Using spirometry to rule out restriction in patients with concomitant low forced vital capacity and obstructive pattern.

Abstract:
BACKGROUND
Different formulas have been proposed to exclude restriction based on spirometry, however none of them have specifically tested the patients whose spirometry show both obstruction and a low forced vital capacity (FVC).

STUDY OBJECTIVE
The study was designed to create an algorithm that would better predict the absence of restriction in such patients.

DESIGN
Retrospective analysis of prospectively collected data.

METHODS
A cohort of consecutive adults that underwent complete pulmonary function testing from 2002-2004 was analyzed. The data was randomly split into two groups to allow for derivation and then validation of a predictive formula. Patients were randomly assigned into either a "derivation" or "validation" group. In the derivation group, stepwise logistic regression was used to determine a formula and optimal cut-off value for the variable with the best discriminative capacity. The formula was applied subsequently to the validation group to test the results and compared to previously published formula.

RESULTS
The study group contained 766 patients. We determined that the variable with the highest association with TLC was [(FEV(1)/FVC) % predicted/FVC % predicted]. A value of ≥1.11 was found to be the maximal cutoff to predict the absence of restriction. The formula was applied to a validation group (n=397) and performed better than prior published algorithm with a sensitivity, specificity, positive predictive value and negative predictive value of 95%, 44%, 22%, and 98%, respectively.

CONCLUSION
Our formula performs superior to the previously published algorithms in patients with concomitant low FVC and obstruction to exclude restriction.

Khalid|Imran|I|
Morris|Zachary Q|ZQ|
Khalid|Tabindeh J|TJ|
Nisar|Amina|A|
Digiovine|Bruno|B|

spirometry
restriction
Algorithm
total lung capacity.


Histogram Analysis Comparison of Monoexponential, Advanced Diffusion-Weighted Imaging, and Dynamic Contrast-Enhanced MRI for Differentiating Borderline From Malignant Epithelial Ovarian Tumors.

Abstract:
BACKGROUND
The accurate preoperative differentiation between borderline and malignant epithelial ovarian tumors (BEOTs vs. MEOTs) is crucial for determining the proper surgical strategy and improving the patient's postoperative quality of life. Several diffusion and perfusion MRI technologies are valuable for the differentiation; however, which is the best remains unclear.

PURPOSE
To compare the whole solid-tumor volume histogram analysis of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced MRI (DCE-MRI) in the differentiation of BEOTs vs. MEOTs and to identify the correlations between the perfusion parameters from IVIM and DCE-MRI.

STUDY TYPE
Retrospective.

POPULATION
Twenty patients with BEOTs and 42 patients with MEOTs.

FIELD STRENGTH/SEQUENCE
1.5T/DWI, DKI, and IVIM models fitting from 13 different b factors and 40 phases DCE-MRI.

ASSESSMENT
Histogram metrics were derived from the apparent diffusion coefficient (ADC), diffusion kurtosis (K), diffusion coefficient (Dk), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), volume transfer constant (Ktrans ), rate constant (kep ), and extravascular extracellular volume fraction (ve ).

STATISTICAL TESTS
The Mann-Whitney U-test and receiver operating characteristic curve were used to determine the best histogram metrics and parameters. Multivariate logistic regression analysis was used to determine the best combined model for each two from the four technologies. Spearman's rank correlation was used to analyze the correlations between the IVIM and DCE-MRI parameters.

RESULTS
ADC, D, Dk, and D* were significantly higher in BEOTs than in MEOTs (P < 0.05). K, Ktrans , kep , and ve were significantly lower in BEOTs than in MEOTs (P < 0.05). The 10th percentile of Dk was the most reliable single metric, with an area under the curve (AUC) of 0.921. Dk combined with Ktrans yielded the highest AUC of 0.950. A weak inverse correlation was found between D and Ktrans (r = -0.320, P = 0.025) and between D and kep (r = -0.267, P = 0.037).

DATA CONCLUSION
The 10th percentile of Dk was the most valuable metric and Dk combined with Ktrans had the best performance for differentiating BEOTs from MEOTs. There was no evident link between perfusion-related parameters derived from IVIM and DCE-MRI.

LEVEL OF EVIDENCE
4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:257-268.

He|Mengge|M| Song|Yang|Y|0000-0001-7426-4496 Li|Haiming|H| Lu|Jing|J| Li|Yongai|Y| Duan|Shaofeng|S| Qiang|Jinwei|J|0000-0002-6327-1401

D038524:Diffusion Magnetic Resonance Imaging

histogram analysis
diffusion-weighted imaging
contrast-enhanced imaging
magnetic resonance imaging
ovarian neoplasm


Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Abstract:
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-symptom disease with widespread evidence of disrupted systems. The authors hypothesize that it is caused by the upregulation of the corticotropin-releasing factor receptor type 2 (CRFR2) in the raphé nuclei and limbic system, which impairs the ability to maintain homeostasis. The authors propose utilizing agonist-mediated receptor endocytosis to downregulate CRFR2.

Materials and Methods
This open-label trial tested the safety, tolerability and efficacy of an acute dose of CT38s (a short-lived, CRFR2-selective agonist, with no known off-target activity) in 14 ME/CFS patients. CT38s was subcutaneously-infused at one of four dose-levels (i.e., infusion rates of 0.01, 0.03, 0.06, and 0.20 μg/kg/h), for a maximum of 10.5 h. Effect was measured as the pre-/post-treatment change in the mean 28-day total daily symptom score (TDSS), which aggregated 13 individual patient-reported symptoms.

Results
ME/CFS patients were significantly more sensitive to the transient hemodynamic effects of CRFR2 stimulation than healthy subjects in a prior trial, supporting the hypothesized CRFR2 upregulation. Adverse events were generally mild, resolved without intervention, and difficult to distinguish from ME/CFS symptoms, supporting a CRFR2 role in the disease. The acute dose of CT38s was associated with an improvement in mean TDSS that was sustained (over at least 28 days post-treatment) and correlated with both total exposure and pre-treatment symptom severity. At an infusion rate of 0.03 μg/kg/h, mean TDSS improved by -7.5 ± 1.9 (or -25.7%, p = 0.009), with all monitored symptoms improving.

Conclusion
The trial supports the hypothesis that CRFR2 is upregulated in ME/CFS, and that acute CRFR2 agonism may be a viable treatment approach warranting further study.

Clinical Trial Registration
ClinicalTrials.gov, identifier NCT03613129.

Pereira|Gerard|G|
Gillies|Hunter|H|
Chanda|Sanjay|S|
Corbett|Michael|M|
Vernon|Suzanne D|SD|
Milani|Tina|T|
Bateman|Lucinda|L|

corticotropin-releasing factor receptor 2

myalgic encephalomyelitis chronic fatigue syndrome


CT Enterography score: a potential predictor for severity assessment of active ulcerative colitis.

Abstract:
BACKGROUND
Evaluate the possibility of CT enterography (CTE) score system as a predictor in assessing active ulcerative colitis (UC) severity.

METHODS
Forty-six patients with active UC with CTE and colonoscopy were enrolled. Based on modified Mayo score, patients were divided into three groups: mild (n = 10), moderate (n = 17) and severe (n = 19). A cumulative CTE score was calculated in each patient and its correlation with modified Mayo score was analyzed. The optimal cutoff values of CTE score were determined by receiver operating characteristic (ROC) curves analysis.

RESULTS
Significant between-group differences were observed in CTE spectrums of mucosal bubbles, mural stratification, loss of haustration, enlarged mesenteric lymph nodes and engorged mesenteric vessels (P < 0.05). The cumulative CTE scores were significant difference between three groups (CTE score:4.9 ± 2.3, 7.6 ± 2.6, and 10.9 ± 2.0, respectively, P < 0.01). The cumulative CTE score showed a positive correlation with modified Mayo score (r = 0.835, P < 0.05). The optimal cut-off value for CTE score predicting moderate and severe UC was 9.5 (area under the curve [AUC]:0.847, sensitivity:78.9%, specificity:82.4%).

CONCLUSION
Disease severity assessment by CTE score demonstrates strong positive correlation with severity established modified Mayo score. CTE score system maybe a potential predictor for active UC severity assessment.

Jia|Yingmei|Y| Li|Chang|C| Yang|Xiaoyan|X| Dong|Zhi|Z| Huang|Kun|K| Luo|Yanji|Y| Li|Xuehua|X| Sun|Canhui|C| Feng|Shi-Ting|ST| Li|Zi-Ping|ZP|

Ulcerative colitis
Modified Mayo score
Computed tomography enterography
Disease activity
Multi-slice computed tomography


Effect of single-point mutations on the stability and immunogenicity of a recombinant ricin A chain subunit vaccine antigen.

Abstract: There is great interest in the design and development of highly thermostable and immunogenic protein subunit vaccines for biodefense. In this study, we used two orthogonal and complementary computational protein design approaches to generate a series of single-point mutants of RiVax, an attenuated recombinant ricin A chain (RTA) protein subunit vaccine antigen. As assessed by differential scanning calorimetry, the conformational stabilities of the designed mutants ranged from 4°C less stable to 4.5°C more stable than RiVax, depending on solution pH. Two more thermostable (V18P, C171L) and two less thermostable (T13V, S89T) mutants that displayed native-like secondary and tertiary structures (as determined by circular dichroism and fluorescence spectral analysis, respectively) were tested for their capacity to elicit RTA-specific antibodies and toxin-neutralizing activity. Following a prime-boost regimen, we found qualitative differences with respect to specific antibody titers and toxin neutralizing antibody levels induced by the different mutants. Upon a second boost with the more thermostable mutant C171L, a statistically significant increase in RTA-specific antibody titers was observed when compared with RiVax-immunized mice. Notably, the results indicate that single residue changes can be made to the RiVax antigen that increase its thermal stability without adversely impacting the efficacy of the vaccine.

Thomas|Justin C|JC|
O'Hara|Joanne M|JM|
Hu|Lei|L|
Gao|Fei P|FP|
Joshi|Sangeeta B|SB|
Volkin|David B|DB|
Brey|Robert N|RN|
Fang|Jianwen|J|
Karanicolas|John|J|
Mantis|Nicholas J|NJ|
Middaugh|C Russell|CR|

D000818:Animals
D057134:Antibodies, Neutralizing
D000992:Antitoxins
D001786:Blood Glucose
D002151:Calorimetry
D002942:Circular Dichroism
D004195:Disease Models, Animal
D004355:Drug Stability
D051379:Mice
D008807:Mice, Inbred BALB C
D050505:Mutant Proteins
D017354:Point Mutation
D011041:Poisoning
D011487:Protein Conformation
D055550:Protein Stability
D012276:Ricin
D013050:Spectrometry, Fluorescence
D016019:Survival Analysis
D022223:Vaccines, Subunit
D014614:Vaccines, Synthetic

immunogenicity
ricin
vaccine
antigen
computational protein design
protein stability


Concise set of files for smooth return to work in employees with mental disorders.

Abstract: Sick leave due to mental disorders is a societal problem. It carries a high cost in terms of loss of labor productivity and absenteeism. Partial remission increases the risk of relapse after a return to work. There is sometimes a difference between the ability to return to work as judged by a general practitioner (GP) and the needs of the workplace. GPs are the main controllers of treatment and tend to protect their patients. Communication and agreement by GPs and occupational physicians play an effective role in the return to work. However, it requires considerable effort for both of them to make time to do this. We have developed a concise set of files for a smooth return to work. The files consist of three parts: "Suggestions for corresponding with employees taking sick leave"; "Checklist for smooth return to work"; and "Pattern of living". We put them into practice among 20 companies in Japan from January 2012 to October 2013. The companies had 8244 workers in total and 116 workers were on sick-leave due to mental disorders. Our set of files contributed to sharing the written basic policy of return to work among employees on sick leave with mental disorders, GPs, occupational physicians and personnel officers. That sharing led to facilitating a smooth return to work. Although there are differences in the legal and medical systems between Japan and other countries, our concept of sharing the written basic policy may give some help to occupational physicians in other parts of the world as well.

Yoshitsugu|Kiyoshi|K| Kuroda|Yuko|Y| Hiroyama|Yuji|Y| Nagano|Nobuhisa|N|

Return to work
Sick leave
General practitioner
Workplace
Occupational physician


A predictive probability interim design for phase II clinical trials with continuous endpoints.

Abstract: Molecular targeted therapies come often with lower toxicity profiles than traditional cytotoxic treatments, thus shifting drug development paradigm into establishing evidence of biological activity, target modulation, and pharmacodynamics effects of these therapies in early phase trials. Therefore, these trials need to address simultaneous evaluation of safety, proof-of-concept biological marker activity, or changes in continuous tumor size instead of binary response rate. Interim analyses are typically incorporated in the trial due to concerns regarding excessive toxicity and ineffective new treatment. There is a lack of interim strategies developed to monitor futility and/or efficacy for these types of continuous outcomes, especially in single-arm phase II trials. We propose a 2-stage design based on predictive probability to accommodate continuous endpoints, assuming a normal distribution with known variance. Simulation results and case study demonstrated that the proposed design can incorporate an interim stop for futility as well as for efficacy while maintaining desirable design properties. As expected, using continuous tumor size resulted in reduced sample sizes for both optimal and minimax designs. A limited exploration of various priors was performed and shown to be robust. As research rapidly moves to incorporate more molecular targeted therapies, it will accommodate new types of outcomes while allowing for flexible stopping rules to continue optimizing trial resources and prioritize agents with compelling early phase data.

D017322:Clinical Trials, Phase II as Topic

predictive probability
interim
continuous endpoints
phase II trials
single arm


Slow-theta power decreases during item-place encoding predict spatial accuracy of subsequent context recall.

Abstract: Human hippocampal theta oscillations play a key role in accurate spatial coding. Associative encoding involves similar hippocampal networks but, paradoxically, is also characterized by theta power decreases. Here, we investigated how theta activity relates to associative encoding of place contexts resulting in accurate navigation. Using MEG, we found that slow-theta (2-5Hz) power negatively correlated with subsequent spatial accuracy for virtual contextual locations in posterior hippocampus and other cortical structures involved in spatial cognition. A rare opportunity to simultaneously record MEG and intracranial EEG in an epilepsy patient provided crucial insights: during power decreases, slow-theta in right anterior hippocampus and left inferior frontal gyrus phase-led the left temporal cortex and predicted spatial accuracy. Our findings indicate that decreased slow-theta activity reflects local and long-range neural mechanisms that encode accurate spatial contexts, and strengthens the view that local suppression of low-frequency activity is essential for more efficient processing of detailed information.

Crespo-García|Maité|M|
Zeiller|Monika|M|
Leupold|Claudia|C|
Kreiselmeyer|Gernot|G|
Rampp|Stefan|S|
Hamer|Hajo M|HM|
Dalal|Sarang S|SS|

MEG
Hippocampus
Intracranial EEG
Source localization
Spatial navigation


A single digestion, single-stranded oligonucleotide mediated PCR-independent site-directed mutagenesis method.

Abstract: A PCR-independent in vitro site-directed mutagenesis method was established. Cas12a from Francisella novicida (FnCas12a) linearizes the plasmid with single digestion. T5 exonuclease removes the target nucleotide. A short single- or double-stranded mutagenic oligonucleotide introduces the mutation. This rapid and simple mutagenesis method is referred to as FnCas12a and T5 exonuclease mediated site-directed mutagenesis system (CT5-SDM). The platform is also suitable for the mutagenesis of plasmids larger than 10 kb. KEY POINTS: Site-directed mutagenesis mediated by single-stranded DNA. Removing target site with T5 exonuclease. Highly efficient cleavage of target DNA with FnCas12a.

Dong|Mengjie|M| Wang|Fei|F| Li|Qingqing|Q| Han|Rui|R| Li|Aitao|A| Zhai|Chao|C| Ma|Lixin|L|

D004277:DNA, Single-Stranded
D004926:Escherichia coli
D005603:Francisella
D016297:Mutagenesis, Site-Directed
D009841:Oligonucleotides
D016133:Polymerase Chain Reaction

Single digestion
Single-stranded oligonucleotide
Site-directed mutagenesis
FnCas12a
T5 exonuclease


HPLC-HRMS Quantification of the Ichthyotoxin Karmitoxin from Karlodinium armiger.

Abstract: Being able to quantify ichthyotoxic metabolites from microalgae allows for the determination of ecologically-relevant concentrations that can be simulated in laboratory experiments, as well as to investigate bioaccumulation and degradation. Here, the ichthyotoxin karmitoxin, produced by Karlodinium armiger, was quantified in laboratory-grown cultures using high-performance liquid chromatography (HPLC) coupled to electrospray ionisation high-resolution time-of-flight mass spectrometry (HRMS). Prior to the quantification of karmitoxin, a standard of karmitoxin was purified from K. armiger cultures (80 L). The standard was quantified by fluorescent derivatisation using Waters AccQ-Fluor reagent and derivatised fumonisin B₁ and fumonisin B₂ as standards, as each contain a primary amine. Various sample preparation methods for whole culture samples were assessed, including six different solid phase extraction substrates. During analysis of culture samples, MS source conditions were monitored with chloramphenicol and valinomycin as external standards over prolonged injection sequences (>12 h) and karmitoxin concentrations were determined using the response factor of a closely eluting iturin A2 internal standard. Using this method the limit of quantification was 0.11 μg·mL-1, and the limit of detection was found to be 0.03 μg·mL-1. Matrix effects were determined with the use of K. armiger cultures grown with 13C-labelled bicarbonate as the primary carbon source.

Andersen|Aaron John Christian|AJC|
de Medeiros|Lívia Soman|LS|
Binzer|Sofie Bjørnholt|SB|
Rasmussen|Silas Anselm|SA|
Hansen|Per Juel|PJ|
Nielsen|Kristian Fog|KF|
Jørgensen|Kevin|K|
Larsen|Thomas Ostenfeld|TO|

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

quantify
ichthyotoxic
amphidinol
harmful algal bloom
karlotoxin
polyether
polyketide
quantitation


Performance of transient elastography (TE) and factors associated with discordance in non-alcoholic fatty liver disease.

Abstract:
OBJECTIVE
To determine the accuracy of transient elastography (TE) and factors associated with discordance between TE and liver histology in patients with non-alcoholic fatty liver disease (NAFLD).

METHODS
The accuracy of TE was assessed and compared with the aspartate aminotransferase-to-platelet ratio index (APRI) in patients with histologically proven NAFLD. Factors associated with discordance between liver histology and TE were analyzed.

RESULTS
Altogether 131 patients with a mean age of 49.9 years, including 69 men and 62 women, with NAFLD underwent liver stiffness measurement (LSM) by TE. Among all patients, 120 (91.6%) had a successful LSM with an interquartile to median ratio of 0.15. The accuracy of TE in detecting ≥F3 and F4 fibrosis, assessed by the area under the receiver operating characteristic curve, were 0.77 and 0.95, respectively. The sensitivity and specificity of the optimal LSM cut-off values for detecting ≥F3 fibrosis (sensitivity 70.4% and specificity 66.6%) and F4 (sensitivity 87.5% and specificity 89.3%) were modest, but better than those of APRI. Discordance between TE and histology for fibrosis grading was observed in 22.5% of patients, but it could not be explained by body mass index, alanine aminotransferase level, the length of the biopsied specimens or the grade of steatosis.

CONCLUSION
TE plays an important role in the detection of advanced fibrosis and cirrhosis in patients with NAFLD and its accuracy does not appear to be influenced by components of the disease.

Mahadeva|Sanjiv|S|
Mahfudz|Anis Shafina|AS|
Vijayanathan|Anushya|A|
Goh|Khean-Lee|KL|
Kulenthran|Arumugam|A|
Cheah|Phaik-Leng|PL|

D065626:Non-alcoholic Fatty Liver Disease

transient elastography
accuracy
liver stiffness measurement
liver fibrosis
nonalcoholic fatty liver disease
noninvasive


Cross-cultural adaptation and implementation of Good Life with osteoarthritis in Denmark (GLA:D™): group education and exercise for hip and knee osteoarthritis is feasible in Canada.

Abstract:
OBJECTIVE
Adapt and evaluate the feasibility of implementing Good Life with osteoArthritis in Denmark (GLA:DTM) in Canada for people with mild to severe hip/knee osteoarthritis.

METHODS
Patients triaged to non-surgical management participated in two education sessions and 12 supervised, neuromuscular exercise classes. We used the RE-AIM implementation framework evaluating outcomes of Reach, Effectiveness/Efficacy, Adoption, Implementation and Maintenance. Patients completed surveys pre-program and at 3 months follow-up. Program fidelity was evaluated at four observations against a priori criteria. We conducted semi-structured interviews with therapists post-program.

RESULTS
72 patients consented to participate, 59 started the program and one withdrew on physician advice. The remaining 58 provided follow-up data. Mean age was 67 years; 78% were female and 52% had body mass index (BMI) >25. The effect of the program was demonstrated: 40% improvement in pain with 59% achieving a clinically important improvement of ≥2 points on the Numeric Pain Rating scale. Statistically significant improvement also occurred in the Hip disability/Knee injury and Osteoarthritis Outcome Score subscales. 24% reported increased physical activity. Program fidelity was demonstrated with all criteria met. Therapists emphasized that rolling recruitment allowed appropriate supervision and resulted in participants encouraging each other. 99% of participants indicated they benefitted from and were satisfied with the program and 90% reported using the knowledge daily. 52% were willing to pay >$250 Cdn for the program.

CONCLUSION
GLA:DTM implementation was feasible in the Canadian context with results similar to those of >7,000 participants in Denmark. Implementation and evaluation of GLA:DTM Canada is now occurring nationally.

Davis|A M|AM|
Kennedy|D|D|
Wong|R|R|
Robarts|S|S|
Skou|S T|ST|
McGlasson|R|R|
Li|L C|LC|
Roos|E|E|

D000368:Aged
D000369:Aged, 80 and over
D002170:Canada
D065246:Culturally Competent Care
D004185:Disability Evaluation
D015444:Exercise
D005081:Exercise Therapy
D005240:Feasibility Studies
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D008297:Male
D008875:Middle Aged
D015207:Osteoarthritis, Hip
D020370:Osteoarthritis, Knee
D059408:Pain Management
D010147:Pain Measurement
D010353:Patient Education as Topic
D015397:Program Evaluation

Cross-cultural adaptation
Education
Hip and knee osteoarthritis
Non-surgical management
Neuromuscular exercise
Implementation feasibility study


Linking patient-centered medical home and asthma measures reduces hospital readmission rates.

Abstract:
OBJECTIVE
We sought to achieve 100% compliance with all 3 Children's Asthma Care (CAC; CAC-1, CAC-2, CAC-3) measures and track attendance at follow-up appointments with the patient-centered medical home. The impact of these measures on readmission and emergency department utilization rates was evaluated.

METHODS
This quality improvement study evaluated compliance with CAC measures in pediatric patients aged 2 to 18 years old hospitalized with a primary diagnosis of asthma from January 1, 2008, through June 30, 2012. A multidisciplinary Asthma Task Force was assembled to develop interventions. Attendance at the follow-up appointment was tracked monthly from January 1, 2009. Readmission and emergency department utilization rates were compared between the preimplementation period (January 1, 2006, through December 31, 2007) and the postimplementation period (January 1, 2008, through June 30, 2012).

RESULTS
The preimplementation period included 231 subjects and the postimplementation period included 532 subjects. Compliance with CAC-3 was 95% from October 1, 2009, through June 30, 2012. Compliance with the postdischarge follow-up appointment was 69% from January 1, 2009 through September 30, 2009, increasing significantly to 90% from October 1, 2009, through June 30, 2012 (P < .001). Postimplementation readmission rates significantly decreased in the 91- to 180-day postdischarge interval (odds ratio: 0.29; 95% confidence interval: 0.11-0.78).

CONCLUSIONS
In children hospitalized with asthma, compliance with the asthma core measures and the postdischarge follow-up appointment with the primary care provider was associated with reduced readmission rates at 91 to 180 days after discharge. We attribute our results to a comprehensive set of interventions designed by our multidisciplinary Asthma Task Force.

Bergert|Lora|L|
Patel|Shilpa J|SJ|
Kimata|Chieko|C|
Zhang|Guangxiang|G|
Matthews|Wallace J|WJ|

patient-centered medical home
asthma
readmission
follow-up
core measures
home management plan of care


Management of third stage of labor with misoprostol: A comparison of three routes of administration.

Abstract:
BACKGROUND AND CONTEXT
Misoprostol is a versatile drug with an effective uterotonic effect on the postpartum uterine tissue and is used through various routes during the third stage of labor.

AIMS AND OBJECTIVES
A randomized prospective study was carried out to analyze the most effective route for misoprostol administration, with an emphasis on parturients' acceptability and compliance, a possible shortening of the duration of the third stage of labor, minimization of blood loss and possibly reducing the incidence of potential side effects.

MATERIALS AND METHODS
The study groups comprised of 300 healthy parturients, divided randomly into three groups of 100 parturients each, who were administered misoprostol 400 μg through the oral (O), rectal (R), and sublingual (S) routes, respectively, during the third stage of labor. Estimation of blood loss was measured in terms of fall in hemoglobin, hematocrit, and packed cell volume (PCV) levels, and duration of the third stage of labor was also compared.

RESULTS
The mean duration for the third stage of labor was significantly shorter in group S (3.62 minutes) as compared to R (4.12 minutes), and O (4.94 minutes) (P = 0.02). The average blood loss was observed to be the least in the group S (210 ml) as compared to group R (230 ml), and group O. The incidence of shivering and fever was observed to be significantly higher (25 and 15%) in the parturients of group S (P < 0.05).

CONCLUSIONS
All routes were equally effective in managing the third stage of labor, but administration of misoprostol through the rectal route evoked better acceptability, comparable efficacy, and had an incidence of minimal side effects.

Bajwa|Sukhwinder Kaur|SK|
Bajwa|Sukhminder Jit Singh|SJ|
Kaur|Harpreet|H|
Goraya|S P S|SP|
Singh|Anita|A|
Kaurishar|Harpreet|H|

Labor misoprostol uterotonics postpartum hemorrhage


A commentary on some epidemiology data for chlorpyrifos.

Abstract: Extensive animal and human studies on chlorpyrifos (CPF) point to changes in a blood enzyme as its first biological effect, and governments and health groups around the world have used this effect in the determination of its safe dose. Preventing this first biological effect, referred to in risk assessment parlance as the critical effect, is part and parcel of chemical regulation in general and of CFP specifically. Rauh et al. (2011), one of the published studies from the Columbia Center for Children's Environmental Health (CCCEH), reported evidence of deficits in Working Memory Index and Full-Scale IQ in children at 7 years old as a function of prenatal CPF exposures that are much lower than levels causing cholinesterase inhibition. Since the raw data on which Rauh et. al. (2011) publicly-funded (in part) findings were based have not been made available despite repeated requests, we show extracted data in Fig. 1A and 1E of Rauh et al. (2011), and plotted these extracted data as response versus log dose, a common risk assessment approach. Surprisingly, a significant portion of the data stated to be available in Rauh et al. (2011) were not found in these published figures, perhaps due to data point overlay. However, the reported associations of chlorpyrifos levels with Working Memory and Full Scale IQ were also not replicated in our analysis due perhaps to this missing data. Multiple requests were made to Rauh et al. (2011) for access to data from this, in part, publicly funded study, so that confirmation could be attempted. This general lack of data and inconsistency with cholinergic responses in other researches raises concerns about the lack of data transparency.

Dourson|Michael|M| Gadagbui|Bernard|B| Onyema|Chijioke|C| McGinnis|Patricia|P|

Chlorpyrifos
Working memory index
Cholinesterase inhibition
Chlorpyrifos-oxon
Full-scale IQ scores
Science transparency


Symptom practice guide for telephone assessment of patients with cancer treatment-related cardiotoxic dyspnea: Adaptation and evaluation of acceptability.

Abstract:
Background
Patients with cancer treatment-related cardiotoxicity, which may manifest as heart failure (HF), can present with dyspnea. Nurses frequently assess, triage and offer self-care strategies to patients experiencing dyspnea in both the cardiology and oncology settings. However, there are no known tools available for nurses to manage patients in the setting of cancer treatment-related cardiotoxicity. The objective of this study was to adapt and evaluate the acceptability of an evidence-informed symptom practice guide (SPG) for use by nurses over the telephone for the assessment, triage, and management of patients experiencing dyspnea due to cancer treatment-related cardiotoxicity.

Methods
The CAN-IMPLEMENT© methodology guided this descriptive study. A systematic search was conducted in four databases to identify cardio-oncology and HF guidelines and systematic reviews. Screening was conducted by two reviewers, with data extracted into a recommendation matrix from eligible guidelines and systematic reviews on: assessment criteria, medications, and/or self-care strategies to manage dyspnea. Healthcare professionals with an expertise in oncology and/or cardiology were recruited using purposeful and snowball sampling. Evaluation of acceptability of the adapted SPG was gathered through semi-structured interviews and a survey with open- and closed-ended questions. Quantitative findings and participant feedback from the interviews and the open-ended survey questions were analyzed descriptively.

Results
Of 490 citations, seven HF guidelines were identified. Evidence from these guidelines was added to the original SPG. Eleven healthcare professionals completed the interview and acceptability survey. The adapted SPG was iteratively revised three times during the interviews. The original SPG was adaptable, and participants indicated the adapted SPG was comprehensive, easy to follow, and would be useful in clinical practice.

Conclusions
This study highlights the lack of knowledge tools and available clinical practice guidelines to guide healthcare professionals to assess, triage and/or offer self-care strategies to patients with cancer treatment-related cardiotoxic dyspnea. Moreover, most nurses require assistance to differentiate among the various causes of dyspnea from oncology treatment in order to triage severity appropriately. Further research should focus on evaluating the validity of the adapted SPG in clinical practice.

Kelly|F|F|
Carroll|S L|SL|
Carley|M|M|
Dent|S|S|
Shorr|R|R|
Hu|J|J|
Morash|R|R|
Stacey|D|D|

Symptom practice guide
Cancer treatment-related cardiotoxicity
Self-management/care


Cell number explains the intraspecific spur-length variation in an Aquilegia species.

Abstract: Variations of nectar spur length allow pollinators to utilize resources in novel ways, leading to the different selective pressures on spurs and allowing taxa to diversify. However, the mechanisms underlying spur length variation remain unclear. Interspecific comparisons of spur length suggest that both cell division and anisotropic expansion could explain the changes of spur length, and that hormone-related genes contribute to the process of spur formation. In contrast, little is known about intraspecific spur length variation. In Aquilegia rockii, spur length varies strikingly, ranging from 1 mm to 18 mm. To examine the potential mechanisms underlying spur length variation in A. rockii, we observed cell morphology and analyzed RNA-seq of short- and long-spurred flowers. Scanning electron microscopy revealed that at two positions on spurs there were no differences in either cell density or cell anisotropy between short- and long-spurred flowers, suggesting that in A. rockii changes in cell number may explain variations in spur length. In addition, we screened transcriptomes of short- and long-spurred flowers for differentially expressed genes; this screen identified several genes linked to cell division (e.g., F-box, CDKB2-2, and LST8), a finding which is consistent with our analysis of the cellular morphology of spurs. However, we did not find any highly expressed genes involved in the hormone pathway in long-spurred flowers. In contrast to previous hypotheses that anisotropic cell expansion leads to interspecific spur variation in Aquilegia, our results suggest that cell number changes and related genes are mainly responsible for spur length variations of A. rockii. Furthermore, the underlying mechanisms of similar floral traits in morphology may be quite different, enriching our understanding of the mechanisms of flower diversity in angiosperms.

Zhou|Zhi-Li|ZL| Duan|Yuan-Wen|YW| Luo|Yan|Y| Yang|Yong-Ping|YP| Zhang|Zhi-Qiang|ZQ|

Cell number
Nectar spur
Aquilegia rockii
Columbine
Floral polymorphism
Intraspecific variation


Different sized wheat bran fibers as fat mimetic in biscuits: its effects on dough rheology and biscuit quality.

Abstract: The aim of this study is to investigate the effects of various particle sized and different amount of plant fibers as fat mimetic for biscuit formulations instead of biscuit fat. The fibers with different particle sizes were obtained from wheat bran and used instead of fat in biscuit formulations. The texture, rheology and quality analyses of low-fat biscuit (30, 20 and 10% fat) were performed and compared with those of the full-fat control sample (40% fat). Results showed that wheat bran fiber with bigger particle size (Long Fiber, LF) were more favorable in terms of textural properties of the dough and the quality parameters of biscuits while the fibers with smaller particle size (Medium Fiber, MF and Small Fiber, SF) improved viscoelastic properties of dough similar to the control. Although the use of these fibers in the production of low-fat biscuits were suitable in terms of workability of dough increasing fiber content and/or reducing fiber size resulted in harder biscuits with lower spread ratio. This study showed that the texture of biscuits was greatly dependent on the texture of the dough.

Fiber
Fat mimetic
Biscuit
Dough
Rheology


The Tanzanian trauma patients' prehospital experience: a qualitative interview-based study.

Abstract:
OBJECTIVES
We sought to characterise the prehospital experience of Tanzanian trauma patients, and identify barriers and facilitators to implement community-based emergency medical systems (EMS).

SETTINGS
Our study was conducted in the emergency department of an urban national referral hospital in Tanzania.

PARTICIPANTS
A convenience sample of 34 adult trauma patients, or surrogate family members, presenting or referred to an urban referral emergency department in Tanzania for treatment of injury, participated in the study.

INTERVENTIONS
Participation in semistructured, iteratively developed interviews until saturation of responses was reached.

OUTCOMES
A grounded theory-based approach to qualitative analysis was used to identify recurrent themes.

RESULTS
We characterised numerous deficiencies within the existing clinic-to-hospital referral network, including missed/delayed diagnoses, limited management capabilities at pre-referral facilities and interfacility transfer delays. Potential barriers to EMS implementation include patient financial limitations and lack of insurance, limited public infrastructure and resources, and the credibility of potential first aid responders. Potential facilitators of EMS include communities' tendency to pool resources, individuals' trust of other community members to be first aid responders, and faith in community leaders to organise EMS response. Participants expressed a strong desire to learn first aid.

CONCLUSIONS
The composite themes generated by the data suggest that there are myriad structural, financial, institutional and cultural barriers to the implementation of a formal prehospital system. However, our analysis also revealed potential facilitators to a first-responder system that takes advantage of close-knit local communities and the trust of recognised leaders in society. The results suggest favourable acceptability for community-based response by trained lay people. There is significant opportunity for care improvements with short trainings and low-cost supply planning. Further research looking at the effects of delay on outcomes in this population is needed.

Kuzma|Kristin|K|
Lim|Andrew George|AG|
Kepha|Bernard|B|
Nalitolela|Neema Evelyne|NE|
Reynolds|Teri A|TA|

ACCIDENT & EMERGENCY MEDICINE
TRAUMA MANAGEMENT


Translation and validation study of the prodromal questionnaire brief version into Indonesian language.

Abstract:
BACKGROUND AND AIM
Psychosis is a mental disorder resulting in high disability impacts. Many studies show that early detection of prodromal symptoms may improve prognosis. Psychotic prodromal symptoms may mimic other mental health conditions such as depression, anxiety or learning difficulties. The aim of this study was to analyze validity, reliability, sensitivity and specificity of the Prodromal Questionnaire Brief Version (PQ-B) Indonesian version to detect psychotic prodromal symptoms.

METHOD
The PQ-B was translated into Indonesian then back-translated into English. Subjects included in this study were 50 children and adolescent psychiatric patients from Cipto Mangunkusumo National Hospital, aged 10-18 years old. Validity measurement was performed by comparing the total score and distress score of PQ-B with the categorical scale of Structured Interview for Prodromal Symptoms (SIPS) as the gold standard using Spearman correlation. Total scale and subscale reliability were examined using the Cronbach's Alpha.

RESULTS
Analysis with Spearman correlation showed significant results of both PQ-B total score with diagnosis of SIPS (r = 0.374 and p = 0.007); and PQ-B distress score with diagnosis of SIPS (r = 0.400 and p = 0.004). Cronbach Alpha coefficient was equal to 0.853 for all scales. The sensitivity of the PQ-B in the Indonesian language is 70%, and the specificity is 72%, whereas, in the original language (English), the sensitivity and specificity is 88% and 68%.

CONCLUSION
This study provides evidence of good validity, reliability, sensitivity, and specificity of PQ-B Indonesian language to detect prodromal symptoms of those who seek help in the psychiatric outpatient clinic.

Kaligis|Fransiska|F|
Ismail Marsubrin|Raden Irawati|RI|
Wiguna|Tjhin|T|
Noorhana|S W|SW|
Almasyhur|Alfi Fajar|AF|

D011569:Psychiatric Status Rating Scales

Translation Validation Prodromal Psychosis PQ-B Adolescent


Structure-based design, synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors.

Abstract: To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC50=1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50=5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C]=4%, po, 5mg/kg, once-daily) and COLO205 (T/C=13%, po, 15 mg/kg, once-daily) mouse xenograft models.

Matsumoto|Shigemitsu|S| Miyamoto|Naoki|N| Hirayama|Takaharu|T| Oki|Hideyuki|H| Okada|Kengo|K| Tawada|Michiko|M| Iwata|Hidehisa|H| Nakamura|Kazuhide|K| Yamasaki|Seiji|S| Miki|Hiroshi|H| Hori|Akira|A| Imamura|Shinichi|S|

D004354:Drug Screening Assays, Antitumor

D040301:Vascular Endothelial Growth Factor Receptor-2


From cranial nerve palsy to seizures-All the signs that lead to secondary Fahr's syndrome.

Abstract: Neuroimaging scan and calcium/phosphorus metabolism evaluation should be considered in patients with new onset of neuropsychiatric symptoms, to provide an earliest detection of pathological and metabolic alterations, such as Fahr's syndrome.

Fahr´s syndrome
cognitive impairment
hypoparathyroidism
seizure


Environmentally Relevant Iron Oxide Nanoparticles Produce Limited Acute Pulmonary Effects in Rats at Realistic Exposure Levels.

Abstract: Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the potential toxicity of FeOxNPs of different forms (Fe3O4, α-Fe2O3 and γ-Fe2O3) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more cytotoxic than either form of Fe2O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague-Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects.

D000082662:Magnetic Iron Oxide Nanoparticles

iron oxide
nanoparticle
rat
ultrafine
inhalation
lung
omics


Agronomic and financial benefits of direct Minjingu phosphate rock use in acidic humic nitisols of Upper Eastern Kenya.

Abstract: A major constraint to crop production in Sub-Saharan Africa is nutrient deficiency, especially phosphorus (P) deficiency. Phosphorus plays a crucial role in photosynthesis but is usually deficient in acidic soils since it is converted to less available forms, affecting crop yields. There is a need to improve phosphorus availability to crops for maximum production. This study assessed Minjingu phosphate rock fertilizer's impact on maize yields, soil chemical composition, and cost-effectiveness in acidic humic nitisols of Tharaka Nithi County, Upper Eastern Kenya. A field experiment in a randomized complete block design (RCBD) was set during long rains (SR2017) and Short rains (LR2018) seasons. The treatments were Minjingu phosphate rock, manure, Tithonia diversifolia, Minjingu phosphate rock + manure, Tithonia diversifolia + Minjingu phosphate rock, Calcium Ammonium Nitrate (CAN) + Triple Superphosphate (TSP), and a control. Soil samples were collected at a depth of 0-20 cm before and at the end of the experiment for pH, P-sorption, and other soil nutrient determinations. Other auxiliary data collected included labor and input costs besides output prices. The CAN+TSP treatment had significantly higher grain yields (6.86 Mg ha-1), while Minjingu phosphate rock on its own had the second-lowest than the control treatment (3.0 Mg ha-1). Also, a similar trend in the stover yields was observed. Minjingu phosphate rock combined with either manure or Tithonia diversifolia led to a significant increase (over 100%) in the phosphorous levels. Sole application of Minjingu phosphate rock increased soil iron levels while magnesium, copper, and zinc levels decreased significantly. Other than the control, all treatments significantly lowered the P-sorption levels. However, CAN+TSP had the highest P-sorption (913 mg kg-1)while Tithonia diversifolia had the lowest (744 mg kg-1). During the LR2018 season, all treatments reached a break-even point, and the net benefit was significantly higher at P < 0.05. Conclusively, the use of phosphate rock, either solely or in combination with organic elements, improved yields, soil chemical composition, P-sorption and was very cost-effective.

Ndeleko-Barasa|E M|EM|
Mucheru-Muna|M W|MW|
Ngetich|K F|KF|

Maize yields
Tithonia diversifolia
Animal manure
Cost-benefit analysis
Phosphorus-sorption


The Triple Roles of Glutathione for a DNA-Cleaving DNAzyme and Development of a Fluorescent Glutathione/Cu2+-Dependent DNAzyme Sensor for Detection of Cu2+ in Drinking Water.

Abstract: Pistol-like DNAzyme (PLDz) is an oxidative DNA-cleaving catalytic DNA with ascorbic acid as cofactor. Herein, glutathione was induced into the reaction system to maintain reduced ascorbic acid levels for higher efficient cleavage. However, data indicated that glutathione played triple roles in PLDz-catalyzed reactions. Glutathione alone had no effect on PLDz, and showed inhibitory effect on ascorbic acid-induced PLDz catalysis, but exhibited stimulating effect on Cu2+-promoted self-cleavage of PLDz. Further analysis of the effect of glutathione/Cu2+ on PLDz indicated that H2O2 played a key role in PLDz catalysis. Finally, we developed a fluorescent Cu2+ sensor (PL-Cu 1.0) based on the relationship between glutathione/Cu2+ and catalytic activity of PLDz. The fluorescent intensity showed a linear response toward the logarithm concentration of Cu2+ over the range from 80 nM to 30 μM, with a detection limit of 21.1 nM. PL-Cu 1.0 provided only detection of Cu2+ over other divalent metal ions. Ca2+ and Mg2+ could not interfere with Cu2+ detection even at a 1000-fold concentration. We further applied PL-Cu 1.0 for Cu2+ detection in tap and bottled water. Water stored in copper taps overnight had relatively high Cu2+ concentrations, with a maximum 22.3 μM. Trace Cu2+ (52.2 nM) in deep spring was detected among the tested bottled water. Therefore, PL-Cu 1.0 is feasible to detect Cu2+ in drinking water, with a practical application.

glutathione
DNAzyme
Cu2+
sensor
drinking water


Relationship between Serum Osteocalcin Level and Gestational Diabetes Mellitus: A Case-Control Study.

Abstract:
Background
Osteocalcin (OC) is the most common noncollagenous protein in bone matrix, which is synthesized only in bone tissue and by osteoblasts. The potential role of osteocalcin on glucose and fat metabolism has been previously reported. The aim of this study was to compare the serum OC level in pregnant women with and without gestational diabetes mellitus (GDM).

Methods
In the present case-control study, all pregnant women who were referred to a obstetrics and gynecology clinic in Sari, Iran, and met the inclusion criteria underwent an overall screening with a 75-g glucose tolerance test (GTT) at week 24 to 28 of gestation. The study was conducted between September 2018 and February 2019. Based on criteria, the pregnant women with confirmed GDM were matched with pregnant women without GDM in terms of baseline characteristics such as chronological age and BMI. The serum OC levels were also measured if vitamin D and calcium levels were normal. All data were analyzed using SPSS 21.

Results
The two groups with and without GDM had no significant difference in terms of age, BMI and OC level. There was no significant correlation between age and BMI with OC level in healthy pregnant women, respectively (P=0.49 and P=0.58). The correlation between BMI and age with OC level in GTT-positive pregnant women was 0.05 and -0.172, respectively, which was not significant (P=0.77 and P=0.36).

Conclusion
According to the results of this study, there is no significant difference of serum OC levels in pregnant women with GDM compared to healthy pregnancy. Given that the levels of serum insulin or insulin resistance have not been assessed, these indices are recommended to be evaluated in future studies.

Peivandi|Saloumeh|S| Yaghoubinia|Kamelia|K| Kashi|Zahra|Z| Moradi|Siavash|S| Habibi|Ali|A|

Osteocalcin
Gestational
Diabetes
Vitamin D


Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day?

Abstract: 'IDegLira' combines insulin degludec (IDeg) with the glucagon-like peptide-1 analog liraglutide (Lira) at a ratio of 1 unit IDeg to 0.036 mg Lira. The two components have complementary therapeutic actions for the treatment of Type 2 diabetes. Studies have shown that combinations of basal insulin with glucagon-like peptide-1 receptor agonists can be clinically successful, lowering elevated blood glucose with a low risk of hypoglycemia and weight gain. IDegLira is being assessed in a series of studies (two already published), which provide insights into its clinical utility in previously insulin-naive patients and those failing to achieve good glycemic control on a basal-only insulin regimen. This article critically examines the available data to assess the product's likely clinical profile.

D001786:Blood Glucose
D003924:Diabetes Mellitus, Type 2
D004338:Drug Combinations
D052216:Glucagon-Like Peptide 1
D006801:Humans
D007004:Hypoglycemic Agents
D007328:Insulin
D049528:Insulin, Long-Acting
D000069450:Liraglutide
D016896:Treatment Outcome

insulin degludec
liraglutide
Type 2 diabetes
basal insulin
DUAL study
combination therapy
incretin therapy


Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis.

Abstract:
Resminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy. However, the molecular mechanisms behind this synergism have not been explored yet. In this work, we aimed to analyze whether resminostat regulates epithelial-mesenchymal and stemness phenotype as a mechanism of sensitization to sorafenib. Three HCC cell lines with differences in their epithelial/mesenchymal characteristics were treated with resminostat and sorafenib alone, or in combination. Resminostat prevented growth and induced cell death in the HCC cells, in a time and dose dependent manner. A collaborative effect between resminostat and sorafenib was detected in the mesenchymal HCC cells, which were insensitive to sorafenib-induced apoptosis. Expression of mesenchymal-related genes was decreased in resminostat-treated HCC cells, concomitant with an increase in epithelial-related gene expression, organized tight junctions and reduced invasive growth. Moreover, resminostat down-regulated CD44 expression, coincident with decreased capacity to form colonies at low cell density.

CONCLUSION
Resminostat shifts mesenchymal cells towards a more epithelial phenotype, lower invasive and stemness properties, which may contribute to the sensitization to sorafenib-induced apoptosis.

Soukupova|Jitka|J| Bertran|Esther|E| Peñuelas-Haro|Irene|I| Urdiroz-Urricelqui|Uxue|U| Borgman|Matthias|M| Kohlhof|Hella|H| Fabregat|Isabel|I|

resminostat
HCC
sorafenib
EMT
HDAC inhibitors


Resiniferatoxin induces death of bladder cancer cells associated with mitochondrial dysfunction and reduces tumor growth in a xenograft mouse model.

Abstract: Bladder cancer (BC) is the fifth most common non-cutaneous malignancy and the most common form of BC in Western countries is transitional cell carcinoma. Resiniferatoxin (RTX) has found therapeutic usefulness for the treatment of bladder dysfunction but no data are available on its use as chemotherapeutic agent. The aim of this work is to evaluate the use of RTX as new anti-cancer drug in BC therapy. The effects of RTX on cell viability and cell death were evaluated on T24 and 5637 BC cell lines by MTT assay, cell cycle analysis, Annexin-V/PI staining and agarose gel electrophoresis of DNA. Mitochondrial depolarization and ROS production were assessed by flow cytometry. ADP/ATP ratio was measured by bioluminescence and caspase 3 cleavage by Western blot. For in vivo experiments, athymic nude mice, xenografted with T24 cells, received subcutaneous administrations of RTX. Tumor volumes were measured and immunohistochemistry was performed on tumor sections. Our data demonstrated that RTX influences cell cycle and induces necrotic cell death of BC cells by altering mitochondrial function, leading to depolarization, increase in ADP/ATP ratio and ROS production. Moreover, RTX is able to reduce tumor growth in a xenograft mouse model. Overall, we demonstrated that RTX induces necrotic cell death of BC cells and reduces tumor growth in a xenograft mouse model of BC, suggesting RTX as a new potential anti-cancer drug in BC chemotherapy.

Farfariello|Valerio|V|
Liberati|Sonia|S|
Morelli|Maria Beatrice|MB|
Tomassoni|Daniele|D|
Santoni|Matteo|M|
Nabissi|Massimo|M|
Giannantoni|Antonella|A|
Santoni|Giorgio|G|
Amantini|Consuelo|C|

D023041:Xenograft Model Antitumor Assays

Resiniferatoxin
Bladder cancer
Xenograft
Mitochondria
Necrosis


Combination of best promoter and micellar catalyst for more than kilo-fold rate acceleration in favor of chromic acid oxidation of D-galactose to D-galactonic acid in aqueous media at room temperature.

Abstract: Picolinic acid, 2,2'-bipyridine and 1,10-phenanthroline promoted Cr(VI) oxidation of D-galactose to D-galactonic acid in three representative aqueous micellar media has been studied. The anionic surfactant (SDS) accelerated the rate of reaction while the cationic surfactant (CPC) and neutral surfactant (TX-100) retarded the reaction rate. Combination of bipy and SDS is the best choice for chromic acid oxidation of D-galactose to D-galactonic acid in aqueous media although 1,10-phenanthroline is best promoter in absence of micellar catalyst.

Saha|Rumpa|R|
Ghosh|Aniruddha|A|
Sar|Pintu|P|
Saha|Indrajit|I|
Ghosh|Sumanta K|SK|
Mukherjee|Kakali|K|
Saha|Bidyut|B|

d-galactose
Picolinic acid
1,10-Phenanthroline
Cr(VI)
2,2′-Bipyridine
Micellar catalysis


Heavy metal contamination in sandy beach macrofauna communities from the Rio de Janeiro coast, Southeastern Brazil.

Abstract: We evaluated concentrations of eight heavy metals Cr, Zn, Pb, Ni, Cu, Cd, Co and V, in tissues of representative macrofauna species from 68 sandy beaches from the coast of Rio de Janeiro state. The links between contamination levels and community descriptors such as diversity, evenness, density and biomass, were also investigated. Metal concentrations from macrofaunal tissues were compared to maximum permissible limits for human ingestion stipulated by the Brazilian regulatory agency (ANVISA). Generalized linear models (GLM's) were used to investigate the variability in macrofauna density, richness, eveness and biomass in the seven different regions. A non-metric multidimensional scaling analysis (n-MDS) was used to investigate the spatial pattern of heavy metal concentrations along the seven regions of Rio de Janeiro coast. Variation partitioning was applied to evaluate the variance in the community assemblage explained by the environmental variables and the heavy metal concentrations. Our data suggested high spatial variation in the concentration of heavy metals in macrofauna species from the beaches of Rio de Janeiro. This result highlighted a diffuse source of contamination along the coast. Most of the metals concentrations were under the limits established by ANVISA. The variability in community descriptors was related to morphodynamic variables, but not with metal contamination values, indicating the lack of direct relationships at the community level. Concentration levels of eight heavy metals in macrofauna species from 68 sandy beaches on Rio de Janeiro coast (Brazil) were spatially correlated with anthropogenic activities such as industrialization and urbanization.

Cabrini|Tatiana M B|TMB|
Barboza|Carlos A M|CAM|
Skinner|Viviane B|VB|
Hauser-Davis|Rachel A|RA|
Rocha|Rafael C|RC|
Saint'Pierre|Tatiana D|TD|
Valentin|Jean L|JL|
Cardoso|Ricardo S|RS|

Benthos
Chemical pollutant
Environmental factors
Management
Southeast Brazil


Immune status and epidemiological characteristics of human immunodeficiency virus seroconverters in Korea, 1999-2009.

Abstract:
OBJECTIVES
The detection of HIV seroconverters increased annually since HIV antigen/antibody testing kits have been available widely in South Korea. This study aimed to identify the epidemiological characteristics of HIV seroconverters and their immune level at HIV diagnosis.

METHOD
We analyzed the epidemiological and immunological characteristics of 341 HIV seroconverters among 6,008 HIV-diagnosed individuals from 1999 and 2009. The analysis of immune level and epidemiological factors of HIV seroconverters was conducted by using chi-square test on SAS version 9.1.

RESULTS
The seroconverters among newly-identified HIV cases each year increased from 0.5% in 1999 to over 5% or in 2009. The sex ratio of seroconverters was 18:1 (male:female), and 33% were in their 30s, and 28% were in their 20s. Reasons for HIV testing were involvement in voluntary test due to risky behaviors (43%), and health check-up (36%). Discovery of HIV infection occurred primarily in hospitals (84%). Among seroconverters, 55 percent had a CD4 T-cell count of more than 350/μl.

CONCLUSION
Korean HIV seroconverters tended to be younger at diagnosis, diagnosed during a voluntary test, and their CD4+ T-cell counts at HIV diagnosis were higher than those of non-seroconverters aall HIV-infected individuals. This study of HIV seroconverters will be important foundational in future studies on HIV incidence, disease progress, and survival rate.

Wang|Jin-Sook|JS|
Kim|Na-Young|NY|
Sim|Hyo Jung|HJ|
Choi|Byeong-Sun|BS|
Kee|Mee-Kyung|MK|


Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and behavioural assessment in zebrafish model.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children.

AIM OF THE STUDY
To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy.

MATERIALS AND METHODS
Suvarna Bhasma was characterised by physicochemical characterization techniques such as scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and atomic emission spectroscopy (ICP-AES). Toxicity of Suvarna Bhasma was studied in Holtzman rats with daily oral dose from 3 mg/kg (therapeutic dose, TD) up to 30 mg/kg (10 TD) body weight for 90 days. Behavioural study, such as motor and geotactic behaviour were examined in zebrafish model to find out any sign of neurotoxicity or behavioural changes due to Suvarna Bhasma administration.

RESULTS
Suvarna Bhasma has two types of gold particles, large ones (~60 μm) having irregular shapes, and nano-sized spherical particles (starting from ~10 nm), the latter coated with Fe, Si, O, P and Na. XRD study revealed that all the peaks of Suvarna Bhasma match well with pure gold (face centred cube) with crystallites size 45 ± 2.8 nm. In rat studies, some change in biochemical parameters such as urea, creatinine and alanine aminotransferase (ALT) was observed mainly at the higher therapeutic dose; however, those parameters were within the normal range. There were no significant macroscopic as well as microscopic treatment-related alteration observed, in any of the organs and tissues evaluated. In zebrafish behavioural study, the motor parameters of Suvarna Bhasma treated fish showed normal behaviour analogous to the vehicle control group. Interestingly, the geotactic behaviour showed anxiolytic effects of Suvarna Bhasma as evidenced by the time spent in the upper zone, and average swimming height. The anxiolytic effects persisted for more than 30 days after withdrawing the Suvarna Bhasma treatment.

CONCLUSIONS
Suvarna Bhasma contained spherical gold nanoparticles. It was nontoxic in rat model at the does tested. Suvarna Bhasma has anxiolytic effects in zebrafish behavioural model.

Biswas|Snehasis|S| Dhumal|Rohit|R| Selkar|Nilakash|N| Bhagat|Sharad|S| Chawda|Mukesh|M| Thakur|Kapil|K| Gudi|Ramacharya|R| Vanage|Geeta|G| Bellare|Jayesh|J|

Suvarnaprashana
Zebrafish behaviour
Anxiolytic effects
Gold nanoparticle
Novel tank experiment
Swarna Bhasma


Design and Realization of Integrated Management System for Data Interoperability between Point-of-Care Testing Equipment and Hospital Information System.

Abstract:
OBJECTIVES
The purpose of this study was to design an integrated data management system based on the POCT1-A2, LIS2-A, LIS2-A2, and HL7 standard to ensure data interoperability between mobile equipment, such as point-of-care testing equipment and the existing hospital data system, its efficiency was also evaluated.

METHODS
The method of this study was intended to design and realize a data management system which would provide a solution for the problems that occur when point-of-care testing equipment is introduced to existing hospital data, after classifying such problems into connectivity, integration, and interoperability. This study also checked if the data management system plays a sufficient role as a bridge between the point-of-care testing equipment and the hospital information system through connection persistence and reliability testing, as well as data integration and interoperability testing.

RESULTS
In comparison with the existing system, the data management system facilitated integration by improving the result receiving time, improving the collection rate, and by enabling the integration of disparate types of data into a single system. And it was found out that we can solve the problems related to connectivity, integration and interoperability through generating the message in standardized types.

CONCLUSIONS
It is expected that the proposed data management system, which is designed to improve the integration point-of-care testing equipment with existing systems, will establish a solid foundation on which better medical service may be provided by hospitals by improving the quality of patient service.

Park|Ki Sang|KS|
Heo|Hyuk|H|
Choi|Young Keun|YK|

Hospital Information System
Clinical Laboratory Information Systems
Database Management Systems
Medical Order Entry Systems
Point-of-Care Systems


Two CHRN susceptibility variants for COPD are genetic determinants of emphysema and chest computed tomography manifestations in Chinese patients.

Abstract: Quantitative computed tomography (CT) measures of emphysema have been shown to be associated with increased mortality in humans, but genetic variants affecting the quantitative parameters of chest CT that measure degree of emphysema have not yet been examined. In this study, using available chest CT data from a total of 344 emphysema patients, we assessed the correlations between five chronic obstructive pulmonary disease (COPD) susceptibility variants in the cholinergic receptor nicotinic (CHRN) genes and the degree of emphysema and chest CT manifestations. We verified that most of the parameters were significantly correlated with the degree of emphysema. Compared to rs76071148AA and TT genotype carriers, the rs76071148AT genotype carriers exhibited a decreased probability of having severe emphysema (odds ratio [OR] =0.63, 95% confidence interval [CI] =0.40-0.99), whereas the variant rs8040868C allele was negatively correlated with the emphysema index (P=0.002). Interestingly, further stratification analysis grouped by spirometry-diagnosed COPD status revealed that the variant rs8040868C (CT + CC) genotypes exerted a protective effect against severe emphysema with borderline significance (OR =0.41, 95% CI =0.16-1.05) and affected the mean lung density, emphysema index, ratio of airway wall thickness to airway dimensions (AWT/AD), and AWT grade in spirometry-diagnosed non-COPD subjects. The rs76071148 variant was also significantly associated with AWT/AD and AWT grade in those individuals. In summary, we determined that rs8040868 and rs76071148 are promising indicators of the degree of emphysema and chest CT manifestations, especially in spirometry-diagnosed non-COPD subjects.

Zhao|Zhuxiang|Z| Jiang|Changbin|C| Zhao|Dongxing|D| Li|Yujun|Y| Liang|Chunxiao|C| Liu|Weifeng|W| Wei|Shuquan|S| Zhou|Yumin|Y| Zhao|Ziwen|Z| Ran|Pixin|P|

D020022:Genetic Predisposition to Disease

D029424:Pulmonary Disease, Chronic Obstructive

COPD
emphysema
CT manifestation
CHRN variant


Mussel-Inspired Polydopamine Functionalized Plasmonic Nanocomposites for Single-Particle Catalysis.

Abstract: Polydopamine functionalized plasmonic nanocomposites with well-distributed catalytically active small gold nanoislands around large gold core were fabricated without using any chemical reductant or surfactant. The optical properties, surface molecular structures, and ensemble catalytic activity of the gold nanocomposites were investigated by time-of-flight secondary ion mass spectrometry and UV-vis spectroscopy, respectively. Moreover, the considerable catalytic activity of the nanocomposites toward 4-nitrophenol reduction was real time monitored by dark-field spectroscopy techniques at the single-nanoparticle level avoiding averaging effects in bulk systems. According to the obtained plasmonic signals from individual nanocomposites, the electron charging and discharging rates for these nanocomposites during the catalytic process were calculated. Our results offer new insights into the design and synthesis of plasmonic nanocomposites for future catalytic applications as well as a further mechanistic understanding of the electron transfer during the catalytic process at the single-nanoparticle level.

polydopamine
plasmonic nanocomposites
single-particle catalysis
ToF-SIMS
dark-field microscopy


Traumatic vertebral artery injury: a review of the screening criteria, imaging spectrum, mimics, and pitfalls.

Abstract:
Purpose
Traumatic vertebral artery injury (TVAI) can have a varied clinical presentation and appearance on imaging. In this review, we present the screening criteria, spectrum of imaging features, grading, and imaging pitfalls of TVAI. Our review focuses on the imaging of TVAI on computed tomography angiography (CTA), magnetic resonance angiography (MRA), and cases of TVAI mimics.

Imaging
The imaging spectrum on CTA can range from either focal or long segment luminal stenosis (the most common findings), smooth or tapered narrowing of lumen, string of pearls appearance, concentric intramural haematoma, intimal flap (the most definite sign), and double lumen of the artery. On time-of-flight MRA, the most common findings include loss of flow void within the vessel due to slow flow, thrombosis or occlusion, and hyperintense signal within the vessel wall due to intramural haematoma on T1 fat-saturated images.

Conclusion
The reader should be aware of the screening criteria, common and uncommon findings, variant anatomy, artifacts, and mimics of TVAI when evaluating cases of craniocervical trauma, to be competent in calling in or ruling out injury.

Sharma|Pranav|P|
Hegde|Rahul|R|
Kulkarni|Ashwini|A|
Sharma|Salil|S|
Soin|Priti|P|
Kochar|Puneet S|PS|
Kumar|Yogesh|Y|

traumatic vertebral artery injury
magnetic resonance angiography
CT angiography
digital subtraction angiography
vertebral artery dissection


The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After First Attack: A Randomized Clinical Trial.

Abstract:
OBJECTIVE
Epilepsy is a serious, potentially life-shortening brain disorder that occurs in patients of all ages and races. A total of 2-4% of people have experienced seizures at least once in their lifetime. Although treatment usually begins after a seizure, it is an important question whether the first cases of seizure do need to be treated by antiepileptic drugs. In this manner, we compare the recurrence rates of epilepsy in first seizure patients treated with sodium valproic acid as an antiepileptic drug versus a placebo.

MATERIAL & METHODS
In a randomized clinical trial study, 101 first seizure patients were randomly divided into two groups: one group was treated with antiepileptic drugs (sodium valproate 200mg, three times a day) and the other group was given a placebo. The recurrence rate of seizures was evaluated and compared between the groups after 6 months of follow up.

RESULTS
Eight recurrence cases were detected. All recurrence cases came from the placebo group, with four patients suffering an additional seizure after four months and between 4-6 month follow up. A comparison of recurrence rate detected a statistically significant difference between the drug group and placebo group.

CONCLUSION
Our data shows that the recurrences occurred only in the placebo group with the difference between the recurrence rates in the placebo versus drug-treated was significant. Our results suggest that drug therapy for people after their first seizure attack might reduce the probability of seizure recurrence.

Assarzadegan|Farhad|F|
Tabesh|Hanif|H|
Hesami|Omid|O|
Derakhshanfar|Hojjat|H|
Beladi Moghadam|Nahid|N|
Shoghli|Arya|A|
Beale|Andrew David|AD|
Hosseini-Zijoud|Seyed-Mostafa|SM|

Recurrence rate
Seizure
Epilepsy
Sodium valproate


Musculoskeletal Complaints in Occupational Therapists Compared to the General Population: A Cross-Sectional Study in Germany.

Abstract: Occupational therapists (OTs) are exposed to physical factors at work, which can lead to an increased risk of musculoskeletal disorders. Most studies examining musculoskeletal complaints in OT report that the neck, shoulders, and lower back are most often afflicted. The aim of the present study was to examine the impact of work as an OT (focusing on specific work tasks) on specific musculoskeletal complaints compared to the general working population. A cross-sectional study involving a self-administered standardized questionnaire was conducted from January until October 2015 in Germany. In OT and the comparison group, the highest 12-month prevalence of musculoskeletal disorders were observed for the lower back, the neck, and the shoulders. In contrast, elevated prevalence ratios (PR) were found for OT in the thumbs (PR = 2.7; 95% CI = 1.9-3.8), the wrists (PR = 1.4; 95% CI = 1.1-1.8), and the elbows (PR = 1.5; 95% CI = 1.0-2.2). OTs were particularly exposed to high exertion hand activity and several stressful postures at work. In conclusion, OTs seem to be at risk of developing work-related musculoskeletal complaints in the thumbs, wrists, and elbows. Preventive measures should help to reduce the exposures caused by highly repetitive and forceful hand activities.

Zenker|Ronny|R| Girbig|Maria|M|0000-0002-9300-3969 Hegewald|Janice|J|0000-0003-3388-161X Gilewitsch|Irina|I| Wagner|Mandy|M| Nienhaus|Albert|A| Seidler|Andreas|A|

musculoskeletal complaints
occupational therapists
general population
musculoskeletal diseases
occupational health
work-related complaints
work-related diseases


Consensus document on dog and cat allergy.

Abstract: The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.

Dávila|I|I|
Domínguez-Ortega|J|J|
Navarro-Pulido|A|A|
Alonso|A|A|
Antolín-Amerigo|D|D|
González-Mancebo|E|E|
Martín-García|C|C|
Núñez-Acevedo|B|B|
Prior|N|N|
Reche|M|M|
Rosado|A|A|
Ruiz-Hornillos|J|J|
Sánchez|M C|MC|
Torrecillas|M|M|

allergen immunotherapy
allergic sensitisation
furry animals
hypersensitivity


Sleep and pain interference in individuals with chronic pain in mid- to late-life: The influence of negative and positive affect.

Abstract: Poor sleep and chronic pain are known to be interrelated, but the influence of negative and positive affect on this relationship is not fully understood. The present study sought to examine whether negative and positive affect mediate the relationship between sleep and pain interference. Secondary data analysis from Midlife in the United States (MIDUS-III) was used to examine 948 individuals with chronic pain (mean age = 64.73 years). Sleep disturbance was conceptualized as the sum of self-reported difficulty with sleep-onset latency, wake after sleep onset, early morning awakening and daytime sleepiness, and total sleep time was assessed via self-reported sleep duration. Pain interference was operationalized as the sum of pain-related interference with general activity, relationships and enjoyment of life. Finally, items from the Positive and Negative Affect Schedule were used to measure affect. Mediation analyses revealed that sleep disturbance indirectly predicted pain interference via both negative affect (β = 0.15, confidence interval: 0.10, 0.21) and positive affect (β = 0.18, confidence interval: 0.12, 0.25). Similarly, negative (β = -0.003, confidence interval: -0.01, -0.001) and positive affect (β = -0.003, confidence interval: -0.01, -0.001) also mediated the effect between total sleep time and pain interference. This study highlights the unique role of negative and positive affect on pain interference for individuals with chronic pain in mid- to late-life. Additionally, findings suggest that holistic treatment approaches, which assess both sleep and affect in the context of chronic pain, may be beneficial.


Assessing the goodness of fit of personal risk models.

Abstract: We describe a flexible family of tests for evaluating the goodness of fit (calibration) of a pre-specified personal risk model to the outcomes observed in a longitudinal cohort. Such evaluation involves using the risk model to assign each subject an absolute risk of developing the outcome within a given time from cohort entry and comparing subjects' assigned risks with their observed outcomes. This comparison involves several issues. For example, subjects followed only for part of the risk period have unknown outcomes. Moreover, existing tests do not reveal the reasons for poor model fit when it occurs, which can reflect misspecification of the model's hazards for the competing risks of outcome development and death. To address these issues, we extend the model-specified hazards for outcome and death, and use score statistics to test the null hypothesis that the extensions are unnecessary. Simulated cohort data applied to risk models whose outcome and mortality hazards agreed and disagreed with those generating the data show that the tests are sensitive to poor model fit, provide insight into the reasons for poor fit, and accommodate a wide range of model misspecification. We illustrate the methods by examining the calibration of two breast cancer risk models as applied to a cohort of participants in the Breast Cancer Family Registry. The methods can be implemented using the Risk Model Assessment Program, an R package freely available at http://stanford.edu/~ggong/rmap/.

Gong|Gail|G|
Quante|Anne S|AS|
Terry|Mary Beth|MB|
Whittemore|Alice S|AS|

D056808:Biostatistics
D001943:Breast Neoplasms
D015331:Cohort Studies
D003198:Computer Simulation
D005260:Female
D006801:Humans
D008137:Longitudinal Studies
D015233:Models, Statistical
D057285:Precision Medicine
D011336:Probability
D016016:Proportional Hazards Models
D012044:Regression Analysis
D012306:Risk
D018570:Risk Assessment
D012307:Risk Factors

goodness of fit
absolute risk
cohort data
efficient score statistics
personal disease risk
standardized residuals


Drug-drug interaction database for safe prescribing of systemic antifungal agents.

Abstract:
Introduction
A drug-drug interaction (DDI) describes the influence of one drug upon another or the change in a drug's effect on the body when the drug is taken together with a second drug. A DDI can delay, decrease or enhance absorption or metabolism of either drug. Several antifungal agents have a large number of potentially deleterious DDIs.

Methods
The antifungal drug interactions database https://antifungalinteractions.org/was first launched in 2012 and is updated regularly. It is available as web and app versions to allow information on potential drug interactions with antifungals with a version for patients and another for health professionals. A new and updated database and interface with apps was created in 2019. This allows clinicians and patients to rapidly check for DDIs. The database is fully referenced to allow the user to access further information if needed. Currently DDIs for fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, terbinafine, amphotericin B, caspofungin, micafungin and anidulafungin are cross-referenced against 2398 other licensed drugs, a total of nearly 17,000 potential DDIs.

Results
The database records 541 potentially severe DDIs, 1129 moderate and 1015 mild DDIs, a total of 2685 (15.9%).

Conclusion
As the online database and apps are free to use, we hope that widespread acceptance and usage will reduce medical misadventure and iatrogenic harm from unconsidered DDIs.

antifungal
antifungal interactions
antifungal stewardship
cytochrome P450
drug–drug interaction


Extended Internal Limiting Membrane Peeling in Complex Pediatric Rhegmatogenous Retinal Detachment.

Abstract:
PURPOSE
To assess the feasibility and investigate the anatomical and functional outcomes of extended internal limiting membrane (ILM) peeling with pars plana vitrectomy (PPV) for complex pediatric rhegmatogenous retinal detachment (RRD).

METHODS
This was a retrospective interventional case series where children (≤18 years) with RRD and severe PVR (grade C) were included. All eyes underwent PPV with ILM peeling up to 2-disk diameter beyond the vascular arcades. The main outcome measures were assessment of feasibility of ILM peeling in the pediatric RRD and evaluation of the rate of complete retinal reattachment and corrected-distance visual acuity (CDVA) at the final follow-up.

RESULTS
A total of 29 eyes (25 patients) were enrolled in this study. ILM peeling performed on these children was not more difficult than in adult eyes. After a mean follow-up of 18 months, the patients achieved final CDVA better than 20/200 in 37.9%. The initial retinal reattachment was 55.2% while the final anatomical success was 86.2%.

CONCLUSION
Vitrectomy with ILM peeling is technically feasible in pediatric RRD, limiting epiretinal proliferation and achieving favorable anatomical outcomes in cases of complex pediatric RRD. The long-term effects of ILM peeling need further investigation.

Abdullatif|Abdussalam M|AM|
Macky|Tamer A|TA|
Mortada|Hassan A|HA|

Internal limiting membrane
Pediatric
Rhegmatogenous retinal detachment
Pars plana vitrectomy


A Novel Prototype Device for Microencapsulation of Benznidazole: In Vitro/In Vivo Studies.

Abstract: This study was aimed to design a simple and novel prototype device for the production of polymeric microparticles. To prove the effectiveness of this device, benznidazole microparticles using chitosan as carrier and NaOH, KOH, or SLS as counter ions were used. For comparison, benznidazole microparticles were prepared by the conventional dripping technique (syringe and gauge) using the same excipients. Microparticles were characterized in terms of encapsulation efficiency, particle shape, size and surface topography, crystallinity characteristics, thermal behavior, and dissolution rate. Then, the pharmacokinetic parameters were evaluated after the oral administration of the microparticles to healthy Wistar rats. The prepared formulations, by means of this device, showed good drug encapsulation efficiency (> 70%). Release studies revealed an increased dissolution of benznidazole from chitosan microparticles prepared using the novel device. It achieved more than 90% in 60 min, while those of the conventional microparticles and raw drug achieved 65% and 68%, respectively, during the same period. Almost spherical benznidazole microparticles with a smooth surface and size around 10-30 μm were observed using scanning electron microscopy. Thermal analysis and X-ray diffraction studies suggested a partial reduction of drug crystallinity. Moreover, the relative oral bioavailability of the novel benznidazole microparticles showed that the area under the curve for the microencapsulated drug was 10.3 times higher than the raw drug. Thus, these findings indicate that the designed glass prototype device is a useful alternative to formulate benznidazole polymeric microparticles with improved biopharmaceutical properties and could be useful for other therapeutic microparticulate systems.

Barrera|María G|MG|
Tejada|Guillermo|G|
Leonardi|Darío|D|
Lamas|María C|MC|
Salomón|Claudio J|CJ|

prototype device
microencapsulation
benznidazole
chitosan
bioavailability


Conformations of macromolecules and their complexes from heterogeneous datasets.

Abstract: We describe a new generation of algorithms capable of mapping the structure and conformations of macromolecules and their complexes from large ensembles of heterogeneous snapshots, and demonstrate the feasibility of determining both discrete and continuous macromolecular conformational spectra. These algorithms naturally incorporate conformational heterogeneity without resort to sorting and classification, or prior knowledge of the type of heterogeneity present. They are applicable to single-particle diffraction and image datasets produced by X-ray lasers and cryo-electron microscopy, respectively, and particularly suitable for systems not easily amenable to purification or crystallization.

D000465:Algorithms
D020285:Cryoelectron Microscopy
D007834:Lasers
D046911:Macromolecular Substances
D008968:Molecular Conformation
D014961:X-Ray Diffraction

macromolecular conformations
X-ray lasers
cryo-electron microscopy
dimensionality reduction
macromolecular structure
manifold embedding


Fusiform dilatation of the outer contour of a dissected anterior cerebral artery revealed by magnetic resonance cisternography in a patient with simultaneous cerebral infarction and subarachnoid hemorrhage.

Abstract: A 46-year-old man presented with right hemiparesis. Cranial magnetic resonance (MR) imaging revealed both an acute cerebral infarction in the territory of the left anterior cerebral artery (ACA) and a thin subarachnoid hemorrhage in the left superior frontal sulcus. MR angiography revealed stenosis at the A2 segment of the left ACA. MR cisternography was, therefore, performed on day 12 after admission using sagittal, 3-dimensional, heavily T2-weighted images. Fusiform dilatation of the outer contour was confirmed by MR cisternography at the region of narrowing identified by MR angiography. This case indicates that the combination of MR cisternography and angiography can be useful for detecting ACA dissection.

Kato|Yuji|Y| Hayashi|Takeshi|T| Uchino|Akira|A| Kakehi|Yoshiaki|Y| Yamane|Fumitaka|F| Ishihara|Shoichiro|S| Tanahashi|Norio|N|

D000784:Aneurysm, Dissecting
D020771:Anterior Cerebral Artery
D002544:Cerebral Infarction
D006801:Humans
D009682:Magnetic Resonance Spectroscopy
D008297:Male
D008875:Middle Aged
D013345:Subarachnoid Hemorrhage

magnetic resonance cisternography
cerebral infarction
subarachnoid hemorrhage
Anterior cerebral artery dissection


Dynamic changes in biomarkers in acute human immunodeficiency virus infections: a case report.

Abstract:
BACKGROUND
The highest incidence of human immunodeficiency virus infection in China is among men who have sex with men. This case report aims to describe the dynamic changes in biomarkers in an acute human immunodeficiency virus infection of a Han Chinese man who has sex with men, and to illustrate the possibility of using these biomarkers for the early detection of human immunodeficiency virus infection in Chinese hospital settings.

CASE PRESENTATION
The 25-year-old Han Chinese male patient presented himself with an 8-day history of symptoms and signs of upper respiratory viral infections to a sexually transmitted infection clinic of a hospital setting in Shanghai. The viral load of human immunodeficiency virus, p24 antigen-antibody complex, and lymphocyte subsets of blood samples were repeatedly measured over the next 39 days. The human immunodeficiency virus from serum was genotyped. This patient was diagnosed as a human immunodeficiency virus infection, and the viral genotype was CRF 01_AE. The onset of the symptoms and signs was 12 days after his last reported unprotected intercourse with a human immunodeficiency virus -infected man. The patient had detectable levels of p24 antigen at his first visit, 20 days after infection, and the HIV viral load was at the highest point (8 × 106 copies/ml). A low concentration of antibody to HIV was observed in the patient's serum 10 days after his 1st visit (30 days after infection). The confirmation of human immunodeficiency virus infection by Western blot assays was made at day 20 after his 1st visit (40 days after infection).

CONCLUSIONS
Symptoms of acute human immunodeficiency virus infection are non-specific. Specific laboratory markers appear shortly after HIV infections. The first biomarker detected from serum is the viral RNA and p24 antigen, followed by HIV-specific antibody. The results suggest that there are urgent needs for both human immunodeficiency virus antigen and antibody testing in routine medical practice, and that human immunodeficiency virus RNA testing should be recommended to detect early infection. Ethics approval was obtained from the Ethics Board of the Shanghai Dermatology Hospital.

Gu|Wei-Ming|WM| Hu|Yi|Y| Hu|Wei-Zhong|WZ| Xu|Biao|B|

Biomarkers
China
Men who have sex with men
p24 antigen
Antibody testing
Acute infection
HIV case report


Detection of macroalgae blooms by complex SAR imagery.

Abstract: Increased frequency and enhanced damage to the marine environment and to human society caused by green macroalgae blooms demand improved high-resolution early detection methods. Conventional satellite remote sensing methods via spectra radiometers do not work in cloud-covered areas, and therefore cannot meet these demands for operational applications. We present a methodology for green macroalgae bloom detection based on RADARSAT-2 synthetic aperture radar (SAR) images. Green macroalgae patches exhibit different polarimetric characteristics compared to the open ocean surface, in both the amplitude and phase domains of SAR-measured complex radar backscatter returns. In this study, new index factors are defined which have opposite signs in green macroalgae-covered areas, compared to the open water surface. These index factors enable unsupervised detection from SAR images, providing a high-resolution new tool for detection of green macroalgae blooms, which can potentially contribute to a better understanding of the mechanisms related to outbreaks of green macroalgae blooms in coastal areas throughout the world ocean.

Shen|Hui|H| Perrie|William|W| Liu|Qingrong|Q| He|Yijun|Y|

Green macroalgae blooms
Synthetic aperture radar (SAR)
High resolution early detection
Unsupervised SAR index factor


European society of contraception statement on contraception in obese women.

Abstract: The obesity 'epidemic' continues to increase, mostly but not only in developed countries. As overweight and obese women are at an increased risk for venous thromboembolism (VTE) at baseline and at a much higher risk during pregnancy, it is essential to help these women to plan pregnancies carefully and to use contraceptives with a positive ratio of benefits versus risks. The Expert Group on hormonal and molecular contraception of the European Society of Contraception convened to review the existing evidence and propose recommendations to the prescribers in line with most recent studies and with the Medical Eligibility Criteria of the World Health Organisation.

Merki-Feld|Gabriele S|GS|
Skouby|Sven|S|
Serfaty|David|D|
Lech|Medard|M|
Bitzer|Johannes|J|
Crosignani|Pier Giorgio|PG|
Cagnacci|Angelo|A|
Sitruk-Ware|Regine|R|

Obesity
Contraceptive failure
Depo-medroxyprogesterone
Efficacy
Hormonal contraception
Progestin-only contraception
Thromboembolic risk
Weight


Basolateral amygdala lesions abolish mutual reward preferences in rats.

Abstract: In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding ("Both Reward") or not rewarding a partner rat ("Own Reward"), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected.

Hernandez-Lallement|Julen|J|
van Wingerden|Marijn|M|
Schäble|Sandra|S|
Kalenscher|Tobias|T|

Basolateral amygdala
Lesion
Rat
Pro-social
Pro-social Choice Task


Lin28-mediated temporal promotion of protein synthesis is crucial for neural progenitor cell maintenance and brain development in mice.

Abstract: Neural progenitor cells (NPCs) undergo rapid proliferation during neurulation. This rapid growth generates a high demand for mRNA translation in a timing-dependent manner, but its underlying mechanism remains poorly understood. Lin28 is an RNA-binding protein with two paralogs, Lin28a and Lin28b, in mammals. Mice with Lin28b deletion exhibit no developmental defects, whereas we have previously reported that Lin28a deletion leads to microcephaly. Here, we find that Lin28a/b double knockout (dKO) mice display neural tube defects (NTDs) coupled with reduced proliferation and precocious differentiation of NPCs. Using ribosomal protein 24 hypomorphic mice (Rpl24 ) as a genetic tool to dampen global protein synthesis, we found that Lin28a compound mutants exhibited NTDs resembling those seen in Lin28a/b dKO mice. Increased NPC numbers and brain sizes in Lin28a-overexpressing mice were rescued by Rpl24 heterozygosity. Mechanistically, polysome profiling revealed reduced translation of genes involved in the regulation of cell cycle, ribosome biogenesis and translation in dKO mutants. Ribosome biogenesis was reduced in dKO and increased in Lin28a-overexpressing NPCs. Therefore, Lin28-mediated promotion of protein synthesis is essential for NPC maintenance and early brain development.

Herrlinger|Stephanie|S| Shao|Qiang|Q|0000-0001-5307-8264 Yang|Mei|M| Chang|Qing|Q| Liu|Yang|Y| Pan|Xiaohan|X| Yin|Hang|H| Xie|Li-Wei|LW| Chen|Jian-Fu|JF|0000-0002-8869-5913

Protein synthesis
Neural progenitor cell
Lin28
Neural tube defect
Ribosome biogenesis


The combined effects of rising temperature and salinity may halt the future proliferation of symbiont-bearing foraminifera as ecosystem engineers.

Abstract: Rising sea surface temperatures and extreme heat waves are affecting symbiont-bearing tropical calcifiers such as corals and Large Benthic Foraminifera (LBF). In many ecosystems, parallel to warming, global change unleashes a host of additional changes to the marine environment, and the combined effect of such multiple stressors may be far greater than those of temperature alone. One such additional stressor, positively correlated to temperature in evaporation-dominated shallow-water settings is rising salinity. Here we used laboratory culture experiments to evaluate the combined thermohaline tolerance of one of the most common LBF species and carbonate producer, Amphistegina lobifera. The experiments were done under ambient (39 psu) and modified (30, 45, 50 psu) salinities and at optimum (25 °C) and warm temperatures (32 °C). Calcification of the A. lobifera holobiont was evaluated by measuring alkalinity loss in the culturing seawater, as an indication of carbonate ion uptake. The vitality of the symbionts was determined by monitoring pigment loss of the holobiont and their photosynthetic performances by measuring dissolved oxygen. We further evaluated the growth of Peneroplis (P. pertusus and P. planatus), a Rhodophyta bearing LBF, which is known to tolerate high temperatures, under elevated salinities. The results show that the A. lobifera holobiont exhibits optimal performance at 39 psu and 25 °C, and its growth is significantly reduced upon exposure to 30, 45, 50 psu and under all 32 °C treatments. Salinity and temperature exhibit a significant interaction, with synergic effects observed in most treatments. Our results confirm that Peneroplis has a higher tolerance to elevated temperature and salinity compared to A. lobifera, implying that a further increase of salinity and temperatures may result in a regime shift from Amphistegina- to Peneroplis-dominated assemblages.

Kenigsberg|Chen|C| Titelboim|Danna|D| Ashckenazi-Polivoda|Sarit|S| Herut|Barak|B| Kucera|Michal|M| Zukerman|Yuval|Y| Hyams-Kaphzan|Orit|O| Almogi-Labin|Ahuva|A| Abramovich|Sigal|S|

Large Benthic Foraminifera
Calcification rates
Global warming
Net photosynthesis
Salinity rise
Symbiosis