Significantly higher expression levels of androgen receptor are associated with erythroblastosis virus E26 oncogene related gene positive prostate cancer.

Abstract: Erythroblastosis virus E26 related gene (ERG) overexpression is correlated with the TMPRSS2-ERG fusion gene, a rearrangement known to be present in about 50% of cases of prostate cancer. Androgen receptor (AR) is a known regulator of the TMPRSS2 gene. Despite knowledge of this relationship, limited data is available on the specific relationship of AR expression to TMPRSS2-ERG fusion (ERG) status in prostate cancer (PCa). We used multiplexed immunohistochemistry, multispectral imaging technology and tissue microarray (TMA) to elucidate this relationship. Two prostate tissue microarrays were created from two cohorts of hormonal naïve patients' prostatectomy specimens: progression TMA (pTMA, from 95 PCa patients) and outcome TMA (oTMA, from 183 PCa patients with at least 5-year follow-up information). Each of the two TMAs were triple-stained with ERG, AR and E-cadherin antibodies and visualized with a different chromogen. We found marked difference in AR expression levels between ERG positive (ERG(+)) and ERG negative (ERG(-)) prostate cancer. The difference was significant in localized (pT2) prostate cancer. We also found that AR expression levels were significantly higher in PCa tissue compared to benign prostate tissue, with the highest expression levels in ERG(+) metastatic cancer. Neither AR nor ERG expression was associated with clinical outcome. Our findings confirm that TMPRSS2-ERG fusion is AR-dependent and is associated with increased AR expression. Our data suggest that the AR pathway may play an important role in the development of ERG(+) PCa and ERG status may be useful in stratifying PCa patients for hormonal therapy.


Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.

Abstract: Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb3 and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley & Sons, Inc.

Boutin|Michel|M| Lavoie|Pamela|P| Abaoui|Mona|M| Auray-Blais|Christiane|C|

D002851:Chromatography, High Pressure Liquid

ultra-performance liquid chromatography (UPLC)


An abrupt increment in the respiratory rate is a sign of neonatal pneumothorax.

Abstract:
OBJECTIVE
The objective of the present study was to investigate the early clinical signs of neonatal pneumothorax.

METHODS
A case-control study at a level III referral center from 2006 to 2012 was conducted. For each neonate with pneumothorax (Group I), one control subject (Group II) was identified by selecting an infant born within the same week with a gestational age of ± 7 days and with a birth weight within 10% of the index case. The primary outcome was to investigate the clinical findings preceding the onset of pneumothorax. Secondary outcome was to assess the risk factors.

RESULTS
Of the 1375 infants admitted, 39 had a pneumothorax. Patients with pneumothorax showed significantly increased respiratory rates preceding the definitive diagnosis when compared with control patients (median: 16 (0-58) versus 4 (0-10); p < 0.001). An increase in the respiratory rate was found to be a significant clinical parameter preceding the diagnosis of pneumothorax (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.12-2.14, p < 0.001; R(2) = 0.80). Sensitivity and specificity of this sign were found to be 77 and 90%, respectively.

CONCLUSION
An abrupt increase in the respiratory rate would be used as a reliable parameter to help determine an impending pneumothorax in neonates.

Cizmeci|Mehmet Nevzat|MN|
Kanburoglu|Mehmet Kenan|MK|
Akelma|Ahmet Zulfikar|AZ|
Andan|Hilal|H|
Akin|Kayihan|K|
Tatli|Mustafa Mansur|MM|


Drug resistance pattern of Mycobacterium tuberculosis in the province with highest incidence of tuberculosis in Iran.

Abstract:
OBJECTIVE/BACKGROUND
Incidence of tuberculosis (TB) in Golestan Province is consistently higher than other provinces of Iran. This study aimed to determine the rate of drug resistance to first-line antibiotics in Mycobacterium tuberculosis (MTB) isolates recovered from new cases in this province.

METHODS
The sputum and broncho-alveolar lavage samples from 3828 patients who were suspected for active TB were collected from March 2015 to July 2015. All specimens were subjected to smear microscopy and culture. Drug susceptibility testing to rifampicin, isoniazid, ethambutol, and streptomycin was performed on Löwenstein-Jensen medium using proportion method.

RESULTS
Of 3828 clinical specimens, 40 were culture-positive for MTB. The mean age of patients was 48.6±17.5years and 23 (57%) patients were male. Thirty-eight patients were native Iranians while two (5%) were immigrant patients from Turkmenistan and Afghanistan. A set of 34 (85%) isolates were pan-susceptible, six (15%) were resistant to at least one drug, and one isolate (2.5%) was multidrug resistant.

CONCLUSIONS
The rate of drug resistance in this study area point to the necessity for further enforcement of TB treatment and disease control management. Future studies are recommended for assessments of drug resistance pattern of MTB isolates in Golestan Province.

Mansoori|N|N|
Douraghi|Masoumeh|M|
Vaziri|F|F|
Rajabloo|A A|AA|
Sheikhi|M|M|
Taziki|M|M|
Atarjalali|M|M|

Mycobacterium tuberculosis
Tuberculosis
Iran
Multidrug resistant


Apically extruded debris and irrigants during root canal filling material removal using Reciproc Blue, WaveOne Gold, R-Endo and ProTaper Next systems.

Abstract: The present study aimed to compare the amount of apically extruded debris and irrigants produced by various nickel-titanium instruments.  A total of 100 single-rooted mandibular premolar teeth were root canal treated and prepared for agar gel model. The root canal fillings were removed using Reciproc Blue, ProTaper Next, R-Endo, WaveOne Gold systems or hand instrumentation. The mean weights of apically extruded materials were calculated. Data were statistically analyzed using one-way ANOVA and post hoc Bonferroni tests.  Hand instrumentation resulted in significantly more debris and irrigants than other systems (P<0.05). The mean amount of apically extruded debris and irrigants produced by Reciproc Blue system was significantly greater than motordriven instruments (P<0.05). No significant difference was detected between ProTaper Next and WaveOne Gold systems (P>0.05), while they both produced significantly less apically extruded material than R-Endo system (P<0.05).  All the instruments caused apical extrusion. ProTaper Next and WaveOne Gold systems were associated with significantly less apical extrusion.

nickel-titanium
Agar gel model
apical extrusion
retreatment


La prise en charge des exacerbations aiguës de l'asthme chez les enfants.

Abstract: Les enfants et les adolescents atteints d'exacerbations aiguës de l'asthme se rendent souvent à l'urgence à cause de signes de détresse respiratoire. Les épisodes les plus graves ont un potentiel mortel. Pour que les traitements soient efficaces, le patient doit faire l'objet d'une évaluation exacte et rapide de la gravité de la crise d'asthme. Le présent document de principes traite de l'évaluation, de la prise en charge et de la disposition des patients pédiatriques ayant un diagnostic connu d'asthme qui consultent à cause d'une exacerbation aiguë. Les directives portent sur l'évaluation de la gravité de l'asthme, les considérations thérapeutiques, le plan de congé approprié, le suivi et la prescription de corticostéroïdes inhalés pour éviter de nouvelles exacerbations et limiter la morbidité chronique.

Trottier|Evelyne D|ED|
Chan|Kevin|K|
Allain|Dominic|D|
Chauvin-Kimoff|Laurel|L|

prise en charge
disposition
asthme
enfants d’âge préscolaire
prise en charge d’urgence
pédiatrie


Preparation of glutaraldehyde-treated lipase-inorganic hybrid nanoflowers and their catalytic performance as immobilized enzymes.

Abstract: The use of protein-inorganic hybrid nanoflowers for the immobilization of enzymes has received a significant degree of attention owing to their capability to retain high enzymatic activity and stability. However, the relative lack of reusability due to the weakness of the flower-like structure has limited their practical applications. Herein, we have developed a simple but efficient method to synthesize highly robust enzyme-inorganic hybrid nanoflowers, which relies on further crosslinking of the enzyme molecules entrapped in the hybrid nanoflowers by treatment with glutaraldehyde (GA). By employing lipase from Candida rugosa as a model enzyme with copper phosphate during 3days incubation followed by the additional GA treatment for only 1h, we could successfully synthesize GA-treated lipase nanoflowers having similar flower-like morphology and hydrolytic activity (ca. 95% compared with the free lipase) as conventionally synthesized lipase nanoflowers without GA treatment. Importantly, the conventional lipase nanoflowers seemed not to be reusable because they lost most of their activity (∼90%) after recycling 4 times, whereas GA-treated lipase nanoflowers exhibited higher retention of their initial activity (over 70%) after 4 reuses, which was also accompanied by an efficient maintenance of their flower-like morphology. Based on our results, we expect that this simple GA-mediated strategy to synthesize enzyme-inorganic hybrid nanoflowers can be readily extended to other enzymes for various biotechnological applications.

Lee|Hye Rin|HR|
Chung|Minsoo|M|
Kim|Moon Il|MI|
Ha|Sung Ho|SH|

Protein-inorganic hybrid nanoflowers
Reusability
Candida rugosa lipase
Glutaraldehyde treatment


Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis.

Abstract: We aimed to assess suicidality risk amongst people who had had anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16-78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality (p = 0.039); insomnia, aggression, mania, depression and delusion were also more common (p < 0.05). The use of antidepressants (p < 0.001) and recurrence of encephalitis (p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary.

Anti-NMDAR encephalitis
Predictors
Psychiatric symptom
Suicidal rate


Quality Assessment of Reporting Performance for EGFR Molecular Diagnosis in Non-Small Cell Lung Cancer.

Abstract:
BACKGROUND
Reports serve as a bridge between laboratories and clinicians, help synthesize an overwhelming amount of raw data into evidence-based medicine, and play a significant role in designing clinical treatments. In an effort to guarantee high-quality epidermal growth factor receptor (EGFR) gene mutation testing and reporting performance, the National Center for Clinical Laboratories launched a proficiency testing (PT) scheme reflecting clinical practices in China since 2014. This study focuses on the quality assessment of gene mutation reports.

MATERIALS AND METHODS
Fifty-three laboratories that submitted reports in both 2014 and 2016 EGFR gene mutation PT schemes were selected for report analysis and comparison according to predefined evaluation criteria.

RESULTS
The average score for reports from 2014 was 14 out of 30 points. The overall scores for reports from 2016 improved substantially, yielding an average score of 20 out of 30 points. Among the evaluation criteria, general items were well documented in the reports. However, items specific to molecular diagnosis were far from satisfactory, and some items were even missing.

CONCLUSION
The quality assessment of clinical written reports from 2014 and 2016 demonstrates that substantial improvements have been made in overall reporting performance. However, not all statements pertaining to important elements met expectations. To continue education, repeated PT schemes need to be executed in a timely fashion to expose and address existing shortcomings in clinical reports. There remains ample room for improvement towards generating concise, comprehensive, and readable reports.

IMPLICATIONS FOR PRACTICE
This article compares the quality of clinical gene mutation reports submitted in 2014 to those submitted in 2016 epidermal growth factor receptor proficiency testing schemes, exposes the existing shortcomings, and discusses ways to communicate results more effectively in the future. The findings demonstrate that notable progress was observed in the overall reporting performance. However, key points specific to molecular diagnosis were far from expectation, and some items were even missing. Standardization needs to be emphasized to improve the report format and content. This article provides a reference that laboratories can use to write concise, comprehensive, and readily accessible clinical reports.

Han|Yanxi|Y| Zhang|Rui|R| Lin|Guigao|G| Zhang|Kuo|K| Xie|Jiehong|J| Li|Jinming|J|

Epidermal growth factor receptor gene mutation


Relevance of the listener's motor system in recalling phrases enacted by the speaker.

Abstract: Memory for series of action phrases improves in listeners when speakers accompany each phrase with congruent gestures compared to when speakers stay still. Studies reveal that the listeners' motor system, at encoding, plays a crucial role in this enactment effect. We present two experiments on gesture observation, which explored the role of the listeners' motor system at recall. The participants listened to the phrases uttered by a speaker in two conditions in each experiment. In the gesture condition, the speaker uttered the phrases with accompanying congruent gestures, and in the no-gesture condition, the speaker stayed still while uttering the phrases. The participants were then invited, in both conditions of the experiments, to perform a motor task while recalling the phrases proffered by the speaker. The results revealed that the advantage of observing gestures on memory disappears if the listeners move at recall arms and hands (same motor effectors moved by the speaker, Experiment 1a), but not when the listeners move legs and feet (different motor effectors from those moved by the speaker, Experiment 1b). The results suggest that the listeners' motor system is involved not only during the encoding of action phrases uttered by a speaker but also when recalling these phrases during retrieval.

motor system
Enactment
gesture observation
memory for actions


Microglia Mediate the Occurrence and Development of Alzheimer's Disease Through Ligand-Receptor Axis Communication.

Abstract: Alzheimer's disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.

Jian|Chongdong|C| Wei|Lei|L| Mo|Ruikang|R| Li|Rongjie|R| Liang|Lucong|L| Chen|Liechun|L| Zou|Chun|C| Meng|Youshi|Y| Liu|Ying|Y| Zou|Donghua|D|

intercellular communication
LASSO
support vector machine
Alzheimer’s disease
receptor ligand axis


Mode of birth in twins: data and reflections.

Abstract: Our primary objective was to compare neonatal and maternal outcomes in women with twin pregnancies, beyond 32 weeks, having a planned vaginal birth or a planned caesarean section (CS). This was a retrospective cohort study from a single tertiary centre over nine years. 534 sets of twins ≥32 + 0 weeks of gestation were included. 401 sets were planned vaginally and 133 sets were planned by CS. We compared a composite adverse perinatal outcome (perinatal mortality or serious neonatal morbidity; five minute APGAR score ≤4, neurological abnormality and need for intubation) and a composite maternal adverse outcome (major haemorrhage, trauma or infection) between the groups. There were no significant differences. Given the similarity of these results with several other larger studies of twin birth, we sought to look at reasons why there is still a rising rate of CS for twin births. We further make suggestions for keeping this rate to a sensible minimum. Impact statement What is already known on this subject? The largest randomised controlled study comparing planned vaginal birth with planned CSs for lower risk twins between 32 and 39 weeks of gestation, showed no added safety from planned CS. However, in most of the Western countries this conclusion has failed to increase the number of planned vaginal births for lower risk twins. What do the results of this study add? This observational study from a single tertiary centre provides external validation of the twin trial results in a practical day-to-day setting. It also provides insights as to how planned vaginal birth can be developed and maintained, with a key focus on safety and maternal participation in decision making. It does focus on consent and providing accurate data. What are the implications of these findings for clinical practice and/or further research? There are good grounds to encourage vaginal birth for low-risk twin pregnancies. The trend of rising caesarean rates in low-risk twin pregnancies worldwide will erode important skills for the conduct of vaginal births without any clear benefit for mothers or babies. The current situation demands careful thought about implementing innovative training opportunities for younger obstetricians. Finally, we need intelligent responses to many non-evidence-based factors which can drive clinical practice.

Reitter|A|A|
Daviss|B A|BA|
Krimphove|M J|MJ|
Johnson|K C|KC|
Schlößer|R|R|
Louwen|F|F|
Bisits|A|A|

planned vaginal birth
twin birth
Birth mode
multiple pregnancies
perinatal and maternal outcome


Coronary stent thrombosis with vorapaxar versus placebo: results from the TRA 2° P-TIMI 50 trial.

Abstract:
BACKGROUND
Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease.

OBJECTIVES
The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting.

METHODS
TRA 2° P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria.

RESULTS
A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001).

CONCLUSIONS
The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2° P-TIMI 50] [P04737]; NCT00526474).

Bonaca|Marc P|MP|
Scirica|Benjamin M|BM|
Braunwald|Eugene|E|
Wiviott|Stephen D|SD|
O'Donoghue|Michelle L|ML|
Murphy|Sabina A|SA|
Morrow|David A|DA|

stent
antiplatelet therapy
DES
PAR-1
atherothrombosis
thienopyridine


Conservative management of lymphoedema in children: a systematic review.

Abstract:
PURPOSE
A systematic literature review was conducted to determine best practice conservative management of pediatric lymphoedema.

METHOD
The PRISMA protocol was followed; a search of Ovid Medline, Cinahl and Scopus was conducted using the search terms children OR pediatric OR adolescent AND lymphoedema OR lymphedema. Studies about management or treatment of lymphoedema in children were included while studies about filariasis, imaging, pathology, secondary lymphoedema, surgical techniques, central lymphoedema and those with participants with a median age greater than 18 years were excluded.

RESULTS
Of 738 possible studies identified, eight studies were eligible for inclusion in the review: four case reports, two retrospective service reviews and two prospective studies investigating different interventions. All studies were rated using the NHMRC hierarchy of evidence and appraised by both authors using the McMaster University Critical Review Form. Studies were of low quality with poor descriptions of management, small sample size, unclear and inconsistent methodology and irreproducible outcome measures.

CONCLUSION
This review identified low level evidence to support the use of pneumatic compression in the management of pediatric lymphoedema. Further research is required to identify optimal parameters for application of pneumatic compression and to investigate the use of other interventions for conservative management of pediatric lymphoedema.

D048228:Intermittent Pneumatic Compression Devices

Lymphoedema
pediatric
disease-management
management: self-management
therapeutics


Vaccination Vehicles for COVID-19 Immunization - China, 2021.

Abstract:
Background
Recently, developed vaccination vehicles were repurposed and deployed for coronavirus disease 2019 (COVID-19) vaccination in China. We described the vehicles and reported an evaluation of vaccination throughput of these vehicles for COVID-19 vaccination in China.

Methods
We obtained daily reports of COVID-19 vaccine doses administered in vehicles in Hubei Province between March 16 and 29 of 2021. We determined the rate of COVID-19 vaccines given and evaluated the applicability of vaccination vehicles for COVID-19 vaccination.

Results
Vehicles with 2 vaccination stations are suitable for several real-world scenarios. Vehicles administered an average of 72 COVID-19 vaccine doses per hour, with an upper limit of 145 doses per hour.

Conclusion
Vaccination vehicles can save human and financial resources and provide high quality, effective, convenient, and rapid on-site vaccination services; they can increase the pace of COVID-19 vaccination.

Lei|Hong|H| Cao|Lingsheng|L| Gong|Yi|Y| Yu|Wenzhou|W| Cao|Lei|L| Ye|Jiakai|J| Song|Yifan|Y| Li|Li|L|

vaccination
vaccination vehicle
COVID-19


A large genomic insertion containing a duplicated follistatin gene is linked to the pea aphid male wing dimorphism.

Abstract: Wing dimorphisms have long served as models for examining the ecological and evolutionary tradeoffs associated with alternative phenotypes. Here, we investigated the genetic cause of the pea aphid (Acyrthosiphon pisum) male wing dimorphism, wherein males exhibit one of two morphologies that differ in correlated traits that include the presence or absence of wings. We mapped this trait difference to a single genomic region and, using third generation, long-read sequencing, we identified a 120 kb insertion in the wingless allele. This insertion includes a duplicated follistatin gene, which is a strong candidate gene in the minimal mapped interval to cause the dimorphism. We found that both alleles were present prior to pea aphid biotype lineage diversification, we estimated that the insertion occurred millions of years ago, and we propose that both alleles have been maintained in the species, likely due to balancing selection.

genomics
wing dimorphism
genetics
Acyrthosiphon pisum
dispersal
evolutionary biology
gene duplication
genetic mapping
polymorphism


Segmental analysis of antidepressant and antipsychotic drugs in the hair of schizophrenic patients.

Abstract: Hair analysis is useful for documenting long-term exposure to drugs. The potential of hair analysis for therapeutic drug monitoring within the forensic field has been studied, but reference values for some antidepressants and antipsychotics in the hair of individuals undergoing chronic therapy are still lacking. In the present study, a method was developed and validated for the determination of 23 analytes, including antidepressants, antipsychotics, and related metabolites, in human hair by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hair samples (10 mg) were extracted with a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3) utilizing cryogenic grinding. The present method demonstrated sufficient selectivity, robustness, and accuracy. Sixteen analytes in hair were reported in 46 psychiatric patients receiving fixed drug dosages. To the best of our knowledge, the hair concentrations of perphenazine and norolanzapine, as well as the concentrations of amisulpride, aripiprazole and its metabolite dehydroaripiprazole, olanzapine, and sulpiride, in hair from individuals receiving fixed dosages is reported for the first time. A significant relationship between the administered dose and the concentration in the proximal hair segment was found only for clozapine, norclozapine, and chlorpromazine. The results confirmed that the idea of using hair concentrations to monitor a daily dose is inapplicable.

antidepressants and antipsychotics
hair analysis
LC-MS/MS
dose-concentration relationship
metabolite-to-drug ratio


Production and purification of recombinant enteropeptidase expressed in an insect-baculovirus cell system.

Abstract: Enteropeptidase (EC 3.4.21.9) is the glycoprotein enzyme in the small intestine that triggers the activation of the zymogens in pancreatic juice by converting trypsinogen into trypsin. Because of its physiological significance, there have been many studies on the expression, purification, and characterization of enteropeptidase from different species. The baculovirus expression system has been commonly used in research communities and scientific industries for the production of high levels of recombinant proteins, which require posttranslational modifications for functional activity. In the present study, we isolated bovine enteropeptidase catalytic subunit gene from Bos taurus indicus (GenBank accession no. KC756844), and cloned it in pFast Bac HT "A" baculovirus expression donor vector, under the polyhedrin promoter. Recombinant bovine enteropeptidase was expressed in SF-9 insect cells with high expression levels. Recombinant enteropeptidase was purified using Ni-NTA affinity chromatography. A 6-mg quantity of pure active protein was obtained from 100 mL culture using this approach. Its activity and kinetic parameters were determined by cleavage of its fluorogenic substrate Gly-(Asp) 4-Lys-β-naphthylamide. The recombinant bovine enteropeptidase showed a K m value of 0.75 ± 0.02 mM with K cat 25 ± 1 s.

enteropeptidase
baculovirus
insect cells
Ni-NTA affinity chromatography
Gly-(Asp) 4-Lys-β-naphthylamide
bacmids


Proteome Profiling of Wheat Shoots from Different Cultivars.

Abstract: Wheat is a cereal grain and one of the world's major food crops. Recent advances in wheat genome sequencing are by now facilitating its genomic and proteomic analyses. However, little is known about possible differences in total protein levels of hexaploid versus tetraploid wheat cultivars, and also knowledge of phosphorylated wheat proteins is still limited. Here, we performed a detailed analysis of the proteome of seedling leaves from two hexaploid wheat cultivars (Triticum aestivum L. Pavon 76 and USU-Apogee) and one tetraploid wheat (T. turgidum ssp. durum cv. Senatore Cappelli). Our shotgun proteomics data revealed that, whereas we observed some significant differences, overall a high similarity between hexaploid and tetraploid varieties with respect to protein abundance was observed. In addition, already at the seedling stage, a small set of proteins was differential between the small (USU-Apogee) and larger hexaploid wheat cultivars (Pavon 76), which could potentially act as growth predictors. Finally, the phosphosites identified in this study can be retrieved from the in-house developed plant PTM-Viewer (bioinformatics.psb.ugent.be/webtools/ptm_viewer/), making this the first searchable repository for phosphorylated wheat proteins. This paves the way for further in depth, quantitative (phospho)proteome-wide differential analyses upon a specific trigger or environmental change.

Vu|Lam Dai|LD|
Verstraeten|Inge|I|
Stes|Elisabeth|E|
Van Bel|Michiel|M|
Coppens|Frederik|F|
Gevaert|Kris|K|
De Smet|Ive|I|

proteome
wheat
leaf
mass spectrometry
phosphoproteome


Serum carnitine levels of children with epilepsy: Related factors including valproate.

Abstract:
OBJECTIVE
This study measured the serum carnitine levels in patients with epilepsy and determined the factors contributing to low carnitine levels.

METHODS
We measured the serum carnitine levels in 94 consecutive patients with epilepsy, including the free carnitine (FC) and acylcarnitine fractions, using an enzyme cycling method. We defined a low FC as a serum FC level < 36 μmol/L. Age, body mass index (BMI), standard deviation score of BMI (BMI-SDS), use of valproate, cognitive disorder, and feeding problems differed between patients with low and normal FC. In patients taking valproate, the associations of the serum FC level with the platelet count and serum ammonia and amylase levels were analyzed.

RESULTS
Univariate analysis showed that a low BMI and BMI-SDS, the use of valproate, and cognitive disorder were more frequent in patients with a low FC. Logistic regression analysis revealed that a low BMI-SDS and cognitive disorders were independently associated with a low FC. Among the patients taking valproate, a low BMI-SDS and age were associated with a low FC. The serum FC and ammonia levels were inversely correlated, whereas no correlation was observed between the serum FC level and platelet count or serum amylase level.

CONCLUSION
A low BMI and cognitive disorders were related to a low FC in patients with epilepsy and the serum carnitine levels should be monitored in these patients.

Okumura|Akihisa|A| Kurahashi|Hirokazu|H| Iwayama|Hideyuki|H| Numoto|Shingo|S|

Valproate
Free carnitine
Body mass index
Cognitive disorder
Ammonia


Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

Abstract: The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under-researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets.

D010523:Peripheral Nervous System Diseases

innate immune system
macrophage
fibroblast
adaptive immune system
lymphocytes
nodes of Ranvier


Concerned Whether You'll Make It in Life? Status Anxiety Uniquely Explains Job Satisfaction.

Abstract: Ever feel concerned that you may not achieve your career goals or feel worried about where your life is going? Such examples may reflect the experience of status anxiety, that is, concerns that one may be stuck or not able to move up in life, or worries that one may be too low in standing compared to society's standards. Status anxiety is believed to be exacerbated by economic inequality and negatively affect well-being. While job satisfaction is an important determinant of well-being, no research has examined whether status anxiety can also help explain people's satisfaction with their jobs. We tested whether status anxiety differs from other organizational constructs and uniquely relates to job satisfaction among full-time working adults. In a pilot study, we found that status anxiety is separate from the concept of job insecurity (e.g., perceived threat of job loss). Results of our main study also indicated that higher status anxiety significantly predicted lower job satisfaction beyond several other indicators of organizational attitudes (job insecurity, occupational self-efficacy, distributive, procedural, and interactional justice), as well as the tendency to seek status and several background factors (e.g., income, education, perceived socioeconomic status). We discuss the unique role of status anxiety in job satisfaction and the implications of this research to our understanding of status concerns, as well as organizational attitudes and policies.

status anxiety
job satisfaction
well-being
job insecurity
occupational self-efficacy
interactional justice
distributive justice
procedural justice


Molecular Epidemiology and Phylogeny of Crimean-Congo Haemorrhagic Fever (CCHF) Virus of Ixodid Ticks in Khorasan Razavi Province of Iran.

Abstract:
Background
Crimean-Congo hemorrhagic fever (CCHF) is a fatal disease caused by Nairovirus classified within the Bunyaviridae family. The virus is transmitted to humans through the bites of infected ticks or direct contact with viremic animals or humans. The current study aimed to detect the virus genome in ticks from Khorasan Razavi Province.

Methods
One hundred hard ticks were collected randomly from 100 sheep in four different areas of the province. Collected ticks were kept alive and identified. All the ticks were analyzed for the presence of CCHF virus genome using reverse transcriptase polymerase chain reactions (RT-PCR).

Results
The identified ticks were belonging to Hyalomma marginatum (16% female and 6% male), Rhipicephalus turanicus (52% female and 25% male), and Dermacentor raskemensis (1%). The CCHF virus genome was found in Hyalomma marginatum (5% male from Taibad and Sabzevar region and 1% female from Taibad). Genetic analysis of the virus genome isolated from two regions (Sabzevar and Taibad) showed 100% identity.

Conclusion
This study indicated that CCHF should be regarded as a risk-borne infection in this province. Therefore, special health management is needed to control this disease.

Maghsood|Hossein|H|
Nabian|Sedigheh|S|
Shayan|Parviz|P|
Jalali|Tahmineh|T|
Darbandi|Meysam Saboor|MS|
Ranjbar|Mohammad Mehdi|MM|

Crimean-Congo haemorrhagic fever
Ixodid ticks
Khorasan Razavi province


Gonococcal urethritis caused by a multidrug resistant Neisseria gonorrhoeae strain with high-level resistance to spectinomycin in China.

Abstract: We report a recent (2018) gonorrhoeal urethritis caused by a multidrug-resistant Neisseria gonorrhoeae strain in China. The isolated N. gonorrhoeae strain from a male and female pair expressed high-level resistance to spectinomycin (SPC), azithromycin, and other antibiotics but was sensitive to ceftriaxone. The SPC high-level resistance (MIC = 2048 mg/L) was due to a small deletion in rspE that caused two amino acid changes in ribosomal protein S5.

Chen|Shao-Chun|SC| Hu|Li-Hua|LH| Zhu|Xiao-Yu|XY| Yin|Yue-Ping|YP|

D024901:Drug Resistance, Multiple, Bacterial

urethritis
resistance
Neisseria gonorrhoeae
spectinomycin
treatment failure


About the relationship between ship noise and the occurrence of arterial hypertension in seafarers.

Abstract: No abstract because letter to editor.

noise
arterial hypertension
seafarers
hearing loss


Analysis of Long Non-Coding RNA in Cryptosporidium parvum Reveals Significant Stage-Specific Antisense Transcription.

Abstract: Cryptosporidium is a protist parasite that has been identified as the second leading cause of moderate to severe diarrhea in children younger than two and a significant cause of mortality worldwide. Cryptosporidium has a complex, obligate, intracellular but extra cytoplasmic lifecycle in a single host. How genes are regulated in this parasite remains largely unknown. Long non-coding RNAs (lncRNAs) play critical regulatory roles, including gene expression across a broad range of organisms. Cryptosporidium lncRNAs have been reported to enter the host cell nucleus and affect the host response. However, no systematic study of lncRNAs in Cryptosporidium has been conducted to identify additional lncRNAs. In this study, we analyzed a C. parvum in vitro strand-specific RNA-seq developmental time series covering both asexual and sexual stages to identify lncRNAs associated with parasite development. In total, we identified 396 novel lncRNAs, mostly antisense, with 86% being differentially expressed. Surprisingly, nearly 10% of annotated mRNAs have an antisense transcript. lncRNAs occur most often at the 3' end of their corresponding sense mRNA. Putative lncRNA regulatory regions were identified and many appear to encode bidirectional promoters. A positive correlation between lncRNA and upstream mRNA expression was observed. Evolutionary conservation and expression of lncRNA candidates was observed between C. parvum, C. hominis and C. baileyi. Ten C. parvum protein-encoding genes with antisense transcripts have P. falciparum orthologs that also have antisense transcripts. Three C. parvum lncRNAs with exceptional properties (e.g., intron splicing) were experimentally validated using RT-PCR and RT-qPCR. This initial characterization of the C. parvum non-coding transcriptome facilitates further investigations into the roles of lncRNAs in parasite development and host-pathogen interactions.

Li|Yiran|Y|
Baptista|Rodrigo P|RP|
Sateriale|Adam|A|
Striepen|Boris|B|
Kissinger|Jessica C|JC|

lncRNA
parasite development
transcriptome
Apicomplexa
RNA regulation
stranded RNA-Seq


An Automatic Suturing Machine for Intestinal Anastomosis: Advantages Compared With Hand-Suturing Technique.

Abstract: One of the main procedures in intestinal surgery is anastomosis, which is mostly performed by stapling or hand suturing. Due to limitations of these methods, a novel automatic suturing machine was designed and fabricated in this study, equipped with a needle-driving system; a thread control mechanism, and a linear mechanism, which is applicable in intestinal anastomosis by making continuous sutures. The main advantages of the fabricated machine are employing biocompatible suture, from the tissue's adaptation point of view, and making a uniform suturing pattern, independent of surgeon's skill, and thus offering a greater strength than the hand-sutured specimen. In order to evaluate the capability of the fabricated machine and investigate the validity of the hypothesis made in this study, that is, a more uniform suture will result in a greater mechanical strength of the sutured tissue, in vitro tests were performed on human intestine specimens, which were manually sutured by an expert surgeon and by the automatic suturing machine. The tensile tests with an elongation rate of 5 mm/min were done for 90 specimens, in 9 groups with various suturing configurations. The optimum pattern, from the mechanical strength point of view, was found to be the same in both manual and automatic suturing methods, that is, h7 d6 ( h = distance of suture from the edge of the tissue = 7 mm, and d = distance between stitches = 6 mm). It was also shown that the maximum breaking strength, for the best suturing pattern, h7 d6, is significantly greater when the automatic suturing machine was employed, compared with the hand-sutured tissue ( P < .001).

D013505:Digestive System Surgical Procedures

intestinal anastomosis
hand suturing
design and fabrication
breaking strength
best suturing pattern
automatic stitching
tensile mechanical test


Long-term exposure to microplastics induces oxidative stress and a pro-inflammatory response in the gut of Sparus aurata Linnaeus, 1758.

Abstract: Environmental pollution from plastic debris is a major global concern, being a potential threat to marine organisms and ecosystems. The accumulation of microplastics (MPs) in the oceans has notable ecological implications due to their long persistence, their potential ecotoxicity, and their ability to adsorb other pollutants and act as vectors of pathogens. Nevertheless, whereas the number of investigations documenting the presence of MPs in wild fish has increased, less studies have addressed the toxicological effects associated with the ingestion of MPs in long-term laboratory conditions. The aim of the present study was to assess the physiological response of gilthead seabream (Sparus aurata) exposed to low-density polyethylene (LDPE) MPs during a 90-day exposure followed by an extra 30 days of depuration through the application of oxidative stress biomarkers in the gut. No changes were observed in the Fulton condition factor of fish associated with MP intake. The activities of antioxidant enzymes and glutathione s-transferase and the levels of reduced glutathione progressively increased throughout the study in the MPs-fed group compared to the control group, reaching the highest values at 90 days. Similarly, the activity of the pro-inflammatory enzyme, myeloperoxidase, and the levels of oxidative damage markers -malondialdehyde and protein carbonyls-also increased after 90 days of exposure to an enriched diet with MPs. During the 30-day depuration period, all the biomarkers analysed tended to normalize, with the majority recovering values similar to those of the control group. In conclusion, MPs exposure during 90 days to S. aurata induced oxidative stress and a pro-inflammatory response in gut, and were able to recover after the exposure to MPs was removed.

Solomando|Antònia|A|
Capó|Xavier|X|
Alomar|Carme|C|
Álvarez|Elvira|E|
Compa|Montserrat|M|
Valencia|José María|JM|
Pinya|Samuel|S|
Deudero|Salud|S|
Sureda|Antoni|A|

Microplastics
Oxidative stress
Gilthead seabream
Low-density polyethylene
Toxicity


Trigeminal Neuralgia Caused by Vascular Compression from the Petrous Carotid Artery with Bony Erosion and Meckel Cave Encephalocele: Clinical Imaging with Surgical Video.

Abstract: Trigeminal neuralgia (TN) is most commonly caused by neurovascular compression of the superior cerebellar artery. We present the first reported TN case where nerve compression was caused by the petrous internal carotid artery in the vicinity of a Meckel cave (MC) encephalocele. The patient underwent a pterional craniotomy for decompression of the gasserian ganglion and trigeminal nerve branches. All symptoms were resolved post surgery. We surmise that the principal cause of the TN was vascular compression from an exposed petrous internal carotid artery in the presence of an encephalocele. Causation was irrespective of whether the dehiscence in the petrous apex was a congenital defect or associated with destruction from the encephalocele. Based on this observation, we recommend that surgeons carefully consider all possible causes of patient symptoms as they prepare a meticulous dissection plan to avoid damage to surrounding neurovascular structures.

Erginoglu|Ufuk|U|
Sayyahmelli|Sima|S|
Baskaya|Mustafa K|MK|

Trigeminal neuralgia
Meckel cave
Encephalocele
Petrous internal carotid


Endometriotic Pain Is Associated with Adenomyosis but Not with the Compartments Affected by Deep Infiltrating Endometriosis.

Abstract:
BACKGROUND
The identification of presurgical clinical markers may be helpful to allow the staging of endometriosis severity. It has been suggested that pain characteristics orientate the gynecologist about the anatomical involvement of endometriosis. The study was performed to analyze the correlation between pain symptoms and the anatomical location of endometriosis.

METHODS
One hundred fifty-five consecutive patients with a complete removal of deep infiltrating endometriosis (DIE) were included. Prior to surgery, data on patient and disease characteristics were obtained. The intensity of the pain symptoms was registered using a Visual Analogue Scale. The endometriotic lesions were categorized according to the Enzian morphological classification. Correlation and multivariate analysis were performed to assess the potential associations between pain characteristics (dysmenorrhea, pelvic pain, dyschezia, dyspareunia or dysuria) and the location of endometriosis or other disease-related characteristics (hematuria, rectal bleeding or adenomyosis).

RESULTS
Pelvic pain was significantly associated with the presence of adenomyosis. Dyschezia was correlated with rectal bleeding and dysuria with the presence of hematuria. No relationship was found between other kinds of pain and the morphological location of endometriosis or other disease-related characteristics.

CONCLUSION
Our data suggest that pelvic pain is correlated with the presence of adenomyosis in women with DIE. Further studies are required.

Perelló|Maria Francesca|MF|
Martínez-Zamora|Maria Ángeles|MÁ|
Torres|Ximena|X|
Munrós|Jordina|J|
Balasch Cortina|Juan|J|
Carmona|Francisco|F|

Pain
Adenomyosis
Endometriosis
Marker
Enzian classification


Clinical Research of Combined Intravenous Administration and Topical Application of Tranexamic Acid to a Surgical Wound During Posterior Lumbar Fusion.

Abstract:
BACKGROUND
The safety and effectiveness of combined intravenous and topical administration of tranexamic acid (TXA) on the reduction of blood loss in patients undergoing posterior lumbar fusion are not yet clear. The study aimed to investigate the safety and effectiveness of the combined intravenous and topical administration of TXA on the reduction of blood loss in patients undergoing posterior lumbar fusion.

METHOD
One hundred and eighteen patients who underwent double-segment posterior lumbar decompression and fusion from February 2014 to May 2016 in our hospital were retrospectively reviewed. Patients were divided into two groups, the experimental group and the control group. Preoperative demographics, operative parameters, and adverse effect were recorded and compared.

RESULTS
Intraoperative blood loss, postoperative 24-hour drainage volume, and blood transfusion ratio and volume were significantly lower in the experimental group than in the control group (P < .01); on postoperative 24 hours and 48 hours, hemoglobin and hematocrit levels were significantly higher in the experimental group than in the control group (P < .01). Prothrombin time and fibrinogen content were not significantly different between the 2 groups. The postoperative length of hospital stay was shorter in the experimental group than in the control group (P < .01). No postoperative thrombotic events were reported in either group.

CONCLUSIONS
Combined intravenous and topical administration of TXA seems to be effective and safe in reducing allogenic blood transfusion and blood loss in double-segment posterior lumbar decompression and fusion surgery.

Ou|Yufu|Y| Wei|Jianxun|J| Li|Rongzhu|R| Liang|Bin|B| Qiu|Dezan|D| Wei|Minke|M| Mu|Xiaoping|X| Li|Zhuhai|Z|

D061605:Administration, Intravenous
D000287:Administration, Topical
D000368:Aged
D000933:Antifibrinolytic Agents
D016063:Blood Loss, Surgical
D001803:Blood Transfusion
D005260:Female
D006801:Humans
D008159:Lumbar Vertebrae
D008297:Male
D008875:Middle Aged
D019106:Postoperative Hemorrhage
D012189:Retrospective Studies
D013123:Spinal Fusion
D014148:Tranexamic Acid

tranexamic acid
posterior lumbar fusion
blood loss
blood transfusion
gelatin sponge


Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical Acinetobacter baumannii Lineages.

Abstract: The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In Acinetobacter baumannii, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stability, onset modalities, and phylogenomics were investigated in a clinical A. baumannii sample showing a COL resistant (COLR) phenotype at first isolation. COL-R was confirmed by Minimum-Inhibitory-Concentrations as well as investigated by Resistance-Induction assays and Population-Analysis-Profiles (PAPs) to determine: (i) stability; (ii) inducibility; (iii) heteroresistance. Genomics was performed by Mi-Seq Whole-Genome-Sequencing, Phylogenesis, and Genomic Epidemiology by bioinformatics. COLRA. baumannii were subdivided as follows: (i) 3 A. baumannii with stable and high COL MICs defining the "homogeneous-resistant" onset phenotype; (ii) 6 A. baumannii with variable and lower COL MICs displaying a "COL-inducible" onset phenotype responsible for adaptive-resistance or a "subpopulation" onset phenotype responsible for COL-heteroresistance. COL-R stability and onset strategies were not uniquely linked to the amount of LPS and cell envelope charge. Phylogenomics categorized 3 lineages clustering stable and/or unstable COL-R phenotypes with increasing genomic complexity. Likewise, different nsSNP profiling in genes already associated with COL-R marked the stable and/or unstable COL-R phenotypes. Our investigation finds out that A. baumannii can range through unstable or stable COLR phenotypes emerging via different "onset strategies" within phylogenetic lineages displaying increasing genomic mosaicism.

genomic mosaicism
A. baumannii
phylogenetic lineages
colistin resistance stability


Utilization of open source electronic health record around the world: A systematic review.

Abstract: Many projects on developing Electronic Health Record (EHR) systems have been carried out in many countries. The current study was conducted to review the published data on the utilization of open source EHR systems in different countries all over the world. Using free text and keyword search techniques, six bibliographic databases were searched for related articles. The identified papers were screened and reviewed during a string of stages for the irrelevancy and validity. The findings showed that open source EHRs have been wildly used by source limited regions in all continents, especially in Sub-Saharan Africa and South America. It would create opportunities to improve national healthcare level especially in developing countries with minimal financial resources. Open source technology is a solution to overcome the problems of high-costs and inflexibility associated with the proprietary health information systems.

Electronic health record
healthcare
health information system
electronic medical record
open source software


Comprehension of wh-questions in Turkish-German bilinguals with aphasia: A dual-case study.

Abstract: The aim of our study was to examine the extent to which linguistic approaches to sentence comprehension deficits in aphasia can account for differential impairment patterns in the comprehension of wh-questions in bilingual persons with aphasia (PWA). We investigated the comprehension of subject and object wh-questions in both Turkish, a wh-in-situ language, and German, a wh-fronting language, in two bilingual PWA using a sentence-to-picture matching task. Both PWA showed differential impairment patterns in their two languages. SK, an early bilingual PWA, had particular difficulty comprehending subject which-questions in Turkish but performed normal across all conditions in German. CT, a late bilingual PWA, performed more poorly for object which-questions in German than in all other conditions, whilst in Turkish his accuracy was at chance level across all conditions. We conclude that the observed patterns of selective cross-linguistic impairments cannot solely be attributed either to difficulty with wh-movement or to problems with the integration of discourse-level information. Instead our results suggest that differences between our PWA's individual bilingualism profiles (e.g. onset of bilingualism, premorbid language dominance) considerably affected the nature and extent of their impairments.

wh-questions
Turkish-German bilingualism
wh-in-situ
wh-movement
Bilingual aphasia


Omega-3 Supplementation and Heart Disease: A Population-Based Diet by Gene Analysis of Clinical Trial Outcomes.

Abstract: Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and their metabolites have long been recognized to protect against inflammation-related diseases including heart disease. Recent reports present conflicting evidence on the effects of n-3 PUFAs on major cardiovascular events including death. While some studies document that n-3 PUFA supplementation reduces the risk for heart disease, others report no beneficial effects on heart disease composite primary outcomes. Much of this heterogeneity may be related to the genetic variation in different individuals/populations that alters their capacity to synthesize biologically active n-3 and omega 6 (n-6) PUFAs and metabolites from their 18 carbon dietary precursors, linoleic acid (LA, 18:2 n-6) and alpha-linolenic (ALA, 18:3, n-3). Here, we discuss the role of a FADS gene-by-dietary PUFA interaction model that takes into consideration dietary exposure, including the intake of LA and ALA, n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in determining the efficacy of n-3 PUFA supplementation. We also review recent clinical trials with n-3 PUFA supplementation and coronary heart disease in the context of what is known about fatty acid desaturase (FADS) gene-by-dietary PUFA interactions. Given the dramatic differences in the frequencies of FADS variants that impact the efficiency of n-3 and n-6 PUFA biosynthesis, and their downstream signaling products among global and admixture populations, we conclude that large clinical trials utilizing "one size fits all" n-3 PUFA supplementation approaches are unlikely to show effectiveness. However, evidence discussed in this review suggests that n-3 PUFA supplementation may represent an important opportunity where precision interventions can be focused on those populations that will benefit the most from n-3 PUFA supplementation.

D002986:Clinical Trials as Topic
D004032:Diet
D019587:Dietary Supplements
D015525:Fatty Acids, Omega-3
D014644:Genetic Variation
D006331:Heart Diseases
D006801:Humans

genetic variation
coronary heart disease
FADS gene
n-3 polyunsaturated fatty acids
precision nutrition


Coagulation of humic waters for diffused pollution control and the influence of coagulant type on DOC fractions removed.

Abstract: This study examined the suitability of organic coagulants for treatment of typically humic peat extraction runoff water by comparing their performance with that of ferric sulphate (FS). The influence of coagulant type on dissolved organic carbon (DOC) fractions removed was analysed in detail using LC-OCD-OND (size exclusion liquid chromatography coupled with organic carbon and organic nitrogen detection) fractionation techniques. In general, lower coagulant dosage was needed under acidic (pH 4.5) than neutral (pH 6.5) conditions. Chitosan (Chit) and poly (diallyldimethyl) ammonium chloride (pDMAC) required significantly lower dosage (40-55%) than FS for acceptable purification, while a tannin-based coagulant (Tan2) required substantially higher dosage (55-75%) independent of water pH. FS demonstrated the best removal of DOC (<81%) and phosphorus (<93%) followed by pDMAC, while Chit and Tan2 achieved the highest removal of suspended solids (SS) (<58%), with flocs formed by Tan2 presenting the best settling properties. Higher molecular weight (MW) DOC fractions were more efficiently removed by all coagulants, with FS being the most efficient (biopolymers 69% and humic substances 91%), followed by Tan2. FS also displayed satisfactory removal of lower MW fractions (building blocks ∼46% and low MW neutrals 62%). Overall, FS was the best performing coagulant. Nevertheless, the organic polymers demonstrated satisfactory overall performance, achieving purification rates mostly inside the requirements set by Finnish environmental authorities.

Coagulation
DOC fractionation
LC-OCD-OND
Organic nitrogen
Organic polymers


Measuring enzymatic degradation of degradable starch microspheres using confocal laser scanning microscopy.

Abstract: Degradable starch microspheres (DSM) have long been used for topical haemostasis, temporary vascular occlusion and as drug delivery systems. When used for the latter, exact degradation rates of DSM have high importance, as this ensures a controlled and timed drug delivery. Current methods of analysing degradation rates are based on whole batch measurements, which does not yield information regarding individual times of degradation nor does it provide direct correlation measurements between sphere diameter and specific degradation time. In this paper we present an alternative method for measuring degradation rates of biodegradable starch microspheres using confocal laser scanning microscopy (CLSM). We succeeded in visualizing the degradation by staining the DSM and then following the spheres over time in a confocal microscope, after the addition of α-amylase. Individual degradation rates of single spheres could be followed, allowing a precise correlation measure between sphere size and degradation time. Furthermore, physical abnormalities such as internal cavities were detected within some spheres. These physical differences also had a measurable effect on the rate of degradation. Finally, complete degradation rates could be determined very accurately. To our knowledge, this is the first paper in which DSM degradation is visualized and measured using CLSM. STATEMENT OF SIGNIFICANCE: Using degradable starch microspheres as a drug delivery system, is a continuously evolving field which shows promise in several different areas of illnesses. This paper presents a new method which visualizes enzymatic degradation of starch microspheres in real-time using confocal microscopy. The method is simple, yet the versatility of it suggests that it could be broadly applied within the field of biodegradation. Here, it illuminates a previously uninvestigated parameter: the effect of physical sphere deformities on the rate of degradation. It also provides precise correlation measures between initial sphere size and time of complete degradation.

Thaarup|Ida C|IC|
Gummesson|Camilla|C|
Bjarnsholt|Thomas|T|

Degradation
Degradable starch microspheres
Methods
Confocal microscopy
Drug carrier


Baseline characteristics of COVID-19 Italian patients admitted to Desio Hospital, Lombardy: a retrospective study.

Abstract: The correlation of clinical, radiological and laboratory findings of patients at admission in the Emergency Department (ED) with clinical severity and risk of mortality was investigated. Adult coronavirus disease 2019 (COVID-19) patients hospitalized in March 2020 in Desio Hospital, Lombardy, were retrospectively included in the study, and categorized in terms of disease severity and adverse outcome. Out of the 175 patients enrolled, 79% presented one or more comorbidities, with cardiovascular disease being the most frequent (62%). More than half of the patients showed lymphocytopenia and 20% thrombocytopenia. The patients in the severe group presented higher absolute neutrophil count (ANC), C-reactive protein (CRP), AST, LDH, procalcitonin (PCT) and BUN values compared to the non-severe group (p < .05). Increased odds of mortality associated with older age (OR = 22.43; 95% CI 5.22-96.27), partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) ratio < 200 (OR = 4.97; 95% CI 1.55-15.84), clinical severity (OR = 21.32; 95% CI 2.27-200.13), creatinine > 106.08 µmol/L (OR = 2.87; 95% CI 1.04-7.92) and creatine kinase > 2.90 µkat/L (OR = 3.80; 95% CI 1.31-10.9) were observed on admission (p < .05). The above findings may contribute to identify early risk factors of poor prognosis, and to select the most appropriate management for patients.

Sulejmani|Adela|A| Galimberti|Elisa|E| Giacobone|Chiara|C| Milano|Antonio|A| Scopetta|Elena|E| Intra|Jari|J| Falbo|Rosanna|R| Sarto|Cecilia|C| Leoni|Valerio|V| Brambilla|Paolo|P|

COVID-19
mortality
comorbidities
lymphocytopenia
older age
PaO2/FIO2 ratio


Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals.

Abstract:
AIM
Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs.

METHODS
The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60 mL min(-1) 1.73 m(-2) ] and 659 controls (eGFR of ≥90 mL min(-1) 1.73 m(-2) ). The genotypes for 29 polymorphisms of 28 candidate genes were determined.

RESULTS
The χ(2) test revealed that rs4845625 (T→C) of IL6R, rs4773144 (A→G) of COL4A1, rs9319428 (G→A) of FLT1, and rs46522 (T→C) of UBE2Z were significantly (P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P = 0.0065) greater and eGFR was significantly (P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype.

CONCLUSION
The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.

Horibe|Hideki|H| Fujimaki|Tetsuo|T| Oguri|Mitsutoshi|M| Kato|Kimihiko|K| Matsuoka|Reiko|R| Abe|Shintaro|S| Tokoro|Fumitaka|F| Arai|Masazumi|M| Noda|Toshiyuki|T| Watanabe|Sachiro|S| Yamada|Yoshiji|Y|

D020022:Genetic Predisposition to Disease

polymorphism
receptors
genetics
interleukin-6
kidney failure
renal insufficiency


BFF: Bayesian, Fiducial, and Frequentist Analysis of Cognitive Engagement among Cognitively Impaired Older Adults.

Abstract: Engagement in cognitively demanding activities is beneficial to preserving cognitive health. Our goal was to demonstrate the utility of frequentist, Bayesian, and fiducial statistical methods for evaluating the robustness of effects in identifying factors that contribute to cognitive engagement for older adults experiencing cognitive decline. We collected a total of 504 observations across two longitudinal waves of data from 28 cognitively impaired older adults. Participants' systolic blood pressure responsivity, an index of cognitive engagement, was continuously sampled during cognitive testing. Participants reported on physical and mental health challenges and provided hair samples to assess chronic stress at each wave. Using the three statistical paradigms, we compared results from six model testing levels and longitudinal changes in health and stress predicting changes in cognitive engagement. Findings were mostly consistent across the three paradigms, providing additional confidence in determining effects. We extend selective engagement theory to cognitive impairment, noting that health challenges and stress appear to be important moderators. Further, we emphasize the utility of the Bayesian and fiducial paradigms for use with relatively small sample sizes because they are not based on asymptotic distributions. In particular, the fiducial paradigm is a useful tool because it provides more information than p values without the need to specify prior distributions, which may unduly influence the results based on a small sample. We provide the R code used to develop and implement all models.

Bayesian
frequentist
cognitive engagement
cognitive impairment
fiducial paradigm


Appraising drought hazard during Boro rice growing period in western Bangladesh.

Abstract: Drought is one of the critical agro-meteorological hazards in the world including Bangladesh. Rice is the major food grain in Bangladesh, and drought has threatened the food grain and the country's food security. However, drought hazard (DH) in the Boro rice growing period and their associations are less investigated in Bangladesh. Hence, we intend to appraise the DH in the vegetative, reproductive, and ripening phases and the whole growing season based on the daily temperature, precipitation data, and yearly rice phenology dataset from 8 meteorological stations in western Bangladesh from 1980 to 2013. The Mann-Kendall (M-K) test was employed to identify the trend in phenology dates and drought hazard. The standardized precipitation evapotranspiration index (SPEI) was adopted to compute the DH. The results show that moderate to severe drought events occurred in western Bangladesh during Boro rice growing period. The transplanting dates were delayed in the southwestern part by a rate of 1.31 day/year along with a trend towards a shorter and more humid ripening phase (p < 0.05). By contrast, transplanting dates were started earlier in the northwestern part with a rate of - 0.48 day/year along with the enhanced length of the reproductive and the ripening phases (p < 0.10). We appraised the DH during each Boro rice growing season, where the ripening phase faced a more severe DH than other phases that were most susceptible to water stress conditions. There was a strong association between DH and crop yield loss during the whole growth period in the study area.

Islam|Abu Reza Md Towfiqul|ARMT|https://orcid.org/0000-0001-5779-1382

Drought Hazard
Rice phenology
Mann-Kendall
SPEI
Yield loss rate


A comparative study evaluating the role of adductor canal block catheter versus intraarticular analgesic infusion on knee pain and range of motion in the immediate postoperative period: a prospective multicenter trial.

Abstract: Postoperative pain after total knee arthroplasty (TKA) is an important determinant of hospital stay and rehabilitation and thereby functional outcome. Adductor canal block (ACB) and intraarticular analgesic infiltration through catheters (IAC) are techniques of multimodal analgesia which have shown to control postoperative pain satisfactorily. The aim of this study is to evaluate the efficacy of ACB versus IAC in reducing immediate postoperative pain and thereby allow early rehabilitation. A multicenter quasi-experimental study was conducted on 511 patients undergoing unilateral primary TKA from March 2016 to April 2017 who either received ACB with catheter (Group I, n = 350 patients) or IAC (Group II, n = 172 patients) for postoperative pain control. All the patients were assessed for severity of pain by Visual Analogue Scale at 8, 24, 48, 72 h postoperatively and knee range of motion (ROM) on the day of discharge. There was no significant difference in pain scores on postoperative day (POD) 0 (1.09 ± 0.30 vs. 0.98 ± 0.46, p = 0.45) and POD 1 (1.21 ± 0.45 vs. 1.00 ± 0.00, p = 0.11) and in mean ROM on the day of discharge between ACB and IAC (88.40° ± 7.96° vs. 88.34° ± 5.74°; p = 0.93) groups. This study shows that both ACB and IAC provide satisfactory postoperative analgesia with sparing of quadriceps function and good knee ROM leading to early rehabilitation and reduced hospital with no advantage of one technique over another.

D059787:Acute Pain
D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D000779:Anesthetics, Local
D018771:Arthralgia
D019645:Arthroplasty, Replacement, Knee
D002406:Catheterization, Peripheral
D006801:Humans
D007719:Knee Joint
D008875:Middle Aged
D009407:Nerve Block
D010147:Pain Measurement
D010149:Pain, Postoperative
D011184:Postoperative Period
D011446:Prospective Studies
D052097:Quadriceps Muscle
D016059:Range of Motion, Articular

Adductor canal block
Total knee arthroplasty
Intraarticular catheter
Local infiltration analgesia


Overexpression of SlMDHAR in transgenic tobacco increased salt stress tolerance involving S-nitrosylation regulation.

Abstract: Protein S-nitrosylation, which refers to the redox-based posttranslational modification of a cysteine thiol by the attachment of a nitric oxide (NO) group, modulates a variety of enzyme activities. Monodehydroascorbate reductase (MDHAR) is essential for ascorbic acid (AsA) regeneration, which protects plant cells against damage by detoxifying reactive oxygen species (ROS). However, the relationship between S-nitrosylation and the role of tomato MDHAR (SlMDHAR) under salt stress remains unclear. In this paper, we show that the SlMDHAR mRNA expression, enzyme activity, protein level, total S-nitrosylated proteins and S-nitrosylated SlMDHAR protein level in tomato leaves significantly increase after NaCl treatment. To further evaluate the function of SlMDHAR under salt stress, overexpressed transgenic tobacco plants were used. The germination rate and root length of the overexpressed plants under NaCl stress were significantly higher than those of wild-type (WT) plants. Meanwhile, the transgenic plants had lower ROS accumulation, higher antioxidant enzyme activities and AsA-DHA ratio, more proline and soluble sugar contents than those in WT plants under salt stress. With a higher expression of stress-related genes, the transgenic plants demonstrated lower Na+ and higher K+ accumulation compared with WT plants. The NO accumulation and S-nitrosylated MDHAR level were higher in transgenic plants than in WT plants after NaCl treatment. In contrast, virus-induced gene silencing (VIGS) of SlMDHAR tomato plants showed enhanced sensitivity to salt stress and have lower S-nitrosylated MDHAR protein. These results suggested that SlMDHAR confers salt stress tolerance by alleviating oxidative damage probably involving the S-nitrosylation of MDHAR.

Qi|Qi|Q| Yanyan|Dong|D| Yuanlin|Liang|L| Kunzhi|Li|L| Huini|Xu|X| Xudong|Sun|S|

D018506:Gene Expression Regulation, Plant


Fast Crystal Growth Induces Mobility and Tension in Supercooled o-Terphenyl.

Abstract: A photobleaching method was used to measure the reorientation of dilute probes in liquid o-terphenyl near a crystal growth front. Near the glass-transition temperature Tg, mobility in the supercooled liquid was enhanced within ∼10 μm of the crystal growth front, by as much as a factor of 4. This enhanced mobility appears to be caused by tension created in the sample as a result of the density difference between the supercooled liquid and crystal. The maximum observed mobility enhancement corresponds to a tension of about -8 MPa, close to the cavitation limit for liquid o-terphenyl. Whereas the observed mobility near the growing crystal is not large enough to explain the extraordinary fast crystal growth observed near Tg in o-terphenyl and some other low-molecular-weight glassformers, these observations suggest that cavitation or fracture plays a key role in releasing tension and allowing fast crystal growth to occur at a steady rate.

Paeng|Keewook|K|
Powell|C Travis|CT|
Yu|Lian|L|
Ediger|M D|MD|

GC crystal
molecular mobility
organic glassformers
rotational diffusion


Effect of SMYD3 on biological behavior and H3K4 methylation in bladder cancer.

Abstract:
Purpose
Our goal was to investigate the effect of SMYD3 on the biological behavior and histone 3 lysine-4 (H3K4) methylation of bladder cancer (BLAC).

Patients and methods
qRT-PCR identified that SMYD3 expression level in BLAC cell lines (T24, 5637, BUI-87 and J-82) and human normal uroepithelial cell line SV-HUC1. We also constructed green fluorescence protein lentiviral vector using the gene short hairpin RNA (shRNA) system. We used Western blot to analyze the SMYD3, H3K4me1, H3K4me2 and H3K4me3 expression levels in shRNA transfection lines. We also performed a colony-forming assay to determine colony-forming ability, cell counting kit-8 for cell proliferation detection, Transwell assay to determine cell migration and invasion and Annexin V-FITC/PI double staining to analyze cell apoptosis.

Results
The SMYD3 expression level was significantly higher in BLAC cell lines (T24, 5637, BUI-87 and J-82) than in human normal uroepithelial cell line SV-HUC1, and exhibited the highest expression level in T24 cells, among the cell lines tested. qRT-PCR and Western blot analysis results showed that SMYD3 was successfully suppressed in shRNA transfection lines, and identified that SMYD3 suppression resulted inhibited H3K4me2 and H3K4me3 but not H3K4me1. SMYD3 knockdown cells accelerated cell apoptosis and exhibited low cell colony-forming ability, proliferation ability, inhibition of cell migration and invasion compared with normal cells.

Conclusion
SMYD3 may be activated in BLAC cells to increase H3K4 activity to modulate cell proliferation, migration and invasion ability. The data will be a useful source for future therapy.

Wu|Xiang|X| Xu|Qingjiang|Q| Chen|Pingzhou|P| Yu|Chenbo|C| Ye|Liefu|L| Huang|Chen|C| Li|Tao|T|

SMYD3
H3K4 methylation
bladder cancer
cell proliferation


Objective Assessment of Venous Pulse Wave Velocity in Healthy Humans.

Abstract: Central venous pressure and volume status are relevant parameters for characterization of a patient's hemodynamic condition; however, their invasive assessment is affected by various risks while non-invasive approaches provide limited and subjective indications. Here we explore the possibility of assessing venous pulse wave velocity (vPWV), a potential indicator of venous pressure changes. In eight healthy patients, pressure pulses were generated artificially in the leg veins by rapid compression of the foot, and their propagation was detected at the level of the superficial femoral vein with Doppler ultrasound. Changes in leg venous pressure were obtained by raising the trunk from the initial supine position by 30° and 60°. vPWV increased from 1.78 ± 0.06 m/s (supine) to 2.26 ± 0.19 m/s (60°) (p < 0.01) and exhibited an overall linear relationship with venous pressure. These results indicate that vPWV can be easily assessed, and is a non-invasive indicator of venous pressure changes.

Ermini|Leonardo|L|
Ferraresi|Carlo|C|
De Benedictis|Carlo|C|
Roatta|Silvestro|S|

Pulse wave velocity
Central venous pressure
Hemodynamics
Echo Doppler


Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.

Abstract:
BACKGROUND
Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress.

OBJECTIVE
We performed a large comprehensive study on how coffee consumption is associated with telomere length.

METHODS
We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables.

RESULTS
Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non-coffee drinkers, multivariable ORs for those drinking 2 to <3 and ≥3 cups of coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37).

CONCLUSIONS
We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and longevity.

Liu|Jason J|JJ|
Crous-Bou|Marta|M|
Giovannucci|Edward|E|
De Vivo|Immaculata|I|

coffee
telomere
telomere length
caffeine
decaffeinated coffee
epidemiology


Relationship of Test Positivity Rates with COVID-19 Epidemic Dynamics.

Abstract: Detection and isolation of infected people are believed to play an important role in the control of the COVID-19 pandemic. Some countries conduct large-scale screenings for testing, whereas others test mainly people with high prior probability of infection such as showing severe symptoms and/or having an epidemiological link with a known or suspected case or cluster of cases. However, what a good testing strategy is and whether the difference in testing strategy shows a meaningful, measurable impact on the COVID-19 epidemic remain unknown. Here, we showed that patterns of association between effective reproduction number (Rt) and test positivity rate can illuminate differences in testing situation among different areas, using global and local data from Japan. This association can also evaluate the adequacy of current testing systems and what information is captured in COVID-19 surveillance. The differences in testing systems alone cannot predict the results of epidemic containment efforts. Furthermore, monitoring test positivity rates and severe case proportions among the nonelderly can predict imminent case count increases. Monitoring test positivity rates in conjunction with the concurrent Rt could be useful to assess and strengthen public health management and testing systems and deepen understanding of COVID-19 epidemic dynamics.

Furuse|Yuki|Y|0000-0002-4663-6069
Ko|Yura K|YK|
Ninomiya|Kota|K|
Suzuki|Motoi|M|
Oshitani|Hitoshi|H|

COVID-19
epidemics
pandemic
effective reproduction number
surveillance
SARS-CoV-2
laboratory diagnosis
outbreaks


Terminal Ligand and Packing Effects on Slow Relaxation in an Isostructural Set of [Dy(H2 dapp)X2 ]+ Single Molecule Magnets*.

Abstract: We report three structurally related single ion Dy compounds using the pentadentate ligand 2,6-bis((E)-1-(2-(pyridin-2-yl)-hydrazineylidene)ethyl)pyridine (H2 dapp) [Dy(H2 dapp)(NO3 )2 ]NO3 (1), [Dy(H2 dapp)(OAc)2 ]Cl (2) and [Dy(H2 dapp)(NO3 )2 ]Cl0.92 (NO3 )0.08 (3). The (H2 dapp) occupies a helical twisted pentagonal equatorial arrangement with two anionic ligands in the axial positions. Further influence on the electronic and magnetic structure is provided by a closely associated counterion interacting with the central N-H group of the (H2 dapp). The slow relaxation of the magnetisation shows that the anionic acetates give the greatest slowing down of the magnetisation reversal. Further influence on the relaxation properties of compounds1 and 2 is the presence of short nitrate-nitrate intermolecular ligand contact opening further lattice relaxation pathways.

magnetism
axiality
SMM
dysprosium
magnetic relaxation


Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: An in vitro and in situ study.

Abstract:
OBJECTIVES
To test the role of exopolysaccharide (EPS) polymers matrix to modulate the composition/virulence of biofilms growing on titanium (Ti) surfaces, the effect on antibiotic susceptibility, and whether a dual-targeting therapy approach for disrupted EPS matrix could improve the antimicrobial effect.

MATERIALS AND METHODS
A microcosm biofilm model using human saliva as inoculum was used, and the microbial composition was assessed by checkerboard DNA-DNA hybridization. EPS-enriched biofilms virulence was tested using fibroblast monolayer. Povidone-iodine (PI) was used as EPS-targeting agent followed by amoxicillin + metronidazole antibiotic to reduce bacterial biomass using an in situ model.

RESULTS
An EPS-enriched environment, obtained by sucrose exposure, promoted bacterial accumulation and led to a dysbiosis on biofilms, favoring the growth of Streptococcus, Fusobacterium, and Campylobacter species and even strict anaerobic species related to peri-implant infections, such as Porphyromonas gingivalis and Tannerella forsythia (~3-fold increase). EPS-enriched biofilm transitioned from a commensal aerobic to a pathogenic anaerobic profile. EPS increased biofilm virulence promoting higher host cell damage and reduced antimicrobial susceptibility, but the use of a dual-targeting approach with PI pre-treatment disrupted EPS matrix scaffold, increasing antibiotic effect on in situ biofilms.

CONCLUSION
Altogether, our data provide new insights of how EPS matrix creates an environment that favors putative pathogens growth and shed light to a promising approach that uses matrix disruption as initial step to potentially improve implant-related infections treatment.

D000077317:Extracellular Polymeric Substance Matrix

biofilms titanium biomaterials antibiotic microbiology


Combined treatment of an aortosplenic bypass followed by coil embolization in the treatment of pancreaticoduodenal artery aneurysms caused by median arcuate ligament compression: a report of two cases.

Abstract:
BACKGROUND
Pancreaticoduodenal artery aneurysms (PDAAs) are rare visceral aneurysms, and prompt intervention/treatment of all PDAAs is recommended at the time of diagnosis to avoid rupture of aneurysms. Herein, we report two cases of PDAA caused by the median arcuate ligament syndrome, treated with surgical revascularization by aortosplenic bypass followed by coil embolization.

CASE PRESENTATION
Case 1 A 54-year-old woman presented with a chief complaint of severe epigastralgia and was diagnosed with two large fusiform inferior PDAAs and celiac axis occlusion. To preserve the blood flow of the pancreatic head, duodenum, liver, and spleen, we performed elective surgery to release the MAL along with aortosplenic bypass. At 6 days postoperatively, transcatheter arterial embolization was performed. At the 8-year 6-month follow-up observation, no recurrent perfusion of the embolized PDAAs or rupture had occurred, including the non-embolized small PDAA, and the bypass graft had excellent patency. Case 2 A 39-year-old man who had been in good health was found to have a PDAA with celiac stenosis during a medical checkup. Computed tomography and superior mesenteric arteriography showed severe celiac axis stenosis and a markedly dilated pancreatic arcade with a large saccular PDAA. To preserve the blood flow of the pancreatic arcade, we performed elective surgery to release the MAL along with aortosplenic bypass. At 9 days postoperatively, transcatheter arterial embolization was performed. At the 6-year 7-month follow-up observation, no recurrent perfusion or rupture of the PDAA had occurred, and the bypass graft had excellent patency.

CONCLUSION
Combined treatment with bypass surgery and coil embolization can be an effective option for the treatment of PDAAs associated with celiac axis occlusion or severe stenosis.

Embolization
Pancreaticoduodenal artery aneurysm
Bypass surgery


Imaging the Cancer Immune Environment and Its Response to Pharmacologic Intervention, Part 2: The Role of Novel PET Agents.

Abstract: Although 18F-FDG PET/CT is widely available and is increasingly being used to monitor response to immunotherapy and simultaneously identify immune-related adverse events, there are several challenges in interpreting the results of this investigation, especially early in the course of treatment. It also has limited utility in selecting the optimal type of immunotherapy. As knowledge about immune contexture increases, new targets that may be amenable to imaging are being defined. These exciting advances, coupled with increasingly sophisticated methods for generating radiopharmaceuticals, provide the potential for either replacing or complementing 18F-FDG PET/CT in the selection and monitoring of immunotherapy. Approaches include imaging specific characteristics of immune cell infiltrates or aspects of the tumor microenvironment that are known to be associated with suppression of the innate and adaptive immune response. Following a large body of preclinical work, promising agents that are entering into early clinical evaluation are discussed. We suggest a speculative algorithm as to how these might be used in routine practice, subject to validation in clinical trials.

D000072078:Positron Emission Tomography Computed Tomography

PET
radiopharmaceuticals
immune checkpoint
molecular imaging
oncology: melanoma


Peripheral blood molecular measurable residual disease is sufficient to identify patients with acute myeloid leukaemia with imminent clinical relapse.

Abstract: Longitudinal molecular measurable residual disease (MRD) sampling after completion of therapy serves as a refined tool for identification of imminent relapse of acute myeloid leukaemia (AML) among patients in long-term haematological complete remission. Tracking of increasing quantitative polymerase chain reaction MRD before cytomorphological reappearance of blasts may instigate individual management decisions and has paved the way for development of pre-emptive treatment strategies to substantially delay or perhaps even revert leukaemic regrowth. Traditionally, MRD monitoring is performed using repeated bone marrow aspirations, albeit the current European LeukemiaNet MRD recommendations acknowledge the use of peripheral blood as an alternative source for MRD assessment. Persistent MRD positivity in the bone marrow despite continuous morphological remission is frequent in both core binding factor leukaemias and nucleophosmin 1-mutated AML. In contrast, monthly assessment of MRD in peripheral blood superiorly separates patients with imminent haematological relapse from long-term remitters and may allow pre-emptive therapy of AML relapse.

measurable residual disease
acute myeloid leukaemia
quantitative polymerase chain reaction
pre-emptive therapy
molecular relapse


ATP-binding cassette transporters and cholesterol translocation.

Abstract: Cholesterol, a major component of mammalian cell membranes, plays important structural and functional roles. However, accumulation of excessive cholesterol is toxic to cells. Aberrant cholesterol trafficking and accumulation is the molecular basis for many diseases, such as atherosclerotic cardiovascular disease and Tangier's disease. Accumulation of excessive cholesterol is also believed to contribute to the early onset of Alzheimer's disease. Thus, cellular cholesterol homeostasis is tightly regulated by uptake, de novo synthesis, and efflux. Any surplus of cholesterol must either be stored in the cytosol in the form of esters or released from the cell. Recently, several ATP-binding cassette (ABC) transporters, such as ABCA1, ABCG1, ABCG5, and ABCG8 have been shown to play important roles in the regulation of cellular cholesterol homeostasis by mediating cholesterol efflux. Mutations in ABC transporters are associated with several human diseases. In this review, we discuss the physiological roles of ABC transporters and the underlying mechanisms by which they mediate cholesterol translocation.

cholesterol efflux
ABC transporters
HDL
LDL
atherosclerosis
membrane proteins


Growth charts for Thai children with Prader-Willi syndrome aged 0-18 years.

Abstract:
BACKGROUND
Prader-Willi syndrome (PWS) is a multisystem genetic disorder, which has a typical eating behavior and growth pattern. In the infancy period, children with PWS have low body weight followed by hyperphagia in later childhood. Disease-specific growth charts have been recommended for monitoring PWS patients. Previous literature demonstrated growth differences among individuals with PWS of different ethnicity.

METHODS
A retrospective multicenter study was performed in PWS patients from different areas of Thailand included collaboration with the Thai PWS support group during 2000-2017. Baseline characteristics and anthropometric data were reviewed. Both growth hormone and non-growth hormone received patients were included, but the data after receiving GH were excluded before curve construction. Growth charts for Thai PWS compared to the 50th normative centile were constructed using Generalized Least Squares (GLS) methods. Curve smoothing was performed by Fractional Polynomials and Exponential Transformation.

RESULT
One hundred and thirteen patients with genetically confirmed PWS (55 males and 58 females) were enrolled. Fifty percent of patients were diagnosed less than 6 months of age. We developed growth charts for non-growth hormone treated Thai children with PWS aged between 0 and 18 years. A growth pattern was similar to other ethnicities while there were some differences. Mean birth weight of PWS patients was less than that of typical newborns. Mean adult height at 18 years of age in Thai children with PWS was lower than that in American children, but taller than Japanese. Mean weight of Thai PWS males at 18 years of age was more than those from other countries.

CONCLUSION
This study is the first to document PWS-specific growth charts in Southeast Asian population. These growth charts will be useful in improving the quality of patient care and in evaluating the impact of growth hormone treatment in the future.

Growth chart
Prader-Willi syndrome
Body weight
Southeast Asian
Body height
Head circumference


Systematic review of ratios between disease /health periodontitis modulators and meta-analysis of their levels in gingival tissue and biological fluids.

Abstract:
OBJECTIVE
The ratio between molecules which acts towards the diseased or healthy phenotype determine whether the periodontitis lesions will progress or stabilize. Considering gingival tissue and biofluids, we aimed to present a systematic review (qualitative analysis) on the ratios between disease/health periodontitis modulators, and a meta-analysis (quantitative analysis) of their levels in individuals with periodontitis compared to controls.

DESIGN
Electronic searches of the PubMed, Scopus, EMBASE and Web of Science databases were conducted for publications up to May 2020.

RESULTS
A total of 53 publications were included in the systematic review, being 22 of them focusing on the ratios between Interleukin [IL]-1/IL-10, IL-6/IL-10, IL-1/IL-1RA and RANKL/OPG. Twenty-one publications were eligible for meta-analyses. The ratios of IL-1, IL-6 and RANKL mRNA levels were significantly higher in diseased gingival tissue, as well as their protein levels in gingival crevicular fluid (GCF) of periodontitis individuals. Considering the saliva levels, the RANKL/OPG ratio was higher in periodontitis subjects in comparison to controls. Meta-analyses showed higher IL-1β, IL-1α, IL-6 and IL-10 gene expressions in gingival tissue and protein levels in GCF, while RANKL was higher in GCF of periodontitis individuals in comparison to controls.

CONCLUSIONS
Both the ratios and meta-analyses showed higher levels of modulators in gingival tissue and GCF of diseased individuals.

Caldeira|François Isnaldo Dias|FID|
Hidalgo|Marco Antonio Rimachi|MAR|
De Carli Dias|Marina Lara|ML|
Scarel-Caminaga|Raquel Mantuaneli|RM|
Pigossi|Suzane Cristina|SC|

Periodontitis
Adaptive immunity
Cytokines
Immunity
Innate


Seasonal prevalence of gastrointestinal parasites in desi fowl (Gallus gallus domesticus) in and around Gannavaram, Andhra Pradesh.

Abstract: A study was carried out to know the prevalence of gastrointestinal parasites in desi fowl in and nearby villages of Gannavaram, Andhra Pradesh for a period of 1 year. Screening of 492 samples comprising faecal samples and gastrointestinal tracts from freshly slaughtered desi birds at local poultry shops and samples from post mortem examinations at NTR College of Veterinary Science, Gannavaram revealed 63.21 % of gastrointestinal parasites. Faecal samples were examined by floatation technique using salt solution and samples positive for coccidian oocysts were sporulated in 2.5 % potassium dichromate solution for species identification. Adult worms were identified after routine processing and mounting. The species identified includes Davainea proglottina, Raillietina cesticillus and Raillietina echinobothrida in cestodes (32.47 %), Ascaridia galli, Capillaria annulata, Heterakis gallinarum in nematodes (39.87 %), Eimeria tenella, Eimeria acervulina and Eimeria necatrix in Eimeria spp. (39.87 %). Ascaridia galli and R. cesticillus and A. galli and Eimeria spp. were common in mixed infection (12.86 %). Ascaridia galli was the more prevalent species. No trematode parasite was identified during the study period. Significant (p = 0.001) relationship between the seasonality and prevalence of gastrointestinal parasites was observed (χ2 = 17.46, df = 2). Data revealed high prevalence in rainy season (43.41 %) followed by summer (38.91 %) and winter (17.68 %) seasons for all parasites except for A. galli and C. annulata infections which were higher in summer season. Results indicated high prevalence of gastrointestinal parasites in desi fowl in study area emphasizing the need of improved management practices of backyard poultry.

Sreedevi|C|C|
Jyothisree|Ch|Ch|
Rama Devi|V|V|
Annapurna|P|P|
Jeyabal|L|L|

Season
Prevalence
Gastrointestinal parasites
Desi fowl