Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer.

Abstract: The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical trial. Further, the associations between CYP27A1 expression with other primary tumor pathological features and clinical outcomes were studied in two additional independent cohorts. Statin treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in tumors. However, these changes were not associated with anti-proliferative responses to statin treatment. CYP27A1 was heterogeneously expressed among primary tumors, with high expression significantly associated with high tumor grade, ER negativity and basal-like subtype. High CYP27A1 expression was independently prognostic for longer recurrence-free and overall survival. Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer seemed limited to women aged ≤50 years. These results establish a link between CYP27A1 and breast cancer pathobiology and prognosis and propose that the efficacy of statins in reducing serum lipids does not directly translate to anti-proliferative effects in tumors. Changes in other undetermined serum or tumor factors suggestively mediate the anti-proliferative effects of statins in breast cancer.

Kimbung|Siker|S|
Chang|Ching-Yi|CY|
Bendahl|Pär-Ola|PO|
Dubois|Laura|L|
Thompson|J Will|JW|
McDonnell|Donald P|DP|
Borgquist|Signe|S|


Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans.

Abstract: MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the post-transcriptional regulation of protein-coding genes. miRNAs modulate lifespan and the aging process in a variety of organisms. In this study, we identified a role of miR-83 in regulating lifespan of Caenorhabditis elegans. mir-83 mutants exhibited extended lifespan, and the overexpression of miR-83 was sufficient to decrease the prolonged lifespan of the mutants. We observed upregulation of the expression levels of a set of miR-83 target genes in young mir-83 mutant adults; while different sets of genes were upregulated in older mir-83 mutant adults. In vivo assays showed that miR-83 regulated expression of target genes including din-1, spp-9 and col-178, and we demonstrated that daf-16 and din-1 were required for the extension of lifespan in the mir-83 mutants. The regulation of din-1 by miR-83 during aging resulted in the differential expression of din-1 targets such as gst-4 and gst-10. In daf-2 mutants, the expression level of miR-83 was significantly reduced compared to wild-type animals. We identified a role for miR-83 in modulating lifespan in C. elegans and provided molecular insights into its functional mechanism.

Dzakah|Emmanuel Enoch|EE|
Waqas|Ahmed|A|
Wei|Shuai|S|
Yu|Bin|B|
Wang|Xiaolin|X|
Fu|Tao|T|
Liu|Lei|L|
Shan|Ge|G|

D018507:Gene Expression Regulation, Developmental


PET and MRI detection of early and progressive neurodegeneration in spinocerebellar ataxia type 36.

Abstract:
BACKGROUND
The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans.

METHODS
Twenty SCA36 patients underwent a study consisting of FDG-PET and MRI scans. Clinical motor evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA). FDG-PET was carried out using a voxel-by-voxel and region-of-interest analysis. MRI evaluation was based on visual inspection and volumetric analysis.

RESULTS
SARA ranged from 0 to 24.5 (4 patients asymptomatic, 3 with unspecific symptoms, and 13 with cerebellar signs). FDG-PET revealed hypometabolism in the asymptomatic stage in the vermis and right cerebellar hemisphere. In the ataxic stage, hypometabolism spread to both cerebellar hemispheres and the brain stem. MRI was normal in asymptomatic and preataxic individuals and showed superior cerebellar vermis atrophy early in the ataxic stage, diffuse cerebellar atrophy some years into the disease course, and a pattern of olivopontocerebellar atrophy in the oldest patients. There was no significant cerebellar atrophy in patients younger than 50 years.

CONCLUSIONS
We present the first FDG-PET study of SCA36 and one of the largest neuroimaging study of SCAs. Our results revealed neuronal dysfunctions in the vermis and right cerebellar hemisphere as soon as a decade before the onset of motor symptoms. In the ataxic stage, dysfunctions spread to both hemispheres and the brain stem. © 2016 International Parkinson and Movement Disorder Society.

Aguiar|Pablo|P| Pardo|Julio|J| Arias|Manuel|M| Quintáns|Beatriz|B| Fernández-Prieto|Montse|M| Martínez-Regueiro|Rocío|R| Pumar|José-Manuel|JM| Silva-Rodríguez|Jesús|J| Ruibal|Álvaro|Á| Sobrido|María-Jesús|MJ| Cortés|Julia|J|

PET
MRI
neurodegeneration
ataxia
preataxic stage


Application of the Functional Lumen Imaging Probe to Esophageal Disorders.

Abstract: The functional luminal imaging probe (FLIP) provides a novel method to evaluate esophageal physiology and function in both health and disease. FLIP enables assessment of a previously underexplored component of esophageal function, distensibility, by utilizing high-resolution impedance planimetry to evaluate the relationship of the esophageal luminal geometry with pressure during controlled volumetric distension. Recent studies have described the potential utility of FLIP to evaluate the severity and effectiveness of therapy for esophageal diseases including achalasia, gastroesophageal reflux disease, and eosinophilic esophagitis. This review summarizes these emerging clinical applications of FLIP in the evaluation and management of esophageal diseases.

Functional lumen imaging probe
Impedance planimetry
Achalasia
Gastroesophageal reflux disease
Eosinophilic esophagitis


The State of Ambient Air Quality in Two Ugandan Cities: A Pilot Cross-Sectional Spatial Assessment.

Abstract: Air pollution is one of the leading global public health risks but its magnitude in many developing countries' cities is not known. We aimed to measure the concentration of particulate matter with aerodynamic diameter <2.5 µm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) pollutants in two Ugandan cities (Kampala and Jinja). PM2.5, O3, temperature and humidity were measured with real-time monitors, while NO2 and SO2 were measured with diffusion tubes. We found that the mean concentrations of the air pollutants PM2.5, NO2, SO2 and O3 were 132.1 μg/m3, 24.9 µg/m3, 3.7 µg/m3 and 11.4 μg/m3, respectively. The mean PM2.5 concentration is 5.3 times the World Health Organization (WHO) cut-off limits while the NO2, SO2 and O3 concentrations are below WHO cut-off limits. PM2.5 levels were higher in Kampala than in Jinja (138.6 μg/m3 vs. 99.3 μg/m3) and at industrial than residential sites (152.6 μg/m3 vs. 120.5 μg/m3) but residential sites with unpaved roads also had high PM2.5 concentrations (152.6 μg/m3). In conclusion, air pollutant concentrations in Kampala and Jinja in Uganda are dangerously high. Long-term studies are needed to characterize air pollution levels during all seasons, to assess related public health impacts, and explore mitigation approaches.

Kirenga|Bruce J|BJ|
Meng|Qingyu|Q|
van Gemert|Frederik|F|
Aanyu-Tukamuhebwa|Hellen|H|
Chavannes|Niels|N|
Katamba|Achilles|A|
Obai|Gerald|G|
van der Molen|Thys|T|
Schwander|Stephan|S|
Mohsenin|Vahid|V|

particulate matter
nitrogen dioxide
sulfur dioxide
ozone
Kampala
Jinja
Uganda
ambient air pollution


Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson's disease: a meta-analysis.

Abstract:
BACKGROUND
Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson's disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use.

METHODS
Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson's disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality.

RESULTS
Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD - 7.00, 95% CI - 8.35 to - 5.65, P < 0.00001) for total UPDRS score (nine trials; MD - 5.74, 95% CI - 7.71 to - 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD - 1.61, 95% CI - 2.18 to - 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD - 0.38, 95% CI - 0.61 to - 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD - 5.71, 95% CI - 7.11 to - 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83-3.00, P = 0.16).

CONCLUSIONS
S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

Jiang|De-Qi|DQ| Li|Ming-Xing|MX| Jiang|Li-Lin|LL| Chen|Xiao-Bai|XB| Zhou|Xing-Wen|XW|

D000073216:Mental Status and Dementia Tests

Selegiline
Levodopa
Meta-analysis
Safety
UPDRS
Parkinson’s disease


Health Effects Associated With Pre- and Perinatal Exposure to Arsenic.

Abstract: Inorganic arsenic is a well-established human carcinogen, able to induce genetic and epigenetic alterations. More than 200 million people worldwide are exposed to arsenic concentrations in drinking water exceeding the recommended WHO threshold (10μg/l). Additionally, chronic exposure to levels below this threshold is known to result in long-term health effects in humans. The arsenic-related health effects in humans are associated with its biotransformation process, whereby the resulting metabolites can induce molecular damage that accumulates over time. The effects derived from these alterations include genomic instability associated with oxidative damage, alteration of gene expression (including coding and non-coding RNAs), global and localized epigenetic reprogramming, and histone posttranslational modifications. These alterations directly affect molecular pathways involved in the onset and progression of many conditions that can arise even decades after the exposure occurs. Importantly, arsenic metabolites generated during its biotransformation can also pass through the placental barrier, resulting in fetal exposure to this carcinogen at similar levels to those of the mother. As such, more immediate effects of the arsenic-induced molecular damage can be observed as detrimental effects on fetal development, pregnancy, and birth outcomes. In this review, we focus on the genetic and epigenetic damage associated with exposure to low levels of arsenic, particularly those affecting early developmental stages. We also present how these alterations occurring during early life can impact the development of certain diseases in adult life.

arsenic
genetics
epigenetics
fetal development
DNA methylation
in utero exposure


Review of Sertoli cell dysfunction caused by COVID-19 that could affect male fertility.

Abstract: Spermatogenesis is a complex and elaborate differentiation process and is vital for male fertility. Sertoli cells play a major role in fertility and induce spermatogenesis by protecting, nourishing, and supporting germ cells. It has been speculated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could directly affect the male reproductive system, and therefore heredity and fertility. The similarity of SARS-CoV-2 to SARS-CoV could confirm this hypothesis because both viruses use angiotensin-converting enzyme (ACE2) as the receptor to enter human cells. ACE2 is expressed by Sertoli cells and other testicular cells, therefore COVID-19 has the potential to impair fertility by destroying Sertoli cells. This hypothesis should be evaluated and confirmed by monitoring fertility in patients with COVID-19.

Sertoli cells
COVID-19
Male fertility
Germ cells
SARS coronaviruses


AGAP2-AS1 serves as an oncogenic lncRNA and prognostic biomarker in glioblastoma multiforme.

Abstract: Long noncoding RNA (lncRNA) AGAP2 antisense RNA 1 (AGAP2-AS1) has been suggested to function as an oncogenic lncRNA in lung cancer, breast cancer, and anaplastic glioma. However, the expression pattern and molecular mechanism of AGAP2-AS1 in glioblastoma multiforme (GBM) remains unknown. The purpose of this study is to present more evidence about the clinical and biological function of AGAP2-AS1 in GBM. In our results, we found AGAP2-AS1 expression was increased in GBM compared with adjacent normal brain tissues or low-grade glioma tissues, and there was no significantly different between low-grade glioma tissues and normal tissues. Kaplan-Meier survival analysis indicated patients with GBM having high-expression of AGAP2-AS1 had shorter overall survival time than those with low expression of AGAP2-AS1. The loss-of-function studies showed that downregulation of AGAP2-AS1 depressed cell proliferation, migration, and invasion, and promoted cell apoptosis in GBM. In summary, AGAP2-AS1 is a prognostic biomarker for patients with GBM, and functions as an oncogenic lncRNA to modulate GBM cell proliferation, apoptosis, migration, and invasion, which suggests that AGAP2-AS1 is potential therapeutic target for GBM.

D060888:Real-Time Polymerase Chain Reaction

AGAP2-AS1
lncRNA
glioblastoma multiforme
glioma
GBM


Performing Gadoxetic Acid-Enhanced MRI After CT for Guiding Curative Treatment of Early-Stage Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

Abstract:
OBJECTIVE
We determined the cost-effectiveness of two different diagnostic imaging strategies in guiding curative treatment of early-stage hepatocellular carcinoma (HCC).

MATERIALS AND METHODS
We developed a decision analytic model using as its starting point a cohort of patients aged 55 years with early-stage HCC detected at dynamic multiphasic CT and with Child-Pugh class A cirrhosis. The model compared two strategies on the initial workup: conventional CT strategy using dynamic multiphasic CT only and gadoxetic acid-enhanced MRI strategy using additional gadoxetic acid-enhanced MRI after initial CT. A Markov cohort model simulated a cohort of patients after curative or adjuvant treatment, with follow-up over the remaining life expectancy. We analyzed mean life-years gain, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratio (ICER). To evaluate results, we performed one-way, two-way, and probabilistic sensitivity analyses.

RESULTS
The life expectancies and QALY were 7.22 years and 5.08 for the conventional CT strategy and 7.79 years and 5.52 for the gadoxetic acid-enhanced MRI strategy, respectively. The expected costs were $99,770 for conventional CT and $105,025 for gadoxetic acid-enhanced MRI in the United States. The ICER with gadoxetic acid-enhanced MRI was $11,957, as opposed to that with conventional CT, which was lower than the cost-effectiveness threshold of $50,000/QALY. One-way, two-way, and probabilistic sensitivity analyses showed unchanged results over an acceptable range.

CONCLUSION
Gadoxetic acid-enhanced MRI after CT is cost-effective for detecting additional HCC in patients with early-stage HCC who can undergo curative treatment (besides liver transplantation). The cost-effectiveness of gadoxetic acid-enhanced MRI may be considered in the management of patients with early-stage HCC during staging.

Suh|Chong Hyun|CH|
Kim|Kyung Won|KW|
Park|Seong Ho|SH|
Kim|So Yeon|SY|
Woo|Dong-Cheol|DC|
Shin|Sangjin|S|
Pyo|Junhee|J|
Shinagare|Atul B|AB|
Ramaiya|Nikhil H|NH|
Lim|Young-Suk|YS|

D000368:Aged
D006528:Carcinoma, Hepatocellular
D003287:Contrast Media
D003362:Cost-Benefit Analysis
D003661:Decision Support Techniques
D005260:Female
D019786:Gadolinium DTPA
D006801:Humans
D008017:Life Expectancy
D008103:Liver Cirrhosis
D008113:Liver Neoplasms
D008279:Magnetic Resonance Imaging
D008297:Male
D008390:Markov Chains
D008875:Middle Aged
D009367:Neoplasm Staging
D019057:Quality-Adjusted Life Years
D014057:Tomography, X-Ray Computed

hepatocellular carcinoma
cost-effectiveness analysis
quality-adjusted life-years
incremental cost-effectiveness ratios
gadoxetic acid–enhanced MRI


Chitosan polysaccharide as a renewable functional agent to develop antibacterial, antioxidant activity and colourful shades on wool dyed with tea extract polyphenols.

Abstract: Chitosan is a potential renewable, versatile amino polysaccharide which has been approved by food and drug administration for use in food, cosmetics, pharmaceuticals and other industries. In order to determine if chitosan can be utilized in the development of colourful and multifunctional wool fabric without the need of toxic metal salt mordants, we have investigated the colouring, radical scavenging and antibacterial activity of wool dyed with tea extract polyphenols using chitosan as a green pre-treatment finishing agent. UV-vis analysis confirmed the optical properties of tea polyphenols, while Fourier-transform infrared spectroscopy (FT-IR), Scanning electron microscope (SEM) and Thermogravimetric analysis (TGA) spectroscopic characterizations demonstrated binding, surface morphology and thermal stability properties of chitosan coated wool. Colour spectrometry data obtained in terms of CIEL*a*b* values showed an outstanding effect of the chitosan pre-treatment. The Camellia sinensis (tea) extract dyed wool yielded interestingly elegant pale to golden yellowish colours with acceptable wash fastness properties. The chitosan gets its affinity for the wool via hydrogen bonding, electrostatic and van der Waals interactions. The results also showed that chitosan pre-treatment imparts excellent radical scavenging and antibacterial activity against E. coli and S. aureus, and thus offers new opportunities in the realm of natural dyeing.

Shahid-Ul-Islam|||
Butola|B S|BS|
Roy|Anasuya|A|

Chitosan polysaccharide
Antioxidant activity
Antibacterial activity
Tea polyphenols
Wool finishing


Tissue depletion of quinocetone and its five major metabolites in pigs, broilers, and carp fed quinocetone premix.

Abstract: A residue depletion study was performed to investigate the tissue kinetics of quinocetone (1) and its major metabolites. Quinocetone and its major metabolites were simultaneously quantitated with a high-performance liquid chromatography-ultraviolet (HPLC-UV) method. A total of 25 pigs, 30 broilers, and 50 carp were fed 100 mg/kg quinocetone for 90, 42, and 60 days, respectively. Liver, kidney, muscle, and fat (skin) tissues were collected at five different withdrawal times for analysis. Results revealed that quinocetone, 1-desoxyquinocetone (2), carbonyl-reduced 4-desoxyquinocetone (4), 3-methylquinoxaline-2-carboxylic acid (5), and carbonyl-reduced dideoxyquinocetone (6) could be depleted quickly in tissues; by contrast, dideoxyquinocetone, 3, persisted for a long time in the liver. Therefore, the liver is possibly the target tissue of quinocetone, and 3 is the residual marker; the recommended withdrawal times (WDTs) are 0 days in pigs and carp and 3 days in broilers. These results provided clear monitoring tools and technical standards to evaluate the food safety of quinocetone.

Li|Juan|J| Huang|Lingli|L| Pan|Yuanhu|Y| Chen|Dongmei|D| Wang|Xu|X| Ahmad|Ijaz|I| Tao|Yanfei|Y| Liu|Zhenli|Z| Yuan|Zonghui|Z|

tissue depletion
quinocetone
metabolites
withdrawal time
HPLC
estimates of dietary intake


Hybrid phenylthiazole and 1,3,5-triazine target cytosolic leucyl-tRNA synthetase for antifungal action as revealed by molecular docking studies.

Abstract:
BACKGROUND
Leucyl-tRNA synthetase (LeuRS) is one of the essential enzymes belonging to the family of aminoacyl-tRNA synthetases (aaRSs), which executes the translation of genetic code by catalyzing the specific attachment of amino acids to their cognate tRNAs. This process is very crucial for survival of micro-organism and thus the inhibition of LeuRS offered a novel and lucrative target for developing new antimicrobials.

FINDINGS
Docking studies using hybrid phenylthiazole-1,3,5-triazine derivatives revealed that these molecules acted as probable inhibitors of candida albicans cytosolic leucyl-tRNA synthetase.

CONCLUSION
The conjugates of phenylthiazole and 1,3,5-triazine can act as lead molecules towards the development of potential leucyl-tRNA synthetase inhibitors on the basis of molecular docking runs, which contribute to the possible mechanism of antifungal activity of these analogues.

Singh|Udaya Pratap|UP|
Bhat|Hans Raj|HR|
Gahtori|Prashant|P|
Singh|Ramendra K|RK|

phenylthiazole
1,3,5-triazine
Leucyl-tRNA synthetase
Docking


Research progress on the effect of autophagy-lysosomal pathway on tumor drug resistance.

Abstract: Autophagy is an intracellular degradation pathway that is highly conserved during the evolution of eukaryotes and is based on lysosome. Under nutritional deficiencies or stress, cells can clear damaged and necrotic organelles and proteins through autophagy to maintain the homeostasis of cells and organisms. Studies have found that abnormal autophagy is closely related to the occurrence and development of neurodegenerative diseases and tumors. In order to further understand the relationship between lysosomes and autophagy, tumorigenesis and drug resistance, the role of autophagy-lysosomal pathway in tumor resistance and related mechanisms and the relationship between drug resistance and hypoxia-induced autophagy are discussed in this paper.

Li|Jiaxin|J| Liu|Gui|G| Li|Long|L| Yao|Zhigang|Z| Huang|Junhui|J|

Tumor
Drug resistance
Autophagy
Lysosome
Hypoxia


Glycine substitution of α1F64 residue at the loop D of GABAA receptor impairs gating - Implications for importance of binding site-channel gate linker rigidity.

Abstract: GABAA receptors (GABAARs) play a crucial role in mediating inhibition in adult mammalian brains. In the recent years, an impressive progress in revealing the static structure of GABAARs was achieved but the molecular mechanisms underlying their conformational transitions remain elusive. Phenylalanine 64 (α1F64) is located at the loop D of the orthosteric binding site of GABAAR and was found to directly interact with GABA molecule. Mutations of α1F64 were demonstrated to affect not only binding but also some gating properties. Loop D is a rigid β strand which seems to be particularly suitable to convey activatory signaling from the ligand binding site (LBS) to the gate at the channel pore. To test this scenario, we have investigated the substitution of α1F64 with glycine, the smallest amino acid, widely recognized as a rigidity "reducer" of protein structures. To this end, we assessed the impact of the α1F64G mutation in the α1β2γ2L type of GABAARs on gating properties by analyzing both macroscopic responses to rapid agonist applications and single-channel currents. We found that this substitution dramatically altered all gating features of the receptor (opening/closing, preactivation and desensitization) which contrasts with markedly weaker effects of previously considered substitutions (α1F64L and α1F64A). In particular, α1F64G mutation practically abolished the desensitization process. At the same time, the α1F64G mutant maintained gating integrity manifested as single-channel activity in the form of clusters. We conclude that rigidity of the loop D plays a crucial role in conveying the activation signal from the LBS to the channel gate.

Kłopotowski|Karol|K|
Czyżewska|Marta M|MM|
Mozrzymas|Jerzy W|JW|

Loop D
Gating
Phenylalanine 64
GABA(A) receptors
Structure-function relationship


Surgery in a patient with liver disease.

Abstract: Surgery is often needed in patients with concurrent liver disease. The multiple physiological roles of the liver places these patients at an increased risk of morbidity and mortality. Diseases necessitating surgery like gallstones and hernia are more common in patients with cirrhosis. Assessment of severity of liver dysfunction before surgery is important and the risk benefit of the procedure needs to be carefully assessed. The disease severity may vary from mild transaminase rise to decompensated cirrhosis. Surgery should be avoided if possible in the emergency setting, in the setting of acute and alcoholic hepatitis, in a patient of cirrhosis who is child class C or has a MELD score more than 15 or any patient with significant extrahepatic organ dysfunction. In this subset of patients, all possible means to manage these patients conservatively should be attempted. Modified Child-Pugh scores and model for end-stage liver disease (MELD) scores can predict mortality after surgery fairly reliably including nonhepatic abdominal surgery. Pre-operative optimization would include control of ascites, correction of electrolyte imbalance, improving renal dysfunction, cardiorespiratory assessment, and correction of coagulation. Tests of global hemostasis like thromboelastography and thrombin generation time may be more predictive of the risk of bleeding compared with the conventional tests of coagulation in patients with cirrhosis. Correction of international normalized ratio with fresh frozen plasma does not necessarily mean reduction of bleeding risk and may increase the risk of volume overload and lung injury. International normalized ratio liver may better reflect the coagulation status. Recombinant factor VIIa in patients with cirrhosis needing surgery needs further study. Intra-operatively, safe anesthetic agents like isoflurane and propofol with avoidance of hypotension are advised. In general, nonsteroidal anti-inflammatory drug (NSAIDs) and benzodiazepines should not be used. Intra-abdominal surgery in a patient with cirrhosis becomes more challenging in the presence of ascites, portal hypertension, and hepatomegaly. Uncontrolled hemorrhage due to coagulopathy and portal hypertension, sepsis, renal dysfunction, and worsening of liver failure contribute to the morbidity and mortality in these patients. Steps to reduce ascitic leaks and infections need to be taken. Any patient with cirrhosis undergoing major surgery should be referred to a specialist center with experience in managing liver disease.

ASA, American Society of Anesthesiologists

COPD, chronic obstructive pulmonary disease

NSAID, nonsteroidal anti-inflammatory drug

PICD, paracentesis-induced circulatory dysfunction

TIPS, transjugular intrahepatic portosystemic shunt

P P P M M U M M M M M M M M M M M R R M M M M M M


Role of Molecular Epidemiology on Tuberculosis Control in the Middle East Countries: a Systematic Review and Meta-Analysis.

Abstract:
Background
Tuberculosis (TB) is a public health problem in developing countries and yet the numbers of people with the disease are abundant. Early detection of transmission sources and effective treatment of the cases is essential to control the disease which will be possible by application of molecular epidemiology approaches. Studies conducted based on Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) method in Muslim Middle East countries were evaluated to determine their role in TB control.

Materials and Methods
All studies from January 2005 to April 2016 were systematically reviewed in four electronic databases and finally 16 articles were found eligible to be included in this study. The mean clustering rate was determined as 44% and the recent transmission rate was 12.3 to 78.8% with average of 33%.

Results
The results showed that both reactivation and recent transmission were important in developing new cases of TB in Middle East countries; but, reactivation plays a more critical role.

Conclusion
Regarding to ongoing war and immigration in the region along with the increasing of drug-resistant TB, in the case of improper supervision in the future, the disease, especially drug- resistant TB, will be problematic.

Pourostadi|Mahya|M|
Rashedi|Jalil|J|
Mahdavi Poor|Behroz|B|
Samadi Kafil|Hossein|H|
Kazemi|Abdolhassan|A|
Ahmadpour|Ehsan|E|
Asgharzadeh|Mohammad|M|

Molecular epidemiology
tuberculosis
Middle East
transmission
MIRU-VNTR


Microvesicles and chemokines in tumor microenvironment: mediators of intercellular communications in tumor progression.

Abstract: Increasing evidence indicates that the ability of cancer cells to convey biological information to recipient cells within the tumor microenvironment (TME) is crucial for tumor progression. Microvesicles (MVs) are heterogenous vesicles formed by budding of the cellular membrane, which are secreted in larger amounts by cancer cells than normal cells. Recently, several reports have also disclosed that MVs function as important mediators of intercellular communication between cancerous and stromal cells within the TME, orchestrating complex pathophysiological processes. Chemokines are a family of small inflammatory cytokines that are able to induce chemotaxis in responsive cells. MVs which selective incorporate chemokines as their molecular cargos may play important regulatory roles in oncogenic processes including tumor proliferation, apoptosis, angiogenesis, metastasis, chemoresistance and immunomodulation, et al. Therefore, it is important to explore the association of MVs and chemokines in TME, identify the potential prognostic marker of tumor, and develop more effective treatment strategies. Here we review the relevant literature regarding the role of MVs and chemokines in TME.

Bian|Xiaojie|X| Xiao|Yu-Tian|YT| Wu|Tianqi|T| Yao|Mengfei|M| Du|Leilei|L| Ren|Shancheng|S| Wang|Jianhua|J|

Microvesicles
Chemokines
Tumor microenvironment
Tumor progression


Anal intraepithelial neoplasia: review and recommendations for screening and management.

Abstract: Anal cancer is a rare malignancy of the distal gastrointestinal tract, often associated with human papillomavirus, the most common sexually transmitted infection worldwide. Currently available screening methods for anal intraepithelial neoplasia, a precursor for anal cancer, combine anal Papanicolaou cytology and high resolution anoscopy with biopsy of suspicious lesions. Significant barriers to establishing anal cancer screening programmes include the small number of healthcare professionals performing high resolution anoscopy and the lack of data showing that anal cancer screening can reduce morbidity and mortality related to anal carcinoma. Despite several controversies surrounding anal cancer screening, the rising incidence of this disease in some groups supports routine screening programmes in high-risk populations, especially in HIV-positive men who have sex with men. This review outlines the epidemiology of anal intraepithelial neoplasia and anal cancer and summarizes issues related to the introduction of anal cancer screening programmes.

Smyczek|Petra|P|
Singh|Ameeta E|AE|
Romanowski|Barbara|B|

Anal intraepithelial neoplasia
screening
anal cancer
human papillomavirus
men who have sex with men
AIDS
AIN
HIV
HPV
MSM
anal cytology
treatment


Smart consultation for musculoskeletal trauma: accuracy of using smart phones for fracture diagnosis.

Abstract:
INTRODUCTION
Musculoskeletal trauma occupies a significant proportion of the daily workload of most Emergency and Radiology departments. The diagnosis and management of patients with musculoskeletal trauma often require assessment of radiographs along with clinical assessment. With the advent of smart phones we hypothesised that they could be used as a means of smarter communication, particularly for the transfer of radiographic images between healthcare professionals.

PATIENTS AND METHOD
We performed a cross sectional study using thirty radiographs each of the distal radius, ankle and hip. The study was approved by Ethics Committee and all data were anonymized in accordance to Caldicott guidelines and data protection act 1998. Photographs of radiographs were taken using an iphone camera and sent to three independent Orthopaedic Registrars via Multimedia messaging service (MMS). Each Registrar independently assessed these images on their smart phone display in their own time and recorded the specific diagnosis along with the classification of fractures and specific treatment plan. The accuracy of diagnosis on smart phone was measured against the radiology report; and inter observer agreement was assessed among registrars for classification and treatment plan.

RESULTS
The overall accuracy of fracture diagnosis was 97.7% with sensitivity of 100% and specificity of 94.4%. The inter observer agreement analysis showed kappa (k) values of 0.67, 0.67 and 0.71 for classification of wrist, ankle and hip fractures respectively showing substantial agreement while kappa values for management plan were 0.65, 0.88 and 0.65 for the three fractures respectively showing substantial to near perfect agreement.

CONCLUSION
This study suggests that smart phone can be used as a safe and accurate tool for skeletal trauma consultation among oncall doctors and can help reduce the waiting time in emergency departments.

Naqvi|G A|GA|
Daly|M|M|
Dawood|A|A|
Kurkuri|A|A|
Kutty|S|S|


Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair.

Abstract: Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future.

progenitor cell
regeneration
skeletal tissue repair
bone
tendon
ligament
cartilage
fibrocartilage
stem cell


Benchmark study on glyphosate-resistant cropping systems in the United States. Part 7: Effects of weed management strategy (grower practices versus academic recommendations) on the weed soil seedbank over 6 years.

Abstract:
BACKGROUND
Shifts in weed species composition and richness resulting from near-exclusive reliance on herbicides in glyphosate-resistant (GR) cropping systems has necessitated the implementation of alternative weed management tactics to reduce selection pressures of herbicides. We contrasted the response of the weed soil seedbank to effects of weed management strategy, comparing grower practices with academic recommendations for best management practices (BMPs) over 6 years and across five weed hardiness zones in the US Midwest at sites subject to GR cropping systems.

RESULTS
Total weed population density and species richness varied according to cropping system, location and prior year's crop, but less so to weed management strategy. The seedbank population density for 11 of the 14 most frequent weed species was affected by weed management strategy either alone or in an interaction with hardiness zone or year, or both. In only 29% of comparisons was weed population density lower following academic recommendations, and this depended upon prior crop and cropping system. The population density of high-risk weed species was reduced by academic recommendations, but only in two of six years and under continuous GR maize. Overall, the weed population density was decreasing in field halves subject to the BMPs in the academic recommendations relative to grower practices.

CONCLUSION
The soil seedbank is slow to respond to academic recommendations to mitigate glyphosate-resistant weeds, but represents a biological legacy that growers need to keep in mind even when management practices reduce emerged field weed population densities.

Gibson|David J|DJ|
Young|Bryan G|BG|
Owen|Micheal D K|MD|
Gage|Karla L|KL|
Matthews|Joseph L|JL|
Jordan|David L|DL|
Shaw|David R|DR|
Weller|Stephen C|SC|
Wilson|Robert G|RG|

maize
corn
cotton
genetically engineered crops
genetically modified crops
herbicide-resistant weeds
herbicide-tolerant crops
soybean
weed seedbank


Sorption as a rapidly response for oil spill accidents: A material and mechanistic approach.

Abstract: Accidents involving oil transportation has increase due to directly connection with the elevation of global energy demand. The environmental losses are tremendous and brings huge economic issues to remediate the spilled oil. This report presents an up-to-date review on an overall aspects of oil spill remediation techniques, the fundamentals and advantages of sorption, the most applied materials through diverse types of oil spill sites and oils with variety features, highlight to natural materials and future prospective. As the environment preservation progressively becomes a major social concern issue, the achievement of a worldwide distribution process aligned with environmental legislation and economic viability is crucial to the oil industry. For this, a specific preparation considering several scenarios must be carried out regarding minimization of oil spillages. Since the sorbent materials are decisive for sorption, it was approached the main sorbents: natural, graphenic, nano, polymeric and waste materials, and future trends.

Oliveira|Leonardo M T M|LMTM|
Saleem|Junaid|J|
Bazargan|Alireza|A|
Duarte|José Leandro da S|JLDS|
McKay|Gordon|G|
Meili|Lucas|L|

Remediation Sorbents Cleanup Fuels Petroleum


One-inflation and unobserved heterogeneity in population size estimation.

Abstract: We present the one-inflated zero-truncated negative binomial (OIZTNB) model, and propose its use as the truncated count distribution in Horvitz-Thompson estimation of an unknown population size. In the presence of unobserved heterogeneity, the zero-truncated negative binomial (ZTNB) model is a natural choice over the positive Poisson (PP) model; however, when one-inflation is present the ZTNB model either suffers from a boundary problem, or provides extremely biased population size estimates. Monte Carlo evidence suggests that in the presence of one-inflation, the Horvitz-Thompson estimator under the ZTNB model can converge in probability to infinity. The OIZTNB model gives markedly different population size estimates compared to some existing truncated count distributions, when applied to several capture-recapture data that exhibit both one-inflation and unobserved heterogeneity.

Unobserved heterogeneity
Negative binomial
Horvitz-Thompson
Capture-recapture
Count inflation


Retention of a reconstructed nipple using a C-V flap with different layer thicknesses in the C-flap.

Abstract:
BACKGROUND
The C-V flap for nipple reconstruction is now one of standard surgical techniques. But decreased projection is still a problem. In recent years, it has been suggested that projection can be more easily maintained when raising of the C-flap is performed with a split thickness dermis. In this study, we examined whether decrease of projection can be prevented by raising of a C-flap with a split dermis rather than with full dermis.

METHODS
A total of 49 consecutive patients who underwent reconstruction of a nipple using the C-V flap technique were enrolled. The patients included 22 who underwent surgery using a C-flap with a full thickness dermis (Group F), and 27 who underwent surgery with raising of a flap with a split thickness dermis (Group S). The size of the reconstructed nipple was measured at 2 weeks, 6 months and 1 year postoperatively for comparison between Groups F and S.

RESULTS
Partial necrosis of the C-flap end occurred in 4 subjects in only Group S. The decrease in projection after 1 year postoperatively in Group S was significantly lower than that in Group F. In contrast, the teat base size in Group F tended to be greater than that in Group S, suggesting a tendency for an expanded base using a flap with a full dermis.

CONCLUSIONS
Our results indicated that it is recommended to use a C-flap with a split dermis for cases with high projection of the nipple on the contralateral side.

Sowa|Yoshihiro|Y| Itsukage|Sizu|S| Sakaguchi|Kouichi|K| Taguchi|Tetsuya|T| Numajiri|Toshiaki|T|

C-V flap
Nipple reconstruction
breast reconstruction
nipple projection


Psychometric Properties of a Spanish-Language Version of a Short-Form FAMCARE: Applications to Caregivers of Patients With Alzheimer's Disease and Related Dementias.

Abstract: Although family satisfaction is recognized as a critical indicator of quality care for persons with serious illness, Spanish-language measures are limited. The study aims were to develop a Spanish translation of the short-form Family Satisfaction With End-of-Life Care (FAMCARE), investigate its psychometric properties in Hispanic caregivers to patients with Alzheimer's disease and related dementias (ADRD; N = 317; 209 interviewed in Spanish), and add parameters to an existing item bank. Based on factor analyses, the measure was found to be essentially unidimensional. Reliabilities from a graded item response theory model were high; the average estimate was 0.93 for the total and Spanish-language subsample. Discrimination parameters were high, and the model fit adequate. This is the first study to examine the performance of the short-form FAMCARE measure among Hispanics and caregivers to patients with ADRD. The short-form measure can be recommended for Hispanics and caregivers to patients with ADRD.

Teresi|Jeanne A|JA|
Ocepek-Welikson|Katja|K|
Ramirez|Mildred|M|
Ornstein|Katherine A|KA|
Bakken|Suzanne|S|
Siu|Albert|A|
Luchsinger|José A|JA|

FAMCARE
caregivers
item bank
item response theory
Alzheimer’s disease
Spanish language
confirmatory factor analyses
palliative care


Development and validation of a quantitative PCR assay for detection of Terrapene herpesvirus 2 in eastern box turtles (Terrapene carolina carolina).

Abstract: Herpesviruses are associated with disease in many chelonian species, resulting in pathology such as respiratory tract infection, stomatitis, conjunctivitis, hepatitis, and papillomatosis. Herpesvirus-associated fibropapillomas cause significant morbidity and mortality in marine turtles, and have been identified in an eastern box turtle (Terrapene carolina carolina) infected with Terrapene herpesvirus 2 (TerHV2). Further investigation is necessary to understand the impact of carcinogenic herpesviruses on chelonian health; however, reliable and specific methods for detection and quantitation of herpesviral load are lacking. The purpose of this study was to develop and validate a quantitative PCR assay for detection of TerHV2 in box turtles. TaqMan primer-probes were developed targeting the DNA polymerase gene. Inter- and intra-assay variability, linear range of detection, limit of detection, and specificity were assessed. The assay was highly specific for TerHV2, failing to amplify seven closely-related chelonian herpesviruses. It performed with high efficiency (slope = -3.52, R2 = 1, efficiency = 92.29 %), low intra-assay variability and low inter-assay variability (coefficient of variation ≤ 1.25 % at all standard dilutions). Reaction efficiency was not impacted in the presence of box turtle DNA from combined oral/cloacal swabs or whole blood. This qPCR assay has a linear range of detection from 107 to 101 viral copies per reaction and provides a valuable tool in the surveillance and characterization of TerHV2 in box turtles.

Engel|Aubrey I|AI|
Adamovicz|Laura|L|
Wellehan|James F X|JFX|
Allender|Matthew C|MC|

Terrapene herpesvirus 2
Eastern box turtle
Terrapene carolina
Chelonian
qPCR
Epidemiology


A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis.

Abstract: Microglial-derived inflammation has been linked to a broad range of neurodegenerative and neuropsychiatric conditions, including amyotrophic lateral sclerosis (ALS). Using single-cell RNA sequencing, a class of Disease-Associated Microglia (DAMs) have been characterized in neurodegeneration. However, the DAM phenotype alone is insufficient to explain the functional complexity of microglia, particularly with regard to regulating inflammation that is a hallmark of many neurodegenerative diseases. Here, we identify a subclass of microglia in mouse models of ALS which we term RIPK1-Regulated Inflammatory Microglia (RRIMs). RRIMs show significant up-regulation of classical proinflammatory pathways, including increased levels of Tnf and Il1b RNA and protein. We find that RRIMs are highly regulated by TNFα signaling and that the prevalence of these microglia can be suppressed by inhibiting receptor-interacting protein kinase 1 (RIPK1) activity downstream of the TNF receptor 1. These findings help to elucidate a mechanism by which RIPK1 kinase inhibition has been shown to provide therapeutic benefit in mouse models of ALS and may provide an additional biomarker for analysis in ongoing phase 2 clinical trials of RIPK1 inhibitors in ALS.

D053422:Receptor-Interacting Protein Serine-Threonine Kinases

ALS microglia RIPK1 neuroinflammation scRNAseq


Functional survey of decellularized tissues transplantation for infertile females.

Abstract: Numbers of women worldwide face infertility, which will have a significant impact on a couple's life. As a result, assisting with the treatment of these individuals is seen as a critical step. Successful births following uterus and ovary donation have been reported in recent. When immunosuppressive drugs are used in patients who receive donated tissues, there are always problems with the drugs' side effects. In recent years, tissue engineering has mainly been successful in treating infertility using decellularization techniques. Engineered uterus and ovary prevent immunological reactions and do not require immunosuppressive drugs. The most important aspect of using decellularized tissue is its proper function after transplantation. These tissues must be able to produce follicles, secrete hormones and cause pregnancy. This study aimed to investigate research on decellularized tissues and transplanted into the female reproductive system. In this study, just tissues that, after transplantation, have the proper function for fertility were investigated.

Decellularized tissue
Infertility
Tissue engineering
Reproductive system


Total arthroplasty of the hip by fritted alumina prosthesis. Experimental study and 1st clinical applications.

Abstract: A new material is proposed in total hip arthroplasty as a bearing component. The tolerance of dense ceramics was studied, as well as the anchorage of this material into bone. Physical, chemical and mechanical properties of the prosthesis were tested. Two hundred patients have already been operated on, but the follow-up is too short for any conclusion.

D000537:Aluminum Oxide
D019644:Arthroplasty, Replacement, Hip
D002516:Ceramics
D006622:Hip Prosthesis
D006801:Humans
D055585:Physical Phenomena
D011474:Prosthesis Design


Target Doppler Rate Estimation Based on the Complex Phase of STFT in Passive Forward Scattering Radar.

Abstract: This article presents a novel approach to the estimation of motion parameters of objects in passive forward scattering radars (PFSR). In such systems, most frequency modulated signals which are used have parameters that depend on the geometry of a radar scene and an object's motion. Worth noting is that in bistatic (or multistatic) radars forward scattering geometry is present thus in this case only Doppler measurements are available while the range measurement is unambiguous. In this article the modulation factor, also called the Doppler rate, was determined based on the chirp rate (equivalent Doppler rate) estimation concept in the time-frequency (TF) domain. This approach utilizes the idea of the complex phase of the short-time Fourier transform (STFT) and its modification known from the literature. Mathematical dependencies were implemented and verified and the simulation results were described. The accuracy of the considered estimators were also verified using the Cramer-Rao lower bound (CRLB) to which simulated data for the considered estimators was compared. The proposed method was validated using a real-life signal collected from a radar operating in PFSR geometry. The Doppler rate provided by a car crossing the baseline between the receiver and the GSM transmitter was estimated. Finally, the concept of using CR estimation, which in the case of PFSR can be understood as Doppler rate, was confirmed on the basis of both simulated and real-life data.

passive forward scattering radar
forward scattering radar
chirp rate estimation
passive radar
radar measurements
time-frequency analysis


Decreased serum ferritin may be associated with increased restless legs syndrome in Parkinson's disease (PD): a meta-analysis for the diagnosis of RLS in PD patients.

Abstract: Objective: Restless legs syndrome (RLS) is one of the most common non-motor symptoms of Parkinson's disease (PD), but its pathogenesis in a PD background is unclear. Abnormal iron metabolism may be involved, in which case it may be a marker of RLS risk. Here, the literature was systematically searched and meta-analyzed to compare iron metabolism markers between PD patients with or without RLS. Method: The databases PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, Web of Science, and SinoMed were searched for case-control and observational studies examining RLS-related changes in iron metabolism in PD, in terms of serum iron, serum ferritin and hemoglobin. Eligible studies were meta-analyzed using Stata 12.0. Results: Meta-analysis of 11 case-control studies showed that serum ferritin concentration was lower in PD patients with RLS than in those without RLS. (95%CI -0.32 to -0.03, p = 0.018). In contrast, levels of serum iron or hemoglobin did not differ significantly between PD patients with or without RLS. Conclusion: This meta-analysis may provide the first reliable pooled estimate of the correlation between abnormal iron metabolism and RLS in PD. The available evidence indicates that levels of ferritin, but not of serum iron or hemoglobin, correlate significantly with RLS in PD, with lower ferritin levels correlating to greater prevalence of RLS.

Li|Kelu|K| Liu|Bin|B| Wang|Fang|F| Bao|Jianjian|J| Wu|Chongmin|C| Huang|Xiaodong|X| Hu|Fayun|F| Xu|Zhong|Z| Ren|Hui|H| Yang|Xinglong|X|

ferritin
Restless legs syndrome
meta-analysis
Parkinson’s disease


Airflow-field-induced sandwich-type membrane of block copolymer for selective ion separation.

Abstract: A simple and effective airflow method to prepare sandwich-type block copolymer films is reported. The films are composed of three layers: vertically oriented nanocylinders align in both upper and bottom layers and irregular nanocylinders exist in the bulk of the film. The vertically oriented nanocylinders in both sides can provide high accessibility to ions and ensures the exchange of chemical species between the membrane and external environment, while the irregularly oriented nanocylinders in the middle part of the film can prolong the pathway of ions transportation and enhance ions selectivity.

Shan|Feng|F| Lu|Xuemin|X| Guan|Junfang|J| Lu|Qinghua|Q| Feng|Xingliang|X|

block copolymer
ions separation
airflow field
self-assembly


Compositional Characteristics of Glucuronide Conjugates in Regional Glechoma hederacea var. longituba Herbal Extracts Using a Set of Polyphenolic Marker Compounds.

Abstract: Glechoma hederacea var. longituba (GHL) is one of many herbal plants widely used in hot herbal teas and in oriental prescriptions to treat various diseases. Although the beneficial effects of GHL may be influenced by differences in the composition of active constituents in the herbal extracts, there are few reports on the compositional characteristics of GHL herbal extracts to date. In this study, liquid chromatography-mass spectrometry technology was used for comparative analysis of constituents in hot-water extracts of GHL samples obtained from various cultivating provinces in South Korea. A set of marker panel consisting of nine polyphenolic compounds, including glucuronide conjugates in particular, was constructed and used to monitor the compositional characteristics in each GHL extract. Our findings show that some of the marker compounds, including rosmarinic acid, were persistently observed as major constituents in the analyses of the 22 GHL sample extracts, whereas, interestingly, other marker compounds such as polyphenol-glucuronic acid conjugates displayed dramatic differences in compositional ratios. This chromatographic approach using the marker compound panel can be applied to qualitatively and quantitatively evaluate compositional characteristics in the GHL extracts, and can also be useful for quality assays of the GHL herbal plant in medicinal and industrial fields.

compositional characteristics
glucuronide conjugate
Glechoma hederacea var. longituba
polyphenol
LC–mass spectrometry


Upregulation of SERT and ADORA1 in broilers with acute right ventricular failure.

Abstract: Pulmonary hypertension (PH), remains a challenging disease with a large impact on both humans and meat-type chickens. PH is characterized by the onset of idiopathic pulmonary arterial hypertension leading to right ventricular failure. In this experiment relative gene expression of adenosine A1 receptor (ADORA1), serotonin transporter (SERT), phosphodiesterase 5A (PDE5) and troponin T2 were compared in hearts from broilers with acute right ventricular failure and from healthy birds. There were major increases in adenosine A1 receptor (177%) and serotonin transporter (475%), and more modest but significant increases in PDE5 (146%) and troponin T2 (140%) gene expressions in broilers with right ventricular failure compared to healthy birds (P<0.01). This novel report shows that pulmonary hypertension related gene expression in broilers is similar to that in humans. This molecular similarity between PH in broilers and human patients suggests, first, that they will make a suitable animal model for study PH in humans, but also that the literature on PH in humans may be profitably applied to the study of PH in broilers.

Kamely|Mohammad|M|
Karimi Torshizi|Mohammad Amir|MA|
Wideman|Robert F|RF|
West|James|J|

D054706:Cyclic Nucleotide Phosphodiesterases, Type 5

D050486:Serotonin Plasma Membrane Transport Proteins

Pulmonary hypertension
Gene expression
Adenosine
PDE5
Avian model


Analgesic and side effects of intravenous recombinant Phα1β.

Abstract:
Background
Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters.

Methods
Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined.

Results
Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters.

Conclusion
Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.

Side effects, Cardiac function, Motor activity, Biochemicals


Crystal structure, Hirshfeld surfaces and DNA cleavage investigation of two copper(II) complexes containing polypyridine and salicylide ligands.

Abstract: Two copper complexes 1 [Cu2(phen)2(salicylaldehyde)2(ClO4)2] and 2 [Cu2 (2,2'-dipyridyl)2(salicylaldehyde)2(ClO4)2] have been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. These two complexes were display binuclear structure with Cu(II) ions in distorted octahedral environment but antipodal orientation of the binuclear units between them. Molecular Hirshfeld surfaces revealed that the crystal structures of 1 and 2 were supported mainly by H-H, C-H⋯π, π⋯π (C-C), and C-H⋯O intermolecular interactions. DNA cleavage experiments of complexes 1 and 2 revealed that these complexes can intercalation with DNA.

Crystal structure
Hirshfeld surfaces
DNA cleavage
Copper complex


Peering into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness.

Abstract: 2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020-2021 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organization stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and easy cross to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8, its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins, we can be better prepared against H5N8 and other influenza A viruses.

influenza H5N8 reassortment mutation antiviral therapeutics vaccines virus


The presence of idiopathic thrombocytopenic purpura and incidence of acute non-ST elevation myocardial infarction.

Abstract: Platelets play an integral role in the pathogenesis of acute coronary syndrome (ACS). The purpose of this study was to investigate any correlation between immune thrombocytopenia (ITP) and non-ST segment elevation myocardial infarction (NTSEMI), a common presentation of ACS. Using the large Nationwide Inpatient Sample (NIS) database, we studied any correlation between NSTEMI and ITP utilizing ICD-9 codes. We performed uni- and multivariate analysis adjusting for risk factors from the years 2002-2011. Data was extracted from 106,653 ITP patients and 79,636,090 controls. In multiple years of the study period (2002-2011), NSTEMI incidence was significantly higher in ITP patients when compared with non-ITP patients in the univariate analysis (odds ratio average 1.226). However, no significant association was found after adjusting for additional risk factors in multivariate analysis. Based on our large database study, ITP is not independently associated with NSTEMI incidence after adjusting for comorbidity.

Idiopathic thrombocytopenic purpura
Thrombocytopenic
Myocardial infarction
Acute coronary syndrome
ITP
Autoimmune thrombocytopenia
Bleeding
Type 2 myocardial infarction


HCMV-Mediated Interference of Bortezomib-Induced Apoptosis in Colon Carcinoma Cell Line Caco-2.

Abstract: Human cytomegalovirus (HCMV) has been implicated in the development of human malignancies, for instance in colon cancer. Proteasome inhibitors were developed for cancer therapy and have also been shown to influence HCMV infection. The aim of this study was to investigate if proteasome inhibitors have therapeutic potential for colon carcinoma and how this is influenced by HCMV infection. We show by immunofluorescence and flow cytometry that the colon carcinoma cell line Caco-2 is susceptible to HCMV infection. Growth curve analysis as well as protein expression kinetics and quantitative genome analysis further confirm these results. HCMV has an anti-apoptotic effect on Caco-2 cells by inhibiting very early events of the apoptosis cascade. Further investigations showed that HCMV stabilizes the membrane potential of the mitochondria, which is typically lost very early during apoptosis. This stabilization is resistant to proteasome inhibitor Bortezomib treatment, allowing HCMV-infected cells to survive apoptotic signals. Our findings indicate a possible role of proteasome inhibitors in colon carcinoma therapy.

Härtel|Heike|H|
Theiß|Janine|J|
Abdelaziz|Mohammed O|MO|
Raftery|Martin J|MJ|
Pecher|Gabriele|G|
Bogner|Elke|E|0000-0001-7622-2900

apoptosis
human cytomegalovirus
Caco-2 cells
Bortezomib
co-culture
necroptosis


Leaching of benzimidazole antiparasitics in soil columns and in soil columns amended with sheep excreta.

Abstract: Benzimidazoles are anthelmintics frequently used in sheep farming due to the high susceptibility of these animals to parasitic diseases. Sheep excreta are often disposed onto soils as a fertilizer, and they may contain benzimidazole residues that can contaminate soil and water. This work aimed to assess the leaching behavior of benzimidazole drugs (albendazole, fenbendazole, and thiabendazole) and their metabolites in two Brazilian soils of different textural classifications (sandy and clay), as well as sheep excreta-amended soils, following the OECD 312 Guidelines. Ewes received a single oral dose of 10 mg kg-1 b.w. of either albendazole or fenbendazole. The feces were collected at 24, 48, 72, 96, and 120 h post-dose, and the parent drugs and their metabolites extracted using the QuEChERS approach and quantified by UHPLC-MS/MS. For the leaching assays, a benzimidazole solution was directly applied onto the soil columns, or an amount of 5 g of the medicated sheep feces was distributed over the top of the soil columns. In soil samples, benzimidazoles were extracted by solid-liquid extraction and quantified by UHPLC-MS/MS. For the leaching studies, atrazine was used as a reference substance to determine the relative mobility factor of the analytes of interest. Benzimidazoles were considered slightly to moderately mobile in both soils tested, with a leaching distance of up to 25 cm in a 30-cm soil column. Approximately 3 to 6% of the benzimidazoles present in ewe feces were able to leach into the soil columns. This finding is of concern since benzimidazoles are persistent in soil and may pose a risk to soil biota and induce the development of resistant strains of parasites.

Porto|Rafael Silveira|RS|
Pinheiro|Rafael Silvio Bonilha|RSB|
Rath|Susanne|S|

Leaching behavior
Brazilian soils
UHPLC-MS/MS
Sheep feces
Benzimidazoles and metabolites
Mobility in soil


Narratives of meaningful endurance - how migrant women escape the vicious cycle between health problems and unemployment.

Abstract: Migrant women in Europe have a higher incidence of health problems and have disproportionately high unemployment rates. We examine how Dutch and Turkish, Moroccan and Surinamese first and second generation migrant women escape the vicious cycle between health problems and unemployment by using the theory of the Sense of Coherence (SOC). We study how SOC works and whether SOC is also applicable outside the domain of health. Our findings from life story interviews (N = 54) show that women can escape this vicious cycle through the meaningful reconstruction of adversity. Women can put a halt on the on-going negative chain reaction through focusing on the meaning and purpose of adversity. We name such life stories narratives of meaningful endurance, which are characterized by structure, authorship and meaningful reconstruction, in opposition to its counterpart, narratives of non-directional distress. The three respective components of SOC - comprehensibility, manageability and meaningfulness - enable the attainment of a narrative of meaningful endurance and individuals with a stronger SOC are more likely to tell narratives of meaningful endurance. Theoretical and policy implications of our findings are discussed.

Narrative
Women
Health
Unemployment
Sense of coherence
Coping
Migration


Characterization and application of biochar-immobilized crude horseradish peroxidase for removal of phenol from water.

Abstract: Biochar (BC) has attracted much attention as an environmentally friendly material for application in wastewater treatment. In this study, a suitability of wood-derived BC as a support for covalent immobilization of horseradish peroxidase (HRP) across glutaraldehide as crosslinker, known for the capability to remove phenol from water, was investigated. The efficiency of the immobilized HRP in removal of phenol (2 mM) from water at different reaction conditions (varying dosages of polyethylene glycol (PEG300) 0-750 mg/L; H2O2 1.5-3.5 mM, as well as reaction time 5-120 min) and the general toxicity of bio-treated water (Allium cepa test) were measured. All analyzes were performed for free enzyme as well. The immobilized enzyme showed the highest activity at temperature 30 °C and pH 7.0. The greatest efficiency of immobilized enzyme in phenol removing (90 %) was obtained by applying 2.5 mM H2O2 and 1.5 mg/L of PEG300 at pH 7.0 after 2 h of reaction period. After 4 washings, immobilized HRP retained more than 79 % activity with phenol removal of 64 %. Utilizing immobilized enzyme significantly reduces the toxicity of the tested water (80 %), which further suggested that it might be considered as an environmentally acceptable process for wastewater treatment. Possible degradation products remained in treated water were analyzed in water samples by liquid and gas chromatography with mass spectrometry, including also analysis of volatiles by solid phase microextraction technique; different phenol-base compounds were detected.

Petronijević|Mirjana|M|
Panić|Sanja|S|
Savić|Saša|S|
Agbaba|Jasmina|J|
Molnar Jazić|Jelena|J|
Milanović|Marija|M|
Đurišić-Mladenović|Nataša|N|

Horseradish peroxidase
Biochar
Toxicity
Phenol removal
Water treatment


Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation.

Abstract: The present manuscript describes the synthesis, α-amylase inhibition, in silico studies and in-depth quantitative structure-activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. α-Amylase inhibitory potential of all compounds has been explored, where compound 7n exhibits remarkable α-amylase inhibition of 87.5% at 50 µg/mL. Robust QSAR models are made by using the balance of correlation method in CORAL software. The chemical structures at different concentration with optimal descriptors are represented by SMILES. A data set of 66 SMILES of 22 hydrazones at three distinct concentrations are prepared. The significance of the index of ideality of correlation (IIC) with applicability domain (AD) is also studied at depth. A QSAR model with best  = 0.8587 for split 1 is considered as a leading model. The outliers and promoters of increase and decrease of endpoint are also extracted. The binding modes of the most active compound, that is, 7n in the active site of Aspergillus oryzae α-amylase (PDB ID: 7TAA) are also explored by in silico molecular docking studies. Compound 7n displays high resemblance in binding mode and pose with the standard drug acarbose. Molecular dynamics simulations performed on protein-ligand complex for 100 ns, the protein gets stabilised after 20 ns and remained below 2 Å for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to Cα carbon atom is insignificant.

α-amylase inhibition
QSAR
aroyl hydrazone
Benzothiazole
IIC
molecular docking


The toxicity of cadmium-copper mixtures on daphnids and microalgae analyzed using the Biotic Ligand Model.

Abstract: For the prediction of metal mixture ecotoxicity, the BLM approach is promising since it evaluates the amount of metals accumulated on the biotic ligand on the basis of water chemistry, i.e., species (major cations) competing with metals, and related toxicity. Based on previous work by Farley et al. (2015) (MMME research project), this study aimed at modeling toxicity of Cd:Cu mixtures (0:1 - 1:1 - 1:0 - 1:2 - 1:3 - 2:1 - 3:1 - 4:1 - 5:1 - 6:1) to the crustacean Daphnia magna(48-h immobilization tests) and the microalga Pseudokirchneriella subcapitata (72-h growth inhibition tests). The 2012 version of the USGS model was chosen, assuming additivity of effects and accumulation of metals on a single site. The assumption that EDTA could contribute to toxicity through metals complexing was also tested, and potential effects due to reduction of ions Ca2+ absorption by metals were considered. Modeling started with parameter values of Farley et al. (2015) and some of these parameters were adjusted to fit modeled data on observed data. The results show that toxicity can be correctly predicted for the microalgae and that the hypothesis of additivity is verified. For daphnids, the prediction was roughly correct, but taking into account CuEDTA led to more realistic parameter values close to that reported by Farley et al. (2015). However, It seems that, for daphnids responses, metals interact either antagonistically or synergistically depending on the Cu:Cd ratio. Furthermore, synergy could not be explained by additional effects linked to a reduction of Ca absorption since this reduction, mainly due to Cd, increased inversely to synergy. Finally, the USGS model applied to our data was able to predict Cu:Cd mixture toxicity to microalgae and daphnids, giving rise to estimated EC50s roughly reflecting EC50s calculated from observed toxicity.

Mixture Daphnid Microalgae BLM EDTA Bioavailability Cadmium Copper


Elevated levels of both microRNA 378 (miR-378) and kallikrein-related peptidase 4 (KLK4) mRNA are associated with an unfavorable prognosis in triple-negative breast cancer.

Abstract: Triple-negative breast cancer (TNBC) patients have the worst outcome among all breast cancer subtypes. In oral squamous carcinoma cells, miR-378 was reported to target the mRNA of kallikrein-related peptidase 4 (KLK4), resulting in inhibition of cell proliferation, migration and invasion, induction of apoptosis, and reduction of tumor growth in vivo. Similarly, a miR-378/KLK4 axis has been proposed in prostate cancer. Here, we analyzed the correlation between miR-378 and KLK4 mRNA expression and determined the prognostic impact of both factors in TNBC. miR-378 and KLK4 mRNA expression levels were determined by quantitative PCR in tumor tissue of TNBC patients (n=103) and correlated with clinical parameters and patients' survival. There was no significant correlation between miR-378 and KLK4 mRNA expression. In univariate Cox regression analysis, elevated miR-378 expression was significantly associated with shortened disease-free survival (DFS, P=0.047) and overall survival (OS, P=0.031), high KLK4 mRNA levels were linked to a worse DFS (P=0.033). Combination of KLK4 mRNA and miR-378 (KLK4+miR-378, low/low versus high and/or high) allowed even better discrimination between favorable and unfavorable prognosis (DFS, P=0.008; OS, P=0.025). In multivariable analysis, miR-378 and KLK4+miR-378 expression remained independent predictive factors for DFS (P=0.014, P=0.010, respectively) and OS (P=0.016, P=0.049, respectively), while KLK4 mRNA only showed a trend towards significance for DFS (P=0.061). Our findings suggest that in TNBC there is no significant impact of miR-378 on KLK4 expression. Both factors, miR-378 and, to a lesser extent, KLK4 mRNA represent unfavorable prognostic markers in TNBC patients.

Gong|Weiwei|W| Zhu|Caixia|C| Liu|Yueyang|Y| Muckenhuber|Alexander|A| Bronger|Holger|H| Scorilas|Andreas|A| Kiechle|Marion|M| Dorn|Julia|J| Magdolen|Viktor|V| Dreyer|Tobias|T|

miR-378
kallikrein-related peptidase
KLK4
Triple-negative breast cancer
prognostic marker
clinical relevance


Designing optimal formulations for hot-melt coating.

Abstract: Hot-melt coating (HMC) as a solvent-free technology grants faster and more economic coating processes with reduced risk of dissolving the drug during the process. Moreover, traditional coating equipment can be modified to enable the HMC process. Despite the indubitable advantages and feasibility of the process, HMC is not well-known to pharmaceutical industry and its employment is still limited. The main aspect hindering the widespread application of this technique is the need of materials alternative to the conventional polymeric coatings. The current work reviews the published HMC formulations and describes the properties that have led to their selection. As these materials are mainly solid lipid excipients, attention should be paid to their crystallization and solid state behavior, and their impact on the performance of coated drug products, particularly on the stable drug release profile. Although different drug release profiles can be easily tailored, much development work is needed to respond to the unmet requirements of a stable formulation. Ensuring stable solid-state behavior and providing a mechanistic understanding of the macroscopic properties are essential steps towards fulfilling these requirements and establishing of HMC as advanced coating technology for manufacturing of pharmaceutical products.

Lopes|Diogo Gomes|DG|
Salar-Behzadi|Sharareh|S|
Zimmer|Andreas|A|

D002626:Chemistry, Pharmaceutical
D006358:Hot Temperature
D013678:Technology, Pharmaceutical

Hot-melt coating
Solvent-free technology
Stable formulation
Advanced performance
Lipid-based excipients


Irradiation abolishes smooth muscle investment into vascular lesions in specific vascular beds.

Abstract: The long-term adverse effects of radiotherapy on cardiovascular disease are well documented. However, the underlying mechanisms responsible for this increased risk are poorly understood. Previous studies using rigorous smooth muscle cell (SMC) lineage tracing have shown abundant SMC investment into atherosclerotic lesions, where SMCs contribute to the formation of a protective fibrous cap. Studies herein tested whether radiation impairs protective adaptive SMC responses during vascular disease. To do this, we exposed SMC lineage tracing (Myh11-ERT2Cre YFP+) mice to lethal radiation (1,200 cGy) followed by bone marrow transplantation prior to atherosclerosis development or vessel injury. Surprisingly, following irradiation, we observed a complete loss of SMC investment in 100% of brachiocephalic artery (BCA), carotid artery, and aortic arch lesions. Importantly, this was associated with a decrease in multiple indices of atherosclerotic lesion stability within the BCA. Interestingly, we observed anatomic heterogeneity, as SMCs accumulated normally into lesions of the aortic root and abdominal aorta, suggesting that SMC sensitivity to lethal irradiation occurs in blood vessels of neural crest origin. Taken together, these results reveal an undefined and unintended variable in previous studies using lethal irradiation and may help explain why patients exposed to radiation have increased risk for cardiovascular disease.

Newman|Alexandra Ac|AA|
Baylis|Richard A|RA|
Hess|Daniel L|DL|
Griffith|Steven D|SD|
Shankman|Laura S|LS|
Cherepanova|Olga A|OA|
Owens|Gary K|GK|

D000818:Animals
D001012:Aorta, Abdominal
D050197:Atherosclerosis
D001853:Bone Marrow
D016026:Bone Marrow Transplantation
D016122:Brachiocephalic Trunk
D002454:Cell Differentiation
D004195:Disease Models, Animal
D006801:Humans
D008297:Male
D051379:Mice
D000074085:Mice, Knockout, ApoE
D009131:Muscle, Smooth, Vascular
D032389:Myocytes, Smooth Muscle
D014916:Whole-Body Irradiation

Atherosclerosis
Radiation therapy
Vascular Biology


Immunotherapy for non-small cell lung cancer: are we on the cusp of a new era?

Abstract: In this editorial, we highlight the exciting advances in immunotherapy for the treatment of non-small cell lung cancer, with nivolumab being the first immunotherapeutic agent to be approved by the US FDA for the treatment of squamous lung cancer and several other promising immune checkpoint inhibitors currently being evaluated in clinical trials. The next step is to understand the mechanisms of resistance and develop rational combinations in an attempt to further improve the responses and survival in lung cancer.


The Property, Preparation and Application of Topological Insulators: A Review.

Abstract: Topological insulator (TI), a promising quantum and semiconductor material, has gapless surface state and narrow bulk band gap. Firstly, the properties, classifications and compounds of TI are introduced. Secondly, the preparation and doping of TI are assessed. Some results are listed. (1) Although various preparation methods are used to improve the crystal quality of the TI, it cannot reach the industrialization. Fermi level regulation still faces challenges; (2) The carrier type and lattice of TI are affected by non-magnetic impurities. The most promising property is the superconductivity at low temperature; (3) Magnetic impurities can destroy the time-reversal symmetry of the TI surface, which opens the band gap on the TI surface resulting in some novel physical effects such as quantum anomalous Hall effect (QAHE). Thirdly, this paper summarizes various applications of TI including photodetector, magnetic device, field-effect transistor (FET), laser, and so on. Furthermore, many of their parameters are compared based on TI and some common materials. It is found that TI-based devices exhibit excellent performance, but some parameters such as signal to noise ratio (S/N) are still lower than other materials. Finally, its advantages, challenges and future prospects are discussed. Overall, this paper provides an opportunity to improve crystal quality, doping regulation and application of TI.

Tian|Wenchao|W| Yu|Wenbo|W| Shi|Jing|J| Wang|Yongkun|Y|

property
preparation
application
topological insulator
doping
photodetector
magnetic device
FET
laser


Improving the detection specificity of endogenous MRI for reactive oxygen species (ROS).

Abstract:
BACKGROUND
The detection of tissue reactive oxygen species (ROS) using endogenous MRI methods has great potential applications in research and the clinic. We recently demonstrated that ROS produce a significant T1 -shortening effect. However, T1 or T1 -weighted contrast is not specific, as there are many other factors that alter tissue T1 .

PURPOSE
To investigate whether the presence of ROS alters tissue environmental conditions such as the proton exchange rate (K ex ) to improve the detection specificity of endogenous ROS MRI.

STUDY TYPE
Prospective.

SUBJECTS/PHANTOM
The ROS-producing phantoms consisted of fresh egg white treated with H2 O2 and healthy mice injected with pro-oxidative rotenone.

FIELD STRENGTH/SEQUENCE
T1 mapping was performed based on fast spin-echo sequence and K ex was evaluated using chemical exchange saturation transfer (CEST) MRI with varied saturation power (QUESP) on a 9.4 T animal scanner.

ASSESSMENT
Phantom experiments were conducted to evaluate the overall K ex of CEST-expressing metabolites in fresh egg white treated with H2 O2 of various concentrations (0, 0.025, 0.05, 0.1, and 0.25 v/v%). The egg white phantom continuously produced ROS for more than 3 hours. Various experiments were performed to rule out potential contributing factors to the observed K ex changes. In addition, in vivo MRI study was conducted with a well-established rotenone-exposed mouse model.

STATISTICAL TESTS
Student's t-test.

RESULTS
Egg white phantoms treated with H2 O2 of various concentrations showed a 26-85% increase in K ex compared with controls. In addition, the K ex of egg white is negligibly affected by other potential confounding factors, including paramagnetic contrast agents (<11%), oxygen (2.3%), and iron oxidation (<10%). Changes in temperature (<1°C) and pH (ΔpH <0.1) in H2 O2 -treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T1 relaxation time (6%) and increased K ex (9%) in rotenone-treated mice.

DATA CONCLUSION
We demonstrate that the specificity of endogenous ROS MRI can be improved with the aid of proton exchange rate mapping.

LEVEL OF EVIDENCE
2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.

Tain|Rong-Wen|RW|
Scotti|Alessandro M|AM|
Cai|Kejia|K|

reactive oxygen species
proton exchange rate
T1 relaxation time
CEST MRI
free radicals
oxidative stress


Timing of corticosteroids impacts mortality in hospitalized COVID-19 patients.

Abstract: The optimal timing of initiating corticosteroid treatment in hospitalized patients is unknown. We aimed to assess the relationship between timing of initial corticosteroid treatment and in-hospital mortality in COVID-19 patients. In this observational study through medical record analysis, we quantified the mortality benefit of corticosteroids in two equally matched groups of hospitalized COVID-19 patients. We subsequently evaluated the timing of initiating corticosteroids and its effect on mortality in all patients receiving corticosteroids. Demographic, clinical, and laboratory variables were collected and employed for multivariable regression analyses. 1461 hospitalized patients with confirmed COVID-19 were analyzed. Of these, 760 were also matched into two equal groups based on having received corticosteroid therapy. Patients receiving corticosteroids had a lower risk of death than those who did not (HR 0.67, 95% CI 0.67-0.90; p = 0.01). Timing of corticosteroids was assessed for all 615 patients receiving corticosteroids during admission. Patients receiving first dose of corticosteroids > 72 h into hospitalization had a lower risk of death compared to patients with first dose at earlier time intervals (HR 0.56, 95% CI 0.38-0.82; p = 0.003). There was a mortality benefit in patients with > 7 days of symptom onset to initiation of corticosteroids (HR 0.56, 95% CI 0.33-0.95; p = 0.03). In patients receiving oxygen therapy, corticosteroids reduced risk of death in mechanically ventilated patients (HR 0.38, 95% CI 0.24-0.60; p < 0.001) but not in patients on high-flow or other oxygen therapy (HR 0.46, 95% CI 0.20-1.07; p = 0.07) and (HR 0.84, 95% CI 0.35-2.00; p = 0.69), respectively. Timing of corticosteroids initiation was related to in-hospital mortality for COVID-19 patients. Time from symptom onset > 7 days should trigger initiation of corticosteroids. In the absence of invasive mechanical ventilation, corticosteroids should be initiated if the patient remains hospitalized at 72 h. Hypoxia requiring supplemental oxygen therapy should not be a trigger for initiation of corticosteroids unless the timing is appropriate.

Timing Corticosteroids Mortality COVID-19 Treatment Coronavirus


Alternatives in Assessing Mental Healthcare Disparities Using the Behavioral Risk Factor Surveillance System.

Abstract: Purpose: Identification of mental healthcare disparities through scales or questionnaires is an initial step to improve mental healthcare equity. This study was designed to investigate the performance of a single-item question relative to two psychiatric scales with multiple items in assessing mental healthcare disparities among U.S. adults using the Behavioral Risk Factor Surveillance System (BRFSS) data. Methods: The current depression (CD) and serious psychological distress (SPD) were analyzed in 2010 and 2012 with the BRFSS using two multiple-item scales in selected states. Receipt of mental health diagnosis and mental health treatment was ascertained respectively. In both years, a single item of the number of mentally unhealthy days from Centers for Disease Control Health-Related Quality of Life-4 (CDC-HRQOL-4) core questions was used to ascertain frequent mental distress (FMD) in all states. Logistic regression was used to identify mental healthcare disparities among subpopulations. The t-test was used to analyze missing data patterns. Results: Among adults who experienced FMD or CD in 2010, men, persons 65 years of age or older, non-Hispanic Blacks, persons who were currently or never married, and persons who were employed had a lower likelihood of receiving diagnosis of depression. Among adults who experienced FMD or SPD in 2012, men, persons 65 years of age or older, Hispanics and Blacks, persons who were currently employed or homemakers/students, and persons without healthcare coverage had a lower likelihood to receive mental health treatment. The missing rates of FMD were 1.8% (2010) and 1.4% (2012), while the missing rates of Patient Health Questionnaire 8 (PHQ-8) and Kessler 6 (K6) were 12.8% (2010) and 17.4% (2012). The samples with missing data were different from those without. Conclusions: The single-item question is a valuable alternative in a large population surveillance to identify vulnerable subpopulations for lower mental health diagnosis and treatment.

Liu|Jin|J|
Jiang|Ning|N|
Fan|Amy Z|AZ|
Weissman|Rebecca|R|

mental healthcare disparities
diagnosis
treatment
subpopulation
missing data


Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

Abstract: Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.

Kocsis|Kitti|K| Frank|Rita|R| Szabó|József|J| Knapp|Levente|L| Kis|Zsolt|Z| Farkas|Tamás|T| Vécsei|László|L| Toldi|József|J|

acetyl-l-carnitine
neuroprotection
long-term potentiation
PI3K/Akt
ischemia
oxygen–glucose deprivation


Patients' perspectives on factors facilitating adherence to tuberculosis treatment in Iquitos, Peru: a qualitative study.

Abstract:
BACKGROUND
Tuberculosis is a major global health problem and one of the greatest barriers to its control is poor adherence to treatment. Peru has one of the highest burdens of TB in South America, with an incidence rate of 123 per 100,000 populations. There is currently a lack of evidence in South America about factors that facilitate adherence to treatment, with most previous research focusing on factors that negatively influence adherence to TB treatment.

SETTING
This study was conducted in Iquitos, the capital city of the Loreto region, north-eastern Peru. Loreto has a high incidence of tuberculosis, estimated at 99 per 100,000 population, and a high poverty rate.

METHODS
Twenty face-to-face, semi-structured interviews were conducted at two healthcare centres. Data collected from the interviews was analysed using thematic content analysis.

RESULTS
Three main themes emerged from the data set. Personal Qualities, such as responsibility and determination, were perceived as important factors facilitating adherence. Participants described their Trust in Healthcare Providers positively, particularly focusing on their trust in clinical staff, although knowledge of tuberculosis and its treatment was limited. Social Support, from a variety of sources, was also seen as a driving factor for continued adherence.

CONCLUSIONS
The results suggest that more emphasis should be placed on educating tuberculosis patients about their disease and its treatment. Additionally, consideration should be given to improving the social support available to patients, for example with tuberculosis support groups involving 'expert' tuberculosis patients.

Anthoney|James|J|
De Wildt|Gilles|G|
Meza|Graciela|G|
Skelton|John|J|
Newell|Ian|I|

Adherence Tuberculosis Peru Qualitative Adult Compliance Therapeutics


The pandemic semesters: Examining public opinion regarding online learning amidst COVID-19.

Abstract: The current educational disruption caused by the COVID-19 pandemic has fuelled a plethora of investments and the use of educational technologies for Emergency Remote Learning (ERL). Despite the significance of online learning for ERL across most educational institutions, there are wide mixed perceptions about online learning during this pandemic. This study, therefore, aims at examining public perception about online learning for ERL during COVID-19. The study sample included 31,009 English language Tweets extracted and cleaned using Twitter API, Python libraries and NVivo, from 10 March 2020 to 25 July 2020, using keywords: COVID-19, Corona, e-learning, online learning, distance learning. Collected tweets were analysed using word frequencies of unigrams and bigrams, sentiment analysis, topic modelling, and sentiment labeling, cluster, and trend analysis. The results identified more positive and negative sentiments within the dataset and identified topics. Further, the identified topics which are learning support, COVID-19, online learning, schools, distance learning, e-learning, students, and education were clustered among each other. The number of daily COVID-19 related cases had a weak linear relationship with the number of online learning tweets due to the low number of tweets during the vacation period from April to June 2020. The number of tweets increased during the early weeks of July 2020 as a result of the increasing number of mixed reactions to the reopening of schools. The study findings and recommendations underscore the need for educational systems, government agencies, and other stakeholders to practically implement online learning measures and strategies for ERL in the quest of reopening of schools.

Emergency Remote Learning
schools
reopening
COVID‐19
online teaching and learning


Transfection of immortalized keratinocytes by low toxic poly(2-(dimethylamino)ethyl methacrylate)-based polymers.

Abstract: Skin carcinoma are among the most spread diagnosed tumours in the world. In this study, we investigated the transfection of immortalized keratinocytes, used as an in vitro model for skin carcinoma, using antisense technology and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)-based polymers, with original architecture and functionalities. We tested PDMAEMA polymers with different structures: linear, with two (DEA-PDMAEMA) or three (TEA-PDMAEMA) arms. The cytotoxicity of these polymers was assessed over a wide range of apparent M n (from 7600 to 64 600). At a N/P ratio of 7.38, cytotoxicity increases with the M n. Keratinocytes were transfected with a fluorescent oligonucleotide and then analyzed by flow cytometry. For the three architectures tested, the percentage of transfected cells and abundance of internalized oligonucleotide were closely related to the M n of the polymer. Confocal microscopy and FACS analyses showed a wide spread fine granular distribution of the oligonucleotide up to 3 days post-transfection. Then, we assessed the silencing efficiency of the polymers, targeting GFP in GFP expressing keratinocytes. The maximal silencing effect (±40%) was obtained using a DEA-PDMAEMA polymer (M n = 30 300). These results suggest that PDMAEMA-based polymers can be efficiently used to transfect immortalized keratinocytes and, thus, open new perspectives in the therapy of skin carcinoma.

Van Overstraeten-Schlögel|Nancy|N|
Ho-Shim|Yong|Y|
Tevel|Virginie|V|
Bontems|Sébastien|S|
Dubois|Philippe|P|
Raes|Martine|M|

D006576:Heterocyclic Compounds, 4 or More Rings

TRANSFECTION
KERATINOCYTES
SKIN CARCINOMA
2-(DIMETHYLAMINO)ETHYL METHACRYLATE
ANTISENSE OLIGONUCLEOTIDE
HOSTASOL


The Effect of the Targeted Recombinant Toxin DARPin-PE40 on the Dynamics of HER2-Positive Tumor Growth.

Abstract: The development of targeted toxins based on non-immunoglobulin targeting molecules appears to be one of the most advanced approaches in the targeted therapy of malignant tumors with a high expression of the HER2 receptor. Earlier, we showed that the targeted toxin DARPin-PE40 consisting of the HER2-specific non-immunoglobulin polypeptide (the targeting module) and a fragment of Pseudomonas exotoxin A (the toxic module) exhibits an antitumor effect in vivo against the HER2-positive adenocarcinoma xenograft. In this work, an in-depth analysis of the effect of DARPin-PE40 on the growth dynamics of experimental xenograft tumors was carried out. DARPin-PE40 was shown to inhibit tumor growth at a dose of 25 and 50 μg/animal and to cause tumor node reduction at a dose of 80 μg/animal, followed by growth resumption at the end of therapy. An evaluation of the tumor growth dynamics revealed statistically significant differences in tumor volume in mice in the experimental groups compared to the control group. The results testify to the potential of using the created targeted toxin as an agent for the targeted therapy of HER2-overexpressing tumors.

Sokolova|E A|EA|
Proshkina|G M|GM|
Kutova|O M|OM|
Balalaeva|I V|IV|
Deyev|S M|SM|

targeted therapy
HER2 receptor
Pseudomonas aeruginosa exotoxin A
non-immunoglobulin module DARPin


Investigating the experiences of New Zealand MRI technologists: Exploring intra-orbital metallic foreign body safety practices.

Abstract:
INTRODUCTION
Qualitative research is lacking regarding the experiences of magnetic resonance imaging (MRI) technologists and their involvement in workplace safety practices. This article provides a gateway to explore, describe and document experiences of MRI technologists in New Zealand (NZ) pertaining to intra-orbital metallic foreign body (IMFB) safety practices.

METHODS
This phenomenological study describes the experiences of seven MRI technologists all with a minimum of 5 years' NZ work experience in MRI. The MRI technologists were interviewed face-to-face regarding their professional IMFB workplace experiences in order to explore historical, current and potential issues.

RESULTS
Findings demonstrated that aspects of organization and administration are fundamentally important to MRI technologists. Varying levels of education and knowledge, as well as experience and skills gained, have significantly impacted on MRI technologists' level of confidence and control in IMFB practices. Participants' descriptions of their experiences in practice regarding decision-making capabilities further highlight the complexity of these themes. A model was developed to demonstrate the interrelated nature of the themes and the complexity of the situation in totality.

CONCLUSIONS
Findings of this study have provided insight into the experiences of MRI technologists pertaining to IMFB safety practices and highlighted inconsistencies. It is hoped that these findings will contribute to and improve the level of understanding of MRI technologists and the practices and protocols involved in IMFB safety screening. The scarcity of available literature regarding IMFB safety practices highlights that more research is required to investigate additional aspects that could improve MRI technologists' experiences.

MRI technologist
Intra-orbital metallic foreign body
safety practices
lived experiences