The current commercial production of natural astaxanthin is mainly carried out using Haematococcus pluvialis vegetative cells in the "two-stage" batch mode. The motile vegetative cells are more sensitive to stress than nonmotile vegetative cells, thereby affecting the overall astaxanthin productivity in H. pluvialis cultures. In this study, we compared the differences between motile cells and nonmotile cells in astaxanthin productivity, morphological changes, the mortality rate, and the diameter of the formed cysts. The experimental design was achieved by two different types H. pluvialis cell under continuous light of 80 μmol photons m−2 s−1 for a 9-day induction period. The highest astaxanthin concentration of 48.42 ± 3.13 mg L−1 was obtained in the nonmotile cell cultures with the highest the productivity of 5.04 ± 0.15 mg L−1 day−1, which was significantly higher than that in the motile cell cultures. The microscopic examination of cell morphological showed a large number of photooxidative damaged cells occurring in the motile cell cultures, resulting in higher cell mortality rate (22.2 ± 3.97%) than nonmotile cell cultures (9.6 ± 0.63%). In addition, the analysis results of cell diameter statistics indicated that nonmotile cells were more conducive to the formation of large astaxanthin-rich cysts than motile cells. In conclusion, the works presented here suggest that the accumulation of astaxanthin was significantly improved by nonmotile cells of H. pluvialis, which provided a possibility of optimizing the existing H. pluvialis cultivation strategy for the industrial production.
http://bit.ly/2SckERA
Δευτέρα 4 Φεβρουαρίου 2019
Accumulation of Astaxanthin Was Improved by the Nonmotile Cells of Haematococcus pluvialis
Determination of Haematological Reference Ranges in Healthy Adults in Three Regions in Ghana
Laboratory results interpretation for diagnostic accuracy and clinical decision-making in this period of evidence-based medicine requires cut-off values or reference ranges that are reflective of the geographical area where the individual resides. Several studies have shown significant differences between and within populations, emphasizing the need for population-specific reference ranges. This cross-sectional experimental study sought to establish the haematological reference values in apparently healthy individuals in three regions in Ghana. Study sites included Nkenkaasu, Winneba, and Nadowli in the Ashanti, Central, and Upper West regions of Ghana, respectively. A total of 488 healthy participants were recruited using the Clinical and Laboratory Standards Institute (United States National Consensus Committee on Laboratory Standards, NCCLS) Guidance Document C28A2. Medians for haematological parameters were calculated and reference values determined at and percentiles and compared with Caucasian values adopted by our laboratory as reference ranges and values from other African and Western countries. RBC count, haemoglobin, and haematocrit (HCT) were significantly higher in males compared to females. There were significant intraregional and interregional as well as international variations of haematological reference ranges in the populations studied. We conclude that, for each geographical area, there is a need to establish geography-specific reference ranges if accurate diagnosis and concise clinical decisions are to be made.
http://bit.ly/2UIjAle
Macrophage Migration Inhibitory Factor Levels in Gingival Crevicular Fluid, Saliva, and Serum of Chronic Periodontitis Patients
Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.
http://bit.ly/2SfSMMw
Synthesis, Characterization, and Application of Poly(4,4'-Cyclohexylidene Bisphenol Oxalate) for Solid-Phase Extraction of DNA
The present study has synthesized poly(4,4'-cyclohexylidene bisphenol oxalate) by the condensation of oxalyl chloride with 4,4'-cyclohexylidene bisphenol, where its efficacy was tested for the solid-phase extraction of DNA. The synthesized polymer in the form of a white powder was characterized by FTIR, TGA-DTG, SEM, and BET analysis. The study utilized solid-phase application of the resulting polymer to extract DNA. The analysis of results provided the information that the extraction efficiency is a strong dependent of polymer amount and binding buffer type. Among the three types of buffers tested, the GuHCl buffer produced the most satisfactory results in terms of yield and efficiency of extraction. Moreover, the absorbance ratio of A260/A280 in all of the samples varied from 1.682 to 1.491, thereby confirming the capability of poly(4,4'-cyclohexylidene bisphenol oxalate) to elute pure DNA. The results demonstrated an increased DNA binding capacity with respect to increased percentage of the polymer. The study has concluded that poly(bisphenol Z oxalate) can be applied as one of the potential candidates for the high efficiency extraction of DNA by means of a simple, cost-effective, and environmentally friendly approach compared to the other traditional solid-phase methods.
http://bit.ly/2UH5Kzk
Changes in Lipid Indices in HIV+ Cases on HAART
We assess long-term changes in lipid levels in human immunodeficiency disease- (HIV-) infected patients undergoing highly active antiretroviral treatment (HAART) and their association with diabetes mellitus (DM) and thyroid dysfunction. We observed changes in the levels of total cholesterol (TC) and total triglyceride (TG) of 63 HIV-infected patients in the 6 years from starting HAART and analyzed correlations between relevant parameters. TC levels of patients with normal baseline TC levels as well as those diagnosed with DM or impaired fasting glucose (IFG) increased significantly (
http://bit.ly/2SbXSJi
Comparison of Laparoscopic and Conventional Cystotomy/Partial Cystectomy in Treatment of Liver Hydatidosis
Introduction. Hydatidosis is a zoonotic infection and treatment is mandatory to avoid complications. Surgery remains the first choice in the treatment especially for CE2-CE3b cysts. Open or laparoscopic approaches are available. However, comparative studies are limited. Materials and Methods. Data of patients who underwent cystotomy/partial cystectomy for liver hydatidosis between January 2012 and September 2016 (n=77) were evaluated retrospectively. Recurrent cases and the patients with previous hepatobiliary surgery were excluded. 23 patients were operated upon laparoscopically and named as Group 1. 48 patients operated conventionally named as Group 2. Demographics, cyst characteristics, operative time, length of hospital stay, recurrences, and surgery related complications were evaluated. Results. Groups were similar in terms of demographics, cyst characteristics, and operative time. The length of hospital stay was 3.4 days in Group 1 and 4.7 days in Group 2 (p=0,007). The mean follow-up period was 17.8 months and 21.7 months, respectively (p=0.170). Overall complication rates were similar in two groups (p=0.764). Three conversion cases occurred (13%). One mortality was seen in Group 2. Four recurrences occurred in each group (17% versus 8.3%, respectively) (p=0.258). Conclusions. Laparoscopy is a safe and feasible approach for surgical treatment of liver hydatidosis. Recurrence may be prevented by selection of appropriate cases in which exposure of cysts does not pose an intraoperative difficulty.
http://bit.ly/2UH615k
Differential localizations of protein phosphatase 1 isoforms determine their physiological function in the heart
http://bit.ly/2HPl37t
Beckwith–Wiedemann syndrome in diverse populations
Beckwith–Wiedemann syndrome (BWS) is the most common epigenetic overgrowth disorder and presents with patients affected by a variety of clinical features. Although genotype–phenotype correlations have been demonstrated in BWS and although BWS has been reported to occur equally among racial and ethnic backgrounds, no study to date has evaluated the frequency of findings in different backgrounds. In this study, we evaluated the incidence of clinical features and molecular diagnoses among patients with BWS in Caucasian, Mixed, and non‐Caucasian groups. These results suggest that clinical features and molecular diagnoses differ between race/ethnicity groups and raise the possibility of race and ethnicity effects on genotype–phenotype correlations in BWS.
http://bit.ly/2DVtPx7
Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum
The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late‐onset proximal muscle weakness; to a severe presentation of prenatal‐onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Here, we propose to expand the phenotypic spectrum for MuSK deficiency to include isolated VCP with the absence of other classical myasthenic symptoms. We evaluated two brothers who presented in the neonatal period with respiratory failure secondary to isolated VCP. Research‐based exome sequencing revealed biallelic likely pathogenic variants in MUSK (MIM:601296). Both children had normal gross motor and fine motor development. One brother had speech delay, likely due to a combination of tracheostomy status and ankyloglossia. This case report suggests that CMS should be on the differential diagnosis for familial recurrence of VCP.
http://bit.ly/2MQTJoc
A Leiomyosarcoma of Inferior Vena Cava Presenting as a Liver Metastasis Mass in a Patient with History of Transitional Cell Carcinoma
Abstract
The most probable diagnosis for a newly detected mass in the cancer patients is secondary metastasis. However, the multiple primary tumors should not be off the table of diagnoses. In this study, a 70-year-old man with the history of transitional cell carcinoma (TCC) was reported who had been referred due to a newly detected mass in the hepatic segment one which adhered to the inferior vena cava (IVC). Although the most probable diagnosis according to the patient's medical history was secondary metastasis, the biopsy revealed a leiomyosarcoma (LMS) tumor. Therefore, a mass biopsy can be determinative for confirming the diagnosis and further management of cancer patients with a newly detected mass.
http://bit.ly/2Twrmyt
The pretreatment platelet count is an independent predictor of tumor progression in patients undergoing transcatheter arterial chemoembolization with hepatitis B virus-related hepatocellular carcinoma
Future Oncology, Ahead of Print.
http://bit.ly/2t3uQg6
Viper as a Batesian Model – its Role in an Ecological Community
Abstract
Appearance of Old world vipers of genus Vipera serves various purposes including crypsis and aposematism. Recent research showed that the zigzag pattern represents strong signal to predators to avoid vipers as a prey. It is also possible that vipers function within ecological community as Batesian model for numerous mimics, including other reptiles, birds, and invertebrates. It is then showed that Batesian models need to have prominent features to sustain the mimicry system. The main modulation of this system is presented here as iconicity. Iconicity is treated as quantitative variable resulting from open dynamic process with multiple inputs, also including iconicity of previous states of system. Batesian mimicry is based on mimics adopting the iconicity of the model. It is an example of ecological facilitation, and as such, it is part of niche construction. Since Batesian mimicry is based on semiotic processes, it is a special case of ecological facilitation, namely semiotic facilitation.
http://bit.ly/2MQNtwI
Negative impact of carbapenem methylation on the reactivity of {beta}-lactams for cysteine acylation revealed by quantum calculations and kinetic analyses [Chemistry; Biosynthesis]
The Ldtfm L,D-transpeptidase mediates resistance to most β-lactam antibiotics in Enterococcus faecium by replacing classical peptidoglycan polymerases. The catalytic Cys of Ldtfm is rapidly acylated by β-lactams belonging to the carbapenem class but not by penams and cephems. We previously reported quantum calculations and kinetic analyses for Ldtfm and showed that the inactivation profile is not determined by differences in drug binding (KD values in the 50-80 mM range). Here, we analyze the reaction of a Cys sulfhydryl with various β-lactams in the absence of the enzyme environment in order to compare the intrinsic reactivity of drugs belonging to the penam, cephem, and carbapenem classes. For this purpose, we synthesized cyclic Cys-Asn to generate a soluble molecule with a sulfhydryl closely mimicking a cysteine in a polypeptide chain thereby avoiding free reactive amino and carboxyl groups. Computational studies identified a thermodynamically favored pathway involving a concerted rupture of the β-lactam amide bond and formation of an amine anion. Energy barriers indicated that the drug reactivity was the highest for non-methylated carbapenems, intermediate for methylated carbapenems and cephems, and the lowest for penams. Electron withdrawing groups were key reactivity determinants by enabling delocalization of the negative charge of the amine anion. Acylation rates of cCys-Asn determined by spectrophotometry revealed the same order in the reactivity of β-lactams. We concluded that the rate of Ldtfm acylation is largely determined by the β-lactam reactivity with one exception as the enzyme catalytic pocket fully compensated for the detrimental effect of carbapenem methylation.
http://bit.ly/2GouSXH
Whole genome sequencing for drug resistance profile prediction in Mycobacterium tuberculosis [Mechanisms of Resistance]
Whole genome sequencing allows rapid detection of drug-resistant Mycobacterium tuberculosis isolates. However, the availability of high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data has thus far been limited.
We determined drug resistance profiles of 176 genetically diverse clinical M. tuberculosis isolates from Democratic Republic of the Congo, Ivory Coast, Peru, Thailand and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD BACTEC MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. We compared DST results with predicted drug resistance profiles inferred by whole genome sequencing.
Classification of strains by the two phenotypic DST methods into resistotype/wild type populations was concordant in 73-99 % of cases, depending on the drug. Our data suggests that the established critical concentration (5 mg/L) for ethambutol resistance (MGIT 960 system) is too high and may misclassify strains as susceptible, compared to 7H10 agar dilution. Increased minimal inhibitory concentrations were explained by mutations identified by whole genome sequencing. Using whole genome sequences, we were able to predict quantitative drug resistance levels for the majority of drug resistance mutations. Predicting quantitative levels of drug resistance by whole genome sequencing was partially limited due to incompletely understood drug resistance mechanisms. The overall sensitivity and specificity of whole genome-based DST were 86.8 % and 94.5 %, respectively.
Despite some limitations, whole genome sequencing has the potential to infer resistance profiles without the need for time-consuming phenotypic methods.
http://bit.ly/2SuameP
In Vitro Activity of Tebipenem (SPR859) Against Penicillin-Binding Proteins of Gram-negative and Gram-positive Bacteria [Mechanisms of Action]
Tebipenem (SPR859) is the microbiologically active form of SPR994, tebipenem-pivoxil, an orally available carbapenem with activity against extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae. Measurement of the relative binding of SPR859 to the bacterial cell targets revealed that it is a potent inhibitor of multiple penicillin-binding proteins (PBPs), but primarily a Gram-negative PBP2 inhibitor, similar to other compounds in this class. These data support further clinical development of SPR994.
http://bit.ly/2GoFciy
Impact of Pre-existing Hepatitis C Virus Genotype 6 NS3, NS5A and NS5B Polymorphisms on Their In Vitro Susceptibility to Inhibition by Direct-Acting Antiviral Agents [Antiviral Agents]
HCV genotype (GT)-6 is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with HCV GT-6a where high response rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse with 29 reported subtypes. We explored the diversity of GT-6 polymorphisms at residues associated with DAA resistance, their impact on DAA in vitro potency when evaluated in a GT-6a consensus replicon and their association with specific GT-6 subtypes. GT-6 sequences from 25 patient-derived samples and 105 sequences from the US HCV database were compared and substitutions at resistance-associated residue positions were phenotyped against different DAAs. Pre-existing resistance-associated substitutions (RASs) to NS3 protease (A156V, D168E) and NS5B nucleotide (L159F, S282C) inhibitors were rare (<4%). Pre-existing RASs to NS5A inhibitors were common, especially at L28 (A/F/G/M/T/V) and R30 (E/N/S). In vitro susceptibilities of NS5A-L28A and -L28T were dramatically reduced against all tested NS5A drugs (EC90 range 119-2032nM) compared with susceptibilities against a GT-6a consensus replicon (EC90 range 0.1-19nM). These L28 RASs pre-existed in combination with R30S (EC90[lsqb]L28A-R30S[rsqb] ≥720nM or EC90[lsqb]L28T-R30S[rsqb] ≥128nM against tested DAAs) or as L28T-L31I (EC90[lsqb]tested DAAs[rsqb] >5000nM) and were detected in evaluated GT-6b or -6f sequences. NS5A-L28A-R30A, observed in GT-6r, did not replicate. In conclusion, HCV GT-6b, GT-6f and GT-6r sequences harbored highly resistant RASs to all evaluated NS5A drugs. Monitoring of response rates in patients infected with these GT-6 subtypes treated with NS5A drug-containing regimens is therefore suggested to confirm any association between noted NS5A polymorphisms and treatment failure.
http://bit.ly/2Srf3WM
"Resurrecting old {beta}-lactams": the potent inhibitory activity of temocillin against multi-drug resistant Burkholderia spp. isolates from the United States [Mechanisms of Resistance]
Burkholderia spp. are opportunistic human pathogens that infect persons with cystic fibrosis and the immunocompromised. Burkholderia spp. express class A and C β-lactamases, which are transcriptionally regulated by PenRA through linkage to cell wall metabolism and β-lactam exposure. The potency of temocillin, a 6-methoxy-β-lactam was tested against a panel of multi-drug resistant (MDR) Burkholderia spp. In addition, the mechanistic basis of temocillin activity was assessed and compared to ticarcillin. Susceptibility testing with temocillin and ticarcillin was conducted, as well as biochemical analysis of the PenA1 class A β-lactamase and AmpC1 class C β-lactamase. Molecular dynamics simulations (MDS) were performed using PenA1 with temocillin and ticarcillin. The majority (86.7%) of 150 MDR Burkholderia strains were susceptible to temocillin, while only 4% of the strains were susceptible to ticarcillin. Neither temocillin nor ticarcillin induced bla expression. Ticarcillin was hydrolyzed by PenA1 (kcat/Km = 1.7±0.2 μM-1s-1), while temocillin was slow to form a favorable complex (Kiapp = ~2 mM). Ticarcillin and temocillin were both potent inhibitors of AmpC1, with Ki app values of 4.9±1.0 μM and 4.3±0.4 μM, respectively. MDS of PenA revealed that ticarcillin is in an advantageous position for acylation and deacylation. Conversely, with temocillin, active site residues K73 and S130 are rotated and the catalytic water molecule is displaced, thereby slowing acylation and allowing the 6-methoxy of temocillin to block deacylation. Temocillin is a β-lactam with potent activity against Burkholderia spp. as it does not induce bla expression and is poorly hydrolyzed by endogenous β-lactamases.
http://bit.ly/2GoF9TU
An in vitro Mechanistic Study of the Distribution of Lascufloxacin into the Epithelial Lining Fluid [Pharmacology]
The present study aimed to clarify the mechanism underlying the high distribution of lascufloxacin in epithelial lining fluid (ELF). Involvement of transporters was examined by transcellular transport across Calu-3 and transporter-overexpressing cells; the binding of lascufloxacin to ELF components was examined by an organic solvent-water partitioning system that employed pulmonary surfactant and phospholipids. Transcellular transport across the transporter-overexpressing cells indicated lascufloxacin to be a substrate of both P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP); therefore, its transport across Calu-3 cells was inhibited by P-gp and BCRP inhibitors. However, permeability and efflux ratios of lascufloxacin were similar to those of the other quinolones with relatively low ELF distribution, indicating the existence of another mechanism for lascufloxacin distribution in ELF. Amongst pulmonary surfactants, which are a primary component of ELF, lascufloxacin preferentially bound to phosphatidylserine (PhS) from several phospholipids, and the binding was significantly higher than that for other quinolones. This binding was saturable with two apparent classes of binding sites, and inhibited by some weakly basic drugs, indicating the presence of an ionic bond. In conclusion, the results of this study suggest that the binding of lascufloxacin to PhS in the pulmonary surfactant is the major mechanism of the high distribution of lascufloxacin in the ELF.
http://bit.ly/2SsXOnX
Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy [Pharmacology]
This retrospective study included pediatric intensive care unit patients receiving continuous venovenous hemodiafiltration (CVVHDF) being treated with cefepime. Free drug concentration time above one and four times a presumed MIC of 8 mcg/mL were calculated. Four patients received doses ranging from 48 to 64 mg/kg/dose every six to twelve hours. Three patients achieved 100% fT>1xMIC with the fourth achieving 98% fT>1xMIC. Therapeutic drug monitoring should be considered for critically ill patients receiving cefepime on CVVHDF.
http://bit.ly/2GoEMJ0
A FASII inhibitor prevents staphylococcal evasion of daptomycin by inhibiting phospholipid decoy production [Mechanisms of Action]
Daptomycin is a treatment of last resort for serious infections caused by drug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus. We have shown recently that S. aureus can evade daptomycin by releasing phospholipid decoys that sequester and inactivate the antibiotic, leading to treatment failure. Since phospholipid release occurs via an active process, we hypothesised that it could be inhibited, thereby increasing daptomycin efficacy. To identify opportunities for therapeutic interventions that block phospholipid release, we first determined how the host environment influenced the release of phospholipids and inactivation of daptomycin by S. aureus. The addition of certain host-associated fatty acids to the growth medium enhanced phospholipid release. However, in serum, the sequestration of fatty acids by albumin restricted their availability to S. aureus sufficiently to prevent their use in the generation of released phospholipids. This finding implied that in host tissues S. aureus may be completely dependent upon endogenous phospholipid biosynthesis to generate lipids for release, providing a target for therapeutic intervention. To test this, we exposed S. aureus to AFN-1252, an inhibitor of the staphylococcal FASII fatty acid biosynthetic pathway, together with daptomycin. AFN-1252 efficiently blocked daptomycin-induced phospholipid decoy production, even in the case of isolates resistant to AFN-1252, which prevented the inactivation of daptomycin and resulted in sustained bacterial killing. In turn, daptomycin prevented the fatty acid-dependent emergence of AFN-1252-resistant isolates in vitro. In summary, AFN-1252 significantly enhances daptomycin activity against S. aureus in vitro by blocking the production of phospholipid decoys, whilst daptomycin blocks the emergence of resistance to AFN-1252.
http://bit.ly/2SxqJXU
Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis [Experimental Therapeutics]
Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence.
http://bit.ly/2GoEJNk
Impact of an antimicrobial stewardship intervention on within and between patient daptomycin resistance evolution in vancomycin-resistant Enterococcus faecium. [Clinical Therapeutics]
Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem, and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. To assess the impact of the intervention, daptomycin prescribing patterns and clinically-reported culture results from VRE faecium blood stream infections (BSI) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis. We corrected for a change in MIC testing methodology by retesting 262 isolates using E-test and broth microdilution. Hospital-wide and within-patient resistance patterns of corrected daptomycin MICs are reported. Our data show that daptomycin prescriptions decreased from an average of 287 days of therapy/month pre-intervention, to 151 days of therapy/month post-intervention. Concurrently, the proportion of patients experiencing an increase in daptomycin minimum inhibitory concentration (MIC) during an infection declined from 14.6% (7/48 patients) in 2014 to 1.9% (1/54 patients) in 2017. Hospital-wide resistance to daptomycin also decreased in the post-intervention period, but this was not maintained. This study shows that an antimicrobial stewardship guided intervention reduced daptomycin use and improved individual level outcomes but had only transient impact on the hospital-level trend.
http://bit.ly/2StsiGv
Abrogation of triazole resistance upon deletion of CDR1 in a clinical isolate of Candida auris [Mechanisms of Resistance]
Candida auris has rapidly emerged as a healthcare-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to C. albicans CDR1 and MDR1 among three triazole-resistant clinical isolates, as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete C. auris CDR1 and MDR1 in both a triazole-resistant clinical isolate and the susceptible reference strain, and observed MIC for all clinically available triazoles decreased as much as 128-fold in the CDR1 deletion strains. The findings of this work reveal for the first time that both C. auris CDR1 and MDR1 are more highly expressed among triazole-resistant clinical isolates of C. auris, and that the overexpression of CDR1 is a significant contributor to clinical triazole resistance.
http://bit.ly/2Suag74
In vitro antimicrobial activity of diacerein on 76 gram-positive cocci isolates from bacterial keratitis patients and an in vivo study of diacerein eye drops on Staphylococcus aureus keratitis in mice [Experimental Therapeutics]
Bacterial keratitis is an aggressive infectious corneal disease. With the continuing rise in antibiotic resistance and a decline in the discovery of new antibiotics, new antimicrobial drugs are now required. In the present study, we determined the antibacterial activity of diacerein, an anti-inflammatory drug, against 76 Gram-positive cocci isolated from bacterial keratitis patients in vitro and anti-Staphylococcus aureus activity in mouse bacterial keratitis model in vivo. The minimum inhibitory concentrations (MICs) of diacerein were tested using the broth microdilution method in vitro. A BALB/c Staphylococcus aureus keratitis animal model was selected and the corneal clinical observation, viable bacteria and Hematoxylin-eosin and Gram staining of infected corneas were measured to evaluate antibacterial efficacy of diacerein eye drops in vivo. An in vivo eye irritation study was carried out by a modified Draize test in rabbits. Our in vitro results showed that diacerein possesses satisfactory antibacterial activity against the majority of Gram-positive cocci (60/76), including all 57 tested Staphylococcus and 3 Enterococcus. The in vivo experiment showed that diacerein eye drops reduced bacterial load and improved ocular clinical scores after topical administration of diacerein drops on infected corneas. The ocular irritation test revealed that diacerein eye drop had excellent ocular tolerance. These results indicated that diacerein possesses in vivo anti-Staphylococcus aureus activity. We suggest that diacerein is a possible topically administered drug for Staphylococcus aureus-infected patients, especially those with ocular surface inflammatory disorders.
http://bit.ly/2GoEB0i
Clinical and Molecular Characteristics of qacA/B-Positive Methicillin-resistant Staphylococcus aureus Causing Bloodstream Infections [Epidemiology and Surveillance]
The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA/B-chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA/B-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B. The annual frequency of qacA/B-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA/B-positive MRSA had common risk factors for healthcare-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive-care-unit-acquired bacteremia, and nosocomial infection. The qacA/B-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-β-lactam antibiotics. The qacA/B-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common healthcare-associated MRSA strain in South Korea. In multivariable analyses, qacA/B-positive MRSA isolates were found to be associated with agr dysfunction (aOR, 6.45; 95% CI, 2.59–16.10), ST5 MRSA strain (aOR 4.96; 95% CI, 1.85–13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20–10.83), and antibiotic use within the previous 3 months (aOR, 2.59; 95% CI, 1.20–5.59). These findings suggest that the microbiological features of qacA/B carriage may provide a selective advantage for specific MRSA strains in hospital environments.
http://bit.ly/2SxqwUC
Viability Screen of LOPAC1280 Reveals Tyrosine Kinase Inhibitor Tyrphostin A9 as a Novel Partner Drug for Artesunate Combinations to Target the Plasmodium falciparum Ring Stage [Experimental Therapeutics]
The emergence of artemisinin-resistant P. falciparum poses a major threat to current frontline artemisinin combination therapies. Artemisinin resistance is widely associated with mutations in the PfKelch13 propeller region leading to delayed parasite clearance and increased survival of early ring stage parasites. There is therefore a need to discover novel drugs that are effective against artemisinin-resistant P. falciparum. In view of this, our study aims to identify compounds from the Library of Pharmacologically Active Compounds1280 (LOPAC1280) that could increase the efficacy of artesunate and be used as a potential partner drug for treatment against artemisinin-resistant falciparum malaria. By using a modified ring stage survival assay, we performed a high throughput screening of 1280 compounds from the LOPAC library in combination with artesunate against P. falciparum IPC 5202 field isolate harboring R539T mutation at the PfKelch13 propeller region. The potencies of the hits were determined through dose-dependent isobologram analyses against both IPC 5202 and CamWT_C580Y field isolates; the latter with more prevalent C580Y mutation characteristic of artemisinin resistance. We identified tyrphostin A9 with synergistic and additive activity against both parasite strains when dosed in combination with artesunate. These findings provide promising novel artesunate combinations that can target the P. falciparum artemisinin resistant ring stage and insights that may aid in a better understanding of the mechanism involved in ART resistance.
http://bit.ly/2GoEx0y
Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections [Clinical Therapeutics]
Opisthorchiasis, caused by the food-borne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao PDR, pharmacokinetic samples from 125 adult and adolescent O. viverrini patients treated with 400 mg tribendimidine were obtained following the design of an sparse sampling scheme at 20 min, 2, 7.75, 8 and 30 h after treatment, using dried blood spot sampling. Pharmacokinetic data for the metabolites dADT and adADT were pooled with data from two previous dose-ascending trials and evaluated using nonlinear mixed-effects modelling. The observed pharmacokinetic data were described using a flexible transit absorption model for the active metabolite dADT followed by one-compartment disposition models for both metabolites. Significant covariates were age, body weight, formulation, and breaking of the enteric coating on the tablets. There were significant associations between O. viverrini cure and both dADT Cmax and AUC (p-values <0.001), with younger age associated with a higher probability of cure. Modelling and simulation of exposures in a patients with different weight and age combinations showed that an oral single dose of 400 mg tribendimidine attained therapeutic success in over 90% of adult patients. Our data confirmed that tribendimidine could be a valuable novel alternative to the standard treatment praziquantel for the treatment of O. viverrini infections.
http://bit.ly/2Sxqvjw
Genetic ancestry-dependent differences in breast cancer-induced field defects in the tumor-adjacent normal breast
Purpose: Genetic ancestry influences evolutionary pathways of cancers. However, whether ancestry influences cancer-induced field defects is unknown. The goal of this study was to utilize ancestry-mapped true normal breast tissues as controls to identify cancer-induced field defects in normal tissue adjacent to breast tumors (NATs) in women of African American (AA) and European (EA) ancestry. Experimental Design: A tissue microarray (TMA) comprising breast tissues of ancestry-mapped 100 age-matched healthy women from the Komen Tissue Bank (KTB) at Indiana University and tumor-NAT pairs from 100 women (300 samples total) was analyzed for the levels of ZEB1, an oncogenic transcription factor that is central to cell fate, mature luminal cell enriched estrogen receptor alpha (ERa), GATA3, FOXA1 and for immune cell composition. Results: ZEB1+ cells, which were localized surrounding the ductal structures of the normal breast, were enriched in the KTB-normal of AA compared to KTB-normal of EA women. By contrast, in EA women, both NATs and tumors compared to KTB-normal contained higher levels of ZEB1+ cells. FOXA1 levels were lower in NATs compared to KTB-normal in AA but not in EA women. We also noted variations in the levels of GATA3, CD8+ T cells, PD1+ immune cells, and PDL1+ cell but not CD68+ macrophages in NATs of AA and EA women. ERa levels did not change in any of our analyses, pointing to the specificity of ancestry-dependent variations. Conclusions: Genetic ancestry-mapped tissues from healthy individuals are required for proper assessment and development of cancer-induced field defects as early cancer detection markers.
http://bit.ly/2GbyEof
Single-cell profiling of cutaneous T-cell lymphoma reveals underlying heterogeneity associated with disease progression
Purpose: Cutaneous T cell lymphomas (CTCL), encompassing a spectrum of T-cell lymphoproliferative disorders involving the skin, have collectively increased in incidence over the last 40 years. Sézary syndrome (SS) is an aggressive form of CTCL characterized by significant presence of malignant cells in both the blood and skin. The guarded prognosis for SS reflects a lack of reliably effective therapy, due in part to an incomplete understanding of disease pathogenesis. Methods: Using single-cell sequencing of RNA and the machine-learning reverse graph embedding approach in the Monocle package, we defined a model featuring distinct transcriptomic states within SS. Gene expression used to differentiate the unique transcriptional states were further utilized to develop a boosted tree classification for early versus late CTCL disease. Results: Our analysis showed the involvement of FOXP3+ malignant T cells during clonal evolution, transitioning from FOXP3+ T cells to GATA3+ or IKZF2+ (HELIOS) tumor cells. Transcriptomic diversities in a clonal tumor can be used to predict disease stage, and we were able to characterize a gene signature that predicts disease stage with close to 80% accuracy. FOXP3 was found to be the most important factor to predict early disease in SS, along with another 19 genes used to predict CTCL stage. Conclusions: This work offers insight into the heterogeneity of SS, providing better understanding of the transcriptomic diversities within a clonal tumor. This transcriptional heterogeneity can predict tumor stage and thereby offer guidance for therapy.
http://bit.ly/2D9drqV
Turning Observed Founder Alleles into Expected Relationships in an Intercross Population
Pedigree-derived relationships for individuals from an intercross of several lines cannot easily account for the segregation variance that is mainly caused by loci with alternative alleles fixed in different lines. However, when all founders are genotyped for a large number of markers, such relationships can be derived for descendants as expected genomic relationships conditional on the observed founder allele frequencies. A tabular method was derived in detail for autosomes and the X chromosome. As a case study, we analyzed litter size and body weights at three different ages in an advanced mouse intercross (29 generations, total pedigree size 19,266) between a line selected for high litter size (FL1) and a highly inbred control line (DUKsi). Approximately 60% of the total genetic variance was due to segregation variance. Estimated heritability values were 0.20 (0.03), 0.34 (0.04), 0.23 (0.03), 0.41 (0.03) and 0.46 (0.02) for litter size, litter weight and body weight at ages of 21, 42 and 63 days, respectively (standard errors in brackets). These values were between 12% and 65% higher than observed in analyses that treated founders as unrelated. Fields of applications include experimental populations (selection experiments or advanced intercross lines) with a limited number of founders, which can be genotyped at a reasonable cost. In principle any number of founder lines can be treated. Additional genotypes from individuals in later generations can be combined into a joint relationship matrix by capitalizing on previously published approaches.
http://bit.ly/2GmvGN0
Novel Third-Generation EGFR Tyrosine Kinase Inhibitors and Strategies to Overcome Therapeutic Resistance in Lung Cancer
EGFR-activating mutations are observed in approximately 15% to 20% of patients with non–small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. The compound has received additional FDA approval as first-line therapy with improvement in progression-free survival by suppressing the activating mutation and preventing the rise of the dominant resistance clone. Drug development has been breathtaking in this space with other third-generation compounds at various stages of development: rociletinib (CO-1686), olmutinib (HM61713), nazartinib (EGF816), naquotinib (ASP8273), mavelertinib (PF-0647775), and AC0010. However, therapeutic resistance after the administration of third-generation inhibitors is complex and not fully understood, with significant intertumoral and intratumoral heterogeneity. Repeat tissue and plasma analyses on therapy have revealed insights into multiple mechanisms of resistance, including novel second site EGFR mutations, activated bypass pathways such as MET amplification, HER2 amplification, RAS mutations, BRAF mutations, PIK3CA mutations, and novel fusion events. Strategies to understand and predict patterns of mutagenesis are still in their infancy; however, technologies to understand synthetically lethal dependencies and track cancer evolution through therapy are being explored. The expansion of combinatorial therapies is a direction forward targeting minimal residual disease and bypass pathways early based on projected resistance.
http://bit.ly/2GmCDgV
Genome-wide screening and functional analysis identifies tumor suppressor long non-coding RNAs epigenetically silenced in hepatocellular carcinoma
Long non-coding RNAs (lncRNA) play critical roles in the development of cancer including hepatocellular carcinoma (HCC). However, the mechanisms underlying their deregulation remain largely unexplored. In this study, we report that two lncRNA frequently downregulated in HCC function as tumor suppressors and are epigenetically silenced by histone methyltransferase EZH2. lncRNAs TCAM1P-004 and RP11-598D14.1 were inhibited by EZH-mediated trimethylation of H3K27me3 at their promoters. Downregulation of TCAM1P-004 and RP11-598D14.1 were frequently observed in HCC tumors compared to adjacent normal tissues. Both lncRNAs inhibited cell growth, cell survival, and transformation in HCC cells in vitro as well as tumor formation in vivo. Using RNA pull-down and mass spectrometry, we demonstrated that TCAM1P-004 bound IGF2BP1 and HIST1H1C, while RP11-598D14.1 bound IGF2BP1 and STAU1. These lncRNA-protein interactions were critical in regulating p53, MAPK, and HIF1-α pathways that promoted cell proliferation in HCC. Overexpression of EZH2 was critical in repressing TCAM1P-004 and RP11-598D14.1, and EZH2-TCAM1P-004/RP11-598D14.1-regulated pathways were prevalent in human HCC. Aberrant suppression of TCAM1P-004 and RP11-598D14.1 led to loss of their tumor suppressor effects by disrupting the interaction with IGF2BP1, HIST1H1C and STAU1, which in turn promoted HCC development and progression. Collectively, these findings demonstrate the role of TCAMP1P-004 and RP11-598D14.1 in suppressing tumor growth and suggest that EZH2 may serve as a therapeutic target in HCC.
http://bit.ly/2SvnKiM
Targeting APLN/APLNR improves anti-angiogenic efficiency and blunts pro-invasive side effects of VEGFA/VEGFR2-blockade in glioblastoma
Anti-angiogenic therapy of glioblastoma with bevacizumab, a vascular endothelial growth factor-A (VEGFA)-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles of the pro-angiogenic receptor APLNR and its cognate ligand apelin in VEGFA/VEGFR2 anti-angiogenic therapy against distinct subtypes of glioblastoma. In proneural glioblastoma, apelin levels were downregulated by VEGFA or VEGFR2 blockade. A central role for apelin/APLNR in controlling glioblastoma vascularization was corroborated in a serial implantation model of the angiogenic switch that occurs in human glioblastoma. Apelin and APLNR are broadly expressed in human glioblastoma, and knockdown or knockout of APLN in orthotopic models of proneural or classical glioblastoma subtypes significantly reduced glioblastoma vascularization compared with controls. However, reduction in apelin expression led to accelerated glioblastoma cell invasion. Analysis of stereotactic glioblastoma biopsies from patients as well as from in vitro and in vivo experiments revealed increased dissemination of APLNR-positive tumor cells when apelin levels were reduced. Application of apelin-F13A, a mutant APLNR ligand, blocked tumor angiogenesis and glioblastoma cell invasion. Furthermore, co-targeting VEGFR2 and APLNR synergistically improved survival of mice bearing proneural glioblastoma. In summary, we show that apelin/APLNR signaling controls glioblastoma angiogenesis and invasion and that both pathological features are blunted by apelin-F13A. We suggest that apelin-F13A can improve the efficiency and reduce the side effects of established anti-angiogenic treatments for distinct glioblastoma subtypes.
http://bit.ly/2Gpy4Tg
Tumour-reactive T cell subsets in the microenvironment of ovarian cancer
Tumour-reactive T cell subsets in the microenvironment of ovarian cancer
Tumour-reactive T cell subsets in the microenvironment of ovarian cancer, Published online: 05 February 2019; doi:10.1038/s41416-019-0384-y
Tumour-reactive T cell subsets in the microenvironment of ovarian cancerhttps://go.nature.com/2S8lHlo
January 2019 Briefing
Here are what the editors at HealthDay consider to be the most important developments in Family Practice for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...
http://bit.ly/2GlIWBg
Washington State Measles Cases Now at 48 Since Jan. 1
MONDAY, Feb. 4, 2019 -- There have been 48 confirmed cases of measles in Washington state since the start of the year as health officials struggle to stop the spread of the infectious disease. Since Jan. 1, there have been 47 confirmed cases in...
http://bit.ly/2D8V6u8
Cancer Survivors Face Hardship Over Medical Bills
MONDAY, Feb. 4, 2019 -- Cancer survivors carry greater financial burdens related to medical debt payments and bills versus patients without a cancer history, and younger survivors face the greatest hardships, according to a study published online...
http://bit.ly/2GbqUTd
Updated ACIP Immunization Schedule Released for Adults
MONDAY, Feb. 4, 2019 -- The Advisory Committee on Immunization Practices has released its updated adult immunization schedule for 2019; the schedule was published online Feb. 5 in the Annals of Internal Medicine. David K. Kim, M.D., from the U.S....
http://bit.ly/2DctioE
Expanded Recall of Warfarin Level Monitoring Test Strips
MONDAY, Feb. 4, 2019 -- Certain lots of Roche Diagnostics test strips should not be used with CoaguChek test meter devices to check levels of the blood thinner warfarin because patients may get inaccurate results and be at risk for serious injury or...
http://bit.ly/2GcHnq0
Early Tau Deposition Elevated for Women Versus Men
MONDAY, Feb. 4, 2019 -- For older adults on the Alzheimer disease trajectory, women have elevated early tau deposition compared with men, according to a study published online Feb. 4 in JAMA Neurology. Rachel F. Buckley, Ph.D., from Massachusetts...
http://bit.ly/2D7VxVJ
Pediatric Perioperative DNR Orders: A Case Series in a Children’s Hospital
Do-not-resuscitate (DNR) orders are common among children receiving palliative care, who may nevertheless benefit from surgery and other procedures. Although anesthesia, surgery, and pediatric guidelines recommend systematic reconsideration of DNR orders in the perioperative period, data regarding how clinicians evaluate and manage DNR orders in the perioperative period is limited.
http://bit.ly/2MPaCzZ
Next-generation whole exome sequencing of glioblastoma with a primitive neuronal component
Abstract
Glioblastoma with a primitive neuronal component (GBM-PN) was renamed from glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) in the new WHO classification of tumors of the central nervous system in 2016. GBM-PN is a rare variant of glioblastoma. There were not so many publications on the investigation of GBM-PN. We did whole exome sequencing for 11 GBM-PN cases and found that the percentage of TP53, PIK3CA, PIK3R1, or PTEN mutation in our GBM-PN cases (72.7%, 27.3%, 27.3%, and 27.3% respectively) was much higher than that in cases in TCGA GBM 2008, TCGA GBM 2013, and TCGA lower-grade glioma databases. The findings indicate that GBM-PN is a distinct variant of glioblastoma. The next-generation sequencing can play a role in the diagnosis of GBM-PN especially for small biopsy cases. Eight out of 11 cases showed mutations in PTEN–PI3K pathway, which indicates that targeted therapeutic agents (PI3K inhibitors, mTORC1 inhibitors or dual PI3K/mTOR inhibitors) may be used for the treatment of GBM-PN in the future.
http://bit.ly/2DVGEY3
Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose
Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity.
http://bit.ly/2t6cP0M
Using the Proton Energy Spectrum and Microdosimetry To Model Proton Relative Biological Effectiveness
Using Monte Carlo simulations, the microdosimetric kinetic model (MKM) was applied to three previously published proton relative biological effectiveness (RBE) studies. The MKM fitting was compared to a generic RBE model as a function of dose averaged linear energy transfer (LETD). Analysis of the fittings reveal no clear advantage to using one model over the other and we conclude that both the MKM and LETD based proton RBE models are appropriate.
http://bit.ly/2DUrxhB
Thoracic Aortic Intima-Media Thickness in Preschool Children Born Small for Gestational Age
To assess thoracic aortic intima-media thickness (aIMT) as a marker of thoracic aortic remodeling in children born small for gestational age (SGA).
http://bit.ly/2SdQXiT
Prevalence of Asthma and Allergies and Risk of Relapse in Childhood Nephrotic Syndrome: Insight into Nephrotic Syndrome Cohort
To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses.
http://bit.ly/2UG088t
Use of a Probiotic to Enhance Iron Absorption in a Randomized Trial of Pediatric Patients Presenting with Iron Deficiency
To evaluate the efficacy of low dose ferrous sulfate for the treatment of iron deficiency and if the probiotic Lactobacillus plantarum 299v (LP299v) enhances treatment.
http://bit.ly/2UIjrhI
Cardiac Autonomic Function in Adults Born Preterm
To evaluate cardiac autonomic function in adults born preterm.
http://bit.ly/2SdR0ez
Compounded Topical Pain Creams to Treat Localized Chronic Pain A Randomized Controlled Trial
http://bit.ly/2MMQ8HO
Annals Graphic Medicine: Introducing “Dr. Mom” and “Progress Notes”
http://bit.ly/2WBLeCd
Recognizing the Potential for Overdiagnosis: Are High-Sensitivity Cardiac Troponin Assays an Example?
http://bit.ly/2RDGxEe
Emergency Department Environmental Contamination With Methicillin-Resistant Staphylococcus aureus After Care of Colonized Patients
Methicillin-resistant Staphylococcus aureus (MRSA) transmission dynamics in the emergency department (ED) are not well defined; environmental surfaces may serve as reservoirs for transmission. This study investigates the effect of patients with a history of MRSA colonization or infection on subsequent MRSA contamination of the ED environment.
http://bit.ly/2MP5tYp
Clinical Practice Guideline for Emergency Department Procedural Sedation With Propofol: 2018 Update
We update an evidence-based clinical practice guideline for the administration of propofol for emergency department procedural sedation. Both the unique considerations of using this drug in the pediatric population and the substantial new research warrant revision of the 2007 advisory. We discuss the indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, and adverse events for propofol sedation.
http://bit.ly/2DVa3BP
Tumour-reactive T cell subsets in the microenvironment of ovarian cancer
https://go.nature.com/2GbHRg2
Blood Safety and Emerging Infections: Balancing Risks and Costs
http://bit.ly/2D8ICCM
The U.S. Environmental Protection Agency's Proposed Transparency Rule Threatens Health
http://bit.ly/2B7jBrB
Fracture Risk After Initiation of Use of Canagliflozin A Cohort Study
http://bit.ly/2Del4fI
Avoiding Pitfalls While Implementing New Guidelines on Student Documentation
http://bit.ly/2DcdDpm
Screening the Blood Supply for Zika Virus in the 50 U.S. States and Puerto Rico A Cost-Effectiveness Analysis
http://bit.ly/2DdmG9t
Contraception
Contraception counseling and provision are vital components of comprehensive health care. Unplanned pregnancy can be devastating to any woman but is particularly dangerous for those with chronic illness. Internal medicine providers are in a unique position to provide contraception, as they often intersect with women at the moment of a new medical diagnosis or throughout care for a chronic problem. A shared decision-making approach can engage patients and ensure that they choose a contraceptive method that aligns with their reproductive plans and medical needs.
http://bit.ly/2Gf5J2L
Early tumor shrinkage after first-line medical treatment of metastatic colorectal cancer: a meta-analysis
Abstract
Background
Early tumor shrinkage (ETS) is a response-related endpoint of clinical trials of chemotherapy (CHT) of patients with metastatic colorectal cancer (mCRC). It identifies a dimensional reduction of tumor size by at least 20–30% after 6–8 weeks of CHT.
Methods
A literature search of randomized trials of systemic treatment including CHT with or without antiangiogenics or anti-EGFR inhibitors in patients with mCRC has been conducted, and studies reporting the results of the relationship of ETS with overall survival (OS) and progression-free survival (PFS) were selected.
Results
Twelve trials, including 3117 patients, have been included; all data were retrospective and only 72% of the enrolled patients have been evaluated for ETS. Two meta-analyses, each including 20 study cohorts from the selected 12 trials, reported a strong relationship of ETS with OS (HR 0.62; CIs 0.55–0.69) and of ETS with PFS (HR 0.66; CIs 0.60–0.73). However, both meta-analyses displayed a high level of heterogeneity. Among nine possible moderators, three variables (median age, surgery of metastases, and publication year) were able to explain at least a part of this heterogeneity.
Conclusion
ETS is a simple and interesting intermediate endpoint for clinical practice and future trials of medical treatments of patients with mCRC, but a large prospective analysis and validation are mandatory.
http://bit.ly/2G93AFC
What can cause gum pain?
There are many possible causes of gum pain, including gum disease, mouth injuries, infections, abscesses, and ulcers. Without treatment, some causes of gum pain can lead to tooth decay and tooth loss. Learn more here.
http://bit.ly/2t9arGl
Policy Statements on the Effects of Media Overlook Scientific Complexity
As different forms of media infuse everyday life, several organizations and associations have issued public statements about the various effects of media exposure. However, a scholarly review suggests that many of these statements do not accurately reflect the available scientific evidence, offering overly simplified or one-sided accounts of the scientific research. The findings are published in Advances in Methods and Practices in Psychological Science, a journal of the Association for Psychological Science.
"Although there certainly are some pretty good media policy statements out there, many of the policy statements were not very accurate and where there were inaccuracies, these tended to lean in the direction of conclusions that were generally scarier than could be defended by the actual data," says psychology researcher Christopher J. Ferguson of Stetson University, who coauthored the paper with fellow media researchers. "There's no assumption of bad faith, of course, but it seems many professional organizations are struggling to develop policy statements that effectively communicate the complicated, messy and nuanced nature of many media effects fields."
Ferguson and his coauthors are all researchers with expertise in some aspect of media effects, although they don't always draw the same conclusions about the impact of different forms of media. They consider ongoing discussion and debate to be an important part of the scientific process, but they noticed that many organizations' policy statements about media effects didn't acknowledge that any such debate was taking place.
"We were curious to know how often this was happening and, if this was happening a lot, point out directions that could lead to more accurate statements in the future," says Ferguson.
Using Google Scholar and targeted web searches, the team of researchers identified media effects policy statements produced by professional advocacy organizations that represent scholars or clinicians in relevant fields (e.g., American Academy of Pediatrics, American Psychological Association). These searches produced 24 public statements, with the earliest issued in the early 1990s. The statements covered impacts resulting from media violence, screen time, sexual content, and more "general" effects.
The research team broke into subgroups to evaluate each type of statement, using a standardized rubric focused on specific characteristics: citation bias, false consistency, lack of clarity of transparency, overgeneralization, exaggeration, insulation, and noncredible sources.
In general, the researchers found a noticeable increase in the frequency of media effects statements in the last 30 years. Most of the 24 policy statements came from organization-based committees and were produced by scholars who had interest and expertise in the field.
The research team found that the majority of statements, 19 out of 24, showed citation bias, citing evidence that supported a specific conclusion without mentioning existing evidence that did not support the conclusion. Similarly, 22 out of 24 statements were characterized by false consistency, implying that the evidence on media effects was more consistent than it was in actuality. And only one statement made any reference to the existence of diverse viewpoints among scholars in that area.
The team concluded that 15 out of the 24 statements overgeneralized results, applying media effects findings to contexts far beyond the scope of the original research. And 19 out of 24 statements made exaggerated claims about media effects, suggesting public health or other societal impacts without noting the small or trivial size of the effects found in many research studies.
Most of the statements did not provide detailed information about who produced the statement or how they were selected. They also did not indicate how the data that informed the statements were selected.
Ferguson and colleagues suggest that these findings have important implications for both policymakers and parents.
"Since these are 'policy statements,' presumably they are staking out policy positions the organizations would like to see policymakers move on. But policymakers may need to be cautious not to mistake these policy positions for a fair summary of current research," Ferguson says. "The other group of concern is parents, since many parents may become needlessly worried about media effects when policy statements proclaim the evidence to be stronger, more consistent, or more applicable to real life behaviors than it actually is."
Based on their findings, the research team devised a checklist for best practices that, if followed, would substantively improve the accuracy and quality of such policy statements:
- Acknowledge disconfirmatory data
- Focus on the magnitude of effects
- Acknowledge limitations of research methods
- Solicit balanced views
- Avoid secondary sources
- Distinguish scientific statements from advocacy statements
- Release fewer statements
- Be mindful of unintended harms
- Prioritize and encourage open science practices
The authors of this research serve as members of the New Media, Public Education and Public Policy Committee of the Society for Media Psychology and Technology (Division 46 of the American Psychological Association).
All data and materials have been made publicly available via the Open Science Framework. This article has received badges for Open Data and Open Materials.
http://bit.ly/2UDsCjh
CDC Examines Safety of Recombinant Zoster Vaccine
MONDAY, Feb. 4, 2019 -- During the first eight months of recombinant zoster vaccine (RZV) use, there were reports of 4,381 adverse events, 3 percent of which were serious, according to research published in the Feb. 1 issue of the U.S. Centers for...
http://bit.ly/2RDdosO
Some Obesity-Related Cancers Increasing in Younger Adults
MONDAY, Feb. 4, 2019 -- The incidence of some obesity-related cancers is increasing in younger generations, according to a study published online Feb. 3 in The Lancet Public Health. Hyuna Sung, Ph.D., from the American Cancer Society in Atlanta, and...
http://bit.ly/2WGCLxC
Severe Maternal Morbidity, Mortality Up With Infertility Tx
MONDAY, Feb. 4, 2019 -- Women with infertility-treated pregnancy have an increased risk for severe maternal morbidity or maternal death, with invasive infertility treatment associated with an increased likelihood of having three or more severe...
http://bit.ly/2RDZeHE
High Physical Activity Levels Tied to Coronary Artery Calcification
MONDAY, Feb. 4, 2019 -- High levels of physical activity correlate with prevalent coronary artery calcification (CAC) but are not linked to increased mortality, according to a study published online Jan. 30 in JAMA Cardiology. Laura F. DeFina, M.D.,...
http://bit.ly/2WP2kN4
Sponge Cytology-Sampling Device Promising for Barrett Esophagus Dx
MONDAY, Feb. 4, 2019 -- A swallowable cellular retrieval capsule sponge cytology-sampling device, EsophaCap, in combination with a methylation biomarker panel represents a promising strategy for diagnosing Barrett esophagus (BE), according to a...
http://bit.ly/2RIihRu
E-Cigarette Use Linked to Cigarette Initiation in Adolescents
MONDAY, Feb. 4, 2019 -- Electronic cigarette use is associated with an increased risk for cigarette initiation and use in adolescents, according to a study published online Feb. 1 in JAMA Network Open. Kaitlyn M. Berry, M.P.H., from the Boston...
http://bit.ly/2WH0VIj
Tofacitinib Benefits Sustained for Two Years in Patients With RA
MONDAY, Feb. 4, 2019 -- The clinical benefits of tofacitinib in combination with methotrexate are sustained over two years among patients with rheumatoid arthritis (RA), according to a study published online Jan. 22 in Arthritis &...
http://bit.ly/2RCvbQL
After Elbow Surgery, Children May Be Overprescribed Opioids
MONDAY, Feb. 4, 2019 -- Opioids may be overprescribed to children after orthopedic surgery for supracondylar humerus fractures, according to a study published in the Jan. 16 issue of The Journal of Bone & Joint Surgery. Apurva Shah, M.D., from...
http://bit.ly/2WGCKty
Frailty Tied to Liver Transplant Wait-List Mortality in Cirrhosis
MONDAY, Feb. 4, 2019 -- In patients with cirrhosis, frailty is more frequently observed in those with ascites or hepatic encephalopathy (HE) and is independently associated with liver transplant wait-list mortality, according to a study published...
http://bit.ly/2REoH3J
Unrestrained Driver Predicts Unrestrained Child Passenger
MONDAY, Feb. 4, 2019 -- An unrestrained driver is a strong predictor for having an unrestrained child passenger in both fatal and nonfatal crashes, according to a study published online Feb. 4 in Pediatrics. Douglas R. Roehler, Ph.D., M.P.H., from...
http://bit.ly/2WHWcG5
Tox and Hound – Not For Human Consumption
by Dan Rusyniak At my poison center we have seen an increasing number of a calls related to a drug I had never heard of – Tianeptine. Tianewhat? Yes, I thought the same. Although I had not heard of it, this is a drug that has been around since the 1970's. Synthesized in the 60's […]
EMCrit Project by Tox & Hound.
http://bit.ly/2DRfelZ
Putting Yourself in Their Shoes May Make You Less Open to Their Beliefs
Trying to take someone else's perspective may make you less open to their opposing views, according to findings published in Psychological Science, a journal of the Association for Psychological Science.
"As political polarization in America has increased, there has been a lot of discussion about how to bring people with opposing views to the table, in order to have more productive dialogues," says lead researcher Rhia Catapano of the Stanford University Graduate School of Business. "Our findings show that self-persuasion can be an effective way to move people from entrenched views, but that perspective taking can actually undermine its effectiveness."
Although policymakers and pundits often refer to perspective taking when they talk about addressing polarization, the scientific evidence for its effectiveness as a self-persuasion strategy is mixed. On the one hand, people might generate more persuasive arguments or relate more to alternative viewpoints after taking someone else's perspective. On the other hand, it's possible that trying to see things from the other side could make people more entrenched in their views, especially when they view alternative perspectives in a competitive light.
Catapano and colleagues hypothesized that taking the perspective of someone with an opposing opinion may backfire when that person is seen as having very different values.
For their first online experiment, the researchers recruited participants from Reddit with the aim of reaching a large sample of people interested in political issues. The 484 participants completed a survey, in which they reported demographic information and rated their support for universal health care (from 0, strongly against, to 100, strongly support).
The participants then received information about the person they would supposedly be interacting with in the next task: a 22-year-old White male from Ohio. Importantly, the partner's political ideology and attitude toward universal health care were always opposite those of each participant.
Half of the participants were instructed to reflect on their partner's intentions and interests and visualize his life and experiences. And all of the participants generated an argument that their partner might give in support of his attitude toward universal health care.
At the beginning of the experiment, the two groups of participants reported similar initial attitudes toward universal health care. However, those who engaged in the perspective taking exercise reported less receptiveness and showed less attitude change compared with the control group. As the researchers hypothesized, personal values helped to explain this effect – participants who engaged in perspective taking reported that their worldview and morals were less aligned with their partner's compared with those in the control group.
And the researchers replicated these findings with another online sample of 998 participants recruited from Amazon MTurk.
"When people try to take the perspective of those on the other side, they're actually quite good at it. They write arguments that people on that side might actually come up with, rather than dismissing the task or writing poor arguments on purpose," Catapano explains. "The problem is that the arguments appeal to the values of the person whose perspective they're taking, rather than their own values."
But what if people felt as though they were taking the perspective of someone who holds similar values despite having a different opinion?
Findings from a second online experiment suggest that perspective taking enhances participants' openness to an alternative viewpoint when their values are congruent with those of their partner.
Together, the findings shed light on the self-persuasion strategies that are most likely to help bridge ideological divides. Intriguingly, simply generating arguments for the other side – the control condition in each experiment – actually seemed to increase participants' receptiveness.
"Having people think of arguments for the opposing view but without engaging in perspective taking, was quite effective in opening people up to the opposing view," says Catapano. "We found that encouraging."
Coauthors on the research include Zakary L. Tormala of the Stanford University Graduate School of Business and Derek D. Rucker of the Kellogg School of Management at Northwestern University.
The experiments reported in this article were preregistered via the Open Science Framework and the stimuli, analysis code, and anonymized data for the experiments are available online (Experiment 1; Experiment 1 replication; Experiment 2). This article has received the badges for Open Data, Open Materials, and Preregistration.
http://bit.ly/2MOqpiv
Why Travel for Complex Cancer Surgery? Americans React to ‘Brand-Sharing’ Between Specialty Cancer Hospitals and Their Affiliates
Abstract
Introduction
Leading cancer hospitals have increasingly shared their 'brand' with smaller hospitals through affiliations. Because each brand evokes a distinct reputation for the care provided, 'brand-sharing' has the potential to impact the public's ability to differentiate the safety and quality within hospital networks. The general public was surveyed to determine the perceived similarities and differences in the safety and quality of complex cancer surgery performed at top cancer hospitals and their smaller affiliate hospitals.
Methods
A national, web-based KnowledgePanel (GfK) survey of American adults was conducted. Respondents were asked about their beliefs regarding the quality and safety of complex cancer surgery at a large, top-ranked cancer hospital and a smaller, local hospital, both in the presence and absence of an affiliation between the hospitals.
Results
A total of 1010 surveys were completed (58.1% response rate). Overall, 85% of respondents felt 'motivated' to travel an hour for complex surgery at a larger hospital specializing in cancer, over a smaller local hospital. However, if the smaller hospital was affiliated with a top-ranked cancer hospital, 31% of the motivated respondents changed their preference to the smaller hospital. When asked to compare leading cancer hospitals and their smaller affiliates, 47% of respondents felt that surgical safety, 66% felt guideline compliance, and 53% felt cure rates would be the same at both hospitals.
Conclusions
Approximately half of surveyed Americans did not distinguish the quality and safety of surgical care at top-ranked cancer hospitals from their smaller affiliates, potentially decreasing their motivation to travel to top centers for complex surgical care.
http://bit.ly/2Tr4S1O
Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients
Abstract
Background
The impact of the neoadjuvant chemoradiation-to-surgery (CRT-S) interval in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR) and overall survival (OS).
Methods
National Cancer Data Base patients with CRT followed by surgery were studied. CRT-S interval was studied as a continuous (weeks) and categorical variable (quintiles: 15–37, 38–45, 46–53, 54–64, and 65–90 days, with n = 1016, 1063, 1081, 1083, and 938 patients, respectively).
Results
A total of 5181 patients were included; 81% had adenocarcinoma. There was a significant increase of pCR rate across quintiles (18%, 21%, 24%, 25%, and 29%, p < 0.001) and per week increase of CRT-S interval [odds ratio (OR) 1.11, p < 0.001]. The 90-day mortality increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5%, and 8.2%, p = 0.02) and through weeks (OR 1.05, p = 0.03). Mean OS across CRT-S quintiles was 36.4, 35.1, 33.9, 33.2, and 30.7 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval [hazard ratio (HR) 1.02, p = 0.02], especially among the last quintile (CRT-S = 65–90 days: HR 1.2, p = 0.009). The squamous cell carcinoma (SCC) and pCR groups had similar OS across CTR-S intervals.
Conclusions
Despite the higher pCR rate with longer CRT-S interval, surgery is optimal less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. In patients with SCC and those with pCR, prolonged CRT-S interval had no impact on OS. Further studies are needed to consolidate our findings.
http://bit.ly/2t2DkEn
Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology
http://bit.ly/2I0XI2K
Cone beam computed tomography evaluation of staged lateral ridge augmentation using platelet rich fibrin or resorbable collagen membranes in a randomized controlled clinical trial
Abstract
Objectives
To evaluate the volumetric changes following lateral alveolar ridge augmentation using autogenous bone graft covered by either a platelet rich fibrin membrane (test group) or an inorganic bovine bone substitute and a resorbable collagen barrier membrane (control group).
Material and methods
A total of 27 partially edentulous patients (test n=14, control n=13) with the indication for lateral bone block augmentation were included in this randomized, controlled clinical trial. Cone beam computed tomography (CBCT) examination was performed prior to grafting and 2 weeks and 6 months after grafting. The volumetric changes between the various examinations times were evaluated by planimetric measurements on two‐dimensional CBCT images of the grafted regions.
Results
The mean bone volumetric loss in the test group was 14.7%, SD± 8.9%, while the mean bone volume loss in the control group was 17.8%, SD± 13.3%. This difference was not significant (P=0.48). A total of ten patients were operated in the incisor and canine region with a mean bone volume loss of 23.41% SD, ±10.87%, while 17 patients were operated in the premolar region with at mean bone volume loss of 11.89% SD ±9.05%. This difference was significant (P=0.01).
Conclusion
The test and control group demonstrated no overall difference in volumetric bone changes of the augmented bone at the 6‐month follow‐up. The second major finding revealed a significantly larger amount of bone resorption in the incisor and canine region than in the premolar region of the maxilla, particularly in the control group.
This article is protected by copyright. All rights reserved.
http://bit.ly/2DSl0DU
Citrus Alkaline Extract Delayed the Progression of Pulmonary Fibrosis by Inhibiting p38/NF-B Signaling Pathway-Induced Cell Apoptosis
Objective. To investigate the intervention effect and functioning mechanism of citrus alkaline extract (CAE) on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. 42 C57BL/6 male mice were assigned randomly to the normal group, model group, low (16mg/kg), medial (32mg/kg) and high (64mg/kg) CAE dosage groups, prednisone group (6mg/kg), and pirfenidone group (100mg/kg), respectively. One day after model construction, intragastric administration was applied to the mice once a day for 28 days and then killed. Body weights of mice were recorded. Their pulmonary tissues were subjected to HE staining and Masson's staining and then their degree of pulmonary alveolitis as well as pulmonary fibrosis was scored. Contents of hydroxyproline (HYP) and prostaglandin E2 (PGE2) in pulmonary tissues and levels of interleukin-17 (IL-17) in serum and bronchoalveolar lavage fluid (BALF) were determined by ELISA method. Expression of collagen I, collagen III, and Prosurfactant protein C (Pro-SPC) proteins in pulmonary tissue were measured immunohistochemically and that of nuclear transcription factor B (NF-B) and vimentin was determined by the immunofluorescence method. Apoptosis of pulmonary tissue was tested by the Tunel staining method, while the expression of MAPK-related protein was recorded by Western Blot assay. Results. After CAE treatment, the body weight, PGE2 level, and Pro-SPC protein expression of pulmonary fibrosis mice were increased, while the score of pulmonary alveolitis and pulmonary fibrosis, levels of HYP and cell apoptosis, IL-17 contents of serum and BALF in pulmonary tissues, and expression of collagen I, collagen III, vimentin, NF-B, and p-p38 were reduced. Conclusion. CAE effectively delayed the progression of BLM-induced pulmonary fibrosis in pulmonary fibrosis mice and a possible mechanism is the inhibition of cell apoptosis of NF-B/p38-mediated signaling pathway.
http://bit.ly/2GaZNYa
A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death
Abstract
The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.
http://bit.ly/2UEo8co
Pembrolizumab Now Second Immunotherapy Approved to Treat Merkel Cell Carcinoma
FDA has approved pembrolizumab (Keytruda) to treat people with Merkel cell carcinoma, a rare and deadly form of skin cancer. The approval covers use of the drug to treat locally advanced or metastatic forms of the disease.
http://bit.ly/2Gn5nWO
“There is no reward penny for going out and picking up youths”: issues in the design of accessible youth healthcare services in rural northern Sweden
There is a continuing challenge to ensure equitable access to youth healthcare services in small rural communities. Sweden's 'youth clinic' system is an attempt to provide comprehensive youth health services f...
http://bit.ly/2GaLu6a
Multilocus sequence typing (MLST), porA and flaA typing of Campylobacter jejuni isolated from cats attending a veterinary clinic
Campylobacter is a major cause of gastroenteritis in humans and pet ownership is a risk factor for infection. To study the occurrence, species distribution and sequence-based types of Campylobacter spp. in pet ca...
http://bit.ly/2G98ORA
Prevalence and factors associated with depression among hospital admitted patients in South Ethiopia: cross sectional study
Identifying factors associated with depression will help health care providers to design programs which improve quality of services provided to the inpatients. The aim of this study was to assess the prevalenc...
http://bit.ly/2D5lYeA
Isolation and biochemical characterization of a metagenome-derived 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase gene from subtropical marine mangrove wetland sediments
3-Deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAHPS) is a key rate-limiting enzyme in aromatic amino acid anabolism. A new Iβ-type DAHPS gene (aro1A) was identified in a metagenomic library from subtropic...
http://bit.ly/2BgUXEU
Antimicrobial potential of toothpaste formulated from extracts of Syzygium aromaticum, Dennettia tripetala and Jatropha curcas latex against some oral pathogenic microorganisms
The need for a broad spectrum antimicrobial mouthwash is highly desirable to reduce, control and prevent various types of dental diseases. Hence, research into the production of herbal toothpaste to suppress t...
http://bit.ly/2Tx9Iuu
In silico genome analysis reveals the metabolic versatility and biotechnology potential of a halotorelant phthalic acid esters degrading Gordonia alkanivorans strain YC-RL2
Members of genus Gordonia are known to degrade various xenobitics and produce secondary metabolites. The genome of a halotorelant phthalic acid ester (PAEs) degrading actinobacterium Gordonia alkanivorans strain ...
http://bit.ly/2BkZ0jE
Prognostic values of mid-radiotherapy 18 F-FDG PET/CT in patients with esophageal cancer
Abstract
Background
To identify whether early metabolic responses as determined using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) during radiotherapy (RT) predict outcomes in patients with esophageal cancer.
Methods
Twenty-one patients with esophageal cancer who received pre-treatment 18F-FDG PET/CT (PET1) and inter-fractional 18F-FDG PET/CT (PET2) after 11 fractions of RT (median 23.1 Gy, 2.1 Gy per fraction) were retrospectively reviewed. The region of interest for each calculation was delineated using "PET Edge". We calculated PET parameters including maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The relative changes (%) were calculated using the logarithmically transformed parameter values for the PET1 and PET2 scans. Multivariate analysis of locoregional recurrence and distant failures were performed using Cox regression analysis. After identifying statistically significant PET parameters for discriminating responders from non-responders, receiver operating characteristics curve analyses were used to assess the potentials of the studied PET parameters.
Results
After a median follow-up of 13 months, the 1-year overall and progression-free survival rates were 79.0% and 34.4%, respectively. Four patients developed locoregional recurrences (LRRs) and 8 had distant metastases (DMs). The 1-year overall LRR-free rate was 76.9% while the DM-free rate was 60.6%. The relative changes in MTV (ΔMTV) were significantly associated with LRR (p = 0.03). Conversely, the relative changes in SUVmean (ΔSUVmean) were associated with the risk of DM (p = 0.02). An ΔMTV threshold of 1.14 yielded a sensitivity of 60%, specificity of 94%, and an accuracy of 86% for predicting an LRR. Additionally, a ΔSUVmean threshold of a 35% decrease yielded a sensitivity of 67%, specificity of 83%, and accuracy of 76% for the prediction DM.
Trial registration
Retrospectively registered.
Conclusions
Changes in tumor metabolism during RT could be used to predict treatment responses, recurrences, and prognoses in patients with esophageal cancer.
http://bit.ly/2Glt2qF
Accurate identification and epidemiological characterization of Burkholderia cepacia complex: an update
Bacteria belonging to the Burkholderia cepacia complex (Bcc) are among the most important pathogens isolated from cystic fibrosis (CF) patients and in hospital acquired infections (HAI). Accurate identification o...
http://bit.ly/2DRacWS
Decreased fracture incidence with traditional Chinese medicine therapy in patients with osteoporosis: a nationwide population-based cohort study
There are no published studies regarding the efficacy of traditional Chinese medicine (TCM) for the prevention of osteoporotic fracture. Therefore, we conducted this nationwide, population-based cohort study t...
http://bit.ly/2D4HMHb
Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase
This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase.
http://bit.ly/2GbTrb2
Exercise and resveratrol increase fracture resistance in the 3xTg-AD mouse model of Alzheimer’s disease
Alzheimer's disease (AD) and osteoporosis are progressive diseases that affect the elderly population. Both conditions are associated with fracture risk that is greater than twice that of the healthy populatio...
http://bit.ly/2G9Id7e
Partial volume correction for arterial spin labeling using the inherent perfusion information of multiple measurements
Arterial spin labeling (ASL) provides a noninvasive way to measure cerebral blood flow (CBF). The CBF estimation from ASL is heavily contaminated by noise and the partial volume (PV) effect. The multiple measu...
http://bit.ly/2t1GLeo
Intrascleral Fixation of an Intraocular Lens through the Pars Plana Prevents Corneal Endothelial Damage
We report two cases of aphakia in whom an intraocular lens (IOL) was intrasclerally fixated through the pars plana to minimize further corneal endothelial damage. A modified lock-and-lead technique was used. A sclerotomy and scleral incision were made 2.5 mm from the limbus. A 24-G catheter needle was used for penetration of the leading haptic, and two ultrathin 30-G needles were used to bury the ends of the haptics. The scleral incision was sutured with 8-0 nylon. Corneal endothelial cells were preserved after surgery. Neither intra- nor postoperative complications were observed. Intrascleral fixation of an IOL through the pars plana effectively minimizes further damage to corneal endothelial cells in select cases.
Case Rep Ophthalmol 2019;10:53–60
http://bit.ly/2GlbQlg
The impact of homocysteine, B12, and D vitamins levels on functional neurocognitive performance in HIV-positive subjects
The correlation among high levels of total homocysteine, low levels of B12vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of...
http://bit.ly/2RyWPOF
APACHE-II score for anti-tuberculosis tolerance in critically ill patients: a retrospective study
To investigate the status of anti-tuberculosis treatment in critically ill patients, and to explore the value of APACHE-II score in guiding anti-tuberculosis treatment.
http://bit.ly/2WHyud2
Incidence and predictors of LTFU among adults with TB/HIV co-infection in two governmental hospitals, Mekelle, Ethiopia, 2009–2016: survival model approach
Lost to follow-up (LTFU) negatively affects the treatment success of Anti-Retroviral Therapy (ART) and thus, increases Tuberculosis-Human Immunodeficiency Virus (TB/HIV) related morbidity, mortality and hospit...
http://bit.ly/2RDETSW
Systems Pharmacology-Based Approach to Comparatively Study the Independent and Synergistic Mechanisms of Danhong Injection and Naoxintong Capsule in Ischemic Stroke Treatment
To provide evidence for the better clinical use of traditional Chinese medicine preparations (TCMPs), comparison of the pharmacological mechanisms between TCMPs with similar therapeutic effect is necessary. However, methodology for dealing with this issue is still scarce. Danhong injection (DHI) and Naoxintong capsule (NXT) are representative TCMPs for ischemic stroke (IS) treatment, which are also frequently used in combination. Here they were employed as research objects to demonstrate the feasibility of systems pharmacology approach in elucidation of the independent and combined effect of TCMPs. By incorporating chemical screening, target prediction, and network construction, a feasible systems pharmacology model has been established to systematically uncover the underlying action mechanisms of DHI, NXT, or their pair in IS treatment. Systematic analysis of the created TCMP-Compound-Target-Disease network revealed that DHI and NXT shared common targets such as PTGS2, F2, ADRB1, IL6, ALDH2, and CCL2, which were involved in the vasomotor system regulation, blood-brain barrier disruption, redox imbalance, neurotrophin activity, and brain inflammation. In comparative mechanism study, the merged DHI/NXT-IS PPI network and pathway enrichment analysis indicated that DHI and NXT exerted the therapeutic effects mainly through immune system and VEGF signaling pathways. Meanwhile, they had their own unique pathways, e.g., calcium signaling pathway for DHI and gap junction for NXT. While for their synergistic mechanism, DHI and NXT participated in chemokine signaling pathway, T cell receptor signaling pathway, VEGF signaling pathway, gap junction, and so on. Our study provided an optimized strategy for dissecting the different and combined effect of TCMPs with similar actions.
http://bit.ly/2HQfVQO
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
