Epigenetic modifications of DAPK and p16 genes contribute to arsenic-induced skin lesions and nondermatological health effects.

Abstract: Over 26 million people in West Bengal, India, are exposed to very high levels of arsenic through drinking water, leading to several deleterious endpoints including cancers. To elucidate the role of promoter methylation in arsenic-induced dermatological and nondermatological health effects, methylation status of p16 and DAPK genes was determined. A case-control study was conducted involving 72 individuals with arsenic-induced skin lesions (cases) and 50 individuals without skin lesions (controls), having similar arsenic exposure through drinking water. Methylation status was determined by bisulfite conversion of genomic DNA and methylation-specific PCR. Expression of the genes was determined by real-time PCR and Western blot analysis. Associations between the promoter methylation status and nondermatological health effects were determined from epidemiological survey data. Significant hypermethylation was found in the promoters of both DAPK and p16 genes in the cases compared with the controls resulting in downregulation of both the genes in the cases. There was a 3.4-fold decrease in the expression of death-associated protein kinase and 2.2-fold decrease in gene expression of p16 in the cases compared to the controls, the lowest expression being in the cancer tissues. Promoter hypermethylation of the genes was also associated with higher risk of developing arsenic-induced skin lesions, peripheral neuropathy, ocular and respiratory diseases. This study for the first time makes an attempt to correlate epigenetic modifications of the tumor suppressor genes with dermatological and nondermatological health outcomes in a population chronically exposed to arsenic.

Banerjee|Nilanjana|N|
Paul|Somnath|S|
Sau|Tanmoy J|TJ|
Das|Jayanta K|JK|
Bandyopadhyay|Apurba|A|
Banerjee|Saptarshi|S|
Giri|Ashok K|AK|

DAPK
p16
nondermatological health effects
arsenic
hypermethylation
skin lesions.


The effect of flavonoid quercetine on the indices of nitric oxide system in rats with chronic enterocolitis combined with streptozotocin-induced diabetes.

Abstract:
OBJECTIVE
Introduction: Chronic hyperglycemia is accompanied by significant physiological, biochemical, and histological changes, e.g. development of oxidative and nitrosative stress that affects the motor activity of the intestine. The aim: The present study was designed to evaluate the indices of nitric oxide (NO) system in blood serum and a colon tissue supernatant of rats with chronic enterocolitis combined with streptozotocin-induced diabetes.

PATIENTS AND METHODS
Materials and methods: The total NOS activity was performed by monitoring the rate of conversion of L-arginine into citrulline. The total contents of NO metabolites was assessed by evaluation of their amount, which included nitrite ions that were previously presented in the sample (NO2-) and also nitrate ions reducted to nitrites (NO3-).

RESULTS
Results and conclusions: Thus, in rats with modeled chronic enterocolitis activation of nitroxydergic process in blood serum and colon tissue has been established. Herewith more pronounced intensification of nitroxydergic processes was observed in rats with chronic enterocolitis combined with streptozotocin-induced diabetes. The liposomal form of quercetin - Lipoflavon significantly reduces nitrosative stress in rats with chronic enterocolitis combined with streptozotocin-induced diabetes.

Krynytska|Іnna|І| Kushynska|Mariia|M| Pavlenko|Iryna|I| Marushchak|Mariya|M|

quercetin
nitric oxide
enterocolitis
diabetes
NO-synthase


Effect of parathyroidectomy on epicardial fat thickness as a cardiovascular risk factor in patients with primary hyperparathyroidism

Abstract:
Background/aim
Several  studies  demonstrated  that  primary  hyperparathyroidism  is  related  to  increased  risk  for  cardiovascular  diseases (CVDs), and risk is decreased by parathyroidectomy. Epicardial fat thickness (EFT) has been postulated as a new marker of CVD risk. We evaluated the impact of parathyroidectomy on EFT in patients with primary hyperparathyroidism (PHPT).

Materials and methods
Thirty-four  PHPT  patients  (29  female,  5  male)  and  28  age-  and  sex-matched  controls  (19  female,  9  male)  were included in the study. Demographic, anthropometric, and biochemical data were recorded both before parathyroidectomy and 6 months after the procedure. Epicardial fat thickness was measured by transthoracic echocardiography.

Results
Mean  age  was  53.15  ±  8.44  years.  Mean  preoperative  EFT  was  higher  than  mean  EFT  in  the  control  group  (0.49  ±  0.07  cm  to  0.46  ±  0.08  cm,  P:  0.0005),  and  EFT  decreased  after  parathyroidectomy  (0.49  ±  0.07  cm  to  0.44  ±  0.08  cm,  P:  0.0005).  Systolic  blood pressure and calcium, parathormone, and hsCRP levels decreased after parathyroidectomy (P < 0.05). Vitamin D levels increased (P  <  0.05).  Diastolic  blood  pressure,  body  mass  index,  carotid  intima-media  thickness,  and  HOMA-IR,  fasting  plasma  glucose,  and  phosphorus levels were unchanged after parathyroidectomy (P > 0.05). Preoperatively, EFT was correlated with SBP (r: 0.360, P: 0.0285) and age (r: 0.466, P: 0.0036). Multiple linear regression used to identify independent predictors of change in epicardial fat did not find any predictor of change in epicardial fat (P > 0.05).

Conclusion
EFT was decreased by parathyroidectomy in patients with primary hyperparathyroidism.However, the decrease in EFT was not correlated with any of the cardiovascular risk factors. More comprehensive studies evaluating the potential relation between PHPT and EFT need to be conducted.

epicardial fat thickness
Primary hyperparathyroidism
cardiometabolic risk factors


An outbreak investigation of Legionella non-pneumophila Legionnaires' disease in Sweden, April to August 2018: Gardening and use of commercial bagged soil associated with infections.

Abstract: In early June 2018, an increase in non-travel-related cases of Legionella non-pneumophila Legionnaires' disease (LD) was observed in Sweden and a national outbreak investigation was started. Outbreak cases were defined as notified confirmed or probable cases of L. non-pneumophila LD, with symptom onset after 1 April 2018. From April to August 2018, 41 cases were reported, 30 of whom were identified as L. longbeachae. We conducted a case-control study with 27 cases and 182 matched controls. Results from the case-control study indicated that gardening and handling commercial bagged soil, especially dusty dry soil, were associated with disease. L. longbeachae was isolated in soils from cases' homes or gardens, but joint analysis of soil and human specimens did not identify any genetic clonality. Substantial polyclonality was noted between and within soil samples, which made finding a genetic match between soil and human specimens unlikely. Therefore, whole genome sequencing may be of limited use to confirm a specific soil as a vehicle of transmission for L. longbeachae. Handling soil for residential gardening was associated with disease and the isolation of L. longbeachae in different soils provided further evidence for Legionella non-pneumophila infection from soil.

Löf|Emma|E|
Chereau|Fanny|F|
Jureen|Pontus|P|
Andersson|Sabina|S|
Rizzardi|Kristina|K|
Edquist|Petra|P|
Kühlmann-Berenzon|Sharon|S|
Galanis|Ilias|I|
Schönning|Caroline|C|
Kais|Madeleine|M|
Tideholm Nylén|Anne|A|
Wallensten|Anders|A|
Roth|Adam|A|
|||

outbreak
Legionella non-pneumophila
soil
Legionella longbeachae
Legionnaires’ disease
case control study


Hair mercury concentrations in residents of Sundarban and Calcutta, India.

Abstract: Few studies on hair mercury have been conducted in India despite the fact that India is the world's third largest producer of coal and coal is India's primary energy source. No studies have been conducted in the Indian state of West Bengal which has a coastline with the Bay of Bengal. This study examined the concentration of mercury in hair in two diverse populations in West Bengal, India: Sundarban, a mangrove wetland where fishing is a common occupation, and Calcutta, a megacity and India's oldest functioning port. Individuals from whom scalp hair was collected (N=100) were asked a series of questions on occupation, education, age, smoking and alcohol consumption, and fish consumption. SAS was utilized to generate descriptive statistics including frequency and univariate analyses and to perform regression analyses to determine significant predictors of hair mercury in this population. The mean hair mercury increased across the first three age categories (<21, 21-30, 31-45) and decreased in the fourth category (>45). Hair mercury concentration was significantly higher among residents of Sundarban compared to Calcutta (p=0.0005). In multivariable analysis, location (Sundarban vs. Calcutta) and age were significant predictors of hair mercury concentration (p=0.0120 and p=0.0161, respectively). Average hair mercury concentrations in this study were not particularly elevated. Smoking and alcohol consumption were predictors of hair mercury concentration. The hair mercury in Sundarban residents compared to Calcutta residents may be elevated due to greater consumption of fish and type of fish consumed.

Gibb|Herman|H|
O'Leary|Keri Grace|KG|
Sarkar|Santosh Kumar|SK|
Wang|Jing|J|
Liguori|Lisa|L|
Rainis|Holly|H|
Smith|Katy A|KA|
Chatterjee|Mousumi|M|

Hair mercury
India
Fishing
Fish consumption
Methylmercury


Combined effects of the light touch and cognitive task affect the components of postural sway.

Abstract: The light touch (LT) of the fingertip on a rigid surface and the performance of a cognitive task (CT) affect the postural control. The current study examined the mechanisms involved in the control of postural sway (i.e., Rambling and Trembling components of the center of pressure) with the LT and CT performed individually or simultaneously. Thirteen adults stood on a force plate for 70 s while performed the LT, CT (visual searching of specific letters) or both tasks simultaneously. COP, Rambling, and Trembling mean amplitude and speed were computed. COP and Rambling trajectories were highly and Trembling moderately reduced with LT. The CT affected mainly the Rambling component, supporting the role of supraspinal control of postural sway. These findings suggested that while LT influences both supraspinal and peripheral control mechanisms, CT influences mostly the supraspinal mechanisms involved in postural sway. The combined effects of LT and CT improve the postural control with no negative consequences on CT performance.

Garbus|Rafaela Barroso de Souza Costa|RBSC|

de Freitas|Sandra Maria Sbeghen Ferreira|SMSF|

Cognitive task
Postural sway
Rambling
Trembling
Somatosensory information
Suprapostural task


The Orphan Crop Crassocephalum crepidioides Accumulates the Pyrrolizidine Alkaloid Jacobine in Response to Nitrogen Starvation.

Abstract: Crassocephalum crepidioides is an African orphan crop that is used as a leafy vegetable and medicinal plant. Although it is of high regional importance in Sub-Saharan Africa, the plant is still mainly collected from the wild and therefore efforts are made to promote its domestication. However, in addition to beneficial properties, there was first evidence that C. crepidioides can accumulate the highly toxic pyrrolizidine alkaloid (PA) jacobine and here it was investigated, how jacobine production is controlled. Using ecotypes from Africa and Asia that were characterized in terms of their PA profiles, it is shown that the tetraploid C. crepidioides forms jacobine, an ability that its diploid close relative Crassocephalum rubens appears to lack. Evidence is provided that nitrogen (N) deficiency strongly increases jacobine in the leaves of C. crepidioides, that this capacity depends more strongly on the shoot than the root system, and that homospermidine synthase (HSS) activity is not rate-limiting for this reaction. A characterization of HSS gene representation and transcription showed that C. crepidioides and C. rubens possess two functional versions, one of which is conserved, that the HSS transcript is mainly present in roots and that its abundance is not controlled by N deficiency. In summary, this work improves our understanding of how environmental cues impact PA biosynthesis in plants and provides a basis for the development of PA-free C. crepidioides cultivars, which will aid its domestication and safe use.

Schramm|Sebastian|S|
Rozhon|Wilfried|W|
Adedeji-Badmus|Adebimpe N|AN|
Liang|Yuanyuan|Y|
Nayem|Shahran|S|
Winkelmann|Traud|T|
Poppenberger|Brigitte|B|

alkaloids
domestication
Yoruba bologi
ebolo
fireweed
genome
neglected crop
nutrients


The effect of air exposure on leucocyte and cytokine activation in an in-vitro model of cardiotomy suction.

Abstract:
INTRODUCTION
Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response.

OBJECTIVE
An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate.

METHODS
Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37oC.

RESULTS
Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours.

CONCLUSION
This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.

Toomasian|Cory J|CJ|
Aiello|Salvatore R|SR|
Drumright|Benjamin L|BL|
Major|Terry C|TC|
Bartlett|Robert H|RH|
Toomasian|John M|JM|0000-0002-4055-0395

leucocytes
cytokines
cardiotomy suction
CPB
CD11-b


Feasibility of improving cerebral autoregulation in acute intracerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study.

Abstract:
BACKGROUND
Cerebral autoregulation is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral hemorrhage, impairment of cerebral autoregulation has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger hematoma volume. Hypocapnia has been shown to improve cerebral autoregulation despite concerns over hypoperfusion and consequent ischemic risks, and it is therefore hypothesized that hypocapnia (via hyperventilation) in acute intracerebral hemorrhage may improve cerebral autoregulation and consequently clinical outcome.

AIMS
To assess the feasibility and acceptability of the first cerebral autoregulation-targeted intervention in acute intracerebral hemorrhage utilizing a simple bed-side hyperventilatory maneuver.

METHODS
Twelve patients with acute intracerebral hemorrhage within 48 h of onset were enrolled. The experimental setup measured cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), and end-tidal CO2 (EtCO2, capnography) at baseline, and in response to hypocapnia (-5 mmHg below baseline) achieved via a 90-s hyperventilatory maneuver. Cerebral autoregulation was evaluated with transfer function analysis and autoregulatory index calculations.

RESULTS
We observed tolerance to the protocol in a cohort of mild (National Institutes of Health Scale 4) supratentorial intracerebral hemorrhage patients with small volume hematomas without intraventricular extension. Importantly, a significant difference was noted between ipsilateral autoregulatory index at baseline 4.8 (1.7) and autoregulatory index during hypocapnic intervention 7.0 (0.8) (p = 0.0004), reflecting improved cerebral autoregulation, though a dose-dependent effect of EtCO2 on autoregulatory index was not observed.

CONCLUSIONS
In this small study, there was no observed effect on 14-day death and disability in recruited participants. This is the first report of improvement in cerebral autoregulation in acute intracerebral hemorrhage using a non-invasive interventional maneuver, through induction of hypocapnia via hyperventilation.ClinicalTrials.gov Identifier: NCT03324321URL: https://clinicaltrials.gov/ct2/show/NCT03324321.

Hemorrhage
intervention
blood pressure
carbon dioxide
hemodynamics


Local Recurrent Phyllodes Tumors of the Breast: Clinical and Sonographic Features.

Abstract:
OBJECTIVES
The purpose of this study was to investigate the clinical, pathologic, and sonographic features of local recurrent phyllodes tumors of the breast and provide evidence for diagnosing tumor recurrence.

METHODS
A total of 127 patients with phyllodes tumors who underwent surgery from 1993 to 2012 were followed. The clinical, pathologic, and sonographic features of local recurrent tumors were analyzed.

RESULTS
Of the 127 patients, pathologic diagnoses were benign, borderline, and malignant in 75 (59.1%), 41 (32.3%), and 11 (8.7%) patients, respectively. The patients were followed for a mean duration ± SD of 50.9 ± 42.1 months (range, 2-225 months). Twenty-one patients had local recurrence, for a recurrence rate of 16.5%. The benign, borderline, and malignant recurrence rates were 14.7%, 17.1%, and 27.3%. The local recurrence in the 21 patients occurred after a mean interval of 19.4 ± 13.4 months. The mean times to local recurrence were 20.2 ± 12.1, 16.9 ± 10.8, and 20.3 ± 19.0 months for benign, borderline, and malignant tumors. The histologic characteristics of the recurrent tumors were similar to those of the initial tumors in 14 patients (66.7%), whereas the characteristics changed in 7 (33.3%). The sonographic features of the recurrent tumors were as follows: 69.4% were lobulated; 88.9% appeared as well-defined lesions; 41.7% had posterior acoustic enhancement; 11.1% had intramural cystic areas; and 83.4% had moderate or marked blood flow.

CONCLUSIONS
The recurrence rate for phyllodes tumors is high. One to 2 years after surgery is the key time for follow-up. The sonographic features contribute to recurrence diagnosis.

Xiao|Mengsu|M| Zhu|Qingli|Q| Jiang|Yuxin|Y| Li|Jianchu|J| Wang|Hongyan|H| Zhang|Jing|J| You|Shanshan|S| Liu|He|H|

local recurrence
phyllodes tumor
breast
breast ultrasound


Corrigendum: YAP and TAZ Regulate Cc2d1b and Purβ in Schwann Cells.

Abstract: [This corrects the article DOI: 10.3389/fnmol.2019.00177.].

Belin|Sophie|S|
Herron|Jacob|J|
VerPlank|Jordan J S|JJS|
Park|Yungki|Y|
Feltri|Laura M|LM|
Poitelon|Yannick|Y|


Abstract:
Aim and objective
To evaluate the antimicrobial efficacy of triple antibiotic paste and propolis extracts as an intracanal medicament in young permanent teeth.

Materials and methods
A total of 30 single-rooted non-vital young permanent teeth with open apex were selected randomly from the children aged between 7 years and 14 years with no systemic complications. Group I-triple antibiotic paste and group II be propolis allocating 15 teeth in each group. After access opening, the first sample (S1) was collected by inserting paper point into the root canal, the second sample (S2) was collected immediately after irrigation, and the third sample (S3) was collected after post-intracanal medication after 3-4 weeks. Samples were sent for microbiological analysis to assess the bacterial count, and for the obtained data, statistical analysis was done.

Results
The mean colony count among the triple antibiotic paste group was 1906.75. After access opening, which was reduced to 315.12 after irrigation, and after 3-4 weeks, it was 817.25. There was a significant difference between sample 1, sample 2, and sample 3 (p value = 0.008). The mean colony count among the propolis group was 1427.87 after access opening, which was reduced to 436.00 after irrigation, and after 3-4 weeks, it has reduced to 252.37. There was a significant difference between sample 1, sample 2, and sample 3 (p value = 0.032). Intergroup comparison between the groups showed no statistical difference between the samples.

Conclusion
Propolis exhibited similar antimicrobial efficacy, which is comparable to triple antibiotic paste. So, propolis can be utilized as an intracanal medicament in young permanent teeth with an open apex.

Clinical significance
Propolis is a naturally occurring flavonoid-rich resinous product with antibacterial, antifungal, antiviral, immunomodulatory, and antioxidant effects. It is safe without any drug allergies and bacterial sensitivity and is a promising alternative to triple antibiotic paste for disinfecting non-vital young permanent teeth.

How to cite this article
Lillygrace E, Kethineni B, Puppala R, et al. Antimicrobial Efficacy of Triple Antibiotic Paste and Propolis as an Intracanal Medicament in Young Permanent Teeth: An In Vivo Study. Int J Clin Pediatr Dent 2021;14(2):243-248.

Lillygrace|Edara|E|
Kethineni|Balaji|B|
Puppala|Ravindar|R|
Raichurkar|Hemanth Kl|HK|
Ambati|Srilekha|S|
Saikiran|Kanamarlapudi V|KV|

Triple antibiotic paste
Propolis
Young permanent teeth
Sodium hypochlorite


Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems.

Abstract: Fungal two-component regulatory systems incorporate receiver domains into hybrid histidine kinases (HHKs) and response regulators. We constructed a nonredundant database of 670 fungal receiver domain sequences from 51 species sampled from nine fungal phyla. A much greater proportion (21%) of predicted fungal response regulators did not belong to known groups than previously appreciated. Receiver domains in Rim15 response regulators from Ascomycota and other phyla are very different from one another, as are the duplicate receiver domains in group XII HHKs. Fungal receiver domains from five known types of response regulators and 20 known types of HHKs exhibit distinct patterns of amino acids at conserved and variable positions known to be structurally and functionally important in bacterial receiver domains. We inferred structure/activity relationships from the patterns and propose multiple experimentally testable hypotheses about the mechanisms of signal transduction mediated by fungal receiver domains.

Bourret|Robert B|RB|0000-0002-6666-9220
Foster|Clay A|CA|
Goldman|William E|WE|

receiver domain
two-component regulatory systems
hybrid histidine kinase
response regulator
fungi


Correlations between three patient-assessed shoulder instability scales.

Abstract:
PURPOSE
To evaluate the correlations between three patient-assessed shoulder instability scales before and after Latarjet stabilisation for traumatic anteroinferior glenohumeral instability.

METHODS
Records of 30 men and 2 women (mean age, 26.7 years) who had not undergone surgery for antero-inferior shoulder instability and records of 31 men and one woman (mean age, 27 years) who had undergone Latarjet stabilisation for anteroinferior shoulder instability and had been followed up for a mean period of 21.3 months were reviewed. Correlations between the Western Ontario Shoulder Instability Index (WOSI), the Melbourne Instability Shoulder Score (MISS), and the L'Insalata Shoulder Questionnaire (L'Insalata) were assessed.

RESULTS
The mean score of each scale was significantly greater in the postoperative than preoperative group (p<0.001). Within each group, the mean scores of the 3 scales differed significantly (ANOVA, p=0.001). The mean L'Insalata score was significantly higher than the mean WOSI and MISS scores (p<0.01, posthoc analysis), but the latter 2 scores did not differ significantly (p>0.01, post-hoc analysis). Correlations of all scale pairs were significant (p<0.001). The WOSIMISS correlations in the pre- and post-operative groups were moderate. The L'Insalata-WOSI correlations in the pre- and post-operative groups were moderate and high, respectively. The L'Insalata-MISS correlations in the pre- and post-operative groups were high and moderate, respectively.

CONCLUSION
The MISS and WOSI scales are moderately correlated. Correlation of the L'Insalata scale with other scales depends on the operative status of the patient. The use of the L'Insalata scale alone is not recommended.

Taylor|David|D|
Garewal|Devinder|D|
Evans|Matthew C|MC|

questionnaires
patient outcome assessment
shoulder dislocation


Costs of sialendoscopy and impact on health-related quality of life.

Abstract:
PURPOSE
To analyse costs related to the diagnosis and treatment of patients with sialolithiasis and sialadenitis managed with sialendoscopy, and to prospectively evaluate the impact of sialendoscopy on health-related quality of life (HRQoL) in a longitudinal follow-up study.

METHODS
All patients undergoing sialendoscopy or sialendoscopy-assisted surgery at a tertiary care university hospital between January 2014 and May 2016 were identified from a surgical database, and the direct hospital costs were retrospectively evaluated from 1 year before to 1 year after the sialendoscopy. The 15D HRQoL questionnaire and a questionnaire exploring the use of health care services during the preceding 3 months were mailed to the patients before sialendoscopy as well as at 3 and 12 months after the operation.

RESULTS
A total of 260 patients were identified. Mean total hospital costs, costs related to the sialendoscopy, and complications were significantly higher in sialolithiasis patients than in patients with other diagnoses. 74 patients returned the baseline 15D questionnaire, and 51 patients all three 15D questionnaires. At baseline, the dimensions "discomfort and symptoms" and "distress" were lower in patients than in age- and gender-standardised general population, but the total 15D score did not differ significantly. The dimension "discomfort and symptoms" improved significantly at 3 and 12 months postoperatively, and the mean total HRQoL score improved in patients with sialolithiasis at 3 months postoperatively.

CONCLUSIONS
The costs related to sialendoscopy are substantial and the cost-effectiveness of sialendoscopy warrants further studies. However, sialendoscopy seems to reduce patients' discomfort and ailments and to improve HRQoL at least in patients with sialolithiasis.

Costs
Sialendoscopy
Health-related quality of life
Quality of life
Sialadenitis
Cost-effectiveness


High pressure promotes alpha-synuclein aggregation in cultured neuronal cells.

Abstract: α-Synuclein is found in plaques associated with Parkinson's and other neurodegenerative diseases. Changes in α-synuclein oligomerization are thought to give rise to nucleation of neurodegenerative plaques. Here, we investigated the effect of hydrostatic pressure on the aggregation of α-synuclein in cultured neuronal cells. We found that hydrostatic pressure is associated with a transition from monomeric to higher order α-synuclein aggregates. We then tested whether this aggregation is associated with the loss of binding partners, such as phospholipase Cβ. We found that increased pressure reduces the level of PLCβ1 and the amount of α-synuclein/PLCβ1 complexes. These studies suggest that pressure promotes release of α-synuclein from protein partners promoting its oligomerization.

Aggregation
Hydrostatic pressure
Alpha synuclein
Parkinson’s disease
Phospholipase beta 1


Cardiotoxicity in metastatic melanoma patients treated with BRAF and MEK inhibitors in a real-world setting.

Abstract:
BACKGROUND
Combination therapy with BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved the outcome for patients with BRAF-mutated melanoma. A reduction in left ventricular ejection fraction (LVEF) is a known side effect during treatment with BRAF/MEKi. This study aimed to analyze sequential multigated acquisition (MUGA) scans for the evaluation of LVEF and provide real-world data on cardiotoxicity induced by BRAF/MEKi in advanced melanoma.

METHODS
All patients with advanced melanoma treated with dabrafenib and trametinib at Herlev and Gentofte Hospital, Denmark, between March 2015 and September 2019, were included retrospectively. MUGA scans performed at baseline and every three months during treatment were analyzed. Cardiotoxicity was defined as a decline of ≥10 percentage point (pp) to an LVEF <50% (major cardiotoxicity) or a decline in LVEF of ≥15 pp but remaining >50% (minor cardiotoxicity).

RESULTS
A total of 139 patients were included. Forty-six patients (33%) met our criteria for cardiotoxicity; 31 patients (22%) experienced minor cardiotoxicity and 15 patients (11%) experienced major cardiotoxicity. Median time to decline in LVEF was 94 days, and all clinically significant declines in LVEF occurred before evaluation at six months. Reversibility of LVEF was seen in 80% of patients, three patients were not evaluable for reversibility. A low left ventricular peak emptying rate adjusted for heart rate (LVPERadj) at baseline was found a potential risk factor for the development of major cardiotoxicity (RR = 0.159, p = 0.001).

CONCLUSION
A decline in LVEF is common for patients with advanced melanoma treated with BRAF/MEKi but rarely clinically significant. No significant decline in LVEF was observed after evaluation at six months, therefore routine monitoring of LVEF might be stopped after six to nine months of BRAF/MEKi therapy. A low LVPERadj might be a risk factor for the development of cardiotoxicity and is suggested for further investigation.

Pedersen|Sidsel|S|
Larsen|Kirstine Ostenfeld|KO|
Christensen|Alex Hørby|AH|
Svane|Inge Marie|IM|0000-0002-9451-6037
Zerahn|Bo|B|
Ellebaek|Eva|E|0000-0001-6748-9232

cardiotoxicity
multigated acquisition
BRAF/MEK inhibition
equilibrium radionuclide angiography
malignant melanoma


Next-Generation Sequencing-Based Cancer Panel Data Conversion Using International Standards to Implement a Clinical Next-Generation Sequencing Research System: Single-Institution Study.

Abstract:
BACKGROUND
The analytical capacity and speed of next-generation sequencing (NGS) technology have been improved. Many genetic variants associated with various diseases have been discovered using NGS. Therefore, applying NGS to clinical practice results in precision or personalized medicine. However, as clinical sequencing reports in electronic health records (EHRs) are not structured according to recommended standards, clinical decision support systems have not been fully utilized. In addition, integrating genomic data with clinical data for translational research remains a great challenge.

OBJECTIVE
To apply international standards to clinical sequencing reports and to develop a clinical research information system to integrate standardized genomic data with clinical data.

METHODS
We applied the recently published ISO/TS 20428 standard to 367 clinical sequencing reports generated by panel (91 genes) sequencing in EHRs and implemented a clinical NGS research system by extending the clinical data warehouse to integrate the necessary clinical data for each patient. We also developed a user interface with a clinical research portal and an NGS result viewer.

RESULTS
A single clinical sequencing report with 28 items was restructured into four database tables and 49 entities. As a result, 367 patients' clinical sequencing data were connected with clinical data in EHRs, such as diagnosis, surgery, and death information. This system can support the development of cohort or case-control datasets as well.

CONCLUSIONS
The standardized clinical sequencing data are not only for clinical practice and could be further applied to translational research.

translational research information system


Skin Rash and Interstitial Pneumonia Can Be a Fatal Combination: A Rare Case of Anti-Melanoma Differentiation-Associated Gene 5 (MDA5)-Associated Interstitial Lung Disease.

Abstract:
We report the case of a 62-year-old male patient fully vaccinated for COVID-19, admitted to our emergency room for persistent fever associated with exertional dyspnoea, skin lesions, diffuse myalgias and arthralgias not responsive to broad-spectrum antibiotic and antiviral therapy, who developed a rapidly progressive refractory to treatment interstitial lung disease due to anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, that required mechanical ventilation and ECMO. Here, we highlight the importance of always considering alternative diagnoses, i.e. viral and autoimmune diseases, including anti-MDA5 antibody screening, when dealing with patients with a skin rash, seronegative polyarthralgias and interstitial pneumonia, or acute respiratory distress syndrome of unknown origin.

LEARNING POINTS
MDA5-associated dermatomyositis is a rare systemic syndrome associated with rapidly progressive and treatment-refractory interstitial lung disease.The anti-MDA5 antibody is the key biomarker for the diagnosis.Early diagnosis is crucial to promptly start aggressive immunosuppressive therapy with the aims of improving prognosis and reducing mortality.

Borio|Giorgia|G| Terracciano|Chiara|C| Buttafava|Federico|F| Vercelli|Andrea|A| Pagani|Laura|L| Zanzani|Chiara|C| Manicardi|Alessandra|A| Magnacavallo|Andrea|A| Poggiali|Erika|E|

MDA5-associated interstitial lung disease


Abstract: Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.-Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.

Kanetake|Tsukasa|T| Sassa|Takayuki|T| Nojiri|Koki|K| Sawai|Megumi|M| Hattori|Satoko|S| Miyakawa|Tsuyoshi|T| Kitamura|Takuya|T| Kihara|Akio|A|

myelin
aldehyde
ALDH3A2
sphingolipid
fatty acid 2-hydroxylase


Subacute effects of rose Bengal/Green light cross linking on rabbit thin corneal stability and safety.

Abstract:
BACKGROUND AND PURPOSE
The purpose of this study was to investigate the subacute effects of Rose Bengal (RB) and 532 nm green light-induced photochemical crosslinking (RB-PCL) on rabbit thin corneal stability and safety in vivo.

MATERIALS AND METHODS
Rabbit thin corneal models with 250 μm thickness were created by photorefractive keratectomy surgery. Photochemical crosslinking with green light (wavelength 532 nm) at an illumination intensity of 0.4 W/cm2 for 250 s (100 J/cm2 ) was performed, followed by antibiotic treatment and slit lamp monitoring for four weeks. At the end of week four, corneal biomechanical stiffness, biochemical resistance to collagenase digestion, and corneal cellular morphology were assessed. The penetration depth of RB into the corneal stromal was measured by confocal microscopy.

RESULTS
At the end of week 4, RB-PCL had increased corneal tensile strength by an average 2.5-fold and had extended the corneal collagenase digestion time from 10.17 ± 2.93 to 15.83 ± 2.64 days. RB penetrated approximately 90 µm into the corneal stroma. RB-PCL did not alter the corneal endothelial and stromal morphology at the cellular or subcellular levels, according to electron microscopic examination.

CONCLUSIONS
RB and 532 nm green light irradiation effectively induced crosslinking in rabbit thin cornea, by increasing both the biomechanical stiffness and the biochemical resistance without evidence of morphological damage to the corneal endothelium or stroma. This study demonstrated the efficacy of RB-PCL in strengthening thin cornea at four weeks after the treatment, providing a potential and possibly better option for treating corneal ectasia disorders in cases where corneal thickness is less than 400 µm. Lasers Surg. Med. 50:324-332, 2018. © 2017 Wiley Periodicals, Inc.

Wang|Ti|T| Zhu|Lu|L| Zhu|Jingyin|J| Peng|Yinbo|Y| Shen|Nianci|N| Yu|Yan|Y| Yao|Min|M|

Rose Bengal
collagenase
tensile strength
corneal crosslinking
photochemical activation


Therapeutic potential of naringin in neurological disorders.

Abstract: Neurological illnesses are multifactorial incurable debilitating disorders that may cause neurodegeneration. These diseases influence approximately 30 million people around the world. Despite several therapies, effective management of such disorders remains a global challenge. Thus, natural products might offer an alternative therapy for the treatment of various neurological disorders. Polyphenols, such as curcumin, resveratrol, myricetin, mangiferin and naringin (NRG) have been shown to possess promising potential in the treatment of neurogenerative illness. In this review, we have targeted the therapeutic potential of naringin as a neuroprotective agent. The overall neuroprotective effects and different possible underlying mechanisms related to NRG are discussed. In light of the strong evidence for the neuropharmacological efficacy of NRG in various experimental paradigms, it is concluded that this molecule should be further considered and studied as a potential candidate for neurotherapeutics, focusing on mechanistic and clinical trials to ascertain its efficacy.

Ahmed|Salman|S|
Khan|Haroon|H|
Aschner|Michael|M|
Hasan|Muhammad Mohtasheemul|MM|
Hassan|Sherif T S|STS|

Polyphenols
Neuroprotective
Antineuroinflammation
Antioxidant
Naringin antiapoptotic


Multifunctional modification of cotton using layer-by-layer finishing with chitosan, sodium lignin sulphonate and boric acid.

Abstract: Functionally modified fabrics produced using sustainable techniques are in huge demand in today's world. In the present work, cotton fabric was modified using layer-by-layer two-stage finishing method using a solution of chitosan in citric acid (CS) and sodium lignin sulphonate (SLS) with boric acid (BA), thus granting several performance traits like wrinkle-free, antibacterial, flame retardant, UV protection and antioxidant properties. The finished fabric was evaluated for several textile properties like tensile strength, bending length, crease recovery, whiteness index and functional properties like antibacterial activity, UV protection, flame retardancy and antioxidant properties under standard conditions. The finished cotton showed an increase in CRA, antibacterial activity in the range 70-89%, UPF in the excellent range, much higher LOI values with a decrease in heat release and antioxidant activity of higher than 93%. The novel method of multifunctional finishing of cotton by layer-by-layer technique is explored.

Safi|Khalid|K| Kant|Kamal|K| Bramhecha|Indrajit|I| Mathur|Prasun|P| Sheikh|Javed|J|

Chitosan
Sodium lignin sulphonate
Multifunctional cotton


Cerebrospinal Fluid and Plasma Small Extracellular Vesicles and miRNAs as Biomarkers for Prion Diseases.

Abstract: Diagnosis of transmissible spongiform encephalopathies (TSEs), or prion diseases, is based on the detection of proteinase K (PK)-resistant PrPSc in post-mortem tissues as indication of infection and disease. Since PrPSc detection is not considered a reliable method for in vivo diagnosis in most TSEs, it is of crucial importance to identify an alternative source of biomarkers to provide useful alternatives for current diagnostic methodology. Ovine scrapie is the prototype of TSEs and has been known for a long time. Using this natural model of TSE, we investigated the presence of PrPSc in exosomes derived from plasma and cerebrospinal fluid (CSF) by protein misfolding cyclic amplification (PMCA) and the levels of candidate microRNAs (miRNAs) by quantitative PCR (qPCR). Significant scrapie-associated increase was found for miR-21-5p in plasma-derived but not in CSF-derived exosomes. However, miR-342-3p, miR-146a-5p, miR-128-3p and miR-21-5p displayed higher levels in total CSF from scrapie-infected sheep. The analysis of overexpressed miRNAs in this biofluid, together with plasma exosomal miR-21-5p, could help in scrapie diagnosis once the presence of the disease is suspected. In addition, we found the presence of PrPSc in most CSF-derived exosomes from clinically affected sheep, which may facilitate in vivo diagnosis of prion diseases, at least during the clinical stage.

cerebrospinal fluid
plasma
extracellular vesicle
prion
PMCA
bioassay


Psychometric properties of the Youth Anxiety Measure for DSM-5, Part I (YAM-5-I) in a community sample of Spanish-speaking adolescents.

Abstract:
BACKGROUND
Anxiety disorders are among the most common mental disorders in adolescence. There is a need for brief screening tools to identify adolescents at risk for anxiety disorders. The Youth Anxiety Measure for DSM-5 has been recently developed to assess youths' anxiety symptoms in terms of the current classification system. The goal of this study is to provide a first test of its psychometric properties in a community sample of adolescents in Spain.

METHODS
The sample consisted of 505 13- to 17-year-old adolescents who completed Part I of the YAM-5 (YAM-5-I), which measures symptoms of the major anxiety disorders.

RESULTS
Data indicated that the YAM-5-I displays appropriate internal consistency reliability. In addition, support was also found for the construct validity of the measure: most items loaded on a factor that represented the hypothesized anxiety syndromes, although it should also be noted that some items exhibited issues and therefore had to be discarded.

LIMITATIONS
Cross-cultural and trans-national studies are needed to determine psychometric properties of scale across languages and cultures.

CONCLUSIONS
Our findings suggest that the YAM-5-I has satisfactory psychometric properties, which indicates that it can be used as a screening tool in Spanish-speaking adolescents from the general population.

Garcia-Lopez|Luis-Joaquin|LJ|
Saez-Castillo|Antonio J|AJ|
Fuentes-Rodriguez|Gema|G|

D039721:Diagnostic and Statistical Manual of Mental Disorders

Youth Anxiety Measure for DSM-5
Adolescence
Assessment
Anxiety disorders symptoms


Neurological complications of breast cancer: A prospective cohort study.

Abstract:
OBJECTIVES
Neurological complications secondary to breast cancer treatment may be an important contributor to these patients morbidity. We aimed to quantify the incidence of neurological complications of breast cancer treatment during the first year after diagnosis.

MATERIALS AND METHODS
We performed a prospective cohort study with 506 patients recruited at the Portuguese Institute of Oncology of Porto, among those newly diagnosed. Participants underwent a neurological examination before treatment, after surgery, after chemotherapy (whenever applicable) and at one year after enrollment. The Montreal Cognitive Assessment was used to assess cognitive function, at baseline and at one year. We computed one-year cumulative incidence estimates and the corresponding 95% confidence intervals (95%CI) for each of the neurological complications.

RESULTS
Just over half of women had breast cancer stage 0 or I. A total of 6.9% were submitted to neoadjuvant chemotherapy but most of them completed adjuvant treatment - endocrine therapy, radiotherapy or chemotherapy (83.9%, 73.0% and 52.5%, respectively). The cumulative incidence of at least one oncological-related neurological complication during the first year after diagnosis was 48.4% (95%CI: 44.1-52.8); the most frequent were neuropathic pain (30.8%, 95%CI: 27.0-35.0), chemotherapy-induced peripheral neuropathy (16.8%, 95%CI: 13.8-20.3), phantom breast pain/syndrome (16.6%, 95%CI: 13.6-20.1) and cognitive decline (8.1%, 95%CI: 5.8-11.1).

CONCLUSIONS
Neurological complications were a frequent side-effect of breast cancer management in the first year after diagnosis, especially neuropathic pain and chemotherapy-induced peripheral neuropathy. Accurate diagnosis and treatment of these complications are important to minimize the burden associated with breast cancer treatment in breast cancer survivors.

Pereira|Susana|S|
Fontes|Filipa|F|
Sonin|Teresa|T|
Dias|Teresa|T|
Fragoso|Maria|M|
Castro-Lopes|José Manuel|JM|
Lunet|Nuno|N|

Neuropathic pain
Breast Neoplasm
Nervous system diseases
Polyneuropathies


Screening for HIV-Associated Neurocognitive Disorder (HAND) in Adults Aged 50 and Over Attending a Government HIV Clinic in Kilimanjaro, Tanzania. Comparison of the International HIV Dementia Scale (IHDS) and IDEA Six Item Dementia Screen.

Abstract: Validated screening tools for HIV-associated neurocognitive disorders (HAND) are lacking for the newly emergent ageing population of people living with HIV (PLWH) in sub-Saharan Africa (SSA). We aimed to validate and compare diagnostic accuracy of two cognitive screening tools, the International HIV dementia scale (IHDS), and the Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in Tanzania. A systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic in Tanzania were screened with the IHDS and IDEA. HAND were diagnosed by consensus American Academy of Neurology (AAN) criteria based on detailed clinical neuropsychological assessment. Strict blinding was maintained between screening and clinical evaluation. Both tools had limited diagnostic accuracy for HAND (area under the receiver operating characteristic (AUROC) curve 0.639-0.667 IHDS, 0.647-0.713 IDEA), which was highly-prevalent (47.0%). Accurate HAND screening tools for older PLWH in SSA are needed.

Screening
HIV
IHDS
Sub-Saharan Africa
Cognitive impairment
Older adults


Global and Regional Ventilation during High Flow Nasal Cannula in Patients with Hypoxia.

Abstract:
Background
High flow nasal cannula (HFNC) is known to increase global ventilation volume in healthy subjects. We sought to investigate the effect of HFNC on global and regional ventilation patterns in patients with hypoxia.

Methods
Patients were randomized to receive one of two oxygen therapies in sequence: nasal cannula (NC) followed by HFNC or HFNC followed by NC. Global and regional ventilation was assessed using electric impedance tomography.

Results
Twenty-four patients participated. Global tidal variation (TV) in the lung was higher during HFNC (NC, 2,241 ± 1,381 arbitrary units (AU); HFNC, 2,543 ± 1,534 AU; P < 0.001). Regional TVs for four iso-gravitational quadrants of the lung were also all higher during HFNC than NC. The coefficient of variation for the four quadrants of the lung was 0.90 ± 0.61 during NC and 0.77 ± 0.48 during HFNC (P = 0.035). Within the four gravitational layers of the lung, regional TVs were higher in the two middle layers during HFNC when compared to NC. Regional TV values in the most ventral and dorsal layers of the lung were not higher during HFNC compared with NC. The coefficient of variation for the four gravitational layers of the lung were 1.00 ± 0.57 during NC and 0.97 ± 0.42 during HFNC (P = 0.574).

Conclusions
In patients with hypoxia, ventilation of iso-gravitational regions of the lung during HFNC was higher and more homogenized compared with NC. However, ventilation of gravitational layers increased only in the middle layers. (Clinical trials registration number: NCT02943863).

electric impedance
oxygen inhalation therapy
pulmonary ventilation


The complete mitochondrial genome of natural Misgurnus bipartitus (Cypriniformes: Cobitidae).

Abstract: Misgurnus bipartitus, a small sized freshwater fish species, is one of the most important cultured fish in East Asia. In this study, the complete mitochondrial genome of M. bipartitus is sequenced to be 16,636 bp in length, including 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, a control region and the origin of the light strand replication. The overall base composition of M. bipartitus in descending order is A 29.79%, T 27.95%, C 25.90% and G 16.36%, with a slight A + T bias. The mitogenome sequence data may provide useful information to the population genetics analysis of M. bipartitus and the elucidation of evolutionary mechanisms in Cobitidae.

Huang|Songqian|S| Tian|Xianchang|X| Wang|Weimin|W| Song|Wen|W| Zhang|Xiujie|X| Bai|Xiaohui|X| Cao|Xiaojuan|X|

mitochondrial genome
Misgurnus bipartitus
Cobitidae


Patient and Family Preferences on Health System-Led Direct Contact for Cascade Screening.

Abstract: Health benefits to relatives of people at known genetic risk for hereditary cancer syndromes is key to realizing the promise of precision medicine. We conducted a qualitative study to design a patient- and family-centered program for direct contact of relatives to recommend cascade genetic testing. We conducted two rounds of data collection using focus groups followed by individual interviews with patients with HBOC or Lynch syndrome and a separate sample of people with a family history of hereditary cancers. Results indicate that U.S.-based health system-led direct contact of relatives is acceptable to patients and families, should take a programmatic approach, include consent of relatives before proband testing, complement to existing patient-mediated disclosure, and allow for relative control of information. Our findings suggest a set of requirements for U.S.-based direct contact programs that could ultimately benefit more relatives than current approaches.

cascade screening
precision medicine
genetic testing
ELSI
family communication


Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge.

Abstract: Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans and glycoproteins. Alteration of its integrity contributes to chronic vascular inflammation and leads to the development of cardiovascular diseases. Myeloperoxidase (MPO), a highly abundant enzyme released by polymorphonuclear neutrophils, binds to the GLX and deleteriously affects vascular EC functions. The focus of this study was to elucidate the mechanisms of MPO-mediated alteration of GLX molecules, and to unravel subsequent changes in endothelial integrity and function. MPO binding to GLX of human ECs and subsequent internalization was mediated by cell surface heparan sulfate chains. Moreover, interaction of MPO, which is carrying a cationic charge, with anionic glycosaminoglycans (GAGs) resulted in reduction of their relative charge. By means of micro-viscometry and atomic force microscopy, we disclosed that MPO can crosslink GAG chains. MPO-dependent modulation of GLX structure was further supported by alteration of wheat germ agglutinin staining. Increased expression of ICAM-1 documented endothelial cell activation by both catalytically active and also inactive MPO. Furthermore, MPO increased vascular permeability connected with reorganization of intracellular junctions, however, this was dependent on MPO's catalytic activity. Novel proteins interacting with MPO during transcytosis were identified by proteomic analysis. Altogether, these findings provide evidence that MPO through interaction with GAGs modulates overall charge of the GLX, causing modification of its structure and thus affecting EC function. Importantly, our results also suggest a number of proteins interacting with MPO that possess a variety of cellular localizations and functions.

Kolářová|Hana|H| Víteček|Jan|J| Černá|Anna|A| Černík|Marek|M| Přibyl|Jan|J| Skládal|Petr|P| Potěšil|David|D| Ihnatová|Ivana|I| Zdráhal|Zbyněk|Z| Hampl|Aleš|A| Klinke|Anna|A| Kubala|Lukáš|L|

Myeloperoxidase
Endothelial cells
Glycocalyx
Vascular inflammation
Inflammation
Cardiovascular diseases
Glycosaminoglycan
Proteomic analysis


Temporal integration of soil N2O fluxes: validation of IPNOA station automatic chamber prototype.

Abstract: The assessment of nitrous oxide (N2O) fluxes from agricultural soil surfaces still poses a major challenge to the scientific community. The evaluations of integrated soil fluxes of N2O are difficult owing to their lower emissions when compared with CO2. These emissions are also sporadic as environmental conditions act as a limiting factor. A station prototype was developed to integrate annual N2O and CO2 emissions using an automatic chamber technique and infrared spectrometers within the LIFE project (IPNOA: LIFE11 ENV/IT/00032). It was installed from June 2014 to October 2015 in an experimental maize field in Tuscany. The detection limits for the fluxes were evaluated up to 1.6 ng N-N2O m2 s-1 and 0.3 μg C-CO2 m2 s-1. A cross-comparison carried out in September 2015 with the "mobile IPNOA prototype"; a high-sensibility transportable instrument already validated provided evidence of very similar values and highlighted flux assessment limitations according to the gas analyzers used. The permanent monitoring device showed that temporal distribution of N2O fluxes can be very large and discontinuous over short periods of less than 10 days and that N2O fluxes were below the detection limit of the instrumentation during approximately 70% of the measurement time. The N2O emission factors were estimated to 1.9% in 2014 and 1.7% in 2015, within the range of IPCC assessments.

Laville|P|P| Bosco|S|S| Volpi|I|I| Virgili|G|G| Neri|S|S| Continanza|D|D| Bonari|E|E|

Nitrous oxide
Agricultural managements
Auto-chamber
Laser spectrometry
N-fertilizer


Isothiocyanates suppress the invasion and metastasis of tumors by targeting FAK/MMP-9 activity.

Abstract: Isothiocyanates, which are present as glucosinolate precursors in cruciferous vegetables, have strong activity against various cancers. Here, we compared the anti-metastatic effects of isothiocyanates (benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN)) by examining how they regulate MMP-9 expression. Isothiocyanates, particularly PEITC, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 activity and invasion in various cancer cell lines. By contrast, N-methyl phenethylamine, a PEITC analog without an isothiocyanate functional group, had no effect. A reporter gene assay demonstrated that BITC, PEITC, and SFN suppressed TAP-induced MMP-9 expression by inhibiting AP-1 and NF-κB in U20S osteosarcoma cells. All three compounds reduced phosphorylation of FAK, ERK1/2, and Akt. In addition, MMP-9 expression was downregulated by inhibiting FAK, ERK1/2, and Akt. Isothiocyanates-mediated inhibition of FAK phosphorylation suppressed phosphorylation of ERK1/2 and Akt in U2OS and A549 cells, along with the translocation of p65 and c-Fos, suggesting that isothiocyanates inhibit MMP-9 expression and cell invasion by blocking phosphorylation of FAK. Furthermore, isothiocyanates, abolished MMP-9 expression and tumor metastasis in vivo with the following efficacy: PEITC>BITC>SFN. Thus, isothiocyanates act as anti-metastatic compounds that suppress MMP-9 activity/expression by inhibiting NF-κB and AP-1 via suppression of the FAK/ERK and FAK/Akt signaling pathways.

Jeong|Yun-Jeong|YJ| Cho|Hyun-Ji|HJ| Chung|Fung-Lung|FL| Wang|Xiantao|X| Hoe|Hyang-Sook|HS| Park|Kwan-Kyu|KK| Kim|Cheorl-Ho|CH| Chang|Hyeun-Wook|HW| Lee|Sang-Rae|SR| Chang|Young-Chae|YC|

isothiocyanates
metastasis
FAK
MMP-9
cancer invasion


The role of CE-MRA of the supraortic vessels in the detection of associated intracranial pathology.

Abstract:
BACKGROUND
Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a very popular imaging technique in the evaluation of the extracranial vessels pathology, while it is not commonly used to rule out intracranial vascular pathology. On the contrary, 3D time of flight MRA (TOF-MRA) has a solid role in the study of intracranial arterial vessels disease.

MATERIALS AND METHODS
One hundred and eight patients were consecutively included in the study. All patients were submitted to a 3 Tesla 3D CE-MRA imaging to rule out extracranial vessels pathology. A comparison was made with a 3D-TOF sequence acquired at the same time in the assessment of intracranial vessels diseases such as steno-occlusion, dissection, and aneurysms.

RESULTS
With regard to steno-occlusive disease, Spearman's rank correlation coefficient was of 0.56 for stenosis detection and of 0.57 for occlusive disease detection. The two techniques shared similar results in the evaluation of anterior circulation, while 3D-TOF found higher grades of stenosis for posterior circulation. With regard to dissection, Spearman's rank correlation coefficient was of 0.7. 3D-TOF depicted more intramural hematoma (Spearman's rank = 0.46), while CE-MRA showed more pseudo-aneurysms (Spearman's rank = 0.56). Both the technique equally evaluated the presence of intracranial aneurysms (Spearman's rank = 1).

CONCLUSION
CE-MRA can be considered a reliable tool to rule out intracranial pathology associated to supraortic steno-occlusive disease, also allowing time reduction. In the suspicion of dissection a T1-weighted sequence has to be added to detect the presence of a subacute vessel wall hematoma.

3D-time of flight magnetic resonance angiography


The use of hospital consumer assessment of healthcare services and the Press Ganey medical practice surveys in guiding surgical patient care practices.

Abstract:
Background
Patient satisfaction questionaries have become popular in the past decade after the institution of the Patient Care and Affordable Care Act of 2010. This study evaluated whether the Hospital Consumer Assessment of Healthcare Services (H-CAHPS) and Press Ganey scores improved after institutional changes to the rounding system.

Methods
In the summer of 2017, utilizing H-CAHPS and Press Ganey scores, we asked whether switching from mid-level rounding providers to resident physicians improved patient care. Pre- and post-intervention groups, each lasting four quarters, were divided into care provided by mid-level personnel versus residents. For these periods, H-CAHPS respondent data were compared by a Chi-squared test (P < 0.05), while Press Ganey responses were analyzed with an independent samples t-test (P < 0.05).

Results
Significant improvement was noted in patients answering "Definitely yes" in recommending our institution in both H-CAHPS and Press Ganey satisfaction surveys. Significant improvement regarding the speed of discharge, instructions for post-hospital care, and the overall rating of care given was observed in the Press Ganey responses alone.

Conclusion
Significant improvement in satisfaction was noted in the Press Ganey responses regarding the discharge process and speed of discharge. The quality of this last encounter likely contributed to+ the significant improvement observed in both the H-CAPHS and Press Ganey Scores for an overall hospital stay and the percentage of those definitely recommending our institution.

Mao|Gordon|G|
Gigliotti|Michael Joseph|MJ|
Dupre|Derrick|D|


Development-Dependent Changes in the NR2 Subtype of the N-Methyl-D-Aspartate Receptor in the Suprachiasmatic Nucleus of the Rat.

Abstract: The suprachiasmatic nucleus (SCN) is the main brain clock that regulates circadian rhythms in mammals. The SCN synchronizes to the LD cycle through the retinohypothalamic tract (RHT), which projects to ventral SCN neurons via glutamatergic synapses. Released glutamate activates N-methyl-D-aspartate (NMDA) receptors, which play a critical role in the activation of signaling cascades to enable phase shifts. Previous evidence indicates that presynaptic changes during postnatal development consist of an increase in RHT fibers impinging on SCN neurons between postnatal day (P) 1 to 4 and P15. The aim of this study was to evaluate postsynaptic developmental changes in the NR2 subunits that determine the pharmacological and biophysical properties of the neuronal NMDA receptors in the ventral SCN. To identify the expression of NR2 subtypes, we utilized RT-PCR, immunohistochemical fluorescence, and electrophysiological recordings of synaptic activity. We identified development-dependent changes in NR2A, C, and D subtypes in mRNA and protein expression, whereas NR2B protein was equally present at all analyzed postnatal ages. The NR2A antagonist PEAQX (100 nM) reduced the frequency of NMDA excitatory postsynaptic currents (EPSCs) at P8 significantly more than at P34, but the antagonists for NR2B (3 μM Ro 25-6981) and NR2C/D (150 nM PPDA) did not influence NMDA EPSCs differently at the 2 analyzed postnatal ages. Our results point to P8 as the earliest analyzed postnatal age that shows mRNA and protein expression similar to those found at the juvenile stage P34. Taken together, our findings indicate that postsynaptic development-dependent modifications in the NR2 subtypes of the NMDA receptor could be important for the synchronization of ventral SCN neurons to the LD cycle at adult stages.

NR2
SCN
retinohypothalamic tract
glutamate
NMDA
development


Antimalarial activity and metabolism of dihydroartemisinin-derived dimer.

Abstract: The dihydroartemisinin-derived dimer (DHA dimer) was synthesized, and its antimalarial activities were evaluated both in vitro and in vivo. The dimer IC50 value of 0.51 ± 0.12 nM in vitro was significantly lower than that of DHA at 1.81 ± 0.70 nM. The dimer ED50 values were 0.44 ± 0.03 and 0.18 ± 0.03 mg/(kg·day) in vivo for intragastric (i.g.) and intravenous (i.v.) groups, respectively, to Plasmodium yoelii rodent malaria. It also performed better relative to those of DHA which had ED50 values of 0.76 ± 0.03 mg/(kg·day) (i.g.) and 0.32 ± 0.03 mg/(kg·day) (i.v.). Moreover, the recrudescence rate, negative conversion rate, and cure rate of the dimer showed superior performance. Furthermore, the metabolites and major metabolic pathways of the dimer in rats were preliminarily investigated using the HPLC-HRMSn method. Twenty-seven metabolites, including DHA, 11 metabolites of DHA, and 15 other novel metabolites, were detected in rats after i.g. administration of dimer. The metabolic pathways of the 15 novel metabolites were inferred: deoxygenation, hydroxylation, and hydroxylation with dehydration.

Zhang|Guoshun|G| Dai|Hualing|H| Ren|Guolian|G| Xiao|Xiaoyang|X| Zhao|Lele|L| Wang|Ruili|R| Zhang|Shuqiu|S|

D002851:Chromatography, High Pressure Liquid

Antimalarial activity
Metabolism
Dihydroartemisinin-derived dimer
Pharmacodynamics


The stigma perceived by people bereaved by suicide and other sudden deaths: A cross-sectional UK study of 3432 bereaved adults.

Abstract:
OBJECTIVE
To test the hypothesis that perceived stigma scores in young adults bereaved by suicide are significantly higher than in young adults bereaved by other sudden deaths, whether blood-related to the deceased or not.

METHODS
We conducted a cross-sectional study of all staff and students aged 18-40 at 37 UK higher educational institutions in 2010, and identified 3432 respondents who had experienced a sudden bereavement of a close contact since reaching the age of 10, either due to sudden natural causes, sudden unnatural causes, or suicide. We used multivariable regression to compare scores on the stigma, shame, responsibility and guilt subscales of the Grief Experience Questionnaire, adjusting for socio-demographic factors and pre-bereavement psychopathology.

RESULTS
People bereaved by suicide (n=614) had higher stigma scores than people bereaved by sudden natural death (n=2106; adjusted coefficient=2.52; 95% CI=2.13-2.90; p=<0.001) and people bereaved by sudden unnatural death (n=712; adjusted coefficient=1.69; 95% CI=1.25-2.13; p=<0.001). Shame, responsibility and guilt scores were also significantly higher in people bereaved by suicide, whether compared with bereavement by sudden natural death or sudden unnatural death. Associations were not modified by whether the bereaved was blood-related to the deceased or not.

CONCLUSIONS
Stigma was perceived more acutely by the relatives and friends of those who died by suicide than those bereaved by other causes of sudden natural or sudden unnatural death. Their high levels of perceived stigma, shame, responsibility and guilt require qualitative investigation to identify whether these grief dimensions limit social functioning, help-seeking behaviour and/or support offered.

Pitman|Alexandra L|AL|
Osborn|David P J|DP|
Rantell|Khadija|K|
King|Michael B|MB|

Stigma Bereavement Suicide Shame Responsibility Guilt


Optimization of bioengineered heparin/heparan sulfate production for therapeutic applications.

Abstract: Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug. 1 Bioengineering heparin by expressing serglycin in mammalian cells is a promising approach that was recently reported by the authors. 2 This addendum explores the approaches that the authors are taking to increase the yield of recombinantly expressed serglycin decorated with heparin/heparan sulfate focusing on cell culture and bioreactor conditions and proposes that the cell microenvironment is a key modulator of heparin biosynthesis.

Heparin
heparan sulfate
serglycin
microenvironment
mast cells
recombinant expression


Floquet-Dirac fermions in monolayer graphene by Wannier functions.

Abstract: Wannier functions have been widely applied in the study of topological properties and Floquet-Bloch bands of materials. Usually, the real-space Wannier functions are linked to the k-space Hamiltonian by two types of Fourier transform (FT), namely lattice-gauge FT (LGFT) and atomic-gauge FT (AGFT), but the differences between these two FTs on Floquet-Bloch bands have rarely been addressed. Taking monolayer graphene as an example, we demonstrated that LGFT gives different topological descriptions on the Floquet-Bloch bands for the structurally equivalent directions which are obviously unphysical, while AGFT is immune to this dilemma. Using AGFT, we showed that linearly polarized laser could effectively manipulate the properties of the Dirac fermions in graphene, such as the location, generation and annihilation of Dirac points. This proposal offers not only deeper understanding on the role of Wannier functions in solving the Floquet systems, but also a promising platform to study the interaction between the time-periodic laser field and materials.

monolayer graphene
Wannier functions
linearly polarized laser
Floquet Dirac fermions
non-equilibrium band structure


Identification and characterization of dysregulated P-element induced wimpy testis-interacting RNAs in head and neck squamous cell carcinoma.

Abstract: It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC.

Saad|Maarouf A|MA|
Ku|Jonjei|J|
Kuo|Selena Z|SZ|
Li|Pin Xue|PX|
Zheng|Hao|H|
Yu|Michael Andrew|MA|
Wang-Rodriguez|Jessica|J|
Ongkeko|Weg M|WM|

head and neck squamous cell carcinoma
alcohol
epigenetics
piwi-interacting RNA


New Job, New Challenges: Life After Radiology Training.

Abstract:
OBJECTIVE
Beginning a new job after radiology training is exciting but can also be nerve-racking. The key challenge remains making the strange familiar and assimilating with the new practice as soon as possible. This process is complicated and may require learning new policies, getting to know new colleagues, adapting to new surroundings, and learning new skills.

CONCLUSION
This article provides strategies to navigate professionally and adapt to a new environment.

Lalwani|Neeraj|N|
Shanbhogue|Krishna P|KP|
Jambhekar|Kedar|K|
Jha|Saurabh|S|
Ram|Roopa|R|
Itri|Jason Neil|JN|
Tappouni|Rafel|R|

new job
difficult personalities
new faculty
promotion
settling in
teaching
workplace


Safety and Efficacy of Furosap®, a Patented Trigonella foenum-graecum Seed Extract, in Boosting Testosterone Level, Reproductive Health and Mood Alleviation in Male Volunteers.

Abstract:
BACKGROUND
The medicinal herb fenugreek (Trigonella foenum-graecum) seeds, fortified with dietary fibers and furostanolic saponins including protodioscin, have demonstrated a significant contribution to human health. In our laboratories, Furosap®, a patented 20% protodioscin-enriched extract was developed from fenugreek seeds.

OBJECTIVE
In an open-label, one-arm, single-center longitudinal study, we examined the safety and efficacy of Furosap® on free and total testosterone levels, fasting blood sugar, blood pressure, sperm count, motility and morphology, dihydroepiandrosterone sulfate (DHEA-S), sexual health, reflex erection, mood alleviation, mental alertness, and total blood chemistry analyses over a period of 12 weeks in healthy male volunteers.

METHODS
Institutional Ethics Committee approvals and Clinicaltrials.gov registration were obtained. Effect of Furosap® (500 mg/day) was examined of free and total testosterone levels, sperm count, motility and morphology, sexual health, mood and mental alertness, and total blood chemistry analyses in 100 healthy volunteers (age 35-60 Y) over a period of 12 consecutive weeks.

RESULTS
No changes were observed in body weight and BMI. Both systolic and diastolic blood pressure, and DHEA levels significantly decreased. Free and bound testosterone levels improved significantly at 12 weeks of treatment. Sperm motility significantly increased at 8- and 12-weeks of treatment, while abnormal sperm morphology significantly decreased at 12-weeks of treatment. Mental alertness, mood, and reflex erection score significantly alleviated. An age-induced increasing effect was observed. Furthermore, cardiovascular health and libido significantly improved. Blood chemistry analyses exhibited broad spectrum safety. A decreasing trend was observed in total cholesterol, triglycerides, and VLDL levels, while an increasing trend was observed in HDL level at 12 weeks of treatment. LDL level decreased significantly at 12-weeks of treatment. No adverse events were observed.

CONCLUSION
Results demonstrate that Furosap® is safe and effective in improving testosterone levels, cardiovascular health, healthy sperm profile, mental alertness in human male volunteers.

safety
Furosap®
mood alleviation
protodioscin
fenugreek seeds
Trigonella foenum-graceum
testosterone booster


Factors associated with independent nurse prescribers' antibiotic prescribing practice: a mixed-methods study using the Reasoned Action Approach.

Abstract:
BACKGROUND
The number of nurse prescribers is increasing, yet little evidence exists about their antibiotic prescribing behaviour.

AIM
To measure nurse independent prescribers' (NIPs) intention to manage patients, presenting with an upper respiratory tract infection (URTI) for the first time, without prescribing an antibiotic and to examine the determinants of this behaviour.

METHODS
This was a mixed-method study using the Reasoned Action Approach (RAA). Content analysis of data from 27 telephone interviews with NIPs informed the development of a questionnaire which was tested for validity and reliability and used in a national survey of NIPs across Scotland. Descriptive and inferential statistical analysis was carried out to determine intention to manage patients without prescribing an antibiotic and the significant influences on this intention.

FINDINGS
From 184 participants it was found that NIPs intended to manage patients, presenting with a URTI for the first time, without prescribing an antibiotic. Key determinants were perceived norm, perceived behavioural control, and moral norm. Significant beliefs were positive social influence from other non-medical prescribers (P = 0.007) and nurse prescribers (P = 0.045), the enablers of prescriber experience and confidence (P ≤ 0.001), and the barrier of pressure from patients/carers (P = 0.010).

CONCLUSION
The findings provide reassurance that NIPs intend to prescribe appropriately. The identification of nurse-specific barriers and enablers to this intention should be acknowledged and targeted in future interventions to manage this behaviour.

Ness|V|V| Currie|K|K| Reilly|J|J| McAloney-Kocaman|K|K| Price|L|L|

D000900:Anti-Bacterial Agents
D011307:Drug Prescriptions
D006801:Humans
D015203:Reproducibility of Results
D012606:Scotland
D011795:Surveys and Questionnaires

Nurse
Prescribing
Reasoned Action Approach
Behaviour
Intention
Upper respiratory tract infections


Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome.

Abstract:
BACKGROUND
Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR-335-5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling.

METHODS
ACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, and VCAM-1 levels were tested in ACS mice. Additionally, Notch signaling-related genes and matrix metalloproteinases (MMPs) were measured after miR-335-5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined.

RESULTS
miR-335-5p targeted JAG1 and mediated Notch signaling in ACS. miR-335-5p up-regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway-related genes, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, VCAM-1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR-335-5p overexpression and Notch signaling inhibition.

CONCLUSIONS
Overexpression of miR-335-5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.

atherosclerotic vulnerable plaque
acute coronary syndrome
revascularization
notch signaling
JAG1
innate immune response of macrophage
microRNA-335-5p


Sedation or general anesthesia for transcatheter aortic valve implantation (TAVI).

Abstract: Transfemoral transcatheter aortic valve implantation (TAVI) is nowadays a routine therapy for elderly patients with severe aortic stenosis (AS) and high perioperative risk. With growing experience, further development of the devices, and the expansion to "intermediate-risk" patients, there is increasing interest in performing this procedure under conscious sedation (TAVI-S) rather than the previously favoured approach of general anesthesia (TAVI-GA). The proposed benefits of TAVI-S include; reduced procedure time, shorter intensive care unit (ICU) length of stay, reduced need for intraprocedural vasopressor support, and the potential to perform the procedure without the direct presence of an anesthetist for cost-saving reasons. To date, no randomized trial data exists. We reviewed 13 non-randomized studies/registries reporting data from 6,718 patients undergoing TAVI (3,227 performed under sedation). Patient selection, study methods, and endpoints have differed considerably between published studies. Reported rates of in-hospital and longer-term mortality are similar for both groups. Up to 17% of patients undergoing TAVI-S require conversion to general anesthesia during the procedure, primarily due to vascular complications, and urgent intubation is frequently associated with hemodynamic instability. Procedure related factors, including hypotension, may compound preexisting age-specific renal impairment and enhance the risk of acute kidney injury. Hypotonia of the hypopharyngeal muscles in elderly patients, intraprocedural hypercarbia, and certain anesthetic drugs, may increase the aspiration risk in sedated patients. General anesthesia and conscious sedation have both been used successfully to treat patients with severe AS undergoing TAVI with similar reported short and long-term mortality outcomes. The authors believe that the significant incidence of complications and unplanned conversion to general anesthesia during TAVI-S mandates the start-to-finish presence of an experienced cardiac anesthetist in order to optimize patient outcomes. Good quality randomized data is needed to determine the optimal anesthetic regimen for patients undergoing TAVI.

Mayr|N Patrick|NP|
Michel|Jonathan|J|
Bleiziffer|Sabine|S|
Tassani|Peter|P|
Martin|Klaus|K|

transcatheter aortic valve replacement (TAVR)


Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.

Abstract: PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK-3β pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-α concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3β proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β.

Mao|Lun-Lin|LL| Hao|Dong-Lin|DL| Mao|Xiao-Wei|XW| Xu|Yuan-Feng|YF| Huang|Ting-Ting|TT| Wu|Bo-Na|BN| Wang|Li-Hui|LH|

D000071679:Glycogen Synthase Kinase 3 beta

Bisperoxovanadium (Bpv)
Middle cerebral artery occlusion (MCAO)
Akt
Ischemic stroke
(GSK-3β)
Glycogen synthase kinase 3β
Phosphatidylinositol 3-kinase (PI3K)


Genomic sequences of two novel HLA-C alleles, HLA-C*15:143 and HLA-C*07:109:02.

Abstract: Two novel HLA-C alleles, C*07:109:02 and C*15:143, were characterized in two Spanish individuals.

Balas|A|A|0000-0001-7137-3304
García-Sánchez|F|F|
Alenda|R|R|
Vicario|J L|JL|

D018380:Hematopoietic Stem Cell Transplantation


'Staying alive' with antiretroviral therapy: a grounded theory study of people living with HIV in Peru.

Abstract:
BACKGROUND
To achieve an optimal quality of life through chronic disease management, people living with HIV (PLHIV) must adhere to antiretroviral therapy (ART). ART has been available throughout Peru since 2004 without cost in all regions; yet only 60% (43 200) of PLHIV receive ART and 32% are virally suppressed. Despite the low adherence, little is known about the experience of PLHIV with ART adherence in the context of Latin America.

METHODS
A constructivist grounded theory design was used to understand the ART adherence experiences of PLHIV in Northern Peru. Unstructured interviews were conducted with 18 participants resulting in theoretical saturation. All interviews were recorded, immediately transcribed and analysed concurrently with data collection using constant comparative analysis with Atlas.ti (V.8) software. Rigour was maintained through openness, reflexivity, audit trail, memo writing, debriefings, member checks and positionality.

RESULTS
The core category 'staying alive' emerged through the interaction of four categories, including: (1) overcoming barriers; (2) working with the healthcare team; (3) tailoring self-care strategies; and (4) appreciating antiretrovirals. Adherence is not a spontaneous outcome, instead, the surprise of HIV diagnosis transitions to living with HIV as a chronic disease. The healthcare team helps PLHIV realise ART is their life source by enhancing, supporting and facilitating self-care and overcoming barriers.

CONCLUSION
Adherence emerges from experiential learning as PLHIV recognised ART as their life source in balance with their desire to continue living a normal life. Social support and healthcare team interventions help PLHIV implement tailored self-care strategies to overcome personal, social, and structural barriers to adherence. Healthcare professionals need to recognise the challenges confronted by PLHIV as they learn how to continue living while trying to stay alive.

D066296:Grounded Theory
D015658:HIV Infections
D006801:Humans
D055118:Medication Adherence
D010568:Peru
D011788:Quality of Life

HIV
AIDS
health systems
public health
qualitative study


LncRNAs in Secondary Hair Follicle of Cashmere Goat: Identification, Expression, and Their Regulatory Network in Wnt Signaling Pathway.

Abstract: Long noncoding RNAs (lncRNAs) are a novel class of eukaryotic transcripts. They are thought to act as a critical regulator of protein-coding gene expression. Herein, we identified and characterized 13 putative lncRNAs from the expressed sequence tags from secondary hair follicle of Cashmere goat. Furthermore, we investigated their transcriptional pattern in secondary hair follicle of Liaoning Cashmere goat during telogen and anagen phases. Also, we generated intracellular regulatory networks of upregulated lncRNAs at anagen in Wnt signaling pathway based on bioinformatics analysis. The relative expression of six putative lncRNAs (lncRNA-599618, -599556, -599554, -599547, -599531, and -599509) at the anagen phase is significantly higher than that at telogen. Compared with anagen, the relative expression of four putative lncRNAs (lncRNA-599528, -599518, -599511, and -599497) was found to be significantly upregulated at telogen phase. The network generated showed that a rich and complex regulatory relationship of the putative lncRNAs and related miRNAs with their target genes in Wnt signaling pathway. Our results from the present study provided a foundation for further elucidating the functional and regulatory mechanisms of these putative lncRNAs in the development of secondary hair follicle and cashmere fiber growth of Cashmere goat.

Bai|Wen L|WL|
Zhao|Su J|SJ|
Wang|Ze Y|ZY|
Zhu|Yu B|YB|
Dang|Yun L|YL|
Cong|Yu Y|YY|
Xue|Hui L|HL|
Wang|Wei|W|
Deng|Liang|L|
Guo|Dan|D|
Wang|Shi Q|SQ|
Zhu|Yan X|YX|
Yin|Rong H|RH|

Secondary hair follicle
Cashmere goat
Regulatory network
Wnt signaling pathway
lncRNA expression


Iatrogenic severe hyperglycemia due to parenteral administration of glucose in children - a case series.

Abstract:
BACKGROUND
Iatrogenic severe hyperglycemia (ISH) caused by glucose-containing i.v. solution is a potentially fatal treatment error. The objective of this study was to investigate the causes, circumstances, course of disease, and complications of ISH > 300 mg/dl (16.7 mmol/l) in neonates and children.

METHODS
We emailed a survey to 105 neonatal and pediatric intensive care units in Germany, Austria, and Switzerland, asking to retrospectively report cases of ISH.

RESULTS
We received 11 reports about premature infants to children. Four patients (36%) had poor outcome: 2 died and 2 suffered persistent sequelae. The highest observed blood glucose was at median 983 mg/dl (54.6 mmol/l) (range 594-2240 mg/dl; 33.0-124.3 mmol/l) and median time to normoglycemia was 7 h (range 2-23). Blood glucose was higher and time to normoglycemia longer in patients with poor outcome. Invasive therapy was required in 73% (mechanical ventilation) and 50% (vasopressor therapy) of patients, respectively. Administration of insulin did not differ between outcome groups. Patients with poor outcome showed coma (100% vs. 40%) and seizures (75% vs. 29%) more frequently than those with good outcome.

CONCLUSIONS
ISH is a severe condition with high morbidity and mortality. Further research to amplify the understanding of this condition is needed, but focus should largely be held on its prevention.

Iatrogenic
Hyperglycemia
Administration
Glucose
Treatment error
Pediatric
Parenteral feeding
Parenteral nutrition


Will the Antarctic tardigrade Acutuncus antarcticus be able to withstand environmental stresses related to global climate change?

Abstract: Because conditions in continental Antarctica are highly selective and extremely hostile to life, its biota is depauperate, but well adapted to live in this region. Global climate change has the potential to impact continental Antarctic organisms because of increasing temperatures and ultraviolet radiation. This research evaluates how ongoing climate changes will affect Antarctic species, and whether Antarctic organisms will be able to adapt to the new environmental conditions. Tardigrades represent one of the main terrestrial components of Antarctic meiofauna; therefore, the pan-Antarctic tardigrade Acutuncus antarcticus was used as model to predict the fate of Antarctic meiofauna threatened by climate change. Acutuncus antarcticus individuals tolerate events of desiccation, increased temperature and UV radiation. Both hydrated and desiccated animals tolerate increases in UV radiation, even though the desiccated animals are more resistant. Nevertheless, the survivorship of hydrated and desiccated animals is negatively affected by the combination of temperature and UV radiation, with the hydrated animals being more tolerant than desiccated animals. Finally, UV radiation has a negative impact on the life history traits of successive generations of A. antarcticus, causing an increase in egg reabsorption and teratological events. In the long run, A. antarcticus could be at risk of population reductions or even extinction. Nevertheless, because the changes in global climate will proceed gradually and an overlapping of temperature and UV increase could be limited in time, A. antarcticus, as well as many other Antarctic organisms, could have the potential to overcome global warming stresses, and/or the time and capability to adapt to the new environmental conditions.

Antarctica
Ultraviolet radiation
Meiofauna
Desiccation
Life history traits
Thermo-tolerance


Preparation and Characterization of Sodium Alginate-Based Oxidized Multi-Walled Carbon Nanotubes Hydrogel Nanocomposite and its Adsorption Behaviour for Methylene Blue Dye.

Abstract: Herein, a sodium alginate/poly (acrylic acid)/oxidized-multi-walled carbon nanotubes hydrogel nanocomposite (SA/p(AAc)/o-MWCNTs HNC) was synthesized by in situ free-radical polymerization method. The synthesized SA/p(AAc)/o-MWCNTs HNC was used to remove methylene blue (MB) from aqueous solution. The synthesized HNC was confirmed by employing various characterization techniques. The SA/p(AAc)/o-MWCNTs HNC exhibited a maximum swelling capacity of 2265.4% at pH 8.0. The influence of vital parameters in the sorption process including the initial pH, adsorption dose, contact time and concentration were systematically examined on a batch mode. Subsequently, adsorption kinetics as well as isotherm models were applied to assess the nature and mechanism of the adsorption process. Adsorption kinetics were best described by pseudo-second-order model, while the Langmuir isotherm model governed the adsorption isotherm. The SA/p(AAc)/o-MWCNTs HNC exhibited a maximum adsorption capacity of 1596.0 mg/g at 25°C. This adsorbent showed excellent MB uptake and good regeneration ability.

multi-walled carbon nanotubes
hydrogel nanocomposite
sodium alginate
adsorption process
methylene blue 2


Iterative simulations to estimate the elastic properties from a series of MRI images followed by MRI-US validation.

Abstract: The modeling of breast deformations is of interest in medical applications such as image-guided biopsy, or image registration for diagnostic purposes. In order to have such information, it is needed to extract the mechanical properties of the tissues. In this work, we propose an iterative technique based on finite element analysis that estimates the elastic modulus of realistic breast phantoms, starting from MRI images acquired in different positions (prone and supine), when deformed only by the gravity force. We validated the method using both a single-modality evaluation in which we simulated the effect of the gravity force to generate four different configurations (prone, supine, lateral, and vertical) and a multi-modality evaluation in which we simulated a series of changes in orientation (prone to supine). Validation is performed, respectively, on surface points and lesions using as ground-truth data from MRI images, and on target lesions inside the breast phantom compared with the actual target segmented from the US image. The use of pre-operative images is limited at the moment to diagnostic purposes. By using our method we can compute patient-specific mechanical properties that allow compensating deformations. Graphical Abstract Workflow of the proposed method and comparative results of the prone-to-supine simulation (red volumes) validated using MRI data (blue volumes).

Elastic properties
Breast
Deformable models
Image alignment
Magnetic resonance imaging


The influence of parental practices on child promotive and preventive food consumption behaviors: a systematic review and meta-analysis.

Abstract:
BACKGROUND
The family is an important social context where children learn and adopt eating behaviors. Specifically, parents play the role of health promoters, role models, and educators in the lives of children, influencing their food cognitions and choices. This study attempts to systematically review empirical studies examining the influence of parents on child food consumption behavior in two contexts: one promotive in nature (e.g., healthy food), and the other preventive in nature (e.g., unhealthy food).

METHODS
From a total of 6,448 titles extracted from Web of Science, ERIC, PsycINFO and PubMED, seventy eight studies met the inclusion criteria for a systematic review, while thirty seven articles contained requisite statistical information for meta-analysis. The parental variables extracted include active guidance/education, restrictive guidance/rule-making, availability, accessibility, modeling, pressure to eat, rewarding food consumption, rewarding with verbal praise, and using food as reward. The food consumption behaviors examined include fruits and vegetables consumption, sugar-sweetened beverages, and snack consumption.

RESULTS
Results indicate that availability (Healthy: r = .24, p < .001; Unhealthy: r = .34, p < .001) and parental modeling effects (Healthy: r = .32, p < .001; Unhealthy: r = .35, p < .001) show the strongest associations with both healthy and unhealthy food consumption. In addition, the efficacy of some parenting practices might be dependent on the food consumption context and the age of the child. For healthy foods, active guidance/education might be more effective (r = .15, p < .001). For unhealthy foods, restrictive guidance/rule-making might be more effective (r = -.11, p < .01). For children 7 and older, restrictive guidance/rule-making could be more effective in preventing unhealthy eating (r = - .20, p < .05). For children 6 and younger, rewarding with verbal praise can be more effective in promoting healthy eating (r = .26, p < .001) and in preventing unhealthy eating (r = - .08, p < .01).

CONCLUSIONS
This study illustrates that a number of parental behaviors are strong correlates of child food consumption behavior. More importantly, this study highlights 3 main areas in parental influence of child food consumption that are understudied: (1) active guidance/education, (2) psychosocial mediators, and (3) moderating influence of general parenting styles.

Yee|Andrew Z H|AZ|
Lwin|May O|MO|
Ho|Shirley S|SS|

Parent Child Food Consumption Eating Healthy Unhealthy Fruits Vegetables Nutrition Sugar


Plasma polymerized carvone as an antibacterial and biocompatible coating.

Abstract: Antibacterial coating is important to prevent the colonization of medical devices by biofilm forming bacteria that would cause infection and sepsis in patients. Current coating techniques such as immobilization of antimicrobial compounds, time-releasing antibiotic agents and silver nanoparticles, require multiple processing steps, and they have low efficacy and low stability. We proposed a single-step plasma polymerization of an essential oil known as carvone to produce a moderately hydrophobic antibacterial coating (ppCar) with an average roughness of <1nm. ppCar had a static water contact angle of 78°, even after 10days of air aging and it maintained its stability throughout 24h of LB broth immersion. ppCar showed promising results in the live-dead fluorescence assay and crystal violet assay. The biofilm assay showed an effective reduction of E. coli and S. aureus bacteria by 86% and 84% respectively. ppCar is also shown to rupture the bacteria membrane for its bactericidal effects. The cytotoxicity test indicated that the coating is not cytotoxic to the human cell line. This study would be of interest to researcher keen on producing a bacteria-resistance and biocompatible coating on different substrates in a cost-effective manner.

Chan|Yuen Wah|YW|
Siow|Kim Shyong|KS|
Ng|Pei Yuen|PY|
Gires|Usup|U|
Yeop Majlis|Burhanuddin|B|

D061307:Human Umbilical Vein Endothelial Cells

Plasma polymerization
Antibacterial coating
Biofilm
Roughness
Cytotoxicity
Bacterial infections


Isolation and characterization of ACE-I inhibitory peptides from ribbonfish for a potential inhibitor of the main protease of SARS-CoV-2; an in-silico analysis.

Abstract: Recently, multi-functional fish peptides (FWPs) have gained a lot of attention because of their different biological activities. In the present study, three Angiotensin-I Converting Enzyme (ACE-I) inhibitory peptides [Ala-Pro-Asp-Gly (APDG), Pro-Thr-Arg (PTR), and Ala-Asp (AD)] were isolated and characterized from ribbonfish protein hydrolysate (RFPH) and described their mechanism of action on ACE activity. As per the results peptide PTR showed ≈ 2 and 2.5-fold higher enzyme inhibitory activity (IC50 = 0.643 ± 0.0011 μM) than APDG (IC50 = 1.061 ± 0.0127 μM) and AD (IC50= 2.046 ± 0.0130 μM). Based on experimental evidence, peptides were used for in silico analysis to check the inhibitory activity of the main protease (PDB: 7BQY) of SARS-CoV-2. The results of the study reveal that PTR (-46.16 Kcal/mol) showed higher binding affinity than APDG (-36.80 Kcal/mol) and AD (-30.24 Kcal/mol) compared to Remdesivir (-30.64 Kcal/mol). Additionally, physicochemical characteristics of all the isolated peptides exhibited appropriate pharmacological properties and were found to be nontoxic. Besides, 20 ns molecular dynamic simulation study confirms the rigid nature, fewer confirmation variations and binding stiffness of the peptide PTR with the main protease of SARS-CoV-2. Therefore, the present study strongly suggested that PTR is the perfect substrate for inhibiting the main protease of SARS-CoV-2 through the in-silico study, and this potential drug candidate may promote the researcher for future wet-lab experiments. This article is protected by copyright. All rights reserved.

SARS-CoV-2
ACE-I inhibitory peptides: LCMS/MS
Fish protein hydrolysate
MD simulations
Molecular docking