Krüppel-like factor 4 synergizes with CREB to increase the activity of apolipoprotein E gene promoter in macrophages.

Abstract: Krüppel-like factor 4 (KLF4) is a critical regulator of monocyte differentiation and macrophage polarization, and it also plays an important role in several vascular diseases, including atherosclerosis. Apolipoprotein E (apoE) is an essential anti-atherosclerotic glycoprotein involved in lipid metabolism, expressed by the liver, macrophages and other cell types. We hypothesized that KLF4 is involved in apoE gene regulation in macrophages. Our experiments showed that differentiation of THP-1 monocytes to macrophages using PMA was associated with a robust induction of both KLF4 and apoE genes. KLF4 bound to the apoE promoter, as revealed by chromatin immunoprecipitation and DNA pull-down (DNAP) assays, and transactivated the apoE promoter in a dose-dependent manner. Using a series of apoE promoter deletion mutants we revealed the biological activity of multiple KLF4 binding sites located in the [-500/-100] region of apoE promoter. Moreover, overexpression of cAMP-response-element-binding protein (CREB) further increased KLF4 up-regulatory effect on apoE promoter. Despite the fact that no putative CREB binding sites were predicted in silico, we found that in macrophages CREB bound to apoE proximal promoter in the region -200/+4 and even more strongly on -350/-274 region. In similar DNAP experiments using cell extracts obtained from monocytes (lacking KLF4), a very weak binding of CREB was detected, indicating that interaction of CREB with apoE promoter takes place indirectly. In conclusion our results show: (i) a robust synchronized induction of KLF4 and apoE expression during differentiation of monocytes to macrophages; (ii) KLF4 up-regulates apoE gene in a dose-dependent manner; (iii) biologically active KLF4 binding sites are present on apoE promoter and (iv) the interaction of KLF4 with CREB results in an enhanced up-regulatory effect of KLF4 on apoE promoter. Taken together these data provide novel knowledge on apoE gene regulation mechanism in macrophages, and offer insight into the therapeutic potential of KLF4 in atherosclerosis.

Stavri|Simona|S|
Simionescu|Maya|M|
Kardassis|Dimitris|D|
Gafencu|Anca V|AV|

D017362:Cyclic AMP Response Element-Binding Protein

CREB
Apolipoprotein E
Macrophage
KLF4
Monocyte differentiation
Gene regulation


Quinoline and quinolone dimers and their biological activities: An overview.

Abstract: Quinoline and quinolone motifs which act as structural subunits of more complex natural products are ubiquitous in nature, and they are useful pharmacophores which play a pivotal role in drug development. Compared with the corresponding monomeric compounds, the dimers usually exhibited some unique properties, so dimers have caused great interests in recent years. Quinline and quinolone dimers possess various biological properties such as antibacterial, anticancer, antimalarial and antitubercular activities, and some of them which are exemplified by piperaquine have already used in clinical practice. Numerous quinline and quinolone dimers have been synthesized and screened for their in vitro and in vivo biological activities, and some of them exhibited promising potency. Therefore, quinline and quinolone dimers have the potential for clinical deployment in the control and eradication of various diseases. This review covers the recent advances of quinline and quinolone dimers as bioactive substances. The structure-activity relationship was also discussed to provide an insight for rational designs of more active quinline and quinolone dimers.

Chu|Xue-Mei|XM| Wang|Cong|C| Liu|Wen|W| Liang|Li-Li|LL| Gong|Kai-Kai|KK| Zhao|Cheng-Ying|CY| Sun|Kun-Lai|KL|

Quinoline
Quinolone
Dimer
Antibacterial
Anticancer
Antimalarial
Antitubercular
Structure-activity relationship


Allium Discoloration: Color Compounds Formed during Pinking of Onion and Leek.

Abstract: Structures and formation pathways of compounds responsible for pink discoloration of onion and leek were studied. A procedure was developed for the isolation and purification of the color compounds from various model systems and their identification by HPLC-DAD-MS/MS. In total, structures of 15 major color compounds were tentatively determined. It was found that the pigment is a complex mixture of highly conjugated species composed of two N-substituted 3,4-dimethylpyrrole-derived rings linked by either a methine or a propenylidine bridge. These two-ring units are further modified by various C1- and C3-side chains. Experiments with isotope-labeled thiosulfinates revealed that the methine bridge and C1-side chains originate from the methyl group of methiin, whereas the C3 units are derived from the propenyl group of isoalliin.

Kubec|Roman|R| Urajová|Petra|P| Lacina|Ondřej|O| Hajšlová|Jana|J| Kuzma|Marek|M| Zápal|Jakub|J|

D002851:Chromatography, High Pressure Liquid

Allium
discoloration
pinking
onion
leek
thiosulfinate
isoalliin
dipyrromethane
plant pigment
pyrrole


Injured vs. uninjured elbow opening on clinical stress radiographs and its relationship to ulnar collateral ligament injury severity in throwers.

Abstract:
BACKGROUND
Stress radiography measures medial joint space opening of the elbow, but its value in the management of throwing athletes is unclear. The purpose of this study was to analyze the relationship between medial joint opening (gapping and excess opening) and ulnar collateral ligament (UCL) injury severity on magnetic resonance imaging, as well as to explore factors related to the unexpected finding of a greater opening of the uninjured elbow compared with the injured elbow (negative excess opening) with valgus stress radiography.

METHODS
Medial joint space measurements were independently performed by 2 raters in a clinical series of 74 patients evaluated with standardized valgus stress radiography as part of their clinical workup for throwing-related medial elbow pain. Demographic data were collected by chart review, and UCL injury severity was classified based on available imaging into intact UCLs, partial-thickness tears of the anterior bundle, or full-thickness tears of the anterior bundle.

RESULTS
Joint gapping was related to UCL injury severity (P = .003), and group-level comparison showed a difference among tear severity groups (P = .050). Excess opening was not significantly related to UCL injury severity (P = .109). A negative excess opening was observed in 22% of patients, but no factors corroborating guarding or a mechanical explanation were significant for a decreased medial joint opening of the injured elbow compared with the uninjured elbow.

CONCLUSIONS
Medial joint gapping was correlated to UCL injury severity in throwing athletes with medial elbow pain and a clinical suggestion of UCL injury, but no association between injury severity and excess opening was observed in this clinical series, which may limit the usefulness of stress radiography in the clinical workup of throwing athletes.

Molenaars|Rik J|RJ|
Medina|Giovanna I S|GIS|
Eygendaal|Denise|D|
Oh|Luke S|LS|

clinical
ulnar collateral ligament
injury severity
stress radiography
throwing athletes
magnetic resonance imaging
Valgus
medial joint gapping


Extracellular Matrix for Myocardial Repair.

Abstract: Multiple strategies have been investigated to restore functional myocardium following injury or disease including the local administration of cytokines or chemokines, stem/progenitor cell therapy, mechanical circulatory support, pharmacologic use, and the use of inductive biomaterials. The use of xenogeneic biologic scaffolds composed of extracellular matrix (ECM) has been shown to facilitate functional restoration of several tissues and organs including the esophagus, skeletal muscle, skin, and myocardium, among others. The present chapter describes the current understanding of specific components of biologic scaffolds composed of ECM, the mechanisms by which ECM bioscaffolds promote constructive cardiac remodeling after injury, determinants of remodeling outcome, and the versatility of ECM as a potential cardiac therapeutic.

Extracellular matrix
Cardiac patch
Decellularization
Heart valves
Hydrogels
Macrophage
Whole-organ engineering


Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy.

Abstract:
OBJECTIVE
To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T).

METHODS
In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS) <smallest detectable change (SDC) at week 72.

RESULTS
Of 318 patients enrolled, 271 completed the follow-up for 72 weeks and were subjects of the analyses. Factors [odds ratio (95% confidence interval)] significantly associated with the HAQ-DI ≤0.5 were SDAI remission at week 24 [2.99 (1.42-6.28), p = 0.004], baseline HAQ-DI [0.28 (0.18-0.45), p = 1.3 × 10-7], and baseline vdH-mTSS [0.986 (0.976-0.996), p = 0.009]. A factor associated with ΔvdH-mTSS < SDC was SDAI remission at week 24 [3.53 (1.62-7.71), p = 0.002].

CONCLUSION
Predictive validity of SDAI remission for good outcomes was verified in a T2T-implementing cohort in the current clinical settings.

Hirano|Fumio|F| Yokoyama|Waka|W| Yamazaki|Hayato|H| Amano|Koichi|K| Kawakami|Atsushi|A| Hayashi|Taichi|T| Tamura|Naoto|N| Yasuda|Shinsuke|S| Dobashi|Hiroaki|H| Fujii|Takao|T| Ito|Satoshi|S| Kaneko|Yuko|Y| Matsui|Toshihiro|T| Okuda|Yasuaki|Y| Saito|Kazuyoshi|K| Suzuki|Fumihito|F| Yoshimi|Ryusuke|R| Sakai|Ryoko|R| Koike|Ryuji|R| Kohsaka|Hitoshi|H| Miyasaka|Nobuyuki|N| Harigai|Masayoshi|M| |||

Simplified disease activity index
Rheumatoid arthritis
Treat-to-target
Health assessment questionnaire
Modified Sharp score


Cytotoxic compound triacremoniate from Marine Fungus Acremonium citrinum. MMF4.

Abstract: Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds β-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38.

Wang|Xiao-Yao|XY| Ye|Xian-Sheng|XS| Gao|Shuo|S| Liu|Jin-Xi|JX| Tian|Wen-Jing|WJ| Wang|Guang-Hui|GH| Chen|Hai-Feng|HF| Lin|Ting|T|

Acremonium citrinum
Apoptosis
HeLa
PARP
JNK
P38


Effect of tumor properties on energy absorption, temperature mapping, and thermal dose in 13.56-MHz radiofrequency hyperthermia.

Abstract: Computational techniques can enhance personalized hyperthermia-treatment planning by calculating tissue energy absorption and temperature distribution. This study determined the effect of tumor properties on energy absorption, temperature mapping, and thermal dose distribution in mild radiofrequency hyperthermia using a mouse xenograft model. We used a capacitive-heating radiofrequency hyperthermia system with an operating frequency of 13.56 MHz for in vivo mouse experiments and performed simulations on a computed tomography mouse model. Additionally, we measured the dielectric properties of the tumors and considered temperature dependence for thermal properties, metabolic heat generation, and perfusion. Our results showed that dielectric property variations were more dominant than thermal properties and other parameters, and that the measured dielectric properties provided improved temperature-mapping results relative to the property values taken from previous study. Furthermore, consideration of temperature dependency in the bio heat-transfer model allowed elucidation of precise thermal-dose calculations. These results suggested that this method might contribute to effective thermoradiotherapy planning in clinics.

Prasad|Bibin|B|
Kim|Subin|S|
Cho|Woong|W|
Kim|Suzy|S|
Kim|Jung Kyung|JK|

Tumor property
Energy absorption
Temperature mapping
Thermal dose
Hyperthermia
Mouse model


Effectiveness and complications of primary C-clamp stabilization or external fixation for unstable pelvic fractures.

Abstract:
BACKGROUND AND PURPOSE
Unstable pelvic fractures frequently require emergency stabilization using a C-clamp or external (CC/EF) fixation. However, the effectiveness of this intervention and associated complications are still a matter of debate.

PATIENTS AND METHODS
The analysis used data available from the German Pelvic Trauma Registry to study general complications, infections and mortality after primary stabilization using CC/EF in 5,499 patients (n = 957 with vs n = 4,542 without). Furthermore, the subgroups with secondary surgery (n = 713 vs n = 1,695), and ilio-sacral screw implantation following C-clamp stabilization were evaluated (n = 24 vs n = 219). Calculated odds ratios were adjusted for potential confounders.

RESULTS
Patients treated by CC/EF were younger (45 ± 20 vs 62 ± 24 years), had more C-type fractures (65% vs 28%), higher ISS (≥25 63% vs 20%) and displacement (≥3 mm 81% vs 41%), and more complex fractures (32% vs 5%). These features were independent risk factors for complications (p < 0.001). While mortality was reduced after CC/EF stabilization by 32% (OR 0.68 95%CI 0.49-0.95), the risk for general complications was slightly increased (OR 1.25 95% CI 1.02-1.53). In patients undergoing secondary surgery, CC/EF fixation had no influence on mortality, general complications or infections. Related to preceding C-clamp stabilization (OR 4.67 95% CI 1.06-20.64), the risk for infection increased from 3.2% to 20.8% in ilio-sacral screw fixation.

INTERPRETATION
Primary stabilization of unstable pelvic fractures with C-clamp or external fixation is associated with a decreased mortality and was not an independent risk factor for complications after secondary surgery. However, the risk for infection after ilio-sacral screw fixation increased almost 5-fold after C-clamp use.

Schmal|Hagen|H|
Larsen|Morten Schultz|MS|
Stuby|Fabian|F|
Strohm|Peter C|PC|
Reising|Kilian|K|
Goodwin Burri|Kelly|K|

Complication
Unstable pelvic fracture
Registry
Mortality
Emergency fixation
Logistic regression models
Treatment


Use of UHPLC high-resolution Orbitrap mass spectrometry to investigate the genes involved in the production of secondary metabolites in Aspergillus flavus.

Abstract: The fungus Aspergillus flavus is known for its ability to produce the toxic and carcinogenic aflatoxins in food and feed. While aflatoxins are of most concern, A. flavus is predicted to be capable of producing many more metabolites based on a study of its complete genome sequence. Some of these metabolites could be of great importance in food and feed safety. Here we describe an analytical methodology based on Orbitrap HRMS technology that allows the untargeted determination of fungal metabolites, in support of the study of the function of genes involved in secondary metabolism in fungi. The applied strategy implies the detection and identification of differentially expressed metabolites in extracts of wild-type and mutant fungal strains, using Orbitrap high-resolution mass spectrometry (HRMS) accurate mass data. The suitability of this approach was demonstrated by the confirmation of previously characterised genes involved in the aflatoxin biosynthetic pathway, namely a polyketide synthase (pksA), an oxidoreductase (ordA) and a methyltransferase (omtA) gene. Subsequently, the proposed methodology was applied for the detection and identification of metabolites produced by a yet uncharacterised gene cluster in A. favus, cluster 23. Comparative Orbitrap HRMS analysis of extracts of A. flavus wild-type strain and an over-expression mutant for the transcription factor of gene cluster 23 (lepE) demonstrated that this gene cluster is responsible for the production a set of 2-pyridone derivatives, the leporins. Besides the known derivatives leporin B and leporin B precursor that could be identified by automatic de-replication of the accurate mass data, five other compounds belonging to this class of fungal secondary metabolites were detected and identified for the first time, combining MS and multiple-stage MS data.

Arroyo-Manzanares|Natalia|N|
Di Mavungu|José Diana|JD|
Uka|Valdet|V|
Malysheva|Svetlana V|SV|
Cary|Jeffrey W|JW|
Ehrlich|Kenneth C|KC|
Vanhaecke|Lynn|L|
Bhatnagar|Deepak|D|
De Saeger|Sarah|S|

D015966:Gene Expression Regulation, Fungal

high-resolution mass spectrometry
Aspergillus spp.
comparative metabolomics
gene function


Phosphatidylinositol 4-kinase III beta is the target of oxoglaucine and pachypodol (Ro 09-0179) for their anti-poliovirus activities, and is located at upstream of the target step of brefeldin A.

Abstract: In recent years, phosphatidylinositol 4-kinase III beta (PI4KB) has emerged as a conserved target of anti-picornavirus compounds. In the present study, PI4KB was identified as the direct target of the plant-derived anti-picornavirus compounds, oxoglaucine and pachypodol (also known as Ro 09-0179). PI4KB was also identified as the target via which pachypodol interferes with brefeldin A (BFA)-induced Golgi disassembly in non-infected cells. Oxysterol-binding protein (OSBP) inhibitor also has interfering activity against BFA. It seems that this interference is not essential for the anti-poliovirus (PV) activities of BFA and PI4KB/OSBP inhibitors. BFA inhibited early to late phase PV replication (0 to 6 hr postinfection) as well as PI4KB inhibitor, but with some delay compared to guanidine hydrochloride treatment. In contrast with PI4KB/OSBP inhibitors, BFA inhibited viral nascent RNA synthesis, suggesting that BFA targets some step of viral RNA synthesis located downstream of the PI4KB/OSBP pathway in PV replication. Our results suggest that PI4KB is a major target of anti-picornavirus compounds identified in vitro for their anti-picornavirus activities and for some uncharacterized biological phenomena caused by these compounds, and that BFA and PI4KB/OSBP inhibitors synergistically repress PV replication by targeting distinct steps in viral RNA replication.

Arita|Minetaro|M|
Philipov|Stefan|S|
Galabov|Angel S|AS|

D017853:Phosphotransferases (Alcohol Group Acceptor)

phosphatidylinositol 4-kinase III beta
oxoglaucine
pachypodol (Ro 09-0179)
poliovirus


The meninges enhance leukaemia survival in cerebral spinal fluid.

Abstract: Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS-directed therapies that are also associated with significant short- and long-term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS.

Basile|Patrick|P|
Jonart|Leslie M|LM|
Ebadi|Maryam|M|
Johnson|Kimberly|K|
Kerfeld|Morgan|M|
Gordon|Peter M|PM|

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

cerebral spinal fluid
central nervous system
cell death
acute lymphpoblastic leukaemia
cell adhesion


3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels.

Abstract: Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to their excellent biocompatibility. HA can be Ultraviolet (UV)-crosslinked by modification with methacrylic anhydride (HA-MA) and crosslinked by modification with 3,3'-dithiobis(propionylhydrazide) (DTP) (HA-SH) via click reaction. In the study presented in this paper, a 3D-bioprinted, double-crosslinked, hyaluronic-acid-based hydrogel for wound dressing was proposed. The hydrogel was produced by mixing HA-MA and HA-SH at different weight ratios. The rheological test showed that the storage modulus (G') of the HA-SH/HA-MA hydrogel increased with the increase in the HA-MA content. The hydrogel had a high swelling ratio and a high controlled degradation rate. The in vitro degradation test showed that the hydrogel at the HA-SH/HA-MA ratio of 9:1 (S9M1) degraded by 89.91% ± 2.26% at 11 days. The rheological performance, drug release profile and the cytocompatibility of HA-SH/HA-MA hydrogels with loaded Nafcillin, which is an antibacterial drug, were evaluated. The wound dressing function of this hydrogel was evaluated by Live/Dead staining and CCK-8 assays. The foregoing results imply that the proposed HA-SH/HA-MA hydrogel has promise in wound repair applications.

Si|Haopeng|H| Xing|Tianlong|T| Ding|Yulong|Y| Zhang|Hongbo|H| Yin|Ruixue|R| Zhang|Wenjun|W|0000-0001-7973-8769

3D bioprinting
wound dressing
double-crosslinked
hyaluronic acid
biodegradable


Higher levels of (Internet) Gaming Disorder symptoms according to the WHO and APA frameworks associate with lower striatal volume.

Abstract:
Background and aims
Growing concerns about the addictive nature of Internet and computer games led to the preliminary recognition of Internet Gaming Disorder (IGD) as an emerging disorder by the American Psychiatric Association (APA) and the official recognition of Gaming Disorder (GD) as a new diagnosis by the World Health Organization (WHO). While the definition of clear diagnostic criteria for (I)GD represents an important step for diagnosis and treatment of the disorder, potential neurobiological correlates of the criteria remain to be explored.

Methods
The present study employed a dimensional Magnetic Resonance Imaging (MRI) approach to determine associations between (I)GD symptom-load according to the APA and WHO diagnostic frameworks and brain structure in a comparably large sample of n = 82 healthy subjects.

Results
Higher symptom-load on both, the APA and WHO diagnostic frameworks convergently associated with lower volumes of the striatum.

Discussion
The results from this exploratory study provide the first initial evidence for a neurobiological foundation of the proposed diagnostic criteria for (I)GD according to both diagnostic classification systems and suggest that the transition from non-disordered to disordered gaming may be accompanied by progressive neuroplastic changes in the striatum, thus resembling progressive changes in other addictive disorders.

Conclusions
The proposed (I)GD criteria in both diagnostic systems were associated with neurostructural alterations in the striatum, suggesting an association with progressive changes in the motivational systems of the brain.

Zhou|Xinqi|X|
Wu|Renjing|R|
Liu|Congcong|C|
Kou|Juan|J|
Chen|Yuanshu|Y|
Pontes|Halley M|HM|
Yao|Dezhong|D|
Kendrick|Keith M|KM|
Becker|Benjamin|B|0000-0002-9014-9671
Montag|Christian|C|0000-0001-8112-0837


Effects of football fitness training on lymphedema and upper-extremity function in women after treatment for breast cancer: a randomized trial.

Abstract:
BACKGROUND
Breast cancer survivors are encouraged to be physically active. A recent review suggests that football training is an effective exercise modality for women across the lifespan, positively influencing health variables such as strength, fitness and social well-being. However, football is a contact sport, potentially posing an increased risk of trauma-related injury. Against this backdrop, breast cancer survivors are advised to avoid trauma or injury to the affected or at-risk arm in order to protect against lymphedema onset or exacerbation. The aim of this study was therefore to evaluate the feasibility and safety of Football Fitness training in relation to lymphedema and upper-extremity function after treatment for breast cancer.

MATERIAL AND METHODS
Sixty-eight women aged 18-75 years, who had received surgery for stage I-III breast cancer and completed (neo) adjuvant chemotherapy and/or radiotherapy within five years, were randomized (2:1) to a Football Fitness group (FFG, n = 46) or a control group (CON, n = 22) for twelve months. Secondary analyses using linear mixed models were performed to assess changes in upper-body morbidity, specifically arm lymphedema (inter-arm volume % difference, dual energy X-ray absorptiometry; extracellular fluid (L-Dex), bioimpedance spectroscopy), self-reported breast and arm symptoms (EORTC breast cancer-specific questionnaire (BR23) and upper-extremity function (DASH questionnaire) at baseline, six- and twelve-month follow-up.

RESULTS
We observed similar point prevalent cases of lymphedema between groups at all time points, irrespective of measurement method. At the six-month post-baseline assessment, reductions in L-Dex (extracellular fluid) were found in FFG versus CON. These significant findings were not maintained at the twelve-month assessment. No difference between groups was observed for inter-limb volume difference %, nor any of the remaining outcomes.

CONCLUSION
While superiority of Football Fitness was not observed, the results support that participation in Football Fitness training is feasible and suggests no negative effects on breast cancer-specific upper-body morbidity, including lymphedema.

TRIAL REGISTRATION
The trial was registered at ClinicalTrials.gov. NCT03284567.

lymphedema
Breast cancer
exercise
upper-body morbidity
soccer


The Effect of Concerns About COVID-19 on Anxiety, Stress, Parental Burnout, and Emotion Regulation: The Role of Susceptibility to Digital Emotion Contagion.

Abstract: Background and aims: The COVID-19 pandemic has caused social and economic turmoil, which has led to enormous strain for many families. Past work with pandemic outbreaks suggests that media attention can increase anxiety and compensatory behaviors. Social isolation can lead to increase in online communication and parents who use social media may be affected by other people's emotions online through what is known as digital emotion contagion (DEC). The current study aimed to examine the role of DEC in the relationship between stress, concern about COVID-19, parental burnout and emotion regulation (ER). Methods: In April 2020, an online survey was advertised in Social Media Parenting Groups and published on FIU Psychology online research system SONA. Data were analyzed using correlational analysis, linear and multiple linear regression, and moderation analysis. Results: Concern about COVID-19 predicted stress, depression, and parental burnout. Susceptibility to DEC significantly increased the impact of stress on parental burnout. Having relatives infected with COVID-19 increased the effect of DEC on parental burnout. A higher level of ER buffered the relationship between emotion contagion and concern about COVID-19. Conclusion: These findings suggest that susceptibility to digital emotion contagion may have a negative effect on parents. Digital emotion contagion may increase parental burnout and is tied to stress.

Prikhidko|Alena|A|
Long|Haiying|H|
Wheaton|Michael G|MG|

concern about COVID-19
COVID-19
parental burnout
emotion regulation
digital emotion contagion


The Relationship Between Obstructive Sleep Apnea and Pediatric Obesity: A Nationwide Analysis.

Abstract:
OBJECTIVE
Pediatric obstructive sleep apnea (OSA) can have both acute and chronic consequences when untreated. We hypothesize that a link exists between childhood obesity and OSA at nationwide level, with race, gender, and socioeconomic status conferring their own risk for pediatric OSA.

METHODS
This study examined nationwide discharges in 2016 using the Kids' Inpatient Database (KID). The International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes for obesity (E66.0) and OSA (G47.33) were used. Prevalence rates and odds ratios (ORs) were used to quantify associations between the obesity and OSA groups in the general pediatric inpatient population. Multiple binary logistic regression was utilized to compare cohorts of pediatric inpatient admissions.

RESULTS
There were 36 266 285 weighted discharges in the 2016 KID. Among patients included in our dataset, 0.426% (26 684) were diagnosed with obesity and 0.562% (35 242) had OSA. Obesity was independently associated with a significantly increased risk of OSA (OR = 22.89; 95% C.I. = 21.99-23.84). Within the OSA inpatient population, obesity was associated with non-Hispanic black race, Hispanic ethnicity, and Native American race/ethnicity (OR = 1.45, 1.32, 2.51; 95% C.I. = 1.33-1.58, 1.21-1.44, 1.73-3.63).

CONCLUSIONS
Obesity is independently associated with OSA in children after controlling for adenotonsillar hypertrophy. Non-Hispanic black race and Hispanic ethnicity are independent risk factors for OSA and are associated with obesity in the OSA inpatient population, which suggests that obesity may play a role in the increased risk of OSA within these groups.

pediatric obesity
obesity
pediatric obstructive sleep apnea
OSA risk
kids’ inpatient database
nationwide database


Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases.

Abstract: Circular RNA (circRNA) is a type of non-coding RNA characterized by a covalently closed continuous loop. CircRNA is generated by pre-mRNA through back-splicing and is probably cleared up by extracellular vesicles. CircRNAs play a pivotal role in the epigenetic regulation of gene expression at transcriptional and post-transcriptional levels. Recently, circRNAs have been demonstrated to be involved in the regulation of liver homeostasis and diseases. However, the epigenetic role and underlying mechanisms of circRNAs in chronic liver diseases remain unclear. This review discussed the role of circRNAs in non-neoplastic chronic liver diseases, including alcoholic liver disease (ALD), metabolic-associated fatty liver disease (MAFLD), viral hepatitis, liver injury and regeneration, liver cirrhosis, and autoimmune liver disease. The review also highlighted that further efforts are urgently needed to develop circRNAs as novel diagnostics and therapeutics for chronic liver diseases.

Zeng|Xianhui|X|0000-0002-2865-7560 Yuan|Xianglei|X| Cai|Qiuyu|Q| Tang|Chengwei|C| Gao|Jinhang|J|


Circular RNA hsa_circ_0007364 increases cervical cancer progression through activating methionine adenosyltransferase II alpha (MAT2A) expression by restraining microRNA-101-5p.

Abstract: Emerging evidence suggested that circular RNAs (circRNAs) play critical roles in cervical cancer (CC) progression. However, the roles and molecular mechanisms of hsa_circ_0007364 in the tumorigenesis of CC remain unclear. In the present study, we used bioinformatics analysis and a series of experimental analysis to characterize a novel circRNA, hsa_circ_0007364 was up-regulated and associated with advanced clinical features in CC patients. Hsa_circ_0007364 inhibition notably suppressed the proliferation and invasion abilities of CC cells in vitro and reduced tumor growth in vivo. Moreover, hsa_circ_0007364 was uncovered to sponge miR-101-5p. Additionally, methionine adenosyltransferase II alpha (MAT2A) was verified as a target gene of miR-101-5p, and its downregulation reversed the inhibitory effects of hsa_circ_0007364 knockdown on CC progression. Therefore, we suggested that hsa_circ_0007364 might serve as an oncogenic circRNA in CC progression by regulating the miR-101-5p/MAT2A axis, which provides a potential therapeutic target to the treatment. Research highlights hsa_circ_0007364 was upregulated in CC hsa_circ_0007364 promoted CC cell progression hsa_circ_0007364/miR-101-5p/MAT2A axis in CC.

Chen|Hongfei|H| Gu|Bin|B| Zhao|Xiang|X| Zhao|Yupeng|Y| Huo|Shuning|S| Liu|Xiang|X| Lu|Huihong|H|

D015972:Gene Expression Regulation, Neoplastic


Non-traumatic vertebral artery dissection presenting with unilateral cervical pain, hemilateral vision problems and headache.

Abstract: Spontaneous vertebral artery dissection is a rare condition, mainly affecting young adults with non-specific symptoms, which are often considered not severe. We report a case of a non-traumatic vertebral artery dissection in a 30-year-old woman. Our patient presented with unilateral right-sided neck pain and frontal headache during 3 weeks and recently developed right-sided vision problems. History and clinical findings were non-specific. Neurovascular imaging showed a right-sided vertebral artery dissection from C2 to C6 with an intima flap at C5-C6. The patient was observed in the stroke unit for 1 week and antithrombotics were given during 3 months. There was a complete revascularization of the vertebral artery after 3 months. A review of literature is given concerning predisposing factors, clinical symptoms, neurovascular imaging and treatment options.

van der Mieren|Gerry|G|
Mertens|Tom|T|
Somville|Francis J|FJ|

non-traumatic
vertebral artery dissection
unilateral
Neck pain


Early Treatment with Human Albumin Solution in Continuous Renal Replacement Patients.

Abstract:
AIMS
To study the impact of early human albumin solution (HAS) in continuous renal replacement therapy (RRT) patients.

METHODS
Analysis of Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data.

RESULTS
Of 1,464 patients, 500 (34%) received early albumin. These patients had higher illness severity scores, greater use of mechanical ventilation, and 90-day mortality (51 vs. 41%; p < 0.001). However, early albumin carried similar RRT dependence risk among survivors at day 90 (4.9 vs. 5.8%; p = 0.62). On Cox proportional hazards regression, with standardized inverse probability of treatment weighting, early albumin was not associated with increased mortality (hazard ratio [HR]: 1.23, 95% CI: 0.97-1.55; p = 0.09) or recovery to RRT independence (HR: 0.92, 95% CI: 0.78-1.10; p = 0.38).

CONCLUSIONS
Early albumin was administered to one-third of RENAL trial patients and in those with greater illness severity. Early albumin was not independently associated with mortality risk or rate of recovery to RRT independence.

O'Brien|Zachary|Z| Finnis|Mark|M| Gallagher|Martin|M| Bellomo|Rinaldo|R|

D000079664:Continuous Renal Replacement Therapy

Albumin
Continuous renal replacement therapy
Acute kidney injury


Automation and adaptation: Nurses' problem-solving behavior following the implementation of bar coded medication administration technology.

Abstract: The most common change facing nurses today is new technology, particularly bar coded medication administration technology (BCMA). However, there is a dearth of knowledge on how BCMA alters nursing work. This study investigated how BCMA technology affected nursing work, particularly nurses' operational problem-solving behavior. Cognitive systems engineering observations and interviews were conducted after the implementation of BCMA in three nursing units of a freestanding pediatric hospital. Problem-solving behavior, associated problems, and goals, were specifically defined and extracted from observed episodes of care. Three broad themes regarding BCMA's impact on problem solving were identified. First, BCMA allowed nurses to invent new problem-solving behavior to deal with pre-existing problems. Second, BCMA made it difficult or impossible to apply some problem-solving behaviors that were commonly used pre-BCMA, often requiring nurses to use potentially risky workarounds to achieve their goals. Third, BCMA created new problems that nurses were either able to solve using familiar or novel problem-solving behaviors, or unable to solve effectively. Results from this study shed light on hidden hazards and suggest three critical design needs: (1) ecologically valid design; (2) anticipatory control; and (3) basic usability. Principled studies of the actual nature of clinicians' work, including problem solving, are necessary to uncover hidden hazards and to inform health information technology design and redesign.

Holden|Richard J|RJ|
Rivera-Rodriguez|A Joy|AJ|
Faye|Héléne|H|
Scanlon|Matthew C|MC|
Karsh|Ben-Tzion|BT|

bar coded medication administration (BCMA)


Grass carp (Ctenopharyngodon idella) ATF6 (activating transcription factor 6) modulates the transcriptional level of GRP78 and GRP94 in CIK cells.

Abstract: ATF transcription factors are stress proteins containing alkaline area-leucine zipper and play an important role in endoplasmic reticulum stress. ATF6 is a protective protein which regulates the adaptation of cells to ER stress by modulating the transcription of UPR (Unfolded Protein Response) target genes, including GRP78 and GRP94. In the present study, a grass carp (Ctenopharyngodon idella) ATF6 full-length cDNA (named CiATF6, KT279356) has been cloned and identified. CiATF6 is 4176 bp in length, comprising 159 nucleotides of 5'-untranslated sequence, a 1947 nucleotides open reading frame and 2170 nucleotides of 3'-untranslated sequences. The largest open reading frame of CiATF6 translates into 648 aa with a typical DNA binding domain (BRLZ domain) and shares significant homology to the known ATF6 counterparts. Phylogenetic reconstruction confirmed its closer evolutionary relationship with other fish counterparts, especially with Zebrafish ATF6. RT-PCR showed that CiATF6 was ubiquitously expressed and significantly up-regulated after stimulation with thermal stress in all tested grass carp tissues. In order to know more about the role of CiATF6 in ER stress, recombinant CiATF6N with His-tag was over-expressed in Rosetta Escherichia coli, and the expressed protein was purified by affinity chromatography with Ni-NTA His-Bind Resin. In vitro, gel mobility shift assays were employed to analyze the interaction of CiATF6 protein with the promoters of grass carp GRP78 and GRP94, respectively. The result has shown that CiATF6 could bind to these promoters with high affinity by means of its BRLZ mainly. To further study the transcriptional regulatory mechanism of CiATF6, Dual-luciferase reporter assays were applied. Recombinant plasmids of pGL3-GRP78P and pGL3-CiGRP94P were constructed and transiently co-transfected with pcDNA3.1-CiATF6 (pcDN3.1-CiATF6-nBRLZ, respectively) into C. idella kidney (CIK) cells. The result has shown that CiATF6 could activate CiGRP78 and CiGRP94 promoters.

Wang|Xiangqin|X| Zhang|Tao|T| Mao|Huiling|H| Mi|Yichuan|Y| Zhong|Bin|B| Wei|Lili|L| Liu|Xiancheng|X| Hu|Chengyu|C|

D051702:Activating Transcription Factor 6

ATF6
GRP78 and GRP94
Endoplasmic reticulum stress
Transcriptional control
Unfolded protein respond


Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation.

Abstract: A current and major unanswered question is why the highly sensitive central CO2/H(+) chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔVE/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P < 0.05), and glutamine and dopamine were significantly below pre-CBD levels (P < 0.05). Serotonin, substance P, and epinephrine were variable but not significantly (P > 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase-expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex.

Miller|Justin Robert|JR|
Neumueller|Suzanne|S|
Muere|Clarissa|C|
Olesiak|Samantha|S|
Pan|Lawrence|L|
Hodges|Matthew R|MR|
Forster|Hubert V|HV|


HIV prescriptions on the frontlines: Primary care providers' use of antiretrovirals for prevention in the Southeast United States, 2017.

Abstract: HIV disproportionately affects persons in Southeast United States. Primary care providers (PCPs) are vital for HIV prevention. Data are limited about their prescribing of antiretrovirals (ARVs) for prevention, including non-occupational post-exposure prophylaxis (nPEP), pre-exposure prophylaxis (PrEP), and antiretroviral therapy (ART). We examined these practices to assess gaps. During April-August 2017, we conducted an online survey of PCPs in Atlanta, Baltimore, Baton Rouge, Miami, New Orleans, and Washington, DC to assess HIV-related knowledge, attitudes and practices. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were used to estimate correlates of nPEP, PrEP and ART prescribing practices. Adjusting for MSA and specialty, the weighted sample (n = 820, 29.6% adjusted response rate) comprised 60.2% white and 59.4% females. PCPs reported ever prescribing nPEP (31.0%), PrEP (18.1%), and ART (27.2%). Prescribing nPEP was associated with nPEP familiarity (aPR = 2.63, 95% CI 1.59, 4.35) and prescribing PrEP (aPR = 3.57, 95% CI 2.78, 4.55). Prescribing PrEP was associated with PrEP familiarity (aPR = 4.35, 95% CI 2.63, 7.14), prescribing nPEP (aPR = 5.00, 95% CI 2.00, 12.50), and providing care for persons with HIV (aPR = 1.56, 95% CI 1.06, 2.27). Prescribing ART was associated with nPEP familiarity (aPR = 1.89, 95% CI 1.27, 2.78) and practicing in outpatient public practice versus hospital-based facilities (aPR = 2.14 95% CI 1.51, 3.04), and inversely associated with collaborations involving specialists (aPR = 0.60, 95% CI 0.42, 0.86). A minority of PCPs surveyed from the Southeast report ever prescribing ARVs for prevention. Future efforts should include enhancing HIV care coordination and developing strategies to increase use of biomedical tools.

Henny|Kirk D|KD|
Duke|Christopher C|CC|
Buchacz|Kate|K|
Brooks|John T|JT|
Samandari|Taraz|T|
Sutton|Madeline Y|MY|

D007722:Health Knowledge, Attitudes, Practice

HIV
Prescriptions
Prevention
Primary health care


A Prospective Micro-costing Pilot Study of the Health Economic Costs of Acute Kidney Injury.

Abstract:
Introduction
Acute kidney injury (AKI) prevalence in the UK is estimated to be approximately 20% of all emergency admissions. Complications of AKI have a huge impact on health care costs. Most studies that have researched the economic costs of AKI have used macro-level costing using national tariffs and applying this to hospital episode statistics.

Methods
The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study was a pilot study that tested the provision of early specialist advice to improve outcomes for patients with AKI. As part of this prospective study, we undertook a health economics substudy that involved micro-costing to help more accurately define the total cost per patient.

Results
We found that the total cost of providing an AKI alert system and an outreach service (intervention group) was lower than current practice (control group) for patients with AKI. Overall, an episode of AKI that required inpatient care costs approximately £5000 over 12 months, which is somewhat higher than previous UK estimates. Although it was feasible to collect the required complex dataset needed to conduct a health economics analysis of an outreach service, significant amounts of time and resources needed to be dedicated to this endeavor.

Conclusion
We showed that it is possible to demonstrate a clearer, more detailed picture of the prolonged economic costs of AKI for a health care system, as part of a substudy of a larger trial. A larger scale, randomized controlled trial of AKI outreach is needed, with a prospective full economic evaluation conducted alongside the trial.

Mistry|Hema|H|
Abdelaziz|Tarek Samy|TS|
Thomas|Mark|M|


Use of social network analysis in the development, dissemination, implementation, and sustainability of health behavior interventions for adults: A systematic review.

Abstract: Interest in conceptualizing, measuring, and applying social network analysis (SNA) in public health has grown tremendously in recent years. While these studies have broadened our understanding of the role that social networks play in health, there has been less research that has investigated the application of SNA to inform health-related interventions. This systematic review aimed to capture the current applied use of SNA in the development, dissemination, implementation, and sustainability of health behavior interventions for adults. We identified 52 articles published between 2004 and 2016. A wide variety of study settings were identified, most commonly in the US context and most often related to sexual health and HIV prevention. We found that 38% of articles explicitly applied SNA to inform some aspect of interventions. Use of SNA to inform intervention development (as opposed to dissemination, implementation, or sustainability) was most common. The majority of articles represented in this review (n = 39) were quantitative studies, and 13 articles included a qualitative component. Partial networks were most represented across articles, and over 100 different networks measures were assessed. The most commonly described measures were network density, size, and degree centrality. Finally, very few articles defined SNA and not all articles using SNA were theoretically-informed. Given the nascent and heterogeneous state of the literature in this area, this is an important time for the field to coalesce on terminology, measures, and theoretical frameworks. We highlight areas for researchers to advance work on the application of SNA in the design, dissemination, implementation and sustainability of behavioral interventions.

Shelton|Rachel C|RC|
Lee|Matthew|M|
Brotzman|Laura E|LE|
Crookes|Danielle M|DM|
Jandorf|Lina|L|
Erwin|Deborah|D|
Gage-Bouchard|Elizabeth A|EA|

D015438:Health Behavior
D006296:Health Services
D006801:Humans
D011634:Public Health
D060756:Social Networking

Social network analysis
Implementation
Health behavior
Intervention


Idiopathic non-familial acro-osteolysis: a rare case report.

Abstract: A 25-year-old woman patient presented with shortening of fingers with racket nails and numerous yellowish papules over the hands and forearms for 21 years. X-ray of the hands revealed destructive osteolytic changes in all the terminal phalanges. Skin biopsy from the yellowish papules showed epidermal proliferation, perivascular mononuclear infiltrate, thickening of dermal collagen, septal fibrosis and loss of adipocytes mimicking sclerodermatous changes in the dermis and hypodermis. The patient did not have any history of similar illness in the family or occupational exposure to vinyl chloride. After excluding all other possibilities of acral-osteolysis, we diagnosed the case as idiopathic non-familial variety of acro-osteolysis. This is a rare entity characterized by terminal resorption of fingers, sometimes associated with Raynaud's phenomena and yellowish cutaneous papules.

Datta|Pijush K|PK|
Ghosh|Sanjay|S|
De|Abhishek|A|


The effective quadriceps and patellar tendon moment arms relative to the tibiofemoral finite helical axis.

Abstract: The moment arm is a crucial parameter for understanding musculoskeletal dynamics as it defines how linear muscle force is transformed into a moment. Yet, for the quadriceps tendon this parameter cannot be directly calculated, as the patella creates a dynamic fulcrum. Thus, the effective quadriceps moment arm (EQma) was developed to define the quadriceps force to tibial moment relationship. In vivo data in regards to the EQma are lacking and the critical question of how patellofemoral kinematics may influence the EQma remains unresolved. Therefore, the purpose of this study was to quantify the in vivo EQma during a knee extension exercise in asymptomatic controls and to correlate the EQma with sagittal plane patellofemoral kinematics. While subjects (30F/10M, 26.5±5.6 years, 167.5±10.2 cm, 62.6±10.7 kg) cyclically flexed-extended their knees within the MR scanner, dynamic cine-phase contrast and cine MR images were acquired. From these data, patellofemoral kinematics, the ratio of the patellar tendon to quadriceps force, the patellar tendon moment arm, and the EQma were quantified. The EQma trended upwards (32.9-45.5 mm (females) and 31.5-47.1 mm (males)) as the knee angle decreased (50-10°). The quadriceps had a mechanical advantage (ratio of patellar to quadriceps tendon forces >1.0) for knee angles ≤20°. The EQma did not correlate with sagittal plane patellofemoral kinematics. As this is the first study to characterize the EQma in vivo during dynamic volitional activity, in a large group of asymptomatic controls, it can serve as a foundation for future knee joint models and to explore how pathological conditions affect the EQma.

Im|Hyun Soo|HS|
Goltzer|Oren|O|
Sheehan|Frances T|FT|

Musculoskeletal
Dynamics
Muscle force
In vivo
Patellofemoral
Modeling
MRI
Reliability
Torque


Brown adipose activation and reversible beige coloration in adipose tissue with multiple accumulations of 18F-fluorodeoxyglucose in sporadic paraganglioma: A case report.

Abstract: In pheochromocytoma/paraganglioma, nontumorous high 18F-fluorodeoxyglucose accumulations are observed in both beige and brown adipose tissues. Recognizing this feature of 18F-fluorodeoxyglucose accumulation can help physicians make precise diagnoses and help them avoid the pitfalls of a false-positive 18F-fluorodeoxyglucose positron emission tomography result, preventing unnecessary interventions.

paraganglioma
pheochromocytoma
beige adipose tissue
catecholamine
fluorodeoxyglucose


Marketing with tobacco pack onserts: a qualitative analysis of tobacco industry documents.

Abstract:
BACKGROUND
Cigarette packs are a form of advertising that distributes brand information wherever smokers go. In the 21st century, tobacco companies began using onserts on cigarette packs to communicate new advertising messages to smokers.

METHODS
We reviewed tobacco industry documents dated 1926 to 2017 to identify how the tobacco industry developed and used onserts in marketing and to serve the industry's political and legal objectives.

RESULTS
Onserts added to cigarette packs became a more cost-effective way for brands to market in the year 2000. Manufacturers then began studying them, finding that new messages were appealing, while repeated messages were ignored. By 2005, tobacco companies were using onserts to effectively communicate about new tobacco products and packaging changes. They also used repeated 'corporate responsibility' messages that were, according to the industry's own research, likely to be ignored.

CONCLUSIONS
Tobacco companies have expanded on cigarette pack-based advertising. Twenty-first century onserts simultaneously seek to increase sales using materials that are novel, attractive and provide independent value, while undercutting public health messages about the risks of tobacco use using materials that repeat over time and are comparatively unattractive. Health authorities can use this industry research to mandate onserts to communicate effective health messages.

tobacco industry documents
advertising
tobacco control


Efficient One-Pot Access to Trisubstituted 2-Benzazepin-3-ones as Constrained Pseudopeptide Analogues and Privileged Scaffolds.

Abstract:
BACKGROUND
Benzazepines received great attention in the field of medicinal chemistry since this scaffold has been recognized to belong to the important family of privileged templates. More specifically, the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) is used as a core structure in a variety of constrained therapeutic peptide (turn) mimetics.Most of the synthetic approaches towards this template have focused on cyclizations which form the central 7-membered azepine ring.

OBJECTIVE
Previous investigations in our group allowed an expansion of the substitution patterns in the 4-amino-benzazepin-3-one scaffold by introduction of methyl substituents at positions 4 and 5 of the azepinone ring system, but also to 1-aryl substituted compounds. These were the only trisubstituted analogues obtained to date. To introduce an additional point of diversification and conformational constraint useful for peptide mimicry, one can use bifunctional substrates in the Ugi reaction as reported in the present manuscript.

METHOD
The 1-carboxamido-substituted Aba scaffold has been synthesized via the Ugi-3CR reaction starting from N-Phth-protected 2-formyl-L-Phe-OH with a set of amine and isocyanide derivatives. The most suited reaction conditions were applied, involving preformation of the imine in MeOH (0.1 M) in the presence of anhydrous Na2SO4 during 2 hours at room temperature, followed by the addition of an equimolar quantity of isocyanide prior to heating the reaction mixture at 80 °C for 20 hours, using sealed vial reaction conditions.

RESULTS
The substituted Aba scaffolds were isolated in moderate yields (and diastereomeric ratio). This is due to the requirement for a double N-phthaloyl protection of the bifunctional building block, which prevents the use of an excess of amine reagent to drive the reaction conversion to completion, and some starting substrate always remains. Despite the moderate yields, the methodology is efficient since it only requires a limited number of synthetic steps in a final one-pot reaction. In most cases, the diastereomers could be separated by preparative RP-HPLC or via silica gel column chromatography. This is interesting from a medicinal chemistry point of view, since access is provided to the individual diastereomers.

CONCLUSION
We have developed an efficient and useful one-pot strategy to access 1-substituted 4- aminobenzazepinone (Aba) derivatives via the Ugi-3CR reaction. To the best of our knowledge, these scaffolds are only accessible through the presented methodology. The obtained structural complexity, as well as the substitution versatility of these trisubstituted scaffolds, will allow their use in various biological applications.

der Poorten|Olivier Van|OV|
Jida|Mouhamad|M|
Tourwe|Dirk|D|
Ballet|Steven|S|

conformationally constrained amino acids


Droplet and Aerosol Generation With Endonasal Surgery: Methods to Mitigate Risk During the COVID-19 Pandemic.

Abstract:
OBJECTIVE
To define the aerosol and droplet risks associated with endonasal drilling and to identify mitigation strategies.

STUDY DESIGN
Simulation series with fluorescent 3-dimensional (3D) printed sinonasal models and deidentified cadaveric heads.

SETTINGS
Dedicated surgical laboratory.

SUBJECTS AND METHODS
Cadaveric specimens irrigated with fluorescent tracer and fluorescent 3D-printed models were drilled. A cascade impactor was used to collect aerosols and small droplets of various aerodynamic diameters under 15 µm. Large droplet generation was measured by evaluating the field for fluorescent debris. Aerosol plumes through the nares were generated via nebulizer, and mitigation measures, including suction and SPIWay devices, nasal sheaths, were evaluated regarding reduction of aerosol escape from the nose.

RESULTS
The drilling of cadaveric specimens without flexible suction generated aerosols ≤3.30 µm, and drilling of 3D sinonasal models consistently produced aerosols ≤14.1 µm. Mitigation with SPIWay or diameter-restricted SPIWay produced same results. There was minimal field contamination in the cadaveric models, 0% to 2.77% field tarp area, regardless of drill burr type or drilling location; cutting burr drilling without suction in the 3D model yielded the worst contamination field (36.1%), followed by coarse diamond drilling without suction (19.4%). The simple placement of a flexible suction instrument in the nasal cavity or nasopharynx led to complete elimination of all aerosols ≤14.1 µm, as evaluated by a cascade impactor positioned immediately at the nares.

CONCLUSION
Given the findings regarding aerosol risk reduction, we strongly recommend that physicians use a suction instrument in the nasal cavity or nasopharynx during endonasal surgery in the COVID-19 era.

Dharmarajan|Harish|H|
Freiser|Monika E|ME|
Sim|Edward|E|
Boorgu|Devi Sai Sri Kavya|DSSK|
Corcoran|Timothy E|TE|
Wang|Eric W|EW|
Gardner|Paul A|PA|
Snyderman|Carl H|CH|

D017758:Infectious Disease Transmission, Patient-to-Professional

D057605:Natural Orifice Endoscopic Surgery

droplet
aerosol
endonasal
COVID-19
prevention
safety
skull base


Unidirectional barbed suture for vaginal cuff closure without backward stitch in total laparoscopic hysterectomy.

Abstract:
AIM
To evaluate the safety and efficacy of unidirectional barbed suture technique for vaginal cuff closure in total laparoscopic hysterectomy (TLH).

METHODS
In a retrospective chart review, data were analyzed from 165 patients who underwent a TLH with an unidirectional barbed suture technique for vaginal cuff closure from January 2012 to June 2016 at tertiary-care university-based teaching hospital and academic affiliated hospital. Vaginal cuff was closed by single layer 3/0 V-Loc unidirectional 9″, 180 day Absorbable Wound Closure Device (Covidien Healthcare, Mansfield, MA) and the suture was not stitched backward to secure distal end.

RESULTS
A total of 165 patients were included and the median age was 50 years (range, 35-84 years). The median completion time for hysterectomy time was 100 min (range, 40-240 min) and the median vaginal cuff closure time was 7 min (range, 4-15 min). The median estimated blood loss was 87.8 mL (range 30-250 mL) and the median uterine weight was 200 g (range, 40-900 g). Intraoperative complication included bladder perforation (1.2%) and postoperative complications were vaginal cuff dehiscence (1.8%), cuff cellulitis (0.6%), vesicovaginal fistula (0.6%) and unexplained fever (0.6%).

CONCLUSION
According to the results of current study, the use of unidirectional barbed suture without backward stitching appears to be safe for the vaginal cuff closure in TLH.

unidirectional
barbed suture
cuff closure
total laparoscopic hysterectomy
without stitch technique


Gender Differences in the Relationship of Waist Circumference to Coronary Artery Lesions and One-Year Re-Admission Among Coronary Artery Disease Patients with Normal Body Mass Index.

Abstract:
Purpose
The study explored the association of waist circumference (WC) with the severity of cardiovascular diseases and hospital readmission of coronary artery disease (CAD) patients with normal body mass index (BMI).

Patients and Methods
213 female and 431 male normal-BMI CAD patients were enrolled and assigned in three groups based on their gender-specific WC tertiles. Their cardiovascular risk factors and coronary angiography characteristics were analyzed in a cross-sectional study, and the gender-specific relationship between WC and one-year re-admission rate was prospectively explored.

Results
The cross-sectional analysis showed that for male normal-BMI CAD patients, diabetes and dyslipidemia prevalence, Apo B/A1, hs-CRP, and uric acid levels triglycerides-glucose index, the incidence of left main disease, three vessel disease, calcification lesion, total occlusive lesion, and complex lesion, as well as Gensini score was in the order of WC tertile 3 > WC tertile 2 > WC tertile 1. In addition, male normal-BMI CAD patients in the highest WC tertile were at an increased risk of severe CAD (OR=2.21), and the correlation was still statistically significant even after adjusting for potential cardiovascular risk factors (OR=1.87). For female normal-BMI CAD patients, as the WC tertiles increased, uric acid level, the prevalence of three vessel disease, diffuse lesion, and complex lesion gradually increased (P <0.05), but no significant difference was found in the risk of severe CAD among different WC groups (all P >0.05). Prospective analyses showed that the higher the WC tertile was, the higher the one-year re-admission rate in men, but not in women, and after adjusting for other risk factors, men with the highest WC tertile showed more than twice the risk of patients with the lowest WC tertile.

Conclusion
Male but not female, normal-BMI CAD patients with increased WC had more severe CAD and a higher risk of one-year re-admission rate.

Luan|Hui|H| Song|Yan|Y| Cao|Lifei|L| Wang|Ping|P| Zhu|Danjun|D| Tian|Gang|G|

one-year re-admission with adverse cardiovascular event


Development of solid-phase microextraction to study dissolved organic matter--polycyclic aromatic hydrocarbon interactions in aquatic environment.

Abstract: Solid-phase microextraction coupled with gas chromatography and mass spectrometry (SPME-GC-MS) was developed for the study of interactions between polycyclic aromatic hydrocarbons (PAHs) and dissolved organic matter (DOM). After the determination of the best conditions of extraction, the tool was applied to spiked water to calculate the dissolved organic carbon water distribution coefficient (K(DOC)) in presence of different mixtures of PAHs and Aldrich humic acid. The use of deuterated naphthalene as internal standard for freely dissolved PAH quantification was shown to provide more accuracy than regular external calibration. For the first time, K(DOC) values of 18 PAHs were calculated using data from SPME-GC-MS and fluorescence quenching; they were in agreement with the results of previous studies. Competition between PAHs, deuterated PAHs and DOM was demonstrated, pointing out the non-linearity of PAH-DOM interactions and the stronger interactions of light molecular weight PAHs (higher K(DOC) values) in absence of high molecular weight PAHs.

de Perre|Chloé|C|
Le Ménach|Karyn|K|
Ibalot|Fabienne|F|
Parlanti|Edith|E|
Budzinski|Hélène|H|

Solid-phase microextraction
Interactions
Aquatic environment
Polycyclic aromatic hydrocarbons
Dissolved organic matter
Gas chromatography–mass spectrometry


A classification-based approach to semi-supervised clustering with pairwise constraints.

Abstract: In this paper, we introduce a neural network framework for semi-supervised clustering with pairwise (must-link or cannot-link) constraints. In contrast to existing approaches, we decompose semi-supervised clustering into two simpler classification tasks: the first stage uses a pair of Siamese neural networks to label the unlabeled pairs of points as must-link or cannot-link; the second stage uses the fully pairwise-labeled dataset produced by the first stage in a supervised neural-network-based clustering method. The proposed approach is motivated by the observation that binary classification (such as assigning pairwise relations) is usually easier than multi-class clustering with partial supervision. On the other hand, being classification-based, our method solves only well-defined classification problems, rather than less well specified clustering tasks. Extensive experiments on various datasets demonstrate the high performance of the proposed method.

Śmieja|Marek|M|
Struski|Łukasz|Ł|
Figueiredo|Mário A T|MAT|

D016000:Cluster Analysis
D016208:Databases, Factual
D016571:Neural Networks, Computer
D000069553:Supervised Machine Learning

Semi-supervised clustering
Pairwise constraints
Neural networks
Siamese neural networks
Deep learning


Antimicrobial, antioxidant and antitumor activities of silver nanoparticles synthesized by Allium cepa extract: A green approach.

Abstract: An economic and efficient method for the synthesis of silver nanoparticles (AgNPs) was performed using onion (Allium cepa) extract as reducing and capping agent. UV-vis spectroscopy confirmed the formation of silver nanoparticles by observing the typical surface plasmon resonance peak at 420 nm. Transmission electron microscopy studies revealed that AgNPs were spherical in shape with a size range of 10-23 nm. AgNPs were further demonstrated by the characteristic peaks observed in the XRD image. The possible functional groups of AgNPs were identified by FTIR analysis. AgNPs exhibited potential antimicrobial activity against all the microbial strains tested. Antioxidant activity of AgNPs revealed that they can be used as potential radical scavenger against deleterious damages caused by the free radicals. Additionally, AgNPs had antitumor activities against human breast (MCF-7), hepatocellular (HepG-2) and colon (HCT-116) carcinoma cell lines in a dose-dependent manner with IC50 of 1.6, 2.3 and 2.2 μg/ml, respectively. The overall results indicate promising baseline information for the potential uses of AgNPs in the treatment of infectious diseases and tumors.

Antimicrobial
Antioxidant
Silver nanoparticles
Characterization
Cytotoxic activity


Diagnostic utility of clinical and biochemical parameters in pancreatic head malignancy patients with normal carbohydrate antigen 19-9 levels.

Abstract:
BACKGROUND
Carbohydrate antigen (CA)19-9 that is the most widely used biomarker for pancreatic cancer has certain limitations in diagnosis, which results in a tough job to distinguish pancreatic cancer from benign tumors with normal CA19-9. The aim of this study was to investigate the diagnostic utility of clinical parameters and serum markers in patients with pancreatic head masses but without elevated CA19-9.

METHODS
Retrospectively, 106 (69 malignant, 37 benign) of 487 patients admitted for pancreatic head masses were enrolled with CA19-9 level of <37u/ml. Clinical parameters and serum biomarkers were assessed. Among the patients with pancreatic head mass, male individuals (p=0.025) and elder individuals (p<0.001) were more likely to have cancer; and cancer patients were more likely to present with abdominal-pain (p=0.023), weight-loss (p=0.013) and jaundice (p<0.001). Serum bilirubin levels among malignancies, including total bilirubin (p<0.001), direct bilirubin (p<0.001) and indirect bilirubin (p<0.001), were considerably higher than those of benign ones. Logistic regression further concluded that age-distribution, abdominal-pain and direct-bilirubin were three independent factors correlating with final diagnosis. However, CEA (p=0.156) was not sufficient enough to exclude pancreatic cancer.

CONCLUSIONS
In patients with pancreatic head masses and CA19-9 of <37u/ml, age-distribution, abdominal-pain and direct bilirubin might be helpful in differential diagnosis. CEA was insufficient for exclusion of malignancy.

pancreatic head malignancy
biomarker
diagnosis
clinical parameter


Implementation of an established algorithm and modifications for the identification of epilepsy patients in the veterans health administration.

Abstract: Identification of epilepsy patients from administrative data in large managed healthcare organizations is a challenging task. The objectives of this report are to describe the implementation of an established algorithm and different modifications for the estimation of epilepsy prevalence in the Veterans Health Administration (VHA). For the prevalence estimation during a given time period patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical encounters were identified. In contrast to the established algorithm, which required inclusion of diagnoses data from the time period of interest only, variants were tested by considering diagnoses data beyond prevalence period for improving sensitivity. One variant excluded data from diagnostic EEG and LTM clinics to improve specificity. Another modification also required documentation of seizures on the problem list (electronic list of patients' established diagnoses). Of the variants tested, the one excluding information from diagnostic clinics and extending time beyond base period of interest for clinical encounters was determined to be superior. It can be inferred that the number of patients receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are needed for future prevalence estimation due to significant efforts presented. This review is not only beneficial for researchers interested in VHA related data but can also be helpful for managed healthcare organizations involved in epilepsy care aiming at accurate identification of patients from large administrative databases.

Rehman|Rizwana|R|
Everhart|Amanda|A|
Frontera|Alfred T|AT|
Kelly|Pamela R|PR|
Lopez|Maria|M|
Riley|Denise|D|
Sajan|Sheela|S|
Schooff|David M|DM|
Tran|Tung T|TT|
Husain|Aatif M|AM|

D014493:United States Department of Veterans Affairs

Epilepsy
Prevalence
Administrative databases
Epidemiology
Veterans health administration data


Effect of high concentration of ammonium on production of n-caproate: Recovery of a high-value biochemical from food waste via lactate-driven chain elongation.

Abstract: Ammonium accumulation is inevitable during the fermentation of food waste (FW), challenging the application of chain elongation process upgrading FW into the high-value biochemical n-caproate, which is a medium chain carboxylate. This study is the first to investigate ammonium inhibition of lactate-driven chain elongation process. The short-term exposure of a Clostridium IV-dominated chain elongating reactor microbiome at an ammonium concentration of 1-4 g L-1 linearly decreased n-caproate production by 25-80%. High levels of ammonium (≥5 g L-1) could cause failure of chain elongation, shifting the product from n-caproate to propionate. The involved mechanisms revealed that ammonium reshaped the microbial community from Clostridium IV domination to Clostridium IV and Propionibacterium co-domination (based on 16S rRNA sequencing) and reduced the activities of key enzymes involved in the reversed β-oxidization pathway. We propose an effective strategy from our study, which is the first one to do in our knowledge, to upgrade raw FW without dilution to n-caproate: lowering the ammonium accumulation to 1.0 g L-1 at the setup phase for adaptation and prolonging the hydraulic retention time (10 days) during the operation phase for the colonization of chain-elongation bacteria. These findings lay a foundation for the implementation of the LCE process on FW, providing an alternative way to alleviate the global FW crisis.

Wei|Yong|Y| Ren|Bing|B| Zheng|Shaorui|S| Feng|Xin|X| He|Yong|Y| Zhu|Xiaoyu|X| Zhou|Lixiang|L| Li|Dong|D|

Ammonium
n-caproate
Food waste
Chain elongation
Lactate


Bridging complexity theory and resilience to develop surge capacity in health systems.

Abstract: Purpose Health systems are periodically confronted by crises - think of Severe Acute Respiratory Syndrome, H1N1, and Ebola - during which they are called upon to manage exceptional situations without interrupting essential services to the population. The ability to accomplish this dual mandate is at the heart of resilience strategies, which in healthcare systems involve developing surge capacity to manage a sudden influx of patients. The paper aims to discuss these issues. Design/methodology/approach This paper relates insights from resilience research to the four "S" of surge capacity (staff, stuff, structures and systems) and proposes a framework based on complexity theory to better understand and assess resilience factors that enable the development of surge capacity in complex health systems. Findings Detailed and dynamic complexities manifest in different challenges during a crisis. Resilience factors are classified according to these types of complexity and along their temporal dimensions: proactive factors that improve preparedness to confront both usual and exceptional requirements, and passive factors that enable response to unexpected demands as they arise during a crisis. The framework is completed by further categorizing resilience factors according to their stabilizing or destabilizing impact, drawing on feedback processes described in complexity theory. Favorable order resilience factors create consistency and act as stabilizing forces in systems, while favorable disorder factors such as diversity and complementarity act as destabilizing forces. Originality/value The framework suggests a balanced and innovative process to integrate these factors in a pragmatic approach built around the fours "S" of surge capacity to increase health system resilience.

D003266:Continuity of Patient Care
D003695:Delivery of Health Care
D006801:Humans
D017146:Models, Organizational
D055872:Surge Capacity

Complexity theory
Resilience
Surge capacity
Health systems
Crisis


The association between gender and pediatric respiratory morbidity.

Abstract:
OBJECTIVE
To evaluate the association between newborn gender and the risk for later pediatric respiratory morbidity.

STUDY DESIGN
A population based cohort analysis was performed by comparing the risk of long-term respiratory morbidity (until 18 years of age) according to gender. Respiratory morbidity included hospitalizations involving pneumonia, asthma, bronchitis, bronchiolitis, upper respiratory tract infection (URTI), influenza, and bronchiectasis. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were constructed to compare cumulative respiratory morbidity. A Cox proportional hazards model controlled for confounders.

RESULTS
During the study period 240 953 newborns met the inclusion criteria. Among them, 118 113 were females (49.0%) and 122 840 were males (51.0%). During the 18 years of follow-up, 13 719 (5.7%) different newborns were hospitalized with respiratory related morbidity. Males had significantly higher rates of respiratory morbidity as compared with females (6.4% vs 4.9% respectively, P < 0.001, OR 1.32, 95% CI 1.28-1.37). Specifically, pneumonia, bronchitis, asthma, bronchiolitis, and URTI were significantly more common in males. Males exhibited higher total cumulative respiratory morbidity (log rank P < 0.001), as well as higher cumulative morbidity in several sub-categories. These sub-categories included pneumonia, bronchitis, asthma, bronchiolitis, and URTI (P < 0.05 in all). The Cox regression model demonstrated male gender to be an independent risk factor for pediatric respiratory morbidity while adjusting for gestational age, birthweight, and other confounders (HR 1.29, 95% CI 1.25-1.34, P < 0.001).

CONCLUSIONS
Males are at an increased risk for pediatric respiratory morbidity, independent of obstetrical characteristics such as gestational age and birthweight.

Ben-Shmuel|Atar|A|0000-0001-8200-1960 Sheiner|Eyal|E| Wainstock|Tamar|T| Landau|Daniella|D| Vaknin|Flear|F| Walfisch|Asnat|A|

gender
respiratory morbidity
epidemiology
pulmonology


Serological evolution in early syphilis.

Abstract:
INTRODUCTION
The evolution of syphilis after treatment could be affected by different factors, for example HIV. In consequence, HIV positive patients are sometimes treated with more doses of penicillin (PBG). The aim of the study is to describe and compare the serological evolution by different factors in patients with early syphilis in Barcelona.

METHODS
The serological control was made over the following year. A time analysis was performed through the study of Kaplan- Meier curves.

RESULTS
The serological control was made in 208 patients, 42.5% of whom were HIV-positive. In a Kaplan-Meier curve the median of days needed to observe the cure was 99 [97-105] without differences depending on HIV, previous syphilis, stage or RPR titters. A better evolution was observed in patients treated with doxycycline P=.02.

CONCLUSIONS
The serological evolution is similar in HIV-negative and HIV-positive patients treated according to current recommendations, observing the cure at 3 month after treatment.

Arando|Maider|M|
Mota-Foix|Miriam|M|
Armegol|Pere|P|
Barberá|María Jesús|MJ|
Esperalba|Juliana|J|
Vall-Mayans|Martí|M|

Serological evolution
Early syphilis
Evolución serológica
Human immunodeficiency virus
Sífilis precoz
Virus de la inmunodeficiencia humana


Measurements of association constants between enantiomers and chiral selectors by capillary gas chromatography. Theoretical and practical considerations.

Abstract: The association constants of several volatile enantiomers with octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin at temperatures between 50 and 100 °C were measured by gas-liquid chromatography using capillary columns coated with different amounts of chiral selector dissolved in polysiloxane OV-1701 and prepared with a precisely determined phase ratio. Simple expressions were deduced to estimate the apparent distribution constants from accurate hold-up and retention times along with that known phase ratio at each temperature. The enantiomer-chiral selector association constants were then calculated from the linear regression of the apparent constants as a function of the chiral selector concentration. One aim of this study consisted in discussing all the experimental uncertainties inherent in the determination of enantiomer/selector association constants with chiral analytes, and how these fundamental measurements can be performed precisely without resorting to the use of reference solutes.

Lebed|Pablo J|PJ|
Keunchkarian|Sonia|S|
Osorio Grisales|Jaiver|J|
Castells|Cecilia B|CB|


Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions.

Abstract:
Introduction
This study investigated alternative pre-analytical handling of blood for neurofilament light (NfL) analysis where resources are limited.

Method
Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48-hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters.

Results
Delayed centrifugation (R2 = 0.991) and DPS (discovery cohort, R2 = 0.954; confirmatory cohort, DPS: R2 = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2 = 0.995) and shaking (R2 = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS.

Discussion
DPS or delayed centrifugation are viable pre-analytical procedures for the accurate quantification of plasma NfL.

Simrén|Joel|J|
Ashton|Nicholas J|NJ|
Blennow|Kaj|K|
Zetterberg|Henrik|H|

neurofilament light
dried plasma spots
dried blood spots
pre‐analytical handling


Expression of Cyclin D1 and P16 in Esophageal Squamous Cell Carcinoma.

Abstract: BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Many genes including cyclin D1 and p16 play important role in its carcinogenesis. We aimed to analyze the expressions of cyclin D1 and p16 with the various clinicopathological characteristics of ESCC. METHODS We examined 30 biopsy samples of ESCC for cyclin D1 and p16 protein expressions using immunohistochemistry. Immunointensity was classified as no immunostaining (-), weakly immunostaining (+), weak immunostaining (++) and strongly positive immunostaining (+++). RESULTS Out of the 30 cases, positive expression of cyclin D1 was detected in 26 cases (86.7%). The percentage of tumors with invasion to the adventitia (88.2%), lymph node metastasis (87.5%), and tumors which were poorly differentiated (92.9%) were higher in cyclin D1 positive tumors than in the cyclin D1 negative tumors. However no significant association was found between cyclin D1 expression and the different clinicopathological parameters.There were 22 cases of ESCC (73.3 %) which showed negativity for p16. The percentage of tumors with invasion to the adventitia (82.4%) and poorly differentiated tumors (92.9%) were higher in the p16 negative tumors than in the p16 positive tumors. There was significant association between the histological grade and p16 expression (p=0.012). However, there were no significant association with regard to site, size and lymph node status of the tumors and p16 expression. CONCLUSION The study shows that alterations of cyclin D1 and p16 play an important role in ESCC. Loss of p16 expression was associated with poor differentiation.

Dey|Biswajit|B| Raphael|Vandana|V| Khonglah|Yookarin|Y| GiriLynrah|Kyrshanlang|K|

Cyclin D1
P16
Esophageal squamous cell carcinoma
Immunohistochemistry


How are social determinants of health integrated into epigenetic research? A systematic review.

Abstract:
OBJECTIVE
We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of health (SDOH).

METHODS
Using comprehensive search procedures, we identified studies that consider the impact of SDOH on DNA methylation (DNAm), the most common measure of epigenetic change in research on human adult populations. We analyzed the studies to determine: 1) which populations and environments have been investigated in the literature; 2) how SDOH are defined and operationalized; 3) which SDOH have been linked to DNAm; and 4) what lessons from the SDOH literature can be better integrated into future studies exploring the social determinants of health and epigenetic outcomes.

RESULTS
We identified 67 studies, with 39 to 8397 participants. The SDOH most commonly considered were early life socioeconomic exposures and early life trauma or mental health. Our review highlights four broad challenges: a) high dependence on convenience sampling, b) limited racial/ethnic, and geographic diversity in sampling frames, c) overreliance on individual sociodemographic characteristics as proxies for broader stratification processes, and d) a focus on downstream social determinants of health and individualized experiences with social stressors.

CONCLUSIONS
Future social epigenetics research should prioritize larger, more diverse and representative population-based samples and employ the SDOH framework to better inform the conceptualization of research questions and interpretation of findings. In particular, the simplified depiction of race/ethnicity, gender, and socioeconomic status as individual-level characteristics should be updated with an explicit acknowledgement that these characteristics are more accurately interpreted as cues used by society to differentiate subpopulations. Social epigenetics research can then more clearly elucidate the biological consequences of these social exposures for patterns of gene expression, subsequent disease etiology, and health inequities.

Evans|Linnea|L| Engelman|Michal|M| Mikulas|Alex|A| Malecki|Kristen|K|

Social determinants of health
Epigenetics
DNA methylation
Health inequities
Weathering


Discovery of a spontaneous portosystemic shunt following portal vein embolization.

Abstract:
INTRODUCTION
Right portal vein embolization (PVE) has become a crucially important option in the minimally-invasive treatment of hepatocellular carcinoma or secondary liver malignancy before partial hepatectomy or trisegmentectomy to reduce perioperative morbidity. The main goal of PVE is to increase the volume of the future liver remnant (FLR), which can provide complete liver metabolic functionality without risk of developing posthepatectomy liver failure, also known as "small for size syndrome." PVE accomplishes this via the redirection of portal venous flow toward the left portal vein circulation resulting in an increased left hepatic lobe volume.

CASE REPORT
We present a patient with a noncirrhotic liver and a previously unknown portal venous to systemic venous shunt that became apparent after a right PVE was completed. Left untreated, this shunt would have undoubtedly jeopardized the FLR volume.

CONCLUSION
The presence of previously undetected portosystemic shunting is a potential cause for otherwise assumed idiopathic PVE failure, and the goal of this article is to underscore the importance of evaluating for these shunts before PVE.

D004621:Embolization, Therapeutic
D006801:Humans
D008107:Liver Diseases
D011169:Portal Vein

portosystemic shunt
portal vein embolization
hepatocellular carcinoma
hepatectomy


Substantial air quality and climate co-benefits achievable now with sectoral mitigation strategies in China.

Abstract: China is the world's top carbon emitter and suffers from severe air pollution. We examine near-term air quality and CO2 co-benefits of various current sector-based policies in China. Using a 2015 base case, we evaluate the potential benefits of four sectoral mitigation strategies. All scenarios include a 20% increase in conventional air pollution controls as well as the following sector-specific fuel switching or technology upgrade strategies. Power sector (POW): 80% replacement of small coal power plants with larger more efficient ones; Industry sector (IND): 10% improvement in energy efficiency; Transport sector (TRA): replacement of high emitters with average vehicle fleet emissions; and Residential sector (RES): replacement of 20% of coal-based stoves with stoves using liquefied petroleum gas (LPG). Conducting an integrated assessment using the regional air pollution model WRF-Chem, we find that the IND scenario reduces national air-pollution-related deaths the most of the four scenarios examined (27,000, 24,000, 13,000 and 23,000 deaths reduced annually in IND, POW, TRA and RES, respectively). In addition, the IND scenario reduces CO2 emissions more than 8times as much as any other scenario (440, 53, 0 and 52Mt CO2 reduced in IND, POW, TRA and RES, respectively). We also examine the benefits of an industrial efficiency improvement of just 5%. We find the resulting air quality and health benefits are still among the largest of the sectoral scenarios, while the carbon mitigation benefits remain more than 3 times larger than any other scenario. Our analysis hence highlights the importance of even modest industrial energy efficiency improvements and air pollution control technology upgrades for air quality, health and climate benefits in China.

Peng|Wei|W|
Yang|Junnan|J|
Wagner|Fabian|F|
Mauzerall|Denise L|DL|

Co-benefits
Sectoral mitigation
Air pollution
WRF-Chem
Industrial energy efficiency
Climate change


Testing the effects of species interactions and water limitation on tree seedling biomass allocation and physiology.

Abstract: Species interactions mediate tree responses to water limitation because competition and/or facilitation alter plant physiology and growth. However, because it is difficult to isolate the effects of plant-plant interactions and water limitation from other environmental factors, the mechanisms underlying tree physiology and growth in coexisting plants under drought are poorly understood. We investigated how species interactions and water limitation impact the physiology and growth of trembling aspen (Populus tremuloides), narrowleaf cottonwood (Populus angustifolia) and ponderosa pine (Pinus ponderosa) seedlings in a controlled environment growth chamber, using aspen as a focal species. Seedlings were grown in pots alone or with a con- or hetero-specific seedling, and were subjected to a water limitation treatment. Growth, water status and physiological traits were measured before, during and after the treatment. Under well-watered conditions, the presence of another seedling affected growth or biomass allocation in all species, but did not impact the physiological traits we measured. Under water limitation, the presence of a competing seedling had a marginal impact on seedling growth and physiological traits in all species. Throughout the study, the magnitude and direction of seedling responses were complex and often species-specific. Our study serves as an important step toward testing how species' interactions modify physiological responses and growth in well-watered and water-limited periods.

Kerr|Kelly L|KL|
Zenes|Nicole|N|
Trugman|Anna T|AT|
Anderegg|William R L|WRL|

water limitation
seedlings
biomass allocation
physiology
competition
growth
growth chamber
forest
water-use strategy


Crystal structure of 3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-4-carbaldehyde.

Abstract: In the title compound, C15H13N3O, the pyrrolyl and phenyl rings make dihedral angles of 58.99 (5) and 34.95 (5)°, respectively, with the central pyrazole ring. In the crystal, weak, pairwise C-H⋯O inter-actions across centers of symmetry form dimers, which are further associated into corrugated sheets running approximately parallel to (100) via weak C-H⋯N inter-actions.

Mague|Joel T|JT|
Mohamed|Shaaban K|SK|
Akkurt|Mehmet|M|
El-Emary|Talaat I|TI|
Albayati|Mustafa R|MR|

crystal structure
pyrazole ring
dimers
pyrrolyl ring


UPR modulation of host immunity by Pseudomonas aeruginosa in cystic fibrosis.

Abstract: Cystic fibrosis (CF) is a progressive multiorgan autosomal recessive disease with devastating impact on the lungs caused by derangements of the CF transmembrane conductance regulator (CFTR) gene. Morbidity and mortality are caused by the triad of impaired mucociliary clearance, microbial infections and chronic inflammation. Pseudomonas aeruginosa is the main respiratory pathogen in individuals with CF infecting most patients in later stages. Despite its recognized clinical impact, molecular mechanisms that underlie P. aeruginosa pathogenesis and the host response to P. aeruginosa infection remain incompletely understood. The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) γ (PPARγ), has shown to be reduced in CF airways. In the present study, we sought to investigate the upstream mechanisms repressing PPARγ expression and its impact on airway epithelial host defense. Endoplasmic reticulum-stress (ER-stress) triggered unfolded protein response (UPR) activated by misfolded CFTR and P. aeruginosa infection contributed to attenuated expression of PPARγ. Specifically, the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway led to the enhanced expression of the CCAAT-enhancer-binding-protein homologous protein (CHOP). CHOP induction led to the repression of PPARγ expression. Mechanistically, we showed that CHOP induction mediated PPARγ attenuation, impacted the innate immune function of normal and ∆F508 primary airway epithelial cells by reducing expression of antimicrobial peptide (AMP) and paraoxanse-2 (PON-2), as well as enhancing IL-8 expression. Furthermore, mitochondrial reactive oxygen species production (mt-ROS) and ER-stress positive feedforward loop also dysregulated mitochondrial bioenergetics. Additionally, our findings implicate that PPARγ agonist pioglitazone (PIO) has beneficial effect on the host at the multicellular level ranging from host defense to mitochondrial re-energization.

Bedi|Brahmchetna|B|
Lin|Kuo-Chuan|KC|
Maurice|Nicholas M|NM|
Yuan|Zhihong|Z|
Bijli|Kaiser|K|
Koval|Michael|M|
Hart|C Michael|CM|
Goldberg|Joanna B|JB|
Stecenko|Arlene|A|
Sadikot|Ruxana T|RT|

cystic fibrosis transmembrane conductance regulator


Review of the genus Meganola Dyar, 1898 of Ivory Coast and adjacent areas with descriptions of 5 new species and several taxonomic updates (Lepidoptera, Nolidae, Nolinae)-Taxonomic studies on West African Nolinae I.

Abstract: The present paper contains the first comprehensive taxonomic summary of the Meganola Dyar, 1898 species recorded in Ivory Coast and adjacent areas. 35 species are recorded in total with 28 species having been collected on recent African Natural History Research Trust expeditions. All species are listed with label data of specimens examined together with 56 colour and 52 black and white illustrations of the adults and their genitalia. A Lectotype is designated for Meganola furvitincta (Hampson, 1914), five species are described as new to science (Meganola smithi, M. taiana, M. subchionea, M. cinereoparva, M. hackeri spp. n.) and 23 new synonymies are established: Meganola endoscota undosaria Hacker, 2012 syn. n., M. kaduna Hacker, 2012 syn. n., M. mabiriaria Hacker, 2012 syn. n. and M. simplicifacta Hacker, 2012 syn. n. are synonymised with M. endoscota (Hampson, 1914); M. polioleuca Hacker, 2012 syn. n. is synonymised with M. mesonephele (Hampson, 1914); M. togatulella Hacker, 2012 syn. n., M. subterminalis Hacker, 2012 syn. n. and M. lupii Hacker Hausmann, 2012 syn. n. are synonymised with M. lucia (van Son, 1933); M. septima Hacker, 2012 syn. n., M. octava Hacker, 2012 syn. n., M. heteromorpha Hacker, 2012 syn. n., M. dissoluta Hacker, 2012 syn. n., M. brachyvalva Hacker, 2012 syn. n. and M. pseudofuscata Hacker, 2012 syn. n. are synonymised with M. monofascia (van Son, 1933); M. mbala Hacker, 2014 syn. n. and M. poliographa Hacker, 2012 syn. n. are synonymised with M. furvitincta (Hampson, 1914); M. obscuritata Hacker, 2012 syn. n. is synonymised with M. spermophaga (Fletcher, 1962); M. tabbertiella Hacker Hoppe, 2012 syn. n., M. amaniella Hacker, 2012 syn. n. and M. fuscostriata Hacker, 2012 syn. n. are synonymised with M. pyrrhomorpha Hacker, 2012; M. longisigna Hacker, 2012 syn. n. and M. politzari Hacker, 2012 syn. n. are synonymised with M. foviferoides (Poole, 1989); Meganola eburneana Hacker, 2012 syn. n. is synonymised with M. illaudata (Fletcher, 1958). The hitherto unknown males of Meganola dananae Hacker, 2012, M. rhyssomorpha Hacker, 2012 and M. mesothermoides (Poole, 1989) as well as females of M. microfascia Hacker, 2012 and M. palaeographa Hacker, 2012 are illustrated for the first time and several new distribution records are provided.

Lepidoptera, Nolini, taxonomy, lectotype designation, new synonymy, new record, Afrotropics


Synthesis of N,S-Doped Carbon Quantum Dots for Use in Organic Solar Cells as the ZnO Modifier To Eliminate the Light-Soaking Effect.

Abstract: Zinc oxide (ZnO) is one of the most extensively used electron-transporting layers (ETLs) in organic solar cells. However, owing to numerous surface defects and mismatched energy bands with the photoactive layer, light-soaking process is usually required to achieve a high device performance for the ZnO-based cells. Herein, we reported the synthesis of N,S-doped carbon quantum dots (N,S-CQDs) by a simple hydrothermal treatment using ascorbic acid and ammonium persulfate as reagents. As characterized by high-resolution transmission electron microscopy and X-ray diffraction, the synthesized CQDs were found to be 2-7 nm in dimensions, having a graphite-structured core and amorphous carbon on the shell. Fourier transform infrared and X-ray photoelectron spectroscopy analyses confirmed that these CQDs are highly nitrogen- and sulfur-doped, which leads to efficient (with a quantum yield of 33%) downconversion and excitation-dependent photoluminescence character. Application of these N,S-CQDs as surface modifier for ZnO layer in inverted organic solar cells was investigated. Results indicate that the cells with N,S-CQDs-decorated ZnO ETL showed higher power conversion efficiency without S-shaped kink in the current density-voltage curves. The performance improvement and the elimination of light-soaking effect for ZnO:N,S-CQDs cells are attributed to the ZnO surface defect passivation by N,S-CQDs, as confirmed by fluorescence spectroscopy and scanning Kelvin probe microscopy. The cells with N,S-CQDs-modified ZnO ETL showed a high power conversion efficiency of 9.31%, which is higher than the reference ZnO cells. The current work provides a feasible way to achieve shell element-doped CQDs for specific application in organic electronic devices.

N,S-doped carbon quantum dots
organic solar cells
ZnO
light-soaking effect
surface passivation


Eosinophilic cellulitis successfully treated with Methotrexate.

Abstract: Eosinophilic cellulitis is a rare inflammatory skin disease of unknown aetiology, first described by George Wells in 1971 as a recurrent granulomatous dermatitis with eosinophilia. It is typically characterised by recurrent pruritic erythematous plaques, vesicles or bullae usually involving the extremities and trunk. Many cases of eosinophilic cellulitis are difficult to treat and traditionally require long course of oral steroids, resulting in steroid side effects. This case adds to the literature in that we report the use of methotrexate to treat eosinophilic cellulitis, as a safe and efficacious therapeutic alternative.

eosinophilic cellulitis
methotrexate
Well syndrome
corticosteroids
flame figures


Population Dependency of Measles, Syphilis, and Amebiasis in Japan and Community Evolution.

Abstract: The population dependency of measles, syphilis, and amebiasis was expressed as P = kNm, where P, N, and m were number of patients, population size, and a constant (～2 for measles, and 1.3～1.4 for syphilis and amebiasis), respectively. The population size dependency emerged only when conditions other than population size, such as infant mortality, hygienic condition, vaccination practices, and others, improved to the same level in all the prefectures in Japan. The formation of prefectures and municipalities was well simulated by the random coin toss assuming that people are attracted to a community with a probability proportional to the number of the residents to the 1.3rd power. When the number of inflow population was plotted against the number of the resident population in a prefecture, or when the number of coins that were added in a round was plotted against the number of coins that were present before the coin toss, the plots fell on a straight line with the slope ～1.3, which was almost the same as the slope obtained when the number of cases of syphilis or amebiasis was plotted against the population size.

measles
population size dependency
amebiasis and syphilis
fractal
simulating community evolution