Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis.

Abstract: The reproductive system complications of genital chlamydial infection include fallopian tube fibrosis and tubal factor infertility. However, the molecular pathogenesis of these complications remains poorly understood. The induction of pathogenic epithelial-mesenchymal transition (EMT) through microRNA (miRNA) dysregulation was recently proposed as the pathogenic basis of chlamydial complications. Focusing on fibrogenesis, we investigated the hypothesis that chlamydia-induced fibrosis is caused by EMT-driven generation of myofibroblasts, the effector cells of fibrosis that produce excessive extracellular matrix (ECM) proteins. The results revealed that the targets of a major category of altered miRNAs during chlamydial infection are key components of the pathophysiological process of fibrogenesis; these target molecules include collagen types I, III, and IV, transforming growth factor β (TGF-β), TGF-β receptor 1 (TGF-βR1), connective tissue growth factor (CTGF), E-cadherin, SRY-box 7 (SOX7), and NFAT (nuclear factor of activated T cells) kinase dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1a (Dyrk1a). Chlamydial induction of EMT resulted in the generation of α-smooth muscle actin (α-SMA)-positive myofibroblasts that produced ECM proteins, including collagen types I and III and fibronectin. Furthermore, the inhibition of EMT prevented the generation of myofibroblasts and production of ECM proteins during chlamydial infection. These findings may provide useful avenues for targeting EMT or specific components of the EMT pathways as a therapeutic intervention strategy to prevent chlamydia-related complications.

Igietseme|Joseph U|JU|
Omosun|Yusuf|Y|
Nagy|Tamas|T|
Stuchlik|Olga|O|
Reed|Matthew S|MS|
He|Qing|Q|
Partin|James|J|
Joseph|Kahaliah|K|
Ellerson|Debra|D|
George|Zenas|Z|
Goldstein|Jason|J|
Eko|Francis O|FO|
Bandea|Claudiu|C|
Pohl|Jan|J|
Black|Carolyn M|CM|

D000077293:Receptor, Transforming Growth Factor-beta Type I

D018125:Receptors, Transforming Growth Factor beta

Chlamydia
fibrosis
epithelial-mesenchymal transition (EMT)
miRNAs
myofibroblasts
Chlamydia trachomatis
extracellular matrix proteins


The Impact of Tai Chi Exercise on Health Care Utilization and Imputed Cost in Residents of Low-Income Senior Housing.

Abstract:
Background/Objectives
This study was designed to test the impact of Tai Chi (TC) on healthcare utilization and cost in older adults living in low-income senior housing. We hypothesized that TC would improve overall health enough to reduce the use of emergency department (ED) and inpatient services.

Design
Cluster randomized controlled trial with randomization at the housing site level.

Setting
Greater Boston, Massachusetts.

Participants
The study includes 6 sites with 75 individuals in the TC treatment condition and 6 sites with 67 individuals in the health education control condition.

Intervention
Members of the treatment group received up to a year-long intervention with twice weekly, in-person TC exercise sessions along with video-directed exercises that could be done independently at home. The comparison group received monthly, in-person healthy aging education classes (HE). Study recruitment took place between August, 2015 and October, 2017. Key outcomes included acute care utilization (inpatient stays, observation stays and emergency department visits). In addition, the cost of utilization was estimated using the age, sex and race adjusted allowed amount from Medicare claims for a geographically similar population aged ≥ 65.

Results
The results suggested a possible reduction in the rate of ED visits in the TC group vs. controls (rate ratio = 0.476, p-value = 0.06), but no findings achieved statistical significance. Adjusted estimates of imputed costs of ED and hospital care were similar between TC and HE, averaging approximately $3,000 in each group.

Conclusion
ED utilization tended to be lower over 6 to 12 months of TC exercises compared to HE in older adults living in low-income housing, although estimated costs of care were similar.

Tai Chi
cost
healthcare utilization
adverse events


Nonylphenol effects on the HPA axis of the bioindicator vertebrate, Podarcis sicula lizard.

Abstract: Nonylphenol (NP) is an endocrine disruptor widely distributed in the environment. It accumulates in the lipids of living organisms and enters the human food chain. The main source of human exposure is expected to be food, drinking water and foodstuff contaminated through leaching from packaging or pesticide formulation applications. NP acts as an estrogenic compound and it is able to mimic the action of estradiol 17β (E2) by binding to the estrogen receptor (ER). The aim of the present study was to investigate the NP effects on the hypothalamic-pituitary-adrenal gland (HPA) axis of the bioindicator Podarcis sicula lizard. A time-dependent stimulation of the HPA axis and variations of both catecholamine plasma levels were showed. Moreover, NP effects on adrenal gland morphology were evaluated by light and transmission electron microscopy. Clear morphological signs of adrenal gland stimulation such as an increase of steroidogenic cord diameter and vascularization, a strong escalation of adrenaline cell number and a decrease of noradrenaline cells were observed. The notably elevated levels of adrenal hormones suggested a permanent turning on of hypothalamic corticotropin releasing factor (CRF) secretion together with a lack of the negative feedback of HPA axis, perturbing systemic responses of the organism. Our data may help to predict the biological alterations induced by NP and to extend its impact upon adrenal function.

De Falco|Maria|M|
Sellitti|Anna|A|
Sciarrillo|Rosaria|R|
Capaldo|Anna|A|
Valiante|Salvatore|S|
Iachetta|Giuseppina|G|
Forte|Maurizio|M|
Laforgia|Vincenza|V|


Ozonized water as an alternative to alcohol-based hand disinfection.

Abstract:
BACKGROUND
Hand hygiene plays a vital role in the prevention of transmission of micro-organisms. Ozone (O3) is a highly reactive gas with a broad spectrum of antimicrobial effects on bacteria, viruses, and protozoa. It can easily be produced locally in small generators, and dissolved in tap water, and quickly transmits into ordinary O2 in the surrounding air.

AIM
To compare ozonized tap water and alcohol rub in decontamination of bacterially contaminated hands.

METHODS
A cross-over study among 30 nursing students. Hands were artificially contaminated with Escherichia coli (ATCC 25922), then sanitized with ozonized tap water (0.8 or 4 ppm) or 3 mL standard alcohol-based rub (Antibac 85%). The transient microbes from fingers were cultivated and colony-forming units (cfu)/mL were counted. The test procedure was modified from European Standard EN 1500:2013.

FINDINGS
All contaminated hands before disinfection showed cfu >30,000/mL. The mean (SD) bacterial counts in (cfu/mL) on both hands combined were 1017 (1391) after using ozonized water, and 2337 (4664) after alcohol hand disinfection. The median (range) values were 500 (0-6700) and 250 (0-16,000) respectively (non-significant difference). Twenty per cent of participants reported adverse skin effects (burning/dryness) from alcohol disinfection compared with no adverse sensations with ozone.

CONCLUSION
Ozonized tap water is an effective decontaminant of E. coli, and it could be an alternative to traditional alcohol-fluid hand disinfectants both in healthcare institutions and public places. Ozonized water may be especially valuable for individuals with skin problems.

Breidablik|H J|HJ|
Lysebo|D E|DE|
Johannessen|L|L|
Skare|Å|Å|
Andersen|J R|JR|
Kleiven|O T|OT|

Ozone
Hand disinfection
Alcohol rub
E. coli


Antioxidant response of cucumber (Cucumis sativus) exposed to nano copper pesticide: Quantitative determination via LC-MS/MS.

Abstract: Targeted metabolomics aims to provide a new approach to investigate metabolites and gather both qualitative and quantitative information. We describe a protocol for extraction and analysis of plant metabolites, specifically 13 secondary metabolites (antioxidants) using liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS), with high linearity (R2 > 0.99) and reproducibility (0.23-6.23 R%) with low limits of detection (>0.001 ng/mL) and quantification (>0.2 ng/mL). The protocol was applied to study the antioxidant response of cucumber plants exposed to nanocopper pesticide. Dose-dependent changes in antioxidant concentrations were found, and 10 antioxidants were significantly consumed to scavenge reactive oxygen species, protecting plants from damage. Levels of three antioxidants were up-regulated, as a response to the depletion of the other antioxidants, signaling activation of the defense system. We demonstrated that the reported LC-MS/MS method provides a quantitative analysis of antioxidants in plant tissues, for example to investigate interactions between plants and nanomaterials.

Huang|Yuxiong|Y|
Adeleye|Adeyemi S|AS|
Zhao|Lijuan|L|
Minakova|Anastasiia S|AS|
Anumol|Tarun|T|
Keller|Arturo A|AA|

D002853:Chromatography, Liquid
D003300:Copper
D018553:Cucumis sativus
D010575:Pesticides
D015203:Reproducibility of Results
D053719:Tandem Mass Spectrometry

Antioxidants Cucumber LC-MS/MS Metabolites Extraction Nanoparticle


Anti-Inflammatory Response and Muscarinic Cholinergic Regulation during the Laxative Effect of Asparagus cochinchinensis in Loperamide-Induced Constipation of SD Rats.

Abstract: Several types of saponins and herbal plants containing saponins have been reported to have anti-inflammatory or laxative activities. To verify the therapeutic effects of saponin-enriched extracts of Asparagus cochinchinensis (SPA) on the anti-inflammatory response and on the cholinergic regulation in the gastrointestinal system, an alteration on the constipation phenotypes, on the inflammatory responses, and on the muscarinic cholinergic regulation were investigated in the transverse colons of Sprague Dawley (SD) rats with loperamide (Lop)-induced constipation after the treatment of SPA. Significant increases were observed on the total number of stools, the gastrointestinal transit, the thickness of the mucosal layer, the flat luminal surface, the number of paneth cells, and the lipid droplets in the Lop + SPA-treated group as compared to the Lop + Vehicle-treated group. SPA treatment induced the recovery of inflammatory cytokines (TNF-α, IL-1β) and IL-6), inflammatory mediators (NF-κB and iNOS), the total number of infiltered mast cells, and mucin secretion. Also, some similar improvements were observed on the levels of acetylcholine esterase (AChE) activity and on the phosphorylation of myosin light chains (MLC) as well as the expression of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators. The results presented herein provide the first strong evidence that SPA stimulates anti-inflammatory responses and the muscarinic cholinergic regulation when exerting its laxative effects in the chronic constipation of Lop-induced models.

Kim|Ji Eun|JE|
Park|Ji Won|JW|
Kang|Mi Ju|MJ|
Choi|Hyeon Jun|HJ|
Bae|Su Ji|SJ|
Choi|You Sang|YS|
Lee|Young Ju|YJ|
Lee|Hee Seob|HS|
Hong|Jin Tae|JT|0000-0002-6534-9575
Hwang|Dae Youn|DY|

Asparagus cochinchinensis
constipation
cytokines
acetylcholine esterase
muscarinic acetylcholine receptors
inflammation


(-)-6-epi-Artemisinin, a Natural Stereoisomer of (+)-Artemisinin in the Opposite Enantiomeric Series, from the Endemic Madagascar Plant Saldinia proboscidea, an Atypical Source.

Abstract: Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.

Randrianarivo|Saholinirina|S|
Rasolohery|Claudine|C|
Rafanomezantsoa|Sitraka|S|
Randriamampionona|Heriniaina|H|
Haramaty|Liti|L|
Rafanomezantsoa|Roger Marie|RM|
Andrianasolo|Eric H|EH|

Saldinia proboscidea
SARS-CoV-2 inhibitor
Artemisia species
antimalaria
antiproliferative


Branched Sialylated N-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H.

Abstract: Proper N-glycosylation of proteins is important for normal brain development and nervous system function. Identification of the localization, carrier proteins and interacting partners of N-glycans is essential for understanding the roles of glycoproteins. The present study examined the N-glycan A2G'2F (Galβ1-3GlcNAcβ1-2Manα1-6[Galβ1-3GlcNAcβ1-2Manα1-3]Manβ1-4GlcNAcβ1-4[Fucα1-6]GlcNAc-). A2G'2F has a branched sialic acid structural feature, and branched sialylated A2G'2F is a major N-glycan in the mouse brain. Its expression in the mouse brain increases during development, suggesting that branched sialylated N-glycans play essential roles during brain development. However, the carrier proteins, interacting partners and localization of branched sialylated N-glycans remain unknown. We previously improved our method for analyzing N-glycans from trace samples, and here we succeeded in detecting A2G'2F in small fragments excised from the two-dimensional electrophoresis gels of subcellular fractionated mouse brain proteins. A2G'2F was accumulated in mouse brain synaptosomes. We identified calreticulin as one of the candidate A2G'2F carriers and found calreticulin expression in both the endoplasmic reticulum and synaptosomal fractions. Calreticulin was observed in dendritic spines of cultured cortical neurons. Synthesized branched sialylated glycan clusters interacted with sialic acid-binding immunoglobulin-like lectin H (Siglec-H), which is known to be a microglia-specific molecule. Taken together, these results suggest that branched sialylated A2G'2F in synaptosomes plays a role in the interaction of dendritic spines with microglia.Key words: N-glycan, subcellular fractionation, calreticulin, dendritic spine, Siglec-H.

Handa-Narumi|Mai|M| Yoshimura|Takeshi|T| Konishi|Hiroyuki|H| Fukata|Yuko|Y| Manabe|Yoshiyuki|Y| Tanaka|Katsunori|K| Bao|Guang-Ming|GM| Kiyama|Hiroshi|H| Fukase|Koichi|K| Ikenaka|Kazuhiro|K|

N-glycan
subcellular fractionation
calreticulin
dendritic spine
Siglec-H


Bortezomib Facilitates Reparative Dentin Formation after Pulp Access Cavity Preparation in Mouse Molar.

Abstract:
INTRODUCTION
The aim of this study was to evaluate in vitro and ex vivo roles of bortezomib, a proteasome inhibitor that binds to the active site of the 26S proteasome, in tertiary dentin formation.

METHODS
We established pulpal access cavity preparation that was treated with or without bortezomib before direct pulp capping with a calcium hydroxide-based material. We also analyzed bone morphogenetic protein (Bmp)- and Wnt-related signaling molecules using quantitative real-time polymerase chain reaction.

RESULTS
In the short-term observation period, the bortezomib-treated pulp specimens showed the period-altered immunolocalization patterns of nestin, CD31, and myeloperoxidase, whereas the control specimens did not. The bortezomib-treated group showed a complete dentin bridge with very few irregular tubules after 42 days. The micro-computed tomographic images showed more apparent dentin bridge structures in the treated specimens than were in the controls. Quantitative real-time polymerase chain reaction analysis showed up-regulated Bmp and Wnt.

CONCLUSIONS
These findings revealed that treatment with 1 μmol/L bortezomib induced reparative dentin formation that facilitated the maintenance of the integrity of the remaining pulpal tissue via early vascularization and regulation of Bmp and Wnt signaling.

Jung|Jae-Kwang|JK| Gwon|Gi-Jeong|GJ| Neupane|Sanjiv|S| Sohn|Wern-Joo|WJ| Kim|Ki-Rim|KR| Kim|Ji-Youn|JY| An|Seo-Young|SY| Kwon|Tae-Yub|TY| An|Chang-Hyeon|CH| Lee|Youngkyun|Y| Kim|Jae-Young|JY| Ha|Jung-Hong|JH|

reparative dentin formation
Cavity preparation
vascularization
Wnt signaling
dentin-pulp complex


A novel GATA6 mutation in a child with congenital heart malformation and neonatal diabetes.

Abstract: Diabetes in neonates is a monogenetic disease and genetic analysis is warranted to allow best treatment, prognosis, and genetic counseling. Transcription factor mutations may have a variable expression and different organs may be involved.

Eifes|Serge|S|
Chudasama|Kishan K|KK|
Molnes|Janne|J|
Wagner|Kerstin|K|
Hoang|Tuyen|T|
Schierloh|Ulrike|U|
Rocour-Brumioul|Danielle|D|
Johansson|Stefan|S|
Njølstad|Pål R|PR|
de Beaufort|Carine|C|

GATA6
heart malformation
neonatal diabetes
transcription factor mutation
Exocrine pancreas dysfunction
intrauterine growth retardation


The demise of bloodletting.

Abstract: Bloodletting was a practice favoured by doctors and barber-surgeons for many centuries, and is now, perhaps surprisingly, still employed for a few specific indications. The effectiveness of bloodletting for treating diseases such as pneumonia was convincingly challenged in the mid-nineteenth century, but medical conservatism ensured the practice continued well into the twentieth century. As late as 1942, a famous medical textbook considered bloodletting appropriate treatment for pneumonia.

Bloodletting pneumonia lancets leeches transfusion


Comparison of dental and skeletal indices between patients under haemodialysis and peritoneal dialysis with healthy individuals in digital panoramic radiography.

Abstract:
OBJECTIVE
The aim was to compare dental and skeletal indices in panoramic radiography between patients undergoing haemodialysis, peritoneal dialysis and age- and sex-matched control group.

METHODS
In this comparative cross-sectional study, quantitative Indices including Antegonial Index (AI), Mental Index (MI), Panoramic Mandibular Index (PMI) and qualitative indices including Mandibular Cortical Index (MCI) and Trabecular Pattern (TP) were evaluated in panoramic images of 32 haemodialysis patients, 14 patients under peritoneal dialysis and 52 healthy individuals. The images were also investigated for pulp canal calcification, pulp stones, soft tissue calcification, changes in or loss of lamina dura, radiolucencies associated with brown tumour and ridge resorption. The indices were compared between the three groups and were investigated for association with the patients' blood test parameters and their diseases causing chronic renal failure (CRF). Intraobserver agreement for the 2-week interval of assessment was calculated for the indices.

RESULTS
MI (p = 0.574) and PMI (p = 0.100) were not significantly different, but AI (p = 0.01), MCI (p < 0.001) and TP (p = 0.002) were significantly different between the two case groups and the control group. The prevalence of pulp calcification (p = 0.03) and ridge resorption (p = 0.005) was higher in the haemodialysis group. Soft tissue calcification (p = 0.85) and lamina dura changes (p = 0.9) showed no significant difference. Brown tumours were observed in only one case in the haemodialysis group.

CONCLUSIONS
AI, MCI and TP showed a reduction in mineral density of the cortical and trabecular bone in CRF patients and more severely in patients under haemodialysis than those under peritoneal dialysis.

Abdinian|Mehrdad|M|
Salehi|Mohammad Mahdi|MM|
Mortazavi|Mojgan|M|
Salehi|Hassan|H|
Kazemi Naeini|Maryam|M|

D015519:Bone Density
D003430:Cross-Sectional Studies
D006801:Humans
D008334:Mandible
D010530:Peritoneal Dialysis
D011862:Radiography, Panoramic
D006435:Renal Dialysis

Peritoneal Dialysis
Panoramic Radiography
Chronic Renal Failure
Renal Dialysis


Treatment of radiation-induced hemorrhagic gastritis with prednisolone: a case report.

Abstract: Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding. It is a serious complication arising from radiation therapy, and the standard treatment method has not been established. The initial injury is characteristically acute inflammation of gastric mucosa. We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma. The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb. Multiple hemorrhagic patches with active oozing were found over the antrum. Anti-secretary therapy was initiated for hemostasis, but melena still occurred off and on. Finally, he was successfully treated by prednisolone therapy. We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis.

Zhang|Lan|L| Xie|Xiao-Ying|XY| Wang|Yan|Y| Wang|Yan-Hong|YH| Chen|Yi|Y| Ren|Zheng-Gang|ZG|

Hemorrhagic gastritis
Prednisolone
Gastrointestinal bleeding
Radiation
Hepatocellular carcinoma


Evidence for defective Rab GTPase-dependent cargo traffic in immune disorders.

Abstract: A fully functional immune system is essential to protect the body against pathogens and other diseases, including cancer. Vesicular trafficking provides the correct localization of proteins within all cell types, but this process is most exquisitely controlled and coordinated in immune cells because of their specialized organelles and their requirement to respond to selected stimuli. More than 60 Rab GTPases play important roles in protein trafficking, but only five Rab-encoding genes have been associated with inherited human disorders, and only one of these (Rab27a) causes an immune defect. Mutations in RAB27A cause Griscelli Syndrome type 2 (GS2), an autosomal recessive disorder of pigmentation and severe immune deficiency. In lymphocytes, Munc13-4 is an effector of Rab27a, and mutations in the gene encoding this protein (UNC13D) cause Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL3). The immunological features of GS2 and FHL3 include neutropenia, thrombocytopenia, and immunodeficiency due to impaired function of cytotoxic lymphocytes. The small number of disorders caused by mutations in genes encoding Rabs could be due to their essential functions, where defects in these genes could be lethal. However, with the increasing use of next generation sequencing technologies, more mutations in genes encoding Rabs may be identified in the near future.


Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study.

Abstract:
BACKGROUND
Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive.

PURPOSE
We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis.

METHODS
A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74).

RESULTS
Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA2 DS2 -VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P < .001). During follow-up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient-years, HR 4.4 95% Cl 1.8-11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient-years, HR 1.70 95% CI 1.05-2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient-years).

CONCLUSION
Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.

D019918:Heart Valve Prosthesis Implantation

paroxysmal atrial fibrillation
mortality
aortic valve replacement
bioprosthesis
stroke


Understanding the personal and community impact of long QT syndrome: A perspective from Gitxsan women.

Abstract: There is a disproportionately high rate of hereditary long QT syndrome (LQTS) in Northern British Columbia First Nations people, largely due to a novel missense variant in KCNQ1 (p.V205M). The variant has been previously described predisposing those affected to syncope, arrhythmia, and sudden death. Although the biological aspects of LQTS have been explored extensively, less research has been done into the impact of living with a genetic variant that predisposes one to sudden death, and no previous studies have provided cultural insights from a First Nations community. The goal of this study was to explore what facilitates and hinders resiliency and coping for those living with LQTS. Participants were invited to partake in their choice of one-to-one interviews, Photovoice, and Talking Circles. This paper presents the findings from the interview portion of the study. Interviews were recorded, transcribed, and analyzed qualitatively using the systematic text condensation method. Ten women shared their personal experiences of living with LQTS through individual interviews. Half of the women had tested positive for the p.V205M variant, and the other half were awaiting results. In general, learning about a LQTS diagnosis was perceived as traumatic, with gradual acceptance that led to coping. The main factors found to facilitate resiliency and coping were positive family relationships, spirituality, and knowledge about LQTS. The main factors found to hinder resiliency and coping were a poor understanding of the biological or clinical aspects of LQTS, conflicting medical advice (especially regarding physical activity) and LQTS not being taken seriously by social contacts and healthcare providers. It appears that learning to live with LQTS is an ongoing process, requiring balance and interconnectedness between all aspects of well-being.

D020022:Genetic Predisposition to Disease

cultural competence
genetic counseling
genetic testing
lived experience
underrepresented populations


Novel approach to investigate the mechanical properties of crumb matrix during storage - Re-engineering of gas-free crumb pellets.

Abstract: Since commonly used texture profile analysis (TPA) depend on gas volume fraction, a detailed development of mechanistic relationships between firming-relevant additives and structural crumb matrix alterations often fail. Thus, a method to prepare gas-free crumb pellets was developed to exclude porosity effects. Therefore, reference white bread crumb was freeze-dried, crushed and rehydrated with either distilled water or maltose solution to the native moisture content. Freeze-dried crumb matrix, rehydrated after baking with maltose solution (0.5 g maltose/100 g flour), did not retard firming in comparison to reference pellets (crumb matrix rehydrated with water). Thus, maltose showed no functionality on pellet firming during storage. However, crumb pellets exhibited a reduced firmness, when maltose was added during dough preparation resulting in an altered crumb formation. Additionally, results demonstrated, that differences between leavening methods (chemical vs. biological) on firming kinetics were not significant, which was confirmed by comparable Avrami firming rates k.

Bread
Maltose
Firming
Anti-firming
Freshness
Retrogradation
Staling
Texture analysis


CDKN2B Methylation Correlates with Survival in AML Patients.

Abstract: Aberrant DNA methylation has been reported as an important phenotype in acute myeloid leukemia. However the clinical significance of methylation changes has not been clear yet. In this study methylation Specific Melting Curve Analysis (MS-MCA) and real time PCR was used to assess the CDKN2B promoter hyper-methylation and gene expression in 59 Iranian acute myeloid leukemia (AML) patients. The incidence of aberrant hyper methylation of CDKN2B gene and cytogenetic abnormalities were 37.3% (22 of 59 patients) and 35.6% (21 of 59) respectively in our patients. We observed that CDKN2B expression level was lower than normal mesenchymal stem cells. Our data revealed significant correlation between methylated CDKN2B promoter region and mRNA gene expression (P= 0.007). Also, our data indicated that AML patients with aberrant methylation of CDKN2B gene had a lower survival rates (P=0.043). In addition, they had a higher proportion of leukemic blast cells (P=0.022) and higher white blood cell count in peripheral blood (P=0.0123). Aberrant methylation of CDKN2B was observed to higher in M2 subtype and lower in M3 and M4 subtypes. Although, we observed a significant correlation between Methylation and survival, there was no significant correlation between CDKN2B methylation and treatment outcome of AML patients (P=0.187). Furthermore, our data didn't illustrated a significant correlation between CDKN2B expression and survival (P=0.93). In conclusion our study showed that the aberrant methylation is one of molecular mechanisms involved in CDKN2B gene expression, moreover we can consider the CDKN2B methylation, as a prognostic marker in predict AML patients' survival.

Kamali Dolatabadi|Esmat|E|
Ostadali Dehaghi|Mohammadreza|M|
Amirizadeh|Naser|N|
Parivar|Kazem|K|
Mahdian|Reza|R|

Methylation
AML
Epigenetic
Melting curve analysis (MCA)
Real-Time PCR


Clinical and Spectral-Domain Optical Coherence Tomography Appearance of Optic Disc Melanocytoma: A New Classification and Differentiation from Pigmented Choroidal Lesions.

Abstract:
AIMS
The aim of this paper was to compare the features of both the classic, darkly pigmented and the atypical, more lightly pigmented optic disc melanocytoma with those of pigmented choroidal lesions.

METHODS
We analyzed the spectral-domain optical coherence tomography (SD-OCT) features of 9 eyes with optic disc melanocytoma and compared them with those of choroidal melanoma and nevus.

RESULTS AND CONCLUSION
We identified 2 categories of SD-OCT findings in optic disc melanocytoma: (a) type 1, the typical, prominent, hyperpigmented lesion with SD-OCT findings of a hyperreflective, disorganized overlying retina and a posterior hyporeflective shadow, and (b) the less common, atypical, minimally pigmented type 2 lesion overlaid by a relatively well-organized retina that lacks a posterior hyporeflective shadow. Choroidal lesions were characterized by tumor confined beneath the clearly visible hyperreflective line of the photoreceptor and retinal pigment epithelium, with minimal disorganization of the overlying retina.

Apinyawasisuk|Supanut|S|
McCannel|Tara|T|
Arnold|Anthony C|AC|

Spectral-domain optical coherence tomography


Not all headaches are migraines.

Abstract: A 40-year-old Somali woman presented features of a right-sided cavernous sinus syndrome which was confirmed with neuroimaging. Although initial investigations were equivocal for an infectious etiology, subsequent investigations led to a diagnosis of tuberculosis as the cause for right-sided cavernous sinus syndrome. This case illustrates that, although the incidence of tuberculosis cavernous sinus syndrome is reportedly low, patients originating from tuberculosis endemic regions warrant scrupulous investigations in order not to miss the diagnosis and effect appropriate treatment.

Chih-Hui Tien|Melissa|M|
Ramachandran|Prashanth|P|
White|Owen B|OB|
Lee|Andrew G|AG|

headache
cavernous sinus
tuberculosis
lymphadenopathy
ophthalmoplegia


Out-of-hours workload among Norwegian general practitioners - an observational study.

Abstract:
BACKGROUND
Repeated studies of working hours among Norwegian regular general practitioners (RGPs) have shown that the average total number of weekly working hours has remained unchanged since 1994 and up until 2014. For both male and female RGPs, the mean total weekly working hours amounted to almost 50 h in 2014. In recent years, Norwegian RGPs have become increasingly dissatisfied. They experience significantly increased workload without compensation in the form of more doctors or better payment. A study from the Norwegian Directorate of Health in 2018 (the RGP study) showed that Norwegian RGPs worked 55.6 h weekly (median 52.5). 25% of the respondents worked more than 62.2 h weekly. Based on data from the RGP study we investigated Norwegian RGP's out-of-hours (OOH) work, how the working time was distributed, and to what extent the OOH work affected the regular working hours.

METHODS
In early 2018, an electronic survey was sent to all 4640 RGPs in Norway. Each RGP reported how many minutes that were spent that particular day on various tasks during seven consecutive days. Working time also included additional tasks in the municipality, other professional medical work and OOH primary health care. Differences were analysed by independent t-tests, and regression analyses.

RESULTS
One thousand eighty hundred seventy-six RGPs (40.4%) responded, 640 (34.1%) had registered OOH work. Male RGPs worked on average 1.5 h more doing regular work than did females (p = 0.001) and on average 2.3 h more OOH work than females (p = 0.079). RGPs with no OOH work registered a mean of 1.0 h more clinical work than RGPs working OOH (p = 0.043). There was a large variation in OOH working hours. A linear regression analysis showed that male RGPs and RGPs in rural areas had the heaviest OOH workload.

CONCLUSIONS
One in three Norwegian RGPs undertook OOH work during the registration week in the RGP study. OOH work was done in addition to a sizeable regular workload as an RGP. We found small gender differences. OOH work was not compensated with reduced regular RGP work.

Workload
Observational study
Survey
Family medicine
General practice
Out-of-hours medical care
Primary care


The moderating and mediating roles of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being.

Abstract: This study explored the moderating and mediating influences of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being. In total, 301 (130 males) university students completed the Five-Facet Mindfulness Questionnaire, Index of Well-being, Self-acceptance Questionnaire, and Tolerance Scale. The results showed that the positive link between mindfulness and subjective well-being was significantly mediated by self-acceptance only. Tolerance played a moderating role. The implications of the results for relevant research and mindfulness training were discussed.

Xu|Wei|W|
Oei|Tian Ps|TP|
Liu|Xinghua|X|
Wang|Xiaoming|X|
Ding|Chen|C|

self-acceptance
tolerance
mindfulness
subjective well-being
mediating effect
moderating effect


Current state of dialysis access management in Korea.

Abstract: The prevalence rate and the incidence rate of hemodialysis and functioning kidney transplant recipients have continuously increased; on the contrary, those of peritoneal dialysis have continuously decreased since 2006. Dialysis patients have been getting older and have been maintained on dialysis longer. Diabetic nephropathy was the leading cause of end stage renal disease. The type of hemodialysis vascular access has been stable during the last 5 years (arteriovenous fistulas 76%, arteriovenous grafts 16%, central venous catheters 8% at 2016). Peritoneal dialysis catheter was mostly inserted surgically (67%), and swan neck straight tip peritoneal dialysis catheter was the most commonly used (48%). Vascular access was managed by radiologists and surgeons, and the management was fragmented among them in the past. However, since the nephrologists became interested in and knowledgeable about the vascular access, they began to play roles in vascular access management. Vascular access has been mostly created by vascular surgeons (≈60%); tunneled central venous hemodialysis catheter insertion and endovascular intervention such as percutaneous transluminal angioplasty (PTA) and thrombectomy have been mostly performed by radiologists (≈70%). Tunneled hemodialysis catheter insertion and endovascular intervention by nephrologists have slowly but consistently increased. Recently, the number of central venous hemodialysis catheter insertion has decreased, and tunneled hemodialysis catheter has been inserted more than non-tunneled hemodialysis catheter, indicating that vascular access has been created timely and the vascular access team has been educated about and following international guidelines.

Kim|Yong-Soo|YS|
Kim|Yaeni|Y|
Shin|Seok Joon|SJ|
Lee|Hyung Seok|HS|
Kim|Sung Gyun|SG|
Cho|Seong|S|
Na|Ki Ryang|KR|
Kim|Jin Kuk|JK|
Kim|Seung Jung|SJ|
Kim|Young Ok|YO|
Jin|Dong-Chan|DC|

D019917:Blood Vessel Prosthesis Implantation

D010043:Outcome and Process Assessment, Health Care

vascular access
Renal replacement therapy
interventional nephrology
peritoneal access


Histological, Physiological, and Comparative Proteomic Analyses Provide Insights into Leaf Rolling in Brassica napus.

Abstract: Moderate leaf rolling is important in ideotype breeding, as it improves photosynthetic efficiency and therefore increases crop yields. To understand the regulatory network of leaf rolling in Brassica napus, a down-curved leaf mutant ( Bndcl1) has been investigated. Physiological analyses indicated that the chlorophyll contents and antioxidant enzyme activities were remarkably increased and the photosynthetic performance was significantly improved in Bndcl1. Consistent with these findings, 943 differentially accumulated proteins (DAPs) were identified in the Bndcl1 mutant and its wild-type plants using iTRAQ-based comparative proteomic analyses. Enrichment analysis of proteins with higher abundance in Bndcl1 revealed that the functional category "photosynthesis" was significantly overrepresented. Moreover, proteins associated with oxidative stress response and photosystem II repairing were also up-accumulated in Bndcl1, which might help the mutant to sustain the photosynthetic efficiency under unfavorable conditions. Histological observation showed that the mutant displayed defects in adaxial-abaxial patterning. Important DAPs associated with leaf polarity establishment were detected in Bndcl1, including ribosomal proteins, proteins involved in post-transcriptional gene silencing, and proteins related to brassinosteroid. Together, our findings may help clarify the mechanisms underlying leaf rolling and its physiological effects on plants and may facilitate ideotype breeding in Brassica napus.

Chen|Wenjing|W| Wan|Shubei|S| Shen|Linkui|L| Zhou|Ying|Y| Huang|Chengwei|C| Chu|Pu|P|0000-0003-1058-6263 Guan|Rongzhan|R|

D018506:Gene Expression Regulation, Plant

leaf rolling
Brassica napus
photosynthesis
adaxial-abaxial polarity
leaf proteome


Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver.

Abstract: At present, no reports are focused on fluoride-induced hepatic inflammatory responses in human beings and animals. This study aimed to investigate the mRNA and protein levels of inflammatory cytokines and signaling molecules for evaluating the effect of different doses (0, 12, 24, and 48 mg/kg) of sodium fluoride (NaF) on inflammatory reaction in the mouse liver by using methods of experimental pathology, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. We found that NaF in excess of 12 mg/kg caused the hepatic inflammatory responses, and the results showed that NaF activated the mitogen-activated protein kinases (MAPKs) signaling pathway by markedly increasing (p < 0.01 or p < 0.05) mRNA and protein levels of apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated protein kinase kinases 1/2 (MEK1/2), extracellular signal-regulated protein kinases 1/2 (Erk1/2), mitogen-activated protein kinase kinases 4/7 (MEK4/7), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38) and mitogen-activated protein kinase kinases 3/6 (MEK3/6), and the nuclear factor-kappa B (NF-κB) signaling pathway by increasing (p < 0.01 or p < 0.05) the production of NF-κB and inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-β) and reducing (p < 0.01 or p < 0.05) the production of the inhibitory kappa B (IκB). Thus, NaF that caused the hepatic inflammatory responses was characterized by increasing (p < 0.01 or p < 0.05) the production of pro-inflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) via the activation of MAPKs and NF-κB pathways, and by significantly inhibiting (p < 0.01 or p < 0.05) the production of anti-inflammatory mediators including interleukin-4 (IL-4) and transforming growth factor beta (TGF-β).

Chen|Linlin|L| Kuang|Ping|P| Liu|Huan|H| Wei|Qin|Q| Cui|Hengmin|H| Fang|Jing|J| Zuo|Zhicai|Z| Deng|Junliang|J| Li|Yinglun|Y| Wang|Xun|X| Zhao|Ling|L|

Sodium fluoride
Inflammatory responses
MAPK
NF-κB
Liver


Analysis of Radiation Effects in Digital Subtraction Angiography of Intracranial Artery Stenosis.

Abstract:
BACKGROUND
Intracranial artery stenosis (IAS) is the most common cause for acute cerebral accidents. Digital subtraction angiography (DSA) is the gold standard to detect IAS and usually brings excess radiation exposure to examinees and examiners. The artery pathology might influence the interventional procedure, causing prolonged radiation effects. However, no studies on the association between IAS pathology and operational parameters are available.

METHODS
A retrospective analysis was conducted on 93 patients with first-ever stroke/transient ischemic attack, who received DSA examination within 3 months from onset in this single center. Comparison of baseline characteristics was determined by 2-tailed Student's t-test or the chi-square test between subjects with and without IAS. A binary logistic regression analysis was performed to determine the association between IAS pathology and the items with a P value <0.05 in Student's t-test or chi-square test.

RESULTS
There were 93 candidates (42 with IAS and 51 without IAS) in this study. The 2 groups shared no significance of the baseline characteristics (P > 0.05). We found a significantly higher total time, higher kerma area product, greater total dose, and greater DSA dose in the IAS group than in those without IAS (P < 0.05). A binary logistic regression analysis indicated the significant association between total time and IAS pathology (P < 0.05) but no significance in kerma area product, radiation dose, and DSA dose (P > 0.05).

CONCLUSIONS
IAS pathology would indicate a prolonged total time of DSA procedure in clinical practice. However, the radiation effects would not change with pathologic changes.

Guo|Chaoqun|C| Shi|Xiaolei|X| Ding|Xianhui|X| Zhou|Zhiming|Z|

Radiation
Intracranial artery stenosis
Association
Operation


Ordinal response generalized difference in differences with varying categories: The health effect of a disability program in Korea.

Abstract: We consider the use of difference in differences (DD) to evaluate the effect of an activity assistance program on the health of severely disabled Koreans. There are, however, 2 problems in the data: the number of response categories for self-assessed health changed over the waves of the repeated cross-section survey and the "parallel untreated response path" assumption for DD is suspect. We show how to overcome these problems by renormalizing parameters and applying "generalized difference in differences (GDD)." We find a significantly positive effect of the program with DD, but not with GDD. Our solutions should prove useful in applications in which one or other of these problems arise.

ordinal response
generalized difference in differences
difference in differences
self-assessed health


General practitioners' views and preferences about quality improvement feedback in preventive care: a cross-sectional study in Switzerland and France.

Abstract:
BACKGROUND
Feedback is widely used as a strategy to improve the quality of care in primary care settings. As part of a study conducted to explore the quality of preventive care, we investigated general practitioners' (GPs) views on the usefulness of feedback and their preferences regarding how feedback is provided.

METHODS
This cross-sectional study was conducted in 2015 among randomly selected community-based GPs in two regions of Switzerland and France. GPs were asked to complete an anonymous questionnaire about how often they provided 12 measures of preventive care: blood pressure, weight and height measurements, screening for dyslipidemia, at-risk drinking (and advice to reduce for at-risk drinkers), smoking (and advice to stop for smokers), colon and prostate cancer, and influenza immunization for patients >65 years and at-risk patients. They were also asked to estimate the usefulness of a feedback regarding their preventive care practice, reason(s) for which a feedback could be useful, and finally, to state which type of feedback they would like to receive. Chi-square tests were used to compare frequencies. Multivariate logistic regression was used to identify factors associated with GPs considering feedback as useful.

RESULTS
Five hundred eighteen of 1100 GPs (47.1%) returned the questionnaire. They were predominantly men (62.5%) and most (40.1%) were aged between 55 and 64 years old. Overall, 44.3% stated that a feedback would be useful. Younger GPs and those carrying out more measures of preventive care were more likely to consider feedback useful. The two main reasons for being interested in feedback were to receive knowledge about the study results and to modify or improve practice. The two preferred feedback interventions were a brief report and a report with specific information regarding prevention best practice, whereas less than 1% would like to discuss the results face-to-face with the study investigators.

CONCLUSIONS
These findings suggest that GPs have preferences regarding the types of feedback they would like to receive. Because the implementation of guidelines is highly related to the acceptance of feedback, we strongly encourage decision makers to take GPs' preferences into account when developing strategies to implement guidelines, in order to improve the quality of primary care.

Sebo|Paul|P|0000-0001-7616-0017
Maisonneuve|Hubert|H|
Fournier|Jean-Pascal|JP|
Senn|Nicolas|N|
Haller|Dagmar M|DM|

Quality improvement
Feedback
Preventive care
Primary care


Partial Hepatectomy for the Resistant Fasciola Hepatica Infection in a Child.

Abstract: Fascioliasis is an emerging and important chronic parasitic disease caused by two trematode liver fluke species: Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica) infecting several herbivorous mammals including cattle, goats, sheep, and humans. We report a 9-year-old girl who suffered from F. hepatica infection and underwent right hepatectomy because of increasing abdominal pain resistant to anthelmintic chemotherapy. When anthelmintic drug treatment is not effective and abdominal pain persists, surgical resection including hepatectomy should be kept in mind for resistant F. hepatica infection.

Belgin|Gülhan|G|
S|Kanık Yüksek|KY|
H|Tezer|T|
A|Özkaya Parlakay|ÖP|
B|Dalgıç|D|
A|Dalgıç|D|
G|Yilmaz|Y|


Dipeptidyl peptidase-4 activity might be a link between tumour necrosis factor alpha and insulin resistance in type 1 diabetes.

Abstract: Tumour necrosis factor alpha (TNF α) leads to β cell damage in type 1 diabetes (T1DM) but also causes insulin resistance (IR). It modulates dipeptidyl peptidase-4 (DPP-4) activity, adipokine linked with both IR and T1DM. We were interested if there is an association of TNF α in conjunction with DPP-4 and IR in T1DM. DPP-4 activity, TNF α concentration measurements, and insulin sensitivity calculation using estimated glucose disposal rate (eGDR) equation were performed in 70 T1DM patients. They were divided into two groups according to eGDR median. The group with higher IR had higher value of DPP-4 activity (27.57 ± 1.77 vs. 18.33 ± 1.14, p < 0.001) and TNF α concentration (12.91 ± 0.83 vs. 6.72 ± 0.36, p < 0.001). TNF α concentration and DPP-4 activity negatively correlated with eGDR (r = -0.616, p < 0.001 and r = -0.643, p < 0.001) while correlating positively with each other (r = 0.422; p = 0.001). The linear regression showed that eGDR decreases for 0.166 mg kg(-1) min(-1) by TNF α concentration increase of 1 pg/mL (p < 0.001) and for 0.090 mg kg(-1) min(-1) by DPP-4 activity increase of 1 U/L (p = 0.001) when adjusted for age, gender disease duration, glycated haemoglobin, body mass index and waist-to-hip ratio. eGDR decreased by additional 0.60 mg kg(-1) min(-1) (B = -0.150, p < 0.001) when DPP-4 activity was additionally adjusted for TNF α. TNF α concentration is associated with IR, correlates with its severity and increases the drop in insulin sensitivity modulated by DPP-4 activity. Whether TNF α involvement in the insulin signalling pathway is mediated by DPP-4 activity needs to be further evaluated.

Duvnjak|Lea|L|
Blaslov|Kristina|K|
Perković|Matea Nikolac|MN|
Ćuća|Jadranka Knežević|JK|

D001786:Blood Glucose
D003922:Diabetes Mellitus, Type 1
D018819:Dipeptidyl Peptidase 4
D005260:Female
D006442:Glycated Hemoglobin A
D006801:Humans
D007333:Insulin Resistance
D008297:Male
D008875:Middle Aged
D014409:Tumor Necrosis Factor-alpha

Dipeptidyl peptidase-4
Tumour necrosis factor alpha
Type 1 diabetes
Insulin sensitivity


Hydrothermal modifications of nonconventional kithul (Caryota urens) starch: physico-chemical, rheological properties and in vitro digestibility.

Abstract: Effect of hydrothermal modifications (autoclaving, annealing and heat moisture treatment) on physico-chemical, rheological properties and in vitro digestibility of kithul starch was studied. Annealing and heat moisture treatment decreased swelling index, solubility and increased crystalline properties as compared with autoclaving. Autoclaving, annealing and heat moisture treatment caused significant morphological damages such as large holes and fissures on the kithul starch, in addition, granules changed from oval to donut shape. Heat moisture treatment formed higher number of agglomerated starch granules. Light transmittance decreased after hydrothermal modifications. Autoclaving and annealing increased the pasting viscosities (except break down viscosity) of kithul starch. A significant increase (p ≤ 0.05) in peak temperature, conclusion temperature and enthalpy was found in annealed and heat moisture treated kithul starches. The digestibility of kithul starch decreased with increasing resistant starch after annealing and heat moisture treatment. Autoclaved, annealed and heat moisture treated kithul starches exhibited higher value of storage modulus (G') and loss modulus (G″) than native kithul starch. It entail to higher firmness of modified starch gel. The current study showed that the remarkable changes formed by hydrothermal modifications increased the industrial acceptance of kithul starch.

Hydrothermal modifications
Rheology
In vitro digestibility
Kithul starch
Thermal properties


Hepatitis C Virus and Human Cytomegalovirus-Natural Killer Cell Subsets in Persistent Viral Infections.

Abstract: Hepatitis C virus (HCV) and human cytomegalovirus (HCMV) are prominent examples of RNA and DNA viruses, respectively, that establish a persistent infection in their host. HCV affects over 185 million patients worldwide, who are at high risk for developing liver fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma. Recent breakthroughs in HCV therapy, using direct-acting antivirals have provided the opportunity to monitor natural killer (NK) cells after clearance of a chronic infection. There is now increasing evidence that the individual NK cell repertoire before infection is predictive for the course of disease. HCMV affects the majority of the global population. While being asymptomatic in healthy individuals, HCMV represents a severe clinical challenge in immunocompromised patients. Both viral infections, HCV and HCMV, lead to long-lasting and profound alterations within the entire NK cell compartment. This review article, will discuss the diverse range of changes in the NK cell compartment as well as potential consequences for the course of disease.

Pollmann|Julia|J| Rölle|Alexander|A| Hofmann|Maike|M| Cerwenka|Adelheid|A|

hepatitis C virus
human cytomegalovirus
chronic infection
natural killer cells
natural killer subsets


Use of Diagnostic CT and Patient Retention in a Lung Cancer Screening Program.

Abstract:
PURPOSE
The aims of this study were to assess the rate of subsequent diagnostic chest CT examinations in a lung cancer screening (LCS) program and examine the effect on retention of patients in the program.

METHODS
Patients who underwent LCS CT between June 2011 and August 2018 were included. The occurrence of patients' being subsequently imaged with diagnostic CT versus LCS CT and the effect this had on patients' returning for LCS CT (patient retention) were evaluated. Multivariable logistic regression was used to evaluate variables associated with undergoing diagnostic CT and risk factors associated with loss of patient retention.

RESULTS
Of the 5,912 patients who underwent LCS CT, 2,756 underwent subsequent diagnostic or LCS chest CT. Increasing Lung-RADS® score was more likely to lead to subsequent diagnostic chest CT (P < .0001). A total of 1,240 patients underwent at least three chest CT examinations in the time interval. For the 711 patients whose subsequent CT studies were for LCS, 585 (82%) were retained, whereas of the 529 patients who underwent subsequent diagnostic CT, only 208 (39%) were retained (P < .0001). For the 197 subsequent diagnostic CT examinations performed for pulmonary nodule or screening indications, 81 patients (41%) returned for LCS CT, compared with 498 of 612 patients (81%) who underwent subsequent LCS CT (P < .0001). In multivariable analysis, subsequent diagnostic chest CT and increasing Lung-RADS score were associated with loss of retention.

CONCLUSIONS
A higher Lung-RADS score is a risk factor for subsequent diagnostic chest CT, and this is an independent risk factor for loss from the LCS program.

retention
Lung cancer screening
adherence
follow-up


Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

Abstract:
BACKGROUND
To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes.

METHODS
We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes.

RESULTS
Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors.

CONCLUSION
SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.

Bae|Jae Hyun|JH|
Park|Eun-Gee|EG|
Kim|Sunhee|S|
Kim|Sin Gon|SG|
Hahn|Seokyung|S|
Kim|Nam Hoon|NH|

Network meta-analysis
Albuminuria
Diabetes mellitus, type 2
Diabetic nephropathies
Dipeptidyl-peptidase IV inhibitors
Kidney failure, chronic
Sodium-glucose transporter 2 inhibitors


Efficacy and safety of hyperbaric oxygen therapy for moderate-to-severe ulcerative colitis: a protocol for a systematic review and meta-analysis.

Abstract:
INTRODUCTION
Ulcerative colitis (UC) is a type of inflammatory bowel disease, and 62% of patients with UC felt that it is difficult for them to live a normal life. Furthermore, some researches have shown that about 15% of patients with UC undergo at least one extreme clinical course in their lifetime, and 10%-30% of patients with UC oblige colectomy. Although many investigations have demonstrated that HBO2 has a beneficial impact on UC treatment, a systematic review and meta-analysis are unavailable. Therefore, a meta-analysis is essential to assess the efficacy and safety of HBO2 in treating UC.

METHODS AND ANALYSIS
A systematic search plan will be performed in the following seven databases with a restriction of time from inception to September 2020 to filter the eligible studies: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP) and Chinese Biomedical Database WanFang. Other related resources will be also searched. Two independent reviewers will choose eligible researches and extract data. The risk of bias will be evaluated based on Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale. Eventually, a systematic review and meta-analysis will be performed via the Review Manager V.5.3 statistical software and STATA V.14.0 software.

ETHICS AND DISSEMINATION
This study will not involve the individual patient and any ethical problems since its outcomes are based on published data. Therefore, no ethical review and approval are required. We plan to publish the study in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER
CRD42020210244.

Luo|Lihong|L|0000-0001-9055-1137 Qing|Lei|L| Yao|Chengjiao|C| Liu|Dongying|D| Li|Yilin|Y| Li|Tinglin|T| Feng|Peimin|P|

D002681:China
D003093:Colitis, Ulcerative
D006801:Humans
D006931:Hyperbaric Oxygenation
D015201:Meta-Analysis as Topic
D012107:Research Design
D000078202:Systematic Reviews as Topic

inflammatory bowel disease
adult gastroenterology
coeliac disease
endoscopy


Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis.

Abstract: The study aims to explore the potential of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in improving the topical delivery of capsaicin (CAP) by in vitro and in vivo studies. The lipidic nanoparticles were prepared by solvent diffusion method and were characterized for average particle size, zeta potential and entrapment efficiency. TEM photomicrographs revealed that the particles were nanometric in size. Higher amount of CAP can be encapsulated in the NLCs (87.4 ± 3.28) as compared with SLNs (79.7 ± 2.93%). The cumulative amounts of CAP permeated through the skin and retained in the SC were higher in the case of NLCs as compared with plain drug solution and SLNs. SLNs and NLCs exhibited minimum to no irritation. All the results concluded that NLCs and SLNs have shown a good ability to increase drug accumulation in the various skin layers but NLCs may be a more potential carrier for topical delivery of CAP for an effective therapy of psoriasis.

Agrawal|Udita|U|
Gupta|Madhu|M|
Vyas|S P|SP|

skin
lipidic nanoparticle
topical delivery
CAP


Contemporary proteomic research on lignocellulosic enzymes and enzymolysis: A review.

Abstract: This review overviewed the current researches on the isolation of novel strains, the development of novel identification protocols, the key enzymes and their synergistic interactions with other functional enzyme systems, and the strategies for enhancing enzymolysis efficiencies. The main obstacle for realizing biorefinery of lignocellulosic biomass to biofuels or biochemicals is the high cost of enzymolysis stage. Therefore, research prospects to reduce the costs for lignocellulose hydrolysis were outlined.

Enzyme
Enzymolysis
Identification
Proteomic analysis


Antibiotic anisomycin induces cell cycle arrest and apoptosis through inhibiting mitochondrial biogenesis in osteosarcoma.

Abstract: The anti-cancer activities of antibiotic anisomycin have been demonstrated in kidney, colon and ovarian cancers whereas its underlying mechanisms are not well elucidated. In this work, we investigated whether anisomycin is effective in sensitizes osteosarcoma cell response to chemotherapy. We show that anisomycin inhibits proliferation via inducing osteosarcoma cell arrest at G2/M phase, accompanied by the increased levels of mitotic marker cyclin B and the decreased levels of Rb and E2F-1. Anisomycin also induces apoptosis in a caspase-dependent manner in osteosarcoma cells. Importantly, anisomycin is less effective in normal control NIH3T3 cells compared to osteosarcoma cells. In addition, anisomycin inhibits osteosarcoma growth in xenograft mouse model and enhances the inhibitory effects of doxorubicin in osteosarcoma in vitro and in vivo. Mechanistically, anisomycin targets mitochondrial biogenesis in osteosarcoma as shown by the decreased mitochondrial membrane potential, suppressed mitochondrial respiration via decreasing complex I activity, reduced ATP production. Furthermore, mitochondrial biogenesis stimulator acetyl-L-Carnitine (ALCAR) significantly rescues the inhibitory effects of anisomycin in osteosarcoma cells. Our work demonstrates that anisomycin is active against osteosarcoma cells and the molecular mechanism of its action is the inhibition of mitochondrial biogenesis.

Cao|Chuanhua|C| Yu|Haiying|H| Wu|Feng|F| Qi|Huixiong|H| He|Jingbo|J|

Anisomycin
Osteosarcoma
Mitochondria biogenesis


Cognitive and Affective Empathy in Huntington's Disease.

Abstract:
BACKGROUND
Empathy is a multidimensional construct and a key component of social cognition. In Huntington's disease (HD), little is known regarding the phenomenology and the neural correlates of cognitive and affective empathy, and regarding how empathic deficits interact with other behavioral and cognitive manifestations.

OBJECTIVE
To explore the cognitive and affective empathy disturbances and related behavioral and neural correlates in HD.

METHODS
Clinical and sociodemographic data were obtained from 36 healthy controls (HC) and 54 gene-mutation carriers (17 premanifest and 37 early-manifest HD). The Test of Cognitive and Affective Empathy (TECA) was used to characterize cognitive (CE) and affective empathy (AE), and to explore their associations with grey matter volume (GMV) and cortical thickness (Cth).

RESULTS
Compared to HC, premanifest participants performed significantly worse in perspective taking (CE) and empathic distress (AE). In symptomatic participants, scores were significantly lower in almost all the TECA subscales. Several empathy subscales were associated with the severity of apathy, irritability, and cognitive deficits. CE was associated with GMV in thalamic, temporal, and occipital regions, and with Cth in parietal and temporal areas. AE was associated with GMV in the basal ganglia, limbic, occipital, and medial orbitofrontal regions, and with Cth in parieto-occipital areas.

CONCLUSION
Cognitive and affective empathy deficits are detectable early, are more severe in symptomatic participants, and involve the disruption of several fronto-temporal, parieto-occipital, basal ganglia, and limbic regions. These deficits are associated with disease severity and contribute to several behavioral symptoms, facilitating the presentation of maladaptive patterns of social interaction.

Puig-Davi|Arnau|A| Martinez-Horta|Saul|S| Sampedro|Frederic|F| Horta-Barba|Andrea|A| Perez-Perez|Jesus|J| Campolongo|Antonia|A| Izquierdo-Barrionuevo|Cristina|C| Pagonabarraga|Javier|J| Gomez-Anson|Beatriz|B| Kulisevsky|Jaime|J|

empathy
social cognition
Huntington’s disease
magnetic resonance imaging
voxel-based morphometry


Endovascular Treatment of Post-thrombotic Venous Ilio-Femoral Occlusions: Prognostic Value of Venous Lesions Caudal to the Common Femoral Vein.

Abstract:
OBJECTIVES
To propose a scale of severity for post-thrombotic venous lesions (PTVLs) after ilio-femoral deep venous thrombosis and to compare the grade with the results of endovascular treatment of ilio-femoral PTVLs.

METHODS
In this retrospective monocentric observational study, we included 95 patients treated for ilio-femoral PTVLs. We proposed a four-grade scale evaluating the severity of PTVLS caudal to the common femoral vein based on CT phlebography and per-operative phlebography. For most patients, venous patency was assessed with color duplex ultrasonography and the clinical efficacy of the intervention using the Villalta and CIVIQ scores.

RESULTS
Recanalization was successful in 100% of patients with a morbidity rate of 4%. After a mean follow-up of 21 months, the overall primary patency was 75%, the assisted primary patency 82%, and the secondary patency 93%. Secondary patency was 100% for grade 0-1, 90% for grade 2, and 63% for grade 3 (p < 0.002). There was no correlation between the extension of stenting caudally of the common femoral vein and venous patency. The mean improvements in the Villalta and CIVIQ-20 scores were, respectively, 4.6 (p < 0.0001) and 18 (p < 0.0001); scores were not correlated with the grade of PTVLs in the thigh.

CONCLUSION
Venous patency after endovascular treatment of ilio-femoral PTVLs was strongly linked to the severity of PTVLs caudal to the common femoral vein but not to the extent of stenting.

Deep venous thrombosis
Stent
Iliac vein
Inferior vena cava
Post-thrombotic syndrome


Effects of chitosan fiber addition on the properties of polyurethane with thermo-responsive shape memory.

Abstract: We investigated the effects of the addition of chitosan fiber (biomass nanofiber made by Sugino (BiNFi-s)) to polyether-based thermoplastic polyurethane (TPU) on material properties. BiNFi-s (2 and 5 wt %)/TPU composite materials were prepared via compression molding, and glass fiber (2 and 5 wt %)/TPU composite materials and plain TPU were also prepared for comparison. The glass transition temperature was analyzed using differential scanning calorimetry, and the crystal structure was investigated using X-ray diffraction. 20-mm-long test specimens with cross-sectional dimensions of 1 mm × 1 mm were cut from sheets of the composite materials, and three-point bending tests were carried out using a universal testing machine to investigate their mechanical properties and shape memory. The addition of BiNFi-s or glass fiber to TPU did not influence the glass transition temperature, although the crystal structure changed from semi-crystalline to amorphous. The elastic modulus increased 40% by the addition of 5 wt % BiNFi-s (2.31 MPa) compared with plain TPU (1.65 MPa), and these composites exhibited shape recovery with clinically relevant changes in temperature. The addition of 5 wt % BiNFi-s into TPU resulted in an improvement in the elastic modulus without any decrease in the shape memory effect. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1151-1156, 2017.

Kawaguchi|Kyotaro|K| Iijima|Masahiro|M| Miyakawa|Hiroshi|H| Ohta|Mitsuru|M| Muguruma|Takeshi|T| Endo|Kazuhiko|K| Nakazawa|Futoshi|F| Mizoguchi|Itaru|I|

chitosan
shape memory
thermoplastic polyurethane
mechanical properties
polymer


Neural language processing in adolescent first-language learners.

Abstract: The relation between the timing of language input and development of neural organization for language processing in adulthood has been difficult to tease apart because language is ubiquitous in the environment of nearly all infants. However, within the congenitally deaf population are individuals who do not experience language until after early childhood. Here, we investigated the neural underpinnings of American Sign Language (ASL) in 2 adolescents who had no sustained language input until they were approximately 14 years old. Using anatomically constrained magnetoencephalography, we found that recently learned signed words mainly activated right superior parietal, anterior occipital, and dorsolateral prefrontal areas in these 2 individuals. This spatiotemporal activity pattern was significantly different from the left fronto-temporal pattern observed in young deaf adults who acquired ASL from birth, and from that of hearing young adults learning ASL as a second language for a similar length of time as the cases. These results provide direct evidence that the timing of language experience over human development affects the organization of neural language processing.

Ferjan Ramirez|Naja|N|
Leonard|Matthew K|MK|
Torres|Christina|C|
Hatrak|Marla|M|
Halgren|Eric|E|
Mayberry|Rachel I|RI|


Focal hypermobility observed in cervical arthroplasty with Mobi-C.

Abstract: In recent decades cervical arthroplasty, or cervical disc replacement, has been steadily increasing in popularity as a procedure for the treatment of degenerative pathologies of the cervical spine. This is based on an evolving body of literature that documents superior outcomes in cervical disc replacement over fusion, for both single and double level pathologies, in well selected patients. One of the more recent and popular implants currently on the market is the Mobi-C cervical artificial disc (LDR Medical; Troyes, France). In this paper we report on two cases where focal hypermobility was observed following total disc replacement using the Mobi-C cervical artificial disc. This is followed by a discussion as to potential contributing factors to this hypermobility in relation to both implant design, and operative technique, suggesting potential changes that might prevent this in future patients.

Kerferd|Jack William|JW|
Abi-Hanna|David|D|
Phan|Kevin|K|
Rao|Prashanth|P|
Mobbs|Ralph J|RJ|

cervical, total disc replacement, Mobi-c


Brain-Computer Interface-Based Adaptive Automation to Prevent Out-Of-The-Loop Phenomenon in Air Traffic Controllers Dealing With Highly Automated Systems.

Abstract: Increasing the level of automation in air traffic management is seen as a measure to increase the performance of the service to satisfy the predicted future demand. This is expected to result in new roles for the human operator: he will mainly monitor highly automated systems and seldom intervene. Therefore, air traffic controllers (ATCos) would often work in a supervisory or control mode rather than in a direct operating mode. However, it has been demonstrated how human operators in such a role are affected by human performance issues, known as Out-Of-The-Loop (OOTL) phenomenon, consisting in lack of attention, loss of situational awareness and de-skilling. A countermeasure to this phenomenon has been identified in the adaptive automation (AA), i.e., a system able to allocate the operative tasks to the machine or to the operator depending on their needs. In this context, psychophysiological measures have been highlighted as powerful tool to provide a reliable, unobtrusive and real-time assessment of the ATCo's mental state to be used as control logic for AA-based systems. In this paper, it is presented the so-called "Vigilance and Attention Controller", a system based on electroencephalography (EEG) and eye-tracking (ET) techniques, aimed to assess in real time the vigilance level of an ATCo dealing with a highly automated human-machine interface and to use this measure to adapt the level of automation of the interface itself. The system has been tested on 14 professional ATCos performing two highly realistic scenarios, one with the system disabled and one with the system enabled. The results confirmed that (i) long high automated tasks induce vigilance decreasing and OOTL-related phenomena; (ii) EEG measures are sensitive to these kinds of mental impairments; and (iii) AA was able to counteract this negative effect by keeping the ATCo more involved within the operative task. The results were confirmed by EEG and ET measures as well as by performance and subjective ones, providing a clear example of potential applications and related benefits of AA.

Di Flumeri|Gianluca|G|
De Crescenzio|Francesca|F|
Berberian|Bruno|B|
Ohneiser|Oliver|O|
Kramer|Jan|J|
Aricò|Pietro|P|
Borghini|Gianluca|G|
Babiloni|Fabio|F|
Bagassi|Sara|S|
Piastra|Sergio|S|

adaptive automation
Out-Of-The-Loop
air traffic control
vigilance
electroencephalography
eye-tracking
human–machine interface
passive brain–computer interface


Application of ATR-FTIR spectroscopy for profiling of non-structural carbohydrates in onion (Allium cepa L.) bulbs.

Abstract: Qualitative and quantitative composition of non-structural carbohydrates comprising glucose, fructose, sucrose and fructooligosaccharides (FOS) is one of the key determinants of market suitability, storability and technological processability of onions. To develop a cost-effective and rapid tool for carbohydrate profiling, applicability of attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy of onion juice was investigated with special regard to FOS patterns. As reference, detailed carbohydrate profiles of onion juices were generated by high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD). Hierarchical cluster analysis (HCA) of ATR-FTIR spectra was successfully applied for classifying onions into fresh market, storage and dehydrator type according to HPLC-ELSD profiles. A bootstrapping method for automatized test-set validation by projection to latent structures (PLS) algorithms using HPLC and ATR-FTIR spectroscopy data was developed. Model statistics showed promising perspectives for reliable quantification of individual saccharides and sum parameters. The presented methodology allows estimating the nutritional and pre-biotic value directly during cultivation and processing.

Krähmer|Andrea|A| Böttcher|Christoph|C| Gudi|Gennadi|G| Stürtz|Melanie|M| Schulz|Hartwig|H|

D017550:Spectroscopy, Fourier Transform Infrared

Non-structural carbohydrates
Fructooligosaccharides
Carbohydrate profiling
Onion juice
HPLC-ELSD
Bootstrapping
Quantification
Infrared spectroscopy


In vitro study for the evaluation of transluminal aspiration as a novel treatment option for thrombosis in the HeartWare HVAD.

Abstract:
INTRODUCTION:
Pump thrombosis of left ventricular assist devices remains a devastating complication with high morbidity and mortality. Despite the improvements made, the matter affects many patients and the treatment options are limited to thrombolysis and surgical replacement. An alternative approach using the aspiration Indigo catheter was tested.

METHODS:
An Indigo thrombectomy catheter was used within an in vitro model to assess the direct aspiration of prefabricated clots from three different positions within the HeartWare HVAD (inlet, outlet, and housing). The experiments were conducted with a straight and an angled catheter. The aspiration pressure was constant. The flow, power consumption, and pressure head of the left ventricular assist devices were measured at pre-defined measuring points.

RESULTS:
The device was more effective (success rate 71%) at inlet and outlet of the left ventricular assist device. In addition, the duration of aspiration and the aspiration volume were shorter in comparison to the aspiration in the housing (inlet M = 19.75 s, outlet M = 60.50 s, and housing M = 38.75 s). Moreover, the aspiration volume was associated with the aspiration duration and the weight of thrombi but not with their volume. Noteworthy, the angled catheter showed an improved performance compared to the straight one (67%-33%). The recorded parameters showed no major changes during the use of the catheter. After application of the Indigo catheter, flow and pressure head of the pump could be restored.

CONCLUSIONS:
The aspiration system showed promising results under specific conditions for the treatment of pump thrombosis in an in vitro model. However, further examination, including in vivo experiments, will justify its effectiveness.

Gärtner|Theresa|T|
Beropoulis|Efthymios|E|
Wendl|Regina|R|
Hanke|Jasmin S|JS|
Dogan|Günes|G|
Chatterjee|Anamika|A|
Haverich|Axel|A|
Torsello|Giovanni|G|
Schmitto|Jan D|JD|
Bisdas|Theodosios|T|
Feldmann|Christina|C|

D006333:Heart Failure
D016027:Heart Transplantation
D006353:Heart-Assist Devices
D006801:Humans
D013927:Thrombosis
D016896:Treatment Outcome

HVAD
Pump thrombosis
left ventricular assist device
ventricular assist device
Indigo
aspiration mechanical thrombectomy


Potential neurotoxicity, immunotoxicity, and carcinogenicity induced by metribuzin and tebuconazole exposure in earthworms (Eisenia fetida) revealed by transcriptome analysis.

Abstract: Metribuzin and tebuconazole have been widely used in agriculture for several decades. Apart from endocrine disruption, little is known about their toxicological effects on organisms without thyroid organs, at the transcriptional level. To explore this toxicity, model earthworm species Eisenia fetida, hatched from the same cocoon and cultured under identical environmental conditions, were independently exposed to the two chemicals at non-lethal concentrations in OECD artificial soil for 48 h after exposure. RNA-seq technology was used to analyze and compare the gene expression profiles of earthworms exposed to metribuzin and tebuconazole. The functions of differentially expressed genes and their standard response patterns of upregulated and downregulated expression for both pesticides were verified. The findings demonstrated that metribuzin and tebuconazole are both potentially toxic to earthworms. Toxicological effects mainly involved the nervous system, immune system, and tumors, at the transcriptional level, as well as the induction of cytochrome P450-dependent detoxification and oxidative stress. In addition, the mitogen-activated protein kinase kinase kinase gene was identified as a biomarker, and the mitogen-activated protein kinase signaling pathway was verified to be a part of the adverse outcome pathway of metribuzin and tebuconazole and their structural analogs.

Li|Gang|G| Li|Dongxue|D| Rao|Huixian|H| Liu|Xinjǚ|X|

Transcriptome analysis
Toxicity
Triazinone herbicide
Triazole fungicide


Surgical results in penile fracture: Our single center experience.

Abstract:
INTRODUCTION
Penile fracture arises as a result of a unilateral or bilateral rupture of the tunica albuginea of the corpus cavernosum. It is a rare condition that requires urgent surgical intervention. In this study, we aimed to determine the effectiveness of surgical treatment in penile fracture and its effect on complications.

METHODS
The data of 21 patients who were admitted to the emergency department of our clinic between 2012 and 2019 and underwent emergency surgical repair with the diagnosis of penile fracture were collected retrospectively. The diagnosis of penile fracture was established by anamnesis and physical examination. Age, etiology, duration from trauma to surgery, physical examination findings,length and localization of the tunica albuginea defect, length of hospital stay, and postoperative first-, third- and sixth-month follow-up results were analyzed. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5). Complications such as penile curvature, penile nodule and painful erection were evaluated.

RESULTS
The mean age of the patients was 36.8 ± 8.3 years. The most common reason of penile fracture was manually bending the penis for detumescence. All patients underwent surgery. The mean duration from trauma to surgery was 7.6 ± 3.1 h. The mean length of the tunica albuginea defect was 11 ± 2.5 mm. The mean length of hospital stay was 2.5 ± 0.5 days. The mean IIEF-5 scores in the postoperative first, third and sixth months were 20.5 ± 2.6, 22 ± 2.2, 22.1 ± 1.7, respectively.

CONCLUSION
Penile fracture is a urological emergency, and timely surgery is an effective treatment method for preventing postoperative complications.

Yilmazel|Fatih Kursat|FK|
Sam|Emre|E|
Altay|Mehmet Sefa|MS|
Cinislioglu|Ahmet Emre|AE|
Sam|Emel|E|
Delice|Orhan|O|
Karabulut|Ibrahim|I|

Penile fracture
Urological emergency
Erectile dysfunction
Penile ecchymosis
Penile swelling


Prosocial behavior in aging: which factors can explain age-related differences in social-economic decision making?

Abstract:
OBJECTIVES
Older adults tend to exhibit more prosocial behavior than younger adults. However, little research has focused on understanding the factors that may explain such differences in the social decision-making process. The first aim was to examine if, and to what degree, the content of social information about a recipient has an impact on young vs. older adults' prosocial behavior. The second aim was to understand if empathic concern, Theory of Mind, and reasoning explain the (expected) age differences in prosociality.

DESIGN
Cross-sectional study.

SETTING
The study was conducted in northern Italy in a laboratory setting.

PARTICIPANTS
Forty-eight younger adults (Mage = 23.29; SD = 2.20) and 48 older adults (Mage = 70.19; SD = 5.13).

MEASUREMENTS
Prosocial behavior was measured using the Dictator Game in which participants split a sum of money with recipients presented with four levels of description: no information, physical description, positive psychological description, and negative psychological description. In addition, participants performed tasks on emphatic concern, Theory of Mind, and reasoning.

RESULTS
Results showed that older adults are more prosocial than younger adults in the Dictator Game. This finding was evident when the recipient was described with positive psychological and physical features. This pattern of results was statistically explained by the reduction in reasoning ability.

CONCLUSION
These findings suggest a relationship between age-related reduction in reasoning ability and older adults' prosocial behavior. The theoretical and practical implication of the empirical findings are discussed.

Rosi|Alessia|A|0000-0001-6692-3279 Nola|Marta|M| Lecce|Serena|S| Cavallini|Elena|E|

aging
social-economic decision making
theory of mind
reasoning
Dictator Game
cognition
empathy
individual differences


Influence of heart rate and coronary artery calcification on image quality and diagnostic performance of coronary CT angiography: comparison between 96-row detector dual source CT and 256-row multidetector CT.

Abstract:
BACKGROUND
CT-derived fractional flow reserve (FFRCT) and diagnostic accuracy rely on good image quality during coronary CT angiography (CCTA).

OBJECTIVE
To investigate whether heart rate (HR) and coronary artery calcium (CAC) score decrease image quality and diagnostic performance of two advanced CT scanners including 96-row detector dual source CT (DSCT) and 256-row multidetector CT (MDCT).

METHODS
First, 79 patients who underwent CCTA (42 with DSCT and 37 with MDCT) and invasive coronary angiography (ICA) are enrolled. Next, coronary segments with excellent image quality are evaluated and the percentage is calculated. Then, diagnostic accuracy in detecting significant diameter stenosis is presented with ICA as the reference standard.

RESULTS
Compared with the DSCT, the percentage of coronary segments with excellent image quality is lower (P = 0.010) while diagnostic accuracy on per-segment level is improved (P = 0.037) using MDCT. CAC score≥400 is the only independent factor influencing the percentage of coronary segments with excellent image quality [odds ratio (OR): DSCT, 3.096 and MDCT, 1.982] and segmental diagnostic accuracy (OR: DSCT, 2.630 and MDCT, 2.336) for both scanners. HR≥70 bpm (OR: 5.506) is the independent factor influencing the percentage of coronary segments with excellent image quality with MDCT.

CONCLULSION
During CCTA, CAC score≥400 still decreases the proportion of coronary segments with excellent image quality and diagnostic accuracy with advanced CT scanners. HR≥70 bpm is another factor causing image quality decreasing with MDCT.

Qian|Wen|W| Liu|Wangyan|W| Zhu|Yinsu|Y| Wang|Jun|J| Chen|Yang|Y| Meng|Haoyu|H| Chen|Leilei|L| Xu|Yi|Y| Zhu|Xiaomei|X|

D053805:Fractional Flow Reserve, Myocardial

heart rate
calcium
Coronary angiography
coronary stenosis
multidetector computed tomography


Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation.

Abstract:
BACKGROUND
A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is β cell dysfunction. Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore β cell function is of utmost importance.

METHODS
This study aims to unveil the mechanistic action of mesenchymal stem cells (MSCs) by investigating its impact on isolated human T2DM islets ex vivo and in vivo.

FINDINGS
We propose that MSCs can attenuate β cell dysfunction by reversing β cell dedifferentiation in an IL-1Ra-mediated manner. In response to the elevated expression of proinflammatory cytokines in human T2DM islet cells, we observed that MSCs was activated to secret IL-1R antagonist (IL-1Ra) which acted on the inflammed islets and reversed β cell dedifferentiation, suggesting a crosstalk between MSCs and human T2DM islets. The co-transplantation of MSCs with human T2DM islets in diabetic SCID mice and intravenous infusion of MSCs in db/db mice revealed the reversal of β cell dedifferentiation and improved glycaemic control in the latter.

INTERPRETATION
This evidence highlights the potential of MSCs in future cell-based therapies regarding the amelioration of β cell dysfunction.

Wang|Le|L| Liu|Tengli|T| Liang|Rui|R| Wang|Guanqiao|G| Liu|Yaojuan|Y| Zou|Jiaqi|J| Liu|Na|N| Zhang|Boya|B| Liu|Yan|Y| Ding|Xuejie|X| Cai|Xiangheng|X| Wang|Zhiping|Z| Xu|Xiumin|X| Ricordi|Camillo|C| Wang|Shusen|S| Shen|Zhongyang|Z|

D053590:Interleukin 1 Receptor Antagonist Protein

D045164:Mesenchymal Stem Cell Transplantation

Mesenchymal stem cells
β cell dysfunction
β cell dedifferentiation
Type 2 diabetes mellitus
Inflammation


Comparison of Insulin Pump Therapy and Multiple Daily Injections Insulin Regimen in Patients with Type 1 Diabetes During Ramadan Fasting.

Abstract:
INTRODUCTION
Fasting Ramadan carries a high risk for patients with type 1 diabetes (T1DM). Data on the optimum insulin regimen in these patients are limited.

OBJECTIVES
To compare glucose profiles in patients with T1DM who use continuous subcutaneous insulin infusion (CSII) compared with those who use multiple daily injections (MDI) insulin regimen during Ramadan fast. The primary outcome was rates of hypoglycemia. Other outcomes included glycemic control, number of days needed to break fasting, and acute glycemic complications.

METHODS
Patients with T1DM who were on CSII or MDI and decided to fast Ramadan were recruited. Glucose data collected using self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) were compared in the two groups, CSII and MDI, and glucose control was assessed by measuring serum fructosamine levels.

RESULTS
A total of 156 patients were recruited, 61 on CSII and 95 on MDI. There was no difference in the rate of mild hypoglycemia <4.4 mmol/L (<80 mg/dL) (8.6% ± 6.1% in the CSII group and 9.85% ± 9.34% in the MDI group, P = 0.96). The mean rate of severe hypoglycemia <2.7 mmol/L (<50 mg/dL) was also not different in both groups (0.99% ± 1.7% in the CSII group compared to 1.7% ± 4.7% in the MDI group, P = 0.23). There was no difference in glycemic control as measured by fructosamine levels or the number of days that patients have to stop fasting. Glucose variability was significantly better in CSII group (SMBG; standard deviation [SD] 66.9 ± 15.3 vs. 76.9 ± 29.9, P = 0.02) (CGM; SD 68.1 ± 19.6 vs. 78.7 ± 24.9, P = 0.04). No diabetic ketoacidosis was reported in either group.

CONCLUSION
In patients with T1DM who fast Ramadan, there was no difference in rates of hypoglycemia or hyperglycemia between CSII and MDI. However, CSII was associated with less glucose variability.

Alamoudi|Reem|R| Alsubaiee|Maram|M| Alqarni|Ali|A| Saleh|Yousef|Y| Aljaser|Saleh|S| Salam|Abdul|A| Eledrisi|Mohsen|M|

Insulin pump
Multiple daily injections
Type 1 diabetes
Ramadan
Fasting
Continuous glucose monitoring


Effect of Primary and Secondary Beads of Carbon Enterosorbent on Haematological Parameters and Oxidative Stress Development Caused by Melphalan in Rats.

Abstract: Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer-Emmett-Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1-primary beads with the particle size range of 125-250 µm, and AC2-micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde-dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

Shevchuk|Oksana|O|0000-0003-2473-6381 Snezhkova|Elisaveta|E| Sarnatskaya|Veronika|V| Mikhailenko|Victor|V| Glavin|Alexei|A| Makovetska|Lyudmyla|L| Bardakhivska|Kvitoslava|K| Birchenko|Inna|I| Kozynchenko|Oleksandr|O| Nikolaev|Volodymyr|V|

oxidative stress
melphalan
rats
myelotoxicity
anti-cancer chemotherapy
enterosorption


MitoLink: A generic integrated web-based workflow system to evaluate genotype-phenotype correlations in human mitochondrial diseases: Observations from the GenomeAsia Pilot project.

Abstract: MitoLink is a generic, scalable and modular web-based workflow system developed to study genotype-phenotype correlations in human mitochondrial diseases. MitoLink integrates applications for assessment of genomic variation and currently houses genome-wide datasets from GenomeAsia Pilot project, gnomAD, ClinVar and DisGenNet. In this study, a reference list of nearly 3975 proteins (both nuclear and mitochondrial encoded) with mitochondrial function is reported. This protein set is mapped to disease associated variants in the GenomeAsia Pilot Project and DisGenNet and evaluated for pathogenicity as defined by ClinVar. Observations of shared genetic components in potential comorbidities are discussed from gene-disease network in Asian population, however, the platform is generic and can be applied to any population dataset. MitoLink is a unique customized workflow system that allows for systematic storage, extraction, analysis and visualization of genomic variation to understand genotype-phenotype correlations for mitochondrial diseases. Given the modularity of tool and data integration, MitoLink is a scalable system that can accommodate a diverse set of applications linked via standard data structure within the framework of Galaxy. MitoLink is built on FAIR principles and supports creation of reproducible workflows towards understanding genotype-phenotype correlations across several disease phenotypes globally.

Kumar|Rakesh|R|
K Rajput|Neeraj|N|
Jolly|Bani|B|
Narwade|Amol|A|
Bhardwaj|Anshu|A|

Genotype-phenotype
Mitochondrial diseases
GenomeAsia
Genome variation
Galaxy workflow
NGS


Investigation of some univariate and multivariate spectrophotometric methods for concurrent estimation of Vancomycin and Ciprofloxacin in their laboratory prepared mixture and application to biological fluids.

Abstract: Four simple, rapid, accurate and precise spectrophotometric methods were established and validated in accordance with ICH Q2 (R1) guidelines for the simultaneous determination of Vancomycin (VNC) and Ciprofloxacin (CPR) in their raw materials, laboratory prepared mixtures and pharmaceutics. Method A depends on using first derivative spectrophotometry (D1) where VNC and CPR were resolved at 243.6 and 262.0 nm, respectively. Concerning method B, it is based on utilizing first derivative of ratio spectra (DD1) where determination was performed at the peak maxima at 244.0 nm and 258.0 nm for VNC and CPR, respectively. Two chemometric models were applied for the quantitative analysis of both drugs in their laboratory prepared mixtures, namely, partial least squares (PLS) (method C) and artificial neural network (ANN) (method D). For univariate methods linearity range for both drugs was in the range of 3-30 and 1-10 μg/mL for VNC and CPR, respectively. Multivariate calibration methods using five level, two factor calibration model for the development of 25 mixtures were also applied for the simultaneous estimation of the two drugs in their laboratory prepared mixture using spectral region from 200.0 to 300.0 nm using interval 1 nm. The suggested methods have been successfully extended to the assay of the two studied drugs in laboratory-prepared mixtures and pharmaceuticals with excellent recovery. First derivative spectrophotometry (D1) was also applied for the assay of both analytes in spiked human plasma with good recovery. No interaction with common pharmaceutical additives has been observed which indicate the selectivity of the method. The results obtained were favourably compared with those obtained applying the reported methods. The methods are validated in compliance with the ICH Q2 (R1) guidelines and the measured accuracy and precision are assessed to be within the accepted limits.

El-Aziz|Heba Abd|HA|
Fathy|M E|ME|
El-Enany|N|N|
Aly|F A|FA|
Tolba|M M|MM|

Vancomycin
Ciprofloxacin
First derivative spectrophotometry
Multivariate calibration methods
First derivative ratio spectra
Pharmaceutics and human plasma