods. The primary analysis on the aggregate data from all participants will be a linear mixed model for VAS muscle symptom score, comparing scores during treatment with statin and placebo.
Ethics and disseminationThis trial received a favourable opinion from South Central-Hampshire A Research Ethics Committee. Results will be published in a peer-reviewed medical journal. Dissemination of results to patients will take place via the media, website (statinwise.lshtm.ac.uk) and patient organisations.
Trial registration numberhttp://ift.tt/2ibD808
Prehospital intravenous access for survival from out-of-hospital cardiac arrest: propensity score matched analyses from a population-based cohort study in Osaka, Japan
Objectives
Prehospital intravenous access is a common intervention for patients with out-of-hospital cardiac arrest (OHCA). We aimed to assess the effectiveness of prehospital intravenous access and subsequent epinephrine administration on outcomes among OHCA patients.
MethodsWe conducted a prospective cohort study of patients with OHCA from non-traumatic causes aged ≥18 years in Osaka, Japan from January 2005 through December 2012. The primary outcome was 1-month survival with favourable neurological outcome defined as a cerebral performance category of 1 or 2. The association between intravenous line placement and survival with favourable neurological outcome was evaluated by logistic regression, after propensity score matching for the intravenous access attempt stratified by initial documented rhythm of ventricular fibrillation (VF) or non-VF. The contribution of epinephrine administration to the outcome was also explored.
ResultsAmong OHCA patients during the study period, 3208 VF patients and 38 175 non-VF patients were included in our analysis. Intravenous access attempt was negatively associated with 1-month survival with a favourable neurological outcome in VF group (OR 0.76, 95% CI 0.59 to 0.98), while no association was observed in the non-VF group (OR 1.06, 95% CI 0.84 to 1.34). Epinephrine administration had no positive association in the VF patients (OR 0.75, 95% CI 0.51 to 1.07) and positively associated in the non-VF patients (OR 1.52, 95% CI 1.08 to 2.08) with the favourable neurological outcome.
ConclusionsIntravenous access attempt could be negatively associated with survival with a favourable neurological outcome after OHCA. Subsequent epinephrine administration might be effective for non-VF OHCAs.
http://ift.tt/2jDu8RC
US oncology-wide incidence, duration, costs and deaths from chemoradiation mucositis and antimucositis therapy benefits
Future Oncology, Ahead of Print.
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Emotional distress and subjective impact of the disease in young women with breast cancer and their spouses
Future Oncology, Ahead of Print.
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Design, synthesis and cytotoxic evaluation of novel furo[2,3-b]quinoline derivatives
Abstract
A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized by introducing benzyl ether, benzoate and benzenesulfonate to 6-position of furo[2,3-b]quinoline and their chemical structures were confirmed by ESI-MS, 1H NMR and 13C NMR spectra. All target compounds were evaluated in vitro against four human cancer cell lines (HCT-116, MCF-7, U2OS and A549) by MTT method. Cytotoxic assay showed that compounds 8a, 8e, 10a, 10b and 10c exhibited more potent cytotoxicities compared to 2-bromine-6-hydroxyfuro-[2,3-b]quinoline (7). Compound 10c exhibited higher anti-proliferative activity (IC50 values ranging from 4.32 to 24.96 μM) against four human cancer cell lines (HCT-116, MCF-7, U2OS and A549) and weak cytotoxicity on normal cell HL-7702, which suggested that 10c might be an ideal anticancer candidate. Compounds 8a, 10a, 10b showed good selectivities to MCF-7 and HCT-116, which could be considered as ideal selective candidates for further study. The SARs showed that the introduction of the benzyl ether and benzenesulfonate could significantly improve cytotoxicities, while the benzoate failed to enhance potency obviously.
This article is protected by copyright. All rights reserved.
A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized and screened for cytotoxic activities against four human cancer cell lines.
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Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201
Abstract
Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.
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Hepatitis C testing and re-testing among people attending sexual health services in Australia, and hepatitis C incidence among people with human immunodeficiency virus: analysis of national sentinel surveillance data
Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and inciden...
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Provider initiated tuberculosis case finding in outpatient departments of health care facilities in Ghana: yield by screening strategy and target group
Meticulous identification and investigation of patients presenting with tuberculosis (TB) suggestive symptoms rarely happen in crowded outpatient departments (OPDs). Making health providers in OPDs diligently ...
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“Does the Salmonella Genomic Island 1 (SGI1) confer invasiveness properties to human isolates?”
In the eighties, a multidrug resistant clone of Salmonella Typhimurium DT104 emerged in UK and disseminated worldwide. This clone harbored a Salmonella genomic island 1 (SGI1) that consists of a backbone and a mu...
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Powerful Inference with the D-Statistic on Low-Coverage Whole-Genome Data
The detection of ancient gene flow between human populations is an important issue in population genetics. A common tool for detecting ancient admixture events is the D-statistic. The D-statistic is based on the hypothesis of a genetic relationship that involves four populations, whose correctness is assessed by evaluating specific coincidences of alleles between the groups. When working with high throughput sequencing data calling genotypes accurately is not always possible, therefore the D-statistic currently samples a single base from the reads of one individual per population. This implies ignoring much of the information in the data, an issue especially striking in the case of ancient genomes. We provide a significant improvement to overcome the problems of the D-statistic by considering all reads from multiple individuals in each population. We also apply type-specific error correction to combat the problems of sequencing errors and show a way to correct for introgression from an external population that is not part of the supposed genetic relationship, and how this leads to an estimate of the admixture rate.\\ We prove that the D-statistic is approximated by a standard normal. Furthermore we show that our method outperforms the traditional D-statistic in detecting admixtures. The power gain is most pronounced for low/medium sequencing depth (1-10X) and performances are as good as with perfectly called genotypes at a sequencing depth of 2X. We show the reliability of error correction on scenarios with simulated errors and ancient data, and correct for introgression in known scenarios to estimate the admixture rates.
http://ift.tt/2BBidMe
Pas de deux: An Intricate Dance of Anther Smut and Its Host
The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host, Silene latifolia, serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores. In the current study, transcriptome analyses of the fungus and its host were conducted during discrete stages of bud development so as to identify changes in fungal gene expression that lead to spore development and to identify changes associated with infection in the host plant. In contrast to early biotrophic phase stages of infection for the fungus, the latter stages involve tissue necrosis and in the case of infected female flowers, further changes in the developmental program in which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via Illumina RNA sequencing revealed enrichment of fungal genes encoding small secreted proteins, with hallmarks of effectors and genes found to be relatively unique to the Microbotryum species complex. Host gene expression analyses also identified interesting sets of genes up-regulated, including those involving stress response, host defense response and several agamous-like MADS-box genes (AGL61 and AGL80), predicted to interact and be involved in male gametophyte development.
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Acetylsalicylic Acid Governs the Effect of Sorafenib in RAS- Mutant Cancers
Purpose: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. Experimental Design: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown. In vitro results were confirmed in RAS-mutant xenograft mouse models in vivo. Results: The addition of aspirin but not isobutylphenylpropanoic acid (ibruprofen) or celecoxib (celebrex) significantly increased the in vitro cytotoxicity of sorafenib. Mechanistically, combined exposure resulted in increased BRAF/CRAF dimerization and the simultaneous hyper-activation of the AMPK and ERK pathways. Combining sorafenib with other AMPK activators, like metformin or A769662, was not sufficient to decrease cell viability due to sole activation of the AMPK pathway. The cytotoxicity of sorafenib and aspirin was blocked by inhibition of the AMPK or ERK pathways through shRNA or via pharmacological inhibitors of RAF (LY3009120), MEK (trametinib) or AMPK (compound C). The combination was found to be specific for RAS/RAF-mutant cells and had no significant effect in RAS/RAF-wild type keratinocytes or melanoma cells. In vivo treatment of human xenografts in NSG mice with sorafenib and aspirin significantly reduced tumor volume compared to each single-agent treatment alone. Conclusion: Combined sorafenib and aspirin exerts cytotoxicity against RAS/RAF-mutant cells by simultaneously affecting two independent pathways and represents a promising novel strategy for the treatment of RAS-mutant cancers.
http://ift.tt/2jC4VqK
Packed cell volume and bone marrow cytological responses in Trypanosoma vivax -induced acute trypanosomosis in Nigerian Sokoto Red goats
Abstract
Bone marrow responses have been identified as key determinants of trypanotolerance in cattle as they determine the ability for hemopoietic cell regeneration and control of anemia. However, not much is known about such responses in Nigerian breed of goats known to show different susceptibilities to trypanosome infections. Early bone marrow events associated with pathogenesis of Sokoto Red goats to Trypanosoma vivax were investigated in six goats to assess their role in susceptibility of this goat breed to trypanosomiasis. A total of six Sokoto Red goats of mixed sexes were used. While four of the goats randomly selected were infected with Trypanosoma vivax, the remaining two served as control. The parameters examined included packed cell volume (PCV) and differential bone marrow cytology. Cytological changes in the bone marrow of goats with acute trypanosomosis were compared to the controls. T. vivax caused an acute disease course in the goats resulting to mild drop in PCV and death 2–3 weeks post infection (PI). Associated bone marrow (BM) cytological changes were characterized by moderate erythroid hyperplasia with a resultant lower myeloid:erythroid (M:E) ratio, while the granulocytic maturation rate was 3.15 ± 0.6 and 2.42 ± 0.0 for infected and control animals, respectively. However, significant macrophage (MC) numbers (hyperplasia) were detected in the BM of the infected group. Most of the MCs phagocytized mature red blood cells (RBC) and band or mature white blood cells (WBC) only while no MC phagocytized immature cells. The MCs in BM of control goats phagocytized no blood cells. The study confirmed that mature blood cells form the first cell types to be phagocytized by MCs of BM in the pathogenesis of anemia in T. vivax-infected Sokoto Red goats while early onset of MC hyperplasia and erythrophagocytosis are indicators of susceptibility to trypanosomosis in this breed of goats and perhaps other susceptible ruminants.
http://ift.tt/2iBpO8U
A biocompatible decellularised pulp scaffold for regenerative endodontics
Abstract
Aim
To investigate the feasibility of decellularising the entire dental pulp using a mild treatment protocol to develop a decellularised biological extracellular matrix scaffold for use in regenerative endodontic procedures.
Methodology
Decellularised human dental pulps were assessed using histological and immunohistochemical methods, scanning electron microscope and DNA quantification assay. Cytotoxicity assays to determine decellularised scaffold biocompatibility were also performed. Decellularised scaffolds were seeded with human dental pulp stem cells and cell viability assessed using Live/Dead® stain. Quantitative data were analysed statistically using Student's t-test and one-way analysis of variance to compare mean values between groups depending on group numbers.
Results
Assessment of decellularised tissues revealed an acellular matrix with preservation of native tissue histoarchitecture and composition. Decellularised tissues showed no evidence of cytotoxicity, with cell growth in direct contact with the scaffold and no reduction in cellular activity following extract incubation. Furthermore, the scaffold was able to support human dental pulp stem cell viability and attachment following recellularisation. .
Conclusions
Promising results were observed in developing a decellularised biological scaffold derived from the dental pulp with the perseveration of extracellular structural components which are required for tissue specific regeneration.
This article is protected by copyright. All rights reserved.
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ATR Promotes Faithful Chromosome Segregation in Mitosis [Research Watch]
ATR localized to centromeres to prevent lagging chromosomes independent of its role in replication stress.
http://ift.tt/2AjNjKa
PMN-MDSC Infiltration Blocks the Antitumor Effects of CSF1R Inhibition [Research Watch]
CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.
http://ift.tt/2AoYfV3
SRPK2 Acts Downstream of MTORC1 to Promote De Novo Lipogenesis [Research Watch]
mTORC1-dependent SRPK2 phosphorylation induces splicing of lipogenic transcripts involved in tumor growth.
http://ift.tt/2AjNeWS
Pancreatitis-Induced p62 Accumulation Promotes Pancreatic Cancer [Research Watch]
Defective autophagy and stress in acinar cells drives the progression of PanIN1 lesions to PDAC.
http://ift.tt/2ApnS7V
Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers [Research Articles]
We have profiled, for the first time, an evolving human metastatic microenvironment, measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, ECM organization and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer (HGSOC) metastases that ranged from minimal to extensive disease, we show how non-malignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, whilst also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and twelve other primary solid cancers, suggesting that there may be a common matrix response to human cancer.
http://ift.tt/2Ai6VOV
Genomic landscape of cell-free DNA in patients with colorectal cancer [Research Briefs]
"Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of cancer patients are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cancer patient cohorts can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 colorectal cancer (CRC) patients. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based CRC sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range 1-13, median 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biologic insights.
http://ift.tt/2Ape9Pa
Model for pressure drop and flow deflection in the numerical simulation of stents in aneurysms
Summary
The numerical simulation of flow diverters like stents contributes to the development and improvement of endovascular stenting procedures, leading ultimately to an improved treatment of intracranial aneurysms. Due to the scale difference between the struts of flow diverters and the full artery, it is common to avoid fully resolved simulations at the level of the stent porosity. Instead, the effect of stents on the flow is represented by a heuristic continuum model. However, the commonly used porous media models describe the properties of flow diverters only partially, because they do not explicitly account for the deflection of the flow direction by the stent. We show that this deficiency can be circumvented by adopting the theoretical framework of screen models. The article first reviews existing screen models. It then proposes an explicit formula for the drag and the deflection coefficient, as predicted by each model, for both perpendicular and inclined angles. The results of 2D numerical simulations are used to formulate a generalization of these formulas, to achieve best results in the case of stent modeling. The obtained model is then validated, again through 2D numerical simulation. This article is protected by copyright. All rights reserved.
http://ift.tt/2kezAhR
Correction to: Abstracts
Abstract
Due to an error with the registration system, the following abstract was regrettably omitted from the Poster Sessions. The abstract should have been included as PS-10-021 and displayed on page S166.
http://ift.tt/2zUX2HQ
Frontmatter
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: i-iii
http://ift.tt/2AB33ZR
Maintaining protein composition in cilia
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 1-11
http://ift.tt/2iB2B6M
Eremophilane-type sesquiterpenes from fungi and their medicinal potential
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 13-28
http://ift.tt/2ACbXXf
How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 29-45
http://ift.tt/2iymb3H
Targeted degradomics in protein terminomics and protease substrate discovery
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 47-54
http://ift.tt/2AB2Rd5
Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2–FAM72-|
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 55-61
http://ift.tt/2iB2kAM
Domain topology of human Rasal
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 63-72
http://ift.tt/2AB2LCf
The consequences of deglycosylation of recombinant intra-melanosomal domain of human tyrosinase
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 73-77
http://ift.tt/2iB2doQ
Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 79-92
http://ift.tt/2AB2FKT
The long non-coding RNA CRNDE promotes cervical cancer cell growth and metastasis
Journal Name: Biological Chemistry
Volume: 399
Issue: 1
Pages: 93-100
http://ift.tt/2iBlgPT
Morphological bactericidal fast-acting effects of peracetic acid, a high-level disinfectant, against Staphylococcus aureus and Pseudomonas aeruginosa biofilms in tubing
The bactericidal effect of disinfectants against biofilms is essential to reduce potential endoscopy-related infections caused by contamination. Here, we investigated the bactericidal effect of a high-level di...
http://ift.tt/2BtqIs1
Arsenic Exposure in Incident Hemodialysis Patients
We read with interest the article by Tonelli et al,1 who prospectively examined plasma concentrations of 25 trace elements in 198 incident hemodialysis patients in Canada. Notably, the group reported that some hemodialysis patients have excessive plasma total arsenic concentrations, and the proportion of patients with plasma arsenic concentrations exceeding the 95th percentile was 9.1% to 9.8%. The observation is important, but we believe that dietary intake of organic arsenic compounds should be excluded before any definite conclusions can be drawn.
http://ift.tt/2AlfecP
Vascular Access Outcomes Reported in Maintenance Hemodialysis Trials: A Systematic Review
Many randomized controlled trials have been performed with the goal of improving outcomes related to hemodialysis vascular access. If the reported outcomes are relevant and measured consistently to allow comparison of interventions across trials, such trials can inform decision making. This study aimed to assess the scope and consistency of vascular access outcomes reported in contemporary hemodialysis trials.
http://ift.tt/2ArpC0N
Corticosteroids in IgA Nephropathy
Corticosteroid use in patients with immunoglobulin A nephropathy (IgAN) remains controversial. The KDIGO (Kidney Disease: Improving Global Outcomes) guideline recommended use of renin-angiotensin-aldosterone system (RAAS) inhibitors as the initial approach, followed by a course of corticosteroids in patients with IgAN who have an estimated glomerular filtration rate (eGFR)>50mL/min/1.73m2 and proteinuria with protein excretion > 1g/d.1 The VALIGA (Validation Study of the Oxford Classification of IgAN) retrospective study2 and 2 randomized controlled trials (RCTs)3,4 reported that corticosteroids improved proteinuria and protected kidney function in the long term.
http://ift.tt/2Alf991
Utah responders leave naloxone kits with families of overdose patients
The Unified Fire Authority will also teach everyone how to use the kit in an effort to teach the public how to reverse overdoses
http://ift.tt/2i92U5c
Volume, Dose, and Fractionation Considerations for IMRT-based Re-Irradiation in Head and Neck Cancer: A Multi-Institution Analysis
For patients with squamous cell carcinoma of the head and neck undergoing re-irradiation with IMRT, doses ≥66 Gy may be associated with improved outcomes. Postoperatively, doses of 50-66 Gy appear adequate after removal of gross disease. Hyperfractionation and elective neck irradiation are not associated with an obvious benefit and may increase toxicity.
http://ift.tt/2jE7lFh
Radiation Necrosis and White Matter Lesions in Pediatric Patients with Brain Tumors treated with Pencil Beam Scanning Proton Therapy
Limited clinical data in children treated with pencil beam scanning proton therapy for a brain tumor are available. We retrospectively analyzed our pediatric patients and reviewed magnetic resonance imaging changes after proton therapy, to assess the rate of radiation necrosis and white matter lesions. Overall, children treated with PBS proton therapy demonstrated a low prevalence of symptomatic radiation necrosis and white matter lesions, compared to similar cohorts treated with either proton or photon radiation therapy.
http://ift.tt/2i6vhkh
A prospective multicenter phase II trial of induction chemotherapy followed by bio-chemoradiotherapy for locally advanced recurrent nasopharyngeal carcinoma
In this phase II study, an intensive regimen, consisting of induction docetaxel, cisplatin and fluorouracil followed by weekly docetaxel and cetuximab in concurrence with intensity modulated radiotherapy was shown to be efficacious in treating advanced locally recurrent nasopharyngeal carcinoma. The 3-year progression-free and overall survival rates were 35.7% and 63.8%, respectively. The rate of severe late complication is similar to other contemporary studies employing IMRT.
http://ift.tt/2jDuesH
Mucosal Healing and Long-term Outcomes of Patients With Inflammatory Bowel Diseases Receiving Clinic-based vs Trough Concentration-based Dosing of Infliximab
The trough concentration adapted infliximab treatment (TAXIT) trial demonstrated that maintaining infliximab trough concentrations at 3–7 μg/mL is most effective at inducing remission in patients with inflammatory bowel diseases (IBD), with fewer flares than clinic-based dosing. We performed a follow-up analysis of study participants to explore the correlation between trough dosing strategy and mucosal healing, continued infliximab use, and rates of hospitalization, surgery, and steroid use.
http://ift.tt/2jDfzNP
Elevated serum antiphospholipid antibodies in adults with celiac disease
An increased incidence of thrombosis is suggested in celiac disease. We explored serum levels of antiphospholipid antibodies in untreated and treated adult celiac disease patients.
http://ift.tt/2zG5czO
Efficacy and safety of SIC-8000 (Eleview®) for submucosal injection for Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection in an in vivo porcine model
Submucosal injection is generally required for both endoscopic-mucosal resection (EMR) and submucosal dissection (ESD). SIC-8000 (Eleview™) is a new FDA 510 (k) cleared and CE marked liquid composition for submucosal injection, containing a biocompatible polymer as a cushioning agent.
http://ift.tt/2nmYw7Z
Gene deletions leading to a reduction in the number of cyclopentane rings in Sulfolobus acidocaldarius tetraether lipids
Abstract
The cell membrane of (hyper)thermophilic archaea, including the thermoacidophile Sulfolobus acidocaldarius, incorporate dibiphytanylglycerol tetraether lipids. The hydrophobic cores of such tetraether lipids can include up to eight cyclopentane rings. Presently, nothing is known of the biosynthesis of these rings. In the present study, a series of S. acidocaldarius mutants deleted of genes currently annotated as encoding proteins involved in sugar/polysaccharide processing were generated and their glycolipids were considered. Whereas the glycerol-dialkyl-glycerol tetraether core of a S. acidocaldarius tetraether glycolipid considered here mostly includes four cyclopentane rings, in cells where the Saci_0421 or Saci_1201 genes had been deleted, species containing zero, two or four cyclopentane rings were observed. At the same time, in cells lacking Saci_0201, Saci_0275, Saci_1101, Saci_1249 or Saci_1706, lipids containing mostly four cyclopentane rings were detected. Although Saci_0421 and Saci_1201 are not found in proximity to other genes putatively involved in lipid biosynthesis, homologues of these sequences exist in other Archaea where cyclopentane-containing tetraether lipids are found. Thus, Saci_0421 and Saci_1201 represent the first proteins described that somehow contribute to the appearance of cyclopentane rings in the core moiety of the S. acidocaldarius glycolipid considered here.http://ift.tt/2BCOIKe
Genomic insights into the non-histamine production and proteolytic and lipolytic activities of Tetragenococcus halophilus KUD23
Abstract
Tetragenococcus halophilus KUD23, a non-histamine producer, was isolated from a traditional Korean high-salt fermented soybean paste, doenjang. The strain was safe in terms of antibiotic susceptibility, hemolytic activity, and biofilm formation. It could grow on De Man-Rogosa-Sharpe agar containing 21% (w/v) NaCl, exhibited acid production at 15% NaCl, and had strain-specific proteolytic and lipolytic activities under salt stress. Complete genome analysis of T. halophilus KUD23 and comparative genomic analysis shed light on the genetic background behind these phenotypic characteristics, including non-production of histamine and proteolytic and lipolytic activities.http://ift.tt/2kgYVru
Case Series: Slowing Alpha Rhythm in Late-Stage ALS Patients
To this date, the cognitive abilities of patients in the final stage of Amyotrophic Lateral Sclerosis (ALS) are largely unknown. Residing in a completely locked-in state (CLIS) makes interaction by regular means impossible. Many attempts were made to establish communication through Brain-computer interfaces (BCIs), but success has been very limited (Marchetti and Priftis, 2015). It has been theorized that the loss of motor-functions leads to an extinction of both goal directed thinking and physiological control, leaving only reflex-like responses to fundamental, personal questions (Gallegos-Ayala et al., 2014; Chaudhary et al., 2017).
http://ift.tt/2izmviA
Retraction of: Tumor Protein D52-Like 2 Contributes to Proliferation of Breast Cancer Cells; 10.1089/cbr.2014.1723
Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.
http://ift.tt/2AAgcCh
Retraction of: Tumor Protein D52-Like 2 Accelerates Gastric Cancer Cell Proliferation; 10.1089/cbr.2014.1766
Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.
http://ift.tt/2iBggeo
An Optimized Hemagglutination Inhibition (HI) Assay to Quantify Influenza-specific Antibody Titers
The presented protocols describe how to perform a hemagglutination inhibition assay to quantify influenza-specific antibody titers from serum samples of influenza vaccine recipients. The first assay determines optimal viral antigen concentrations by hemagglutination. The second assay quantifies influenza-specific antibody titers by hemagglutination inhibition.
http://ift.tt/2zI96s5
Automated Robotic Liquid Handling Assembly of Modular DNA Devices
Here, an automated workflow to perform modular DNA "device" assembly using a modular cloning DNA assembly method on liquid-handling robots is presented. The protocol uses an intuitive software tool for generating liquid handler picklists for combinatorial DNA device library generation, which we demonstrate using two liquid handling platforms.
http://ift.tt/2BpznvB
Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis
Abstract
Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically related and clinically unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically related areas compared to unrelated areas (p < 0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p < 0.0001). While most poly-GR dendritic inclusions were pTDP-43 positive, only 4% of pTDP-43 dendritic inclusions were poly-GR positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to dendrites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites.
http://ift.tt/2AytqQ5
Translational Development of Microbiome-Based Therapeutics: Kinetics of E. coli Nissle and Engineered Strains in Humans and Nonhuman Primates
Abstract
Understanding the pharmacology of microbiome-based therapeutics is required to support the development of new medicines. Strains of E. coli Nissle (EcN) were genetically modified and administered to cynomolgus monkeys at doses of 1 × 109 and 1 × 1012 colony-forming units (CFU)/day for 28 days. A clinical study to evaluate the exposure and clearance of EcN in healthy volunteers was also performed. Healthy subjects received oral doses of EcN, 2.5 to 25 × 109 CFU 3 times daily for 28 days or a single day. In cynomolgus monkeys, replicating strains yielded higher fecal concentrations than nonreplicating strains and persisted for longer following cessation of dosing. In the clinical study, all subjects cleared EcN following cessation of dosing with median clearance of 1 week. Quantitative methodology can be applied to microbiome-based therapeutics, and similar kinetics and clearance were observed for EcN in cynomolgus monkeys and humans.
http://ift.tt/2BEGsJN
Exploring fish microbial communities to mitigate emerging diseases in aquaculture
Abstract
Aquaculture is the fastest-growing animal food sector worldwide and expected to further increase to feed the growing human population. However, existing and (re-)emerging diseases are hampering fish and shellfish cultivation and yield. For many diseases, vaccination protocols are not in place and the excessive use of antibiotics and other chemicals is of substantial concern. A more sustainable disease control strategy to protect fish and shellfish from (re-)emerging diseases could be achieved by introduction or augmentation of beneficial microbes. To establish and maintain a 'healthy' fish microbiome, a fundamental understanding of the diversity and temporal-spatial dynamics of fish-associated microbial communities and their impact on growth and health of their aquatic hosts is required. This review describes insights in the diversity and functions of the fish bacterial communities elucidated with next-generation sequencing and discusses the potential of the microbes to mitigate (re-)emerging diseases in aquaculture.http://ift.tt/2kfTdWT
Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing
Radiation Research, Volume 188, Issue 6, Page 661-671, December 2017.
http://ift.tt/2AApC0S
The Impact of Hypoxia on Out-of-Field Cell Survival after Exposure to Modulated Radiation Fields
Radiation Research, Volume 188, Issue 6, Page 636-644, December 2017.
http://ift.tt/2iBcO3c
Lung Cancer Risk from Plutonium: A Pooled Analysis of the Mayak and Sellafield Worker Cohorts
Radiation Research, Volume 188, Issue 6, Page 645-660, December 2017.
http://ift.tt/2iyULL5
Organ Doses Associated with Partial-Body Irradiation with 2.5% Bone Marrow Sparing of the Non-Human Primate: A Retrospective Study
Radiation Research, Volume 188, Issue 6, Page 615-625, December 2017.
http://ift.tt/2AyV4wA
Urinary miRNAs as Biomarkers for Noninvasive Evaluation of Radiation-Induced Renal Tubular Injury
Radiation Research, Volume 188, Issue 6, Page 626-635, December 2017.
http://ift.tt/2iziVoB
Long-Term Deficits in Behavior Performances Caused by Low- and High-Linear Energy Transfer Radiation
Radiation Research, Volume 188, Issue 6, Page 672-680, December 2017.
http://ift.tt/2AyUv5W
Tumor Cell Invasion Induced by Radiation in Balb/C Mouse is Prevented by the Cox-2 Inhibitor NS-398
Radiation Research, Volume 188, Issue 6, Page 605-614, December 2017.
http://ift.tt/2iwvykp
Measurement of DNA-Dependent Protein Kinase Phosphorylation Using Flow Cytometry Provides a Reliable Estimate of DNA Repair Capacity
Radiation Research, Volume 188, Issue 6, Page 597-604, December 2017.
http://ift.tt/2AvrMyN
Nanodosimetric Simulation of Direct Ion-Induced DNA Damage Using Different Chromatin Geometry Models
Radiation Research, Volume 188, Issue 6, Page 690-703, December 2017.
http://ift.tt/2izJSJ0
Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial)
Abstract
Background
The accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) has been improved with the placement of a clip in the positive node prior to treatment. Several methods have been described for clipped node excision during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound (IOUS)-guided excision of the clipped node during SLNB and investigated whether the accuracy of SLNB is improved.
Methods
After approval by the Institutional Ethics Committee, all breast cancer patients undergoing NAT had an US-visible clip placed in the positive node. The ILINA trial consisted of IOUS-guided excision of the clipped node along with SLNB and axillary lymph node dissection (ALND).
Results
Forty-six patients had a clip placed in the positive node. In two (4.3%) cases, the clip could not be seen prior to surgery and the patient underwent ALND; however, the clipped node was successfully removed by IOUS-guided excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with IOUS-guided excision of the clipped node and ALND, and were subsequently included in the ILINA trial. Nine patients were not included (five patients with SLNB only and four patients with ALND without SLNB). SLNB matched the clipped node in 27 (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95% confidence interval 0.1–21.1%).
Conclusions
IOUS-guided excision of the axillary clipped node after NAT was feasible, safe, and successful in 100% of cases. The ILINA trial is accurate in predicting axillary nodal status after NAT.
http://ift.tt/2izclyJ
HBV infection and HCC: the dangerous liaisons'
Long-term relationships are somehow unpredictable. Periods of harmony are often followed by times of conflict with outcomes which are difficult to predict. This precept can apply to the relationship between HBV and human species. HBV acquired at birth or in early childhood establishes lifelong persistent infection in the majority of subjects, which is evolving, and characterised by fluctuations of virological and clinical parameters. The overall impact of these fluctuations in the development of liver fibrosis and hepatocellularcarcinoma has often puzzled clinicians and researchers studying this complex and somewhat fascinating interaction between HBV and our species. An interesting new piece of information, related to this interaction, has now been added, thanks to the work of the group of GA Kim and YS Lim, published in Gut.1
Let's try to first summarise the main points of this puzzle. The early phase of the HBV-host relationship is characterised by normal serum alanine...
http://ift.tt/2j7nm7j
Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma
Objective
Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour microenvironment (TME). Targeting tumour-associated CXCR2+neutrophils (TAN) or tumour-associated CCR2+ macrophages (TAM) alone improves antitumour immunity in preclinical models. However, a compensatory influx of an alternative myeloid subset may result in a persistent immunosuppressive TME and promote therapeutic resistance. Here, we show CCR2 and CXCR2 combined blockade reduces total tumour-infiltrating myeloids, promoting a more robust antitumour immune response in PDAC compared with either strategy alone.
MethodsBlood, bone marrow and tumours were analysed from PDAC patients and controls. Treatment response and correlative studies were performed in mice with established orthotopic PDAC tumours treated with a small molecule CCR2 inhibitor (CCR2i) and CXCR2 inhibitor (CXCR2i), alone and in combination with chemotherapy.
ResultsA systemic increase in CXCR2+ TAN correlates with poor prognosis in PDAC, and patients receiving CCR2i showed increased tumour-infiltrating CXCR2+ TAN following treatment. In an orthotopic PDAC model, CXCR2 blockade prevented neutrophil mobilisation from the circulation and augmented chemotherapeutic efficacy. However, depletion of either CXCR2+ TAN or CCR2+ TAM resulted in a compensatory response of the alternative myeloid subset, recapitulating human disease. This was overcome by combined CCR2i and CXCR2i, which augmented antitumour immunity and improved response to FOLFIRINOX chemotherapy.
ConclusionDual targeting of CCR2+ TAM and CXCR2+ TAN improves antitumour immunity and chemotherapeutic response in PDAC compared with either strategy alone.
http://ift.tt/2Bs8eYK
Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study
Objective
Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study.
DesignDouble-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations.
ResultsThe 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study.
ConclusionVonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated.
Trial registration numbershttp://ift.tt/2j8oS9d
Efficacy of iron supplementation may be misinterpreted using conventional measures of iron status in iron-depleted, nonanemic women undergoing aerobic exercise training [Dietary supplements]
Background: Despite its known detrimental effects, iron deficiency remains the most common micronutrient deficiency in the world. Many interventions that aim to improve iron status involve physically active populations. Intense aerobic exercise training negatively affects iron status; however, the impact of regular moderate aerobic exercise on the effectiveness of iron supplementation remains unclear.
Objective: This study aimed to determine whether aerobic training modifies the assessment of the effectiveness of iron supplementation in improving conventional iron status measures.
Design: Seventy-two iron-depleted, nonanemic Chinese women [serum ferritin (sFer) <25 μg/L and hemoglobin >110 g/L] were included in an 8-wk, partially blinded, randomized controlled trial with a 2 x 2 factorial design including iron supplements (42 mg elemental Fe/d) or placebo and aerobic training (five 25-min sessions/wk at 75–85% of maximum heart rate) or no training. Linear mixed models were used to evaluate the relation between supplement type, training, and changes in iron status over time, measured by sFer, hemoglobin, soluble transferrin receptor (sTfR), and estimated total body iron.
Results: After treatment, both the iron-supplemented trained and untrained groups showed significantly improved sFer, sTfR, and body iron values compared with either of the placebo groups. Similarly, trained participants had significantly higher aerobic fitness measures than untrained participants. Training modified the sFer response to supplementation (training by supplement interaction, P = 0.07), with the iron-supplemented trained group having significantly lower sFer than the iron-supplemented untrained group at week 8 (mean ± SD: 31.8 ± 13.5 and 47.6 ± 15.7 μg/L, respectively; P = 0.042), whereas there was no significant difference between the placebo trained and untrained groups (21.3 ± 12.2 and 20.3 ± 7.0 μg/L, respectively; P = 1.00).
Conclusions: Regular aerobic training reduces the apparent effectiveness of iron supplementation in improving sFer and calls into question whether conventional measures of iron status accurately reflect iron metabolism in physically active, nonanemic women. This trial was registered at clinicaltrials.gov as NCT03002090.
http://ift.tt/2BDCGQS
Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials [Dietary supplements]
Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.
Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management [body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference] and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.
Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols. Random-effects models were used to estimate pooled effect sizes and 95% CIs. Meta-regressions were performed to assess outcomes in relation to the intervention duration, fiber dose, and fiber type. Publication bias was assessed via Begg's and Egger's tests and funnel plot inspection.
Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84 (95% CI: –1.35, –0.32; P = 0.001), body weight by 2.52 kg (95% CI: –4.25, –0.79 kg; P = 0.004), body fat by 0.41% (95% CI: –0.58%, –0.24%; P < 0.001), fasting glucose by 0.17 mmol/L (95% CI: –0.28, –0.06 mmol/L; P = 0.002), and fasting insulin by 15.88 pmol/L (95% CI: –29.05, –2.71 pmol/L; P = 0.02) compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes.
Conclusions: Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity. This trial was registered at clinicaltrials.gov as NCT03003897.
http://ift.tt/2BEqsay
Maternal weight gain and associations with longitudinal fetal growth in dichorionic twin pregnancies: a prospective cohort study [Pregnancy and lactation]
Background: Maternal metabolic demands are much greater with twin gestations; however, there are no accepted recommendations for maternal weight gain in twin pregnancies.
Objective: We assessed the association of maternal weight gain and fetal growth in dichorionic twins throughout pregnancy.
Design: This was a prospective US cohort study (n = 143, 2012–2013) of dichorionic twin pregnancies with known birth outcomes followed from enrollment (11–13 wk) and for ≤6 research visits throughout gestation. Maternal prepregnancy weight was self-reported, and current weight was measured at each research visit and abstracted from prenatal records. Fetal biometry was assessed by ultrasound at each research visit. Maternal weight and twin-pair fetal size trajectories across gestation were modeled. The adjusted associations between maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk and fetal growth at the subsequent week (i.e., 14, 21, 28, and 35 wk, respectively) were estimated with the use of linear regression.
Results: The mean ± SD maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk was 2.8 ± 3.0 kg, 3.9 ± 1.2 kg, 3.8 ± 1.4 kg, and 4.4 ± 2.2 kg, respectively, with a total gain of 17.7 ± 7.4 kg. Maternal weight gain from 0 to 13 wk (first trimester) was not associated with fetal size at 14 wk. Maternal weight gain from 14 to 20 and 21 to 27 wk (second trimester) was significantly associated with increased fetal weight at 21 wk [increase of 10.5 g/kg maternal weight gain (95% CI: 1.2, 19.8 g)] and 28 wk [increase of 21.3 g/kg maternal weight gain (95% CI: 0.6, 42.0 g)]. Maternal weight gain from 14 to 20 wk was associated with increased twin abdominal circumference (AC) and biparietal diameter at 21 wk. Maternal weight gain from 21 to 27 wk was associated with increased femur and humerus lengths at 28 wk.
Conclusion: Maternal weight gain was associated with dichorionic twin fetal growth in the second trimester only, driven by an association with AC earlier in second trimester and long bones later in the second trimester.
http://ift.tt/2kffh3E
Comparison among criteria to define successful weight-loss maintainers and regainers in the Action for Health in Diabetes (Look AHEAD) and Diabetes Prevention Program trials [Obesity and eating disorders]
Background: Given the low rates of successful weight maintenance after lifestyle-induced weight loss, it is critical to develop approaches that distinguish successful weight-loss maintainers from regainers.
Objective: The aim of this study was to compare published categorization criteria that differentiate maintainers and regainers via quantitative agreement.
Design: The study used publicly available data from Look AHEAD (Action for Health in Diabetes; n = 1791) and Diabetes Prevention Program (DPP; n = 613) participants with ≥3% initial weight loss after lifestyle interventions and 4-y follow-up data. Eight previously published criteria defining maintainers and regainers were compared with respect to number of participants and concordance via agreement statistics. Criteria were assessed separately among those with 3–9% and ≥10% initial weight loss.
Results: Regainers had higher body weight at year 4 than did maintainers (mean difference range: 6.6–11.9 kg in Look AHEAD; 11.5–14.6 kg in DPP; P < 0.0001). Assessing concordance among criteria, agreement was dependent on initial weight loss. Among those with 3–9% initial weight loss in both cohorts, 9 of 28 comparisons were concordant (agreement ≥80%). Among those with ≥10% initial weight loss, 7 of 28 comparisons in Look AHEAD and 13 of 28 in the DPP were in high agreement. The definition of successful weight-loss maintenance "regaining ≤25% of initial weight loss during maintenance" showed high agreement with the most commonly used definition of "staying ≥10% below initial weight" among those with ≥10% initial weight loss (agreement: 85.0% in Look AHEAD; 87.4% in DPP). The same definition of ≤25% regain showed high agreement with the definition of staying ≥5% below initial weight among those with 3–9% initial weight loss (agreement: 91.6% in Look AHEAD; 90.5% in DPP).
Conclusions: Although all of the criteria discriminated on the basis of weight loss, many showed low agreement, which limited cross-study comparisons. Among criteria with high agreement, the definition of successful weight maintenance "regaining ≤25% of initial weight loss during maintenance" is a preferred definition of success, given the realistic challenges of maintaining 100% weight loss and flexible application in populations with high initial weight-loss variations. This trial was registered at clinicaltrials.gov as NCT00017953 (Look AHEAD) and NCT00004992 (DPP).
http://ift.tt/2BEqfUO
Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador [International nutrition]
Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63.
Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids.
Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6–9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine-N-oxide (TMAO) with the use of liquid chromatography–tandem mass spectrometry.
Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA.
Conclusion: The findings supported our hypothesis that early introduction of eggs significantly improved choline and other markers in its methyl group metabolism pathway. This trial was registered at clinicaltrials.gov as NCT02446873.
http://ift.tt/2keYGx4
Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial [Obesity and eating disorders]
Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity.
Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake–related appetite ratings in individuals with obesity.
Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m2): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables.
Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals (P = 0.01), after long-term tDCS.
Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362.
http://ift.tt/2BAI6vD
Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial [Vitamins, minerals, and phytochemicals]
Background: Low potassium has been identified both as a risk factor for type 2 diabetes and as a mediator of the racial disparity in diabetes risk. Low potassium could be a potentially modifiable risk factor, particularly for African Americans.
Objective: We sought to determine the effects of potassium chloride (KCl) supplements, at a commonly prescribed dose, on measures of potassium and glucose metabolism.
Design: Among African-American adults with prediabetes, we conducted a double-blinded pilot randomized controlled trial that compared the effects of 40 mEq K/d as KCl supplements with a matching placebo, taken for 3 mo, on measures of potassium and glucose metabolism, with measures collected from frequently sampled oral-glucose-tolerance tests (OGTTs).
Results: Twenty-seven of 29 recruited participants completed the trial. Participants had high adherence to the study medication (92% by pill count). Participants in both groups gained weight, with an overall mean ± SD weight gain of 1.24 ± 2.03 kg. In comparison with participants who received placebo, urine potassium but not serum potassium increased significantly among participants randomly assigned to receive KCl (P = 0.005 and 0.258, respectively). At the end of the study, participants taking KCl had stable or improved fasting glucose, with a mean ± SD change in fasting glucose of –1.1 ± 8.4 mg/dL compared with an increase of 6.1 ± 7.6 mg/dL in those who received placebo (P = 0.03 for comparison between arms). There were no significant differences in glucose or insulin measures during the OGTT between the 2 groups, but there was a trend for improved insulin sensitivity in potassium-treated participants.
Conclusions: In this pilot trial, KCl at a dose of 40 mEq/d did not increase serum potassium significantly. However, despite weight gain, KCl prevented worsening of fasting glucose. Further studies in larger sample sizes, as well as with interventions to increase serum potassium more than was achieved with our intervention, are indicated to definitively test this potentially safe and inexpensive approach to reducing diabetes risk. This trial was registered at clinicaltrials.gov as NCT02236598.
http://ift.tt/2keuBOd
Differential impact of the cheese matrix on the postprandial lipid response: a randomized, crossover, controlled trial [Lipids]
Background: In a simulated gastrointestinal environment, the cheese matrix modulates dairy fat digestion. However, to our knowledge, the impact of the cheese matrix on postprandial lipemia in humans has not yet been evaluated.
Objective: In healthy subjects, we compared the impact of dairy fat provided from firm cheese, soft cream cheese, and butter on the postprandial response at 4 h and on the incremental area under the curve (iAUC) of plasma triglycerides.
Design: Forty-three healthy subjects were recruited to this randomized, crossover, controlled trial. In random order at intervals of 14 d and after a 12-h fast, subjects ingested 33 g fat from a firm cheese (young cheddar), a soft cream cheese (cream cheese), or butter (control) incorporated into standardized meals that were matched for macronutrient content. Plasma concentrations of triglycerides were measured immediately before the meal and 2, 4, 6, and 8 h after the meal.
Results: Cheddar cheese, cream cheese, and butter induced similar increases in triglyceride concentrations at 4 h (change from baseline: +59%, +59%, and +62%, respectively; P = 0.9). No difference in the triglyceride iAUC0–8 h (P-meal = 0.9) was observed between the 3 meals. However, at 2 h, the triglyceride response caused by the cream cheese (change from baseline: +44%) was significantly greater than that induced by butter (change from baseline: +24%; P = 0.002) and cheddar cheese (change from baseline: +16%; P = 0.0004). At 6 h, the triglyceride response induced by cream cheese was significantly attenuated compared with that induced by cheddar cheese (change from baseline: +14% compared with +42%; P = 0.0004).
Conclusion: This study demonstrates that the cheese matrix modulates the impact of dairy fat on postprandial lipemia in healthy subjects. This trial was registered at clinicaltrials.gov as NCT02623790.
http://ift.tt/2BBL6YI
A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults [Aging]
Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging.
Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults.
Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing.
Results: Amyloid was elevated in 26% (n = 33) of participants. HGLDiet pattern adherence (P = 0.01), sugar intake (P = 0.03), and carbohydrate intake (P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level (P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education.
Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer disease risk. This trial was registered at clinicaltrials.gov as NCT02000583.
http://ift.tt/2kfrwxa
Functional vitamin B-6 status and long-term mortality in renal transplant recipients [Nutritional status, dietary intake, and body composition]
Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.
Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.
Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8–6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK:XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status.
Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29–60 nmol/L), 40.1 nmol/L (IQR: 33.0–48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5–24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17–50 nmol/L), 61.5 nmol/L (IQR: 45.6–86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2–40.0 nmol/L), respectively, in RTRs (all P < 0.001). RTRs had a higher median 3-HK:XA ratio (2.38; IQR: 1.68–3.49) than did healthy controls (2.13; IQR: 1.63–2.71) (P < 0.05). In RTRs, the 3-HK:XA ratio was inversely associated with plasma PLP (β = –0.21, P < 0.001). Moreover, a higher 3-HK:XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs.
Conclusions: Vitamin B-6–deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6–sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease. This trial was registered at clinicaltrials.gov as NCT02811835.
http://ift.tt/2BBO5AF
Complementary feeding with cowpea reduces growth faltering in rural Malawian infants: a blind, randomized controlled clinical trial [International nutrition]
Background: Growth faltering is common in rural African children and is attributed to inadequate dietary intake and environmental enteric dysfunction (EED).
Objective: We tested the hypothesis that complementary feeding with cowpea or common bean flour would reduce growth faltering and EED in 6-mo-old rural Malawians compared with the control group receiving a corn-soy blend.
Design: A prospective, double-blind, randomized controlled clinical trial was conducted in which children received daily feeding for 6 mo (200 kcal/d when 6–9 mo old and 300 kcal/d when 10–12 mo old). The primary outcomes were change in length-for-age z score (LAZ) and improvements in EED, as measured by percentage of lactulose excretion (%L). %L <0.2% was considered normal. Anthropometric measurements and %L through urine were compared between each legume group and the control group with Student's t test.
Results: Of the 355 infants enrolled, 291 infants completed the trial, and 288 were breastfed throughout the duration of the study. Cowpea and common bean added 4.6–5.2 g protein/d and 4–5 g indigestible carbohydrate/d to the diet. LAZ and weight-for-height z score were reduced in all 3 groups from 6 to 12 mo of age. The changes in LAZ [mean (95% CI)] for the cowpea, common bean, and control groups from 6 to 9 mo were –0.14 (–0.24, –0.04), –0.27 (–0.38, –0.16), and –0.27 (–0.35, –0.19), respectively. LAZ was reduced less in infants receiving cowpea than in those receiving control food from 6 to 9 mo (P = 0.048). The absolute value of %L did not differ between the dietary groups at 9 mo of age (mean ± SD: 0.30 ± 0.43, 0.23 ± 0.21, and 0.26 ± 0.31 for cowpea, common bean, and control, respectively), nor did the change in %L from 6 to 9 mo.
Conclusion: Addition of cowpea to complementary feeding in Malawian infants resulted in less linear growth faltering. This trial was registered at clinicaltrials.gov as NCT02472262.
http://ift.tt/2kj5I44
The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men: a 10-wk randomized controlled trial [Nutritional status, dietary intake, and body composition]
Background: The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg–1 · d–1. Aging may increase protein requirements, particularly to maintain muscle mass.
Objective: We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.
Design: In this parallel-group randomized trial, 29 men aged >70 y [mean ± SD body mass index (in kg/m2): 28.3 ± 4.2] were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg–1 · d–1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.
Results: Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P = 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with –0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (–0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with –11.7 ± 31.0 W, P = 0.180 in RDA).
Conclusions: Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance. This trial was registered at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12616000310460.
http://ift.tt/2BAHQwF
Pomegranate juice, but not an extract, confers a lower glycemic response on a high-glycemic index food: randomized, crossover, controlled trials in healthy subjects [Carbohydrate metabolism and diabetes]
Background: Low–glycemic index diets have demonstrated health benefits associated with a reduced risk of developing type 2 diabetes.
Objectives: We tested whether pomegranate polyphenols could lower the glycemic response of a high–glycemic index food when consumed together and the mechanism by which this might occur.
Design: We compared the acute effect of a pomegranate juice and a polyphenol-rich extract from pomegranate (supplement) on the bread-derived postprandial blood glucose concentration in 2 randomized, crossover, controlled studies (double-blinded for the supplements), each on 16 healthy volunteers. An additional randomized, crossover, controlled study on 16 volunteers consuming constituent fruit acids in a pH-balanced solution (same pH as pomegranate) and bread was conducted to determine any contributions to postprandial responses caused by acidic beverages.
Results: As primary outcome, the incremental area under the curve for bread-derived blood glucose (–33.1% ± 18.1%, P = 0.000005) and peak blood glucose (25.4% ± 19.3%, P = 0.0004) were attenuated by pomegranate juice, compared with a control solution containing the equivalent amount of sugars. In contrast, the pomegranate supplement, or a solution containing the malic and citric acid components of the juice, was ineffective. The pomegranate polyphenol punicalagin was a very effective inhibitor of human α-amylase in vitro, comparable to the drug acarbose. Neither the pomegranate extract nor the individual component polyphenols inhibited 14C-D-glucose transport across differentiated Caco-2/TC7 cell monolayers, but they inhibited uptake of 14C-glucose into Xenopus oocytes expressing the human glucose transporter type 2. Further, some of the predicted pomegranate gut microbiota metabolites modulated 14C-D-glucose and 14C-deoxy-D-glucose uptake into hepatic HepG2 cells.
Conclusions: These data indicate that pomegranate polyphenols, when present in a beverage but not in a supplement, can reduce the postprandial glycemic response of bread, whereas microbial metabolites from pomegranate polyphenols exhibit the potential to further modulate sugar metabolism much later in the postprandial period. This trial was registered at clinicaltrials.gov as NCT02486978, NCT02624609, and NCT03242876.
http://ift.tt/2BAHI09
A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Periventricular nodular heterotopia (PNH) is the most common form of malformation of cortical development (MCD) in adulthood but its genetic basis remains unknown in most sporadic cases. We have recently developed a strategy to identify novel candidate genes for MCDs and to directly confirm their causative role in vivo.
http://ift.tt/2ANeFtq
Expanding Cancer Clinical Trial Access for Patients with HIV
People with HIV are often excluded from clinical trials for safety reasons. Preliminary results from an NCI-sponsored study of an immunotherapy drug show that people with HIV can safely participate in clinical trials.
http://ift.tt/2AM20GV
Mouth bacteria linked to esophageal cancer
New research reveals that some types of mouth bacteria are linked to higher risk of developing esophageal cancer and some are linked to lower risk.
http://ift.tt/2nkvXYS
The earlier, the better: the effects of different administration timepoints of sorafenib in suppressing the carcinogenesis of VEGF in rats
Abstract
Purpose
To investigate the optimal starting time point of sorafenib therapy in suppressing the tumor-promoting effects of VEGF up-regulation, which is frequently found after local therapy in clinical practice.
Methods
VEGF was intravenously injected to imitate the evaluated expression after local tumor therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly divided into four groups and sorafenib was administered at different timepoints: (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D) initiating sorafenib 72 h post-VEGF injection. The rate of tumor growth, median survival time, expression of VEGF, and microvessel density (MVD), as determined by immunohistochemical (IHC) examination, were compared.
Results
The results revealed that the tumor size and median survival time were significantly different between the three sorafenib groups compared to the control group (p < 0.05). Median survival times were 19.6 ± 1.78, 31.2 ± 6.99, 27.4 ± 4.9, and 26.5 ± 4.6 days in group A, B, C, and D, respectively. Furthermore, there was a difference in statistical significance between the two sorafenib groups B and D (p = 0.04). Tumors were collected for HE staining and IHC examination. The expression levels of VEGF in B, C, and D were 42.8 ± 7.96, 71.9 ± 15.73, and 73.6 ± 13.73, and all of them were significantly lower than that in the control group (88.3 ± 13.61). Furthermore, the level of MVD was 109.2 ± 8.98 in the control group, which was significantly higher than in the three sorafenib groups (45.7 ± 16.92, 77.1 ± 16.29, and 93.6 ± 12.87, all p < 0.05).
Conclusions
According to our results, the most suitable regimen for the administration of sorafenib is before the increased expression of VEGF, which showed a potential advantage for controlling the tumor growth and prolonging the survival time of test animal via inhibiting VEGF-receptor expression through the bifunction of VEGF, and the reduction of tumor angiogenesis.
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Smokers Always Pay Twice
http://ift.tt/2ixGY7q
Monitoring Lung Cancer Screening Use and Outcomes at Four Cancer Research Network Sites
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1827-1835, December 2017.
http://ift.tt/2ixGNZO
Hospital Procalcitonin Testing and Antibiotic Treatment of Patients Admitted for Chronic Obstructive Pulmonary Disease Exacerbation
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1779-1785, December 2017.
http://ift.tt/2AvPUBt
Procalcitonin in Chronic Obstructive Pulmonary Disease Exacerbations: Is It Ready for Primetime Use?
http://ift.tt/2iwxDgc
Refractory Hypoxemia and Acute Respiratory Distress Syndrome Adjunctive Therapies: An Open Question?
http://ift.tt/2kcmYHV
Incorporating Markers of Disease Severity into Near Real-Time Influenza Surveillance
http://ift.tt/2kfj8ha
Unraveling the Cause of Severe Exertional Dyspnea in a Heavy Smoker
http://ift.tt/2kekzN3
The Critical Care Crisis of Opioid Overdoses in the United States
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1803-1809, December 2017.
http://ift.tt/2kek9WZ
Real-Time Surveillance of Influenza Morbidity: Tracking Intensive Care Unit Resource Utilization
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1810-1817, December 2017.
http://ift.tt/2BDtqw6
Sleep Disturbance in Smokers with Preserved Pulmonary Function and with Chronic Obstructive Pulmonary Disease
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1836-1843, December 2017.
http://ift.tt/2keN9ho
Direct Connection: A Man with Lung Nodules and Filling Defects in the Pulmonary Arterial Tree
http://ift.tt/2BEfYrB
Fair Is Fair: Just Visiting Hours and Reducing Inequities
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1744-1746, December 2017.
http://ift.tt/2BEfKRh
Air Pollution and Hospitalization for Bronchiolitis among Young Children
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1796-1802, December 2017.
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Miliary Nodules: Not Always Tuberculosis
http://ift.tt/2BBfVNc
An Unusual Headache in a Patient Treated with Continuous Positive Airway Pressure
http://ift.tt/2BDwKY4
Reply: Improving Care for Patients with Interstitial Lung Disease, Using Machine Learning, Requires Transparency and Reproducibility
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1864-1865, December 2017.
http://ift.tt/2BBHq9D
The Untold Toll of the Opioid Crisis on Intensive Care Units in the United States
http://ift.tt/2kgtWvr
Can a Floppy Upper Airway Lead to Stiff Lungs?
http://ift.tt/2kiI2wJ
Impact of Intrathoracic Pressure in the Assessment of Pulmonary Hypertension in Overweight Patients
Annals of the American Thoracic Society, Volume 14, Issue 12, Page 1861-1863, December 2017.
http://ift.tt/2kfTNnp
Financial Toxicity: A Common but Rarely Discussed Treatment Side Effect
http://ift.tt/2BB6qOb
Pediatric training and practice of Canadian chiropractic and naturopathic doctors: a 2004–2014 comparative study
To assess chiropractic (DC) and naturopathic doctors' (ND) knowledge, attitudes, and behaviour with respect to the pediatric patients in their practice.
http://ift.tt/2BrMXyD
Integrating herbal medicine into mainstream healthcare in Ghana: clients’ acceptability, perceptions and disclosure of use
Although there are current efforts to integrate herbal medicine (HM) into mainstream healthcare in Ghana, there is paucity of empirical evidence on the acceptability and concurrent use of HM, in the formal hea...
http://ift.tt/2j6G4M8
The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model
Conventional scientific studies had supported the use of polysaccharides and β-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the p...
http://ift.tt/2Bs8reO
In vitro and in vivo aphrodisiac properties of the seed extract from Allium tuberosum on corpus cavernosum smooth muscle relaxation and sexual behavior parameters in male Wistar rats
Allium tuberosum is a well-known spice as well as a herb in traditional Chinese medicine, used for increasing libido and treating erectile dysfunction. However, not many studies have b...
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Anticancer activities of ethanol extract from the Antarctic freshwater microalga, Botryidiopsidaceae sp.
Cancer is a leading cause of human death around the world and occurs through the highly complex coordination of multiple cellular pathways. Recent studies have revealed that microalgal extracts exhibit conside...
http://ift.tt/2BqX0UH
Hodgkin lymphoma: A review and update on recent progress
Abstract
Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced-intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long-term treatment toxicities. CA Cancer J Clin 2017. © 2017 American Cancer Society.
http://ift.tt/2zVRa0U
Combined loss of HLA I and HLA II expression is more common in the non-GCB type of diffuse large B-cell lymphoma
Abstract
As an immune escape mechanism tumor cells may downregulate expression of Human Leukocyte Antigens (HLA). Loss of HLA class I and class II has been described in various subtypes of diffuse large B cell lymphoma (DLBCL), including the not otherwise specified (NOS) subgroup. 1,2 We analyzed HLA class I and class II expression in DLBCL not otherwise specified (NOS) to investigate whether there is an association between HLA expression, cell of origin (COO) and the recently reported FOXP1 expression in non-GCB DLBCL. 3
This article is protected by copyright. All rights reserved.
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Preferential Generation of 15-HETE-PE Induced by IL-13 Regulates Goblet Cell Differentiation in Human Airway Epithelial Cells
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 692-701, December 2017.
http://ift.tt/2jBvdcB
Hyaluronan: Local Climate Change in Asthma?
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 635-636, December 2017.
http://ift.tt/2i7wB6s
A Slippery Cause of a Slimy Problem: Mucin Induction by an Esterified Lipid
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 633-634, December 2017.
http://ift.tt/2jBcz4C
MicroRNA-29c Prevents Pulmonary Fibrosis by Regulating Epithelial Cell Renewal and Apoptosis
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 721-732, December 2017.
http://ift.tt/2i7h3j2
Epithelial Cells Induce a Cyclo-Oxygenase-1–Dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 683-691, December 2017.
http://ift.tt/2jD5DUD
Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 702-710, December 2017.
http://ift.tt/2i7h2vu
Loss of Vascular CD34 Results in Increased Sensitivity to Lung Injury
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 651-661, December 2017.
http://ift.tt/2jAEmCr
Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 662-673, December 2017.
http://ift.tt/2ia2c7P
Cytometric Gating Stringency Impacts Studies of Type 2 Innate Lymphoid Cells in Asthma
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 745-747, December 2017.
http://ift.tt/2jBv88N
Hemoglobin α in Pulmonary Endothelium: Ironing Out Nitric Oxide Signaling
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 639-641, December 2017.
http://ift.tt/2i5GdP5
Allergic Airway Disease: More than Meets the IgE?
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 631-632, December 2017.
http://ift.tt/2jCTgrx
The Lung Likes the Little Fella miR-29
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 637-638, December 2017.
http://ift.tt/2i76gpa
MicroRNA Profiling in Asthma: Potential Biomarkers and Therapeutic Targets
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 642-650, December 2017.
http://ift.tt/2jCT8bx
The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 711-720, December 2017.
http://ift.tt/2i762yk
Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 733-744, December 2017.
http://ift.tt/2jCSWJl
December Highlights/Papers by Junior Investigators/NIH News
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page vi-vi, December 2017.
http://ift.tt/2iaqC0B
House Dust Mite–Induced Allergic Airway Disease Is Independent of IgE and FcεRIα
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 6, Page 674-682, December 2017.
http://ift.tt/2jDn8Ef
Synthesis, Adenosine Receptor Binding and Molecular Modeling Studies of Novel Thieno[2,3-d]pyrimidine Derivatives
Abstract
A series of new molecules containing a thieno[2,3-d]pyrimidine scaffold was synthesized and characterized by adopting an efficient synthetic scheme. The effect of a free or substituted amino group at 2-position as well as an oxo-group, imidazole or 1,2,4-triazole ring at 4-position of the scaffold on the affinity and selectivity towards adenosine receptors (ARs) were evaluated. Compounds 17-19 with a free amino group at 2-position along with the presence of an imidazole/1,2,4-triazole ring at 4-position of the scaffold showed selective binding affinities for hA2A AR whereas carbamoylation of the amino group at 2-position (in presence of an oxo-group at 4-position of the scaffold) increased the affinity and selectivity of certain compounds (7-10) for hA3 AR. Molecular dynamics simulation study of one of the most active compound 8 (Ki hA1 > 30 μM, hA2A = 0.65 μM, and hA3 = 0.124 μM) revealed the role of important amino acid residues for imparting good affinity towards hA3 and hA2A ARs. Molecular docking studies were carried out for other compounds by using the crystal structure of hA2A AR and a homology model of hA3 AR to rationalize their structure activity relationships. The molecular docking results were in agreement with the experimental binding affinity data of ARs.
This article is protected by copyright. All rights reserved.
A new series of thieno[2,3-d]pyrimidine derivatives have been synthesized and evaluated in vitro for their binding affinities towards adenosine receptors (ARs) and in silico to gain insight into their molecular binding interactions with the hA2A and hA3 ARs.
http://ift.tt/2zUWWAh
Albumin Human 25 Percent Solution (AlbuRx 25): Product Information Advisory - Fading Print On Label
Audience: Risk Manager, Critical Care Medicine, Emergency Medicine [Posted 12/01/2017] ISSUE: During routine inspection of retained AlbuRx 25% samples CSL Behring noted the potential for fading print with more effect on the expiration dating on the...
http://ift.tt/2i7ByfH
Bull Capsules, Chao Jimengnan Tablets by Nutra Labs: Recall - Undeclared Drug Ingredients
Audience: Consumer [Posted 12/01/2017] ISSUE: Nutra Labs Inc. is voluntarily recalling lots sold by their firm of the male enhancement supplements Bull 1800 mg Capsules with the production date of 05/08/2016, and Chao Jimengnan 150 mg Tablets with...
http://ift.tt/2jCnR91
The Role of Chest Computed Tomography in the Evaluation and Management of the Patient with Chronic Obstructive Pulmonary Disease
http://ift.tt/2AoWeI8
Benefit of the Shorter Multidrug-Resistant Tuberculosis Treatment Regimen in California and Modified Eligibility Criteria
http://ift.tt/2AoW5EA
Signs of Gas Trapping in Normal Lung Density Regions in Smokers
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 11, Page 1404-1410, December 1, 2017.
http://ift.tt/2AnKfuD
Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 11, Page 1456-1462, December 1, 2017.
http://ift.tt/2AjlnGd
Pauca sed Matura: Few, but Ripe
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 11, Page 1361-1362, December 1, 2017.
http://ift.tt/2AoVLWo
Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 11, Page 1396-1403, December 1, 2017.
http://ift.tt/2Ah3RTb
Toward Early Identification of Clinically Relevant Interstitial Lung Disease
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 11, Page 1368-1369, December 1, 2017.
http://ift.tt/2AquzqF
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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