Blockers of the SARS-CoV-2 3a Channel Identified by Targeted Drug Repurposing.

Abstract: The etiological agent of the COVID-19 pandemic is SARS-CoV-2. As a member of the Coronaviridae, the enveloped pathogen has several membrane proteins, of which two, E and 3a, were suggested to function as ion channels. In an effort to increase our treatment options, alongside providing new research tools, we have sought to inhibit the 3a channel by targeted drug repurposing. To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures.

antiviral drugs
bacterial assays
channel blockers
viral channels


Quality concerns in antipsychotic prescribing for youth: a review of treatment guidelines.

Abstract:
BACKGROUND
Antipsychotic prescribing for youth has increased rapidly, is linked with serious health concerns, and lacks clear measures of quality for pediatric care. We reviewed treatment guidelines relevant to 7 quality concepts for appropriate use and management of youth on antipsychotics: 1) use in very young children, 2) multiple concurrent antipsychotics, 3) higher-than-recommended doses, 4) use without a primary indication, 5) access to psychosocial interventions, 6) metabolic screening, and 7) follow-up visits with a prescriber.

METHODS
We searched for clinical practice guidelines meeting the following criteria: developed or endorsed by a national body, published after 2000, and specific treatment recommendations made related to 1 or more of the 7 quality concepts. Sources included electronic databases, the American Academy of Child and Adolescent Psychiatry Web site, and stakeholder and expert advisory committee recommendations. Two raters reviewed the 11 guidelines identified, extracting treatment recommendations, including details that could support measure definitions, and ratings of strength of recommendation and evidence.

RESULTS
All 7 quality concepts were strongly endorsed by 1 or more guidelines, and 2 or more guidelines assigned their highest strength of recommendation ratings to 6 of the 7 concepts. Two guidelines rated evidence, providing high strength of evidence for 2 quality concepts: psychosocial interventions and metabolic monitoring.

CONCLUSIONS
Guidelines provide support for 7 quality concepts addressing antipsychotic prescribing for youth. However, guideline support is often based on strong clinical consensus rather than a robust evidence base.

Kealey|Edith|E|
Scholle|Sarah Hudson|SH|
Byron|Sepheen C|SC|
Hoagwood|Kimberly|K|
Leckman-Westin|Emily|E|
Kelleher|Kelly|K|
Finnerty|Molly|M|

children
adolescents
antipsychotic agents
practice guidelines as topic
quality indicators


The socioeconomic gradient in physical inactivity: evidence from one million adults in England.

Abstract: Understanding the socioeconomic gradient in physical inactivity is essential for effective health promotion. This paper exploits data on over one million individuals (1,002,216 people aged 16 and over) in England drawn from the Active People Survey (2004-11). We identify the separate associations between a variety of measures of physical inactivity with education and household income. We find high levels of physical inactivity. Further, both education and household income are strongly associated with inactivity even when controlling for local area deprivation, the availability of physical recreation and sporting facilities, the local weather and regional geography. Moreover, the gap in inactivity between those living in high and low income households is already evident in early adult life and increases up until about age 85. Overall, these results suggest that England is building up a large future health problem and one that is heavily socially graded.

Farrell|Lisa|L|
Hollingsworth|Bruce|B|
Propper|Carol|C|
Shields|Michael A|MA|

Physical inactivity
England
Education
Income
Area deprivation


Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site.

Abstract: Enzymes use protein architectures to create highly specialized structural motifs that can greatly enhance the rates of complex chemical transformations. Here, we use experiments, combined with ab initio simulations that exactly include nuclear quantum effects, to show that a triad of strongly hydrogen-bonded tyrosine residues within the active site of the enzyme ketosteroid isomerase (KSI) facilitates quantum proton delocalization. This delocalization dramatically stabilizes the deprotonation of an active-site tyrosine residue, resulting in a very large isotope effect on its acidity. When an intermediate analog is docked, it is incorporated into the hydrogen-bond network, giving rise to extended quantum proton delocalization in the active site. These results shed light on the role of nuclear quantum effects in the hydrogen-bond network that stabilizes the reactive intermediate of KSI, and the behavior of protons in biological systems containing strong hydrogen bonds.

Wang|Lu|L|
Fried|Stephen D|SD|
Boxer|Steven G|SG|
Markland|Thomas E|TE|

D001426:Bacterial Proteins
D020134:Catalytic Domain
D006860:Hydrogen Bonding
D016958:Pseudomonas putida
D013251:Steroid Isomerases

ab initio path integral molecular dynamics


Mechanism of lung development in the aetiology of adult congenital pulmonary airway malformations.

Abstract: Congenital pulmonary airway malformations (CPAMs) are rare lung abnormalities that result in cyst formation and are associated with respiratory distress in infants and malignant potential in adults. The pathogenesis of CPAMs remains unknown but data suggest disruption of the normal proximo-distal programme of airway branching and differentiation. Here, we demonstrate that adult human CPAM are lined with epithelium that retains SOX-2 and thyroid transcription factor-1 immunohistochemical markers, characteristic of the developing lung. However, RALDH-1, another key marker, is absent. This suggests a more complex aetiology for CPAM than complete focal arrest of lung development and may provide insight to the associated risk of malignancy.

Taylor|Bethany|B|
Rice|Alexandra|A|
Nicholson|Andrew G|AG|
Hind|Matthew|M|
Dean|Charlotte H|CH|0000-0002-8846-5472

D000080924:Aldehyde Dehydrogenase 1 Family


Rac1 modulates the vitreous-induced plasticity of mesenchymal movement in retinal pigment epithelial cells.

Abstract:
BACKGROUND
The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected.

DESIGN
One-way design with multiple levels and repeated measurement design.

PARTICIPANTS AND SAMPLES
The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes.

METHODS
Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis.

MAIN OUTCOME MEASURES
Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin.

RESULTS
Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766.

CONCLUSIONS
Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy.

Huang|Xiong-gao|XG| Chen|You-zhen|YZ| Zhang|Zhao-tian|ZT| Wei|Yan-tao|YT| Ma|Hai-zhi|HZ| Zhang|Ting|T| Zhang|Shao-chong|SC|

plasticity
retinal pigment epithelial cells
vitreous
proliferative vitreoretinopathy
Rac1 GTPase


Late-onset capsular block syndrome: unusually delayed presentation.

Abstract: Capsular block syndrome (CBS) has been known to occur as a rare complication of cataract surgery with continuous curvilinear capsulorhexis and a posterior-chamber lens implant. Typically, it presents with reduced vision in the early postoperative period and is characterised by a forward displacement of the posterior-chamber intra-ocular lens and an accumulation of intra-capsular opaque material. Management of CBS is usually by Nd:YAG laser capsulotomy. In this report, we describe a unique case of very-delayed-onset CBS with good visual acuity, occurring 8 years after surgery. It was treated successfully with surgical removal of the opaque material.

Rana|M|M|
Jiang|L|L|
Ilango|B|B|
Yang|Y C|YC|

Capsular block syndrome
Capsular bag distension
Posterior capsule
Propionibacterium acnes


Poorly Cohesive (Signet Ring Cell) Carcinoma of the Ampulla of Vater.

Abstract: In the ampulla of Vater, carcinomas with "diffuse-infiltrative"/"signet ring cell" morphology, designated as "poorly cohesive carcinoma" (PCC) in the WHO classification, are very rare and poorly characterized. Nine cases with a classical PCC morphology constituting >50% of the tumor were identified. Mean age was 64.8 years (vs 64.6 in ampullary carcinomas [ACs]) and 6 were males, 3 females. The mean invasive tumor size was 2.5 cm (vs 1.9 in ACs). Other morphologic patterns displayed included cord-like infiltration (n=2), plasmacytoid cells (n=2), and microglandular component (n=4), including goblet cell adenocarcinoma-like foci. None of the cases were associated with dysplasia. By immunohistochemistry, the carcinomas did not show intestinal differentiation (CDX2 0/9, CK20 1/9, MUC2 3/9), MUC1 was positive in 4/9, MUC5AC was positive in 7/8. E-cadherin loss was noted in 4/9. All cases were advanced stage (6/9-pT3, 3/9-pT4) (vs 43% in ACs). Lymph node metastases were identified in 44% (vs 45% in AC). Six patients (67%) died of disease at a median of 25 months, 3 were alive at 13, 15, and 60 months. Overall median survival was significantly worse than that of intestinal-type ACs (26 vs 122 months, P = .006) and trended toward worse than pancreatobiliary type (26 vs 42 months, P = .1). In conclusion, PCCs constitute 2.45% of all ACs. These present as advanced tumors and express upper-gastrointestinal immunoprofile with frequent MUC5AC labeling, which may be helpful in identifying subtle infiltration in the surface mucosa since MUC5AC is not expressed in the ampullary mucosa. Patients have poor prognosis.

signet ring cell
carcinoma
ampulla
adenocarcinoma
diffuse-infiltrative
poorly cohesive cell


Bone heating and implant removal using a high-frequency electrosurgical device: An in vivo experimental study.

Abstract:
OBJECTIVES
Failed implant removal using a high-frequency electrosurgical device (HFED) has been reported to be less invasive than other surgical techniques. We sought to clarify the mechanism of removal torque reduction in an implant by heating with HFED.

MATERIALS AND METHODS
Sixty-eight Wistar rats received titanium implants on the maxillary bone 4 weeks after extraction of the first and second molars. The control group was sacrificed 6 weeks after implant installation. In the experimental group, the implant was heated by HFED for 10 s using three different power outputs, and samples were collected at 3, 7, and 14 days after heating. Removal torque measurement and histological analysis were performed in the control and experimental groups. Implant surfaces were observed using an electron-probe microanalyzer (EPMA). Data were analyzed using Mann-Whitney U test at a significance level of 5%.

RESULTS
The removal torque could not be measured in the control group due to fracture of the implant. After heating, the removal torque was measurable without fracture and decreased significantly at 14 days as compared with that at 3 days (p < .05). Heating with "min" power output resulted in a significantly smaller blank lacunae area and fewer osteoclasts at 14 days after heating (p < .05). EPMA revealed bone matrix adherence to outer surface of heated implant.

CONCLUSIONS
After heating, an enlarged area of blank lacunae around the implant and an increased number of osteoclasts into the bone marrow cavity were observed, which may have contributed to the reduction in removal torque.

animal experiments
bone-implant interactions
material sciences


Trauma and Suicide Risk in College Students: Does Lack of Agency, Lack of Pathways, or Both Add to Further Risk?

Abstract: The present study sought to examine trauma history and hope as predictors of suicide risk in a sample of 561 college students. Furthermore, authors aimed to understand whether the lack of hope agency and hope pathways contributed to further risk for suicide, above and beyond trauma history. Results suggested that trauma history and hope agency were significant and unique predictors of suicide risk among college students. More specifically, hope agency accounted for additional variance in the prediction model of suicide risk, beyond that accounted for by trauma history. Some implications of the present findings for social work practice are discussed.

Lucas|Abigael G|AG|
Chang|Edward C|EC|
Li|Mingqi|M|
Chang|Olivia D|OD|
Yu|Elizabeth A|EA|
Hirsch|Jameson K|JK|

suicide risk
college students
trauma history
hope


Non-Occlusive Retinal Vascular Inflammation and Role of Red Blood Cell Deformability in Birdshot Chorioretinopathy.

Abstract: Purpose: To investigate differences in red blood cell (RBC) deformability between birdshot chorioretinopathy (BCR) subjects and matched controls, and to postulate its relationship with lack of vascular occlusion in BCR. Methods: In a single center, prospective, non-randomized mechanistic study, blood samples were collected from eight healthy controls and nine BCR patients, and subjected to biochemical and hematological tests, as well as RBC indices assessment using dual-beam optical tweezers. Results: The mean age of the controls was 52.37 ± 10.70 years and BCR patients was 53.44 ± 12.39 years. Initial cell size (Io) for the controls was 8.48 ± 0.25 μm and 8.87 ± 0.31 μm for BCR RBCs (p = 0.014). The deformability index (DI) for the controls was 0.066 ± 0.02 and that for BCR RBCs was 0.063 ± 0.03 (p = 0.441). Conclusion: There was no statistically significant difference in DI between RBCs from BCR and healthy controls. This may explain the rare occurrence of retinal vascular occlusion despite the underlying vasculitic pathophysiology of BCR.

Agrawal|Rupesh|R|
Ang|Bryan|B|
Balne|Praveen Kumar|PK|
Richards|Christopher|C|
Smart|Thomas|T|
Cardoso|João|J|
Shima|David|D|
Jones|Philip H|PH|
Pavesio|Carlos|C|

Birdshot chorioretinopathy
red blood cell (RBC)
vascular occlusion
dual-beam optical tweezers
RBC deformability


Identification of Antimicrobial Peptides from Novel Lactobacillus fermentum Strain.

Abstract: Antimicrobial peptides (AMPs) are natural antagonistic tools of many bacteria and are considered as attractive antimicrobial agents for the treatment of bacteria with multidrug resistance. Lactic acid bacteria from the gastrointestinal tract of animals and human produce various AMPs inhibiting the growth of pathogens. Here we report the isolation and identification of novel Lactobacillus fermentum strain HF-D1 from the human gut producing AMPs which prevents the growth of P. aeruginosa and S. marcescens. The active fraction of peptides was obtained from the culture liquid by precipitation at 80% saturation of ammonium sulphate. For peptides identification, the precipitate was treated with guanidine hydrochloride to desorb from proteins, separated with ultrafiltration on spin columns with 10,000 MWCO, desalted with a reversed-phase chromatography and subjected to LC-MS/MS analysis. The in silico analysis of the identified 1111 peptides by using ADAM, CAMPR3 and AMPA prediction servers led to identification of the linear peptide with highly probable antimicrobial activity and further investigation of its antibacterial activity mechanism is promising. By using the dereplication algorithm, the peptide highly similar to non-ribosomal cyclic AMPs originally isolated from Staphylococcus epidermidis has been identified. This indicates that L. fermentum HF-D1 represents a novel strain producing antimicrobial peptides targeting P. aeruginosa and S. marcescens.

D000890:Anti-Infective Agents
D023181:Antimicrobial Cationic Peptides
D001419:Bacteria
D000069196:Gastrointestinal Microbiome
D006801:Humans
D052197:Lactobacillus fermentum

Antimicrobial peptides
Lactobacillus fermentum
Cyclic peptides
Mass-spectrometry


Anlotinib or platinum-pemetrexed as second-line therapy in EGFR T790M-negative lung cancer.

Abstract:
BACKGROUND
Clinical management of T790M-negative patients after first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment failure is controversial. Anlotinib is a novel multi-target TKI for tumor angiogenesis and tumor cell proliferation, and it has been approved as a thirdline or beyond treatment for advanced non-small cell lung cancer (NSCLC). The impact of anlotinib as a second-line therapy compared with platinum-pemetrexed chemotherapy in T790M-negative patients after first-line EGFR-TKIs failed remains unclear.

METHODS
In this retrospective cohort study, we reviewed 20 patients who were given anlotinib and 42 patients who received platinum-pemetrexed chemotherapy as a control after first-line EGFR-TKIs therapy progression. All the patients were confirmed to be T790M-negative using the cobas EGFR Mutation Test. The primary end point included progression-free survival (PFS) time, objective response rate (ORR) and disease control rate.

RESULTS
The duration of PFS was significantly longer in the platinum-pemetrexed group than in the anlotinib group (median, 4.5 vs. 3.0 months; HR, 1.972; 95% CI, 1.078 to 3.607; P=0.021). The response rate was significantly better in the platinum-pemetrexed group (30.9%) than that in the anlotinib group (15%), and disease control rate (DCR) of both groups was 70% and 83%, respectively. All the adverse events in anlotinib group appeared to be manageable.

CONCLUSIONS
Anlotinib was less effective than platinum-pemetrexed chemotherapy in T790M-negative NSCLC patients after disease progression with first-line EGFR-TKIs therapy failure.

Zhong|Run-Bo|RB| Xu|Jian-Lin|JL| Lou|Yu-Qing|YQ| Chu|Tian-Qing|TQ| Zhong|Hua|H| Han|Bao-Hui|BH|

D000971:Antineoplastic Combined Chemotherapy Protocols

epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)


Analysis of bromophenols in various aqueous samples using solid phase extraction followed by HPLC-MS/MS.

Abstract: A reliable and effective method for simultaneous analysis of trace amount of bromophenols (BPs) in various aqueous samples was developed in this study. The aqueous samples must be acidified after sampling to prevent the fast degradation of bromophenols. Solid-phase extraction was chosen to extract and purify the water samples. High performance liquid chromatography coupled with tandem mass spectrometry with an electrospray ionization source (HPLC-ESI-MS/MS) was used for following identification and quantification. Under the optimized condition, fourteen out of fifteen target brominated phenols were successfully separated and detected with the exception of 2,6-bromophenol (2,6-BP) whose response was too low to be quantified by the MS detector. The method was validated by spiking river water and seawater samples with different concentrations of BPs, and the qualified spiking recoveries (64-100%) and precisions (0.4-11% RSD) were obtained. The method detection limits were 0.1-13.9ng/L and 0.1-21.9ng/L for 0.1L of river water and seawater samples, respectively, showing the influences from the sample matrix. The proposed method was successfully applied to the analysis of bromophenol contamination in real water samples, and six bromophenols were identified with a wide concentrations ranging from ng/L to μg/L.

Chi|Xiyuan|X| Liu|Jiyan|J| Yu|Miao|M| Xie|Zhouqing|Z| Jiang|Guibin|G|

Bromophenols
Aqueous samples
Solid phase extraction
LC-MS/MS


C950T and C1181G osteoprotegerin gene polymorphisms in myeloma bone disease.

Abstract:
OBJECTIVES
Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated.

METHODS
C950T and C1181G polymorphisms of the OPG gene were studied in 52 MM patients (36 with bone lesions and 16 without bone lesions) and in another 20 control subjects using DNA sequencing.

RESULTS
1181 G and 950 T alleles were overrepresented in MM patients having bone lesions. 950 TT/1181 GG haplotype frequency and TT/GG combined haplotype were also higher in MM patients having bone lesions compared to MM patients without bone lesions or to control.

DISCUSSION
This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1), and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease.

Sonmez|Mehmet|M| Kazaz|Nazlı|N| Yucel|Burcu|B| Topbas|Murat|M| Ucar|Fahri|F|

Osteoprotegerin
Gene polymorphism
Multiple myeloma


The effect of new complete denture fabrication and simplified dietary advice on nutrient intake and masticatory function of edentulous elderly: A randomized-controlled trial.

Abstract:
BACKGROUND & AIM
Combination of new complete denture fabrication and tailored dietary counseling is necessary to improve nutrient intake of the edentulous elderly. However, there is no evidence on the effect of simple dietary advice combined with new complete denture fabrication on the nutrient intake of the edentulous elderly. The aim of this study was to clarify the combined effect of new complete denture fabrication and simple dietary advice, using a uniform pamphlet, on the nutrient intake and masticatory function of edentulous elderly. The null hypothesis was that there would be no difference in the nutrient intake and masticatory function between edentulous elderly patients provided with simple dietary advice and new complete dentures and those provided with new dentures alone.

METHODS
A double-blind, randomized-controlled, parallel clinical trial was performed on the healthy edentulous elderly who were required to fabricate a new pair of complete denture. The participants were randomly divided into two groups, and each group received different advice: the intervention group received simple dietary advice using a uniform pamphlet, whereas the control group received denture care advice. During the process of new complete denture fabrication, two 20-min one-on-one advice sessions were conducted by a dentist. The primary outcome of this trial was protein intake, which was calculated from the responses in the brief-type self-administered diet history questionnaire (BDHQ). Secondary outcome was masticatory function, which was measured with a color-changeable chewing gum and a test gummy jelly. Outcome assessment was conducted twice, at baseline and at 3 months post-treatment.

RESULTS
Among 70 participants who were randomized, 62 completed this trial. Protein intake in the intervention group significantly increased compared with that in the control group. Masticatory function was not significantly different between groups, but significantly increased at 3 months post-treatment compared with the baseline in both groups.

CONCLUSION
Simple dietary advice using a uniform pamphlet and a new complete denture fabrication increased nutrient intake and masticatory function of healthy edentulous elderly.

CLINICAL TRIAL REGISTRATION NUMBER
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020716 UMIN000017879.

Suzuki|Hiroyuki|H| Kanazawa|Manabu|M| Komagamine|Yuriko|Y| Iwaki|Maiko|M| Jo|Ayami|A| Amagai|Noriko|N| Minakuchi|Shunsuke|S|

Complete denture
Dietary advice
Nutrient intake
Masticatory function
Edentulous
BDHQ


Prior vaccination with recombinant Vesicular Stomatitis Virus - Zaire Ebolavirus vaccine is associated with improved survival among patients with Ebolavirus infection.

Abstract: The second largest Ebolavirus disease (EVD) outbreak ever recorded is currently ongoing in Eastern Democratic Republic of the Congo (DRC). This is the first outbreak for which the recombinant Vesicular Stomatitis Virus - Zaire Ebolavirus (rVSV-ZEBOV) candidate vaccine has been widely administered, using a ring vaccination strategy. We examined whether prior vaccination with rVSV-ZEBOV impacts viral load, organ impairment, and survival among patients with EVD admitted to Ebola Treatment Units (ETUs) in the DRC. We conducted a retrospective observational study of patients admitted to the ETUs in Butembo and Katwa, Eastern DRC, between 30 March and 10 August 2019. We included 257 patients, of whom 44 had been vaccinated prior to admission and 213 were unvaccinated. Vaccinated patients were admitted to hospital sooner than unvaccinated patients (median 2 days (IQR 1.8-4) versus 4 days (IQR 3-6), p < 0.001). Vaccinated patients had a lower viral load at admission compared to those who were unvaccinated: 6.0 log10 cp/mL (IQR 5.0-7.1) versus 6.9 log10 cp/mL (IQR 5.4-7.6), p = 0.017. In a longitudinal analysis of daily viral load measurements, vaccinated patients had an overall viremia 1.32 log10 cp/mL (95% CI 0.58-2.1) lower than unvaccinated patients over the course of their infection. Acute kidney injury at admission was less common in vaccinated patients: OR 0.44 (95% CI 0.20-0.94), p = 0.027. Mortality in vaccinated patients was 10/44 (23%) compared to 117/213 (55%) unvaccinated patients (OR 0.24, 95% CI 0.11-0.51, p < 0.001). In conclusion, prior rVSV-ZEBOV vaccination was associated with reduced severity of infection and improved survival among patients with confirmed EVD treated at ETUs in Eastern DRC. These findings support the efficacy of the rVSV-ZEBOV vaccine in modulating EVD severity.

Kasereka|Masumbuko Claude|MC|
Ericson|Austin D|AD|
Conroy|Andrea L|AL|
Tumba|Lukaba|L|
Mwesha|Ombeni Didier|OD|
Hawkes|Michael T|MT|

D015023:Democratic Republic of the Congo

Ebolavirus
rVSV-ZEBOV
Organ impairment
Survival benefit


DNA Methylation Patterns in the Early Human Embryo and the Epigenetic/Imprinting Problems: A Plea for a More Careful Approach to Human Assisted Reproductive Technology (ART).

Abstract: An increasing number of publications indicate that babies born after IVF (in vitro fertilization) procedures have higher rates of anomalies related to imprinting/epigenetic changes, which may be attributed to suboptimal culture conditions. Appropriate maintenance of DNA methylation during the first few days of an in vitro culture requires a supply of methyl donors, which are lacking in current in vitro culture systems. The absence of protection against oxidative stress in the culture increases the risks for errors in methylation. A decrease in the methylation processes is sometimes observed immediately post fertilization, due to delays that occur during the maternal⁻zygotic transition period. Care should be exercised in ART (assisted reproductive technology) procedures in order to avoid the risk of generating errors in methylation during the in vitro culture period immediately post fertilization, which has an impact on imprinting/epigenetics. Formulation of IVF culture media needs to be re-assessed in the perspective of current knowledge regarding embryo physiology.

D018507:Gene Expression Regulation, Developmental

methylation
imprinting
IVF
culture conditions
epigenesis
maternal to zygotic transition


Effects of alendronate on osteoclast formation and activity in vitro.

Abstract:
INTRODUCTION
Root resorption is a common complication after replantation following traumatic dental avulsion. Endodontic therapy combined with local and intracanal medications aims to avoid osteoclastic activity. In such cases, the application of alendronate (ALN), a bisphosphonate widely used for the treatment of bone disorders, could be of clinical relevance. This study evaluated alendronate biocompatibility on periodontal ligament cells as well as its effects on an in vitro osteoclastogenesis model.

METHODS
Alendronate cytotoxicity (10(-3) to 10(-9) mol/L) in human periodontal ligament fibroblasts, human osteogenic sarcoma cells, and murine osteoclastic precursors (RAW 264.7) was analyzed using cell number determination, cell viability, and proliferation assays. ALN (10(-6) to 10(-12) mol/L) effects on RANKL-induced osteoclastogenesis of RAW cells were assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity and real-time polymerase chain reaction.

RESULTS
ALN at higher concentrations was cytotoxic for all cell types, inhibiting significantly the proliferation of human osteogenic sarcoma cells and human periodontal ligament fibroblasts (≥10(-5) mol/L). TRAP activity and expression of the osteoclast markers TRAP and cathepsin K by RAW-derived osteoclasts decreased significantly with ALN at low concentrations, reaching the maximum effect at 10(-10) mol/L.

CONCLUSIONS
We showed that ALN at very low concentrations is an effective inhibitor of RANKL-generated osteoclasts, without causing cytotoxic effects on their precursors or periapical cells. ALN at such concentrations might be useful to prevent replacement resorption in avulsed teeth.

Martins|Caroline A|CA|
Leyhausen|Gabriele|G|
Volk|Joachim|J|
Geurtsen|Werner|W|

Alendronate
root resorption
dental avulsion
osteoclastogenesis
cytotoxicity
RAW 264.7
RANKL


Metal Oxide Gas Sensors, a Survey of Selectivity Issues Addressed at the SENSOR Lab, Brescia (Italy).

Abstract: This work reports the recent results achieved at the SENSOR Lab, Brescia (Italy) to address the selectivity of metal oxide based gas sensors. In particular, two main strategies are being developed for this purpose: (i) investigating different sensing mechanisms featuring different response spectra that may be potentially integrated in a single device; (ii) exploiting the electronic nose (EN) approach. The former has been addressed only recently and activities are mainly focused on determining the most suitable configuration and measurements to exploit the novel mechanism. Devices suitable to exploit optical (photoluminescence), magnetic (magneto-optical Kerr effect) and surface ionization in addition to the traditional chemiresistor device are here discussed together with the sensing performance measured so far. The electronic nose is a much more consolidated technology, and results are shown concerning its suitability to respond to industrial and societal needs in the fields of food quality control and detection of microbial activity in human sweat.

Ponzoni|Andrea|A| Baratto|Camilla|C| Cattabiani|Nicola|N| Falasconi|Matteo|M| Galstyan|Vardan|V| Nunez-Carmona|Estefania|E| Rigoni|Federica|F| Sberveglieri|Veronica|V| Zambotti|Giulia|G| Zappa|Dario|D|

metal oxides
photoluminescence
magneto-optical Kerr effect
surface ionization
Enterobacter hormaechei
electronic-nose
gas-sensors
nanotubes
nanowires
skin microbiota


Psychological Treatment of Factitious Disorder Imposed on Another/Munchausen by Proxy Abuse.

Abstract: The purpose of this article is to propose management and treatment protocols for family members impacted by MBP abuse. A brief review of psychopathology, co-morbidities, MBP risk level, treatment outcomes, and rationale for treatment is presented, followed by detailed guidance regarding psychological treatment and management. We propose five components of psychotherapy for abusers, best remembered by using the acronym of ACCEPTS: ACknowledgement, Coping, Empathy, Parenting, Taking charge, and Support. Guidance for the treatment of spouses/partners of the abuser, other involved family members/friends, and child victims are also provided.

Factitious disorder imposed on another
Munchausen by proxy
Family treatment


FIB-TEM Study of Magnesium Corrosion Products after 14 Days in the Murine Artery.

Abstract: After a decade of intensive research on magnesium biodegradation, the composition and structure of corrosion products formed during in vivo corrosion are still not precisely known. Focused ion beam (FIB) micromilling and transmission electron microscopy (TEM) were used to elucidate the nanostructure and crystallography of the corrosion products that form at or near the interface between the corrosion products and metallic magnesium. This study built upon previously reported scanning electron microscopy, infrared spectroscopy, and energy dispersive X-ray spectroscopy data. These prior results revealed a duplex corrosion layer comprising a calcium- and phosphorus-containing outer product (near the tissue interface) and a magnesium- and oxygen-containing inner product (near the metallic interface). A specimen that had resided in the murine arterial wall for 14 days was selected for FIB-TEM analysis. Highly oriented, nanocrystalline magnesium oxide was identified near the metallic magnesium, apparently without the co-occurrence of magnesium hydroxide or carbonates. The calcium- and phosphorus-containing surface layer was also examined, and shown to be nearly amorphous.

Bowen|Patrick K|PK|
McNamara|Cameron T|CT|
Mills|Owen P|OP|
Drelich|Jaroslaw|J|
Goldman|Jeremy|J|

magnesium
corrosion products
in vivo
bioabsorbable stent


A two-step drug repositioning method based on a protein-protein interaction network of genes shared by two diseases and the similarity of drugs.

Abstract: The present study proposed a two-step drug repositioning method based on a protein-protein interaction (PPI) network of two diseases and the similarity of the drugs prescribed for one of the two. In the proposed method, first, lists of disease related genes were obtained from a meta-database called Genotator. Then genes shared by a pair of diseases were sought. At the first step of the method, if a drug having its target(s) in the PPI network, the drug was deemed a repositioning candidate. Because targets of many drugs are still unknown, the similarities between the prescribed drugs for a specific disease were used to infer repositioning candidates at the second step. As a first attempt, we applied the proposed method to four different types of diseases: hypertension, diabetes mellitus, Crohn disease, and autism. Some repositioning candidates were found both at the first and second steps.

Drug repositioning
Protein-Protein interaction network
Disease related genes
Drug interaction
Drug target
Side effect
Substructure


Dapagliflozin is associated with improved glycaemic control and weight reduction at 44 months of follow-up in a secondary care diabetes clinic in the UK.

Abstract:
BACKGROUND AND AIMS
We examined HbA1c and cardiovascular risk factors with a median follow-up of 44 months therapy with dapagliflozin.

METHODS
We undertook a clinical practice evaluation of 101 patients attending our clinic.

RESULTS
Dapagliflozin resulted in a significant reduction in HbA1c 82.6 ± 15.7 v 68.7 ± 17.8 mmol/mol.

CONCLUSION
Dapagliflozin maintains glycaemic control along with sustained improvements in weight and no decline in renal function.

Shrikrishnapalasuriyar|Natasha|N|
Shaikh|Ayesha|A|
Ruslan|Aliya Mohd|AM|
Sharaf|Giselle|G|
Udiawar|Maneesh|M|
Price|David E|DE|
Stephens|Jeffrey W|JW|

D000368:Aged
D001559:Benzhydryl Compounds
D003924:Diabetes Mellitus, Type 2
D005260:Female
D005500:Follow-Up Studies
D005960:Glucosides
D006442:Glycated Hemoglobin A
D000085002:Glycemic Control
D006801:Humans
D007004:Hypoglycemic Agents
D008297:Male
D008875:Middle Aged
D063127:Secondary Care
D016896:Treatment Outcome
D006113:United Kingdom
D015431:Weight Loss

Dapagliflozin
HbA1c
Cardiovascular
SGLT2 inhibitor


General public's views on pharmacy public health services: current situation and opportunities in the future.

Abstract:
OBJECTIVES
To explore the experience of and willingness to use seven pharmacy public health services related to cardiovascular risk among the general public in England.

STUDY DESIGN
Mixed-methods study.

METHODS
A mixed-methods study, involving a cross-sectional survey using multiple distribution methods followed by a focus group discussion (FGD) with a sample of survey respondents.

RESULTS
From 3596 approachable individuals, 908 questionnaires were completed (response rate 25.3%). Few respondents (2.1-12.7%) had experienced any of the seven pharmacy public health services. About 40% stated they would be willing to use health check services, fewer (9.3-26.3%) were willing to use advisory services. More females, frequent pharmacy users and those in good health were willing to use services in general (P < 0.05). Smokers, overweight individuals and those with alcohol-related problems were most willing to use specific advisory services supporting their problems (P < 0.05). FGD identified barriers to service use; for example, frequent staff changes, seeing pharmacist as medicines suppliers and concerns about competence for these services.

CONCLUSION
The general public are receptive to pharmacy public health services. Pharmacists must consider barriers if uptake of services is to increase.

Saramunee|K|K| Krska|J|J| Mackridge|A|A| Richards|J|J| Suttajit|S|S| Phillips-Howard|P|P|

D010342:Patient Acceptance of Health Care

General public
Pharmacy public health services
Cardiovascular
Mixed-methods


Atorvastatin favorably modulates proinflammatory cytokine profile in patients following deep vein thrombosis.

Abstract:
BACKGROUND
Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients.

MATERIALS AND METHODS
Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood.

RESULTS
The VTE patients displayed higher C-reactive protein (p=0.013), IL-1b (p=0.03), IL-8 (p=0.03) and vWF (p<0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p=0.0003), IL-8 (p=0.003) and P-selectin (p<0.0001), but increased IL-10 (p=0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p=0.01), IL-6 (p=0.03) and P-selectin (p=0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p<0.05).

CONCLUSION
A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.

Żółciński|Marek|M|
Cieśla-Dul|Mariola|M|
Potaczek|Daniel P|DP|
Undas|Anetta|A|

Venous thromboembolism
Inflammation
Statins


Viral sequences in human cancer.

Abstract: We have developed a virus detection and discovery computational pipeline, Pickaxe, and applied it to NGS databases provided by The Cancer Genome Atlas (TCGA). We analyzed a collection of whole genome (WGS), exome (WXS), and RNA (RNA-Seq) sequencing libraries from 3052 participants across 22 different cancers. NGS data from nearly all tumor and normal tissues examined contained contaminating viral sequences. Intensive computational and manual efforts are required to remove these artifacts. We found that several different types of cancers harbored Herpesviruses including EBV, CMV, HHV1, HHV2, HHV6 and HHV7. In addition to the reported associations of Hepatitis B and C virus (HBV & HCV) with liver cancer, and Human papillomaviruses (HPV) with cervical cancer and a subset of head and neck cancers, we found additional cases of HPV integrated in a small number of bladder cancers. Gene expression and mutational profiles suggest that HPV drives tumorigenesis in these cases.

Cantalupo|Paul G|PG|
Katz|Joshua P|JP|
Pipas|James M|JM|

Cancer TCGA Herpesvirus Metagenomics Papillomavirus Virome


Deciphering the Pharmacological Mechanisms of Ma Xing Shi Gan Decoction against COVID-19 through Integrating Network Pharmacology and Experimental Exploration.

Abstract: The outbreak of new infectious pneumonia caused by SARS-CoV-2 has posed a significant threat to public health, but specific medicines and vaccines are still being developed. Traditional Chinese medicine (TCM) has thousands of years of experience in facing the epidemic disease, such as influenza and viral pneumonia. In this study, we revealed the efficacy and pharmacological mechanism of Ma Xing Shi Gan (MXSG) Decoction against COVID-19. First, we used liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to analyze the chemical components in MXSG and identified a total of 97 components from MXSG. Then, the intervention pathway of MXSG based on these components was analyzed with network pharmacology, and it was found that the pathways related to the virus infection process were enriched in some of MXSG component targets. Simultaneously, through literature research, it was preliminarily determined that MXSG, which is an essential prescription for treating COVID-19, shared the feature of antiviral, improving clinical symptoms, regulating immune inflammation, and inhibiting lung injury. The regulatory mechanisms associated with its treatment of COVID-19 were proposed. That MXSG might directly inhibit the adsorption and replication of SARS-CoV-2 at the viral entry step. Besides, MXSG might play a critical role in inflammation and immune regulatory, that is, to prevent cytokine storm and relieve lung injury through toll-like receptors signaling pathway. Next, in this study, the regulatory effect of MXSG on inflammatory lung injury was validated through transcriptome results. In summary, MXSG is a relatively active and safe treatment for influenza and viral pneumonia, and its therapeutic effect may be attributed to its antiviral and anti-inflammatory effects.

Li|Qianqian|Q| Bai|Chen|C| Yang|Ruocong|R| Xing|Weiying|W| Pang|Xiaohan|X| Wu|Siying|S| Liu|Shaoyang|S| Chen|Jianxin|J| Liu|Tiegang|T| Gu|Xiaohong|X|

Ma Xing Shi Gan decoction
COVID-19
Traditional Chinese Medicine
antiviral
immunomodulatory


Human Secretary Phospholipase A2 Mutations and Their Clinical Implications.

Abstract: Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for hydrolysis of the sn-2 fatty acids of membrane phospholipids to release arachidonic acid. PLA2s are the rate limiting enzyme for the downstream synthesis of prostaglandins and leukotrienes that are the main mediators of inflammation. The extracellular forms of this enzyme are also called the secretary phospholipase A2 (sPLA2) and are distributed extensively in most of the tissues in the human body. Their integral role in inflammatory pathways has been the primary reason for the extensive research on this molecule. The catalytic mechanism of sPLA2 is initiated by a histidine/aspartic acid/calcium complex within the active site. Though they are known to have certain housekeeping functions, certain mutations of sPLA2 are known to be implicated in causation of certain pathologies leading to diseases such as atherosclerosis, cardiovascular diseases, benign fleck retina, neurodegeneration, and asthma. We present an overview of human sPLA2 and a comprehensive compilation of the mutations that result in various disease phenotypes. The study not only helps to have a holistic understanding of human sPLA2 mutations and their clinical implications, but is also a useful platform to initiate research pertaining to structure-function relationship of the mutations to develop effective therapies for management of these diseases.

secretary phospholipase A2
mutations
clinical implications
sPLA2
structure–function relationship


Prospective comparison of PI-RADS version 2 and qualitative in-house categorization system in detection of prostate cancer.

Abstract:
BACKGROUND
Prostate Imaging-Reporting and Data System v. 2 (PI-RADSv2) provides standardized nomenclature for interpretation of prostate multiparametric MRI (mpMRI). Inclusion of additional features for categorization may provide benefit to stratification of disease.

PURPOSE
To prospectively compare PI-RADSv2 to a qualitative in-house system for detecting prostate cancer on mpMRI.

STUDY TYPE
Prospective.

POPULATION
In all, 338 patients who underwent mpMRI May 2015-May 2016, with subsequent MRI/transrectal ultrasound fusion-guided biopsy.

FIELD STRENGTH
3T mpMRI (T2 W, diffusion-weighted [DW], apparent diffusion coefficient [ADC] map, b-2000 DWI acquisition, and dynamic contrast-enhanced [DCE] MRI).

ASSESSMENT
One genitourinary radiologist prospectively read mpMRIs using both in-house and PI-RADSv2 5-category systems.

STATISTICAL TEST
In lesion-based analysis, overall and clinically significant (CS) tumor detection rates (TDR) were calculated for all PI-RADSv2 and in-house categories. The ability of each scoring system to detect cancer was assessed by area under receiver operator characteristic curve (AUC). Within each PI-RADSv2 category, lesions were further stratified by their in-house categories to determine if TDRs can be increased by combining features of both systems.

RESULTS
In 338 patients (median prostate-specific antigen [PSA] 6.5 [0.6-113.6] ng/mL; age 64 [44-84] years), 733 lesions were identified (47% tumor-positive). Predictive abilities of both systems were comparable for all (AUC 76-78%) and CS cancers (AUCs 79%). The in-house system had higher overall and CS TDRs than PI-RADSv2 for categories 3 and 4 (P < 0.01 for both), with the greatest difference between the scoring systems seen in lesions scored category 4 (CS TDRs: in-house 65%, PI-RADSv2 22.1%). For lesions categorized as PI-RADSv2 = 4, characterization of suspicious/indeterminate extraprostatic extension (EPE) and equivocal findings across all mpMRI sequences contributed to significantly different TDRs for both systems (TDR range 19-75%, P < 0.05).

DATA CONCLUSION
PI-RADSv2 behaves similarly to an existing validated system that relies on the number of sequences on which a lesion is seen. This prospective evaluation suggests that sequence positivity and suspicion of EPE can enhance PI-RADSv2 category 4 cancer detection.

LEVEL OF EVIDENCE
1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1326-1335.

Gaur|Sonia|S|
Harmon|Stephanie|S|
Mehralivand|Sherif|S|
Bednarova|Sandra|S|
Calio|Brian P|BP|
Sugano|Dordaneh|D|
Sidana|Abhinav|A|
Merino|Maria J|MJ|
Pinto|Peter A|PA|
Wood|Bradford J|BJ|
Shih|Joanna H|JH|
Choyke|Peter L|PL|
Turkbey|Baris|B|

D038524:Diffusion Magnetic Resonance Imaging

detection prostate cancer PI-RADSv2 mpMRI


Metal-Catalyzed Sequential Formation of Distant Bonds in Organic Molecules: Palladium-Catalyzed Hydrosilylation/Cyclization of 1,n-Dienes by Chain Walking.

Abstract: Sequential formation of distant bonds in organic molecules was achieved for the palladium-catalyzed hydrosilylation/cyclization of various 1,n-dienes by chain walking of the metal catalyst. The reaction was applicable to various 1,n-dienes, including a 1,13-diene, to form a cyclopentane ring as well as a carbon-silicon bond at a remote site. The use of "nondissociative" chain walking provides a fascinating strategy in organic synthesis to functionalize distant parts of organic molecules, in a particular order, within a catalytic cycle by effectively moving the reactive center from a remote position.

hydrosilylation cyclizations alkenes isomerizations palladium


Geometry Design, Principles and Assembly of Micromotors.

Abstract: Discovery of bio-inspired, self-propelled and externally-powered nano-/micro-motors, rotors and engines (micromachines) is considered a potentially revolutionary paradigm in nanoscience. Nature knows how to combine different elements together in a fluidic state for intelligent design of nano-/micro-machines, which operate by pumping, stirring, and diffusion of their internal components. Taking inspirations from nature, scientists endeavor to develop the best materials, geometries, and conditions for self-propelled motion, and to better understand their mechanisms of motion and interactions. Today, microfluidic technology offers considerable advantages for the next generation of biomimetic particles, droplets and capsules. This review summarizes recent achievements in the field of nano-/micromotors, and methods of their external control and collective behaviors, which may stimulate new ideas for a broad range of applications.

Ning|Huanpo|H|
Zhang|Yan|Y|
Zhu|Hong|H|
Ingham|Andreas|A|
Huang|Gaoshan|G|
Mei|Yongfeng|Y|
Solovev|Alexander A|AA|

micromotor fluidic collective catalyst chemoton complex microengine micropump self-assembly sub-system


Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

Abstract: The pathogenesis of the autoimmune rheumatological diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is complex with the involvement of several immune cell populations spanning both innate and adaptive immunity including different T-lymphocyte subsets and monocyte/macrophage lineage cells. Despite therapeutic advances in RA and SLE, some patients have persistent and stubbornly refractory disease. Herein, we discuss stromal cells' dual role, including multipotent mesenchymal stromal cells (MSCs) also used to be known as mesenchymal stem cells as potential protagonists in RA and SLE pathology and as potential therapeutic vehicles. Joint MSCs from different niches may exhibit prominent pro-inflammatory effects in experimental RA models directly contributing to cartilage damage. These stromal cells may also be key regulators of the immune system in SLE. Despite these pro-inflammatory roles, MSCs may be immunomodulatory and have potential therapeutic value to modulate immune responses favorably in these autoimmune conditions. In this review, the complex role and interactions between MSCs and the haematopoietically derived immune cells in RA and SLE are discussed. The harnessing of MSC immunomodulatory effects by contact-dependent and independent mechanisms, including MSC secretome and extracellular vesicles, is discussed in relation to RA and SLE considering the stromal immune microenvironment in the diseased joints. Data from translational studies employing MSC infusion therapy against inflammation in other settings are contextualized relative to the rheumatological setting. Although safety and proof of concept studies exist in RA and SLE supporting experimental and laboratory data, robust phase 3 clinical trial data in therapy-resistant RA and SLE is still lacking.

El-Jawhari|Jehan J|JJ|
El-Sherbiny|Yasser|Y|
McGonagle|Dennis|D|
Jones|Elena|E|

D045164:Mesenchymal Stem Cell Transplantation

Multipotent Mesenchymal Stromal Cells
rheumatoid arthritis
systemic lupus erythematosus
autoimmunity
immune therapy
immunomodulaion


A serological survey of SARS-CoV-2 in cat in Wuhan.

Abstract: COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.


Immunomodulation-Enhanced Nanozyme-Based Tumor Catalytic Therapy.

Abstract: Nanozyme-based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2 O2 ) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation-enhanced nanozyme-based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF-β inhibitor (TI)-loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN-PEG-TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase-like and catalase-like activities under acidic TME, which can decompose H2 O2 into hydroxyl radicals (•OH) and oxygen (O2 ), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2 O2 , which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN-PEG-TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26-tumor-bearing mice models. It is believed that the immunomodulation-enhanced nanozyme-based tumor treatment strategy is a promising tool to kill cancer cells.

tumor catalytic therapy
nanozymes
catalase-like activity
immunomodulation
peroxidase-like activity


Assistive technology use by disability type and race: exploration of a population-based health survey.

Abstract:
PURPOSE
To examine the relationships among Assistive Technology (AT) use, race, type of disability and selected other demographic characteristics.

METHOD
Using 2009 National Health Interview Survey, descriptive statistics, statistical interactions and binary logistic regression were performed to identify, contrast and predict the likelihood of using AT based on the type of disability among African Americans (AAs) and European Americans (EAs).

RESULTS
We found that more AAs (10% within group proportion of total AAs) used AT compared to EAs (7.5% within group proportion of total EAs). Physical (p < 0.001), auditory (p = 0.028) and emotional (p = 0.008) impairments were statistically significant predictors of AT use. However, physical impairment as a predictor of AT use was greater among AAs (OR = 222.49, CI: 64.04-773.04, p < 0.001) than EAs (OR = 50.77, CI: 31.78-81.12, p < 0.001). EAs had a greater number of disabling conditions that predict the use of AT than AAs, whereas AAs had more demographic characteristics beyond race that predict AT use than EAs.

CONCLUSIONS
Disparities were observed in AT usage by disability types and demographic characteristics between AAs and EAs. Moreover, the predictive strength of AT usage based on disability types and other demographic variables differed by races. Overall, the findings about the different relationships among race, disability type, and AT use are found. Implications for Rehabilitation The finding may inform the development of initiatives by rehabilitation leaders to encourage the use of AT by AAs and EAs according to their type of impairment. Having identified physical impairment as statistically significant predictor of AT use greater among AAs, rehabilitation leaders should ensure that people living with those types of disability have access to the corresponding type of AT and can use them effectively.

Ilunga Tshiswaka|Daudet|D|
Loggins Clay|Shondra|S|
Chiu|Chung-Yi|CY|
Alston|Reginald|R|
Lewis|Allen|A|

Assistive technology
disability type
race
disparities
rehabilitation
NHIS


Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease.

Abstract:
BACKGROUND
New noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of Parkinson's disease (PD) diagnosis are urgently needed. Circular RNAs (circRNAs) are stable noncoding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function.

OBJECTIVES
Τhe aims of this study were to identify differentially expressed circRNAs in blood mononuclear cells of patients with idiopathic PD and explore the competing endogenous RNA networks affected.

METHODS
Eighty-seven circRNAs were initially selected based on relatively high gene expression in the human brain. More than half of these were readily detectable in blood mononuclear cells using real-time reverse transcription-polymerase chain reaction. Comparative expression analysis was then performed in blood mononuclear cells from 60 control subjects and 60 idiopathic subjects with PD.

RESULTS
Six circRNAs were significantly down-regulated in patients with PD. The classifier that best distinguished PD consisted of four circRNAs with an area under the curve of 0.84. Cross-linking immunoprecipitation-sequencing data revealed that the RNA-binding proteins bound by most of the deregulated circRNAs include the neurodegeneration-associated FUS, TDP43, FMR1, and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs have the Gene Ontology categories "protein modification" and "transcription factor activity" mostly enriched.

CONCLUSIONS
This is the first study that identifies specific circRNAs that may serve as diagnostic biomarkers for PD. Because they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected. © 2021 Biomedical Research Foundation, Academy of Athens. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

D063990:Gene Ontology
D006801:Humans
D007963:Leukocytes, Mononuclear
D035683:MicroRNAs
D010300:Parkinson Disease
D000079962:RNA, Circular

blood
Parkinson's disease
circRNAs
biomarkers
PBMCs


Effective visual design and communication practices for research posters: Exemplars based on the theory and practice of multimedia learning and rhetoric.

Abstract: Evidence shows that science graduates often do not have the communication skills they need to meet workplace standards and expectations. One common mode of science communication is the poster. In a review of the literature we show that poster design is historically problematic, and that the guidance provided to students as they create posters for assessment is frequently inconsistent. To address this inconsistency we provide some guiding design principles for posters that are grounded in communication theory and the fundamentals of rhetoric. We also present three nondiscipline-specific example posters with accompanying notes that explain why the posters are examples of poor, average, and excellent poster design. The subject matter for the posters is a fabricated set of experiments on a topic that could not actually be the subject of research. Instructors may use these resources with their students, secure in the knowledge that they do not and will never represent an answer set to an extant assessment item. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):249-261, 2017.

Pedwell|Rhianna K|RK|
Hardy|James A|JA|
Rowland|Susan L|SL|

Curriculum design development and implementation

teaching and learning techniques methods and approaches


Causal effect of education on type 2 diabetes: A network Mendelian randomization study.

Abstract:
BACKGROUND
The causality between education and type 2 diabetes (T2DM) remains unclear.

AIM
To identify the causality between education and T2DM and the potential metabolic risk factors [coronary heart disease (CHD), total cholesterol, low-density lipoprotein, triglycerides (TG), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting insulin, fasting glucose, and glycated hemoglobin] from summarized genome-wide association study (GWAS) data used a network Mendelian randomization (MR).

METHODS
Two-sample MR and network MR were performed to obtain the causality between education-T2DM, education-mediator, and mediator-T2DM. Summary statistics from the Social Science Genetic Association Consortium (discovery data) and Neale Lab consortium (replication data) were used for education and DIAGRAMplusMetabochip for T2DM.

RESULTS
The odds ratio for T2DM was 0.392 (95%CI: 0.263-0.583) per standard deviation increase (3.6 years) in education by the inverse variance weighted method, without heterogeneity or horizontal pleiotropy. Education was genetically associated with CHD, TG, BMI, WC, and WHR in the discovery phase, yet only the results for CHD, BMI, and WC were replicated in the replication data. Moreover, BMI was genetically associated with T2DM.

CONCLUSION
Short education was found to be associated with an increased T2DM risk. BMI might serve as a potential mediator between them.

Liao|Li-Zhen|LZ| Chen|Zhi-Chong|ZC| Li|Wei-Dong|WD| Zhuang|Xiao-Dong|XD| Liao|Xin-Xue|XX|

Education
Mendelian randomization
Coronary heart disease
Body mass index
Genome-wide association study
Type 2 diabetes mellitus


KMT2D deficiency confers a therapeutic vulnerability to glycolytic and IGFR inhibitors in melanoma.

Abstract: We reported that histone H3 lysine (K) 4 methyltransferase, KMT2D, serves as a potent tumor-suppressor in melanoma, which was identified via in vivo epigenome-focused RNA interference (RNAi) screen. KMT2D-deficient tumors show substantial reprogramming of key metabolic pathways including glycolysis via reduction of H3K4me1 (Histone H3K4 mono-methylation)-marked active enhancers, conferring sensitivity to inhibitors of glycolysis and IGFR (Insulin Growth Factor Receptor) pathway.

KMT2D
melanoma
glycolysis
enhancer reprogramming


Co-emergence and Collapse: The Mesoscopic Approach for Conceptualizing and Investigating the Functional Integration of Organisms.

Abstract: The fall of reductionist approaches to explanation leaves biology with an unescapable challenge: how to decipher complex systems. This entails a number of very critical questions, the most basic ones being: "What do we mean by 'complex'?" and "What is the system we should look for?" In complex systems, constraints belong to a higher level that the molecular one and their effect reduces and constrains the manifold of the accessible internal states of the system itself. Function is related but not deterministically imposed by the underlying structure. It is quite unlikely that such kind of complexity could be grasped by current approaches focusing on a single organization scale. The natural co-emergence of systems, parts and properties can be adopted as a hypothesis-free conceptual framework to understand functional integration of organisms, including their hierarchical or multilevel patterns, and including the way scientific practice proceeds in approaching such complexity. External, "driving" factors - order parameters and control parameters provided by the surrounding microenvironment - are always required to "push" the components' fate into well-defined developmental directions. In the negative, we see that in pathological processes such as cancer, organizational fluidity, collapse of levels and dynamic heterogeneity make it hard to even find a level of observation for a stable explanandum to persist in scientific practice. Parts and the system both lose their properties once the system is destabilized. The mesoscopic approach is our proposal to conceptualizing, investigating and explaining in biology. "Mesoscopic way of thinking" is increasingly popular in the epistemology of biology and corresponds to looking for an explanation (and possibly a prediction) where "non-trivial determinism is maximal": the "most microscopic" level of organization is not necessarily the place where "the most relevant facts do happen." A fundamental re-thinking of the concept of causality is also due for order parameters to be carefully and correctly identified. In the biological realm, entities have relational properties only, as they depend ontologically on the context they happen to be in. The basic idea of a relational ontology is that, in our inventory of the world, relations are somehow prior to the relata (i.e., entities).

Bizzarri|Mariano|M| Giuliani|Alessandro|A| Pensotti|Andrea|A| Ratti|Emanuele|E| Bertolaso|Marta|M|

mesoscopic way
relational ontology
biological relationships
data emergence
living dynamics
micro-environment
physical constraints
systems thinking


Near-Field Electrospinning and Melt Electrowriting of Biomedical Polymers-Progress and Limitations.

Abstract: Near-field electrospinning (NFES) and melt electrowriting (MEW) are the process of extruding a fiber due to the force exerted by an electric field and collecting the fiber before bending instabilities occur. When paired with precise relative motion between the polymer source and the collector, a fiber can be directly written as dictated by preprogrammed geometry. As a result, this precise fiber control results in another dimension of scaffold tailorability for biomedical applications. In this review, biomedically relevant polymers that to date have manufactured fibers by NFES/MEW are explored and the present limitations in direct fiber writing of standardization in published setup details, fiber write throughput, and increased ease in the creation of complex scaffold geometries are discussed.

near-field electrospinning
melt electrowrite
fiber write
biomedical polymer


Cell biology of primary cell wall synthesis in plants.

Abstract: Building a complex structure such as the cell wall, with many individual parts that need to be assembled correctly from distinct sources within the cell, is a well-orchestrated process. Additional complexity is required to mediate dynamic responses to environmental and developmental cues. Enzymes, sugars and other cell wall components are constantly and actively transported to and from the plasma membrane during diffuse growth. Cell wall components are transported in vesicles on cytoskeletal tracks composed of microtubules and actin filaments. Many of these components, and additional proteins, vesicles, and lipids are trafficked to and from the cell plate during cytokinesis. In this review, we first discuss how the cytoskeleton is initially organized to add new cell wall material or to build a new cell wall, focusing on similarities during these processes. Next, we discuss how polysaccharides and enzymes that build the cell wall are trafficked to the correct location by motor proteins and through other interactions with the cytoskeleton. Finally, we discuss some of the special features of newly formed cell walls generated during cytokinesis.

Cell wall
Diffuse growth
Microtubule
Actin
Trafficking
Cell Plate
Cytoskeleton
Cell division
Cellulose
Phragmoplast


Up-Regulation of Neuronal Nitric Oxide Synthase Expression by Cobalt Chloride Through a HIF-1α Mechanism in Neuroblastoma Cells.

Abstract: Nitric oxide (NO) plays a dual role in response to neural hypoxia. NO is synthesized by three isoforms of nitric oxide synthase (NOS), among which the neuronal NOS (nNOS) is predominant in the nervous system. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is induced under hypoxic conditions, but its correlation with nNOS remains unclear. In the present study, we aimed at clarifying the regulation pattern of the nNOS expression in response to cobalt chloride (CoCl2), a widely used chemical mimic of hypoxia, and the role of HIF-1α in this process in neuroblastoma cells. We found CoCl2 evidently increased the nNOS expression and NO production in human neuroblastoma SK-N-SH cells, but the effect of CoCl2 on NO was partially abrogated by 7-nitroindazole, a selective inhibitor for nNOS. Importantly, we identified a hypoxia response element (HRE) within the nNOS promoter, to which HIF-1α may bind, and CoCl2 greatly enhanced the HIF-1α expression and its binding to the HRE. Meanwhile, we demonstrated that this HRE was functionally important for the activation of the nNOS transcription, and CoCl2 increased the transcriptional activity of the nNOS promoter through this HRE. Taken together, our study shows that CoCl2 may induce the nNOS expression and NO production through a HIF-1α mechanism in neuroblastoma cells, which may provide a potential target for the treatment of neurological hypoxic disorders caused by NO dysregulation.

Li|Guangyu|G| Zhao|Yanyan|Y| Li|Yinghui|Y| Lu|Jingyu|J|

D015972:Gene Expression Regulation, Neoplastic

D051795:Hypoxia-Inducible Factor 1, alpha Subunit


Freezing-Facilitated Dehydration Allowing Deposition of ZnO from Aqueous Electrolyte.

Abstract: When an aqueous NaCl solution with low concentrations of transition metal ions is frozen, most of the solutes are concentrated in the freeze concentrated solutions (FCS). However, Zn2+ is often accumulated at sites where other elements are not detected. X-ray absorption near-edge structure spectroscopy at the Zn K-edge indicates the formation of ZnO. A possible mechanism for the ZnO formation is discussed.

transition metals
freeze concentration
X-ray absorption spectroscopy
ice
zinc oxide


Characterization of the importance of terminal residues for southern rice black-streaked dwarf virus P9-1 viroplasm formations.

Abstract: Southern rice black-streaked dwarf virus (SRBSDV) P9-1 is involved in viroplasm formations in the SRBSDV-infected plants and insects. During infection, SRBSDV P9-1 is an important protein. However, the function characterization of P9-1 octamers in vitro and in yeast is still obscure. In this study, the secondary and 3D structure of SRBSDV P9-1 was predicted, then SRBSDV P9-1 was expressed and analyzed in vitro, a size exclusion chromatography assay showed that P9-1 had the ability to form octamers in vitro. Mutational analysis of terminal residues showed that the C-terminal arm (residues 324-347) of P9-1 was importance for the formation of octamers. Furthermore, a yeast two-hybrid assay showed that there were strong interactions between the full-length P9-1s, after deleting the C-terminal arm of P9-1, the interactions between the truncated P9-1s were disappeared in yeast. Collectively, the non-structural protein P9-1 played an essential role in self-interact viroplasm formation in vitro and in yeast, and the C-terminal arm region of P9-1 was important for assembling octamers in vitro.

Li|Xiangyang|X| Zhang|Weiying|W| Ding|Yan|Y| Wang|Zhenchao|Z| Wu|Zengxue|Z| Yu|Lu|L| Hu|Deyu|D| Li|Pei|P| Song|Baoan|B|

D017434:Protein Structure, Tertiary
D011994:Recombinant Proteins
D012087:Reoviridae
D012441:Saccharomyces cerevisiae
D014764:Viral Proteins

Viroplasm formation
Function characterization
P9-1 octamers
C-terminal arm
South rice black-streaked dwarf virus


Performance of blood pressure measurements at an initial screening visit for the diagnosis of hypertension in children.

Abstract: Hypertension in children is defined as sustained elevated blood pressure (BP) over several visits. For the screening of hypertension, it is standard to obtain several BP readings at the initial visit. There is however no recommendation on the minimum number of readings needed. We evaluated the performance of BP readings obtained at one initial screening visit to predict the diagnosis of hypertension in children. In a school-based study conducted in Switzerland, BP was measured three times on up to three visits in 5207 children. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of elevated BP at the initial screening visit for the identification of hypertension were estimated using the 1st, 2nd, and 3rd BP readings (R1, R2, R3), as well as (R1 + R2)/2 and (R1 + R2 + R3)/3). These performance indices were compared with the reference method (R2 + R3)/2. The ability of BP readings to discriminate children with and without hypertension was evaluated with receiver operating characteristic curve analysis. The prevalence of systolic/diastolic hypertension was 2.2%. The greatest performance to identify children with hypertension was obtained with R2 (sensitivity: 97%; specificity: 88%; PPV: 15%; NPV: 100%) and the reference method, (R2 + R3)/2 (sensitivity: 100%; specificity: 90%; PPV: 18%; NPV: 100%). The ability to discriminate using R1, R2, (R1 + R2)/2, and (R2 + R3)/2 for the identification of hypertension was strong (AUC: 0.89, 0.93, 0.92, and 0.95, respectively). Obtaining two BP readings and using only the second one at a screening visit may be sufficient as initial step for the identification of hypertension in children.

Outdili|Zaïneb|Z|0000-0002-3697-3045 Marti-Soler|Helena|H| Bovet|Pascal|P| Chiolero|Arnaud|A|

screening
hypertension
children
number of readings


New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis.

Abstract: A number of genes have been linked to familial forms of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Over 150 mutations within the gene encoding superoxide dismutase 1 (SOD1) have been implicated in ALS, but why such mutations lead to ALS-associated cellular dysfunction is unclear. In this study, we identify how ALS-linked SOD1 mutations lead to changes in the cellular health of the yeast Saccharomyces cerevisiae We find that it is not the accumulation of aggregates but the loss of Sod1 protein stability that drives cellular dysfunction. The toxic effect of Sod1 instability does not correlate with a loss of mitochondrial function or increased production of reactive oxygen species, but instead prevents acidification of the vacuole, perturbs metabolic regulation and promotes senescence. Central to the toxic gain-of-function seen with the SOD1 mutants examined was an inability to regulate amino acid biosynthesis. We also report that leucine supplementation results in an improvement in motor function in a Caenorhabditis elegans model of ALS. Our data suggest that metabolic dysfunction plays an important role in Sod1-mediated toxicity in both the yeast and worm models of ALS.


Dietary fat and protein intake are not associated with incident biliary sludge and stones during pregnancy.

Abstract:
BACKGROUND
Dietary composition can cause insulin resistance, elevated serum lipid levels, and obesity, all of which predispose to gallstone formation. The effects of dietary fat (including individual fatty acids) and protein on gallstone formation are controversial. The aim of this study was to examine the effects of dietary fat and protein intake on incident gallstone disease during pregnancy, a high-risk time for stone formation.

METHODS
We prospectively studied 3070 pregnant women who underwent serial gallbladder ultrasound examinations during pregnancy and at 4-6 weeks postpartum. All women had at least 2 study ultrasounds for comparison. A semi-quantitative food frequency questionnaire was completed by subjects in the early third trimester. Multivariate logistic regression was performed to assess the risk of incident gallbladder disease across quartiles of intake of total fat, individual fatty acids (polyunsaturated, monounsaturated, saturated, and total trans-fatty acids, as well as cholesterol), protein, and protein subtype (animal or vegetable based).

RESULTS
The cumulative incidence of new biliary sludge/stones or progression of baseline sludge to stones was 10.2% by 4-6 weeks postpartum. There was no association between total dietary fat (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.64-2.18 comparing lowest and highest quartiles) or protein intake (OR, 0.83; 95% CI, 0.44-1.22 comparing lowest and highest quartiles) and incident gallbladder disease. There was also no association between individual fatty acids or protein subtype and gallbladder disease.

CONCLUSIONS
Neither total nor subtype of dietary fat or protein was associated with incident biliary stone or sludge formation in this cohort of pregnant women.

dietary fat
pregnancy
gallstones
dietary protein


ABO-Incompatible Robotic-Assisted Kidney Transplantation in the Obese Recipient.

Abstract: Objective: The objective of this preliminary study was to report and compare the peri-operative and functional results of ABO-incompatible (ABOi) living-donor robotic-assisted kidney transplantation (RAKT), ABO-compatible (ABOc) living-donor RAKT, and ABOi living-donor open kidney transplantation (OKT). Materials and Methods: For the present retrospective study, we analyzed data of consecutive patients who underwent ABOi or ABOc-RAKT and ABOi-OKT, from January 2015 to December 2019, in one French academic center. Patients' baseline characteristics, operative, and functional outcomes were compared between ABOi-RAKT, ABOc-RAKT, and ABOi-OKT. Results: 29 RAKT, including 7 ABOi-RAKT, and 56 ABOi-OKT were performed in our center. Median follow-up was 2.0 years. Median recipient age, pre-emptive kidney transplantation rate, sex ratio and desensitization procedures were similar in ABOi-RAKT, ABOc-RAKT, and ABOi-OKT groups. Recipient BMI at transplantation was statistically higher in ABOi and ABOc-RAKT groups compared to ABOi-OKT. The surgical site complication (principally infection-related) rate was lower in ABOi-RAKT, without statistical differences (0 vs. 8.9%, respectively, in ABOi-RAKT and ABOi-OKT, p = 0.7). The delayed graft function rate was 0% in ABOi-RAKT, 13.6% in ABOc-RAKT, and 10.7% in ABOi-OKT (p = 0.6). The post-transplantation blood transfusion rate was statistically higher in the ABOi-OKT group (14.3 vs. 13.6 vs. 57.1% in ABOi-RAKT, ABOc-RAKT, and ABOi-OKT, respectively, p = 0.001). The kidney graft survival at 1 month and at last follow-up was not different between ABOi-RAKT and ABOi-OKT. Conclusion: Our data support the use of ABOi-RAKT to restore accessibility to kidney transplantation for obese patients to the greatest extent possible. Large series are required to confirm these encouraging data from a single center.

Prudhomme|Thomas|T|
Del Bello|Arnaud|A|
Sallusto|Federico|F|
Lesourd|Marine|M|
Kamar|Nassim|N|
Doumerc|Nicolas|N|

ABO-incompatible
robotic-assisted kidney transplantation
open kidney transplantation
delayed graft function
desensitization protocols


Concomitant Guillain-Barré Syndrome and Acute Transverse Myelitis in an Older Adult-A Case Report.

Abstract:
PURPOSE
Guillain-Barré syndrome concomitant with spinal cord involvement, which is defined as Guillain-Barré syndrome and acute transverse myelitis overlap syndrome, is rarely seen in the elders. Here we present a 68-year-old female patient who developed Guillain-Barré syndrome, as well as acute transverse myelitis at the same episode.

CASE REPORT
This patient developed acute weakness of lower limbs, which then rapidly became tetraplegia and hyporeflexia within 5 days. She also had impaired pinprick and vibration sensations below T4, as well as urinary and defecation incontinence. The nerve conduction studies revealed a motorsensory axonal neuropathy. Cerebrospinal fluid analysis showed albuminocytological dissociation and elevated IgG index. The spinal magnetic resonance imaging study revealed heterogeneously contrastenhanced, long-segmental intramedullary lesion from C2 to T3. Other laboratory findings, including blood anti-aquaporin 4 antibody, were not remarkable. The patient's tetraplegia was gradually improved by plasmapheresis and methylprednisolone pulse therapy.

CONCLUSION
Although Guillain-Barré syndrome and acute transverse myelitis overlap syndrome is occasionally seen in young adults, it could still occur in the elderly patients. Plasmapheresis and steroid pulse therapy could be beneficial to improve functional outcome of patients with this immunemediated neurological disease.

Wu|Ching-I|CI| Wu|Chia-Lun|CL| Chang|Kuo-Hsuan|KH| Huang|Wen-Yi|WY|

Acute transverse myelitis
Demyelinating disease
Guillain-Barré syndrome treatment.


Design, synthesis, and antiviral evaluation of novel piperidine-substituted arylpyrimidines as HIV-1 NNRTIs by exploring the hydrophobic channel of NNIBP.

Abstract: Herein, alkenylpiperidine and alkynylpiperidine moieties were introduced into the left wing of DAPYs (diarylpyrimidines) to explore the new site of the NNIBP (non-nucleoside inhibitor binding pocket) protein-solvent interface region via the structure-based drug design strategy. All the synthesized compounds displayed nanomolar to submicromolar activity against WT (wild-type) HIV-1. Among all, compound FT1 (EC50 = 19 nM) was found to be the most active molecule, which is better than NVP (EC50 = 0.10 μM). In addition, most of the compounds displayed micromolar activity against K103N and E138K mutant strains, while FT1 (EC50(K103N) = 50 nM, EC50(E138K) = 0.19 µM) still has the most effective activity. The molecular dynamics simulation studies revealed that the presence of pyridine moiety of FT1 was essential and played a significant role in its binding with RT (reverse transcriptase).

Zhang|Tao|T|
Zhou|Zhongxia|Z|
Zalloum|Waleed A|WA|
Wang|Zhao|Z|
Fu|Zhipeng|Z|
Cherukupalli|Srinivasulu|S|
Feng|Da|D|
Sun|Yanying|Y|
Gao|Shenghua|S|
De Clercq|Erik|E|
Pannecouque|Christophe|C|
Kang|Dongwei|D|
Zhan|Peng|P|
Liu|Xinyong|X|

HIV-1
NNRTIs
DAPYs
Structure-based drug design
Reverse transcriptase


Weight Loss Improves Pregnancy and Livebirth Outcomes in Young Women with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

Abstract:
Purpose
To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy.

Patients and Methods
Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors.

Results
Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63±12.03 and 67.08±8.18 kg, respectively, 27.06±4.44 and 25.73±3.15 kg/m2, respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00-34.50), and the median relative weight loss was 6.70% (1.00-36.00%) over a median of 12 months (5.00-97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, P=0.000; 64.00% vs 31.58%, P=0.033); weight loss ≥5% significantly increased pregnancy and live birth rate in patients with BMI ≥25 kg/m2. The risk ratio of weight loss ≥5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, P=0.041).

Conclusion
Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥5% increased pregnancy and livebirth rates significantly in overweight and obese women.

Zhang|Yanfang|Y| Li|Dan|D| Yan|Qi|Q| Song|Xueru|X| Tian|Wenyan|W| Wang|Yingmei|Y| Teng|Fei|F| Wei|Likun|L| Wang|Jinghua|J|0000-0003-2619-0570 Zhang|Huiying|H| Xue|Fengxia|F|

weight loss
endometrial cancer
atypical hyperplasia
reproductive outcomes
fertility-sparing therapy


Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase-dependent mechanism.

Abstract:
Background
Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1.

Methods
We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1.

Results
Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition.

Conclusion
Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

Hong|So-Hyeon|SH|
Hwang|Hwan-Jin|HJ|
Kim|Joo Won|JW|
Kim|Jung A|JA|
Lee|You Bin|YB|
Roh|Eun|E|
Choi|Kyung Mook|KM|
Baik|Sei Hyun|SH|
Yoo|Hye Jin|HJ|

Cardiomyocyte
Antioxidant
AMP-activated protein kinases


BMP4 acts as a dorsal telencephalic morphogen in a mouse embryonic stem cell culture system.

Abstract: The concept of a morphogen - a molecule that specifies two or more cell fates in a concentration-dependent manner - is paradigmatic in developmental biology. Much remains unknown, however, about the existence of morphogens in the developing vertebrate central nervous system (CNS), including the mouse dorsal telencephalic midline (DTM). Bone morphogenetic proteins (BMPs) are candidate DTM morphogens, and our previous work demonstrated BMP4 sufficiency to induce one DTM cell fate - that of choroid plexus epithelial cells (CPECs) - in a mouse embryonic stem cell (mESC) culture system. Here we used BMP4 in a modified mESC culture system to derive a second DTM fate, the cortical hem (CH). CH and CPEC markers were induced by BMP4 in a concentration-dependent manner consistent with in vivo development. BMP4 concentrations that led to CH fate also promoted markers for Cajal-Retzius neurons, which are known CH derivatives. Interestingly, single BMP4 administrations also sufficed for appropriate temporal regulation of CH, CPEC, and cortical genes, with initially broad and overlapping dose-response profiles that sharpened over time. BMP4 concentrations that yielded CH- or CPEC-enriched populations also had different steady-state levels of phospho-SMAD1/5/8, suggesting that differences in BMP signaling intensity underlie DTM fate choice. Surprisingly, inactivation of the cortical selector gene Lhx2 did not affect DTM expression levels, dose-response profiles, or timing in response to BMP4, although neural progenitor genes were downregulated. These data indicate that BMP4 can act as a classic morphogen to orchestrate both spatial and temporal aspects of DTM fate acquisition, and can do so in the absence of Lhx2.

Choroid plexus epithelial cell
Cortical hem
ES cell


Religious Relationships with the Environment in a Tibetan Rural Community: Interactions and Contrasts with Popular Notions of Indigenous Environmentalism.

Abstract: Representations of Green Tibetans connected to Buddhism and indigenous wisdom have been deployed by a variety of actors and persist in popular consciousness. Through interviews, participatory mapping and observation, we explored how these ideas relate to people's notions about the natural environment in a rural community on the Eastern Tibetan plateau, in Sichuan Province, China. We found people to be orienting themselves towards the environment by means of three interlinked religious notions: (1) local gods and spirits in the landscape, which have become the focus of conservation efforts in the form of 'sacred natural sites;' (2) sin and karma related to killing animals and plants; (3) Buddhist moral precepts especially non-violence. We highlight the gaps between externally generated representations and local understandings, but also the dynamic, contested and plural nature of local relationships with the environment, which have been influenced and reshaped by capitalist development and commodification of natural resources, state environmental policies, and Buddhist modernist ideas.

Woodhouse|Emily|E|
Mills|Martin A|MA|
McGowan|Philip J K|PJ|
Milner-Gulland|E J|EJ|

Buddhism
Tibetan Plateau
China
Conservation
Religion
Sacred sites


Reverse electron flow-mediated ROS generation in ischemia-damaged mitochondria: role of complex I inhibition vs. depolarization of inner mitochondrial membrane.

Abstract:
BACKGROUND
The reverse electron flow-induced ROS generation (RFIR) is decreased in ischemia-damaged mitochondria. Cardiac ischemia leads to decreased complex I activity and depolarized inner mitochondrial membrane potential (ΔΨ) that are two key factors to affect the RFIR in isolated mitochondria. We asked if a partial inhibition of complex I activity without alteration of the ΔΨ is able to decrease the RFIR.

METHODS
Cardiac mitochondria were isolated from mouse heart (C57BL/6) with and without ischemia. The rate of H2O2 production from mitochondria was determined using amplex red coupled with horseradish peroxidase. Mitochondria were isolated from the mitochondrial-targeted STAT3 overexpressing mouse (MLS-STAT3E) to clarify the role of partial complex I inhibition in RFIR production.

RESULTS
The RFIR was decreased in ischemia-damaged mouse heart mitochondria with decreased complex I activity and depolarized ΔΨ. However, the RFIR was not altered in the MLS-STAT3E heart mitochondria with complex I defect but without depolarization of the ΔΨ. A slight depolarization of the ΔΨ in wild type mitochondria completely eliminated the RFIR.

CONCLUSIONS
The mild uncoupling but not the partially decreased complex I activity contributes to the observed decrease in RFIR in ischemia-damaged mitochondria.

GENERAL SIGNIFICANCE
The RFIR is less likely to be a key source of cardiac injury during reperfusion.

Ross|Thomas|T|
Szczepanek|Karol|K|
Bowler|Elizabeth|E|
Hu|Ying|Y|
Larner|Andrew|A|
Lesnefsky|Edward J|EJ|
Chen|Qun|Q|

D000818:Animals
D004579:Electron Transport
D042967:Electron Transport Complex I
D006861:Hydrogen Peroxide
D051379:Mice
D008810:Mice, Inbred C57BL
D008929:Mitochondria, Heart
D017202:Myocardial Ischemia
D017382:Reactive Oxygen Species

Ischemia
STAT3
Electron transport chain
Reactive oxygen species


Conventional Radiology in Spondyloarthritis.

Abstract: Spondyloarthritides are of a group of inflammatory rheumatic diseases, with negative rheumatoid factor, associated with the HLA-B27 gene. They comprise ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic-related spondylitis. The presence of sacroiliitis represents the most characteristic feature of these disorders and is an important criterion in diagnosis. Nonradiographic axial spondyloarthritis is a new classification concept. Conventional radiography is recommended as the first imaging method to diagnose sacroiliitis and different entities and to monitor established structural changes.

Bazzocchi|Alberto|A|
Aparisi Gómez|Maria Pilar|MP|
Guglielmi|Giuseppe|G|

Ankylosing
Spondylitis
Psoriatic
Arthritis
Reactive
Radiography
Diagnostic imaging
Spondylarthritis


A modified standardized nine hole peg test for valid and reliable kinematic assessment of dexterity post-stroke.

Abstract:
BACKGROUND
Impairments in dexterity after stroke are commonly assessed by the Nine Hole Peg Test (NHPT), where the only outcome variable is the time taken to complete the test. We aimed to kinematically quantify and to compare the motor performance of the NHPT in persons post-stroke and controls (discriminant validity), to compare kinematics to clinical assessments of upper extremity function (convergent validity), and to establish the within-session reliability.

METHODS
The NHPT was modified and standardized (S-NHPT) by 1) replacing the original peg container with an additional identical nine hole pegboard, 2) adding a specific order of which peg to pick, and 3) specifying to insert the peg taken from the original pegboard into the corresponding hole of the target pegboard. Eight optical cameras registered upper body kinematics of 30 persons post-stroke and 41 controls during the S-NHPT. Four sequential phases of the task were identified and analyzed for kinematic group differences. Clinical assessments were performed.

RESULTS
The stroke group performed the S-NHPT slower (total movement time; mean diff 9.8 s, SE diff 1.4), less smoothly (number of movement units; mean diff 0.4, SE diff 0.1) and less efficiently (path ratio; mean diff 0.05, SE diff 0.02), and used increased scapular/trunk movements (acromion displacement; mean diff 15.7 mm, SE diff 3.5) than controls (P < 0.000, r ≥ 0.32), indicating discriminant validity. The stroke group also spent a significantly longer time grasping and releasing pegs relative to the transfer phases of the task compared to controls. Within the stroke group, kinematics correlated with time to complete the S-NHPT and the Fugl-Meyer Assessment (rs 0.38-0.70), suggesting convergent validity. Within-session reliability for the S-NHPT was generally high to very high for both groups (ICCs 0.71-0.94).

CONCLUSIONS
The S-NHPT shows adequate discriminant validity, convergent validity and within-session reliability. Standardization of the test facilitates kinematic analysis of movement performance, which in turn enables identification of differences in movement control between persons post-stroke and controls that may otherwise not be captured through the traditional time-based NHPT. Future research should ascertain further psychometric properties, e.g. sensitivity, of the S-NHPT.

Johansson|Gudrun M|GM|
Häger|Charlotte K|CK|

Stroke
Upper extremity
Clinical laboratory techniques
Outcome assessment


Pre-Competition Weight Loss Models in Taekwondo: Identification, Characteristics and Risk of Dehydration.

Abstract: Athletes use different combinations of weight loss methods during competition preparation. The aim of this study was to identify and characterize pre-competition weight loss models, which describe these combinations. The second aim was to determine if any existing model pose a higher risk of severe dehydration and whether any of the models could be continued as a lower-risk option. The third aim was to explore whether athletes who used different weight management strategies could be differentiated based on age, sex, training experience or anthropometric parameters. Study participants were randomly selected from Olympic taekwondo competitors and 192 athletes were enrolled. Active (47% weight-reducing athletes), passive (31%) and extreme (22%) models have been described. In the extreme model, athletes combined the highest number of different weight loss methods (3.9 ± 0.9 methods vs. 2.4 ± 0.9 in active and 1.5 ± 0.6 in passive), reduced significantly more body mass than others (6.7 ± 3.5% body mass vs. 4.3 ± 1.9% and 4.5 ± 2.4%; p < 0.01) and all of them used methods with the highest risk of severe dehydration. The active and passive models could be continued as a lower-risk option, if athletes do not combine dehydrating methods and do not prolong the low energy availability phase. The extreme model carried the highest risk of severe dehydration. Every fifth weight-reducing taekwondo athlete may have been exposed to the adverse effects of acute weight loss. Taekwondo athletes, regardless of age, sex, training experience and anthropometric parameters, lose weight before the competition and those characteristics do not differentiate them between models.

weight loss
dehydration
body weight
body weight changes
cluster analysis
combat sports
martial arts
young adult


Unexpected Infection with Armillifer Parasites.

Abstract: Visceral pentastomiasis is usually found incidentally during surgery. We describe a case of visceral pentastomiasis discovered during inguinoscrotal hernia surgery for a man from Benin, Africa. Because surgical removal of nymphs is needed for symptomatic patients only, this patient's asymptomatic pentastomiasis was not treated and he recovered from surgery uneventfully.

Potters|Idzi|I|
Desaive|Claude|C|
Van Den Broucke|Steven|S|
Van Esbroeck|Marjan|M|
Lynen|Lutgarde|L|

Armillifer parasites surgery Africa pentastomida snakes