Quality of antenatal care as a risk factor for early onset neonatal infections in Rio de Janeiro, Brazil.

Abstract:
BACKGROUND
Neonatal infection is a serious public health problem. The aim of this study was to assess the influence of the antenatal care on the risk of early-onset neonatal healthcare associated infection in two Brazilian maternities.

METHODS
Cohort study - Newborns admitted at two public neonatal intensive care units from 2008 to 2009 were included in the study. Data on antenatal and perinatal variables were collected from maternal prenatal cards and medical charts. Newborns were actively surveyed for early-onset neonatal healthcare associated infection, defined as a neonatal infection diagnosed within 48h after birth. Multiple logistic regression was used to assess variables independently associated with early-onset neonatal healthcare associated infection.

RESULTS
561 neonate-mother pairs were included in the study. Early-onset neonatal healthcare associated infection was diagnosed in 283 neonates (51%), an incidence rate of 43.5/1000 live births. Neonates whose mothers had less then six antenatal visits were under risk significantly higher for early-onset neonatal healthcare associated infection (OR=1.69, 95% CI=1.11-2.57), after adjusting for birth weight, membranes ruptured for >18h, maternal complications during delivery, maternal infection at admission, and hospital where patients received care.

CONCLUSIONS
The risk of neonatal early-onset neonatal healthcare associated infection was significantly associated with insufficient number of antenatal care visits. Further studies assessing the quality of antenatal care and targeting its improvement are warranted.

Mizumoto|B R|BR|
Moreira|B M|BM|
Santoro-Lopes|G|G|
Cunha|A J|AJ|
Santos|R M R dos|RM|
Pessoa-Silva|C L|CL|
Pinheiro|Azeredo A N|AA|
Ferreira|M|M|
Leobons|M B|MB|
Hofer|Cristina Barroso|CB|

D018445:Infectious Disease Transmission, Vertical

Early-onset healthcare associated infections


The Diphosphorus Complex [Cp2Mo2(CO)4(η2-P2)] as a Building Block for the Synthesis of Mixed-Hybrid Coordination Polymers.

Abstract: The three-component reaction of the tetrahedral diphosphorus complex [Cp2Mo2(CO)4(η2-P2)] (1), with Ag[BF4] (2) in the presence of 2,2'-bipyrimidine (3) leads to the formation of the two novel two-dimensional networks 4 and 5. Compound 4 is a new two-dimensional organometallic-organic hybrid polymer, while derivative 5 represents a unique two-dimensional organometallic-inorganic-organic hybrid polymer. These results show the possibility of synthesizing a new class of coordination polymers, which could not be obtained from two-component reactions with organic molecules in addition of metal ions.

Moussa|Mehdi Elsayed|ME|
Attenberger|Bianca|B|
Fleischmann|Martin|M|
Schreiner|Andrea|A|
Scheer|Manfred|M|0000-0003-2182-5020

Hybrid polymers
2,2′‐Bipyrimidine
Molybdenum
Phosphorus
Self‐assembly


Effects of NSAIDs and paracetamol (acetaminophen) on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons.

Abstract: Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs) very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen), a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP) release, prostaglandin E(2) (PGE(2)) release, and protein kinase C epsilon (PKCɛ) translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs). The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously). While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKCɛ caused by 100 nM thrombin or 1 μM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS) containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the increased levels expressed during treatment with the IS were significantly reduced by all drugs tested, with the exception of ibuprofen. All drugs were able to decrease basal and IS-stimulated PGE(2) release. Our study demonstrates novel mechanisms of action of commonly used NSAIDS.

Vellani|Vittorio|V| Franchi|Silvia|S| Prandini|Massimiliano|M| Moretti|Sarah|S| Castelli|Mara|M| Giacomoni|Chiara|C| Sacerdote|Paola|P|

celecoxib
diclofenac
ibuprofen
nimesulide
PKCɛ
dorsal root ganglia
analgesia
nociceptors


"On Water" Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole.

Abstract: The C3 direct arylation of 1H-indazole and 1H-7-azaindazole has been a significant challenge due to the lack of the reactivity at this position. In this paper, we describe a mild and an efficient synthesis of new series of C3-aryled 1H-indazoles and C3-aryled 1H-7-azaindazoles via a C3 direct arylation using water as solvent. On water, PPh3 was effective as a ligand along with a lower charge of the catalyst Pd(OAc)2 (5 mol%) at 100 °C, leading to C3-aryled 1H-indazoles or C3-aryled 1H-7-azaindazoles in moderate to good yields.

Gambouz|Khadija|K|
El Abbouchi|Abdelmoula|A|
Nassiri|Sarah|S|
Suzenet|Franck|F|
Bousmina|Mostapha|M|
Akssira|Mohamed|M|
Guillaumet|Gérald|G|
El Kazzouli|Saïd|S|0000-0001-5021-3571

arylation
C–H functionalization
azaindazole
green chemistry
indazole
water.


Characterization of burning mouth syndrome profiles based on response to a local anaesthetic lozenge.

Abstract:
OBJECTIVE
Burning mouth syndrome (BMS) is a chronic oral pain condition with unknown aetiology but assumed to involve peripheral/central neuropathological and immune-mediated inflammatory factors. We aimed at characterizing inflammatory and neurogenic profiles and oral symptomatology of patients with BMS based on response to a local anaesthetic lozenge.

METHODS
Patients with BMS were divided into an Effect (n = 13), No effect (n = 8) or Unspecified (n = 2) group according to their response to a local anaesthetic lozenge on oral pain. Inflammation was assessed in blood plasma and saliva by analyses of IL-6, IL-8, IL-17A, IL-23 and TNF-α levels. The degree of inflammation and distribution of oestrogen receptor, NGF, NGF-receptor, TRPV-1 and IL-17F in buccal mucosal tissue were investigated by immunohistochemistry.

RESULTS
Immunoreactivity to the oestrogen receptor was most intense in the Effect group, whereas the No effect group tended to have higher plasma levels of the pro-inflammatory cytokines.

CONCLUSIONS
Our findings indicate that the response to treatment with local anaesthesia enables subgrouping of patients with BMS according to the potential pathogenic mechanisms. Effect of local anaesthesia indicates a peripheral neuropathology involving lack of oestrogen and upregulation of oestrogen receptors, and no effect indicates a systemic inflammation-induced mechanism leading to increased levels of plasma cytokines.

burning mouth syndrome
local anaesthetic lozenge
oestrogen receptor
cytokines


Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia.

Abstract: A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia-reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.

Liu|Yun|Y| Wang|Mengxue|M| Liang|Yin|Y| Wang|Chen|C| Naruse|Keiji|K| Takahashi|Ken|K|0000-0002-7580-8691

D000818:Animals
D002986:Clinical Trials as Topic
D003327:Coronary Disease
D004195:Disease Models, Animal
D004337:Drug Carriers
D055354:Exosomes
D005786:Gene Expression Regulation
D006801:Humans
D035683:MicroRNAs
D015428:Myocardial Reperfusion Injury
D018384:Oxidative Stress
D017382:Reactive Oxygen Species
D016896:Treatment Outcome

oxidative stress
exosome
myocardial infarction
coronary heart disease
exosome therapy
reactive oxygen radicals


The Effect of Moment of Inertia on the Liquids in Centrifugal Microfluidics.

Abstract: The flow of liquids in centrifugal microfluidics is unidirectional and dominated by centrifugal and Coriolis forces (i.e., effective only at T-junctions). Developing mechanisms and discovering efficient techniques to propel liquids in any direction other than the direction of the centrifugal force has been the subject of a large number of studies. The capillary force attained by specific surface treatments, pneumatic energy, active and passive flow reciprocation and Euler force have been previously introduced in order to manipulate the liquid flow and push it against the centrifugal force. Here, as a new method, the moment of inertia of the liquid inside a chamber in a centrifugal microfluidic platform is employed to manipulate the flow and propel the liquid passively towards the disc center. Furthermore, the effect of the moment of inertia on the liquid in a rectangular chamber is evaluated, both in theory and experiments, and the optimum geometry is defined. As an application of the introduced method, the moment of inertia of the liquid is used in order to mix two different dyed deionized (DI) waters; the mixing efficiency is evaluated and compared to similar mixing techniques. The results show the potential of the presented method for pumping liquids radially inward with relatively high flow rates (up to 23 mm³/s) and also efficient mixing in centrifugal microfluidic platforms.

Pishbin|Esmail|E| Eghbal|Manouchehr|M| Fakhari|Sepideh|S| Kazemzadeh|Amin|A| Navidbakhsh|Mehdi|M|

inertia microfluidics disc mixing pump lab-on-a-chip


Asymmetric peptidomimetics containing L-tartaric acid core inhibit the aspartyl peptidase activity and growth of Leishmania amazonensis promastigotes.

Abstract: Aspartyl-type peptidases are promising chemotherapeutic targets in protozoan parasites. In the present work, we identified an aspartyl peptidase activity from the soluble extract of Leishmania amazonensis promastigotes, which cleaved the fluorogenic peptide 7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D-Arg-amide (cathepsin D substrate) under acidic pH conditions at 37°C, showing a KM of 0.58 μM and Vmax of 129.87 fluorescence arbitrary units/s mg protein. The leishmanial aspartyl peptidase activity was blocked by pepstatin A (IC50 = 6.8 μM) and diazo-acetyl-norleucinemetilester (IC50 = 10.2 μM), two classical aspartyl peptidase inhibitors. Subsequently, the effects of 6 asymmetric peptidomimetics, containing L-tartaric acid core, were tested on both aspartyl peptidase and growth of L. amazonensis promastigotes. The peptidomimetics named 88, 154 and 158 promoted a reduction of 50% on the leishmanial aspartyl peptidase activity at concentrations ranging from 40 to 85 μM, whereas the peptidomimetic 157 was by far the most effective, presenting IC50 of 0.04 μM. Furthermore, the peptidomimetics 157 and 154 reduced the parasite proliferation in a dose-dependent manner, displaying IC50 values of 33.7 and 44.5 μM, respectively. Collectively, the peptidomimetic 157 was the most efficient compound able to arrest both aspartyl peptidase activity and leishmanial proliferation, which raises excellent perspectives regarding its use against this human pathogenic protozoan.

Santos|André L S|ALS|
Matteoli|Filipe P|FP|
Sangenito|Leandro S|LS|
Branquinha|Marta H|MH|
Cotrim|Bruno A|BA|
Resende|Gabriel O|GO|

peptidomimetics
L-tartaric acid
aspartyl peptidases
Leishmania amazonensis
aspartyl peptidase inhibitors
anti-Leishmania action


The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID-19?

Abstract: Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in order to replicate. Thus, repurposing drugs that have initially been developed to target growth factor receptors and their signaling in cancer may prove to be a fast track to effective therapies against emerging new viral infections, including the coronavirus disease 19 (COVID-19).

Hondermarck|Hubert|H|
Bartlett|Nathan W|NW|
Nurcombe|Victor|V|

growth factors
tyrosine kinase
COVID‐19
SARS‐CoV‐2
cancer drugs
heparan sulfate
heparin
inhibitors
virus


Rare Lesions of the Internal Auditory Canal.

Abstract:
BACKGROUND
Approximately 95% of tumors occurring within the internal auditory canal (IAC) are vestibular schwannomas. Many undergo stereotactic radiation without definitive tissue diagnosis. Rare IAC tumors are not all radiosensitive and are poorly described.

METHODS
Between 1992 and 2015, 289 consecutive patients with IAC lesions operated on were reviewed retrospectively.

RESULTS
Fifteen patients (5.2%) (16 operations) had unusual histologic findings, including nonvestibular schwannomas (2 facial schwannomas, 2 cochlear schwannomas, 2 intermedius schwannomas), 3 meningiomas, 3 cavernous hemangiomas, a mucosa-associated lymphoid tissue lymphoma, an arachnoid cyst, and a lipochoristoma. None of these rare tumors could be identified before surgery. Three operative approaches were used: the retrosigmoid approach, middle fossa subtemporal approach, or translabyrinthine approach. Few complications occurred, including facial nerve palsy, loss of hearing, and vestibular function. Five-year average follow-up revealed one patient with recurrence.

CONCLUSIONS
Clinical examination and imaging alone were insufficient to correctly identify these tumors. Definitive pathologicdiagnosis should be strongly considered to help tailor treatment.

Watanabe|Kentaro|K|
Cobb|Mary In-Ping Huang|MIH|
Zomorodi|Ali R|AR|
Cunningham|Calhoun D|CD|
Nonaka|Yoichi|Y|
Satoh|Shunsuke|S|
Friedman|Allan H|AH|
Fukushima|Takanori|T|

Mucosa-associated lymphoid tissue (MALT) lymphoma


Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.

Abstract:
BACKGROUND
Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS).

OBJECTIVE
Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment.

METHODS
This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed.

RESULTS
A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE-suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed.

CONCLUSION
ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.

Cohen|Jeffrey A|JA|
Hunter|Samuel F|SF|
Brown|Theodore R|TR|
Gudesblatt|Mark|M|
Thrower|Ben W|BW|
Llorens|Lily|L|
Souza-Prien|Cindy J|CJ|
Ruby|April E|AE|
Chernoff|David N|DN|
Patni|Rajiv|R|

ADS-5102
amantadine
walking
Multiple sclerosis
walking impairment
MS
walking speed


Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients.

Abstract:
BACKGROUND AND PURPOSE
Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation.

METHODS
A chart review was carried out by a multi-professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010.

RESULTS
In all, 955 patients had follow-up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non-existent and do-not-resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm(3) (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012.

CONCLUSIONS
A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end-of-life care.

Sairanen|T|T| Koivisto|A|A| Koivusalo|A-M|AM| Rantanen|K|K| Mustanoja|S|S| Meretoja|A|A| Putaala|J|J| Strbian|D|D| Kaste|M|M| Isoniemi|H|H| Tatlisumak|T|T|

intracerebral hemorrhage
organ donor
acute cerebral hemorrhage
emergency treatment of stroke
transplantation


Knowledge of Cervical Cancer and Human Papillomavirus among Japanese Women.

Abstract:
BACKGROUND
The combination of human papillomavirus (HPV) vaccination and cervical cancer tests are globally recommended. Although knowledge regarding cervical cancer and HPV and experience of HPV vaccination are reportedly closely associated, the associations between knowledge and frequency of cervical cancer testing are unclear.

METHODS
We conducted a questionnaire survey regarding the knowledge of cervical cancer and HPV and experience of HPV vaccination and frequency of cervical cancer testing including cervical cytology and HPV testing.

RESULTS
Among 99 women who visited Tsuruha Festa, most of the 77 non-medical workers who received information on cervical cancer and HPV through the Internet were not more likely to have knowledge about cervical cancer and HPV than were 12 medical workers who had gotten information in vocational school or university curriculum. The rates of HPV vaccination, cervical cytology, and HPV testing were 4.0%, 14.1%, and 4.0%, respectively, among participants and did not differ significantly according to participant job and age. Knowledge about cervical cancer and HPV was associated with experience of HPV vaccination and frequency of cervical cytology and was not associated with frequency of HPV testing.

CONCLUSIONS
We observed insufficient knowledge about cervical cancer and HPV among non-medical workers as well as low HPV vaccination, cervical cytology, and HPV testing rates, and knowledge about cervical cancer and HPV to which frequency of cervical cancer testing were partially related. Therefore, the government should take measures to enhance public awareness about cervical cancer and HPV through social media such as the Internet.<br />.

Nakao|Yuki|Y|
Sasaki|A I|AI|
Obara|Taku|T|
Abe|Shinya|S|
Furusaki|Kaori|K|
Higaki|Mari|M|
Yoshimachi|Shouko|S|
Gotou|Teruaki|T|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

Knowledge
Cervical cancer
human papillomavirus
cervical cancer test
human papillomavirus vaccine


Bioinformatic analyses revealed underlying biological functions correlated with oxaliplatin responsiveness.

Abstract: Colorectal cancer is one of the most common cancers worldwide. Surgery is usually the primary treatment for colon cancers that have not spread to distant sites. However, chemotherapy may be considered after surgery to eliminate remaining cancer cells or in case the cancer has a high risk of recurrence. Oxaliplatin is often used in combination regimens such as FOLFOX, CapeOX, and FOLFOXIRI because of the cost-effectiveness of adjuvant treatment for patients and also the good tolerability profile. However, some patients show resistance to oxaliplatin which causes poor treatment outcomes. Most colon cancer studies focused on treatments and patient survival. Some studies focused on genetic associations of specific genes. However, pathway and network analyses of oxaliplatin resistance in colon cancer cells using gene expression patterns are still lacking. We performed a microarray analysis and found that endothelin-1 (EDN1), dishevelled segment polarity protein (DV1), toll-like receptor 5(TLR5), mitogen-activated protein kinase 3 (MAP2K3), phosphatidylinositol-4,5-bisphosphate 3-kinase, and catalytic subunit beta (PIK3CB) were closely related to responsiveness to oxaliplatin treatment. Furthermore, we found that the signal transduction, melanogenesis, and toll-like receptor signaling pathways might be involved in oxaliplatin-resistant colon cancer. These genes and pathways might be potential targets for improving oxaliplatin treatment in colon cancer patients.

Klahan|Sukhontip|S|
Huang|Chi-Cheng|CC|
Chien|Shu-Chen|SC|
Wu|Mei-Shin|MS|
Wong|Henry Sung-Ching|HS|
Huang|Chien-Yu|CY|
Chang|Wei-Chiao|WC|
Wei|Po-Li|PL|

D015972:Gene Expression Regulation, Neoplastic

Oxaliplatin
Colon cancer
Bioinformatic analysis
Network and pathway analysis


Government health expenditure, out-of-pocket payment and social inequality: A cross-national analysis of China and OECD countries.

Abstract: This study aims to assess the association between Chinese out-of-pocket payments and government health spending, investigating their variation ratio in the context of OECD countries. Aggregated time-series data of 37 countries (from China and official OECD members) were collected from the World Bank Open Data source and analyzed using the multiple linear regression models. Benchmarking approach was applied to evaluate the causes of healthcare expenditure rise per capita. The results showed that China's government health expenditure was positively associated with out-of-pocket payment rise, with a higher variation score of 42.70%. The association was statistically significant at 5%. Likewise, the association between government expenditure and out-of-pocket payment in the OECD countries was positively significant at 1%, and their variation score was 2.41%. Health financing in OECD countries showed higher stability and equity than that in China. Policy implications for China is to reduce the distributional disparity of government health funds by tax adjustments in health services, universal health coverage, the removal of social health insurance disparities, and a single health payment method.

D066150:Organisation for Economic Co-Operation and Development

government health expenditure
out-of-pocket payment
social inequality
China
OECD members


Plant virus directed fabrication of nanoscale materials and devices.

Abstract: Bottom-up self-assembly methods in which individual molecular components self-organize to form functional nanoscale patterns are of long-standing interest in the field of materials sciences. Such self-assembly processes are the hallmark of biology where complex macromolecules with defined functions assemble from smaller molecular components. In particular, plant virus-derived nanoparticles (PVNs) have drawn considerable attention for their unique self-assembly architectures and functionalities that can be harnessed to produce new materials for industrial and biomedical applications. In particular, PVNs provide simple systems to model and assemble nanoscale particles of uniform size and shape that can be modified through molecularly defined chemical and genetic alterations. Furthermore, PVNs bring the added potential to "farm" such bio-nanomaterials on an industrial scale, providing a renewable and environmentally sustainable means for the production of nano-materials. This review outlines the fabrication and application of several PVNs for a range of uses that include energy storage, catalysis, and threat detection.

Culver|James N|JN|
Brown|Adam D|AD|
Zang|Faheng|F|
Gnerlich|Markus|M|
Gerasopoulos|Konstantinos|K|
Ghodssi|Reza|R|

Bio-materials
Nanotechnology
Virus assembly
Virus particles
Virus-like particles


Re-exposure to immunotherapy in metastatic colon cancer: A case report.

Abstract: Re-exposure to immunotherapy in metastatic colorectal cancer may be indicated in selected patients that previously benefitted from immunotherapy with tolerable irAEs.

immunotherapy
colon cancer
microsatellite instability


Conversion of mesenchymal stem cells into a canine hepatocyte-like cells by Foxa1 and Hnf4a.

Abstract:
Introduction
Hepatocytes, which account for the majority of liver tissue, are derived from the endoderm and become hepatocytes via differentiation of hepatic progenitor cells. Induced hepatocyte-like (iHep) cells and artificial liver tissues are expected to become useful, efficient therapies for severe and refractory liver diseases and to contribute to drug discovery research. The establishment of iHep cell lines are needed to carry out liver transplants and assess liver toxicity in the rising number of dogs affected by liver disease. Recently, direct conversion of non-hepatocyte cells into iHep cells was achieved by transfecting mouse adult fibroblasts with the Forkhead box protein A1 (Foxa1) and hepatocyte nuclear factor 4 homeobox alpha (Hnf4α) genes. Here, we applied this conversion process for the differentiation of canine bone marrow stem cells (cBMSCs) into hepatocyte-like cells.

Methods
Bone marrow specimens were collected from four healthy Beagle dogs and used to culture cBMSCs in Dulbecco's Modified Eagle's Medium (DMEM). The cBMSCs displayed the following characteristic features: plastic adherence; differentiation into adipocytes, osteoblasts and chondrocytes; and a cell surface antigen profile of CD29 (+), CD44 (+), CD90 (+), CD45 (-), CD34 (-) and CD14 (-), or CD11b (-) and CD79a (-), or CD19 (-) and HLA class II(-). The cBMSCs were seeded in a collagen I-coated plate and cultured in DMEM with 10% fetal bovine serum and transfected with retroviruses expressing Foxa1 and Hnf4α the following day. Canine iHep cells were differentiated from cBMSCs in culture on day 10, and were analyzed for morphology, RNA expression, immunocytochemistry, urea production, and low-density lipoprotein (LDL) metabolism.

Results
The cBMSCs expressed CD29 (98.06 ± 1.14%), CD44 (99.59 ± 0.27%) and CD90 (92.78 ± 4.89%), but did not express CD14 (0.47 ± 0.29%), CD19 (0.44 ± 0.39%), CD34 (0.33 ± 0.25%), CD45 (0.46 ± 0.34%) or MHC class II (0.54 ± 0.40%). The iHep cells exhibited morphology that included circular to equilateral circular shapes, and the formation of colonies that adhered to each other 10 days after Foxa1 and Hnf4α transfection. Quantitative RT-PCR analysis showed that the expression levels of the genes encoding albumin (ALB) and cadherin (CDH) in iHep cells on day 10 were increased approximately 100- and 10,000-fold, respectively, compared with cBMSCs. Corresponding protein expression of ALB and epithelial-CDH was confirmed by immunocytochemistry. Important hepatic functions, including LDL metabolic ability and urea production, were increased in iHep cells on day 10.

Conclusion
We successfully induced cBMSCs to differentiate into functional iHep cells. To our knowledge, this is the first report of canine liver tissue differentiation using Foxa1 and Hnf4α gene transfection. Canine iHep cells are expected to provide insights for the construction of liver models for drug discovery research and may serve as potential therapeutics for canine liver disease.

Nitta|Suguru|S| Kusakari|Yuto|Y| Yamada|Yoko|Y| Kubo|Takeaki|T| Neo|Sakurako|S| Igarashi|Hirotaka|H| Hisasue|Masaharu|M|

Conversion
Mesenchymal stem cells
hepatocyte
Differentiation
Dog
Bone marrow


Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants.

Abstract:
BACKGROUND
Language plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual's social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the linguistic overlaps across these disorders; investigations into their genetic overlaps are limited. The aim of this study was to assess the potential genetic overlap between language impairment and broader behavioral disorders employing methods capturing both common and rare genetic variants.

METHODS
We employ polygenic risk scores (PRS) trained on specific language impairment (SLI) to evaluate genetic overlap across several disorders in a large case-cohort sample comprising ~13,000 autism spectrum disorder (ASD) cases, including cases of childhood autism and Asperger's syndrome, ~15,000 attention deficit/hyperactivity disorder (ADHD) cases, ~3000 schizophrenia cases, and ~21,000 population controls. We also examine rare variants in SLI/language-related genes in a subset of the sample that was exome-sequenced using the SKAT-O method.

RESULTS
We find that there is little evidence for genetic overlap between SLI and ADHD, schizophrenia, and ASD, the latter being in line with results of linguistic analyses in past studies. However, we observe a small, significant genetic overlap between SLI and childhood autism specifically, which we do not observe for SLI and Asperger's syndrome. Moreover, we observe that childhood autism cases have significantly higher SLI-trained PRS compared to Asperger's syndrome cases; these results correspond well to the linguistic profiles of both disorders. Our rare variant analyses provide suggestive evidence of association for specific genes with ASD, childhood autism, and schizophrenia.

CONCLUSIONS
Our study provides, for the first time, to our knowledge, genetic evidence for ASD subtypes based on risk variants for language impairment.


Nucleic acid-targeted pathogen reduction technique in red blood cells by UV-generated oxygen radicals for optimising recipient safety.

Abstract:
OBJECTIVES
A novel pathogen reduction technique based on vacuum ultraviolet (VUV) irradiation was developed to reduce pathogen numbers in red blood cell (RBC) components.

BACKGROUND
Contaminated blood components pose a great risk of infection in blood recipients. The continuous development of blood screening techniques and pathogen inactivating systems has significantly reduced this risk, but many limitations remain.

METHODS
Escherichia coli and Bacillus cereus, and bacteriophage (BP) and Lentivirus (LV) were spiked into suspended red blood cells (sRBCs) or plasma. VUV light with maximum emission at 185 nm and an average dosage of 164 μW/cm2 was placed 5 cm above the targeted products to reduce the pathogen numbers.

RESULTS
Treatment for 5 minutes was effective; 3 and 10 log reductions of E coli counts were observed in sRBCs and plasma, and 2 and 3 log reductions of B cereus counts were observed in sRBCs and plasma, respectively. The BP titre was reduced by two and five log points in sRBCs and plasma, respectively; the LV titre was reduced by at least three log points in both sRBCs and plasma. VUV-based irradiation of RBCs does not cause significant structural and functional harmful effects. This novel strategy provides moderate photonic energy to generate oxygen radicals from H2 O and O2 and to selectively decrease DNA integrity of the potential pathogens.

CONCLUSION
The VUV-based pathogen reduction technique is a simple and fast procedure with high pathogen reduction efficacy, low toxicity and limited adverse effects on cellular blood products.

pathogen reduction
red blood cell
oxygen radical
vacuum ultraviolet
blood products
blood transfusion


Controlling the viscosities of antibody solutions through control of their binding sites.

Abstract: For biotechnological drugs, it is desirable to formulate antibody solutions with low viscosities. We go beyond previous colloid theories in treating protein-protein self-association of molecules that are antibody-shaped and flexible and have spatially specific binding sites. We consider interactions either through fragment antigen (Fab-Fab) or fragment crystalizable (Fab-Fc) binding. Wertheim's theory is adapted to compute the cluster-size distributions, viscosities, second virial coefficients, and Huggins coefficients, as functions of antibody concentration. We find that the aggregation properties of concentrated solutions can be anticipated from simpler-to-measure dilute solutions. A principal finding is that aggregation is controllable, in principle, through modifying the antibody itself, and not just the solution it is dissolved in. In particular: (i) monospecific antibodies having two identical Fab arms can form linear chains with intermediate viscosities. (ii) Bispecific antibodies having different Fab arms can, in some cases, only dimerize, having low viscosities. (iii) Arm-to-Fc binding allows for three binding partners, leading to networks and high viscosities.

Kastelic|Miha|M|
Dill|Ken A|KA|
Kalyuzhnyi|Yura V|YV|
Vlachy|Vojko|V|

antibodies
Wertheim's theory
aggregation
solution viscosity


Iron absorption from beans with different contents of iron, evaluated by stable isotopes.

Abstract:
BACKGROUND
The introduction of biofortified foods such as beans with higher iron content may be a useful tool in preventing iron deficiency. The biofortification aims to reach the root of the problem of malnutrition, targets the neediest population, uses embedded distribution mechanisms, is scientifically feasible and effective in terms of cost, and complements other ongoing interventions to control micronutrient deficiency. However, to ensure effectiveness, measurement of the absorption of minerals is essential.

OBJECTIVE
The objective of this study was to evaluate the iron bioavailability of common bean BRS Pontal (PO), targeted for biofortification, compared with common bean BRS Estilo in man through reliable techniques that have not been previously used in Brazil.

METHODS
The study included 29 young adult volunteers divided into 2 groups: Group CB (13 subjects) received 100 g of common beans (BRS-Estilo) cooked labeled with iron-58 (58Fe) and Group TBB (16 patients) received 100 g common bean target for iron biofortification (BRS-Pontal), cooked and labeled with iron58 (58Fe). The next day they received the reference dose of ferrous sulfate enriched iron-57 (57Fe). Isotopic evaluation of iron for measurement of iron incorporation into erythrocytes was performed 14 days after consumption. The beans used, were produced, through conventional breeding program, by EMBRAPA/Rice and Beans.

RESULTS
The iron absorption was evaluated by assessing the isotopic enrichment of the stable isotope. Mean iron absorption from the meal with common beans was 0.409% (±0.040%) and mean iron incorporation from the meal with target beans for biofortification 0.407% (±0.038%) and did not differ between the groups.

CONCLUSIONS
This study tested the iron absorption from a single bean meal in healthy volunteers or non anemics, In the present study the iron absorption ratio from common bean Pontal (PO), targeted for biofortification and compared with common bean BRS Estilo was not significantly different. The iron concentration of the TBB, probably was not sufficient to improve higher bioavailability. It is recommended to evaluate the not only the absorption of iron in cultivars that present a higher difference in iron concentration but also in association with other components of the Brazilian diet, such as rice and beans.

Iron absorption
Beans
Stable isotopes
Iron deficiency
Biofortification
Bioavailability
Anemia


Ongoing pharmacovigilance on vaccines.

Abstract: Vaccines have peculiar characteristics as well as their surveillance. Specific requirements, needs and challenges for the vaccine vigilance are discussed in the perspective to improve the whole system in order to guarantee a safer vaccine use and the keeping of the public confidence in vaccinations. Key elements for the routine safety monitoring, new regulations and some available tools are taken into account. Finally, the Italian experience is shortly described.

Pharmacovigilance
Vaccines
Vaccine vigilance
Safety monitoring
AEFI
Vaccine surveillance


Spatial distributive effects of public green space and COVID-19 infection in London.

Abstract: While public green spaces (PGS) are opined to be central in the pandemic recovery, higher accessibility to PGS also mean a higher risk of infection spread from the raised possibility of people encountering each other. This study explores the distributive effects of accessibility of PGS on the COVID-19 cases distribution using a geo-spatially varying network-based risk model at the borough level in London. The coupled effect of social deprivation with accessibility of the PGS was used as an adjustment factor to identify vulnerability. Results indicate that highly connected green spaces with high choice measure were associated with high risk of infection transmission. Socially deprived areas demonstrated higher possibility of infection spread even with moderate connectivity of the PGS. The study demonstrated that only applying a uniform social distancing measure without characterising the infrastructure and social conditions may lead to higher infection transmission.

COVID-19
Pandemic
Risk assessment
Spatial analysis
Urban green space


The Positivity Rate of IA-2A and ZnT8A in the Chinese Han Population With Type 1 Diabetes Mellitus: Association With rs1143627 and rs1143643 Polymorphisms in the IL1B Gene.

Abstract: Objective: To investigate the association between susceptibility to type 1 diabetes mellitus (T1DM) and polymorphisms (rs1143627 and rs1143643) in the interleukin 1 beta (IL1B) gene in the Chinese Han population. Methods: The Meso Scale Discovery (MSD) method was used to detect the concentration of IL-1β in 24 T1DM patients and 27 healthy controls. MassARRAY was used to analyze the polymorphisms in the IL1B gene in 510 patients with classic T1DM and 531 healthy controls. The general data of the T1DM patients and healthy controls were compared by the chi-square test and Mann-Whitney U test. The chi-square test and logistic regression were used to analyze the frequency distributions of alleles and genotypes of polymorphisms in the IL1B gene. The Kruskal-Wallis H test and chi-square test were used for the genotype-phenotype analysis of rs1143627 and rs1143643 in the IL1B gene. Results: ① The concentration of IL-1β in T1DM patients was significantly higher than that in healthy controls. ② rs1143627 and rs1143643 in the IL1B gene were significantly correlated with the positivity rates for IA-2A and ZnT8A; genotype GG at rs1143627 and genotype CC at rs1143643 in the case group showed lower positivity rates for IA-2A and ZnT8A. ③ There was no significant difference in the genotypes or allele frequencies at rs1143627 (GG/GA/AA) or rs1143643 (CC/CT/TT) between the case group and control group (p > 0.05). ④ rs1143627 and rs1143643 were not found to be linked to T1DM susceptibility under different genetic models. Conclusion: rs1143627 and rs1143643 in the IL1B gene correlate with the positivity rate of IA-2A and ZnT8A in Chinese Han individuals with T1DM.

Li|Jiaqi|J| Sun|Xiaoxiao|X| Luo|Shuoming|S| Lin|Jian|J| Xiao|Yang|Y| Yu|Haibo|H| Huang|Gan|G| Li|Xia|X| Xie|Zhiguo|Z| Zhou|Zhiguang|Z|

Chinese han population
type 1 diabetes mellitus
IL-1β
association analysis
interleukin 1 beta gene
single-nucleotide polymorphisms


Neonatal outcome of singleton term breech deliveries in Norway from 1991 to 2011.

Abstract:
INTRODUCTION
The objective of this study was to examine the association between planned mode of delivery and neonatal outcomes in breech deliveries.

MATERIAL AND METHODS
In this retrospective cohort study we studied singleton term breech deliveries in Norway from 1991 to 2011 (n = 30 861) using the Medical Birth Registry of Norway. We compared planned vaginal delivery with planned cesarean delivery across two time periods: from 1 January 1991 to 31 October 2000 (first period) and from 1 November 2000 to 31 December 2011 (second period). Intrapartum and neonatal deaths were validated against source data in medical records, autopsy reports, and other relevant documents. The main outcome measures were intrapartum and neonatal mortality within the first 28 days of life, 5-min Apgar-scores <7 and <4, neonatal intensive care unit stays ≥4 days, respiratory morbidity, and intracranial bleeding disorders.

RESULTS
Rate of planned cesarean delivery increased from 34.4 to 51.3% over the period. Simultaneously, early neonatal mortality rate (0-6 days) declined (from 0.10% to 0.04%, p = 0.04). During the second period, 30.7% of term breech presentations were delivered vaginally. Eight deaths in the planned vaginal vs. four in the planned cesarean groups were observed (OR 2.11 95% CI 0.64-7.01). Neonatal morbidity outcomes were significantly worse in planned vaginal deliveries compared with planned cesarean deliveries in both periods.

CONCLUSION
Overall intrapartum and neonatal mortality decreased during the entire period. Higher mortality in planned vaginal delivery relative to planned cesarean delivery in the second period was not statistically significant. However, neonatal morbidity was significantly higher in planned vaginal than planned cesarean deliveries in both periods. This warrants continuous surveillance of breech deliveries.

Vistad|Ingvild|I|
Klungsøyr|Kari|K|
Albrechtsen|Susanne|S|
Skjeldestad|Finn E|FE|

mode of delivery
birth registry
neonatal mortality
Breech presentation
neonatal morbidity
vaginal breech delivery


Application of light-emitting diodes (LEDs) in cultivation of phototrophic microalgae: current state and perspectives.

Abstract: The quality and regulation of the incident light is crucial in microalgae cultivation processes. Depending on wavelength, spectrum, and intensity, growth characteristics and biochemical composition of these organisms vary. With mainly fluorescent lamps (FL) used previously for illumination, such variabilities could not be studied adequately due to their broad emission spectrum. In contrast, light-emitting diodes (LEDs) emit a very narrow wavelength band and enable flexible photobioreactor designs due to their small size. This review provides a condensed overview on the application of LEDs in microalgal cultivation processes. It summarizes the current availability and applicability of LED technologies as an illumination source for research-focused photobioreactor systems. A particular focus is the use of narrow-wavelength LEDs to address fundamental as well as applied aspects of light color on algae biomass and value-added compound formation. In this respect, the application of internal and external illumination systems is reviewed together with trends in the industrial use of LED systems to intensify algae process efficiency.

Glemser|M|M| Heining|M|M| Schmidt|J|J| Becker|A|A| Garbe|D|D| Buchholz|R|R| Brück|T|T|

Light-emitting diodes
LED
Microalgae
Wavelengths
Photobioreactor


Developmental Dysplasia Treated With Cementless Total Hip Arthroplasty Utilizing High Hip Center Reconstruction: A Minimum 13-Year Follow-up Study.

Abstract:
BACKGROUND
The primary aim of this study was to determine the clinical outcomes at 13-year follow-up of patients diagnosed with developmental dysplasia of the hip and subsequently treated with total hip arthroplasty (THA). The secondary aim was to investigate the effect of hip center location on clinical outcomes and polyethylene wear.

METHODS
We reviewed data from a consecutive series of 104 patients (123 hips) from a single center. Patients were treated with THA with the high hip center (HHC) technique using cementless acetabular shells and highly cross-linked liners. Radiographs were collected preoperatively and through 13-year follow-up to assess degree of dysplasia (Crowe classification), component positioning, occurrence of bone resorption, and polyethylene wear. The Harris Hip Score (HHS) was administered at 4 and 13 years.

RESULTS
No patients were lost to follow-up, and one was revised for femoral loosening. Radiolucency was seen in 20% of patients and was not associated with HHC (P = .560). No patients developed osteolysis. The wear rate was low for all patients (mean: 3 ± 19 μm/y) and not associated with HHC (P = .852). The median 13-year HHS was 91.9 (interquartile range: 84.8-97.0). There was a statistically significant decline from the 4- to 13-year HHS (P < .001) for the Crowe II-IV group, although 82% of these patients remained above 80 points at 13 years. The nondysplastic and Crowe I group showed no longitudinal change in HHS (P = .243).

CONCLUSION
This cup design and highly cross-linked polyethylene liner combination demonstrates excellent clinical outcomes, similar to THA for primary osteoarthritis, through 13-year follow-up in patients with various degrees of developmental dysplasia of the hip and HHC reconstructions.

Galea|Vincent P|VP|
Laaksonen|Inari|I|
Donahue|Gabrielle S|GS|
Fukui|Kiyokazu|K|
Kaneuji|Ayumi|A|
Malchau|Henrik|H|
Bragdon|Charles|C|

cementless total hip arthroplasty
high hip center
developmental dysplasia of the hip
polyethylene wear
patient-reported outcome measures


Combining Direct 3D Volume Rendering and Magnetic Particle Imaging to Advance Radiation-Free Real-Time 3D Guidance of Vascular Interventions.

Abstract:
PURPOSE
Magnetic particle imaging (MPI) is a novel tomographic radiation-free imaging technique that combines high spatial resolution and real-time capabilities, making it a promising tool to guide vascular interventions. Immediate availability of 3D image data is a major advantage over the presently used digital subtraction angiography (DSA), but new methods for real-time image analysis and visualization are also required to take full advantage of the MPI properties. This laboratory study illustrates respective techniques by means of three different patient-specific 3D vascular flow models.

MATERIAL AND METHODS
The selected models corresponded to typical anatomical intervention sites. Routine patient cases and image data were selected, relevant vascular territories segmented, 3D models generated and then 3D-printed. Printed models were used to perform case-specific MPI imaging. The resulting MPI images, direct volume rendering (DVR)-based fast 3D visualization options, and their suitability to advance vascular interventions were evaluated and compared to conventional DSA.

RESULTS
The experiments illustrated the feasibility and potential to enhance image interpretation during interventions by using MPI real-time volumetric imaging and problem-tailored DVR-based fast (approximately 30 frames/s) 3D visualization options. These options included automated viewpoint selection and cutaway views. The image enhancement potential is especially relevant for complex geometries (e.g., in the presence of superposed vessels).

CONCLUSION
The unique features of the as-yet preclinical imaging modality MPI render it promising for guidance of vascular interventions. Advanced fast DVR could help to fulfill this promise by intuitive visualization of the 3D intervention scene in real time.

Magnetic particle imaging
4D visualization
Real-time image processing
Vascular imaging


Common Features of Regulatory T Cell Specialization During Th1 Responses.

Abstract: CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.

Littringer|Katharina|K|
Moresi|Claudia|C|
Rakebrandt|Nikolas|N|
Zhou|Xiaobei|X|
Schorer|Michelle|M|
Dolowschiak|Tamas|T|
Kirchner|Florian|F|
Rost|Felix|F|
Keller|Christian W|CW|
McHugh|Donal|D|
LeibundGut-Landmann|Salomé|S|
Robinson|Mark D|MD|
Joller|Nicole|N|


Facilitating mental health research for patients, clinicians and researchers: a mixed-method study.

Abstract:
OBJECTIVES
Research registers using Consent for Contact (C4C) can facilitate recruitment into mental health research studies, allowing investigators to contact patients based on clinical records information. We investigated whether such a register was useful for mental health research, seeking the perspectives of patients and research investigators.

SETTING AND DESIGN
In 2012, a C4C register was developed in a large secondary mental health provider within the UK; almost 9000 patients have joined. This mixed-method study audited the effectiveness of the register.

PARTICIPANTS
A 'mystery shopper' exercise was conducted, and patients (n=21) were recruited to ask clinicians about the availability of research opportunities. Structured interviews were conducted with patients (n=52) about their experiences of being on the register. Similar interviews were conducted with 18 investigators from 19 studies, who had attempted to use the register to recruit participants.

OUTCOME MEASURES
The impact of C4C on study recruitment, and whether it helped patients learn about research.

RESULTS
So far, the register has provided 928 individuals with 1085 research opportunities (in 60% of cases, the individual agreed to participate in the study). Clinicians were willing to link patients to research opportunities, but often lacked information about studies. For patients, the register provided opportunities which they may not otherwise have; 27 of 52 had participated in studies since joining the register (18 participating for the first time). Most investigators used the register to supplement recruitment to their studies, but described problems in prescreening potential participants from a clinical record for complex studies.

CONCLUSIONS
Although the register helped investigators recruit for studies, and provided patients with research opportunities, clinicians' input is still useful for identifying suitable participants. C4C registers should be adapted to provide clinicians with automatically updated information on local studies allowing them to match patients on their caseload with active studies.

Robotham|D|D| Waterman|S|S| Oduola|S|S| Papoulias|C|C| Craig|T|T| Wykes|T|T|

MENTAL HEALTH
research register
recruitment
participation
gatekeeping


Remembering Hospice.

Abstract: This book review essay discusses The Crisis of US Hospice Care: Family and Freedom at the End of Life (2019), by Harold Braswell.

bioethics
clinical decision-making
end-of-life care
interdependence


Effectiveness of Telerehabilitation in Physical Therapist Practice: An Umbrella and Mapping Review With Meta-Meta-Analysis.

Abstract:
OBJECTIVE
Telerehabilitation is an option that should be adapted as soon as possible to face the crisis caused by coronavirus disease 2019. An umbrella and mapping review with meta-meta-analysis (MMA) of the available scientific evidence was performed to determine whether telerehabilitation could be an effective alternative to conventional rehabilitation in physical therapist practice.

METHODS
A systematic review of reviews and a synthesis of the findings of all systematic evidence published to date with a visual map and a meta-meta-analysis (MMA) were performed. A systematic search was realized in Cochrane Database of Systematic Reviews, MEDLINE (PubMed), and Google Scholar. Two independent reviewers performed a data analysis and assessed the quality of the included reviews, assessing the risk of bias using ROBIS.

RESULTS
Twenty-nine articles that met the inclusion criteria were selected and divided according to the type of patient targeted for rehabilitation (patients with cardiorespiratory, musculoskeletal, and neurological conditions). The MMA regarding physical function between telerehabilitation and usual care rehabilitation did not reveal a statistically significant difference for patients with cardiorespiratory and musculoskeletal conditions. For patients with neurological conditions, the MMA revealed a statistically significant but negligible effect size in 6 reviews in favor of telerehabilitation (standardized mean difference = 0.18; 95% CI = 0.03-0.34).

CONCLUSION
The results of the present review showed that telerehabilitation offers positive clinical results, even comparable to conventional face-to-face rehabilitation approaches.

IMPACT
The advantages of lower cost and less interference by the rehabilitation processes in patients' daily life could justify implementing telerehabilitation in clinical settings in the coronavirus disease 2019 era.

Telerehabilitation
Exercise
Physical Therapy


Influence of molecular structure of astaxanthin esters on their stability and bioavailability.

Abstract: The stability and bioavailability of fourteen astaxanthin esters (Asta-Es) with different molecular structures were investigated using in vitro and in vivo digestion models. The results demonstrated that Asta-E with long-chain and saturated fatty acids were more stable than other types of Asta-E. Astaxanthin diester (Asta-DE) was better than astaxanthin monoester (Asta-ME) and free astaxanthin (F-Asta), as determined based on the degradation rate constant at 60 °C. The absorbability of Asta-Es with different molecular structures was evaluated through the serum concentrations of astaxanthin (Asta). The results indicated that Asta-E with short-chain fatty acids had higher bioavailability than Asta-Es with long-chain fatty acids, whereas Asta-E with high-unsaturation fatty acids had higher bioavailability than Asta-E with low-unsaturation fatty acids. Asta-ME had significantly increased bioavailability compared with Asta-DE. We concluded that the molecular structure of Asta-E could significantly affect their stability and bioavailability.

Yang|Lu|L| Qiao|Xing|X| Gu|Jiayu|J| Li|Xuemin|X| Cao|Yunrui|Y| Xu|Jie|J| Xue|Changhu|C|

D001682:Biological Availability
D004355:Drug Stability
D004952:Esters
D005227:Fatty Acids
D015394:Molecular Structure
D024341:Xanthophylls

Astaxanthin ester
Stability
Bioavailability
Esterification degree
Fatty acid profile
In vitro digestion


A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats.

Abstract: Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

Autoinjectors
manual injection
haematology
buprenorphine
emergency
biochemical parameters


Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats.

Abstract:
BACKGROUND
The FAO has recommended replacing the protein digestibility-corrected amino acid score (PDCAAS) with the digestible indispensable amino acid score (DIAAS).

OBJECTIVE
The objective of this study was to compare aspects underlying the calculation of the DIAAS and PDCAAS, including 1) fecal digestibility vs. ileal digestibility, 2) using a single nitrogen digestibility value for all amino acids, and 3) the effect of truncation. Truncated PDCAAS and untruncated DIAAS values calculated as formally defined were also compared and DIAAS data presented for 14 dietary protein sources.

METHODS
Semisynthetic wheat starch-based diets were formulated to contain the test protein (as consumed by humans) source (whey- and soy-protein isolates, milk-, whey-, rice- and pea- protein concentrates, cooked kidney beans, roasted peanuts, cooked peas, corn-based breakfast cereal, cooked rice, cooked rolled oats, and wheat bran) as the sole nitrogen source and with an indigestible marker (titanium dioxide). Growing male rats (∼250 g bodyweight) were given a basal casein-based diet from day 1 to day 7 and then allocated (n = 6) to the test diets for day 8 to day 14 before ileal digesta were collected after the rats were killed. Total feces were collected from day 11 to day 14.

RESULTS
True fecal nitrogen digestibility was different (P < 0.05; 10% difference on average) from true ileal nitrogen digestibility for 11 of the 14 protein sources. True ileal nitrogen digestibility was different (P < 0.05) from true ileal amino acid digestibility for almost half of the indispensable and conditionally indispensable amino acids (differences ranged from 0.9% to 400%). DIAAS values ranged from 0.01 for a corn-based cereal to 1.18 for milk protein concentrate.

CONCLUSION
Untruncated PDCAAS values were generally higher than a DIAAS values, especially for the poorer quality proteins; therefore, the reported differences in the scores are of potential practical importance for populations in which dietary protein intake may be marginal.

Rutherfurd|Shane M|SM|
Fanning|Aaron C|AC|
Miller|Bruce J|BJ|
Moughan|Paul J|PJ|

amino acid
protein quality
PDCAAS
DIAAS
ileal


English on cigarette packs from six non-Anglophone low- and middle-income countries.

Abstract:
OBJECTIVES
Low- and middle-income countries (LMICs) are vital to the global tobacco market. The pack is key to cigarette branding, and review of cigarette packs revealed English as a common feature. The prevalence of English and its potential branding utility is explored.

METHODS
Every available unique cigarette pack was purchased from diverse retailers in six LMICs where English is not the official language (Bangladesh, Brazil, China, Egypt, Ukraine, Vietnam). Packs' front panels were coded for English on pack fronts. English penetration was quantified by country and a comparison of English use between multinational and national brands was undertaken. A qualitative analysis of symbolic and utilitarian usage of English was conducted.

RESULTS
Of 1303 unique cigarette packs analyzed, 67% (n = 876) included some English. English text conveyed product information and usage instruction. English was more prevalent for multinational brands. Qualitatively, English use frequently connected cigarettes with concepts of quality, style, luxury, and aspirational lifestyle.

CONCLUSIONS
Restricting English use should be incorporated into plain packaging policy to protect populations from deceptive branding practices, specifically presenting cigarettes as an aspirational product.

Smith|Katherine Clegg|KC|
Welding|K|K|
Kleb|C|C|
Washington|C|C|
Cohen|J|J|

Marketing
Product packaging
Qualitative research
Text analysis
Tobacco control


The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification.

Abstract: Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the production of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-κB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-κB signaling in both in vitro and in vivo studies, suggesting that vitamin K may prevent vascular calcification via anti-inflammatory mechanisms. Matrix Gla protein (MGP) is a major inhibitor of soft tissue calcification and contributes to preventing both intimal and medial vascular calcification. Vitamin K may also inhibit progression of vascular calcification by enhancing the activity of MGP through facilitating its γ-carboxylation. In support of this hypothesis, the procalcific effects of warfarin, an antagonist of vitamin K, on arterial calcification have been demonstrated in several clinical studies. Among the inactive MGP forms, dephospho-uncarboxylated MGP (dp-ucMGP) may be regarded as the most useful biomarker of not only vitamin K deficiency, but also vascular calcification and CVD. There have been several studies showing the association of circulating levels of dp-ucMGP with vitamin K intake, vascular calcification, mortality, and CVD. However, additional larger prospective studies including randomized controlled trials are necessary to confirm the beneficial effects of vitamin K supplementation on CV health.

Shioi|Atsushi|A| Morioka|Tomoaki|T|0000-0002-2329-8191 Shoji|Tetsuo|T| Emoto|Masanori|M|

vascular calcification
oncostatin M
matrix Gla protein
atherosclerosis


Management of dysphagia in patients with head and neck cancer.

Abstract: Dysphagia is one of the most common symptoms affecting patients with head and neck cancer. It can lead to several complications and affect patients' quality of life. The advanced practice nurse can play an important role in the plan of care for managing this condition in patients with head and neck cancer.

dysphagia
head and neck cancer
quality of life
advanced practice nurse


EMS blood collection from patients with acute chest pain reduces emergency department length of stay.

Abstract:
BACKGROUND
Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States.

METHODS
A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016-4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin.

RESULTS
The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6-100). NPV improved to 100% (95% CI: 92.9-100) when using the EMS and 3-h ED troponin measures.

CONCLUSIONS
EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway.

Stopyra|Jason P|JP|
Snavely|Anna C|AC|
Ashburn|Nicklaus P|NP|
Nelson|R Darrell|RD|
McMurray|Evan L|EL|
Hunt|Meagan R|MR|
Miller|Chadwick D|CD|
Mahler|Simon A|SA|

EMS
Chest pain
Troponin
Acute coronary syndrome
Prehospital


Virtual screening by 2-D fingerprints, shape and docking for discovering new chemotypes of activator protein-1 inhibitors.

Abstract: Activator protein-1 Fos/Jun proteins bind to cognate DNA and regulate gene expression. Small-molecule inhibitors targeting activator protein-1 DNA binding have been developed in the past decades for therapeutic applications. Recent structural and in silico studies suggest a putative inhibitor binding pocket on the activator protein-1 structure, and computational modeling suggests a consensus binding mode of three classes of known small-molecule inhibitors. Here, virtual screening of two-dimensional fingerprints, shape, and docking was performed in search of novel chemotypes of activator protein-1 inhibitors. A standard score (Z3-score) coalescing top-ranked ligands from the three methods was used and the top-scoring ligands were clustered by similarity. A representative ligand from each large cluster was evaluated using metadynamics simulations and molecular mechanics calculations. Representative hits showed diverse chemotypes and their modeled binding pose on activator protein-1 reproduced key interactions with binding site residues.Communicated by Ramaswamy H. Sarma.

D001665:Binding Sites
D008024:Ligands
D062105:Molecular Docking Simulation
D056004:Molecular Dynamics Simulation
D011485:Protein Binding
D018808:Transcription Factor AP-1

virtual screening
fingerprints
docking
Activator protein-1
metadynamics simulation
data fusion


Perceived benefits and constraints in vehicle automation: Data to assess the relationship between driver's features and their attitudes towards autonomous vehicles.

Abstract: This data article examines the association driver's features, perceptions and attitudes towards autonomous vehicles (AVs). The data was collected using a structured self-administrable and online-based questionnaire, applied to a full sample of 1205 Spanish drivers. The data contains 4 parts: the full set of bivariate correlations between study variables; descriptive statistics and graphical trends for each main study variable according to gender, age group and city/town size; and, finally, the dataset for further explorations in this regard. For more information, it is convenient to read the full article entitled "Perceived safety and attributed value as predictors of the intention to use autonomous vehicles: A national study with Spanish drivers" [1].

Lijarcio|Ignacio|I|
Useche|Sergio A|SA|
Llamazares|Javier|J|
Montoro|Luis|L|

Attitudes
Autonomous vehicles
Perception
Spanish drivers
Intention
Road Safety


Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans.

Abstract: Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective of this study was to evaluate the diagnostic performance of promising biomarkers of liver injury-glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), and microRNA-122 (miR-122) in comparison to the traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually and as a multivariate model in a cohort of acetaminophen overdose (n = 175) subjects and were further tested in cohorts of healthy adults (n = 135), patients with liver damage from various causes (n = 104), and patients with damage to the muscle (n = 74), kidney (n = 40), gastrointestinal tract (n = 37), and pancreas (n = 34). In the acetaminophen cohort, a multivariate model with GLDH, K18, and miR-122 was able to detect DILI more accurately than individual biomarkers alone. Furthermore, the three-biomarker model could accurately predict patients with liver injury compared with healthy volunteers or patients with damage to muscle, pancreas, gastrointestinal tract, and kidney. Expression of K18, GLDH, and miR-122 was evaluated using a database of transcriptomic profiles across multiple tissues/organs in humans and rats. K18 mRNA (Krt18) and MiR-122 were highly expressed in liver whereas GLDH mRNA (Glud1) was widely expressed. We performed a comprehensive, comparative performance assessment of 7 promising biomarkers and demonstrated that a 3-biomarker multivariate model can accurately detect liver injury.

Llewellyn|Heather P|HP|
Vaidya|Vishal S|VS|
Wang|Zhenyu|Z|
Peng|Qinghai|Q|
Hyde|Craig|C|
Potter|David|D|
Wang|Jianying|J|
Zong|Qing|Q|
Arat|Seda|S|
Martin|Matt|M|
Masek-Hammerman|Katherine|K|
Warner|Roscoe|R|
Johnson|Kent|K|
Kullak-Ublick|Gerd A|GA|
Aithal|Guruprasad P|GP|
Dear|James W|JW|
Ramaiah|Shashi K|SK|

D056486:Chemical and Drug Induced Liver Injury

liver
diagnosis
glutamate dehydrogenase
keratin-18
microRNA


P3H4 is correlated with clinicopathological features and prognosis in bladder cancer.

Abstract:
BACKGROUND
Genetic alterations play a significant role in the progression of bladder cancer. Identifying novel biomarkers to personalize the therapeutic regimen and evaluate the prognosis of patients with bladder cancer is vital. Prolyl 3-hydroxylase family member 4 (P3H4) is significantly involved in several types of human cancer. However, the effect of P3H4 in bladder cancer remains unknown.

METHODS
The mRNA expression of P3H4 was measured in 44 paired tumors and adjacent normal tissues by using real-time reverse transcription-polymerase chain reaction. RNA-Seq data of 389 patients with bladder cancer were downloaded to investigate the effect of P3H4 on bladder cancer from The Cancer Genome Atlas (TCGA) project.

RESULTS
P3H4 was overexpressed in bladder cancer compared with the adjacent normal tissue both in our tissue samples and TCGA samples. The mRNA expression of P3H4 was significantly related to several clinicopathological factors of bladder cancer, including age, race category, histologic grade, tumor histologic subtype, and AJCC stage. The high P3H4 expression group had a shorter overall survival (OS) than the low P3H4 expression group. Univariate Cox regression analysis showed that age, angiolymphatic invasion, lymph node metastasis, tumor histologic subtype, metastasis, AJCC stage, and P3H4 were significantly related to OS. Moreover, multivariate Cox analysis revealed that P3H4, as well as age and AJCC stage, was an independent predictor of poor OS.

CONCLUSION
Given its tumorigenic role, P3H4 may serve as a promising tumor-promoting gene in bladder cancer.

D060888:Real-Time Polymerase Chain Reaction

P3H4
Clinicopathological features
Prognosis
Bladder cancer


Endothelium in Aortic Aneurysm Disease: New Insights.

Abstract: Inflammation is recognized as a fundamental element in the development and growth of aortic aneurysms. Aortic aneurysm is correlated with aortic wall deformities and injury, as a result of inflammation, matrix metalloproteinases activation, oxidative stress, and apoptosis of vascular smooth muscle cells. The endothelial wall has a critical part in the inflammation of the aorta and endothelial heterogeneity has proven to be significant for modeling aneurysm formation. Endothelial shear stress and blood flow affect the aortic wall through hindrance of cytokines and adhesion molecules excreted by endothelial cells, causing reduction of the inflammation process in the media and adventitia. This pathophysiological process results in the disruption of elastic fibers, degradation of collagen fibers, and destruction of vascular smooth muscle cells. Consequently, the aortic wall is impaired due to reduced thickness, decreased mechanical function, and cannot tolerate the impact of blood flow leading to aortic expansion. Surgery is still considered the mainstay therapy for large aortic aneurysms. The prevention of aortic dilation, though, is based on the hinderance of endothelial dysregulation with drugs, the reduction of reactive oxygen and nitrogen species, and also the reduction of pro-inflammatory molecules and metalloproteinases. Further investigations are required to enlighten the emerging role of endothelial cells in aortic disease.

Spartalis|Eleftherios|E|
Spartalis|Michael|M|
Athanasiou|Antonios|A|
Paschou|Stavroula A|SA|
Patelis|Nikolaos|N|
Voudris|Vassilis|V|
Iliopoulos|Dimitrios C|DC|

D000818:Animals
D001012:Aorta, Abdominal
D001014:Aortic Aneurysm
D042783:Endothelial Cells
D032389:Myocytes, Smooth Muscle


PMab-52: Specific and Sensitive Monoclonal Antibody Against Cat Podoplanin for Immunohistochemistry.

Abstract: Podoplanin (PDPN) is expressed in several normal tissues, such as lymphatic endothelial cells, podocytes of renal glomerulus, and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet. Although monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, dog PDPN, and bovine PDPN have been established, anticat PDPN (cPDPN) mAbs have not been developed. In this study, we immunized mice with Chinese hamster ovary (CHO)-K1 cell lines expressing cPDPN, and developed anti-cPDPN mAbs. One of the clones, PMab-52 (IgM, kappa), detected cPDPN specifically in flow cytometry and Western blot analysis. PMab-52 is also useful for detecting feline squamous cell carcinoma cells in immunohistochemical analysis. PMab-52 is expected to be useful for investigating the function of cPDPN in feline carcinomas.

Yamada|Shinji|S|
Itai|Shunsuke|S|
Nakamura|Takuro|T|
Yanaka|Miyuki|M|
Saidoh|Noriko|N|
Chang|Yao-Wen|YW|
Handa|Saori|S|
Harada|Hiroyuki|H|
Kagawa|Yumiko|Y|
Ichii|Osamu|O|
Konnai|Satoru|S|
Kaneko|Mika K|MK|
Kato|Yukinari|Y|

monoclonal antibody
cat podoplanin
immunohistochemistry
PDPN


Local injection of lovastatin in biodegradable polyurethane scaffolds enhances bone regeneration in a critical-sized segmental defect in rat femora.

Abstract: Statins, a class of naturally-occurring compounds that inhibit HMG-CoA reductase, are known to increase endogenous bone morphogenetic protein-2 (BMP-2) expression. Local administration of statins has been shown to stimulate fracture repair in in vivo animal experiments. However, the ability of statins to heal more challenging critical-sized defects at the mid-diaphyseal region in long bones has not been investigated. In this study, we examined the potential of injectable lovastatin microparticles combined with biodegradable polyurethane (PUR) scaffolds in preclinical animal models: metaphyseal small plug defects and diaphyseal segmental bone defects in rat femora. Sustained release of lovastatin from the lovastatin microparticles was achieved over 14 days. The released lovastatin was bioactive, as evidenced by its ability to stimulate BMP-2 gene expression in osteoblastic cells. Micro-computed tomography (CT) and histological examinations showed that lovastatin microparticles, injected into PUR scaffolds implanted in femoral plug defects, enhanced new bone formation. Furthermore, bi-weekly multiple injections of lovastatin microparticles into PUR scaffolds implanted in critical-sized femoral segmental defects resulted in increased new bone formation compared to the vehicle control. In addition, bridging of the defect with newly formed bone was observed in four of nine defects in the lovastatin microparticle treatment group, whereas none of the defects in the vehicle group showed bridging. These observations suggest that local delivery of lovastatin combined with PUR scaffold can be an effective approach for treatment of orthopaedic bone defects and that multiple injections of lovastatin may be useful for large defects.

Yoshii|Toshitaka|T|
Hafeman|Andrea E|AE|
Esparza|Javier M|JM|
Okawa|Atsushi|A|
Gutierrez|Gloria|G|
Guelcher|Scott A|SA|

injection
lovastatin
polyurethane
scaffold
bone regeneration
segmental defect
microparticles


Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe.

Abstract:
Background
In Fontan patients with atrial arrhythmias (AA), non-vitamin K antagonist oral anticoagulants(NOACs) have a class III recommendation according to the Pediatric & Congenital Electrophysiology Society (PACES)/Heart Rhythm Society (HRS) guideline in 2014, due to lack of data on outcomes as opposed to evidence of harm. To address this gap in data, we investigated the safety and efficacy of NOACs in adults with a Fontan circulation in a worldwide study.

Methods
This is an international multicentre prospective cohort study, using data from the NOTE (non-vitamin K antagonist oral anticoagulants for thromboembolic prevention in patients with congenital heart disease) registry. The study population comprised consecutive adults with a Fontan circulation using NOACs. Follow-up took place at 6 months and yearly thereafter. The primary endpoints were thromboembolism and major bleeding. Secondary endpoint was minor bleeding.

Results
From April 2014 onward, 74 patients (mean age 32±10 years (range 18-68), 54% male) with a Fontan circulation using NOACs were included. During a median follow-up of 1.2 (IQR 0.8-2.0) years, three thromboembolic events (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) and three major bleedings (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) occurred in five atriopulmonary Fontan and one total cavopulmonary connection Fontan patients with AA. Fifteen patients experienced minor bleeding episodes (15.8 per 100 patient-years (95% CI 9.1 to 25.2)). In patients (n=37) using vitamin K antagonists (VKAs) prior to the initiation of NOAC, annual incidence of historical thromboembolic events and major bleeding were 2.4% (95% CI 0.4% to 7.4%) (n = 2) and 1.2% (95% CI 0.7% to 5.1%) (n = 1), respectively.

Conclusions
In this review of the largest Fontan cohort using NOACs with prospective follow-up, NOACs appear to be well tolerated and their efficacy and safety during short-term follow-up seem comparable to VKAs. Longer term data are required to confirm these promising short-term results.

anticoagulation
fontan circulation
thromboembolism
bleeding
adult congenital heart disease


An Analytical Calculation of Frictional and Bending Moments at the Head-Neck Interface of Hip Joint Implants during Different Physiological Activities.

Abstract: This study predicts the frictional moments at the head-cup interface and frictional torques and bending moments acting on the head-neck interface of a modular total hip replacement across a range of activities of daily living. The predicted moment and torque profiles are based on the kinematics of four patients and the implant characteristics of a metal-on-metal implant. Depending on the body weight and type of activity, the moments and torques had significant variations in both magnitude and direction over the activity cycles. For the nine investigated activities, the maximum magnitude of the frictional moment ranged from 2.6 to 7.1 Nm. The maximum magnitude of the torque acting on the head-neck interface ranged from 2.3 to 5.7 Nm. The bending moment acting on the head-neck interface varied from 7 to 21.6 Nm. One-leg-standing had the widest range of frictional torque on the head-neck interface (11 Nm) while normal walking had the smallest range (6.1 Nm). The widest range, together with the maximum magnitude of torque, bending moment, and frictional moment, occurred during one-leg-standing of the lightest patient. Most of the simulated activities resulted in frictional torques that were near the previously reported oxide layer depassivation threshold torque. The predicted bending moments were also found at a level believed to contribute to the oxide layer depassivation. The calculated magnitudes and directions of the moments, applied directly to the head-neck taper junction, provide realistic mechanical loading data for in vitro and computational studies on the mechanical behaviour and multi-axial fretting at the head-neck interface.

Farhoudi|Hamidreza|H|
Oskouei|Reza H|RH|
Pasha Zanoosi|Ali A|AA|
Jones|Claire F|CF|
Taylor|Mark|M|

frictional moment
head-cup interface
total hip replacement
physical activities


Fibrin biopolymer as scaffold candidate to treat bone defects in rats.

Abstract:
Background
Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs.

Methods
Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis.

Results
It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation.

Conclusions
FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering.

de Oliveira|Alexandre Leite Rodrigues|ALR|

Fibrin biopolymer
Biphasic calcium phosphate
Mesenchymal stem cells
Biomaterials
Bone regeneration
Fibrin sealant


Tyrosine and terezine derivatives from the marine-sponge-derived fungus Phoma herbarum YG5839.

Abstract: A new tyrosine derivative (1), and two new terezine derivatives (2 and 3) were discovered from a marine-sponge-derived fungus Phoma herbarum YG5839. Those compounds were identified by comprehensive spectroscopic analysis, and antifungal activities were conducted against Fusarium oxysporum, Fusarium graminearum, Penicillium italicum, Colletotrictum gloeosporioides and Colletotrichum musae.

Hu|Zhibo|Z|
Gopal|Jannu Vinay|JV|
Liu|Lan|L|
Gao|Zhizeng|Z|

terezine derivatives
Phoma herbarum
tyrosine derivatives
antifungal activity
marine-sponge-derived fungi


ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer.

Abstract: Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3' untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC.

Gorur|Aysegul|A|
Bayraktar|Recep|R|
Ivan|Cristina|C|
Mokhlis|Hamada Ahmed|HA|
Bayraktar|Emine|E|
Kahraman|Nermin|N|
Karakas|Didem|D|
Karamil|Selda|S|
Kabil|Nashwa N|NN|
Kanlikilicer|Pinar|P|
Aslan|Burcu|B|
Tamer|Lulufer|L|
Wang|Zhihui|Z|
Cristini|Vittorio|V|
Lopez-Berestein|Gabriel|G|
Calin|George|G|
Ozpolat|Bulent|B|

therapy
triple-negative breast cancer
breast cancer
miR-22
eEF2K
EF2K
Akt
Src
nanoparticles
tumor suppressor
PI3K
gene regulation
gene silencing
liposomes


H∞ finite-time composite anti-disturbance switching control for switched systems.

Abstract: The paper centers on the H∞ finite-time (FT) composite anti-disturbance switching control (ADSC) issue for switched systems (SSs) suffered from multiple disturbances, the unavailable modeled disturbance and the available un-modeled disturbance. The aim is to arrive at the multiple disturbance suppression in FT. A switching estimator is firstly constructed to observe the modeled disturbance combined with the unavailable system state. A switching controller and a switching law are then co-established to restrain the multiple disturbances in the SSs. A condition is attained to ensure that the H∞ FT composite ADSC issue for the SSs is solvable, even the issue is not solvable for subsystems. A verification example is served to text the reasonability of the developed theory.

Zhao|Ying|Y| Pang|Mingchuan|M| Yu|Shuanghe|S| Li|Lili|L|

Anti-disturbance
Switched systems
Multiple disturbances
FT control


First report of the presence of Acartiabispinosa Carl, 1907 (Copepoda, Calanoida) in a semi-enclosed Bay (Sharm El-Maya), northern Red Sea with some notes on its seasonal variation in abundance and body size.

Abstract: The calanoid copepod, Acartiabispinosa Carl, 1907, is reported for the first time in the Red Sea, where it is found to be an important copepod in the mesozooplankton community structure of the Sharm El-Maya Bay. Female and male are fully redescribed and illustrated of as the mouthparts of this species have never previously been described and figured. Acartiabispinosa was collected in the plankton samples throughout the year and showed two peaks of abundance, a pronounced one in April (4234 individuals m(-3)), and second smaller peak during November (1784 individuals m(-3)). The average total length of females varied between 1.32 and 1.53 mm at the end of June and January respectively. For males, the average total length fluctuated between 1.07 and 1.16 mm at end of June and March respectively. Temperature showed an inverse relationship with the body length (P > 0.001) and seemed to be one of the prime factors affecting the body length of both sexes.

El-Sherbiny|Mohsen M|MM|
Al-Aidaroos|Ali M|AM|

Acartiabispinosa
Red Sea
body size
Copepods
morphology
seasonal abundance


Antiviral effects of selected nucleoside analogues against human parechoviruses A1 and A3.

Abstract: Parechoviruses A (HPeV, Picornaviridae) are neglected human pathogens that cause sepsis-like illness and severe neurological complications in infants. There are no antivirals available for the treatment of HPeV infections. We here report on cell-based assays that allow for medium-throughput antiviral screening of compound libraries against HPeV. The nucleoside viral polymerase inhibitor 2'-C-methylcytidine was identified as being an in vitro replication inhibitor of HPeV1 and HPeV3 that can serve as a reference molecule for further antiviral studies.

Lanko|Kristina|K| Ma|Yipeng|Y| Delang|Leen|L| Mirabelli|Carmen|C| Neyts|Johan|J|

Antivirals
Human parechovirus
Picornaviruses


10 Years of Human-NAO Interaction Research: A Scoping Review.

Abstract: The evolving field of human-robot interaction (HRI) necessitates that we better understand how social robots operate and interact with humans. This scoping review provides an overview of about 300 research works focusing on the use of the NAO robot from 2010 to 2020. This study presents one of the most extensive and inclusive pieces of evidence on the deployment of the humanoid NAO robot and its global reach. Unlike most reviews, we provide both qualitative and quantitative results regarding how NAO is being used and what has been achieved so far. We analyzed a wide range of theoretical, empirical, and technical contributions that provide multidimensional insights, such as general trends in terms of application, the robot capabilities, its input and output modalities of communication, and the human-robot interaction experiments that featured NAO (e.g. number and roles of participants, design, and the length of interaction). Lastly, we derive from the review some research gaps in current state-of-the-art and provide suggestions for the design of the next generation of social robots.

Amirova|Aida|A| Rakhymbayeva|Nazerke|N| Yadollahi|Elmira|E| Sandygulova|Anara|A| Johal|Wafa|W|

review
human-robot interaction
social robot
nao
qualitative
quantitative
humanoid robot
survey


New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities.

Abstract: Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis and migration of cancer cells to neighboring cells and tissues. Morphologically, epithelial cells are transformed to mesenchymal cells, and at molecular level, E-cadherin undergoes down-regulation, while an increase occurs in N-cadherin and vimentin levels. Increasing evidence demonstrates role of EMT in mediating drug resistance of cancer cells. On the other hand, paclitaxel (PTX) and docetaxel (DTX) are two chemotherapeutic agents belonging to taxene family, capable of inducing cell cycle arrest in cancer cells via preventing microtubule depolymerization. Aggressive behavior of cancer cells resulted from EMT-mediated metastasis can lead to PTX and DTX resistance. Upstream mediators of EMT such as ZEB1/2, TGF-β, microRNAs, and so on are involved in regulating response of cancer cells to PTX and DTX. Tumor-suppressing factors inhibit EMT to promote PTX and DTX sensitivity of cancer cells. Furthermore, three different strategies including using anti-tumor compounds, gene therapy and delivery systems have been developed for suppressing EMT, and enhancing cytotoxicity of PTX and DTX against cancer cells that are mechanistically discussed in the current review.

Ashrafizadeh|Milad|M|
Mirzaei|Sepideh|S|
Hashemi|Farid|F|
Zarrabi|Ali|A|
Zabolian|Amirhossein|A|
Saleki|Hossein|H|
Sharifzadeh|Seyed Omid|SO|
Soleymani|Leyla|L|
Daneshi|Salman|S|
Hushmandi|Kiavash|K|
Khan|Haroon|H|
Kumar|Alan Prem|AP|
Aref|Amir Reza|AR|
Samarghandian|Saeed|S|


Longitudinal associations between dietary quality and Alzheimer's disease genetic risk on cognitive performance among African American adults.

Abstract: Poor diet quality (DQ) is associated with poor cognition and increased neurodegeneration, including Alzheimer's disease (AD). We are interested in the role of DQ on cognitive functioning (by sex and increasing genetic risk for AD), in a sample of African American (AA) middle-aged adults. We analysed a sub-group of participants (about 55 % women; mean follow-up time of about 4·7 years) from the Healthy Aging in Neighborhoods of Diversity across the Life Span study with a genetic risk score for AD (hAlzScore). The Healthy Eating Index-2010, Dietary Approaches to Stop Hypertension and the mean adequacy ratio computed at baseline (2004-2009) and follow-up visits (2009-2013) were used to assess initial DQ and change over time. Linear mixed-effects regression models were utilised, adjusting for select covariates, selection bias and multiple testing. DQ change (ΔDQ) was associated with California Verbal Learning Test-List A - overall (0·15 (se 0·06), P = 0·008) and in women (0·21 (se 0·08), P = 0·006), at highest AD risk, indicating protective effects over time. Greater AD risk was longitudinally associated with poorer Clock Command Test scores in men. Poor DQ was positively and cross-sectionally associated with Trails B scores, but in women only. Better-quality diet was associated with a slower decline in verbal memory among AA women, with greater AD risk. Insufficient clinical evidence and/or mixed findings dictate that more studies are needed to investigate brain morphology and volume changes in relation to DQ in an at-risk population for AD, over time.

Hossain|Sharmin|S|0000-0003-1516-3251
Beydoun|May A|MA|
Weiss|Jordan|J|
Kuczmarski|Marie F|MF|
Evans|Michele K|MK|
Zonderman|Alan B|AB|

D020022:Genetic Predisposition to Disease

Genetic risk
Adults
Diet quality
Alzheimer’s disease
Cognitive decline
Health disparities


Renormalization of myoglobin-ligand binding energetics by quantum many-body effects.

Abstract: We carry out a first-principles atomistic study of the electronic mechanisms of ligand binding and discrimination in the myoglobin protein. Electronic correlation effects are taken into account using one of the most advanced methods currently available, namely a linear-scaling density functional theory (DFT) approach wherein the treatment of localized iron 3d electrons is further refined using dynamical mean-field theory. This combination of methods explicitly accounts for dynamical and multireference quantum physics, such as valence and spin fluctuations, of the 3d electrons, while treating a significant proportion of the protein (more than 1,000 atoms) with DFT. The computed electronic structure of the myoglobin complexes and the nature of the Fe-O2 bonding are validated against experimental spectroscopic observables. We elucidate and solve a long-standing problem related to the quantum-mechanical description of the respiration process, namely that DFT calculations predict a strong imbalance between O2 and CO binding, favoring the latter to an unphysically large extent. We show that the explicit inclusion of the many-body effects induced by the Hund's coupling mechanism results in the correct prediction of similar binding energies for oxy- and carbonmonoxymyoglobin.

Weber|Cédric|C|
Cole|Daniel J|DJ|
O'Regan|David D|DD|
Payne|Mike C|MC|

metalloprotein
natural bond orbitals
optical absorption
quantum-mechanical simulation
strong correlation