Validating Utility of Dual Antiplatelet Therapy Score in a Large Pooled Cohort From 3 Japanese Percutaneous Coronary Intervention Studies.

Abstract:
BACKGROUND
The dual antiplatelet therapy (DAPT) score was developed to estimate ischemic and bleeding risks from the DAPT study. However, few studies validated its utility externally. We sought to validate the utility of the DAPT score in the Japanese population.

METHODS
In a pooled cohort of 3 studies conducted in Japan (the CREDO-Kyoto [Coronary Revascularization Demonstrating Outcome Study in Kyoto] Registry Cohort-2, RESET [Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial], and NEXT [NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial]), we compared risks for ischemic and bleeding events from 13 to 36 months after percutaneous coronary intervention among patients with a DAPT score ≥2 (high DS) and a DAPT score <2 (low DS).

RESULTS
Among 12 223 patients receiving drug-eluting stents who were free from ischemic or bleeding events at 13 months after percutaneous coronary intervention, 3944 patients had high DS and 8279 had low DS. The cumulative incidence of primary ischemic end point (myocardial infarction/stent thrombosis) was significantly higher in high DS than in low DS (1.5% versus 0.9%, P=0.002), whereas the cumulative incidence of primary bleeding end point (GUSTO moderate/severe) tended to be lower in high DS than in low DS (2.1% versus 2.7%, P=0.07). The cumulative incidences of cardiac death, myocardial infarction, and stent thrombosis were also significantly higher in high DS than in low DS (2.0% versus 1.4%, P=0.03; 1.5% versus 0.8%, P=0.002; 0.7% versus 0.3%, P<0.001, respectively), whereas the cumulative incidences of noncardiac death and GUSTO severe bleeding were significantly lower in high DS than in low DS (2.4% versus 3.9%, P<0.001; 1.0% versus 1.6%, P=0.03, respectively).

CONCLUSIONS
In the current population, the DAPT score successfully stratified ischemic and bleeding risks, although the ischemic event rate was remarkably low even in high DS. Further studies would be warranted to evaluate the utility of prolonged DAPT guided by the DAPT score.

Yoshikawa|Yusuke|Y| Shiomi|Hiroki|H| Watanabe|Hirotoshi|H| Natsuaki|Masahiro|M| Kondo|Hirokazu|H| Tamura|Toshihiro|T| Nakagawa|Yoshihisa|Y| Morimoto|Takeshi|T| Kimura|Takeshi|T|

dual antiplatelet therapy
percutaneous coronary intervention
DAPT score
drug-eluting stent


Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity.

Abstract: Neuronopathic glycosphingolipidoses are a sub-group of lysosomal storage disorders for which there are presently no effective therapies. Here, we evaluated the potential of substrate reduction therapy (SRT) using an inhibitor of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide (GL1) and related glycosphingolipids. The substrates that accumulate in Sandhoff disease (e.g., ganglioside GM2 and its nonacylated derivative, lyso-GM2) are distal to the drug target, GCS. Treatment of Sandhoff mice with a GCS inhibitor that has demonstrated CNS access (Genz-682452) reduced the accumulation of GL1 and GM2, as well as a variety of disease-associated substrates in the liver and brain. Concomitant with these effects was a significant decrease in the expression of CD68 and glycoprotein non-metastatic melanoma B protein (Gpnmb) in the brain, indicating a reduction in microgliosis in the treated mice. Moreover, using in vivo imaging, we showed that the monocytic biomarker translocator protein (TSPO), which was elevated in Sandhoff mice, was normalized following Genz-682452 treatment. These positive effects translated in turn into a delay (∼28 days) in loss of motor function and coordination, as measured by rotarod latency, and a significant increase in longevity (∼17.5%). Together, these results support the development of SRT for the treatment of gangliosidoses, particularly in patients with residual enzyme activity.

Marshall|John|J|
Nietupski|Jennifer B|JB|
Park|Hyejung|H|
Cao|James|J|
Bangari|Dinesh S|DS|
Silvescu|Cristina|C|
Wilper|Terry|T|
Randall|Kristen|K|
Tietz|Drew|D|
Wang|Bing|B|
Ying|Xiaoyou|X|
Leonard|John P|JP|
Cheng|Seng H|SH|

substrate reduction therapy
Sandhoff disease
glucosylceramide synthase
lysosomal storage disorder
glycosphingolipid
in vivo imaging
GM2 gangliosidosis
tissue mass spectrometry imaging


Chronic Myeloid Leukemia-the Promise of Tyrosine Kinase Inhibitor Discontinuation.

Abstract: Some believe that tyrosine kinase inhibitor (TKI) therapy is as close to perfect as it gets in oncologic therapy. Patients diagnosed with chronic myeloid leukemia (CML) are treated with a daily oral therapy, through which most achieve remission. TKI therapy is not associated with classic chemotherapy side effects, and most patients are able to resume their normal activities of daily living. Moreover, recent data has demonstrated that CML does not affect the life expectancy of patients whose disease is well controlled with a TKI. However, TKI therapy is actually not that perfect. Patients need to stay on therapy forever. They have to remember to take their medications daily. TKIs are expensive, and the financial burden to patient and society cannot be overstated. Most patients' health-related quality of life is affected; common side effects include fatigue, muscle cramps, pain, edema, skin problems, and gastrointestinal symptoms. In addition, concerns about long-term side effects remain. Recently several studies have shown the feasibility and safety of discontinuation in a select group of patients. Herein, we will review the currently available data on stopping TKIs in CML.

Narra|Ravi Kishore|RK|
Flynn|Kathryn E|KE|
Atallah|Ehab|E|

D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Tyrosine kinase inhibitor discontinuation


Endothelin 1 gene as a modifier in dilated cardiomyopathy.

Abstract: Dilated cardiomyopathy (DCM) is a myocardial disease of unknown etiology with left ventricular dilatation and impaired myocardial contractility leading to heart failure. It is considered to be a multifactorial disorder with the interplay of both genetic and environmental factors. One of the possible genes implicated in DCM is endothelin 1 (EDN1). The genetic variants of EDN1 may be involved in the pathophysiology of DCM hence the entire EDN1 gene was screened to examine for the possible genotypic associations with DCM. A total of 115 DCM patients and 250 control subjects were included in the present study. PCR based SSCP analysis was carried out followed by commercial sequencing. Screening of EDN1 revealed two common and two rare polymorphisms. Allelic and genotypic frequencies were estimated in patient and control groups by appropriate statistical tests. The heterozygotes of insertion variation (+138A) were found to exhibit four-fold increase risk to DCM (OR=4.12, 95% CI 2.10-8.08; p=0.0001). The two rare variants (G>A transition (rs150035515) at c.90 and C>T transition (rs149399492) at c.119) observed in the present study were found to be unique in DCM. The secondary mRNA structures of these variations were found to have less free energy than wild type. The haplotype analysis revealed 4A-T to be risk haplotype for DCM (OR 5.90, 95% CI 2.29-15.25, p=0.0001). In conclusion, EDN1 polymorphisms (+138A, A30A, T40I) appear to play a significant role in the pathogenesis of DCM, as they influence the stability of protein. The increased EDN1 production may lead to constriction of coronary arteries, reducing coronary blood flow which may in turn increase the load on left ventricle, impairing contractility of the heart resulting in a DCM phenotype, an end stage of heart failure.

Matsa|Lova Satyanarayna|LS|
Sagurthi|Someswar Rao|SR|
Ananthapur|Venkateshwari|V|
Nalla|Swapna|S|
Nallari|Pratibha|P|

D020022:Genetic Predisposition to Disease

Endothelin
Dilated cardiomyopathy
Hemodynamics
Vasoconstriction


Antifungal therapies in murine infections by Candida kefyr.

Abstract: Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 μg ml-1 at different time points and efficacy of the drugs was evaluated in a systemic model of candidiasis, conducted in immunosuppressed mice, through survival, (1→3)-β-D-glucan levels in serum and fungal load in kidneys. AMB and CFG showed fungicidal and FLC fungistatic activity against both isolates. The three drugs were able to reduce fungal burden in kidneys and (1→3)-β-D-glucan concentration in serum of infected mice, with CFG showing the highest efficacy, followed by FLC. In conclusion, CFG showed efficacy over AMB and FLC against the systemic candidiasis by C. kefyr. The established epidemiological cut-off for anidulafungin seems the best indicator of outcome for echinocandins.

Sanchis|Marta|M| Martin-Vicente|Adela|A| Capilla|Javier|J| Guarro|Josep|J|

antifungals
Candida kefyr
amphotericin B
fluconazole
Caspofungin
murine model


Sclerosing Mediastinitis Presenting as Complete Heart Block.

Abstract: Sclerosing Mediastinitis (SM) is a rare condition which is characterized by the presence of dense fibrosis which infiltrates and encroaches upon various structures in the mediastinal cavity. Depending on the extent and the predominant organ of involvement, the patient presents with symptomatology of dysphagia, superior vena cava compression syndrome or dyspnoea. However, the involvement of the heart is rarely seen. Aetiologies of SM are several, with infections being the most common. We discuss a case of SM involving the oesophagus, descending aorta, hilum of lungs and the heart secondary to mucormycosis in an immunocompetent male.

Bharadwaj|Reena|R|
Madakshira|Manoj Gopal|MG|
Bharadwaj|Prashant|P|
Sidhu|Hardeep Singh|HS|

Mediastinal cavity
Mucormycosis
Immunocompetent


The history of peritoneal dialysis in China: past, present and future trends.

Abstract: Peritoneal dialysis (PD) was introduced in China more than 60 years ago and has grown continuously since then. Now China leads the first of the world in number of patients on PD. In this manuscript a brief review of the history of peritoneal dialysis in China is presented; this includes a description of pioneers and their important contributions, discussion of peritoneal dialysate, the technique of the use of Tenckhoff catheter, the use of continuous ambulatory peritoneal dialysis (CAPD) and dialysis registration. Current ongoing PD research activities among Chinese PD academicians are also discussed. Finally, we present four areas of future focus: 1) the promotion of PD in rural areas where PD use is still very limited due to the lack of PD awareness and education; 2) PD quality management and continuous quality improvement (CQI) program particularly focusing on PD adequacy and patient rehabilitation; 3) development and enforcement of national standards on PD management; 4) multi-center studies to compare the benefits of PD and hemodialysis (HD) that should include survival, rehabilitation and cost-effectiveness.

Bi|Shu-Hong|SH|
Chen|Weiyu|W|
Wu|Jimmy S|JS|
Wang|Tao|T|
Ahmad|Suhail|S|

history
Peritoneal dialysis
China
registration


Nedaplatin Plus Docetaxel Versus Cisplatin Plus Docetaxel as First-Line Chemotherapy for Advanced Squamous Cell Carcinoma of the Lung - A Multicenter, Open-label, Randomized, Phase III Trial.

Abstract:
INTRODUCTION
This study aimed to compare the efficacy of first-line nedaplatin (80 mg/m2) plus docetaxel (75 mg/m2) (ND) versus cisplatin (75 mg/m2) plus docetaxel (75 mg/m2) (CD) in patients with advanced squamous cell lung carcinoma.

METHODS
This open-label randomized controlled phase III trial was performed at 12 hospitals in China. Patients with squamous cell lung carcinoma were randomized to four cycles of ND or CD. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time to progression, best overall response, and adverse events.

RESULTS
In the intent-to-treat analysis set (ND: n = 141; CD: n = 139), median PFS was 4.63 months (95% confidence interval: 4.43-5.10) for the ND and 4.23 months (95% confidence interval: 3.37-4.53) for CD groups (p = 0.056). No significant difference in time to progression was observed between the two groups. Best overall responses and disease control rate were better with ND 51.5%, than with CD 38.1% (p = 0.033 and p = 0.0004, respectively). Grade III or IV adverse events and grade 3-4 nausea and fatigue were more frequent in the CD group compared with the ND group (all p < 0.05).

CONCLUSIONS
There is no improvement in PFS with the nedaplatin and docetaxel combination in the intent-to-treat analysis. More hematologic toxicities were observed in the ND group (compared with CD), whereas more nonhematologic toxicities were observed in the CD group. ND could be a new treatment option for advanced or relapsed squamous cell lung cancer (NCT02088515 at ClinicalTrials.gov).

Lu|Shun|S| Chen|Zhiwei|Z| Hu|Chengping|C| Zhang|Jian|J| Chen|Yuan|Y| Song|Yong|Y| Zhao|Qiong|Q| Fan|Yun|Y| Wu|Gang|G| Ma|Zhiyong|Z| Fang|Jian|J| Yu|Qitao|Q| Liu|Zhe|Z|

D000971:Antineoplastic Combined Chemotherapy Protocols

Nedaplatin
Docetaxel
Cisplatin
Phase III
Squamous cell lung carcinoma
Randomized controlled trial


Case Fatality as an Indicator for the Human Toxicity of Pesticides-A Systematic Scoping Review on the Availability and Variability of Severity Indicators of Pesticide Poisoning.

Abstract:
OBJECTIVE
To investigate if case fatality and other indicators of the severity of human pesticide poisonings can be used to prioritize pesticides of public health concern. To study the heterogeneity of data across countries, cause of poisonings, and treatment facilities.

METHODS
We searched literature databases as well as the internet for studies on case-fatality and severity scores of pesticide poisoning. Studies published between 1990 and 2014 providing information on active ingredients in pesticides or chemical groups of active ingredients were included. The variability of case-fatality-ratios was analyzed by computing the coefficient of variation as the ratio of the standard deviation to the mean.

FINDINGS
A total of 149 papers were identified of which 67 could be included after assessment. Case-fatality-ratio (CFR) on 66 active ingredients and additionally on 13 groups of active ingredients were reported from 20 countries. The overall median CFR for group of pesticides was 9%, for single pesticides 8%. Of those 12 active ingredients with a CFR above 20% more than half are WHO-classified as "moderately hazardous" or "unlikely to present acute hazard". Two of seven pesticides considered "unlikely to present hazard in normal use" showed a CFR above 20%. The cross-study variability of reported case fatality was rather low. Studies most often utilized the Glasgow Coma Score for grading the severity of poisoning.

CONCLUSION
Although human pesticide poisoning is a serious public health problem, an unexpectedly small number of publications report on the clinical outcomes within our study period. However, CFRs of acute human pesticide poisoning are available for several groups of pesticides as well as for active ingredients showing moderate cross-study variability. Our results underline that CFR is an indicator of the human toxicity of pesticides and can be utilized to prioritize highly hazardous pesticides especially since there is limited correspondence between the animal-test-based hazard classification and the human CFR of the respective pesticide. The reporting of available poisoning data should be improved, human case-fatality data are a reasonable tool to be included systematically in the periodic statutory review of pesticides and their regulation.

pesticides
poisoning
case-fatality
severity scores
highly hazardous


Suppression of CSN5 promotes the apoptosis of gastric cancer cells through regulating p53-related apoptotic pathways.

Abstract: As one of the COP9 signalosome complex, CSN5 (also known as Jab1) has been confirmed overexpression in many human cancers and affected multiple pathways associating with cell proliferation and apoptosis. Correlation of CSN5 overexpression with poor prognosis for cancer provides evidence that it is involved in the tumorigenesis. However, little is known about the functional role and the underlying mechanism of CSN5 in gastric cancer progression. In the current study, the effect of CSN5 siRNA (small-interfering RNA) on the proliferation and apoptosis of human gastric cancer cells (AGS and MKN45) were examined. Our results showed that knockdown of CSN5 could inhibit proliferation and promote apoptosis of gastric cancer cells. Additionally, suppression of CSN5 expression contributed to the increased expression levels of p53 and Bax. In conclusion, CSN5 overexpression is significantly correlated with gastric cancer progression, and CSN5 could be a novel target in gastric cancer therapy.

Sang|Miao-Miao|MM| Du|Wen-Qi|WQ| Zhang|Rui-Yan|RY| Zheng|Jun-Nian|JN| Pei|Dong-Sheng|DS|

D015972:Gene Expression Regulation, Neoplastic

D047908:Intracellular Signaling Peptides and Proteins

Apoptosis
Gastric cancer
Proliferation
siRNA
p53
CSN5/Jab1


Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015.

Abstract: In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013-2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.

Kretz|Cecilia B|CB|
Retchless|Adam C|AC|
Sidikou|Fati|F|
Issaka|Bassira|B|
Ousmane|Sani|S|
Schwartz|Stephanie|S|
Tate|Ashley H|AH|
Pana|Assimawè|A|
Njanpop-Lafourcade|Berthe-Marie|BM|
Nzeyimana|Innocent|I|
Nse|Ricardo Obama|RO|
Deghmane|Ala-Eddine|AE|
Hong|Eva|E|
Brynildsrud|Ola Brønstad|OB|
Novak|Ryan T|RT|
Meyer|Sarah A|SA|
Oukem-Boyer|Odile Ouwe Missi|OOM|
Ronveaux|Olivier|O|
Caugant|Dominique A|DA|
Taha|Muhamed-Kheir|MK|
Wang|Xin|X|
|||

D038542:Neisseria meningitidis, Serogroup C

Neisseria meningitidis serogroup C
Niger
Meningococcal meningitis
bacteria
meningitis belt
whole-genome sequencing


Healing of Artificially Created Gap Non-union Using Autologous Cultured Osteoblasts Impregnated Over Three-Dimensional Biodegradable Scaffold: An Experimental Study (Rabbit).

Abstract:
Background
The large bone defect often require bone transplant or its substitutes to restore bone integrity which have some limitations. The study was conducted to analyze role of autologous osteoblast that are amplified in vivo and impregnated in a synthesized three-dimensional gelatin hydroxyapatite scaffold for treating artificially created critical size defect in rabbit's iliac crest.

Methods
In this research, 4-month-old ten healthy white male rabbits of average weight 2-3 kg were chosen. Osteoblasts cells were isolated from the rabbit iliac crest and were taken in transfer medium to the laboratory and cultured for 2-3 weeks. These osteoblast cells were seed on 3-dimensional scaffold and culture the construct for 2 weeks. The cultured autologous osteoblasts over the scaffold were transplanted into the defect by reopening the iliac crest of the same rabbit from which is cells were extracted. Serial radiograph of pelvis was done to see progressive signs of union.

Results
Out of ten rabbits chosen for study two rabbits were passed during study. Gross and radiological examination of rabbits was done at 0, 4, 8 and 12 weeks. Features of union was seen in six rabbits on follow-up. There is no signs of union or minimal new bone formation around the implant material were seen in two case.

Conclusion
The study demonstrated using autologous cultured osteoblasts impregnated over three-dimensional biodegradable scaffold for large bone defect is a good option. The importance of three-dimensional biodegradable scaffold is that it provide scaffolding for sufficient interval for new bone formation.

Singh|Vikas|V|
Singh|Mahipat|M|0000-0002-7129-630X
Belbase|Rupesh Jung|RJ|
Rastogi|Amit|A|


Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor-bearing rats.

Abstract: The response to glucagon and adrenaline in cancer cachexia is poorly known. The aim of this study was to investigate the response to glucagon, adrenergic agonists (α and β) and cyclic adenosine monophosphate (cAMP) on glycogenolysis, gluconeogenesis, and glycolysis in liver perfusion of Walker-256 tumor-bearing rats with advanced cachexia. Liver ATP content was also investigated. Rats without tumor (healthy) were used as controls. Agonists α (phenylephrine) and β (isoproterenol) adrenergic, instead of adrenaline, and cAMP, the second messenger of glucagon and isoproterenol, were used in an attempt to identify mechanisms involved in the responses. Glucagon (1 nM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in the liver of healthy and tumor-bearing rats, but their effects were lower in tumor-bearing rats. Isoproterenol (20 µM) stimulated glycogenolysis, gluconeogenesis, and glycolysis in healthy rats and had virtually no effect in tumor-bearing rats. cAMP (9 µM) also stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in healthy rats but had practically no effect in tumor-bearing rats. Phenylephrine (2 µM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis and these effects were also lower in tumor-bearing rats than in healthy. Liver ATP content was lower in tumor-bearing rats. In conclusion, tumor-bearing rats with advanced cachexia showed a decreased hepatic response to glucagon, adrenergic agonists (α and β), and cAMP in glycogenolysis, gluconeogenesis, and glycolysis, which may be due to a reduced rate of regulatory enzyme phosphorylation caused by the low ATP levels in the liver.

D058646:Adrenergic alpha-1 Receptor Agonists

hepatic response
cancer
ATP
glucose metabolism
hormones


The AtMYB12 activation domain maps to a short C-terminal region of the transcription factor.

Abstract: The Arabidopsis thaliana R2R3-MYB transcription factor MYB12 is a light-inducible, flavonol-specific activator of flavonoid biosynthesis. The transactivation activity of the AtMYB12 protein was analyzed using a C-terminal deletion series in a transient A. thaliana protoplast assay with the goal of mapping the activation domain (AD). Although the deletion of the last 46 C-terminal amino acids did not affect the activation capacity, the deletion of the last 98 amino acids almost totally abolished transactivation of two different target promoters. A domain swap experiment using the yeast GAL4 DNA-binding domain revealed that the region from positions 282 to 328 of AtMYB12 was sufficient for transactivation. In contrast to the R2R3-MYB ADs known thus far, that of AtMYB12 is not located at the rearmost C-terminal end of the protein. The AtMYB12 AD is conserved in other experimentally proven R2R3-MYB flavonol regulators from different species.

D018506:Gene Expression Regulation, Plant

activation domain
transcription factor
MYB12
flavonol regulator
production of flavonol glycosides


Sensitivity analysis of heat and mass transfer characteristics during forced-air cooling process of peaches on different air-inflow velocities.

Abstract: Peach is one of the most perishable fruits. During forced-convection cooling, the heat sources (respiratory and evaporative latent heat) internal to freshly harvested peaches have a remarkable influence on its evaluation of cooling characteristics with respect to various cooling strategies. Therefore, to improve the accuracy of simulation results in peaches cooling, the term of heat source was coded as detailed procedures and included into a computational fluid dynamics (CFD) model. By comparing the temperature simulated with and without considering these heat sources, it is found that a reasonable decrease in variations of cooling performances is obtained with sustained increase in air-inflow velocities. A maximum discrepancy in peaches volume-weighted average temperature (∆T vwa-max) is mainly concentrated in 0.1-0.3°C when the air-inflow velocity not exceeds 1.7 m/s, and its corresponded 7/8ths cooling time (SECT) is also prolonged by 1-6 min. This means that, below 1.7 m/s, these heat sources should be added as a term into the heat transfer equations for modifying the mathematical model inside peaches computational domain. Furthermore, the feasibility of this modeling method is confirmed by a great agreement with experiments, and its modified model has a higher accuracy with the decreased RMSE and MAPE values of 6.90%-11.26% and 7.28%-12.95%, respectively.

freshly harvested peaches
computational fluid dynamics
forced‐air cooling
heat source term
precooling performance


The Amyloid Region of Hfq Riboregulator Promotes DsrA:rpoS RNAs Annealing.

Abstract: Hfq is a bacterial RNA chaperone which promotes the pairing of small noncoding RNAs to target mRNAs, allowing post-transcriptional regulation. This RNA annealing activity has been attributed for years to the N-terminal region of the protein that forms a toroidal structure with a typical Sm-fold. Nevertheless, many Hfqs, including that of Escherichia coli, have a C-terminal region with unclear functions. Here we use a biophysical approach, Synchrotron Radiation Circular Dichroism (SRCD), to probe the interaction of the E. coli Hfq C-terminal amyloid region with RNA and its effect on RNA annealing. This C-terminal region of Hfq, which has been described to be dispensable for sRNA:mRNA annealing, has an unexpected and significant effect on this activity. The functional consequences of this novel property of the amyloid region of Hfq in relation to physiological stress are discussed.

RNA chaperone
DsrA noncoding RNA
RNA/RNA annealing
bacterial amyloid
functional amyloid
stress adaptation


Thermal perception thresholds among workers in a cold climate.

Abstract:
PURPOSE
To investigate whether exposure to cold could influence the thermal perception thresholds in a working population.

METHODS
This cross-sectional study was comprised of 251 males and females and was carried out at two mines in the northern part of Norway and Sweden. The testing included a baseline questionnaire, a clinical examination and measurements of thermal perception thresholds, on both hands, the index (Digit 2) and little (Digit 5) fingers, for heat and cold.

RESULTS
The thermal perception thresholds were affected by age, gender and test site. The thresholds were impaired by experiences of frostbite in the fingers and the use of medication that potentially could affect neurosensory functions. No differences were found between the calculated normative values for these workers and those in other comparative investigations conducted in warmer climates.

CONCLUSIONS
The study provided no support for the hypothesis that living and working in cold climate will lead to impaired thermal perception thresholds. Exposure to cold that had caused localized damage in the form of frostbite was shown to lead to impaired thermal perception.

Neurosensory function
Normative values
Cold temperature
Mine work
Sensory threshold


Incorporating model uncertainty into the evaluation of interventions to reduce microcontaminant loads in rivers.

Abstract: Models of microcontaminant fate and transport in wastewater treatment plants (WWTPs) and rivers have been developed and used to assist decision-making in the field of water management. These models come with parameter uncertainties that must be properly incorporated in the decision-making process. The main goal of this study is to evaluate how the magnitudes of key model parameter uncertainties influence the selection of end-of-pipe interventions (at WWTPs) designed to reduce the microcontaminant loads in rivers. We developed a model that describes the fate and removal of pharmaceuticals in WWTPs and the river network based on 3 key parameters: human pharmaceutical consumption and excretion (F) and the pharmaceutical degradation constants in WWTPs (kWWTP) and rivers (kriver). We modelled the fate and transport of diclofenac in the Llobregat River basin (NE Spain). We calibrated the model using a Bayesian approach, which resulted in an accurate prediction of measured diclofenac loads at 9 locations along the Llobregat River and at the influents and effluents of 2 WWTPs (R2 = 0.95). Using different scenarios, we evaluated three levels of uncertainty in the key model parameters. The first level of uncertainty corresponded to the reference distributions obtained from the Bayesian calibration. Then, for each parameter, we generated a narrower PDF (decreased uncertainty with respect to the reference) and a wider PDF (increased uncertainty). For each level of uncertainty, we evaluated increasing removal efficiencies of diclofenac at the WWTPs, from 38% to 98%. We assumed that removal efficiencies of up to 75% can be achieved by upgrading secondary treatment; beyond 75%, tertiary treatment is needed. The scenario analysis showed that achieving diclofenac removal efficiencies corresponding to tertiary treatment results in apparent concentration reductions (statistically significant differences relative to the reference situation), regardless of the level of uncertainty applied to the model parameters. However, upgrades in the secondary treatment resulted in apparent reductions only in the case of reduced uncertainty. We concluded that model uncertainty greatly influences the decisions that river basin authorities must make to reduce the microcontaminant loads released by WWTPs into rivers. In addition, we discussed research priorities to help reduce model uncertainty and thereby make more appropriate decisions.

Gimeno|P|P| Marcé|R|R| Bosch|Ll|L| Comas|J|J| Corominas|Ll|L|

Uncertainty
Decision-making
Pharmaceuticals
Catchment modelling
Microcontaminant modelling
WWTP upgrades


Efficacy of active compounds of Chanqin granules on airway neurogenic inflammation induced by PM2.5 in vivo.

Abstract:
OBJECTIVE
To investigate the efficacy of active compounds of Chanqin (CQ) granules on PM2.5-induced airway neurogenic inflammation in vivo, and to elucidate the underlying mechanisms of action.

METHODS
The Traditional Chinese Medicine systems pharmacology (TCMSP) database was searched, and the results were combined with oral bioavailability and drug analysis to identify the compounds in CQ granules. The pharmacophore modeling approach was used to predict the compound targets, and the diseases corresponding to the targets were obtained by searching the therapeutic target database (TTD), pharmacogenomics knowledgebase (PharmGKB) and DrugBank databases. Cytoscape software was used to construct the network pharmacological charts for Component-Target and Target-Disease interactions of the CQ granules. Then, the mechanisms of action and effectiveness of CQ granules for the treatment of PM2.5-induced airway neurogenic inflammation were analyzed.

RESULTS
A total of 195 compounds and 171 targets were obtained from the analyses. A total of 569 corresponding diseases were identified for these targets. Component-target and target-disease networks were constructed. The possible mechanisms and effective components in CQ granules for treating airway neurogenic inflammation were analyzed. Quercetin, kaempferol and isorhamnetin, beta-sitosterol and sitosterol, which are typically found in the formulation, have extensive pharmacological activities, including anti-inflammatory, antioxidant and antiviral actions and neuroprotective properties. Among these targets, androgen receptor, estrogen receptor, prostaglandin G/H synthase 2, and inducible nitric oxide synthase play important pathological roles, including the induction of neurogenic inflammation. CQ granules may have therapeutic effectiveness for numerous diseases in addition to respiratory diseases, including neoplasms, digestive system diseases, cardiovascular diseases, respiratory tract diseases and nervous system diseases. In vivo, CQ granules are effective in treating pulmonary inflammation and downregulate neuropeptides in the bronchoalveolar lavage fluid after PM2.5 exposure. CQ granules significantly decreased the levels of neurokinin A, neurokinin B and calcitonin gene-related peptide in the lung and dorsal root ganglia. CQ also significantly suppressed the upregulation of p-extracellular regulated protein kinase 1/2 and p-methyl ethyl ketone 1/2 induced by PM2.5 exposure.

CONCLUSION
CQ granules have potential for the treatment of neurogenic inflammation induced by PM2.5 in vivo, and the mechanism might involve downregulation of neuropeptides in the BALF, lung and dorsal root ganglia.

Neurogenic inflammation
PM2.5
Pharmacology
Neuropeptide
Chan Qin granule
Ganglia, spinal
MAP kinase signaling system


Clinical evaluation of a first trimester pregnancy algorithm predicting the risk of small for gestational age neonates.

Abstract:
BACKGROUND
The Fetal Medicine Foundation developed a multiple logistic regression algorithm for risk prediction of delivering a small for gestational age neonate.

AIM
To validate this algorithm in an Australian population.

METHODS
At the combined first trimester screen participants' medical histories, demographic data, mean arterial pressure, uterine artery pulsatility index and pregnancy-associated plasma protein-A were assessed. After delivery, risk of delivering a small for gestational age neonate at <37 or ≥37 weeks gestation was retrospectively calculated using the Fetal Medicine Foundation algorithm.

RESULTS
Three thousand and eight women underwent prediction of risk for delivering a small for gestational age neonate. The algorithm detected 15.0% (95% CI: 3.2-37.9) of small for gestational age neonates delivered <37 weeks gestation at a fixed 10% false positive rate (or 35.0% (95% CI: 15.4-59.2) at a fixed 20% false positive rate). It detected 23.4% (95% CI: 16.1-30.7) of small for gestational age neonates delivered ≥37 weeks gestation at a fixed 10% false positive rate (or 39.1% (95% CI: 30.7-47.5) at a fixed 20% false positive rate). The algorithm performed significantly better than individual parameters (P < 0.05). The area under the receiver operating characteristic curve was 0.68 (95% CI: 0.56-0.80) and 0.70 (95% CI: 0.65-0.74) for small for gestational age neonates at <37 and ≥37 weeks gestation, respectively.

CONCLUSIONS
The Fetal Medicine Foundation algorithm for first trimester prediction of small for gestational age neonates does not perform as well in an Australian population as in the original United Kingdom cohort. However, it performs significantly better than any individual test parameter in both preterm and term neonates. Incorporation of further variables may help improve screening efficacy.

Graham|Kathryn|K|0000-0002-5245-5491
Park|Felicity|F|
McLennan|Andrew|A|
Pelosi|Marilena|M|
Williams|Paul|P|
Poon|Liona C|LC|
Hyett|Jon|J|

D007236:Infant, Small for Gestational Age

small for gestational age
first trimester screening
mean arterial pressure
PAPP-A
uterine artery Doppler


Radiological prognostic factors of chronic subdural hematoma recurrence: a systematic review and meta-analysis.

Abstract:
PURPOSE
Chronic subdural hematoma (CSDH) is associated with high recurrence rates. Radiographic prognostic factors may identify patients who are prone for recurrence and who might benefit further optimization of therapy. In this meta-analysis, we systematically evaluated pre-operative radiological prognostic factors of recurrence after surgery.

METHODS
Electronic databases were searched until September 2020 for relevant publications. Studies reporting on CSDH recurrence in symptomatic CSDH patients with only surgical treatment were included. Random or fixed effects meta-analysis was used depending on statistical heterogeneity.

RESULTS
Twenty-two studies were identified with a total of 5566 patients (mean age 69 years) with recurrence occurring in 801 patients (14.4%). Hyperdense components (hyperdense homogeneous and mixed density) were the strongest prognostic factor of recurrence (pooled RR 2.83, 95% CI 1.69-4.73). Laminar and separated architecture types also revealed higher recurrence rates (RR 1.37, 95% CI 1.04-1.80 and RR 1.76 95% CI 1.38-2.16, respectively). Hematoma thickness and midline shift above predefined cut-off values (10 mm and 20 mm) were associated with an increased recurrence rate (RR 1.79, 95% CI 1.45-2.21 and RR 1.38, 95% CI 1.11-1.73, respectively). Bilateral CSDH was also associated with an increased recurrence risk (RR 1.34, 95% CI 0.98-1.84).

LIMITATIONS
Limitations were no adjustments for confounders and variable data heterogeneity. Clinical factors could also be predictive of recurrence but are beyond the scope of this study.

CONCLUSIONS
Hyperdense hematoma components were the strongest prognostic factor of recurrence after surgery. Awareness of these findings allows for individual risk assessment and might prompt clinicians to tailor treatment measures.

Chronic subdural hematoma
Recurrence
CSDH
CT
Predictors


Design, synthesis chalcone derivatives as AdipoR agonist for type 2 diabetes.

Abstract: Two structurally novel series of chalcone derivatives were designed and synthesized as potential agents against type 2 diabetes. As a result of the antidiabetic biological evaluation in streptozotocin (STZ)-induced type 2 diabetes animal model, 13e, 13g, and 19f showed more significant reduction in serum Glu, TG, TC levels by contrast to the positive control AdipoRon. In addition to upregulating the expression of AdipoR1 and AdipoR2, 13e and 19f treatment also increased expression of AMPK and PPAR-α. Taken together, these results suggested that 13e and 19f might be a promising compound for type 2 diabetes treatment.

chalcone derivatives
adipoR
type 2 diabetes
expression


Hair analysis for detection of triptans occasionally used or overused by migraine patients-a pilot study.

Abstract:
PURPOSE
The aim of this study is to evaluate the detection rate of almotriptan, eletriptan, frovatriptan, sumatriptan, rizatriptan, and zolmitriptan in the hair of migraineurs taking these drugs; the degree of agreement between type of self-reported triptan and triptan found in hair; if the concentrations in hair were related to the reported cumulative doses of triptans; and whether hair analysis was able to distinguish occasional use from the overuse of these drugs.

METHODS
Out of 300 headache patients consecutively enrolled, we included 147 migraine patients who reported to have taken at least one dose of one triptan in the previous 3 months; 51 % of the patients overused triptans. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed.

RESULTS
All the triptans could be detected in the hair of the patients. The agreement between type of self-reported triptan and type of triptan found in hair was from fair to good for frovatriptan and zolmitriptan and excellent for almotriptan, eletriptan, sumatriptan, and rizatriptan (P < 0.01, Cohen's kappa). The correlation between the reported quantities of triptan and hair concentrations was statistically significant for almotriptan, eletriptan, rizatriptan, and sumatriptan (P < 0.01, Spearman's rank correlation coefficient). The accuracy of hair analysis in distinguishing occasionally users from overusers was high for almotriptan (ROC AUC = 0.9092), eletriptan (ROC AUC = 0.8721), rizatriptan (ROC AUC = 0.9724), and sumatriptan (ROC AUC = 0.9583).

CONCLUSIONS
Hair analysis can be a valuable system to discriminate occasional use from triptan overuse.

Ferrari|Anna|A| Baraldi|Carlo|C| Licata|Manuela|M| Vandelli|Daniele|D| Marchesi|Filippo|F| Palazzoli|Federica|F| Verri|Patrizia|P| Rustichelli|Cecilia|C| Giuliani|Enrico|E| Silingardi|Enrico|E|

Hair analysis
Triptan
Migraine
Medication-overuse headache
Monitoring
ROC curve


Prevalence and molecular characterization of Salmonella enterica serovar Typhimurium from ice and beverages in Jakarta, Indonesia.

Abstract:
OBJECTIVE
The presence of Salmonella enterica serovar Typhimurium becomes a concern in relation to the safety of drinking water and ice. We detected and enumerated the bacteria from ice and beverages collected from several areas in Jakarta. Most Probable Number (MPN) and multiplex PCR method were used. Three sets of primers were used rfbJ, fliC, and fljB. Two Multiplex PCR's were performed, the first is to detect the presence of Salmonella and the second is to confirm the positive isolate of S. enterica serovar Typhimurium.

RESULTS
A total of 50 beverages and 50 ices were collected MPN result ranged from < 3 to > 11,000 MPN/ml. The highest MPN value > 11,000 MPN/ml. The first Multiplex PCR result from beverages, 58% positively contained Salmonella spp. with amplification of fliB gene and no amplification of rfbJ and fliC genes. For ice samples, 2% positively contained Salmonella spp. with rfbJ gene amplification, 62% fliB gene and no amplification of fliC gene. The second Multiplex PCR results from beverages identified 21 positive isolates of S. enterica serovar Typhimurium. In which, 17 isolates contained fljB gene and 4 isolates contained both fljB and rfbJ genes. From ice, 17 isolates having both rfbJ and fljB genes.

Waturangi|Diana E|DE|
Wiratama|Eko|E|
Theresia|Audora Sabatini|AS|

D060885:Multiplex Polymerase Chain Reaction

Salmonella enterica serovar Typhimurium
Ice and beverages
PCR
Virulence


Diverse Bacteriophages Infecting the Bacterial Striped Catfish Pathogen Edwardsiella ictaluri.

Abstract: Bacteriophages infecting Edwardsiella ictaluri have been less investigated, although the host bacterium is one of the most important fish pathogens causing enteric septicemia of catfish (ESC). We present here two distinctly novel bacteriophages vB_EiM_PVN06 and vB_EiA_PVN09 infecting Edwardsiella ictaluri E1, with their geographical origins from the Mekong Delta, Vietnam. Bacteriophage vB_EiM_PVN06 native to a mud sample reveals complete differences of biological properties with the phage vB_EiA_PVN09 originated from a viscus of a healthy catfish (Pangasianodon hypophthalmus) cultured in the same area. Morphological analyses combined with genomic data indicate that phage vB_EiM_PVN06 is classified to Myoviridae family and shares high similarity with E. ictaluri phage PEi21 genome, while vB_EiA_PVN09 is a member of Teseptimavirus genus, Autographiviridae family, and mostly closes to phage vB_EcoP_IME390. The vB_EiA_PVN09 is a T7-like bacteriophage, which has been firstly found infecting to E. ictaluri, and host range analysis also evidences for the cross-infection of this phage to Escherichia coli K12 and Escherichia coli DH5α. Together, our research highlights the diversity of bacteriophages infecting the pathogen E. ictaluri and suggests further explorations of lytic phages in environmental niches, to be exploited in feasible strategies of phage therapy in ESC disease control.

Nguyen|Tan-Trung|TT|0000-0001-5219-8870
Xuan|Tran T T|TTT|
Ngoc|To H|TH|
Duyen|Le T My|LTM|
Vinh|Tu Q|TQ|
My|Pham D T|PDT|
Hoang|Hoang A|HA|
Nga|Le P|LP|

bacteriophages
Edwardsiella ictaluri
Myoviridae
Autographiviridae
Edwardsiella phage
genome analysis
genome comparison


A new scoring system for prediction of fibrosis in chronic hepatitis C.

Abstract:
BACKGROUND
Liver biopsy (LB) is still considered to be the gold standard for assessment of liver fibrosis.

OBJECTIVES
To evaluate the effectiveness of various non-invasive methods for predicting liver fibrosis, including transient elastography (TE), APRI score, Lok score, Forns score, FIB-4 score, Fibrosis Index, King score, and Bonacini score, in comparison with the effectiveness of LB and to create a new scoring system for fibrosis prediction.

PATIENTS AND METHODS
This study included 212 patients with chronic HCV hepatitis. LB, TE, and various biological tests were performed during a single hospital visit. Using established formulae, data from these tests were used to create scores for assessment of liver fibrosis.

RESULTS
The results of all the tests showed significant correlation with histological fibrosis. TE results (r = 0.62), King score (r = 0.57), and APRI score (r = 0.56) showed the closest correlation with severity of fibrosis. The following formula was derived from our data by multiple regression: Predicted liver fibrosis score (PLF score) = 0.956 + 0.084 × TE - 0.004 × King score + 0.124 × Forns score + 0.202 × APRI score. A direct correlation (r = 0.68) was found between the PLF score and liver fibrosis. The cut-off values of the PLF score for various stages of fibrosis were: F ≥ 1, 1.77 (Area under ROC curve (AUROC) = 0.76); F ≥ 2, 2.18 (AUROC = 0.78); F ≥ 3, 2.47 (AUROC = 0.86); and F = 4, 2.98 (AUROC = 0.97).

CONCLUSIONS
We found that our newly developed PLF score, which is derived from the scores of multiple tests, is more strongly correlated with fibrosis than each component score used individually. The PLF score is more effective than TE for predicting severe fibrosis, but they have similar effectiveness in predicting liver cirrhosis.

Bota|Simona|S| Sirli|Roxana|R| Sporea|Ioan|I| Focsa|Mircea|M| Popescu|Alina|A| Danila|Mirela|M| Strain|Mihnea|M| Sendroiu|Madalina|M| Deleanu|Alexandra|A| Dan|Isabel|I|

liver fibrosis
Elastography
chronic HCV hepatitis
Serological test


Prolongation of action potential duration and QT interval during epilepsy linked to increased contribution of neuronal sodium channels to cardiac late Na+ current: potential mechanism for sudden death in epilepsy.

Abstract:
BACKGROUND
Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy. The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (INa).

METHODS AND RESULTS
We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and INa in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of INa (INaL). The increase in INaL was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform NaV1.1 in cardiomyocyte. Epilepsy was also associated with a lower INa activation threshold resulting in increased cell excitability.

CONCLUSIONS
This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy.

Biet|Michael|M|
Morin|Nathalie|N|
Lessard-Beaudoin|Melissa|M|
Graham|Rona K|RK|
Duss|Sandra|S|
Gagné|Jonathan|J|
Sanon|Nathalie T|NT|
Carmant|Lionel|L|
Dumaine|Robert|R|

D062554:NAV1.5 Voltage-Gated Sodium Channel

D060888:Real-Time Polymerase Chain Reaction

action potentials
epilepsy
sodium channels
cardiac
sudden
death
arrhythmias
electrophysiology


Development of Cynicism in Medical Students: Exploring the Role of Signature Character Strengths and Well-Being.

Abstract: Reports of medical students experiencing burnout-related symptoms (e.g., cynicism) have increased in recent years. Little is known about the developmental process of this phenomenon and its relations with signature character strengths and well-being. The aim of this longitudinal analysis was to explore changes in the level of cynicism of medical students while in preclinical education. We further examined how the applicability of signature character strengths and well-being are related to this developmental process. Medical students (N = 99) participated in three online surveys over 3 years during medical school. Latent growth modeling, latent class growth modeling, general mixed modeling was conducted, and post hoc mixed ANOVA, Friedman test and Welch test analyses were examined. The results showed an increase in cynicism among medical students from first to last measurement. Two groups with distinct developmental trajectory patterns of cynicism were identified. Students with high levels of cynicism (high-level group) and students with changing levels of cynicism (increasing group) perceived higher applicability of signature character strengths in private life compared to the study context. Moreover, the high-level group experienced significantly lower psychological well-being (in particular mastery, optimism, and relationship) in their first year of medical education. This explorative study offers a comprehensive understanding of cynicism development in medical students during medical school and its relations to the applicability of signature character strengths and well-being. Prospective replication studies are needed to replicate the results obtained in this study.

Kachel|Timo|T| Huber|Alexandra|A| Strecker|Cornelia|C| Höge|Thomas|T| Höfer|Stefan|S|

cynicism
medical students
signature character strengths
well-being
burnout
growth mixture modeling (GMM)
latent class growth analysis (LCGA)
latent growth modeling (LGM)


N-acetylcysteine inhibits Mancozeb-induced impairments to the normal development of zebrafish embryos.

Abstract: Mancozeb (MZ), a manganese/zinc-containing ethylene-bis-dithiocarbamate (EBCD) fungicide has been claimed to present low acute toxicity and short environmental persistence, however, its effects on embryogenesis in non-target organisms is unclear. Here, we used zebrafish embryos (5 hpf) to assess the potential embryotoxic effects induced by MZ (up to 72 hpf) as well as the role of reactive oxygen species (ROS) in this process by pre-treatment with a classical antioxidant (N-acetylcysteine, NAC). Markers of reactive oxygen species production (ROS), glutathione (GSH) levels and glutathione S-transferase (GST) activity were measured along with genotoxicity (comet assay), cell death (Acridine Orange) and behavioral parameters (spontaneous movement, touch stimulation and swimming response), in order to determine potential mechanisms of embryotoxicity. According to results, MZ was able to induce morphological abnormalities such as body axis distortion, DNA damage, cell death, increased ROS generation and changes in behavioral endpoints during zebrafish development. All these toxic effects were inhibited by the pre-treatment with NAC indicating a key role of redox unbalance during MZ-induced embryotoxicity. At least in our knowledge, this is the first report on the deleterious effect of MZ to the normal embryogenesis of zebrafish. In addition, the importance of ROS generation during this pathophysiological condition was highlighted.

Costa-Silva|Dennis Guilherme da|DGD|
Leandro|Luana Paganotto|LP|
Vieira|Pratícia de Brum|PB|
de Carvalho|Nelson Rodrigues|NR|
Lopes|Andressa Rubim|AR|
Schimith|Lucia Emanueli|LE|
Nunes|Mauro Eugênio Medina|MEM|
de Mello|Renata Siqueira|RS|
Martins|Illana Kemmerich|IK|
de Paula|Adriano Alves|AA|
Cañedo|Andrés Delgado|AD|
Moreira|José Cláudio Fonseca|JCF|
Posser|Thais|T|
Franco|Jeferson Luis|JL|

Fungicide
Embryotoxicity
Reactive oxygen species
Antioxidant
Dithiocarbamate


Obesity and inflammation.

Abstract: The prevalence of obesity has recently increased dramatically and has contributed to the increasing prevalence of various pathological conditions, including type 2 diabetes mellitus, nonalcoholic fatty liver disease, asthma, various types of cancer, cardiovascular and neurodegenerative diseases, and others. Accumulating evidence points to localized inflammation in adipose tissue, which, in turn, promotes systemic low-grade inflammation as a primary force contributing to the development of these pathologies. A better understanding of the underlying mechanisms behind obesity-induced adipose tissue inflammation is required to develop effective therapeutic or prophylactic strategies. This review is aimed to present the current knowledge of adipose tissue inflammation associated with obesity.

Karczewski|Jacek|J| Śledzińska|Ewelina|E| Baturo|Alina|A| Jończyk|Izabela|I| Maleszko|Aleksander|A| Samborski|Paweł|P| Begier-Krasińska|Beata|B| Dobrowolska|Agnieszka|A|

D065626:Non-alcoholic Fatty Liver Disease

obesity
inflammation
adipose tissue
insulin resistance


Nonuniform Deformation of the Patellar Tendon During Passive Knee Flexion.

Abstract: The purpose of this study was to evaluate localized patterns of patellar tendon deformation during passive knee flexion. Ultrasound radiofrequency data were collected from the patellar tendons of 20 healthy young adults during knee flexion over a range of motion of 50°-90° of flexion. A speckle tracking approach was used to compute proximal and distal tendon displacements and elongations. Nonuniform tissue displacements were visible in the proximal tendon (P < .001), with the deep tendon undergoing more distal displacement than the superficial tendon. In the distal tendon, more uniform tendon motion was observed. Spatial variations in percent elongation were also observed, but these varied along the length of the tendon (P < .002), with the proximal tendon remaining fairly isometric while the distal tendon underwent slight elongation. These results suggest that even during passive flexion the tendon undergoes complex patterns of deformation. Proximal tendon nonuniformity may arise from its complex anatomy where the deep tendon inserts onto the patella and the superficial tendon extends to the quadriceps tendon. Such heterogeneity is not captured in whole tendon average assessments, emphasizing the relevance of considering localized tendon mechanics, which may be key to understanding tendon behavior and precursors to injury and disease.

Slane|Laura C|LC|
Bogaerts|Stijn|S|
Thelen|Darryl G|DG|
Scheys|Lennart|L|

ultrasound
speckle tracking
biomechanics
strain


High Rates of Drug-induced Liver Injury in People Living With HIV Coinfected With Tuberculosis (TB) Irrespective of Antiretroviral Therapy Timing During Antituberculosis Treatment: Results From the Starting Antiretroviral Therapy at Three Points in TB Trial.

Abstract:
BACKGROUND
New onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment.

METHODS
Post hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated.

RESULTS
Among 642 patients enrolled, the median age was 34 years (standard deviation, 28-40), and 17.6% had baseline CD4+ cell counts <50 cells/mm3. Overall, 146/472 patients (52, 47, and 47: early, late, and sequential arms) developed new-onset liver injury following TB treatment initiation. The incidence of liver injury post-ART initiation in patients with CD4+ cell counts <200 cells/mm3 and ≥200 cells/ mm3 was 27.4 (95% confidence interval [CI], 18.0-39.8), 19.0 (95% CI, 10.9-30.9), and 18.4 (95% CI, 8.8-33.8) per 100 person-years, and 32.1 (95% CI, 20.1-48.5), 11.8 (95% CI, 4.3-25.7), and 28.2 (95% CI, 13.5-51.9) per 100 person-years in the early, late integrated, and sequential treatment arms, respectively. Severe and life-threatening liver injury occurred in 2, 7, and 3 early, late, and sequential treatment arm patients, respectively. Older age and hepatitis B positivity predicted liver injury.

CONCLUSIONS
High incidence rates of liver injury among cotreated human immunodeficiency virus (HIV)-TB coinfected patients were observed. Clinical guidelines and policies must provide guidance on frequency of liver function monitoring for HIV-TB coinfected patients.

Naidoo|Kogieleum|K|
Hassan-Moosa|Razia|R|
Mlotshwa|Philile|P|
Yende-Zuma|Nonhlanhla|N|
Govender|Dhineshree|D|
Padayatchi|Nesri|N|
Abdool-Karim|Salim S S|SSS|

D056486:Chemical and Drug Induced Liver Injury

liver injury
HIV–TB integration
South Africa
antiretroviral treatment
tuberculosis treatment


MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1.

Abstract:
BACKGROUND
Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression. The aim of the study is to investigate the functional roles of miR-138-5p in breast cancer (BC) cells and explore the underlying mechanisms by identifying its target gene.

METHODS AND RESULTS
Our results first showed that miR-138-5p expression was remarkably decreased in BC tissues and cells using quantitative real-time PCR analysis. Forced expression of miR-138-5p significantly suppressed cell migration and invasion ability of BC using transwell assay. Moreover, miR-138-5p overexpression suppressed cell epithelial-mesenchymal transition (EMT) phenomenon of BC by upregulating E-cadherin expression, but downregulating N-cadherin and Vimentin expression. More importantly, rhomboid domain-containing protein 1 (RHBDD1) was predicted as the direct target of miR-138-5p by TargetScan and miRanda, which was subsequently confirmed by luciferase reporter assay in BC cells. RHBDD1 was up-regulated in BC tissues and negatively correlated with miR-138-5p expression. Furthermore, forced expression of miR-138-5p could down-regulate the expression of RHBDD1, but overexpression of RHBDD1 reversed the suppressive effects of miR-138-5p in BC cell migration, invasion and EMT.

CONCLUSIONS
Our findings revealed the tumor-suppressive role of miR-138-5p in regulating BC migration by targeting RHBDD1, suggesting that miR-138-5p negatively regulating EMT might be a therapeutic target in BC.

Zhao|Chengpeng|C| Ling|Xiaoling|X| Li|Xiangjin|X| Hou|Xiaoming|X| Zhao|Da|D|


Clinics in diagnostic imaging (201). Small bowel intramural haematoma induced by anticoagulation therapy with associated reactive ileus.

Abstract: A 74-year-old woman receiving long-term anticoagulation with warfarin for chronic atrial fibrillation presented with severe acute abdominal pain, diarrhoea and vomiting. Initial laboratory workup revealed a deranged coagulation profile. Computed tomography of the abdomen and pelvis demonstrated spontaneous distal jejunal intramural haematoma with associated reactive ileus. No overt pneumatosis intestinalis, intraperitoneal free gas or haemoperitoneum was seen. Based on clinical and imaging findings, a diagnosis of over-anticoagulation complicated by small bowel intramural haematoma was made. The patient was managed non-operatively with analgesia, cessation of warfarin and reversal therapy with vitamin K. Warfarin therapy was recommenced upon resolution of symptoms and optimisation of coagulation status. The clinical presentation, radiological features and overall management of anticoagulation-induced bleeding are further discussed in this article.

Tan|Timothy Shao Ern|TSE|
Cheong|Sook Chuei Wendy|SCW|
Tan|Tien Jin|TJ|

haematoma
anticoagulants
warfarin
atrial fibrillation
haemorrhage


Manual Therapy Effectively Decreases the Frequency of Joint Bleeding Improves Joint Health and Reduces Pain in Hemophilic Elbow Arthropathy: A Prospective Cohort Study.

Abstract:
Objective
To verify the safety and effectiveness of manual therapy intervention using fascial therapy in adult patients with haemophilic elbow arthropathy.

Methods
Prospective cohort study. A total of 28 patients with haemophilic elbow arthropathy was recruited in 3 cities in Spain. Patients received one-fascial therapy session per week for 3 weeks. The dependent variables were: frequency of joint bleeding, joint pain (visual analogue score) and joint status (Hemophilia Joint Health Score). Outcomes were measured at baseline (T0), post-treatment (T1) and after 3 months' follow-up (T2). Using Student's t-test, the means obtained in the evaluations were compared. The analysis of variance (ANOVA) test of repeated measures provided the intra-subject effect. The chosen level of significance was p < 0.05.

Results
A total of 28 patients were recruited according to the selection criteria. No joint bleeding occurred during or after the intervention. The primary outcome, frequency of bleeding, improved after intervention (p <0.001). The secondary variables joint status and joint pain improved after the experimental period (p <0.001). There were significant changes in the repeated measures factor in the frequency of haemarthrosis (F = 20.61; p = 0.00), joint status (F = 64.11; p = 0.00) and perceived pain (F = 33.15; p = 0.00).

Conclusion
Manual therapy using fascial therapy did not produce haemarthrosis in patients with haemophilic elbow arthropathy. Fascial therapy can improve the perception of pain and joint state,maintaining this improvement after a follow-up period of 3 months.

PÉRez-Llanes|Raúl|R|
Donoso-ÚBeda|Elena|E|
MeroÑO-Gallut|Javier|J|
Lopez-Pina|Jose Antonio|JA|
Cuesta-Barriuso|Rubén|R|

manual therapy
effectiveness
safety
elbow joint
haemophilic arthropathy


Contextual cueing is not flexible.

Abstract: Target detection is faster when search displays repeat, but properties of the memory representations that give rise to this contextual cueing effect remain uncertain. We adapted the contextual cueing task using an ABA design and recorded the eye movements of healthy young adults to determine whether the memory representations are flexible. Targets moved to a new location during the B phase and then returned to their original locations (second A phase). Contextual cueing effects in the first A phase were reinstated immediately in the second A phase, and response time costs eventually gave way to a repeated search advantage in the B phase, suggesting that two target-context associations were learned. However, this apparent flexibility disappeared when eye tracking data were used to subdivide repeated displays based on B-phase viewing of the original target quadrant. Therefore, memory representations acquired in the contextual cueing task resist change and are not flexible.

Yang|Youcai|Y|
Coutinho|Mariana V C|MVC|
Greene|Anthony J|AJ|
Hannula|Deborah E|DE|

Contextual cueing
Eye tracking
Associative memory
Implicit memory
Relational memory
Representational flexibility


Synthesis of Silver Nanoparticles Loaded onto Polymer-Inorganic Composite Materials and Their Regulated Catalytic Activity.

Abstract: We present a novel approach for the preparation of polymer-TiO₂ composite microgels. These microgels were prepared by the in situ hydrolysis and condensation of titanium tetrabutoxide (TBOT) in a mixed ethanol/acetonitrile solvent system, using poly(styrene-co-N-isopropylacrylamide)/poly(N-isopropylacrylamide-co-methacrylic acid) (P(St-NIPAM/P(NIPAM-co-MAA)) as the core component. Silver nanoparticles (AgNPs) were controllably loaded onto the polymer-TiO₂ composite microgels through the reduction of an ammoniacal silver solution in ethanol catalyzed by NaOH. The results showed that the P(St-NIPAM)/P(NIPAM-co-MAA)-TiO₂ (polymer-TiO₂) organic-inorganic composite microgels were less thermally sensitive than the polymer gels themselves, owing to rigid O⁻Ti⁻O chains introduced into the three-dimensional framework of the polymer microgels. The sizes of the AgNPs and their loading amount were controlled by adjusting the initial concentration of [Ag(NH₃)₂]⁺. The surface plasmon resonance (SPR) band of the P(St-NIPAM)/P(NIPAM-co-MAA)-TiO₂/Ag (polymer-TiO₂/Ag) composite microgels can be tuned by changing the temperature of the environment. The catalytic activities of the polymer-TiO₂/Ag composite microgels were investigated in the NaBH₄ reduction of 4-nitrophenol. It was demonstrated that the organic-inorganic network chains of the polymer microgels not only favor the mass transfer of the reactant but can also modulate the catalytic activities of the AgNPs by tuning the temperature.

Yan|Sen|S| Jiang|Chunge|C| Guo|Jianwu|J| Fan|Yinglan|Y| Zhang|Ying|Y|0000-0001-8362-9362

silver nanoparticles
polymer microgels
reduction of 4-nitrophenol (4-NP)
supported catalysts
titania


Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn.

Abstract: Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.

Hallstensen|Randi Fykse|RF|
Bergseth|Grethe|G|
Foss|Stian|S|
Jæger|Steinar|S|
Gedde-Dahl|Tobias|T|
Holt|Jan|J|
Christiansen|Dorte|D|
Lau|Corinna|C|
Brekke|Ole-Lars|OL|
Armstrong|Elina|E|
Stefanovic|Vedran|V|
Andersen|Jan Terje|JT|
Sandlie|Inger|I|
Mollnes|Tom Eirik|TE|

D015395:Histocompatibility Antigens Class I

Eculizumab
Complement
Paroxysmal nocturnal hemoglobinuria
Placenta
Therapy


In vitro evaluation of electrospun PLGA/PLLA/PDLLA blend fibers loaded with naringin for guided bone regeneration.

Abstract: The present study was to evaluate fiber mesh loaded with naringin via electrospinning to guide bone regeneration in vitro. The naringin-loaded fiber mesh was prepared via elctrospinning of PLGA, PLLA, PDLLA blending solution with naringin. SEM showed that naringin decreased the fiber's diameter according to the concentration of naringin. After 20 days' degradation in PBS, the drug-loaded fiber meshes still kept their stability with about 10% decrease in tensile strength. In vitro release experiments showed a sustained and steady naringin releasing profile with little initial burst releasing. Compared to the mats without naringin, the fiber mats loaded with naringin showed the most pronounced enhancement of cell growth when MC3T3-E1 cells were cultured on the fiber mats. The blend fiber loaded with naringin has optimized physical properties and sustained release profile in vitro. The study presents a promising fibrous mesh material for guided bone regeneration therapy.

Guo|Zhenzhao|Z| Wu|Shuai|S| Li|Hong|H| Li|Qiyan|Q| Wu|Gang|G| Zhou|Changren|C|

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

PLGA/PLLA/PDLLA
Naringin
Guided bone regeneration
Electrospinning


Kinetics of biogas production and chemical oxygen demand removal from compost leachate in an anaerobic migrating blanket reactor.

Abstract: In this study, laboratory anaerobic migrating blanket reactor (AMBR) with four units was used to reduce and remove COD leachate of composting process; it was also used to determine the kinetic coefficients of COD removal and biogas and methane gas production in several different OLRs. The maximum concentration of organic matter entering the reactor was 100,000 mg/L and the reactor was under operation for 319 days. The results showed that the COD removal efficiency of AMBR in all concentrations of substrate entering the reactor was above 80%. First-order model and Stover-Kincannon were used to investigate the kinetics of COD removal via AMBR biological process; in addition, the two models of Modified Stover-Kincannon and Van der Meer and Heertjes were used to check the kinetic constants of biogas and methane gas production. The results obtained from the models showed that the experimental data on COD removal were more consistent with the results obtained from Stover-Kincannon model (R2 = 0.999) rather than with the First-order model (R2 = 0.926). Kinetic constants calculated via Stover-Kincannon model were as follows: saturation value constant (KB) and maximum utilization rate constants (Umax), respectively, were 208,600 mg/L d and 172,400 mg/L d. We investigated the linear relationship between the experimental data and the values predicted by the models; as compared with the values predicted by the First-order model, the values predicted by Stover-Kincannon model were closer to the values measured via experiments. Based on the results of the evaluation of kinetic coefficients of Stover-Kincannon model, with the migration of the leachate flow from unit 1 to unit 4, Umax value has fallen significantly. The values of maximum specific biogas production rate (Gmax) and proportionality constant (GB) obtained from the Stover-Kincannon model, respectively, were 35,714 ml/L d and 42.85 (dimensionless) and value of kinetic constant of Van der Meer and Heertjes (ksg) was 0.0473 ml CH4/mg COD.

Ebrahimi|Aliasghar|A|
Hashemi|Hassan|H|
Eslami|Hadi|H|
Fallahzadeh|Reza Ali|RA|
Khosravi|Rasoul|R|
Askari|Roohollah|R|
Ghahramani|Esmail|E|

D057919:Biological Oxygen Demand Analysis

Biogas
Composting
Leachate
Modeling
Biological treatment
Solid waste


Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes.

Abstract: The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs) as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL) scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate) were then mixed with poly-e-caprolactone (PLC) using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.

Patel|Shraddha|S|
Jammalamadaka|Uday|U|
Sun|Lin|L|
Tappa|Karthik|K|
Mills|David K|DK|0000-0002-6489-4520

halloysite nanotubes
nanocontainers
poly-e-caprolactone
nanocomposite mats
drug release
antibiotics
antiseptics


Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma.

Abstract: Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed in pRCC. The upregulation is associated with pRCC adverse features (T1P < T2P < CIMP, Stage1 + 2 < Stage 3 < Stage 4, and N0 < N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation; the latter is correlated with network alterations related to immune regulation, metabolism, and hypoxia. A set of differentially expressed genes (DEFs) was derived from ACHN OIP5 xenografts and primary pRCCs (n = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p < 2 × 10-16) and relapse (p < 2 × 10-16) possibilities. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5. PLK1 inhibitor BI2356 inhibits the growth of xenografts formed by ACHN OIP5 cells. Collectively, the OIP5 network can be explored for personalized therapies in management of pRCC patients.

Chow|Mathilda Jing|MJ|
Gu|Yan|Y|
He|Lizhi|L|
Lin|Xiaozeng|X|
Dong|Ying|Y|
Mei|Wenjuan|W|
Kapoor|Anil|A|0000-0001-9180-8029
Tang|Damu|D|0000-0002-3282-9521

OIP5
papillary renal cell carcinoma
PLK1
therapy
biomarkers
tumorigenesis


Efficacy and safety of polydioxanone thread embedded at specific acupoints for non-specific chronic neck pain: a study protocol for a randomized, subject-assessor-blinded, sham-controlled pilot trial.

Abstract:
BACKGROUND
This study aims to evaluate the efficacy and safety of thread-embedding acupuncture (TEA) with polydioxanone thread embedded at various acupoints, compared with sham TEA, for the treatment of non-specific chronic neck pain.

METHODS/DESIGN
This study will be an 8-week-long, two-armed, parallel, randomized, subject-assessor-blinded, sham-controlled pilot trial. Fifty eligible patients will be randomly allocated into the real TEA group or the sham TEA group. The real TEA group will receive TEA treatment at 14 fixed acupoints in the neck region. The sham TEA group will receive the same treatment as the real TEA group, but with a sham device with the thread removed. Both groups will receive treatment once a week for a total of four sessions. The primary outcome will be the mean change in the visual analog scale (VAS) from baseline to week 6 (2 weeks post intervention). Clinical relevance (ratio of the number of patients with decreases on the VAS of ≥15 mm or with percentiles ≥ 30% and ≥ 50% relative to baseline to the total number of patients), Neck Disability Index, pressure pain threshold, the Hospital Anxiety and Depression Scale, EuroQol 5-Dimensions questionnaire, Patient Global Impression of Change, blinding test, and adverse events will be used to assess secondary outcomes.

DISCUSSION
The results of this study will provide valuable data for a large-scale clinical trial to evaluate the clinical effects of polydioxanone TEA in the treatment of patients with non-specific chronic neck pain.

TRIAL REGISTRATION
Clinical Research Information Service (CRIS), Republic of Korea, KCT0002452 . Registered on 6 September 2017.

D016032:Randomized Controlled Trials as Topic

Efficacy
Polydioxanone
Chronic neck pain
Thread-embedding acupuncture
Randomized sham-controlled trial


Contact Electrification of Individual Dielectric Microparticles Measured by Optical Tweezers in Air.

Abstract: We measure charging of single dielectric microparticles after interaction with a glass substrate using optical tweezers to control the particle, measure its charge with a sensitivity of a few electrons, and precisely contact the particle with the substrate. Polystyrene (PS) microparticles adhered to the substrate can be selected based on size, shape, or optical properties and repeatedly loaded into the optical trap using a piezoelectric (PZT) transducer. Separation from the substrate leads to charge transfer through contact electrification. The charge on the trapped microparticles is measured from the response of the particle motion to a step excitation of a uniform electric field. The particle is then placed onto a target location of the substrate in a controlled manner. Thus, the triboelectric charging profile of the selected PS microparticle can be measured and controlled through repeated cycles of trap loading followed by charge measurement. Reversible optical trap loading and manipulation of the selected particle leads to new capabilities to study and control successive and small changes in surface interactions.

charging profile of individual microparticle


CAM use in dermatology. Is there a potential role for honey, green tea, and vitamin C?

Abstract: Complementary and alternative medicine (CAM) is a group of non-traditional medical practices that includes natural products, manipulations, and mind and body medicine. CAM use has grown and become popular among patients. In dermatology, honey, green tea, and vitamin C have been used as topical treatments for a variety of diseases. We performed a systematic review to explore the cutaneous effects of each of these three products. Honey's unique antibacterial, anti-inflammatory, and antioxidant properties were shown to contribute to wound healing, especially in ulcers and burns. Green tea, among many health benefits, demonstrated protection from ultraviolet-induced events, such as photoimmunosuppression and skin cancer growth. Vitamin C, known for its antioxidant properties and key role in collagen production, has been shown to produce positive effects on skin hyperpigmentation and aging. Future large well-designed clinical trials are needed in order to further investigate the potential of these agents as dermatological therapies.


Remuneration of primary dental care in England: a qualitative framework analysis of perspectives of a new service delivery model incorporating incentives for improved access, quality and health outcomes.

Abstract:
OBJECTIVE
This study aimed to describe stakeholder perspectives of a new service delivery model in primary care dentistry incorporating incentives for access, quality and health outcomes.

DESIGN
Data were collected through observations, interviews and focus groups.

SETTING
This was conducted under six UK primary dental care practices, three working under the incentive-driven contract and three working under the traditional activity-based contract.

PARTICIPANTS
Observations were made of 30 dental appointments. Eighteen lay people, 15 dental team staff and a member of a commissioning team took part in the interviews and focus groups.

RESULTS
Using a qualitative framework analysis informed by Andersen's model of access, we found oral health assessments influenced patients' perceptions of need, which led to changes in preventive behaviour. Dentists responded to the contract, with greater emphasis on prevention, use of the disease risk ratings in treatment planning, adherence to the pathways and the utilisation of skill-mix. Participants identified increases in the capacity of practices to deliver more care as a result. These changes were seen to improve evaluated and perceived health and patient satisfaction. These outcomes fed back to shape people's predispositions to visit the dentist.

CONCLUSION
The incentive-driven contract was perceived to increase access to dental care, determine dentists' and patients' perceptions of need, their behaviours, health outcomes and patient satisfaction. Dentists face challenges in refocusing care, perceptions of preventive dentistry, deployment of skill mix and use of the risk assessments and care pathways. Dentists may need support in these areas and to recognise the differences between caring for individual patients and the patient-base of a practice.

Robinson|Peter G|PG|
Douglas|Gail V A|GVA|
Gibson|Barry J|BJ|
Godson|Jenny|J|
Vinall-Collier|Karen|K|
Pavitt|Sue|S|
Hulme|Claire|C|

D006301:Health Services Needs and Demand

D010342:Patient Acceptance of Health Care

dental
incentives
contract
commissioning
oral health
behaviour change


In-hospital prognosis of first-ever noncardiogenic ischemic stroke in patients with and without indication for prestroke antiplatelet therapy: Chinese Stroke Center Alliance.

Abstract:
Background
It is unknown about the influence of prestroke antiplatelet use on early outcomes in patients with and without the indication. We aimed to evaluate the in-hospital prognosis of first-ever noncardiogenic ischemic stroke patients with and without indications of antiplatelet use for primary prevention.

Methods
This was a retrospective, observational study based on a prospective hospital-based registry (Chinese Stroke Center Alliance). Using the data with 436,660 first-ever noncardiogenic acute ischemic strokes recorded from Aug 1, 2015, to July 31, 2019, from 1,453 hospitals in China, we examined the associations between the indication for prestroke antiplatelet use and in-hospital clinical outcomes.

Results
Among 436,660 first-ever noncardiogenic ischemic stroke patients, 42,409 patients (9.7%) had a documented previous vascular indication and 394,251 (90.3%) did not. Compared to those without, patients with the indication were associated with increased prevalence of in-hospital morbid conditions, including stroke severity (OR 2.71; 95% CI: 2.62-2.81; P<0.0001), length of stay >14 days (OR 1.16; 95% CI: 1.13-1.19; P<0.0001), mortality (OR 2.20; 95% CI: 1.96-2.46, P<0.0001), and recurrence of ischemic stroke and transient ischemic attack (TIA) (OR 1.5; 95% CI: 1.43-1.59, P<0.0001). Among patients without indication, prestroke antiplatelet use was associated with lower mortality (OR 0.73, 95% CI: 0.56-0.96; P=0.0221); while among patients with indication, those receiving prestroke antiplatelet had lower odds ratios in stroke severity (P<0.0001) and disability (P=0.0003) than those who not.

Conclusions
Patients with indications of prestroke antiplatelet use were more likely to have unfavorable outcomes than those without. Prestroke antiplatelet might be associated with lower mortality, less disability, and less stroke severity in certain population groups. Future studies to improve risk prediction rules are needed to guide effective primary prevention for ischemic stroke.

Xu|Yu-Yuan|YY| Gu|Hong-Qiu|HQ| Li|Zi-Xiao|ZX| Xiong|Yun-Yun|YY| Zhou|Qi|Q| Liu|Li-Ping|LP| Zhao|Xing-Quan|XQ| Wang|Yi-Long|YL| Meng|Xia|X| Wang|Yong-Jun|YJ|

prognosis
ischemic stroke
Antiplatelet therapy
primary prevention


Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

Abstract: The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film. A Definitive Screening Design of Experiments (DoE) was used to identify and classify the critical formulation and process variables impacting critical quality attributes (CQA). A total of 14 laboratory-scale DoE formulations were prepared and evaluated for mechanical properties (%elongation at break, yield stress, Young's modulus, folding endurance) and other CQA (dry thickness, disintegration time, dissolution rate, moisture content, moisture uptake, drug assay and drug content uniformity). The main factors affecting mechanical properties were plasticizer to film former ratio and drying temperature. Dissolution rate was found to be sensitive to air flow rate during drying and plasticizer to film former ratio. Data were analyzed for elucidating interactions between different variables, rank ordering the critical materials attributes (CMA) and critical process parameters (CPP), and for providing a predictive model for the process. Results suggested that plasticizer to film former ratio and process controls on drying are critical to manufacture LMT ODF with the desired CQA.

Mazumder|Sonal|S|
Pavurala|Naresh|N|
Manda|Prashanth|P|
Xu|Xiaoming|X|
Cruz|Celia N|CN|
Krishnaiah|Yellela S R|YSR|

Quality by design
Formulation
Process variables
Oral disintegrating films
Lamotrigine
Film former
Critical quality attributes


An Integrated Strategy for Rapid Hemostasis during Tumor Resection and Prevention of Postoperative Tumor Recurrence of Hepatocellular Carcinoma by Antibacterial Shape Memory Cryogel.

Abstract: The inevitable bleeding during tumor resection greatly increases the risk of tumor recurrence caused by metastasis of cancer cells with blood, and hemostasis and prevention of post-operation tumor recurrence is still a challenge. However, a biomaterials approach for rapid hemostasis during tumor resection and simultaneous prevention of tumor recurrence is rarely reported. Here, zeolitic imidazolate framework (ZIF-8) nanoparticle-enhanced multinetwork cryogels are proposed which provide an integrated treatment regimen for rapid hemostasis through intraoperative blood trigger shape recovery and enhanced coagulation, and prevention of postoperative cancer recurrence via sonodynamic anticancer in a hepatocellular carcinoma model. A series of antibacterial shape memory multifunctional cryogels are synthesized based on glycidyl methacrylate-functionalized quaternized chitosan (QCSG), dopamine-modified hyaluronic acid (HA-DA), and hematoporphyrin monomethyl ether (HMME)-loaded dopamine-modified ZIF-8 (ZDH). Blood loss in different bleeding models confirms good hemostasis of ZIF-8 loading cryogels. Besides, in vitro tests confirm that QCSG/HA-DA/ZDH (QH/ZDH) cryogels significantly killed cancer cells by generating reactive oxygen species under ultrasound. Finally, significantly reduced tumor recurrence after the resection of ectopic hepatocellular carcinoma further confirms the good effect of QH/ZDH cryogels in preventing recurrence by a coordinated strategy of intraoperative hemostasis and postoperative sonodynamic therapy by pH-responsive HMME release, showing great potential in clinical application.

Liang|Yongping|Y| Li|Meng|M| Huang|Ying|Y| Guo|Baolin|B|0000-0001-6756-1441

hemostasis
cryogel
ZIF-8
sonodynamic anticancer
cancer recurrence prevention


Dental caries and depression in pregnant women: The role of oral health self-perception as mediator.

Abstract:
OBJECTIVE
This study investigated the role of oral health self-perception as mediator of association between dental caries and depression among pregnant women from the 2015 Pelotas Birth Cohort Study, Brazil.

MATERIALS AND METHODS
Overall, 2,496 pregnant women participated of this oral health sub-study. Data related to demographic and socioeconomic conditions, lifetime and current depression, and oral health self-perception were collected. Participants were also assessed for dental caries (DMF-T index). Depression was assessed using the Edinburgh Postnatal Depression Scale. For analysis, six outcomes related to dental caries experience were considered. Causal mediation analysis was performed using parametric regression models.

RESULTS
When it was assumed that all subjects had poor perception about oral health, it was observed that the presence of moderate/severe depressive signals and symptoms was higher in subjects with dental caries experience (OR 1.13; CI 95% 1.06-1.20), with severity of untreated dental caries (OR 2.08; CI 95% 1.16-3.78), untreated dental caries (OR 1.18; 95% CI 1.07-1.29), tooth loss (OR 1.08; 95% CI 1.02-1.14), and filled tooth (OR 1.07; 95% CI 1.02-1.16).

CONCLUSIONS
Our findings show the effect of dental caries on depression is mediated by self-perception about oral health in pregnant women.

dental caries
depression
pregnant women
cohort studies
epidemiologic research design
epidemiology
self concept
self perception


Neonatal outcomes of macrosomic infants of diabetic and non-diabetic mothers.

Abstract:
OBJECTIVE
To compare neonatal outcomes (including breastfeeding (BF) initiation) of 170 macrosomic IDM with that of 739 macrosomic nIDM.

DESIGN/METHODS
Retrospective cohort investigation of all macrosomic infants born consecutively over a four-year period (2008-2011). Macrosomic (birth weight ≥4000 g) IDM included 100 infants whose mothers had gestational diabetes and 70 whose mothers had pregestational diabetes.

RESULTS
IDM were more likely to be delivered by cesarean to obese women while nIDM were more likely to be delivered vaginally to younger women with a higher level of education. Ethnic distribution (60% white, 20% black, 10% Hispanic and 10% Asian or African) was similar in each group. Forty-nine percent of IDM and 7% of nIDM required NICU admission. Respiratory disorders (mainly TTNB) affected 21% of IDM and 3% of nIDM while hypoglycemia was observed in 36% of IDM and 15% of nIDM. Of the 35 IDM delivered vaginally, 10 were complicated by shoulder dystocia without injury. Conversely, 70 of the 458 nIDM delivered vaginally experienced shoulder dystocia that resulted in 6 limb fractures and 3 brachial plexus injuries. On arrival to labor and delivery, 75% of all women intended to BF; however, at the time of discharge, 65% of women with diabetes and 92% of those without diabetes who intended to BF had initiated BF.

CONCLUSIONS
Both macrosomic IDM and macrosomic nIDM are at risk for significant morbidities. Macrosomic IDM carry a higher risk for NICU admissions, leading to maternal-infant separation, and lower BF initiation rates.

Cordero|L|L|
Paetow|P|P|
Landon|M B|MB|
Nankervis|C A|CA|


Providing a New Aniline Bioisostere through the Photochemical Production of 1-Aminonorbornanes.

Abstract: This report describes the photochemical conversion of aminocyclopropanes into 1-aminonorbornanes via formal [3+2] cycloadditions initiated by homolytic fragmentation of amine radical cation intermediates. Aligning with the modern movement toward sp  -rich motifs in drug discovery, this strategy provides access to a diverse array of substitution patterns on this saturated carbocyclic framework while offering the robust functional group tolerance (e.g. -OH, -NHBoc) necessary for further derivatization. Evaluating the metabolic stability of selected morpholine-based 1-aminonorbornanes demonstrated a low propensity for oxidative processing and no proclivity toward reactive metabolite formation, suggesting a potential bioisosteric role for 1-aminonorbornanes. Continuous flow processing allowed for efficient operation on gram-scale, providing promise for translation to industrially-relevant scales. This methodology only requires low loadings of a commercially-available, visible light-active photocatalyst and a simple salt, thus it stays true to sustainability goals while readily delivering saturated building blocks that can reduce metabolic susceptibility within drug development programs.

Staveness|Daryl|D|
Sodano|Taylor M|TM|
Li|Kangjun|K|
Burnham|Elizabeth A|EA|
Jackson|Klarissa D|KD|
Stephenson|Corey R J|CRJ|

bioisostere
1-aminonorbornane
Aminocyclopropane
homolytic fragmentation
amine radical cation
metabolic stability
photoredox catalysis
radical cyclization


Efficient Photoelectrochemical Route for the Ambient Reduction of N2 to NH3 Based on Nanojunctions Assembled from MoS2 Nanosheets and TiO2.

Abstract: Efficient nitrogen fixation under ambient conditions is an exigent task in both basic research and industrial applications. Recently, reduction of N2 to NH3 based on photocatalysis and/or electrocatalysis offers a possible route to the typical Haber-Bosch process. However, achieving a high yield of N2 reduction reaction (NRR) is still a challenging goal because of the limitations of efficient catalysts. Herein, we propose a photoelectrochemical NRR route based on the rational design of MoS2@TiO2 semiconductor nanojunction catalysts through a facile hydrothermal synthetic method. The developed MoS2@TiO2 photocathode attains a high NH3 yield rate (1.42 × 10-6 mol h-1 cm-2) and a superhigh faradaic efficiency (65.52%), which is the highest record to the best of our knowledge. Moreover, MoS2@TiO2 exhibits high stability over 10 consecutive reaction cycles. Therefore, this work demonstrates an effective NRR photoelectrocatalyst and results in a breakthrough in the low faradaic efficiency because of the interfacial electronic coupling and synergistic effects between the MoS2 and TiO2 components.

faradaic efficiency
MoS@TiO nanojunctions
N reduction reaction
ammonia production
photoelectrocatalysis


Epidemiology of preoperative hematologic assessment of children cared for in a pediatric emergency department.

Abstract:
OBJECTIVE
To assess frequency of preoperative hematologic testing in a tertiary care pediatric emergency department (PED) and how often these values predict clinical outcome or change management decisions.

METHODS
Single-center retrospective cohort study in a tertiary-care children's hospital PED. Patients 0-18years old, presenting between July 1, 2009-July 1, 2011, ultimately undergoing a surgical procedure within 48h of presentation were included. Patients were defined as having "preoperative" hematologic assessment if these studies were performed solely because the child was going to the operative suite. Patients who met trauma team activation criteria, underwent neurosurgical procedures, or had laboratory studies performed prior to PED arrival were excluded. The primary outcome was the prevalence of preoperative laboratory assessment.

RESULTS
528 children were included, of whom 301 (57%) underwent preoperative hematologic laboratory evaluations. Of these 301 patients, 115 (38%) had abnormal hematologic parameters, and only 3 (1%) of these patients had their perioperative management changed. One additional child had intraoperative bleeding that required blood products but did not undergo preoperative hematologic assessment. All four children had medical histories that would have identified their risk for perioperative bleeding events.

CONCLUSION
Preoperative hematologic laboratory assessment occurs frequently in children initially cared for in a tertiary care pediatric emergency department who subsequently undergo operative interventions. Although age-based abnormal hematologic values are often found, rarely are these abnormalities clinically significant. This study suggests that children cared for in a PED without a history concerning for an increased risk of perioperative bleeding does not require preoperative hematologic assessment.

Woll|Christopher|C|
Smith|P Brian|PB|
Fox|James Walter|JW|

Preoperative Hematology Pediatric Emergency Coagulation Screening


A Second Pandemic: Mental Health Spillover From the Novel Coronavirus (COVID-19).

Abstract: The novel coronavirus (COVID-19) pandemic has created an unprecedented global health challenge. There is risk that the outbreak will create a "second pandemic" of mental health crises in health systems and communities. Thus, a comprehensive public health response to the pandemic must include (a) attention to the psychological aspects of hospitalization for patients, families, and staff affected by COVID-19; (b) planning for emergency and acute psychiatric patient care if hospitals become overwhelmed with COVID-19 patients; and (c) innovations for providing mental health care in communities while social distancing is required and health system resources are strained. Nurses and nurse leaders must anticipate these mental health challenges, assist with preparedness in health systems and communities, and advocate for a coordinated response to promote mental wellness and resilience.

Choi|Kristen R|KR|0000-0001-5453-1091
Heilemann|MarySue V|MV|
Fauer|Alex|A|
Mead|Meredith|M|

pandemic
mental health
coronavirus
COVID-19
nursing
psychiatry


Phosphate Dosing in Drinking Water Distribution Systems Promotes Changes in Biofilm Structure and Functional Genetic Diversity.

Abstract: Water utilities treat drinking water by adding phosphate to prevent metal dissolution from water pipe work systems and particularly lead poisoning. Phosphate can be a limiting nutrient for microbial biofilms in DWDS, yet its effects on these microbial consortia are not well understood. This research presents results from phosphate dosing experiments using a real scale chlorinated DWDS, comparing standard phosphate concentrations of United Kingdom drinking water (1 mgP/L) with a double dose (2 mgP/L) commonly used in plumbosolvency treatment. Biofilm development during phosphate treatment experiments was monitored using a holistic approach by combining metagenomics analysis, flow cytometry and SEM characterisation. The increase of phosphate levels in drinking water, reduced biofilm cell numbers and promoted the presence of poorly distributed biofilms on inner pipe surfaces. Metagenomics analysis using genetic markers (16S rRNA and ITS2) showed that phosphate influenced biofilm community structure, particularly fungal composition. Whole metagenome sequencing showed that phosphate enrichment favoured the presence of sequencing reads associated to ATPases, ion transporters and DNA-interacting proteins, whilst reads associated to nitrogen metabolism were predominant in control samples. This research brings new knowledge regarding the influence of phosphate treatment on the composition and structure of biofilms within DWDS, and the implications that this might have for the management of these systems.

Rosales|Esther|E|
Del Olmo|Gonzalo|G|
Calero Preciado|Carolina|C|
Douterelo|Isabel|I|

phosphate
drinking water
biofilms
whole metagenomics
distribution networks