Spindle cell lesions of the superficial soft tissues often pose a diagnostic challenge due to frequently non-specific clinico-radiologic presentation and overlapping microscopic features, therefore immunohistochemistry remains a favored approach in separating them.
Publication date: Available online 3 July 2017
Source:Trends in Biochemical Sciences
Author(s): Hiroshi Yamamoto, Anett Unbehaun, Christian M.T. Spahn
Internal initiation is a 5′-end-independent mode of translation initiation engaged by many virus- and putatively some cell-encoded templates. Internal initiation is facilitated by specific RNA tertiary folds, called internal ribosomal entry sites (IRESs), in the 5′ untranslated region (UTR) of the respective transcripts. In this review we discuss recent structural insight into how established IRESs first capture and then manipulate the eukaryotic translation machinery through non-canonical interactions and by guiding the intrinsic conformational flexibility of the eukaryotic ribosome. Because IRESs operate with reduced complexity and constitute minimal systems of initiation, comparison with canonical initiation may allow common mechanistic principles of the ribosome to be delineated.
http://ift.tt/2tGX6H9
Publication date: Available online 3 July 2017
Source:Trends in Immunology
Author(s): Thomas Simon, Jonathan S. Bromberg
Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. Finally, the role of the laminins in autoimmune diseases and transplantation will be discussed.
http://ift.tt/2tGNLyQ
Publication date: Available online 3 July 2017
Source:Trends in Immunology
Author(s): Ivaylo I. Ivanov
Studying the interactions between commensal microbes and host intestinal tissue networks is challenging due to the complexity and inaccessibility of the system. A recent study reports a novel organ culture system that will enhance our ability to dissect these interactions.
http://ift.tt/2uER6LX
As muscles converge or intermingle around the perioral area, and it change by the sequential therapy for cleft lip and palate (CLP) infants. The force of perioral muscles has a great influence on maxillary development and morphology. Perioral force in CLP infants has not been well studied, and accurate and reliable measurement of perioral force in infants remains a challenge. The aim of this study was to investigate a new way to accurately and reliably measure perioral force in UCLP infants and explore the change before and after cheiloplasty.
http://ift.tt/2tGugXk
Publication date: Available online 3 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Chun-Yu Liu, Chia-Yun Wu, Karineh Petrossian, Tzu-Ting Huang, Ling-Ming Tseng, Shiuan Chen
Endocrine resistance remains a challenge and an unmet need for managing hormone receptor-positive breast cancer. The mechanisms of endocrine resistance are multifaceted and are likely to evolve over time following various single or combination therapies. The purpose of this review article is to provide general understanding of molecular basis of endocrine resistance of breast cancer and to offer comprehensive review on current treatment options and potential new treatment strategies for endocrine resistant breast cancers. Last but not the least, we discuss current challenges and future directions for management of endocrine resistant breast cancers.
http://ift.tt/2uk7geB
Publication date: Available online 4 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of androgen on steroidogenesis, DHT enhanced the expression of progesterogenic factors and enzymes, including StAR, P450scc and 3βHSD, and cellular cAMP synthesis induced by FSH and IGF-I. Of note, treatment with DHT and IGF-I suppressed Smad1/5/8 phosphorylation and transcription of the BMP target gene Id-1, suggesting that androgen and IGF-I counteract BMP signaling that inhibits FSH-induced progesterone synthesis in rat granulosa cells. DHT was revealed to suppress the expression of BMP-6 receptors, consisting of ALK-2, ALK-6 and ActRII, while it increased the expression of inhibitory Smads in rat granulosa cells. In addition, IGF-I treatment upregulated androgen receptor (AR) expression and DHT treatment suppressed IGF-I receptor expression on rat granulosa cells. Collectively, the results indicate that androgen and IGF-I mutually interact and accelerate progesterone production, at least in part, by regulating endogenous BMP signaling in rat granulosa cells. Cooperative effects of androgen and IGF-I counteract endogenous BMP-6 activity in rat granulosa cells, which is likely to be functionally linked to the steroidogenic property shown in the PCOS ovary.
http://ift.tt/2tL8x15
Publication date: Available online 3 July 2017
Source:Free Radical Biology and Medicine
Author(s): Hong Yong Peh, W.S. Daniel Tan, Tze Khee Chan, Chen Wei Pow, Paul S. Foster, W.S. Fred Wong
Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months. γ-Tocotrienol and prednisolone were given orally. Bronchoalveolar lavage (BAL) fluid and lung tissues were assessed for inflammation, oxidative damage, and regulation of transcription factor activities. Emphysema and lung function were also evaluated. γ-Tocotrienol dose-dependently reduced cigarette smoke-induced BAL fluid neutrophil counts and levels of cytokines, chemokines and oxidative damage biomarkers, and pulmonary pro-inflammatory and pro-oxidant gene expression, but restored lung endogenous antioxidant activities. γ-Tocotrienol acted by inhibiting nuclear translocation of STAT3 and NF-κB, and up-regulating Nrf2 activation in the lungs. In mice exposed to 2-month cigarette smoke, γ-tocotrienol ameliorated bronchial epithelium thickening and destruction of alveolar sacs in lungs, and improved lung functions. In comparison with prednisolone, γ-tocotrienol demonstrated better anti-oxidative efficacy, and protection against emphysema and lung function in COPD. We revealed for the first time the anti-inflammatory and antioxidant efficacies of γ-tocotrienol in cigarette smoke-induced COPD models. In addition, γ-tocotrienol was able to attenuate emphysematous lesions and improve lung function in COPD. γ-Tocotrienol may have therapeutic potential for the treatment of COPD.
Publication date: Available online 3 July 2017
Source:DNA Repair
Author(s): Sonia Jimeno, Emilia Herrera-Moyano, Pedro Ortega, Andrés Aguilera
Eukaryotic cells possess several DNA endonucleases that are necessary to complete different steps in DNA metabolism. Rad2/XPG and Rad27/FEN1 belong to a group of evolutionary conserved proteins that constitute the Rad2 family. Given the important roles carried out by these nucleases in DNA repair and their capacity to create DNA breaks, we have investigated the effect that in vivo imbalance of these nucleases and others of the family have on genome integrity and cell proliferation. We show that overexpression of these nucleases causes genetic instability in both yeast and human cells. Interestingly, the type of recombination event and DNA damage induced suggest specific modes and timing of action of each nuclease that are beyond their known DNA repair function and are critical to preserve genome integrity. In addition to identifying new sources of genome instability, a hallmark of cancer cells, this study provides new genetic tools for studies of genome dynamics.
In a double-blinded randomized controlled clinical trial, the impact of face-bow registration for remounting complete dentures (CDs) on the occlusal parameters (part I) was evaluated.
New CDs of 32 patients were duplicated and mounted after intraoral pin registration according to mean settings (group 1) and (group 2) using a face-bow (arbitrary hinge axis). The vertical dimension was reduced to the first occlusal contact point, and a bite record was fabricated in the articulator. The number of contacts and the number of teeth in contact were evaluated by a computer program (laboratory result). After randomization, half of the CDs were adjusted according to protocol of group 1 and group 2 and delivered to the patients. After 3 days (T1) and 84 days (T2), clinical static contact points and teeth in contact were counted. Contact points and teeth in contact of both groups (laboratory results) and at different moments (clinical results) were analyzed statistically with the F test and bootstrapping.
Laboratory: No. 2 (face-bow) showed more occlusal contact points than no. 1 (mean setting), p > 0.05. The number of teeth with at least one occlusal contact was significantly higher in no. 2 (p = 0.027). Clinic: The mean number of teeth with at least one clinical contact point was significantly higher in no. 1 (no. 1 = 7.13, no. 2 = 5.31; p = 0.042). Extent of the vertical shift poorly correlated with number of laboratory occlusal contact points (R 2 = 0.017).
Considering the complex multistep study design, a limited number of participants, and referring to one specific arbitrary face-bow, the following conclusion could be drawn: no substantial difference by the use of the arbitrary face-bow compared to a mean setting could be determined, when changing the vertical dimension in the articulator within a remounting procedure of complete dentures.
Further research is necessary to determine the effects of different arbitrary face-bows on the fabrication and adaptation of removable dentures.
Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Heidi Vreeland, Rodney Weber, Michael Bergin, Roby Greenwald, Rachel Golan, Armistead G. Russell, Vishal Verma, Jeremy A. Sarnat
Although exposure to traffic emissions is frequently associated with negative health impacts, few studies have measured air pollution directly in-vehicle, and limited measurements of daily commuter exposure exist. This research, part of the Atlanta Commuter Exposures (ACE) Study, assesses on-roadway in-cabin particulate pollution (PM2.5) collected from scripted rush hour commutes on highways and on non-highway side streets. Water-soluble extracts from PM2.5 filters were analyzed for oxidative potential of water-soluble species using the dithiothreitol (DTT) assay, and results suggest that there may be substantial gas-phase DTT activity in fresh emissions. We measured DTTv activities (i.e., DTT activity normalized to the sampled air volume) that were on average two times higher than comparable measurements collected by stationary roadside monitoring sites. Although some of this difference may be attributable to positive artifacts due to relatively brief (2-h) quartz filter sampling durations, the current findings provide some indication that commuters encounter notably higher exposure to redox-active PM2.5 in the on-road environment. Strong correlations are observed between water-soluble DTT activity and water-soluble organic carbon (WSOC), specifically for the 'semivolatile' WSOC component (measured as the difference between denuded and non-denuded filters). Although potential for artifacts when measuring DTT activity of fresh emissions using filter-based methods is considerable, these results suggest that semivolatile organic species are important contributors to DTT activity, at least in environments where ambient PM2.5 is dominated by vehicular sources.
Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Ingeborg E. Nielsen, Axel C. Eriksson, Robert Lindgren, Johan Martinsson, Robin Nyström, Erik Z. Nordin, Ioannis Sadiktsis, Christoffer Boman, Jacob K. Nøjgaard, Joakim Pagels
Time-resolved particle emissions from a conventional wood stove were investigated with aerosol mass spectrometry to provide links between combustion conditions, emission factors, mixing state of refractory black carbon and implications for organic tracer methods. The addition of a new batch of fuel results in low temperature pyrolysis as the fuel heats up, resulting in strong, short-lived, variable emission peaks of organic aerosol-containing markers of anhydrous sugars, such as levoglucosan (fragment at m/z 60). Flaming combustion results in emissions dominated by refractory black carbon co-emitted with minor fractions of organic aerosol and markers of anhydrous sugars. Full cycle emissions are an external mixture of larger organic aerosol-dominated and smaller thinly coated refractory black carbon particles. A very high burn rate results in increased full cycle mass emission factors of 66, 2.7, 2.8 and 1.3 for particulate polycyclic aromatic hydrocarbons, refractory black carbon, total organic aerosol and m/z 60, respectively, compared to nominal burn rate. Polycyclic aromatic hydrocarbons are primarily associated with refractory black carbon-containing particles. We hypothesize that at very high burn rates, the central parts of the combustion zone become air starved, leading to a locally reduced combustion temperature that reduces the conversion rates from polycyclic aromatic hydrocarbons to refractory black carbon. This facilitates a strong increase of polycyclic aromatic hydrocarbons emissions. At nominal burn rates, full cycle emissions based on m/z 60 correlate well with organic aerosol, refractory black carbon and particulate matter. However, at higher burn rates, m/z 60 does not correlate with increased emissions of polycyclic aromatic hydrocarbons, refractory black carbon and organic aerosol in the flaming phase. The new knowledge can be used to advance source apportionment studies, reduce emissions of genotoxic compounds and model the climate impacts of refractory black carbon, such as absorption enhancement by lensing.
The herbicide glyphosate (GLY) or 2,4-dichlorophenoxyacetic acids (2,4D) was intercalated in the interlayer region of a Zn-Al-layered double hydroxide (LDH) to obtain LDH-GLY or the LDH-2,4D hybrid composite because of its controlled release. Compared to the physically mixed herbicides, the LDH-herbicide hybrid composite displayed slow-release properties in decarbonated distilled water. The release rate of herbicides was found to be dependent on the carbonate and chloride anion concentrations in solution. The time at which 50% of the herbicides were released from the hybrid composite into solution, t 50, ranged from 6.5 to 18.6 h for LDH-GLY and from 10 to 21.5 h for LDH-2,4D. Our results indicate that the application of LDH-GLY or LDH-2,4D hybrid composite to agricultural areas could reduce the maximum 2,4D or GLY contamination and result in the retardation of herbicides leaching through the soil. This study demonstrates the potential applicability of LDHs as supports for the slow release of acid herbicides.
Staphylococcal enterotoxin A (SEA) was the major virulence factor of Staphylococcus aureus and a biomarker of S. aureus. To establish a fast, low cost, high accuracy, reliable, and simple method for detecting S. aureus, SEA was analyzed by HPLC-ESI-TOF. SEA was not yet commercially available in universal, so SEA was prepared before it was analyzed by HPLC-ESI-TOF. The result showed that high purified SEA was successfully prepared and SEA has normal distribution in mass spectra. A large amount of recombinant SEA (rSEA) was obtained by engineering technology and was purified by Ni affinity chromatography column, and the expression and purity of rSEA and SEA were analyzed by SDS-PAGE. The factors effected on ionization of SEA were studied, and the qualitative analysis of SEA by HPLC-ESI-TOF. The result showed that large amount of SEs expressed within a short time at 28 °C or thereabouts, and there was no impurity bands in electrophorogram after rSEA was purified by Ni affinity chromatography column. In addition, the SEA which had homologous AA sequence with wild SEA was made by rSEA. The retention of SEA in column and ionization of SEA in ESI-TOF were studied for qualitative analysis of S. aureus. The result showed that the content of formic acid in mobile phase was an important factor for ionization of SEs in ESI-TOF. And the result provided theoretical foundation for qualitative detection of S. aureus. [SEs + nH+ + mNH4+]n+m+ was shown on ESI-TOF spectra when SEA was detected by ESI-TOF in positive ion mode, and the numerical value of n+m was less than or equal to the number of basic amino acids in SEs. This method was applied to determine SEA in water samples preliminarily, and the detection limit of SEA in spiked water sample was 3 mg/kg. The limit of detection of 3 mg/kg was low sensitivity for low molecular weight matters, but it was high sensitivity for SEA which had a high molecular weight of 27 kDa. Of SEA, 3 mg/kg was equivalent to 10−4 mmol/kg of SEA. This study can provide evidence for establishing method to determine SEA in real samples.
Without treatment, waterworks sludge is ineffective as an adsorbent. In this study, raw waterworks sludge was used as the raw material to prepare modified sludge particles through high-temperature calcination and alkali modification. The feasibility of using a combination of modified particles and polyaluminum chloride (PAC) as a coagulant for treatment of slightly polluted source water was also investigated. The composition, structure, and surface properties of the modified particles were characterized, and their capabilities for removing ammonia nitrogen and turbidity were determined. The results indicate that the optimal preparation conditions for the modified sludge particles were achieved by preparing the particles with a roasting temperature of 483.12 °C, a roasting time of 3.32 h, and a lye concentration of 3.75%. Furthermore, enhanced coagulation is strengthened with the addition of modified sludge particles, which is reflected by reduction of the required PAC dose and enhancement of the removal efficiency of ammonia nitrogen and turbidity by over 80 and 93%, respectively. Additional factors such as pH, temperature, dose, and dosing sequence were also evaluated. The optimum doses of modified particles and PAC were 40 and 15 mg/L, respectively, and adding modified particles at the same time as or prior to adding PAC improves removal efficiency.
The purposes of the present study are to assess the effects of the GaAlAs diode laser on the periodontal tissues and to investigate its action on the alveolar bone remodeling process during orthodontic tooth movement in normoglycemic and diabetic rats. Sixty adult male Wistar rats were divided into four groups of 15 rats: normoglycemic (N), diabetic (D), laser-normoglycemic (LN), and laser-diabetic (LD) rats. Diabetes mellitus was induced by a single intravenous injection of 40 mg/kg monohydrated alloxan. The orthodontically moved tooth underwent a force magnitude of 20 cN. The laser irradiation with a continuous emission of a 780-nm wavelength, an output power of 20 mW, and a fiber probe with a spot size of 0.04 cm in diameter and an area of 0.00126 cm2 were used. Moreover, an energy density of 640 J/cm2 was applied in an exposition time of 40 s. Histomorphological and immunohistochemical analysis was performed. The photobiomodulation (PBM) strongly stimulated the periodontal tissue response, establishing mainly the balance between the bone formation and resorption. Intense inflammatory cell infiltration and extensive loss of bone tissue were mainly found in the D group from 14 days. The number of osteopontin-positive osteocytes was significantly greater in the LN group, followed by the LD, especially at 7 and 14 days, whereas osteoprotegerin-positive osteoblasts were significantly higher in the LN and LD groups than in the N and D groups, respectively, in all periods. The PBM strongly stimulated the alveolar bone remodeling and favored the continuous reorganization of the soft periodontal tissues, leading to the maintenance and integrity of the periodontal microstructure under orthodontic force, especially in uncontrolled diabetic rats.
This study assessed the effect of curcumin as a photosensitizer in antimicrobial photodynamic therapy (aPDT) for the treatment of induced periodontitis in rats. Periodontitis was induced via a ligature around the mandibular first molar on the left side of 96 rats. The ligature was removed 7 days later, and the animals were randomized into four groups: NT, no local treatment; CUR, irrigation with curcumin solution (40 μM); LED, irradiation with a light-emitting diode (LED, InGaN, 465–485 nm, 200 mW/cm2, 60 s); and aPDT, irrigation with curcumin solution (40 μM) followed by irradiation with LED. Eight animals from each group were euthanized at 7, 15, and 30 days post-treatment. Treatments were assessed using alveolar bone loss (ABL) in the furcation region using histological, histometric, and immunohistochemical analyses. Rats treated with aPDT exhibited less ABL at 7 days compared to the NT group, moderate pattern immunolabeling for osteoprotegerin at 30 days, and a pattern of immunolabeling for RANKL from moderate to low. Treatments resulted in smaller numbers of TRAP-positive cells compared to the NT group. aPDT as monotherapy using curcumin as a photosensitizer and LED as the light source was effective in the treatment of induced periodontitis in rats.
Publication date: Available online 3 July 2017
Source:Clinical Imaging
Author(s): Randy Yeh, Ahmed Mohammed, Aleksandr Margolin, Peter Schlossberg, Rama S. Ayyala
Hypertension is rare in the pediatric population, however renal artery stenosis (RAS) is an important cause that can be difficult to diagnose. Doppler ultrasound is the first line imaging modality, with computed tomography and magnetic resonance imaging as adjunct modalities, all with variable sensitivity for RAS. The gold standard for evaluation of RAS is invasive selective catheter angiography. We present a unique multimodality case of abnormal radiotracer uptake in the renal parenchyma on 123-Iodine metaiodobenzylgunidine (123I MIBG) scan in a patient with unilateral RAS. RAS is a potential cause of a false positive MIBG scan, and proper recognition may lead to accurate diagnosis.
http://ift.tt/2skdREa
Publication date: Available online 3 July 2017
Source:Clinical Imaging
Author(s): Chao Chen, Qinqin Kang, Bing Xu, Hairuo Guo, Qiang Wei, Tiegong Wang, Hui Ye, Xinhuai Wu
PurposeTo compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC).Materials and methodsTumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed.ResultsHigh-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did.ConclusionsTumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC.
http://ift.tt/2tDhiKh
Publication date: Available online 3 July 2017
Source:Clinical Imaging
Author(s): Audree Tadros, Brittany Arditi, Christina Weltz, Elisa Port, Laurie R. Margolies, Hank Schmidt
PurposeTo determine the utility and rate of biopsy in women with a positive history of breast cancer screened with MRI.MethodsRetrospective review of 491 breast MRI screening examinations in women with a personal history of breast cancer.ResultsIn total, 107 biopsies were performed, an average of 0.09 biopsies per person year. The positive predictive value for biopsies prompted by MRI findings was 0.24 (95% C.I. 0.10–0.38). Eight of the nine subsequent cancers were initially identified on screening MRI alone.ConclusionSurveillance MRI in breast cancer survivors may increase detection of subsequent cancers while increasing rate of biopsy.
http://ift.tt/2skecac
Publication date: Available online 3 July 2017
Source:Clinical Imaging
Author(s): Salvatore Rudilosso, Luis San Román, Jordi Blasco, María Hernández-Pérez, Xabier Urra, Ángel Chamorro
PurposeTo assess the reliability of the Fazekas score on brain CT in acute stroke patients.MethodsTwo raters evaluated the Fazekas score in 157 CT scans from consecutive patients with acute stroke.ResultsThe Fazekas scores on brain CT scans showed consistent (weighted κ, 0.73) and moderate (weighted κ, 0.56) interobserver agreement for periventricular and deep white matter areas, respectively. Intraobserver reliability was substantial for both areas (weighted κ, 0.85 and 0.8).ConclusionThe Fazekas score on CT can be used to reliably grade white matter changes, and can be a useful tool when MRI is not available.
http://ift.tt/2tCOuBG
The aim of this study was to report the clinical outcome and toxicity of radiochemotherapy in locally advanced gastric cancer (LAGC) patients treated according to the Intergroup 116 trial protocol in our institution.
We retrospectively reviewed 105 patients with LAGC treated with radical surgery and adjuvant radiochemotherapy. We analyzed overall survival (OS), disease-free survival (DFS), locoregional failure-free survival (LFS), prognostic factors and toxicity.
The mean follow-up was 96.48 months. The majority of tumors were T3–T4 (75%) and 86.6% had nodal metastases. The OS, DFS and LFS rates to 3 years were 53.48%, 52.75% and 81.65%, respectively and to 5 years 40%, 46.73% and 76.77% respectively. The univariate analysis showed that N stage < N2, TN stage < IIIA, R0 resection and N‑ratio < 3 were statistically significant prognostic factors for OS and DFS, T stage < T4 for OS and N‑ratio < 3 for LFS. The group with D2 lymphadenectomy had worse LFS than the D1 group (65.2% vs 88.1%, respectively, p = 0.039) probably due to a significant difference in the proportion node positive patients in the D2 group (94% vs. 78%; p = 0.027). In the multivariate analysis, only R0 resection was statistically significant factor for improved OS (p = 0.018). Acute grade III–IV gastrointestinal and hematologic toxicity rates were 8.5% and 15.2%, respectively and 89.5% completed treatment as planned.
Our results are consistent with those of the Intergroup-0116 trial for LAGC in terms of survival. This regimen is well tolerated and with acceptable toxicity. An R0 resection was an independent prognostic factor for improved OS.
Biodiesels represent more carbon-neutral fuels and are introduced at an increasing extent to reduce emission of greenhouse gases. However, the potential impact of different types and blend concentrations of biodiesel on the toxicity of diesel engine emissions are still relatively scarce and to some extent contradictory. The objective of the present work was to compare the toxicity of diesel exhaust particles (DEP) from combustion of two 1st-generation fuels: 7% fatty acid methyl esters (FAME; B7) and 20% FAME (B20) and a 2nd-generation 20% FAME/HVO (synthetic hydrocarbon biofuel (SHB)) fuel. Our findings indicate that particulate emissions of each type of biodiesel fuel induce cytotoxic effects in BEAS-2B and A549 cells, manifested as cell death (apoptosis or necrosis), decreased protein concentrations, intracellular ROS production, as well as increased expression of antioxidant genes and genes coding for DNA damage-response proteins. The different biodiesel blend percentages and biodiesel feedstocks led to marked differences in chemical composition of the emitted DEP. The different DEPs also displayed statistically significant differences in cytotoxicity in A549 and BEAS-2B cells, but the magnitude of these variations was limited. Overall, it seems that increasing biodiesel blend concentrations from the current 7 to 20% FAME, or substituting 1st-generation FAME biodiesel with 2nd-generation HVO biodiesel (at least below 20% blends), affects the in vitro toxicity of the emitted DEP to some extent, but the biological significance of this may be moderate.
AbstractBackground
Cardiovascular disease (CVD) is the number 1 killer of women in the United States, yet few younger women are aware of this fact. CVD campaigns focus little attention on physicians and their roles in assessing risk.
ObjectivesIn 2014, the Women's Heart Alliance (WHA) conducted a nationwide survey to determine barriers and opportunities for women and physicians with regard to CVD.
MethodsFrom September 18 to 26, 2014, a total of 1,011 U.S. women (age 25 to 60 years) were interviewed using the GfK ("Gesellschaft für Konsumforschung" Knowledge Panel). From May 6 to 12, 2014, the e-Rewards Inc. Physician and Healthcare Professional Panel surveyed 200 primary care physicians (PCPs) and 100 cardiologists.
ResultsOverall, 45% of women were unaware that CVD is the number 1 killer of women; only 11% knew a woman who died from CVD. Overall, 45% of women reported it was common to cancel or postpone a physician appointment until losing weight. CVD was a top concern for only 39% of PCPs, after weight and breast health. A minority of physicians (22% of PCPs and 42% of cardiologists) felt well prepared to assess women's CVD risk and used guidelines infrequently.
ConclusionsCVD in women was not the top concern for women or physicians. Social stigma particularly regarding body weight appeared to be a barrier. Physicians reported limited training and use of guideline assessment, whereas most supported a campaign and improved physician education. Campaigns should make CVD "real" to U.S. women, countering stereotypes with facts and validated assessments. Both community women and physicians endorsed investment in women's CVD research and physician education.
AbstractBackground
Aortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF).
ObjectivesThis study compared indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive control subjects to examine their relationships to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite.
MethodsA total of 22 hypertensive control subjects and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis to measure oxygen consumption. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection.
ResultsArterial load and wave reflections in HFpEF were similar to those in control subjects at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures in control subjects. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p < 0.0001). With peak exercise, increased wave reflections, impaired compliance, and increased resistance and elastance were observed in subjects with HFpEF. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo therapy in a 1:1 double-blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance and elastance and central hemodynamics during exercise.
ConclusionsAbnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF. (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease [EXEC]; NCT01418248. Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction; NCT01932606. Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction; NCT02262078)
Abstract
Oxidative stress occurs whenever the release of reactive oxygen species (ROS) exceeds endogenous antioxidant capacity. In this paper, we review the specific role of several cardiovascular risk factors in promoting oxidative stress: diabetes, obesity, smoking, and excessive pollution. Specifically, the risk of developing heart failure is higher in patients with diabetes or obesity, even with optimal medical treatment, and the increased release of ROS from cardiac mitochondria and other sources likely contributes to the development of cardiac dysfunction in this setting. Here, we explore the role of different ROS sources arising in obesity and diabetes, and the effect of excessive ROS production on the development of cardiac lipotoxicity. In parallel, contaminants in the air that we breathe pose a significant threat to human health. This paper provides an overview of cigarette smoke and urban air pollution, considering how their composition and biological effects have detrimental effects on cardiovascular health.
AbstractBackground
Oxidative/nitrosative stress and endothelial dysfunction are hypothesized to be central to cancer therapeutics–related cardiac dysfunction (CTRCD). However, the relationship between circulating arginine-nitric oxide (NO) metabolites and CTRCD remains unstudied.
ObjectivesThis study sought to examine the relationship between arginine-NO metabolites and CTRCD in a prospective cohort of 170 breast cancer patients treated with doxorubicin with or without trastuzumab.
MethodsPlasma levels of arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethylarginine (MMA) were quantified at baseline, 1 month, and 2 months after doxorubicin initiation. Determinants of baseline biomarker levels were identified using multivariable linear regression, and Cox regression defined the association between baseline levels and 1- or 2-month biomarker changes and CTRCD rate in 139 participants with quantitated echocardiograms at all time points.
ResultsAge, hypertension, body mass index, and African-American race were independently associated with ≥1 of baseline citrulline, ADMA, SDMA, and MMA levels. Decreases in arginine and citrulline and increases in ADMA were observed at 1 and 2 months (all p < 0.05). Overall, 32 participants experienced CTRCD over a maximum follow-up of 5.4 years. Hazard ratios for ADMA and MMA at 2 months were 3.33 (95% confidence interval [CI]: 1.12 to 9.96) and 2.70 (95% CI: 1.35 to 5.41), respectively, and 0.78 (95% CI: 0.64 to 0.97) for arginine at 1 month.
ConclusionsIn breast cancer patients undergoing doxorubicin therapy, early alterations in arginine-NO metabolite levels occurred, and early biomarker changes were associated with a greater CTRCD rate. Our findings highlight the potential mechanistic and translational relevance of this pathway to CTRCD.
Abstract
Vascular disease and heart failure impart an enormous burden in terms of global morbidity and mortality. Although there are many different causes of cardiac and vascular disease, most causes share an important pathological mechanism: oxidative stress. In the failing heart, oxidative stress occurs in the myocardium and correlates with left ventricular dysfunction. Reactive oxygen species (ROS) negatively affect myocardial calcium handling, cause arrhythmia, and contribute to cardiac remodeling by inducing hypertrophic signaling, apoptosis, and necrosis. Similarly, oxidative balance in the vasculature is tightly regulated by a wealth of pro- and antioxidant systems that orchestrate region-specific ROS production and removal. Reactive oxygen species also regulate multiple vascular cell functions, including endothelial and smooth muscle cell growth, proliferation, and migration; angiogenesis; apoptosis; vascular tone; host defenses; and genomic stability. However, excessive levels of ROS promote vascular disease through direct and irreversible oxidative damage to macromolecules, as well as disruption of redox-dependent vascular wall signaling processes.
AbstractBackground
Beneficial effects of high-density lipoproteins (HDL) seem altered in patients with symptomatic cardiovascular disease. We recently demonstrated in a swine model of ischemia-reperfusion (IR) that hypercholesterolemia abolishes HDL-related cardioprotection.
ObjectivesThis study sought to investigate, using the same animal model, whether the reported impairment of HDL cardioprotective function was associated with alterations in HDL remodeling and functionality.
MethodsPigs were fed a normocholesterolemic (NC) or hypercholesterolemic (HL) diet for 10 days, reaching non-HDL cholesterol concentrations of 38.2 ± 3.5 mg/dl and 218.6 ± 27.6 mg/dl, respectively (p < 0.0001). HDLs were isolated, and lipidomics and differential proteomics tests were performed to determine HDL molecular changes. HDL functionality and particle size were determined.
ResultsUsing principal component analysis, we identified 255 molecular lipid species differentially clustered in NC-HDL and HL-HDL. Ninety lipid metabolites were differentially expressed, and 50 showed at least 1.5-fold variation (false discovery rate adjustment q value <0.05). HL-HDLs presented a core enriched in cholesteryl esters and a surface depleted of phosphatidylcholine species containing polyunsaturated and long-chain fatty acids, indicating the presence of mature HDL particles with low surface fluidity. Hypercholesterolemia induced an important change in HDL-transported proteins (576 spots in HL-HDL vs. 621 spots in NC-HDL). HL-HDLs showed a reduced content of lipocalin retinol binding protein 4 and apolipoprotein M and in the retinoic acid-transporter cellular retinoic acid binding protein 1 (p < 0.05 vs. NC-HDL). No changes were observed in apolipoprotein A-I content and profile. Functionally, HL-HDL showed lower antioxidant activity (–35%) and a reduced capacity to efflux cholesterol (–60%) compared to NC-HDL (p < 0.05). Hypercholesterolemia induced larger HDL particles.
ConclusionsWe demonstrate that hypercholesterolemia induces HDL lipidomic changes, losing phosphatidylcholine-lipid species and gaining cholesteryl esters, and proteomic changes, with losses in cardioprotective proteins. These remodeling changes shifted HDL particles toward a dysfunctional state.
AbstractBackground
Although β-blockers increase survival in patients with heart failure (HF), the mechanisms behind this protection are not fully understood, and not all patients with HF respond favorably to them. We recently showed that, in cardiomyocytes, a reciprocal down-regulation occurs between β1-adrenergic receptors (ARs) and the cardioprotective sphingosine-1-phosphate (S1P) receptor-1 (S1PR1).
ObjectivesThe authors hypothesized that, in addition to salutary actions due to direct β1AR-blockade, agents such as metoprolol (Meto) may improve post–myocardial infarction (MI) structural and functional outcomes via restored S1PR1 signaling, and sought to determine mechanisms accounting for this effect.
MethodsWe tested the in vitro effects of Meto in HEK293 cells and in ventricular cardiomyocytes isolated from neonatal rats. In vivo, we assessed the effects of Meto in MI wild-type and β3AR knockout mice.
ResultsHere we report that, in vitro, Meto prevents catecholamine-induced down-regulation of S1PR1, a major cardiac protective signaling pathway. In vivo, we show that Meto arrests post-MI HF progression in mice as much as chronic S1P treatment. Importantly, human HF subjects receiving β1AR-blockers display elevated circulating S1P levels, confirming that Meto promotes S1P secretion/signaling. Mechanistically, we found that Meto-induced S1P secretion is β3AR-dependent because Meto infusion in β3AR knockout mice does not elevate circulating S1P levels, nor does it ameliorate post-MI dysfunction, as in wild-type mice.
ConclusionsOur study uncovers a previously unrecognized mechanism by which β1-blockers prevent HF progression in patients with ischemia, suggesting that β3AR dysfunction may account for limited/null efficacy in β1AR-blocker–insensitive HF subjects.
Diabetic foot ulcer (DFU) is a devastating complication of diabetes.
We aimed to identify genetic contributors of DFU based on a genome-wide association study approach using a Scottish diabetic cohort.
A genome-wide association approach was applied. A case was defined as a diabetic patient (type 1 or type 2) who had ever been recorded in the linked e-health records as having a foot ulcer (current or previous) in at least one foot as well as a positive result of the monofilament test in the longitudinal e-health records. A control in this study was defined as a diabetic individual (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot in the linked e-health records and the monofilament test results of any foot was once recorded to be positive in the longitudinal e-health records.
We have 699 DFU cases and 2,695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The lowest P value of rs80028505 (Chr6p21.31) in the MAPK14 gene was 2.45x10-8. The narrow-sense heritability of this phenotype is 0.06.
We suggest that the MAPK14 gene is associated with DFU.
This article is protected by copyright. All rights reserved.
Publication date: Available online 2 July 2017
Source:International Journal of Psychophysiology
Author(s): Christina Huang, R.N. Gevirtz, Julie Onton, Jose R. Criado
Although there has been much support for HRV Biofeedback as an effective intervention for various disorders, there is a lack of comprehension of the underlying mechanisms. The predominant theories of increased vagal efferents and baroreflex gain are insufficient in explaining the frequent observations that HRV Biofeedback impacts changes in constructs beyond ANS mediation, such as emotion regulation, attentional control, and self-regulatory reserve. It has been suspected that vagal afferent functioning may be the underlying mechanism, but little research has explored this. Previously, researchers measured cortical evoked potentials contingent to the heart, or an indication of vagal afferent functioning (Schandry et al., 1986). Twenty-five participants were randomly stratified to HRV Biofeedback or EMG Biofeedback for four sessions. Repeated measures ANOVAs revealed that the HRV group exhibited statistically significantly increased baseline Heartbeat Event-Related Potentials (updated term for 'evoked potential') while the relaxation control group did not. The results of this study provide initial support to the premise that HRV Biofeedback stimulates changes in the vagal afferent pathway that are longer lasting than simply the short term effects of breathing.
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Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Remziye Olgac, Tugba Soganci, Yasemin Baygu, Yaşar Gök, Metin Ak
Zinc(II) phthalocyanine fused in peripheral positions octa-substituted with alkyl linked carbazole has been prepared by cyclomerization reaction of 4,5-bis(6-carbazole-9-yl-hexylsulfanil)phthalonitrile in the presence of anhydro Zn(II) acetate and a strong organic base (DBU). Synthesis steps were optimized and higher efficiency synthesis was achieved. The purpose of combining of carbazole moieties with phthalocyanine on the peripheral position is to enhance some properties such as photo and electrochemical properties because of strong electron-donating properties of carbazole group. This molecule has been electrochemically polymerized and the electrical and optical properties of the resulting conductive polymer have been investigated. Amperometric detection was carried out following oxygen consumption at −0.7V vs. the Ag reference electrode in phosphate buffer (50mM, pH 6.0). The novel biosensor showed a linear amperometric response for glucose within a concentration range of 0.05mM to 1.5mM (LOD: 0.024mM). This result shows that modification of the proposed biosensor by copolymerization have provided to give perfect response to different glucose concentrations. Because of its superior spectral and electrochemical properties and contained zinc metal which can act as a mediator during biochemical reactions, this material has been used as a glucose biosensor platform to detection for real samples.
Publication date: 15 December 2017
Source:Science of The Total Environment, Volumes 605–606
Author(s): Enrique Arévalo-Gardini, Cesar O. Arévalo-Hernández, Virupax C. Baligar, Zhenli L. He
Peru is one of the leading exporters of organic cacao beans in the world. However, the accumulation of heavy metals in cacao beans represents a problem for cocoa bean export and chocolate quality. The aim of this study was to investigate the distribution and accumulation of heavy metals in cacao leaves and cocoa beans in three major cacao growing regions of Peru. The study was conducted in cacao plantations of 10 to 15years old in three regions of Peru: North (Regions of Tumbes, Piura, Cajamarca, and Amazonas); Center (Regions of Huánuco and San Martin) and South (Junin and Cuzco). Samples of leaf and cacao beans were collected from 70 cacao plantations, and the nature of cacao clone or genotype sampled was recorded. The concentrations of heavy metals such as Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn in leaves and beans were determined using atomic absorption spectrophotometer. Overall, concentrations of heavy metals were below the critical limits; however, the presence of high levels of Cd in cacao grown in Amazonas, Piura, and Tumbes regions is of primary concern. Plantations of cacao with different cacao clones show differences in Cd accumulation both in leaves and cocoa beans. Therefore, it is promising to screen low Cd accumulator cacao genotypes for safe production of cacao on lightly to moderately Cd contaminated soils. Also, synergism between Zn and Cd present both in plant and soil suggests that Zn has a direct effect on Cd accumulation in cacao.
Women today more commonly suffer the morbidity and mortality of eating disorders. Looking through the dual prisms of historical accounts and modern theory the authors examined the meaning of eating disturbance in two cases from the late Middle Ages. The historic role of women and food is explored.
Widely reviewing historical sources and the current academic literature, we gathered data and considered two women, Margery Kempe and Catherine of Siena. They were empowered by their roles as religious mystics, and drew strength from suffering, distress and fasting. We briefly examined them in the context of modern diagnostic and aetiological explanations of eating disorders (particularly Anorexia nervosa).
We present an account of these women's lives. The relevance these cases have for our understanding of patients, eating disorders, and expressions of suffering today is discussed.
Historic accounts provide a rich counterpoint to understanding our present clinical culture of theory and diagnosis. Both our subjects had disturbed eating: one probably died as a consequence of it. Subjective distress was a central component of the life that was desired by each of these women, and they were empowered by their eating disturbance. Food has immense meaning historically, and personally it had meaning for each of our subjects. This is reflected in current clinical experience. The authors suggest we may be aided by adding our cultural, historical and gender based experience of food to our modern biological understanding of eating disorders, to further illuminate the complexities of today's eating disordered patient.
Publication date: Available online 3 July 2017
Source:Medical Hypotheses
Author(s): P.R. Doyon, O. Johansson
While a good number of studies have demonstrated that modern, man-made ambient electromagnetic fields can have both stimulatory and inhibitory effect on immune system function, the precise mechanisms have yet to be completely elucidated. It is hypothesized here, that depending on the parameters, one of the means by which long-term electromagnetic field exposure has the potential to eventually lead to immunosuppression is via downstream inhibition of the enzyme calcineurin — a protein phosphatase, which activates the T-cells of the immune system and can be blocked by pharmaceutical agents.Calcineurin is the target of a class of pharmaceuticals called calcineurin inhibitors (e.g. cyclosporine, pimecrolimus and tacrolimus). When organ transplant recipients take such pharmaceuticals to prevent or suppress organ transplant rejection, one of the major side effects is immunosuppression leading to increased risk of opportunistic infection: e.g., fungal, viral (Epstein-Barr virus, cytomegalovirus), atypical bacterial (Nocardia, Listeria, mycobacterial, mycoplasma), and parasitic (e.g., toxoplasmosis) infections.Frequent anecdotal reports as well as a number of scientific studies have shown that electromagnetic field exposures may indeed produce the same effect: a weakened immune system leading to an increase in the same or similar opportunistic infections: i.e. fungal, viral, atypical bacterial, and parasitic infections.Furthermore, numerous research studies have shown that man-made electromagnetic fields have the potential to open voltage-gated calcium channels, which can in turn produce a pathological increase of intracellular calcium, leading downstream to the pathological production of a series of reactive oxygen species. Finally, there are a number of research studies demonstrating the inhibition of calcineurin by a pathological production of reactive oxygen species.Hence, it is hypothesized here that exposures to electromagnetic fields have the potential to inhibit immune system response by means of an eventual pathological increase in the influx of calcium into the cytoplasm of the cell, which produces a pathological production of reactive oxygen species, which in turn can have an inhibitory effect on calcineurin. Calcineurin inhibition leads to immunosuppression, which in turn leads to a weakened immune system and an increase in opportunistic infection.
Publication date: Available online 2 July 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Hui-Ching Wang, Ching-Yuan Kuo, I-Ting Liu, Tsai-Yun Chen, Yu-Hsiang Chang, Shyh-Jer Lin, Shih-Feng Cho, Yi-Chang Liu, Ta-Chih Liu, Sheng-Fung Lin, Chao-Sung Chang
Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare acquired disorder. The aim of this study was to investigate the demographics, clinical manifestations, and outcomes of PNH patients in southern Taiwan. Data on PNH patients diagnosed over a 30-year period (1985–2015) were retrospectively collected from four tertiary medical centers in southern Taiwan. Blood samples were collected for hematologic panel testing and flow cytometry detection of PNH clones. Radiologic studies were performed to assess the frequency of complications. Twenty-four patients were enrolled in this study. The median duration of disease in the study participants was 10.8 years. The median granulocyte PNH clone size was 92.5% (range, 1.3%–99.8%), and the median lactate dehydrogenase (LDH) level was 2920.2 ± 1462.0 IU/L. The incidence of thromboembolism and impaired renal function was 16.7% and 29.2%, respectively. The primary treatment strategies included steroids (79.2%), androgens (42.0%), eculizumab (33.3%), immunosuppressants (16.7%), and anticoagulants (4.2%). In eight patients treated with eculizumab, there was a marked reduction in the LDH levels of 14.89-fold–1.63-fold that of the upper limit of normal; seven patients exhibited decreased transfusion requirements. Twenty-one patients were alive with regular follow-up at the time of publication. Our study demonstrates that PNH patients in southern Taiwan may exhibit different clinical characteristics and outcomes relative to patients in other countries. There was a trend toward a greater PNH granulocyte clone size, which may lead to more hemolysis. In our study, the percentage of patients with impaired renal function, but not the percentage of patients with thrombotic events, was higher than values reported worldwide and in the observational cross-sectional International PNH Registry. More large-scale studies with comprehensive data on the clinical response to different treatments are needed.
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To describe mandibular premolar root and canal morphology and its variability in Chilean and Belgian samples using cone-beam computed tomography.
A cross-sectional and descriptive study was conducted. A total of 402 mandibular premolars were examined using cone-beam computed tomography images of Chilean and Belgian patients. Premolars that met the inclusion criteria were studied in relation to the number of roots, number of canals, root canal configuration, presence of C-shaped configuration, tooth length, and root length.
The mandibular first premolar frequently presented with one root (94% Chilean; 100% Belgian), as did the mandibular second premolar (99% Chilean; 98% Belgian). One canal was present in 69% of Chilean, and 83% of Belgian mandibular first premolars, and in 95% of Chilean and 91% of Belgian second premolars. A type I root canal configuration was found in 69% of Chilean and 83% of Belgian first premolars and in 95% of Chilean and 92% of Belgian second premolars.
The anatomical parameters analyzed in the Chilean and Belgian samples are similar. However, it should be noted that there are anatomical variations in mandibular premolars.
10-valent pneumococcal conjugate vaccine (PCV10) decreases metabolic activity but not nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.
Vaccine. 2017 Jun 28;:
Authors: Andrade DC, Borges IC, Bouzas ML, Oliveira JR, Fukutani KF, Queiroz AT, de Oliveira CI, Barral A, Van Weyenbergh J, Nascimento-Carvalho C
Abstract
BACKGROUND: The effect of pneumococcal vaccination is widely variable when measured by nasopharyngeal carriage of vaccine and non-vaccine targets. The aim of this study was to compare the carriage rates and metabolic activity of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis among children who were or were not vaccinated with PCV10.
METHODS: We included children with acute respiratory infection aged 6-23months from a cross-sectional study (CHIADO-IVAS). Nasopharyngeal aspirates were collected and respiratory pathogens were quantified by nCounter digital transcriptomics (Nanostring) and metagenomic sequencing of 16S ribosomal RNA (Illumina). The metabolic rate was calculated by the ratio between RNA transcripts and 16S DNA reads.
RESULTS: Out of the 80 patients in this study, 53 were vaccinated with PCV10 and 27 were unvaccinated. There was no difference in nasopharyngeal carriage rates of S. pneumoniae, S. aureus, H. influenzae or M. catarrhalis by either transcriptomic analysis or 16S metagenomics. However, unvaccinated children presented a higher metabolic rate for S. pneumoniae compared to PCV10-vaccinated children (Median [25-75th percentiles]: 126 [22.75-218.41] vs. 0[0-47.83], p=0.004). Furthermore, unvaccinated children presented a positive correlation between mRNA counts and 16S DNA reads for S. pneumoniae (r=0.707; p<0.001) and H. influenzae (r=0.525; p=0.005), in contrast to vaccinated children. No such effect was observed for S. aureus and M. catarrhalis.
CONCLUSIONS: Vaccination by PCV10 exerts a pathogen-specific effect on pneumococcal metabolic rate. Pathogen RNA/DNA ratio might represent a more sensitive readout for vaccine follow-up, as compared to nasopharyngeal carriage.
PMID: 28668567 [PubMed - as supplied by publisher]
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