COVID-19, Coenzyme Q10 and Selenium.

Abstract: In COVID-19 infection, a balance must be achieved in immune defence against the virus without precipitating a cytokine storm, which is responsible for lung injury and respiratory distress in severe cases. The initial immune response and the subsequent resolution of inflammation are likely to be dependent on nutritional status, as one contributing factor. Here, we have reviewed the potential link between two specific nutrients, coenzyme Q10 (CoQ10) and selenium, with effects on oxidative stress and inflammation in viral infection. We conclude that both reagents show promise in the treatment of patients with COVID-19 disease. This could give particular relevance over the next several months as promising vaccines are deployed to minimise the COVID-19 spread and as a potential preventative or mitigating approach for future epidemics and pandemics.


Does Video Laryngoscopy Offer Advantages over Direct Laryngoscopy during Cardiopulmonary Resuscitation?

Abstract:
OBJECTIVE
Interruption of chest compressions should be minimized because of its negative effects on survival. This randomized, controlled, cross-over study aimed to analyze the effectiveness of Macintosh, Miller, McCoy and McGrath laryngoscopes during with or without chest compressions in the scope of a simulated cardiopulmonary resuscitation scenario.

METHODS
The time required for successful tracheal intubation, number of attempts, dental trauma severity and the need for optimization manoeuvres were recorded during cardiopulmonary resuscitation with and without chest compressions. The experience with computer games during the last 10 years were asked to the participants and recorded.

RESULTS
McCoy laryngoscope yielded the shortest time for successful tracheal intubation both in the presence of and without chest compressions. During the use of McCoy laryngoscopes, fewer tracheal intubation attempts, lower incidence of dental trauma and lower visual analogue scale scores on the ease of intubation were recorded. Participants who are experienced computer game players using Macintosh, McCoy and McGrath achieved successful tracheal intubation in a significantly shorter time during resuscitation without chest compressions. Dental trauma incidence and number of tracheal intubation attempts did not show any significant difference between the four laryngoscopes being related to the rate of playing computer games.

CONCLUSION
McGrath video laryngoscopes do not appear to have advantages over direct laryngoscopes for securing a smooth and successful tracheal intubation during rhythmic chest compressions. We believe that as McCoy laryngoscope provided tracheal intubation in a shorter time and with fewer attempts, this laryngoscope may increase the success rate of resuscitation.

Saraçoğlu|Ayten|A|
Bezen|Olgaç|O|
Şengül|Türker|T|
Uğur|Egin Hüsnü|EH|
Şener|Sibel|S|
Yüzer|Fisun|F|

resuscitation
chest compression
Tracheal intubation


Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.

Abstract:
BACKGROUND
Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown.

OBJECTIVES
To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration.

STUDY DESIGN
Prospective experimental study.

METHODS
A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior to and 2, 12 and 24 h after benazepril administration, each horse received intravenous (i.v.) boluses of ANG-I at 20, 60 and 200 ng/kg. Attenuation of the systolic arterial pressure (SBP) response to ANG-I and serum ACE activity were quantified and expressed as percentage of inhibition.

RESULTS
There was a significant effect of benazepril dose (P = 0.004) and time (P = 0.004) on the percentage of inhibition of the systolic pressor response to ANG-I. Regardless of benazepril dose, the percentage of inhibition was significantly greater 2 h after administration of benazepril compared with 12 and 24 h. At an ANG-I dose of 20 ng/kg, the percentage of inhibition after administration of benazepril at 1 mg/kg bwt (46.6 ± 18.9%) was significantly greater than that achieved after 0.5 mg/kg bwt (19 ± 14%) but not significantly different from that achieved at higher doses of benazepril. Benazepril doses ≥1 mg/kg bwt resulted in serum ACE inhibition of at least 90%.

MAIN LIMITATIONS
Small sample size and resulting low statistical power.

CONCLUSIONS
Attenuation of the rise in SBP in response to ANG-I after administration of benazepril is modest in horses despite adequate serum ACE inhibition. A dose of 1 mg/kg bwt would be recommended for future investigations of benazepril for the management of cardiovascular diseases in horses.

Afonso|T|T|
Giguère|S|S|
Rapoport|G|G|
Brown|S A|SA|
Coleman|A E|AE|

horse
ACE inhibitor
cardiology
pressure response to angiotensin


Status and influential factors of vitamin D among children aged 0 to 6 years in a Chinese population.

Abstract:
BACKGROUND
Vitamin D insufficiency and deficiency in childhood are common. However, the status and influential factors of vitamin D during different ages are not clear. This study aimed to survey vitamin D concentrations in children aged 0 to 6 years and explore its influential factors.

METHODS
A total of 6953 children were recruited in Wuxi City of East China from January to December in 2016. Enzyme-linked immunosorbent assay was used to determine the serum concentrations of 25-hydroxyvitamin D [25(OH)D].

RESULTS
The median vitamin D concentrations in the infant group (0-1 years of age) was 69.40 nmol/L, which were higher than that in both the toddlerhood group (1-3 years of age; 62.30 nmol/L) and the preschool group (3-6 years of age; 50.85 nmol/L). In addition, the median vitamin D concentrations were 71.70 nmol/L in summer, which was higher than that in spring (64.25 nmol/L), autumn (62.95 nmol/L) and winter (64.10 nmol/L). However, no difference was observed between genders (P = 0.974). Furthermore, the prevalence of vitamin D deficiency (< 50 nmol/L) was 48.1% in the preschool group (3-6 years of age), which was higher than the 21.2% vitamin D deficiency in the toddlerhood group (1-3 years of age) and the 17.9% vitamin D deficiency in the infant group (0-1 years of age). Interestingly, a nonlinear association between 25(OH) D and air temperature was observed.

CONCLUSIONS
A high prevalence of vitamin D deficiency was common in a Chinese population of children 0-6 years old, especially in the preschool-aged children. Therefore, we suggested that we should pay more attention to vitamin D supplementation in Chinese young children.

Zhang|Heng|H| Li|Zhijuan|Z| Wei|Yarong|Y| Fu|Jinyan|J| Feng|Yaling|Y| Chen|Daozhen|D| Xu|Dexiang|D|

Vitamin D
Children age
Deficiency
Air temperature
Season


Patho-mechanisms of the origins of bronchopulmonary dysplasia.

Abstract: Bronchopulmonary dysplasia (BPD) continues to be one of the most common complications of prematurity, despite significant advancement in neonatology over the last couple of decades. The new BPD is characterized histopathologically by impaired lung alveolarization and dysregulated vascularization. With the increased survival of extremely preterm infants, the risk for the development of BPD remains high, emphasizing the continued need to understand the patho-mechanisms that play a role in the development of this disease. This brief review summarizes recent advances in our understanding of the maldevelopment of the premature lung, highlighting recent research in pathways of oxidative stress-related lung injury, the role of placental insufficiency, growth factor signaling, the extracellular matrix, and microRNAs.

Growth factors
Chronic lung disease
Hyperoxia
Placenta
Preterm lung
miRNA


Children's dental treatment requirements of first permanent molars with poor prognosis.

Abstract:
OBJECTIVES
This retrospective study aimed to (i) survey the correlation between decayed, missing, filled teeth (DMFT), and presence of first permanent molars (FPMs) with poor prognosis and (ii) evaluate the treatment requirements.

MATERIALS AND METHODS
Seven hundred seventy-three children with fully erupted FPMs were included in this study. DMFT for the permanent dentition, FPMs, and Global DMFT were evaluated based on clinical and radiographic evaluation. The ratio of deep dentin caries (DDC) and apical lesion presence among FPMs, including treatment requirements, were analysed. Spearman rank correlation coefficient and t tests were used for statistical analysis.

RESULTS
The caries prevalence was found at 61.4%, where the mean DMFT was calculated as 1.89 ± 2.15. There was a positive correlation between DMFT values and age (rs = 0.27). On the other hand, there was a negative correlation between global DMFT values and age (rs =  - 0.29). Regarding treatment needs of FPM with poor prognosis, 12.03% of the teeth needed pulpectomy, 8.93% pulpotomy, 8.93% pulp capping, and 5.3% extraction. Having higher DMFT values was correlated significantly (p < 0.01) with the presence of DDC (rs = 0.50) and apical lesion (rs = 0.34). Susceptibility to DDC and apical lesions was significantly higher at mandible than maxilla (p < 0.01). The correlation was significant between DMFT values and apical lesion presence (p < 0.01).

CONCLUSION
The ratio of FPMs with poor prognosis was found high in the study group. Treatment requirements of FPMs increased with age, and pulp interventions often took part in the majority. This study successfully concluded that higher DMFT values were correlated with the presence of DDC and apical lesion.

CLINICAL RELEVANCE
FPMs with poor prognosis demonstrate a risk factor for apical lesion presence.

First permanent molar
Permanent dentition
Deep dentin caries
Treatment needs
Dental care for children
Dental caries


Experimental Support That Natural Selection Has Shaped the Latitudinal Distribution of Mitochondrial Haplotypes in Australian Drosophila melanogaster.

Abstract: Cellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude, or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance. Specifically, haplotypes predominating in tropical climates are predicted to encode increased tolerance to heat stress, but decreased tolerance to cold stress. We present direct evidence for these predictions, using mtDNA haplotypes sampled from the Australian distribution of Drosophila melanogaster. We show that the ability of flies to tolerate extreme thermal challenges is affected by sequence variation across mtDNA haplotypes, and that the thermal performance associated with each haplotype corresponds with its latitudinal prevalence. The haplotype that predominates at low (subtropical) latitudes confers greater resilience to heat stress, but lower resilience to cold stress, than haplotypes predominating at higher (temperate) latitudes. We explore molecular mechanisms that might underlie these responses, presenting evidence that the effects are in part regulated by SNPs that do not change the protein sequence. Our findings suggest that standing variation in the mitochondrial genome can be shaped by thermal selection, and could therefore contribute to evolutionary adaptation under climatic stress.

Camus|M Florencia|MF|
Wolff|Jonci N|JN|
Sgrò|Carla M|CM|
Dowling|Damian K|DK|

natural selection
mitochondrial DNA
ecology
evolution
genome evolution
thermal adaptation


More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?

Abstract: The bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a mitochondrial one-carbon folate metabolic enzyme whose role in cancer was not known until recently. MTHFD2 is highly expressed in embryos and a wide range of tumors but has low or absent expression in most adult differentiated tissues. Elevated MTHFD2 expression is associated with poor prognosis in both hematological and solid malignancy. Its depletion leads to suppression of multiple malignant phenotypes including proliferation, invasion, migration, and induction of cancer cell death. The non-metabolic functions of this enzyme, especially in cancers, have thus generated considerable research interests. This review summarizes current knowledge on both the metabolic functions and non-enzymatic roles of MTHFD2. Its expression, potential functions, and regulatory mechanism in cancers are highlighted. The development of MTHFD2 inhibitors and their implications in pre-clinical models are also discussed.

Zhu|Zhiyuan|Z|
Leung|Gilberto Ka Kit|GKK|

metabolic enzyme
cancer metabolism
epigenetic modification
oncogenicity
one carbon metabolism


Spoilage Potential of Pseudomonas (P. fragi, P. putida) and LAB (Leuconostoc mesenteroides, Lactobacillus sakei) Strains and Their Volatilome Profile During Storage of Sterile Pork Meat Using GC/MS and Data Analytics.

Abstract: The aim of the present study was to investigate the evolution of the volatile compounds of aerobically stored sterile pork meat as a consequence of the metabolic activities of inoculated specific spoilage microorganisms. Thus, Pseudomonas fragi, Pseudomonas putida, Lactobacillus sakei and Leuconostoc mesenteroides were inoculated in monocultures, dual cultures and a cocktail culture of all strains on sterile pork meat stored aerobically at 4 and 10 °C. Microbiological and sensory analyses, as well as pH measurements, were performed, along with headspace solid-phase microextraction gas chromatography/mass spectroscopy (headspace SPME-GC/MS) analysis. Data analytics were used to correlate the volatile compounds with the spoilage potential of each stain using multivariate data analysis. The results for the sensory discrimination showed that the volatiles that dominated in spoiled samples consisted mostly of alcohols, ketones and two esters (butyl acetate and ethyl acetate), while at fresh samples, dimethyl sulfide, furans, acetoin and ethyl lactate were detected. On the other hand, 2-butanone, diacetyl and acetaldehyde were among the volatile compounds that were mainly correlated with the inoculated meat during storage. In addition, P. fragi was positively correlated with a higher number of volatiles compared to the other strains, strengthening the hypothesis that volatile compound production is strain-dependent.

sterile pork meat
data analytics
solid-phase microextraction
aerobic storage
gas chromatography-mass spectrometry
metabolomics
specific spoilage organisms


Small angle X-ray scattering and molecular dynamic simulations provide molecular insight for stability of recombinant human transferrin.

Abstract:
Transferrin is an attractive candidate for drug delivery due to its ability to cross the blood brain barrier. However, in order to be able to use it for therapeutic purposes, it is important to investigate how its stability depends on different formulation conditions. Combining high-throughput thermal and chemical denaturation studies with small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, it was possible to connect the stability of transferrin with its conformational changes. Lowering pH induces opening of the transferrin N-lobe, which results in a negative effect on the stability. Presence of NaCl or arginine at low pH enhances the opening and has a negative impact on the overall protein stability.

Statement of Significance
Protein-based therapeutics have become an essential part of medical treatment. They are highly specific, have high affinity and fewer off-target effects. However, stabilization of proteins is critical, time-consuming, and expensive, and it is not yet possible to predict the behavior of proteins under different conditions. The current work is focused on a molecular understanding of the stability of human serum transferrin; a protein which is abundant in blood serum, may pass the blood brain barrier and therefore with high potential in drug delivery. Combination of high throughput unfolding techniques and structural studies, using small angle X-ray scattering and molecular dynamic simulations, allows us to understand the behavior of transferrin on a molecular level.

Kulakova|Alina|A|
Indrakumar|Sowmya|S|
Sønderby|Pernille|P|
Gentiluomo|Lorenzo|L|
Streicher|Werner|W|
Roessner|Dierk|D|
Frieß|Wolfgang|W|
Peters|Günther H J|GHJ|
Harris|Pernille|P|

small angle X-ray scattering
molecular dynamics
stability
transferrin
formulation


Cytomegalovirus meningoencephalitis in a case of severe COVID-19 Pneumonia. A case report.

Abstract: The use of steroids and other immune modulatory therapies in the treatment of severe COVID-19 pneumonia predisposes patients to the reemergence of opportunistic infections. Cytomegalovirus (CMV) reactivation can be one of them. A 55-year-old gentleman with severe COVID-19 pneumonia and hypoxic respiratory failure who was ventilated and received steroids but no other immunomodulatory drugs; had altered sensorium and multiple episodes of seizures in the later course of his illness. Brain MRI showed leptomeningeal enhancement and encephalopathy changes, electroencephalography (EEG) was suggestive of diffuse encephalopathy and his cerebrospinal fluid (CSF) analysis revealed high Cytomegalovirus PCR DNA titers (103,614). The patient made a complete recovery after treatment with Ganciclovir. Altered sensorium in cases of COVID-19 can be multifactorial. High index of suspicion for reactivation of dormant infections is warranted. CMV meningoencephalitis is one of the differential diagnoses. We believe this is the first case reported of CMV meningoencephalitis in the setting of severe COVID-19 infection.

Ananthegowda|Dore C|DC|
Khatib|Mohamad Y|MY|
Ali|Husain S|HS|
Al Wraidat|Mohamed|M|
Imam|Yahia|Y|

Meningoencephalitis
Case report
Steroids
Opportunistic infections
CMV
Ganciclovir
COVID 19
Immunosuppression


Candida albicans and Oral Carcinogenesis. A Brief Review.

Abstract: Current medical knowledge and research on patients' management are still evolving, and several protocols on minimizing risk of infection by Candida spp. among the population have developed. The aim of this work is to review the epidemiological and biomolecular characteristics and the various histopathological carcinogenesis hypothesis mechanisms that can occur during Candida albicans infections. Current evidence from the literature on the role of C. albicans during potentially malignant oral disorders and oral cancer has been sought. Thus, these biomolecular processes can give or contribute to benign lesions, also in precancerous or cancerous situations. Alongside this, the physiological microorganism oral flora (microbiota) can play a crucial role in maintaining oral health during those infections and therefore avoid carcinogenesis.

Candida albicans
oral cancer
inflammation
oncogenesis
oral infections
oral microbiota


Communicating about death and dying with adults with intellectual disabilities who are terminally ill or bereaved: A UK-wide survey of intellectual disability support staff.

Abstract:
BACKGROUND
Illness and death are part of life for everyone, including people with intellectual disabilities. This study investigated the extent to which staff communicate about death with people with intellectual disability facing terminal illness or bereavement.

METHOD
Staff who support people with intellectual disability in the UK (n = 690) completed an electronic survey. Detailed data were obtained from staff where a client had died in the past 12 months (n = 111), was terminally ill (n = 41) or had been bereaved (n = 200). Analysis included descriptive and chi-squared statistics.

RESULTS
52.6% of people with intellectual disability who were terminally ill were told about their illness, and 18.1% were told they would die. Of those experiencing an anticipated bereavement, 32.4% of staff said no one talked about this with them beforehand. A quarter of staff had received training on end of life or bereavement.

CONCLUSION
Death affects many people with intellectual disability. Staff require training and support in communicating death.

communication
death and dying
intellectual disabilities
bereavement
breaking bad news
truth disclosure


The expression of endothelin-1 in chronic lymphocytic leukemia is controlled by epigenetic mechanisms and extracellular stimuli.

Abstract: Endothelin-1 (ET-1) is a hormone peptide widely expressed and is involved in several biological processes, important not only for normal cell function but also for tumor development, including cell proliferation, invasion, metastasis, angiogenesis and osteogenesis. In accordance, ET-1 was already shown to contribute to the growth and progression of many different solid cancers. We recently demonstrated that ET-1 has a role in the pathogenesis of chronic lymphocytic leukemia (CLL) where it is abnormally expressed. In the context of this malignancy, ET-1 is able to mediate survival, drug-resistance and growth signals in leukemic cells. Previous studies, not conducted in CLL, have shown that ET-1 regulatory mechanisms are numerous and cell specific. Here, we valued the expression of ET-1 in CLL, in relation to DNA methylation but also in response to stimulation of some important pathways for the dialogue between CLL and microenvironment. We found that a high methylation of ET-1 first intron affects the basal expression of ET-1 in CLL. Moreover, we showed that the activation of CD40 or Toll-like receptor (TLR) by extracellular stimuli produces an augment of ET-1 level in CLL cells. Finally, we demonstrated the fundamental role of NF-kB signalling pathway in promoting and maintaining ET-1 expression in CLL cells, both in basal conditions and after CD40 activation.

Martinelli|Silvia|S| Maffei|Rossana|R| Fiorcari|Stefania|S| Quadrelli|Chiara|C| Zucchini|Patrizia|P| Benatti|Stefania|S| Potenza|Leonardo|L| Luppi|Mario|M| Marasca|Roberto|R|

D015451:Leukemia, Lymphocytic, Chronic, B-Cell

Endothelin-1
Chronic lymphocytic leukemia
DNA methylation
NF-kB
CD40 stimulation
Transcriptional regulation


Investigation of carbon dynamics in rhizosphere by synchrotron radiation-based Fourier transform infrared combined with two dimensional correlation spectroscopy.

Abstract: Rhizosphere, formed via the input of root exudates, is one of the most dynamic biological interfaces on earth. Investigation of carbon dynamics in rhizosphere is thus crucial for the understanding of soil biogeochemical processes. Herein, synchrotron radiation-based Fourier transform infrared (SR-FTIR) combined with two dimensional correlation spectroscopy (2D-COS) was used to probe and identify the changes of chemical constituents and functional groups of organic carbon on the root/soil interface in rhizosphere of two plants [Leptochloa chinensis (L.) Nees and Cyperus rotundus L.]. The SR-FTIR results showed obviously heterogeneous distributions of functional groups in rhizosphere at microscale. Specifically, regardless of plant species, about 20-30 μm regions in rhizosphere can be affected by root activities. The peak area ratios of organic-OH and aliphatic-C to clay-OH on the root/soil interface in rhizosphere were 4.04-8.48 times higher than that in bulk soil, providing direct evidence of the organic carbon storage due to root activities. 2D-COS analysis suggested that the root activities induced the first adsorption or sequestration of newly organics (3350 cm-1) on the root/soil interface, followed by the destruction of clay-OH (3621 or 860 cm-1), leading to the release of mineral associated organics and nutrients (e.g., 1510 and 1150 cm-1) from the soil. These results can enlarge our knowledge on the concentration, distribution, and dynamics of organic carbon in rhizosphere at the microscale level and also the environmental behaviors and fate of other elements and contaminants that associated with organic carbon in rhizosphere. CAPSULE: SR-FTIR combined with 2D-COS can explore the distribution and dynamics of organic carbon on the root/soil interface in rhizosphere.

Du|Haiyan|H| Yu|Guanghui|G| Guo|Mengjing|M| Xu|Huacheng|H|

D017550:Spectroscopy, Fourier Transform Infrared

Rhizosphere
2D-COS
Root/soil interface
Carbon storage
SR-FTIR spectroscopy


Reconstructing forked corpus spongiosum to correct glans droop in distal/midshaft hypospadias repair.

Abstract:
PURPOSE
We reviewed our experience and efficacy of reconstruction of a forked corpus spongiosum (FCS) to correct glans droop in distal/midshaft hypospadias repair.

METHODS
Eighty-five consecutive patients who underwent distal/midshaft hypospadias repair by the same surgeon in our center from October 2015 to June 2018 were retrospectively analyzed. All cases were accompanied by different degrees of glans droop, which we corrected by cutting off and reconstructing the FCS along the plate. We recorded the degrees of glans droop, development of the FCS, and postoperative complications including residual chordee, fistula, diverticulum, glans dehiscence, meatus stenosis, and urethral stricture.

RESULTS
The follow-up period ranged from 5 to 37 months (mean, 19.7 months). Two patients (2.3%) developed a coronal fistula and underwent a second repair. Two patients (2.3%) developed a mild urethral diverticulum and underwent continued observation. One patient (1.2%) developed a meatus stenosis that resolved after 1 month of meatus expansion combined with external mometasone furoate. No patients developed postoperative residual chordee or urethral stricture.

CONCLUSIONS
The degree of glans droop is closely associated with the development of an FCS. Reconstructing the FCS to correct the glans droop can yield satisfactory outcomes and should be popularized in distal/midshaft hypospadias repair.

D013521:Urologic Surgical Procedures, Male

reconstruction
forked corpus spongiosum
glans droop
Distal/midshaft hypospadias
FCS
chordee


Surface modification of biodegradable magnesium and its alloys for biomedical applications.

Abstract: Magnesium and its alloys are being paid much attention recently as temporary implants, such as orthopedic implants and cardiovascular stents. However, the rapid degradation of them in physiological environment is a major obstacle preventing their wide applications to date, which will result in rapid mechanical integrity loss or even collapse of magnesium-based implants before injured tissues heal. Moreover, rapid degradation of the magnesium-based implants will also cause some adverse effects to their surrounding environment, such as local gas cavity around the implant, local alkalization and magnesium ion enrichment, which will reduce the integration between implant and tissue. So, in order to obtain better performance of magnesium-based implants in clinical trials, special alloy designs and surface modifications are prerequisite. Actually, when a magnesium-based implant is inserted in vivo, corrosion firstly happens at the implant-tissue interface and the biological response to implant is also determined by the interaction at this interface. So the surface properties, such as corrosion resistance, hemocompatibility and cytocompatibility of the implant, are critical for their in vivo performance. Compared with alloy designs, surface modification is less costly, flexible to construct multi-functional surface and can prevent addition of toxic alloying elements. In this review, we would like to summarize the current investigations of surface modifications of magnesium and its alloys for biomedical application. The advantages/disadvantages of different surface modification methods are also discussed as a suggestion for their utilization.

surface modification
biodegradability
biocompatibility
coatings
ion implantation
magnesium alloys


H2O2 priming induces proteomic responses to defense against salt stress in maize.

Abstract:
KEY MESSAGE
H2O2 priming reprograms essential proteins' expression to help plants survive, promoting responsive and unresponsive proteins adjustment to salt stress.

ABSTACRT
Priming is a powerful strategy to enhance abiotic stress tolerance in plants. Despite this, there is scarce information about the mechanisms induced by H2O2 priming for salt stress tolerance, particularly on proteome modulation. Improving maize cultivation in areas subjected to salinity is imperative for the local economy and food security. Thereby, this study aimed to investigate physiological changes linked with post-translational protein events induced by foliar H2O2 priming of Zea mays plants under salt stress. As expected, salt treatment promoted a considerable accumulation of Na+ ions, a 12-fold increase. It drastically affected growth parameters and relative water content, as well as promoted adverse alteration in the proteome profile, when compared to the absence of salt conditions. Conversely, H2O2 priming was beneficial via specific proteome reprogramming, which promoted better response to salinity by 16% reduction in Na+ content and shoots growth improvement, increasing 61% in dry mass. The identified proteins were associated with photosynthesis and redox homeostasis, critical metabolic pathways for helping plants survive in saline stress by the protection of chloroplasts organization and carbon fixation, as well as state redox. This research provides new proteomic data to improve understanding and forward identifying biotechnological strategies to promote salt stress tolerance.

Moura|Arlindo de Alencar Araripe Noronha|AAAN|

Zea mays
Acclimation
Hydrogen peroxide
Na+ ion toxic
Protein modulation
Salt tolerance


Comparison of mediastinal lymph node metastases from adenocarcinoma of the esophagogastric junction versus lower esophageal squamous cell carcinoma with involvement of the esophagogastric junction.

Abstract: The distribution of mediastinal lymph node metastasis in patients with adenocarcinoma of the esophagogastric junction (AEG) remains unclear. Additionally, the distribution of nodal mediastinal metastasis from squamous cell carcinoma (SCC) of the lower esophagus with involvement of the esophagogastric junction remains unclear, given the very limited number of these patients. In this retrospective review, we compared the outcomes of radical lymphadenectomy of the mediastinum, including upper mediastinal lymphadenectomy, between patients with AEG and those with SCC. From 2005 to 2017, 69 consecutive patients underwent esophagectomy via right thoracotomy or minimally invasive esophagectomy for a Siewert type I or II tumor with esophageal invasion ≥3 cm. We analyzed the incidences of mediastinal lymph node metastasis in this group relative to those of 73 patients with SCC with involvement of the esophagogastric junction who consecutively underwent esophagectomy during the same period. Mediastinal lymph node metastasis was seen in 26 of 69 patients with AEG (38%), with upper, middle, lower mediastinal nodal metastasis instances of 20%, 17%, and 23%, respectively. Mediastinal lymph node metastasis was seen in 23 of 73 patients with SCC (32%), with upper, middle, lower mediastinal nodal metastasis instances of 12%, 16%, and 19%, respectively. This mediastinal lymph nodal metastasis distribution did not statistically differ between patients with AEG and those with SCC. The relapse-free survival outcomes were poor for patients with clinical (P < 0.01) or pathological (P < 0.01) nodal metastasis of the mediastinum with AEG. In contrast, patients with clinical or pathological mediastinal nodal metastases of SCC did not have extremely poor survival outcomes, compared to patients with AEG. Despite the limited dataset available for analysis, patients with AEG and those with SCC might exhibit similar incidences and distribution of mediastinal lymph node metastasis. However, the clinical or pathological metastasis of AEG to the mediastinum was associated with poor survival outcomes, even if radical mediastinal lymphadenectomy including the upper mediastinal lymphadenectomy was performed.

Mine|S|S| Watanabe|M|M| Kumagai|K|K| Okamura|A|A| Yuda|M|M| Hayami|M|M| Yamashita|K|K| Imamura|Y|Y| Ishizuka|N|N|

D000077277:Esophageal Squamous Cell Carcinoma

esophageal squamous cell carcinoma (ESCC)


Hyperglycemia in the Posttransplant Period: NODAT vs Posttransplant Diabetes Mellitus.

Abstract:
Objective
To characterize the types of hyperglycemia that occur up to 1 year following liver transplant and to clarify the nomenclature for posttransplant hyperglycemia.

Design
We analyzed 1-year glycemic follow-up data in 164 patients who underwent liver transplant and who had been enrolled in a randomized controlled trial comparing moderate to intensive insulin therapy to determine if patients had preexisting known diabetes, transient hyperglycemia, persistent hyperglycemia, or new-onset diabetes after transplantation (NODAT).

Results
Of 119 patients with posttransplant hyperglycemia following hospital discharge, 49 had preexisting diabetes, 5 had insufficient data for analysis, 48 had transient hyperglycemia (16 resolved within 30 days and 32 resolved between 30 days and 1 year), 13 remained persistently hyperglycemic out to 1 year and most likely had preexisting diabetes that had not been diagnosed or insulin resistance/insulinopenia prior to transplant, and 4 had NODAT (i.e., patients with transient hyperglycemia after transplant that resolved but then later truly developed sustained hyperglycemia, meeting criteria for diabetes).

Conclusions
Distinct categories of patients with hyperglycemia following organ transplant include known preexisting diabetes, persistent hyperglycemia (most likely unknown preexisting diabetes or insulin resistance/insulinopenia), transient hyperglycemia, and NODAT. Those with preexisting diabetes for many years prior to transplant may well have very different long-term outcomes compared with those with true NODAT. Therefore, it would be prudent to classify patients more carefully. Long-term outcome studies are needed to determine if patients with true NODAT have the same poor prognosis as patients with preexisting diabetes (diagnosed and undiagnosed) undergoing transplant.

hyperglycemia
NODAT
diabetes mellitus
transplant
PTDM


Overweight and obesity do not determine worst prognosis in endometrioid endometrial carcinoma.

Abstract:
PURPOSE
The aim of this study was to investigate the impact of body mass index (BMI) on disease-free survival (DFS) and overall survival (OS) in women diagnosed with EEC and treated at the Brazilian National Cancer Institute.

METHODS
The study comprised 849 women diagnosed with EEC who underwent surgical treatment between January, 2000 and December, 2011. The demographic and clinical characteristics of these patients were collected from medical records and their nutritional status was based on the BMI criteria. Univariate (OS and DFS) and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazards models, respectively.

RESULTS
About 83.2% of patients were obese or overweight at time of diagnosis, with a mean BMI of 31.83. Patients were followed for an average of 34.97 months. There were 111 recurrences (13.1%) and 140 deaths (16.5%), with mean DFS of 51.90 months and mean OS of 52.25 months. There was no significant association between BMI and DFS or OS. In multivariate analysis we did not find an increased hazard of recurrence or death among overweight or obese patients.

CONCLUSION
Overweight and obesity had no impact on EEC prognosis on the assessed cohort. Further studies are warranted.

Obesity
Body mass index
Survival
Endometrial cancer


Severe suicidal digoxin and propranolol toxicity with insulin overdose.

Abstract: We present a case of a 32-year-old male doctor, with type I diabetes mellitus on daily insulin therapy, who allegedly consumed large doses of digoxin and propranolol along with simultaneous administration of large dose of insulin with suicidal intent. Initial investigations revealed serum digoxin levels of 7.5 ng/ml, serum insulin 500 μIU/ml, and serum C-peptide 0.43 ng/ml. He was managed with charcoal-based hemoperfusion for digoxin overdose along with injection glucagon for propranolol overdose. His blood sugar levels were maintained with continuous infusion of 20% dextrose till the patient was allowed to take oral diet. Significant clinical improvement was noticed with this therapy which was evident by progressively declining serum digoxin levels, normalization of pulse rate, and adequate blood glucose levels. Finally, with a good hemodynamic profile and a serum digoxin level well within normal limits, he was discharged following consultation with a psychiatrist.

Garg|Ashish|A|
Panda|Soutik|S|
Dalvi|Pradip|P|
Mehra|Saurabh|S|
Ray|Sumit|S|
Singh|Vinod Kumar|VK|

propranolol
hemoperfusion
Digoxin toxicity


Hyponatremia is associated with occurrence of atrial fibrillation in outpatients with heart failure and reduced ejection fraction.

Abstract:
OBJECTIVES
Hyponatremia and atrial fibrillation (AF) have been established as strong predictors for worse clinical outcomes in patients with heart failure (HF). However, little is known about hyponatremia in relation to the occurrence of AF. This study aims to investigate the possible relationship between hyponatremia and AF in patients with chronic HF and reduced ejection fraction (HFrEF).

METHODS
Turkish research team-HF (TREAT-HF) is a network that has been undertaking multicenter, observational cohort studies on HF. A total of 880 patients who had plasma sodium measurement in TREAT-HF data set were included in this study. Hyponatremia was defined as a plasma sodium level of ≤135 mmol/L. The patients were classified into hyponatremia (n=213) or normonatremia (n=667) based on the sodium level.

RESULTS
The rate of AF was found to be 33.3% in patients with hyponatremia and 18.8% in patients with normonatremia (p<0.001). Univariate analysis demonstrated an association between hyponatremia and AF. Furthermore, in multivariate logistic regression model, hyponatremia was also found to be significantly and independently associated with the occurrence of AF (odds ratio [OR]=2.457, 95% confidence interval [CI]=1.586-3.806, p<0.001) in addition to other well-known risk factors for AF.

CONCLUSION
The results of this study showed that AF was more prevalent in outpatients with HFrEF and hyponatremia than in those with HFrEF and normonatremia. These results also suggest that hyponatremia is independently associated with the occurrence of AF.

Cavusoglu|Yuksel|Y|
Kaya|Hakki|H|
Eraslan|Selda|S|
Yilmaz|Mehmet Birhan|MB|

hyponatremia
atrial fibrillation
Heart failure


Insect swarms can be bound together by repulsive forces.

Abstract: The cohesion of insect swarms has been attributed to the fact that the resultant internal interactions of the swarming insects produce, on the average, a centrally attractive force that acts on each individual. Here it is shown how insect swarms can also be bound together by centrally forces that on the average are repulsive (outwardly directed from the swarm centres). This is predicted to arise when velocity statistics are heterogeneous (position-dependent). Evidence for repulsive forces is found in laboratory swarms of Chironomus riparius midges. In homogeneous swarms, the net inward acceleration balances the tendency of diffusion (stochastic noise) to transport individuals away from the centre of the swarm. In heterogenous swarms, turbophoresis --the tendency for individuals to migrate in the direction of decreasing kinetic energy-- is operating. The new finding adds to the growing realization that insect swarms are analogous to self-gravitating systems. By acting in opposition to central attraction (gravity), the effects of heterogeneous velocities (energies) are analogous to the effects of dark energy. The emergence of resultant forces from collective behaviours would not be possible if individual flight patterns were themselves unstable. It is shown how individuals reduce the potential for the loose of flight control by minimizing the influence of jerks to which they are subjected.


Heroin crystal nephropathy.

Abstract: In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy.

Bautista|Josef Edrik Keith|JE|
Merhi|Basma|B|
Gregory|Oliver|O|
Hu|Susie|S|
Henriksen|Kammi|K|
Gohh|Reginald|R|

crystal nephropathy
acute kidney injury
urine microscopy
heroin nephropathy
urinalysis


Six Visual Rating Scales as A Biomarker for Monitoring Atrophied Brain Volume in Parkinson's Disease.

Abstract: The focus of our investigation was to determine the feasibility of using six visual rating scales as whole-brain imaging markers for monitoring atrophied brain volume in Parkinson's disease (PD). This was a prospective cross-sectional single-center observational study. A total of 98 PD patients were enrolled and underwent an MRI scan and a battery of neuropsychological evaluations. The brain volume was calculated using the online resource MRICloud. Brain atrophy was rated based on six visual rating scales. Correlation analysis was performed between visual rating scores and brain volume and clinical features. We found a significant negative correlation between the total scores of visual rating scores and quantitative brain volume, indicating that six visual rating scales reliably reflect whole brain atrophy in PD. Multiple linear regression-based analyses indicated severer non-motor symptoms were significantly associated with higher scores on the visual rating scales. Furthermore, we performed sample size calculations to evaluate the superiority of visual rating scales; the result show that using total scores of visual rating scales as an outcome measure, sample sizes for differentiating cognition injury require significantly fewer subjects (n = 177) compared with using total brain volume (n = 2524). Our data support the use of the total visual rating scores rather than quantitative brain volume as a biomarker for monitoring cerebral atrophy.

Lin|Yu|Y| Fu|Ying|Y| Zeng|Yi-Fang|YF| Hu|Jian-Ping|JP| Lin|Xiao-Zhen|XZ| Cai|Nai-Qing|NQ| Weng|Qiang|Q| Zhao|Yi-Jing|YJ| Lin|Yi|Y| Cao|Dai-Rong|DR| Wang|Ning|N|

visual rating scale
whole brain atrophy
Parkinson’s disease
clinical trials
structural image


Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

Abstract:
BACKGROUND
Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up.

MATERIAL AND METHODS
We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety.

RESULTS
During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted.

CONCLUSIONS
In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Toyserkani|N M|NM|
Jensen|C H|CH|
Tabatabaeifar|S|S|
Jørgensen|M G|MG|
Hvidsten|S|S|
Simonsen|J A|JA|
Andersen|D C|DC|
Sheikh|S P|SP|
Sørensen|J A|JA|

D045164:Mesenchymal Stem Cell Transplantation

Adipose-derived regenerative cells
Breast cancer-related lymphedema
Pilot study
Lymphoscintigraphy
Stromal vascular fraction


The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: a retrospective cohort study.

Abstract:
BACKGROUND
An acute episode of malaria can be followed by multiple recurrent episodes either due to re-infection, recrudescence of a partially treated parasite or, in the case of Plasmodium vivax or P. ovale, relapse from the dormant liver stage of the parasite. The aim of this study was to quantify the impact of recurrent malaria episodes on morbidity and mortality in Papua, Indonesia.

METHODS
We undertook a retrospective analysis of routinely collected data from malaria patients attending the primary referral hospital in Papua, Indonesia, between April 2004 and December 2013. Multi-state modelling was used to estimate the effect of recurring malaria episodes on re-presentation and admission to hospital and death. The risks of early (≤ 14 days) and late (15 to 365 days) hospital admission and death were estimated separately in our study to distinguish between the direct and indirect effects of malaria recurrence on adverse outcomes.

RESULTS
A total of 68,361 patients were included in the analysis, of whom 37,168 (54.4%) presented initially with P. falciparum, 22,209 (32.5%) with P. vivax, and 8984 (13.1%) with other species. During 12 months of follow-up after each of the first four malaria episodes, 10,868 (15.9%) patients were admitted to hospital and 897 (1.3%) died. The risk of re-presenting to the hospital with malaria increased from 34.7% (95% CI 34.4%, 35.1%) at first episode to 58.6% (57.5%, 59.6%) following the third episode of malaria. After adjusting for co-factors, infection with P. vivax was a significant risk factor for re-presentation (hazard ratio (HR) = 1.48 (95% CI 1.44, 1.51)) and late admission to hospital (HR = 1.17 (1.11, 1.22)). Patients infected with P. falciparum had a greater overall rate of mortality within 14 days (HR = 1.54 (1.25, 1.92)), but after multiple episodes of malaria, there was a trend towards a higher rate of early death in patients infected with P. vivax compared to P. falciparum (HR = 1.91 (0.73, 4.97)).

CONCLUSIONS
Compared to patients initially infected with P. falciparum, those infected with P. vivax had significantly more re-presentations to hospital with malaria, and this contributed to a high risk of inpatient admission and death. These findings highlight the importance of radical cure of P. vivax to eliminate the dormant liver stages that trigger relapses.

Dini|Saber|S|
Douglas|Nicholas M|NM|
Poespoprodjo|Jeanne Rini|JR|
Kenangalem|Enny|E|
Sugiarto|Paulus|P|
Plumb|Ian D|ID|
Price|Ric N|RN|
Simpson|Julie A|JA|

Papua
Indonesia
Plasmodium
Vivax
Malaria recurrence
Falciparum


HIV Self-Testing Can Be Liberating to HIV-Positive Women and Their Sexual Partners: A Qualitative Study in Kisumu, Western Kenya.

Abstract:
BACKGROUND
Nearly half of Kenyan men with HIV-positive partners do not know their partner's status. We carried out a qualitative substudy to explore the experiences of a sample of HIV-positive women when distributing HIV self-tests (HIVST) to their sexual partners.

METHODS
HIV-positive women were invited for in-depth interviews to share their experiences in offering HIVST to their partners and how self-testing impacted their relationships.

RESULTS
Two hundred ninety-seven women were randomized to HIVST, 12 of whom self-reported being HIV positive and 11 participated in the interview. Self-testing procedures and interpretation of results were well understood. Participants were strategic in approaching their partners, thus avoided partner violence. Couple testing was high, which strengthened relationships, improved condom use, and empowered women to make joint decisions concerning their health.

CONCLUSIONS
Giving HIV-positive women HIVST kits to distribute to their male partners is feasible and safe. Providers who have challenges reaching male partners with testing should consider HIVST.

Agot|Kawango|K|0000-0002-0475-6951 Wango|Gift-Noelle|GN| Obonyo|Beatrice|B| Thirumurthy|Harsha|H|

D016032:Randomized Controlled Trials as Topic

HIV self-testing
HIV-positive women
sexual partners
Kenya
secondary distribution


Ebola: Impact of hospital's admission policy in an overwhelmed scenario.

Abstract: Infectious disease outbreaks sometimes overwhelm healthcare facilities. A recent case occurred in West Africa in 2014 when an Ebola virus outbreak overwhelmed facilities in Sierra Leone, Guinea and Liberia. In such scenarios, how many patients can hospitals admit to minimize disease burden? This study considers what type of hospital admission policy during a hypothetical Ebola outbreak can better serve the community, if overcrowding degrades the hospital setting. Our result shows that which policy minimizes loss to the community depends on the initial estimation of the control reproduction number, R₀. When the outbreak grows extremely fast (R₀ ≫ 1) it is better (in terms of total disease burden) to stop admitting patients after reaching the carrying capacity because overcrowding in the hospital makes the hospital setting ineffective at containing infection, but when the outbreak grows only a little faster than the system's ability to contain it (R₀ ≳ 1), it is better to admit patients beyond the carrying capacity because limited overcrowding still reduces infection more in the community. However, when R₀ is no more than a little greater than 1 (for our parameter values, 1.012), both policies result the same because the number of patients never exceeds the maximum capacity.

Zahid|Mondal Hasan|MH|
Kribs|Christopher M|CM|

D000354:Africa, Western
D004196:Disease Outbreaks
D058872:Epidemics
D019142:Hemorrhagic Fever, Ebola
D006742:Hospital Bed Capacity
D006760:Hospitalization
D006801:Humans
D055641:Mathematical Concepts
D008954:Models, Biological
D016134:Organizational Policy
D010343:Patient Admission

Ebola
admission policy
overwhelmed healthcare facility
control reproduction number
Overcrowded hospital
basic reproduction number
mathematical model


Nek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer.

Abstract: Hypoxia selects the most aggressive and drug-resistant clones in solid malignancies. One of the pivotal transcription factors induced by hypoxia is Hif-1α. However, in serous ovarian cancer (SEOC), Hif-1α expression is not a prognostic biomarker. This study aims to assess the hypothesis that the serine-threonine kinase Nek6 functions as a downstream effector cooperating with Hif-1α in driving ovarian cancer aggressiveness. Nek6 was overexpressed and Hif-1α was silenced in A2780 cells. Nek6 was also stably silenced in Hey cells. The dependence of Nek6 expression on Hif-1α was assayed as a function of hypoxic growth conditions. Nek6 interaction with the cytoskeletal gateway of drug resistance was investigated with far western blot. The co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts was quantified with qPCR in two cohorts of SEOC patients (346 locally treated patients and 344 from the TCGA dataset). Nek6 expression is induced by hypoxia in a Hif-1α dependent fashion. Nek6 directly interacts with GBP-1, thus being a component of the cytoskeletal gateway of drug resistance. Nek6 overexpression increases and silencing decreases the anchorage-independent growth of cultured cells. In SEOC patients, NEK6 expression is significantly correlated with HIF1A. Co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts identifies a subset of SEOC patients characterized by poor outcome and drug resistance. This study demonstrates the functional relevance of Nek6 in the context of the adaptive response to hypoxia in SEOC. This finding may help identify a sub-population of patients at high risk of relapse to standard first-line chemotherapy.

Donato|Marta De|MD|
Fanelli|Mara|M|
Mariani|Marisa|M|
Raspaglio|Giuseppina|G|
Pandya|Deep|D|
He|Shiquan|S|
Fiedler|Paul|P|
Petrillo|Marco|M|
Scambia|Giovanni|G|
Ferlini|Cristiano|C|


Prognostic value of oxidative stress in patients with acute myocardial infarction complicated by cardiogenic shock: A prospective cohort study.

Abstract:
INTRODUCTION
Cardiogenic shock is a frequent complication of acute myocardial infarction. Similar to ischemia/reperfusion injury, excessive production of reactive oxygen species can be expected in those who experience cardiogenic shock. The aims of this study were to describe the extent and time course of oxidative stress and evaluate the prognostic value of oxidative stress markers in patients who experienced ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock.

METHODS
Plasma/serum levels of selected biomarkers of oxidative stress (oxidised guanine species (OGS), malondialdehyde, and glutathione peroxidase 3) and markers, which simultaneously reflect severe cellular damage (ferric ion reducing antioxidant power (FRAP), Cu/Zn-superoxide dismutase (SOD), and glutathione) were measured seven times per week in a prospective cohort of 82 patients with STEMI complicated by cardiogenic shock.

RESULTS
We found elevated OGS levels in patients who died during three months, which persisted significantly increased the next 12 h compared to surviving patients. A similar time course pattern also exhibited concentrations of FRAP and SOD. The other markers did not change significantly and did not show differences between surviving and non-surviving patients during the monitored period. In addition, a strong relationship between OGS, FRAP, and SOD levels (on admission and 12 h after admission) and 3-month mortality was found.

CONCLUSION
Levels of OGS, FRAP, and SOD within 12 h after hospital admission were revealed as early predictors of the adverse development of STEMI complicated by cardiogenic shock.

Tomandlova|Marie|M|
Parenica|Jiri|J|
Lokaj|Petr|P|
Ondrus|Tomas|T|
Kala|Petr|P|
Miklikova|Marie|M|
Helanova|Katerina|K|
Helan|Martin|M|
Malaska|Jan|J|
Benesova|Klara|K|
Jarkovsky|Jiri|J|
Pavkova Goldbergova|Monika|M|
Tomandl|Josef|J|

D015331:Cohort Studies
D006801:Humans
D009203:Myocardial Infarction
D018384:Oxidative Stress
D011379:Prognosis
D011446:Prospective Studies
D012770:Shock, Cardiogenic

Cardiogenic shock
Reactive oxygen species
Oxidised guanine species
Malondialdehyde
Glutathione
Glutathione peroxidase
FRAP
Cu/Zn-superoxide dismutase
8-Hydroxy-2′-deoxyguanosine


Predicting decline of kidney function in lupus nephritis using urine biomarkers.

Abstract:
OBJECTIVE
To evaluate candidate biomarkers to predict future renal function decline (RFD) in children and adults with lupus nephritis (LN).

METHODS
At the time of enrollment into prospective observational LN cohort studies liver-type fatty acid binding protein (LFABP), albumin, monocyte chemoattractant protein-1 (MCP-1), uromodulin, transferrin, and hepcidin were measured in urine samples of two cohorts of patients with LN, one followed at a pediatric (cohort-1; n = 28) and one at an adult institution (cohort-2; n = 69). The primary outcome was RFD, defined in cohort-1 as a decrease in estimated glomerular filtration rate (eGFR) of ≥20% and in cohort-2 as a sustained increase of ≥25% in serum creatinine concentration (SCr), both from baseline.

RESULTS
All patients (n = 97) had normal eGFR or SCr at the time of urine collection at baseline. RFD occurred in 29% (8/28) of patients in cohort-1 during a mean follow-up of 6.1 months, and in 30% (21/69) of those in cohort-2 during a mean follow-up of 60 months. Individually, in cohort-1, levels of MCP-1, transferrin, LFABP, and albumin were higher in the RFD group than those who maintained renal function, with statistical significance for LFABP and albumin. In cohort-2 the RFD group also had higher levels of urine MCP-1 and albumin than others. The combination of LFABP, MCP-1, albumin, and transferrin had good predictive accuracy for RFD in both cohorts (area under the ROC curve = 0.77-0.82).

CONCLUSION
The combinatorial urine biomarker LFABP, MCP-1, albumin, and transferrin shows promise as a predictor of renal functional decline in LN, and warrants further investigation.

Abulaban|K M|KM|
Song|H|H|
Zhang|X|X|
Kimmel|P L|PL|
Kusek|J W|JW|
Nelson|R G|RG|
Feldman|H I|HI|
Vasan|R S|RS|
Ying|J|J|
Mauer|M|M|
Nelsestuen|G L|GL|
Bennett|M|M|
Brunner|H I|HI|
Rovin|B H|BH|

lupus nephritis
biomarker
renal function decline
SLE
kidney injury


Global 3D parameter of the spine: application of Călugăreanu-White-Fuller theorem in classification of pediatric spinal deformity.

Abstract: Several classification systems of the spinal curves in adolescent idiopathic scoliosis (AIS) have been developed to guide surgical decision-making. The current classification systems are based on the spinal deformity patterns or deformity magnitudes in one or two anatomical planes. Considering the 3D nature of the spinal deformity in AIS, these classifications fail to capture the spine's curve in its entirety. We proposed a classification based on the axial plane and showed that mathematical analysis of the 3D spinal curve, using differential geometry, supports the differences between the subtypes in this classification system. We calculated the writhe and twist of the entire spinal centerline, elements of the Călugăreanu-White-Fuller theorem, in a cohort of 30 right thoracic AIS patients. We also classified this cohort manually based on the vertebral level at which the direction of vertebral rotation caudal to the thoracic curve changes: Lumbar in Group I (V-shaped axial projection) or thoracolumbar in Group II (S-shaped axial projection). The writhe and twist of the spinal curve were significantly different between these manual classification subgroups. Our manual classification distinguished the axial subgroups of right thoracic AIS supported by mathematical specifications of the entire curve in three dimensions. Graphical abstract.

Spine
Classification
Adolescent idiopathic scoliosis
Writhe
Twist
3D curve
Călugăreanu–White–Fuller theorem


Valorization of Waste: Sustainable Organocatalysts from Renewable Resources.

Abstract: One of the greatest challenges facing our society is to reconcile our need to develop efficient and sophisticated chemical processes with the limited resources of our planet and its restricted ability to adsorb pollution. Organocatalysis has allowed many issues to be addressed in the development of sophisticated, but less polluting, processes. However, minimizing waste also means an efficient utilization of raw and renewable materials. Waste biomass represents an alternative to conventional petroleum-based chemical manufacturing and is a highly attractive renewable resource for the production of chemicals and high-value-added organocatalysts. Recent achievements in the use of renewable biomass feedstocks for the synthesis of organocatalysts are presented. Their application in synthetic methodologies, including multicomponent reactions, which are performed under solvent-free conditions or in eco-friendly reaction media, as well as recycling and reusing the organocatalysts, is illustrated. A few pioneering examples that demonstrate the potential of these promoters in asymmetric synthesis have also been documented. In particular, this review covers examples on the use of hetero- and homogeneous organocatalysts derived from 1) waste biopolymers, such as chitosan, alginic acid, and cellulose; ii) renewable platform molecules, such as levoglucosenone, isosorbide, mannose, d-glucosamine, and lecithin; 3) terpenes and rosin, such as pinane, isosteviol, and abietic acid; and iv) natural proteins (gelatin, bovine tendons, silk fibroin proteins).

renewable resources
organocatalysis
biomass
biopolymers
green chemistry


The Deubiquitinating Enzyme USP14 Regulates Leukemic Chemotherapy Drugs-Induced Cell Apoptosis by Suppressing Ubiquitination of Aurora Kinase B.

Abstract:
BACKGROUND/AIMS
Aurora kinase B is a mitotic checkpoint kinase that plays a pivotal role in mitosis by ensuring correct chromosome segregation and normal progression through mitosis. Aurora B has been found to be amplified and overexpressed in several types of leukemia. The deubiquitinating enzyme USP14 is one of three proteasome-associated deubiquitinating enzymes and plays critical roles in diverse biological processes including cancer. However, whether USP14 has a role in leukemia cells remains elusive.

METHODS
Leukemic U937, NB4 and Jurkat cells were treated with diverse apoptosis-inducing drugs. The interaction between USP14 and Aurora B were determined by Western blot. The effect of USP14 in the regulation of Aurora B was detected by cycloheximide (CHX) and deubiquitination assays. FACS assay was used to determine the apoptosis ratio of cells after treatments.

RESULTS
We found that Aurora B was ubiquitinated and degraded during leukemic chemotherapy drugs-induced cell apoptosis. FBXW7 mediated Aurora B ubiquitination and degradation during chemotherapeutic drugs-induced apoptosis. USP14 associated with Aurora B and prevented Aurora B degradation. Functionally, overexpression of USP14 inhibits chemotherapeutic drugs-induced apoptosis in leukemia cells. On the contrary, administration of b-AP15, a specific inhibitor of USP14, significantly increased leukemia cells apoptosis in a dose-dependent manner.

CONCLUSION
Thus, our data suggest that USP14 plays a novel critical role of in leukemia cells apoptosis through Aurora B stabilization and USP14 could be a potential therapeutic target for leukemia.

Song|Chunge|C| Ma|Ruojin|R| Yang|Xiaoyu|X| Pang|Sulei|S|


Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix Ophiopogonis.

Abstract: Radix Ophiopogonis is often an integral part of many traditional Chinese formulas, such as Shenmai injection used to treat cardio-cerebrovascular diseases. This study aimed to investigate the influence of the four active components of Radix Ophiopogonis on the transport activity of OATP1B1 and OATP1B3. The uptake of rosuvastatin in OATP1B1-HEK293T cells were stimulated by methylophiopogonanone A (MA) and ophiopogonin D' (OPD') with EC50 calculated to be 11.33 ± 2.78 and 4.62 ± 0.64 μM, respectively. However, there were no remarkable influences on rosuvastatin uptake in the presence of methylophiopogonanone B (MB) or ophiopogonin D (OPD). The uptake of atorvastatin in OATP1B1-HEK293T cells can be increased by MA, MB, OPD and OPD' with EC50 calculated to be 6.00 ± 1.60, 13.64 ± 4.07, 10.41 ± 1.28 and 3.68 ± 0.85 μM, respectively. The uptake of rosuvastatin in OATP1B3-HEK293T cells was scarcely influenced by MA, MB and OPD, but was considerably increased by OPD' with an EC50 of 14.95 ± 1.62 μM. However, the uptake of telmisartan in OATP1B3-HEK293T cells was notably reduced by OPD' with an IC50 of 4.44 ± 1.10 μM, and barely affected by MA, MB and OPD. The four active components of Radix Ophiopogonis affect the transporting activitives of OATP1B1 and OATP1B3 in a substrate-dependent manner.

Chen|Lin|L| Liu|Linlin|L| Chen|Yu|Y| Liu|Mingyi|M| Xiong|Yuqing|Y| Zhang|Hong|H| Huang|Shibo|S| Xia|Chunhua|C|

D027381:Liver-Specific Organic Anion Transporter 1

D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3

OATP1B1
OATP1B3
methylophiopogonanone A
Ophiopogonin D
ophiopogonin D'
methylophiopogonanone B
interactions


The effect of incidental dural lesions on outcome after decompression surgery for lumbar spinal stenosis: results of a multi-center study with 800 patients.

Abstract:
PURPOSE
Incidental durotomy is one of the most common complications in lumbar spine surgery. There are conflicting reports whether a dural lesion is associated with an inferior outcome after lumbar decompression. This study analyzed the effect of incidental durotomy in this specific group of patients (Dura+) and compared the results with the remaining cohort without dural laceration (Dura-).

METHODS
This prospective multi-center study included 800 patients with lumbar spinal stenosis who underwent exclusive decompression surgery. All procedures were performed as part of a multi-center investigation at three highly specialized spine clinics. Outcome measures (ODI, EQ5D, VASback pain and VASleg pain) were obtained preoperatively as well as 3 and 12 months after surgery. The effect of an incidental durotomy on the clinical outcomes was analyzed statistically between the two cohorts.

RESULTS
An intraoperative dura lesion was recorded in 6.5 % (n = 52/800) of all cases. Both cohorts (Dura+ and Dura-) did not reveal any differences regarding patient demographics, risk factors, or co-morbidities at baseline. The length of the hospital stay was significantly longer for the Dura+ cohort (8.0 vs. 6.4 days; p < 0.01). After 12 months, the Dura- cohort demonstrated a significantly greater improvement in VASback pain in comparison to the Dura+ cohort (Δ21.4 vs. Δ7.2 points; p < 0.05). The differences for the remaining outcome measures were not statistically significant (p > 0.05).

CONCLUSIONS
The results of this study reveal that an incidental durotomy was associated with a significant increase in the patient's length of stay, and risk for re-intervention for the treatment of persisting CSF leakage. In contrast to previous reports which have investigated the effects of incidental durotomies on the clinical outcome after lumbar decompression surgery, our data further suggest a possible inferior outcome in terms of low back pain improvement in the Dura+ cohort, which became clinically apparent at the 12-month follow-up period. Future studies should investigate whether a more pronounced decompression required for adequate exposure and repair of a dural laceration may, ultimately, result in increased segmental instability and in clinically undesirable low back pain.

Kothe|Ralph|R| Quante|M|M| Engler|N|N| Heider|F|F| Kneißl|J|J| Pirchner|S|S| Siepe|C|C|

D019299:Decompression, Surgical
D004388:Dura Mater
D006801:Humans
D007902:Length of Stay
D017116:Low Back Pain
D008159:Lumbar Vertebrae
D011183:Postoperative Complications
D011446:Prospective Studies
D013130:Spinal Stenosis

Lumbar spinal stenosis
Incidental durotomy
Complications
Dural tear
Patient-reported outcomes


Small-cell neuroendocrine carcinoma of the urinary bladder: A case report.

Abstract: Primary neuroendocrine carcinomas of the urinary bladder are rare. A 60-year-old male presented with gross hematuria for the past 3 months. Diagnostic flexible cystoscopy revealed a papillary lesion above the right ureteric orifice. Transurethral resection of bladder tumor was performed and resected tissue was sent for histopathology that revealed high-grade urothelial carcinoma with small-cell neuroendocrine differentiation. Lamina propria, muscularis propria, and perineural invasion was seen which was later also confirmed by immunohistochemistry. The patient received neoadjuvant four cycles of chemotherapy and then underwent radical cystoprostatectomy with ileal conduit. The patient's recovery was uneventful and he is on regular follow-up from the past 12 months without any disease recurrence. Early detection and aggressive management can improve the survival and prognosis of these patients.

Masood|Basit|B|
Iqbal|Nadeem|N|
Iqbal|Waqas|W|
Masood|Yasir|Y|
Akbar|Mian Khalid|MK|
Mamoon|Nadira|N|

neuroendocrine carcinoma
urothelial carcinoma
radical cystoprostatectomy
Aggressive neoplasm


XBP1s Acts as a Tumor Suppressor to Inhibit the EMT Process and Metastasis of Papillary Thyroid Cancer.

Abstract:
Purpose
Papillary thyroid cancer (PTC) patients could obtain poor prognosis if they have lymph node metastasis, identification of informative and robust biomarkers for predicting cervical lymph node metastasis is critical for improving clinical decision-making and patient prognosis.

Materials and Methods
In this study, we analyzed the expression of X box binding protein 1 spliced-form (XBP1s) in 41 PTC tissue samples and extended our findings using public databases, then we investigated how XBP1s' contributed to PTC progression in vitro.

Results
We found that XBP1s' expression was lower in PTC patients with cervical lymph node metastasis than non-metastasis patients by immunohistochemical analysis. With publicly accessible dataset, we showed that the XBP1 transcription was significantly decreased in thyroid cancer (TC) tissues with lymph node metastasis as compared to that without lymph node metastasis. Moreover, we also found that XBP1 expression was significantly correlated with patients' gender, T classification, lymph node metastasis and PTC stages, and low XBP1 expression was associated with poor diseases free survival (DFS). In vitro, XBP1s overexpression could inhibit the invasion, migration, and wound healing capacity of PTC cells. Mechanistically, overexpression of XBP1s could enhance the expression of classical epithelial-mesenchymal transition (EMT) markers such as ZO-1 and E-cadherins, and downregulated N-cadherin in BCPAP cells.

Conclusion
These findings suggest that XBP1s is a prognostic maker for thyroid carcinoma patients, and sustaining XBP1s expression might be a new strategy to control PTC progression.

Yang|Wen|W| Xu|Xia|X| Xu|Ming|M| Zhou|Jun|J|0000-0002-9449-0471 Xi|Zihan|Z| Guo|Hui|H| Ming|Jie|J| Huang|Tao|T|

XBP1s
EMT
papillary thyroid cancer
lymph node metastasis


Spatiotemporal evolution of environment based on integrated remote sensing indexes in arid inland river basin in Northwest China.

Abstract: Arid inland river basin has been regarded as environmental vulnerable and an important protective area in northwest China. Shiyang River Basin (SRB) is one of the most typical areas in arid inland rivers basin in China. The environmental quality evaluation of different periods is significant for environmental control and management of SRB. In this paper, the normalized differential vegetation index (NDVI), wetness index (WI), albedo, index-based built-up index (IBI), salinization index (SI), and land surface temperature (LST) were obtained through Landsat TM and OLI images in 1995, 2000, 2005, 2010, and 2016. Besides, three methods including spatial principal component analysis (SPCA), analytic hierarchy process (AHP), and remote-sensing spatial distance model (RSSDM) were compared to select a reasonable method for environmental evaluation. The AHP method was determined as the final method for objectively evaluating spatiotemporal changes of environment from 1995 to 2016 in SRB. The results showed that the environment deteriorated in 1995-2000 and improved in 2000-2016. The effect of environmental governance was significant in 2010-2016 because of the longtime environmental management between multiple departments. The results indicated that the environmental quality of SRB was generally improved from 1995 to 2016. We found that the improvement areas were mainly concentrated in the oasis and marginal areas, while environmental damage areas were mainly distributed in the urban regions. However, in most areas of the SRB, the environment was still below average level of China, and the roads of the environment management still had a long way to go. We found that spatiotemporal pattern analysis of the environment was of great importance for the formulation of plans for development of this basin and environmental protection measures.

Wei|Wei|W| Guo|Zecheng|Z| Xie|Binbin|B| Zhou|Junju|J| Li|Chuanhua|C|

D003247:Conservation of Natural Resources

Environment
AHP
Spatiotemporal changes
Remote-sensing indexes
The middle-lower of SRB


Assessment of EGFR Gene Expression Following Vitrification of 2-cell and Blastocyst Mouse Embryos.

Abstract:
Background
Exact mechanisms of fetal harm following vitrification are still unknown. This study was conducted to evaluate the cryopreservation impact on the expression of Epidermal Growth Factor Receptor (EGFR) gene in mouse 2-cell and blastocysts.

Methods
To stimulate ovulation in mice, hCG was injected, followed by collecting 2-cells and blastocysts after 44-46 and 88-89 hr, respectively. These embryos were divided into two case and control groups. The fresh case group was cryopreserved using cryotop and warmed after 4 mounts. Normal 2-cells were selected based on their morphology and their RNA was extracted. Quantitative expression of EGFR gene in both groups was investigated by applying real time-PCR.

Results
The statistical Real-Time (RT)-PCR analyses performed using SPSS revealed that the expression level of EGFR gene was diminished in the case group compared to the control group.

Conclusion
The current study indicated the negative effect of cryopreservation on expression amount of EGFR gene in 2-cell and blastocyst mouse embryos.

Gazor|Rouhollah|R|
Eskandari|Mozhgan|M|
Sharafshah|Alireza|A|
Bahadori|Mohammad Hadi|MH|
Golmohammadi|Mohammad Ghasem|MG|
Keshavarz|Parvaneh|P|

Gene expression
Vitrification
Blastocyst
Embryo
Cryopreservation


The association between muscular strength and depression in Korean adults: a cross-sectional analysis of the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI) 2014.

Abstract:
BACKGROUND
There are conflicting researches on the relationship between muscular strength and depression, the most common mental illness. There is no study of relationship between muscular strength and depression using national data from young adults to seniors. For example, there has not been a study done explaining mediating pathways among the influences of handgrip strength on depression. Here, we conducted survey for the association between relative handgrip strength and depression and explain mediated pathways for quality of life.

METHODS
A cross-sectional study was administered to 4298 Korean adult subjects, aged 19-80 years, based on the 6th Korean National Health and Nutrition Examination Survey (KNHANES VI) of 2014. Handgrip strength reported as the average with each hand. The relative handgrip strength is defined as the handgrip strength divided by the body mass index (BMI). We performed analysis for all subjects and age groups (young adult, middle-aged, and elderly). We analyzed the association using multivariate linear regression and logistic regression. We also conducted mediation analysis for quality of life, which was measured by the EuroQol Five-Dimension Questionnaire (EQ5D).

RESULTS
After adjusting for covariates, handgrip strength was inversely associated with the PHQ-9 score (P < 0.05). The odds ratios (OR) of depression symptoms were statistically significant for participants in the first and second quartile of handgrip strength compared to those with the highest quartile in entire sample, young adult, middle-aged, and elderly. There was about a 50% mediation effect of EQ5D in the relationship between handgrip strength and depression.

CONCLUSIONS
Using a large national sample, our results found that lower handgrip strength is associated with an increased risk of depression in Korean adult (young adult, middle-aged, and elderly). Our results suggest that increasing muscular strength may prevent depression in Korean adults.

Lee|Mee-Ri|MR|
Jung|Sung Min|SM|
Bang|Hyuk|H|
Kim|Hwa Sung|HS|
Kim|Yong Bae|YB|

Depression
Quality of life
Hand strength


The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection.

Abstract: The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

Wang|Yifei|Y| Hu|Jianjun|J| Li|Yiding|Y| Xiao|Minglu|M| Wang|Haoqiang|H| Tian|Qin|Q| Li|Zhirong|Z| Tang|Jianfang|J| Hu|Li|L| Tan|Yan|Y| Zhou|Xinyuan|X| He|Ran|R| Wu|Yuzhang|Y| Ye|Lilin|L| Yin|Zhinan|Z| Huang|Qizhao|Q| Xu|Lifan|L|

TCF1
exhaustion
CD8 T cell
chronic viral infection
LCMV


Cost-effectiveness analysis of a multifactorial fall prevention intervention in older home care clients at risk for falling.

Abstract:
BACKGROUND
Falls among older adults can cause serious morbidity and pose economic burdens on society. Older age is a known risk factor for falls and age has been shown to influence the effectiveness of fall prevention programs. To our knowledge, no studies have explicitly investigated whether cost-effectiveness of a multifactorial fall prevention intervention (the intervention) is influenced by age. This economic evaluation explores: 1) the cost-effectiveness of a multifactorial fall prevention intervention compared to usual care for community-dwelling adults ≥ 75 years at risk of falling in Canada; and 2) the influence of age on the cost-effectiveness of the intervention.

METHODS
Net benefit regression was used to examine the cost-effectiveness of the intervention with willingness-to-pay values ranging from $0-$50,000. Effects were measured as change in the number of falls, from baseline to 6-month follow-up. Costs were measured using a societal perspective. The cost-effectiveness analysis was conducted for both the total sample and by age subgroups (75-84 and 85+ years).

RESULTS
For the total sample, the intervention was not economically attractive. However, the intervention was cost-effective at higher willingness-to-pay (WTP) (≥ $25,000) for adults 75-84 years and at lower WTP (< $5,000) for adults 85+ years.

CONCLUSIONS
The cost-effectiveness of the intervention depends on age and decision makers' WTP to prevent falls. Understanding the influence of age on the cost-effectiveness of an intervention may help to target resources to those who benefit most.

TRIAL REGISTRATION
Retrospectively registered. Clinicaltrials.gov identifier: NCT00463658 (18 April 2007).

D000058:Accidental Falls
D000367:Age Factors
D000368:Aged
D000369:Aged, 80 and over
D002170:Canada
D003362:Cost-Benefit Analysis
D005260:Female
D015276:Health Care Rationing
D006699:Home Care Services
D006801:Humans
D057187:Independent Living
D008297:Male
D011634:Public Health
D018570:Risk Assessment
D012307:Risk Factors

Cost-effectiveness analysis
Fall prevention
Older adults
Age
Multifactorial intervention


Conceptualizing and Assessing Everyday Functioning in the Context of HIV-Associated Neurocognitive Disorders.

Abstract: Combination antiretroviral therapy has reduced the rates of severe HIV-associated neurocognitive disorders (HAND), but the prevalence of milder forms of HAND that can affect everyday functioning remains high. As HIV-infected adults approach near-normal life expectancies, they may become increasingly susceptible to declines in everyday functioning secondary to a variety of physical and mental factors, including HAND. Although impairments in everyday functioning are a hallmark of HAND diagnoses and can adversely influence quality of life, there are no gold standard measures of this fundamentally important and complex construct. This chapter provides a brief review of the various self-report, clinician-rated, and performance-based methods by which everyday functioning is measured in the setting of HIV disease, including global activities of daily living and specific domains of medication adherence, financial management, automobile driving, and vocational functioning.

Kordovski|Victoria M|VM|
Tierney|Savanna M|SM|
Woods|Steven Paul|SP|

D000203:Activities of Daily Living
D000328:Adult
D015658:HIV Infections
D006801:Humans
D019965:Neurocognitive Disorders
D009483:Neuropsychological Tests
D011788:Quality of Life

Everyday functioning
HIV
Activities of daily living
Functional living skills
Performance-based assessment
Self-assessment


STAT5BN642H is a driver mutation for T cell neoplasia.

Abstract: STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that expressed either human STAT5B or STAT5BN642H in the hematopoietic compartment. While STAT5B-expressing mice lacked a hematopoietic phenotype, the STAT5BN642H-expressing mice rapidly developed T cell neoplasms. Neoplasia manifested as transplantable CD8+ lymphoma or leukemia, indicating that the STAT5BN642H mutation drives cancer development. Persistent and enhanced levels of STAT5BN642H tyrosine phosphorylation in transformed CD8+ T cells led to profound changes in gene expression that were accompanied by alterations in DNA methylation at potential histone methyltransferase EZH2-binding sites. Aurora kinase genes were enriched in STAT5BN642H-expressing CD8+ T cells, which were exquisitely sensitive to JAK and Aurora kinase inhibitors. Together, our data suggest that JAK and Aurora kinase inhibitors should be further explored as potential therapeutics for lymphoma and leukemia patients with the STAT5BN642H mutation who respond poorly to conventional chemotherapy.

Pham|Ha Thi Thanh|HTT|
Maurer|Barbara|B|
Prchal-Murphy|Michaela|M|
Grausenburger|Reinhard|R|
Grundschober|Eva|E|
Javaheri|Tahereh|T|
Nivarthi|Harini|H|
Boersma|Auke|A|
Kolbe|Thomas|T|
Elabd|Mohamed|M|
Halbritter|Florian|F|
Pencik|Jan|J|
Kazemi|Zahra|Z|
Grebien|Florian|F|
Hengstschläger|Markus|M|
Kenner|Lukas|L|
Kubicek|Stefan|S|
Farlik|Matthias|M|
Bock|Christoph|C|
Valent|Peter|P|
Müller|Mathias|M|
Rülicke|Thomas|T|
Sexl|Veronika|V|
Moriggl|Richard|R|

D019943:Amino Acid Substitution
D000818:Animals
D018414:CD8-Positive T-Lymphocytes
D019175:DNA Methylation
D004273:DNA, Neoplasm
D019337:Hematologic Neoplasms
D006801:Humans
D015458:Leukemia, T-Cell
D016399:Lymphoma, T-Cell
D051379:Mice
D008822:Mice, Transgenic
D020125:Mutation, Missense
D009363:Neoplasm Proteins
D050799:STAT5 Transcription Factor

T cells
Leukemias
Lymphomas
Hematology
Oncology


Modern-day palliative chemotherapy for metastatic colorectal cancer: does colonic resection affect survival?

Abstract:
BACKGROUND
Patients with metastatic colorectal cancer (mCRC) with surgically incurable metastases would be recommended for palliative chemotherapy (PC). The role of surgical intervention is debatable with no conclusive evidence for routine primary tumour resection (PTR) or stoma creation. We aimed to study if surgical intervention conferred a survival benefit in patients with mCRC who received upfront systemic therapy.

METHODS
A retrospective review of a prospectively collected database in a single centre was performed. Patients diagnosed with mCRC from January 2004 to December 2014 were included. We excluded patients who had an upfront surgical intervention, had no treatment with systemic therapy or had attained curative resection. The decision for surgery was based on the outcome of a multidisciplinary tumour board. Demographic, clinicopathological, treatment and follow-up data were collected. Univariate and multivariate analyses were performed.

RESULTS
Out of 408 patients with mCRC with incurable metastases, we analysed 124 patients who had upfront PC. Twenty-nine had PC + PTR (group A), 10 had PC + stoma (group B) and 85 had PC only (group C). Undergoing PTR led to significant improvement in overall survival (OS; 30.8 versus 13.4 versus 11.0 months, P < 0.001). With multivariate analysis, undergoing PTR and receiving biologics were independent good prognostic variables. Surgical resection was safe with minimal complications.

CONCLUSIONS
PTR was found to increase OS while stoma creation had no impact on OS. The benefits and safety of undergoing PTR may be a result of selection bias. Further prospective studies are required to confirm the observations of this study.

D000971:Antineoplastic Combined Chemotherapy Protocols

chemotherapy
colorectal cancer
survival
metastasis
surgical stomas


Reperfusion-triggered stress protein response in the myocardium is blocked by post-conditioning. Systems biology pathway analysis highlights the key role of the canonical aryl-hydrocarbon receptor pathway.

Abstract:
AIMS
Ischaemic post-conditioning (IPost-Co) exerts cardioprotection by diminishing ischaemia/reperfusion injury. Yet, the mechanisms involved in such protection remain largely unknown. We have investigated the effects of IPost-Co in cardiac cells and in heart performance using molecular, proteomic and functional approaches.

METHODS AND RESULTS
Pigs underwent 1.5 h mid-left anterior descending balloon occlusion and then were sacrificed without reperfusion (ischaemia; n= 7), subjected to 2.5 h of cardiac reperfusion and sacrificed (n= 5); or subjected to IPost-Co before reperfusion and sacrificed 0.5 h (n= 4) and 2.5 h (n= 5) afterwards. A sham-operated group was included (n= 4). Ischaemic and non-ischaemic myocardium was obtained for molecular/histological analysis. Proteomic analysis was performed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time-of-flight identification. Potential protein networks involved were identified by bioinformatics and Ingenuity Pathway Analysis (IPA). Cardiac function was assessed by echocardiography. IPost-Co diminished (up to 2.5 h) reperfusion-induced apoptosis of both the intrinsic and extrinsic pathways whereas it did not affect reperfusion-induced Akt/mammalian target of rapamycin (mTOR)/P70S6K activation. Proteomic studies showed that IPost-Co reverted 43% of cardiac cytoplasmic protein changes observed during ischaemia and ischaemia + reperfusion. Systems biology assessment revealed significant changes in the aryl-hydrocarbon receptor (AhR) pathway (cell damage related). Bioinformatic data were confirmed since the expression of HSP90, AhR, ANRT, and β-tubulin (involved in AhR-signalling transduction) were accordingly modified after IPost-Co. IPost-Co rescued 52% of the left ventricle-at-risk compared with reperfusion alone and resulted in a ≈30% relative improvement in left ventricular ejection fraction (P <0.05).

CONCLUSION
IPost-Co improves cardiac function post-myocardial infarction and reduces reperfusion-induced cell damage by down-regulation of the AhR-signalling transduction pathway ultimately leading to infarct size reduction.

Vilahur|Gemma|G|
Cubedo|Judit|J|
Casani|Laura|L|
Padro|Teresa|T|
Sabate-Tenas|Manel|M|
Badimon|Juan J|JJ|
Badimon|Lina|L|

D051784:Aryl Hydrocarbon Receptor Nuclear Translocator

Ischaemic post-conditioning
Proteomics
Cell damage
AhR pathway


Perception of clinical deterioration cues among medical-surgical nurses.

Abstract:
AIM
To examine medical-surgical nurses' capacity and tendency to perceive cues indicating clinical deterioration and nursing characteristics influencing deterioration cue perception.

DESIGN
Cross-sectional, explorative study design.

METHODS
Data were collected over 10 weeks between September-November 2017. Medical-surgical nurses completed an online survey consisting of a demographic questionnaire, the Occupational Fatigue, Exhaustion Recovery scale and 50 detection trials. Descriptive statistics and statistical tests were used to describe and interpret data.

FINDINGS
A significant association was found between nurses' capacity and tendency to perceive deterioration cues. As nurses' capacity to perceive deterioration cues increased, nurses were more likely to classify patient cues as indicators of deterioration. Fatigue, education, and certification were not identified as characteristics associated with deterioration cue perception. However, experience was observed to significantly influence nurses' capacity to perceive deterioration cues based on levels of skills acquisition.

CONCLUSION
Study findings imply that future research should be directed at determining whether other individual factors and organizational system dynamics influence deterioration cue perception.

IMPACT
To better understand how nurses perceive deterioration cues, this study integrated concepts from the Situation Awareness model and Signal Detection Theory. Novice, advanced beginner and competent nurses were found to have a lower capacity to perceive deterioration cues compared with proficient and expert nurses. With simulation increasingly being used as a primary teaching modality in nursing, the development of a simulation-based signal detection training intervention may be beneficial in enhancing deterioration cue perception.

clinical deterioration
nurses
nurses
cue perception
education
situation awareness
signal detection
nursing
psychological


Bioflocculant production from untreated corn stover using Cellulosimicrobium cellulans L804 isolate and its application to harvesting microalgae.

Abstract:
BACKGROUND
Microalgae are widely studied for biofuel production. Nevertheless, harvesting step of biomass is still a critical challenge. Bioflocculants have been applied in numerous applications including the low-cost harvest of microalgae. A major bottleneck for commercial application of bioflocculant is its high production cost. Lignocellulosic substrates are abundantly available. Hence, the hydrolyzates of rice stover and corn stover have been used as carbon source to produce the bioflocculant in previous studies. However, the hydrolyzates of biomass required the neutralization of pH before the downstream fermentation processes, and the toxic by-products produced during hydrolysis process inhibited the microbial activities in the subsequent fermentation processes and contaminated the bioflocculant product. Therefore, strains that can secrete plant cell-wall-degrading enzymes and simultaneously produce bioflocculants through directly degrading the lignocellulosic biomasses are of academic and practical interests.

RESULTS
A lignocellulose-degrading strain Cellulosimicrobium cellulans L804 was isolated in this study, which can produce the bioflocculant MBF-L804 using untreated biomasses, such as corn stover, corn cob, potato residues, and peanut shell. The effects of culture conditions including initial pH, carbon source, and nitrogen source on MBF-L804 production were analyzed. The results showed that over 80 % flocculating activity was achieved when the corn stover, corn cob, potato residues, and peanut shell were used as carbon sources and 4.75 g/L of MBF-L804 was achieved under the optimized condition: 20 g/L dry corn stover as carbon source, 3 g/L yeast extract as nitrogen source, pH 8.2. The bioflocculant MBF-L804 contained 68.6 % polysaccharides and 28.0 % proteins. The Gel permeation chromatography analysis indicated that the approximate molecular weight (MW) of MBF-L804 was 229 kDa. The feasibility of harvesting microalgae Chlamydomonas reinhardtii and Chlorella minutissima using MBF-L804 was evaluated. The highest flocculating efficiencies for C. reinhardtii and C. minutissima were 99.04 and 93.83 %, respectively.

CONCLUSIONS
This study shows for the first time that C. cellulans L804 can directly convert corn stover, corn cob, potato residues and peanut shell into the bioflocculants, which can be used to effectively harvest microalgae.

Liu|Weijie|W|0000-0002-7152-6013 Zhao|Chenchu|C| Jiang|Jihong|J| Lu|Qian|Q| Hao|Yan|Y| Wang|Liang|L| Liu|Cong|C|

Bioflocculant
Corn stover
Cellulosimicrobium cellulans
Biofuels
Microalgae harvest


A population-based study of pyogenic liver abscess in Korea: Incidence, mortality and temporal trends during 2007-2017.

Abstract:
BACKGROUND/AIMS
Although the epidemiology of pyogenic liver abscess (PLA) continues to change, only a few population-based studies have been conducted in Korea. This study investigated the epidemiology and clinical outcomes of PLA patients during a period of 10 years.

METHODS
We analysed the Health Insurance Review and Assessment Service data between 2007 and 2017. The data included annual incidence rates, demographic data, underlying diseases, complications and mortality of PLA patients.

RESULTS
The annual incidence of PLA for all age groups was 10.9 per 100 000 population. The incidence was gradually increased from 5.7 per 100 000 in 2007 to 14.4 per 100 000 in 2017. In patients with liver abscess, the prevalence of diabetes and malignancy were 37.24% and 26.5% respectively. Metastatic infection was reported in 1.74% of the patients, and endophthalmitis was most common. The mean in-hospital mortality was 9.6%, and there was no significant difference in mortality by year during the observation period. Mortality increased with age and was greatly affected by the underlying diseases, especially cancer. Based on the multivariate analysis results, the mortality of PLA patients was associated with older age, female sex, diabetes, malignancy and chronic kidney disease.

CONCLUSION
The PLA incidence is rapidly increasing in Korea, especially in people with comorbidities. In addition, the causes and risk factors of PLA infections are changing and thus further research on epidemiology, different diagnosis and management approaches is required.

Yoo|Jeong-Ju|JJ|0000-0002-7802-0381
Lee|Tae Kyu|TK|
Kyoung|Dae-Sung|DS|
Park|Min-Ae|MA|
Kim|Sang Gyune|SG|0000-0001-8694-777X
Kim|Young Seok|YS|0000-0002-7113-3623

liver abscess
incidence
mortality
epidemiology


Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

Abstract: We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients.

Mijiti|Peierdun|P| Yuexin|Zhang|Z| Min|Liu|L| Wubuli|Maimaitili|M| Kejun|Pan|P| Upur|Halmurat|H|

D023241:Antiretroviral Therapy, Highly Active

prevalence
predictors
anaemia
HIV
antiretroviral therapy
China
AIDS
haemoglobin


Facile green synthesis of silver nanoparticles using Mangifera indica seed aqueous extract and its antimicrobial, antioxidant and cytotoxic potential (3-in-1 system).

Abstract: A novel approach for the utilisation of fruit waste is attempted in the present investigation. Mangifera indica seed aqueous extract was utilised for green synthesis of silver nanoparticles (AgNPs). The phytoconstituents in the seed acted as reducing and stabilising agent for AgNP formation. UV-Vis, Zeta potential, FT-IR, XRD, TEM, SAED, EDX analysis were used to characterise the green synthesised AgNPs. UV-vis spectra showed characteristic spectra at 450 nm; XRD and SAED confirmed the crystalline nature while TEM revealed the shape to be round and average size was 26.85 nm. FT-IR revealed functional groups like alcohol or phenols, carboxylic acids, ketones, amines, aromatic amines, aliphatic amines, alkyl halides and alkynes which were responsible for AgNP formation. The nanoparticles showed more antibacterial activity than antifungal activity and antibacterial activity towards Gram-negative bacteria was more than Gram-positive bacteria. Dose dependent antioxidant activity (DPPH, SO and ABTS) and dose dependent cytotoxic effect against HeLa, MCF-7 and normal fibroblast cell lines was envisaged. The green synthesised AgNPs exhibited three different bioactivities (3-in-1 system) i.e. dose dependent antimicrobial, antioxidant and cytotoxic activity. Fruit waste can be successfully utilised for silver nanoparticles formation which can be therapeutically useful and effective.[Figure: see text]HighlightsSilver nanoparticles were synthesised from M. indica fruit waste i.e. seedCharacterisation by spectroscopic techniques: UV-Vis, Zeta, FTIR, XRD, SAED, EDX and TEM analysis.Silver nanoparticles were 26.85 nm in size and round in shapeAntimicrobial activity against 14 microorganismsAntioxidant activity in terms of DPPH, SO and ABTSCytotoxic activity against HeLa, MCF-7 and Fibroblast normal cell lines.

green synthesis
silver nanoparticles
Mangifera indica
seed
antimicrobial
antioxidant
cytotoxic
Fruit waste