Distribution of black carbon and PAHs in sediments of Peninsular Malaysia.

Abstract: Concentrations, sources and interactions between black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) were investigated in 42 sediment samples collected from riverine, coastal and shelf areas in Peninsular Malaysia. The concentrations of BC measured by benzene polycarboxylic acid (BPCA) method and PAHs showed broad spatial variations between the relatively pristine environment of the East coast and developed environment of the West and South coast ranging from 0.02 to 0.36% dw and 57.7 ng g-1 dw to 19,300 ng g-1 dw, respectively. Among diagnostic ratios of PAHs, the ratios of Ant/(Ant+Phe) and LMW/HMW drew the clearest distinctions between the East coast versus the West and South coast sediments indicating the predominance of petrogenic sources in the former versus pyrogenic sources in the latter. PAHs significantly correlated with BC and total organic carbon (TOC) in the sediments (p < 0.05) having similar correlation coefficients. BC accounted for 6.06 to 30.6% of TOC in sediments.

Vaezzadeh|Vahab|V|
Yi|Xin|X|
Rais|Farah Rasyidah|FR|
Bong|Chui Wei|CW|
Thomes|Margaret William|MW|
Lee|Choon Weng|CW|
Zakaria|Mohamad Pauzi|MP|
Wang|Ai Jun|AJ|
Zhong|Guangcai|G|
Zhang|Gan|G|

Black carbon
PAHs
Benzene polycarboxylic acids
TOC
Sorption
Southeast Asia


Characterization of biofilm production by Pseudomonas fluorescens isolated from refrigerated raw buffalo milk.

Abstract: Pseudomonas fluorescens can often be isolated from refrigerated raw milk. Two strains of P. fluorescens PL5.4 and PL7.1, isolated from raw buffalo milk, were evaluated for their proteolytic capacity, exopolysaccharide production and biofilm production. Proteolytic activity was observed in both strains. The P. fluorescens PL5.4 strain presented fluorescence in the presence of calcofluor, indicating exopolysaccharide production. Both strains were able to produce biofilm at 7 °C for 72 h. For the biofilm production test on stainless steel, adherent cell counts of up to 7.1, 7.3 and 8.8 log CFU/cm2 at 7, 23 and 30 °C were obtained. Through scanning electron microscopy, it was possible to observe the biofilm produced by the P. fluorescens PL5.4 strain. Proper cleaning and disinfection practices in order are important to reduce bacterial contamination and extend the useful life of raw material and its derivatives.

de Souza da Motta|Amanda|A|https://orcid.org/0000-0001-8637-3868

Biofilm
Pseudomonas fluorescens
Raw buffalo milk
Psychrotrophic bacteria


A comparative public health and budget impact analysis of pneumococcal vaccines: The French case.

Abstract: In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy.

Jiang|Yiling|Y| Gervais|Frédéric|F| Gauthier|Aline|A| Baptiste|Charles|C| Martinon|Prescilla|P| Bresse|Xavier|X|

public health
budget impact analysis
pneumococcal conjugate vaccine
invasive pneumococcal diseases
pneumococcal polysaccharide vaccine
epidemiological change


SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.

Abstract: Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question. Herein, we report that superoxide dismutase 1 (SOD1) is a conserved component of the mechanistic target of rapamycin complex 1 (mTORC1) nutrient signaling. mTORC1 regulates SOD1 activity through reversible phosphorylation at S39 in yeast and T40 in humans in response to nutrients, which moderates ROS level and prevents oxidative DNA damage. We further show that SOD1 activation enhances cancer cell survival and tumor formation in the ischemic tumor microenvironment and protects against the chemotherapeutic agent cisplatin. Collectively, these findings identify a conserved mechanism by which eukaryotes dynamically regulate redox homeostasis in response to changing nutrient conditions.

Tsang|Chi Kwan|CK|
Chen|Miao|M|
Cheng|Xin|X|
Qi|Yanmei|Y|
Chen|Yin|Y|
Das|Ishani|I|
Li|Xiaoxing|X|
Vallat|Brinda|B|
Fu|Li-Wu|LW|
Qian|Chao-Nan|CN|
Wang|Hui-Yun|HY|
White|Eileen|E|
Burley|Stephen K|SK|
Zheng|X F Steven|XFS|

D000076222:Mechanistic Target of Rapamycin Complex 1

nutrient
redox
reactive oxygen species
superoxide dismutase 1
rapamycin
cancer
cisplatin
Warburg
ischemia
mTOR


Melatonin Protects Band 3 Protein in Human Erythrocytes against H2O2-Induced Oxidative Stress.

Abstract: The beneficial effect of Melatonin (Mel), recognized as an anti-inflammatory and antioxidant compound, has been already proven to prevent oxidative stress-induced damage associated to lipid peroxidation. As previous studies modeled the impact of oxidative stress on Band 3 protein, an anion exchanger that is essential to erythrocytes homeostasis, by applying H2O2 at not hemolytic concentrations and not producing lipid peroxidation, the aim of the present work was to evaluate the possible antioxidant effect of pharmacological doses of Mel on Band 3 protein anion exchange capability. The experiments have been performed on human erythrocytes exposed to 300 μM H2O2-induced oxidative stress. To this end, oxidative damage has been verified by monitoring the rate constant for SO4= uptake through Band 3 protein. Expression levels of this protein Mel doses lower than 100 µM have also been excluded due to lipid peroxidation, Band 3 protein expression levels, and cell shape alterations, confirming a pro-oxidant action of Mel at certain doses. On the other hand, 100 µM Mel, not provoking lipid peroxidation, restored the rate constant for SO4= uptake, Band 3 protein expression levels, and H2O2-induced cell shape alterations. Such an effect was confirmed by abolishing the endogenous erythrocytes antioxidant system. Therefore, the present findings show the antioxidant power of Mel at pharmacological concentrations in an in vitro model of oxidative stress not associated to lipid peroxidation, thereby confirming Band 3 protein anion exchange capability measurement as a suitable model to prove the beneficial effect of Mel and support the use of this compound in oxidative stress-related diseases affecting Band 3 protein.

D001457:Anion Exchange Protein 1, Erythrocyte

D017392:Thiobarbituric Acid Reactive Substances

Melatonin
Band 3 protein
H2O2
oxidative damage
SO4= uptake


Sperm parameters, protamine deficiency, and apoptosis in total globozoospermia.

Abstract:
BACKGROUND
Globozoospermia is a severe form of teratozoospermia (incidence < 0.1%) in infertile men that is characterized by round headed sperm and acrosomeless in semen.

OBJECTIVE
To compare the semen parameters, protamine deficiency, and apoptosis in ejaculated spermatozoa between globozoospermic and normozoospermic men.

MATERIALS AND METHODS
Thirty six semen samples were divided into two groups including 15 infertile men with total globozoospermic (> 90% round-headed sperm) and 21 healthy donors with normal spermograms as controls. Semen analysis was performed according to World Health Organization criteria (2010). Sperm protamine deficiency was assessed using Chromomycin A3 (CMA3) staining and the rate of apoptotic spermatozoa was evaluated with TUNEL assay.

RESULTS
Sperm concentration, motility, and normal morphology in globozoospermic men were significantly decreased compared with controls (p<0.05). The rate of CMA3-reacted spermatozoa (CMA3+) in globozoospermic men was higher than controls (65.93 ± 11.77 vs. 21.24 ± 7.37, respectively, p<0.0001). The rate of apoptotic spermatozoa (TUNEL positive) were significantly increased in globozoospermic cases with respect to the controls (17.60 ± 10.72 and 5.95 ± 3.02, respectively, p<0.0001). There was no significant correlation between sperm protamine deficiency and apoptosis in globozoospermic men.

CONCLUSION
Globozoospermic samples contain a higher proportion of spermatozoa with abnormal chromatin packaging and DNA fragmentation than normozoospermic samples. Therefore, in addition to absence of acrosome in the spermatozoa of globozoospermic patients, the high percentage of spermatozoa with immature chromatin and apoptotic marker may be considered as the other etiologies of infertility in these patients.

Ghasemzadeh|Jalal|J|
Talebi|Ali Reza|AR|
Khalili|Mohammad Ali|MA|
Fesahat|Farzaneh|F|
Halvaei|Iman|I|
Nabi|Ali|A|
Ashourzadeh|Sareh|S|

Apoptosis
Sperm protamine
DNA damage
Male infertility


Comprehensive characterization and gene expression patterns of LBD gene family in Gossypium.

Abstract: A comprehensive account of the LBD gene family of Gossypium was provided in this work. Expression analysis and functional characterization revealed that LBD genes might play different roles in G. hirsutum and G. barbadense. The Lateral Organ Boundaries Domain (LBD) proteins comprise a plant-specific transcription factor family, which plays crucial roles in physiological processes of plant growth, development, and stress tolerance. In the present work, a systematical analysis of LBD gene family from two allotetraploid cotton species, G. hirsutum and G. barbadense, together with their genomic donor species, G. arboreum and G. raimondii, was conducted. There were 131, 128, 62, and 68 LBDs identified in G. hirsutum, G. barbadense, G. arboreum and G. raimondii, respectively. The LBD proteins could be classified into two main classes, class I and class II, based on the structure of their lateral organ boundaries domain and traits of phylogenetic tree, and class I was further divided into five subgroups. The gene structure and motif composition analyses conducted in both G. hirsutum and G. barbadense revealed that LBD genes kept relatively conserved within the subfamilies. Synteny analysis suggested that segmental duplication acted as an important mechanism in expansion of the cotton LBD gene family. Cis-element analysis predicated the possible functions of LBD genes. Public RNA-seq data were investigated to analyze the expression patterns of cotton LBD genes in various tissues as well as gene expression under abiotic stress treatments. Furthermore, RT-qPCR results found that GhLBDs had various expression regulation under MeJA treatments. Expression analysis indicated the differential functions of cotton LBD genes in response to abiotic stress and hormones.

D018506:Gene Expression Regulation, Plant

LBD gene family
Genome-wide analysis
Lateral root
Methyl jasmonate


Effect of Sodium Selenite on Pathological Changes and Renal Functions in Broilers Fed a Diet Containing Aflatoxin B₁.

Abstract: To evaluate the renal toxicity of dietary aflatoxin B₁ (AFB₁) and ameliorating effects of added dietary sodium selenite in broiler, renal histopathological changes, ultrastructural changes, and renal function parameters were monitored at 7, 14, and 21 days of age. Two hundred one-day-old healthy male Avian broilers were divided into four groups, namely control group, AFB₁ group (0.3 mg/kg AFB₁), +Se group (0.4 mg/kg Se), and AFB₁+Se group (0.3 mg/kg AFB₁+0.4 mg/kg Se). Compared with that of the control group, the relative weight of kidney was increased in the AFB₁ group. There were no significant differences between the AFB₁+Se group and the control group. By histopathological observation, the renal epithelia were swelling and necrosis at 7 and 21 days of age. Ultrastructurally, the lipid droplets and expanded endoplasmic reticulum appeared in the plasma of epithelia cells in the AFB₁ group. Enlarged mitochondria with degenerated cristae were observed in the +Se group. Compared with the control group, the contents of serum creatinine and serum uric acid in the AFB₁ group were increased, while the activity of renal Na⁺-K⁺ ATPase was decreased. When 0.4 mg/kg selenium was added into the diet containing 0.3 mg/kg AFB₁, there were no obvious histological changes in the AFB₁+Se group, and the contents of the serum creatinine and serum uric acid contents and the activity of renal Na⁺-K⁺ ATPase were close to those in the control group. In conclusion, sodium selenite exhibited protective effects on AFB₁-induced kidney toxicity in broilers.

Liang|Na|N| Wang|Fengyuan|F| Peng|Xi|X| Fang|Jing|J| Cui|Hengmin|H| Chen|Zhengli|Z| Lai|Weimin|W| Zhou|Yi|Y| Geng|Yi|Y|

sodium selenite
renal function
broiler
aflatoxin B1
pathological observation
ultrastructural observation


Shiga Toxin-Producing Serogroup O91 Escherichia coli Strains Isolated from Food and Environmental Samples.

Abstract: Shiga toxin-producing Escherichia coli (STEC) strains of the O91:H21 serotype have caused severe infections, including hemolytic-uremic syndrome. Strains of the O91 serogroup have been isolated from food, animals, and the environment worldwide but are not well characterized. We used a microarray and other molecular assays to examine 49 serogroup O91 strains (environmental, food, and clinical strains) for their virulence potential and phylogenetic relationships. Most of the isolates were identified to be strains of the O91:H21 and O91:H14 serotypes, with a few O91:H10 strains and one O91:H9 strain being identified. None of the strains had the eae gene, which codes for the intimin adherence protein, and many did not have some of the genetic markers that are common in other STEC strains. The genetic profiles of the strains within each serotype were similar but differed greatly between strains of different serotypes. The genetic profiles of the O91:H21 strains that we tested were identical or nearly identical to those of the clinical O91:H21 strains that have caused severe diseases. Multilocus sequence typing and clustered regularly interspaced short palindromic repeat analyses showed that the O91:H21 strains clustered within the STEC 1 clonal group but the other O91 serotype strains were phylogenetically diverse.IMPORTANCE This study showed that food and environmental O91:H21 strains have similar genotypic profiles and Shiga toxin subtypes and are phylogenetically related to the O91:H21 strains that have caused hemolytic-uremic syndrome, suggesting that these strains may also have the potential to cause severe illness.

Feng|Peter C H|PCH|
Delannoy|Sabine|S|
Lacher|David W|DW|
Bosilevac|Joseph M|JM|
Fach|Patrick|P|
Beutin|Lothar|L|


Differences in Physicians' Verbal and Nonverbal Communication With Black and White Patients at the End of Life.

Abstract:
CONTEXT
Black patients are more likely than white patients to die in the intensive care unit with life-sustaining treatments. Differences in patient- and/or surrogate-provider communication may contribute to this phenomenon.

OBJECTIVES
To test whether hospital-based physicians use different verbal and/or nonverbal communication with black and white simulated patients and their surrogates.

METHODS
We conducted a randomized factorial trial of the relationship between patient race and physician communication using high-fidelity simulation. Using a combination of probabilistic and convenience sampling, we recruited 33 hospital-based physicians in western Pennsylvania who completed two encounters with prognostically similar, critically and terminally ill black and white elders with identical treatment preferences. We then conducted detailed content analysis of audio and video recordings of the encounters, coding verbal emotion-handling and shared decision-making behaviors, and nonverbal behaviors (time interacting with the patient and/or surrogate, with open vs. closed posture, and touching the patient and physical proximity). We used a paired t-test to compare each subjects' summed verbal and nonverbal communication scores with the black patient compared to the white patient.

RESULTS
Subject physicians' verbal communication scores did not differ by patient race (black vs. white: 8.4 vs. 8.4, P-value = 0.958). However, their nonverbal communication scores were significantly lower with the black patient than with the white patient (black vs. white: 2.7 vs. 2.9, P-value 0.014).

CONCLUSION
In this small regional sample, hospital-based physicians have similar verbal communication behaviors when discussing end-of-life care for otherwise similar black and white patients but exhibit significantly fewer positive, rapport-building nonverbal cues with black patients.

Elliott|Andrea M|AM|
Alexander|Stewart C|SC|
Mescher|Craig A|CA|
Mohan|Deepika|D|
Barnato|Amber E|AE|

Communication
race
disparities
provider behavior
terminal care


Pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of the novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist RG7697 in people with type 2 diabetes mellitus.

Abstract:
AIMS
To investigate the pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of RG7697, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist, in patients with type 2 diabetes mellitus (T2D).

METHODS
A total of 56 patients with T2D received once-daily subcutaneous (s.c.) injection of RG7697 (0.25-2.5 mg) or placebo for 14 days in a randomized, double-blind, dose-escalation study. Adverse events (AEs), vital signs, ECGs and routine laboratory variables were intensively monitored. Drug concentrations, fasting glycaemic variables, 24-hour glucose profiles, glycated haemoglobin (HbA1c) and antibody formation were measured. Several meal tolerance and gastric emptying tests were performed during the study.

RESULTS
Daily s.c. injections of RG7697 were well tolerated by the majority of participants with T2D. The most frequently reported AEs with RG7697 were diarrhoea, nausea and decreased appetite. Asymptomatic events of hypoglycaemia were relatively uniformly distributed across dose groups including placebo. Pharmacokinetic steady-state was achieved within 1 week. Meaningful reductions in fasting, postprandial and 24-hour plasma glucose profile were observed at doses ≥0.75 mg, and were associated with numerical decreases in HbA1c (-0.67% [2.5-mg dose] vs -0.21% [placebo]). Decrease in postprandial insulin at doses ≥1.1 mg suggested improvement in insulin sensitivity. Minimum delay in gastric emptying and body weight reductions numerically greater than placebo (- 3.0 kg vs -0.9 kg) were seen at the highest dose of 2.5 mg.

CONCLUSIONS
Daily doses of RG7697 for 2 weeks were well tolerated by the majority of patients with T2D. Pharmacokinetic data supported once-daily dosing and pharmacodynamic effect displayed dose-dependent reductions in fasting and postprandial plasma glucose, without increasing the risk of hypoglycaemia.

pharmacodynamics
pharmacokinetics
safety
type 2 diabetes mellitus
NNC0090-2746
RG7697, RO6811135
dual GIP/GLP-1 agonist


The rs251684 Variant of PLA2G4C Is Associated with Autism Spectrum Disorder in the Northeast Han Chinese Population.

Abstract:
AIM
To investigate the association between autism spectrum disorder (ASD) and the phospholipase A2 group IVC (PLA2G4C) and phospholipase A2 group XIIA (PLA2G12A) polymorphisms in the Northeast Han Chinese population.

MATERIALS AND METHODS
A total of 68 family trios (children diagnosed with ASD and their unaffected parents) were enrolled. Five single-nucleotide polymorphisms (SNPs) (rs9226, rs1045376, rs251684, rs2307279, and rs156631) in PLA2G4C and four SNPs (rs6533451, rs2285714, rs2285713, and rs11728699) in PLA2G12A were selected and genotyped. The association between the SNPs and ASD was analyzed using the transmission disequilibrium test.

RESULTS
Our results showed a significant association between ASD and the rs251684 variant of PLA2G4C (transmitted/nontransmitted = 36/21, χ2 = 3.947, p = 0.047), but no association between ASD and the other eight SNPs investigated (all p > 0.05). Moreover, we found no preference in the transmission of haplotypes constructed for either PLA2G4C or PLA2G12A.

CONCLUSION
The rs251684 polymorphism of PLA2G4C may be associated with ASD risk.

Liu|Shicheng|S|
Qiu|Shuang|S|
Lu|Yuping|Y|
Kanu|Joseph Sam|JS|
Li|Ri|R|
Bai|Ye|Y|
Zhu|Xiaojuan|X|
Lei|Jie|J|
Xu|Naijun|N|
Yu|Yaqin|Y|
Liu|Yawen|Y|
Jiang|Huiyi|H|

D020022:Genetic Predisposition to Disease

ASD
phospholipase A2 group IVC
phospholipase A2 group XIIA
transmission disequilibrium test
single nucleotide polymorphism


Elements for optimizing a one-step enzymatic bio-refinery process of shrimp cuticles: Focus on enzymatic proteolysis screening.

Abstract: This article complements an earlier work published in 2015 Baron et al. (2015) that showed the interest of a shrimp shells bio-refining process. We compare here the effect of eleven commercial proteases at pH 3.5 or 4.0 on a residual amount of shrimp shells proteins after 6 h at 50 °C. The two pH are obtained when respectively 40 and 25 mmol of formic acid are added to 5 g of mild dried shell. Deproteinisation yield above 95% are obtained. Residual amino acids profile in the solid phase was identical for the eleven proteases except for pepsin which was similar to the raw material profile. A significant relative increase in the proportion of Glycine is observed for the ten other cases. Likewise, shapes of size exclusion chromatograms of the dissolved phase are similar except with pepsin.

Baron|R|R|
Socol|M|M|
Kaas|R|R|
Arhaliass|A|A|
Rodriguez Del Pino|J|J|
Le Roux|K|K|
Donnay-Moreno|C|C|
Bergé|J P|JP|

Bio-refinery
Shrimp cuticles
Acidic enzymatic proteolysis


Montelukast Use Decreases Cardiovascular Events in Asthmatics.

Abstract: Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on eight hundred adult asthmatic patients 18 years or older in Albania, equally distributed into two cohorts, exposed or nonexposed to montelukast usage, matched by age and gender according to information reported in the data collection. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. In summary, 37 (4.6%) of the asthmatic patients, 32 nonexposed, and five exposed to montelukast suffered a major cardiovascular event during the 3-year observation period. All the cardiovascular events, in either group, occurred among patients with an increased cardiovascular risk. Our analyses demonstrate that, independent from gender, exposure to montelukast remained a significant protective factor for incident ischemic events (78% or 76% risk reduction depending on type of analysis). The event-free Kaplan-Meier survival curves confirmed the lower cardiovascular event incidence in patients exposed to montelukast. Our data suggest that there is a potential preventative role of montelukast for incident cardiac ischemic events in the older asthmatic population, indicating a comorbidity benefit of montelukast usage in asthmatics by targeting cysteinyl leukotriene-driven cardiac disease inflammation.

Hoxha|Malvina|M|
Tedesco|Calogero C|CC|
Quaglin|Silvana|S|
Malaj|Visar|V|
Pustina|Linda|L|
Capra|Valerie|V|
Evans|Jilly F|JF|
Sala|Angelo|A|
Rovati|G Enrico|GE|

montelukast
asthma
cardiovascular diseases
inflammation
leukotriene receptors


Associations of Endothelin Polymorphisms and Aneurysm Size at Time of Rupture.

Abstract:
BACKGROUND AND PURPOSE
Aneurysm size is an important risk factor for aneurysm rupture. The pathophysiologic mechanisms underlying aneurysm growth remain poorly understood. Endothelin signaling is critical for cerebrovascular blood flow regulation. The influence of endothelin single nucleotide polymorphisms (SNPs) on aneurysm size at the time of rupture has not been previously investigated.

METHODS
Eight common endothelin SNPs were assessed using blood samples from aneurysmal subarachnoid hemorrhage (aSAH) patients enrolled in the Cerebral Aneurysm Renin Angiotensin System study, a prospective, 2-center study that enrolled aSAH patients and controls in the United States from 2012-2015. Genetic evaluation was performed using 5'exonnuclease (Taqman) genotyping assays. Associations of endothelin SNPs and aneurysm size were analyzed.

RESULTS
One-hundred and forty-nine blood samples from aSAH patients were available for analysis. There was a dominant effect of the G allele of the endothelin receptor type A (EDNRA) SNP rs5335 on aneurysm size ≥7 mm (odds ratio = 2.740, 95% confidence interval 1.039-7.228, P = 0.042) along with associations with race and presence of additional aneurysms. The other endothelin SNPs were not associated with aneurysm size.

CONCLUSIONS
The EDNRA SNP rs5335 was independently associated with aneurysms ≥7 mm in size at the time of rupture. Patients with cerebral aneurysms also carrying the G allele of EDNRA SNP rs5335 may develop larger aneurysms before rupture.

Hendrix|Philipp|P|
Foreman|Paul M|PM|
Starke|Robert M|RM|
Harrigan|Mark R|MR|
Fisher|Winfield S|WS|
Vyas|Nilesh A|NA|
Lipsky|Robert H|RH|
Lin|Minkuan|M|
Walters|Beverly C|BC|
Tubbs|R Shane|RS|
Shoja|Mohammadali M|MM|
Pittet|Jean-Francois|JF|
Mathru|Mali|M|
Griessenauer|Christoph J|CJ|

D015898:Tomography Scanners, X-Ray Computed

Endothelin
Polymorphism
Aneurysm size
Subarachnoid hemorrhage


Development of a nanoparticle-assisted PCR assay for detection of porcine epidemic diarrhea virus.

Abstract: Porcine epidemic diarrhea virus (PEDV) is an important pig pathogen that can cause vomiting, diarrhea, and dehydration, leading to serious damage to the swine industry worldwide. In this study, a nanoparticle-assisted polymerase chain reaction (nanoPCR) assay targeting the N gene of PEDV was developed and the sensitivity and specificity were investigated. Under the optimized conditions for detection of PEDV RNA, the nanoPCR assay was 100-fold more sensitive than a conventional RT-PCR assay. The lower detection limit of the nanoPCR assay was 2.7 × 10(-6) ng/μL of PEDV RNA and no cross-reaction was observed with other viruses. This is the first report to demonstrate the application of a nanoPCR assay for the detection of PEDV. The sensitive and specific nanoPCR assay developed in this study can be applied widely in clinical diagnosis and field surveillance of PEDV-infection.

Yuan|Wanzhe|W| Li|Yanan|Y| Li|Peng|P| Song|Qinye|Q| Li|Limin|L| Sun|Jiguo|J|

D000818:Animals
D018352:Coronavirus Infections
D017931:DNA Primers
D025202:Molecular Diagnostic Techniques
D053758:Nanoparticles
D019590:Nucleocapsid Proteins
D016133:Polymerase Chain Reaction
D053485:Porcine epidemic diarrhea virus
D012680:Sensitivity and Specificity
D013552:Swine
D013553:Swine Diseases
D014730:Veterinary Medicine

Detection
Porcine epidemic diarrhea virus (PEDV)
nanoPCR
RT-PCR


Risk of cancer in patients treated with recombinant human growth hormone in childhood.

Abstract: Recombinant human growth hormone (GH) has been in use for over 30 years, and its indications have gradually expanded from the classical replacement therapy in GH deficiency (GHD) to pharmacological therapy in patients with normal GH secretion. The insulin-like growth factor-I (IGF-I ) is closely GH dependent and is the effector of GH biological actions in peripheral tissues. Since IGF-I has potent mitogenic and antiapoptotic effects, the use of GH, especially outside GHD, has raised safety concern regarding cancer risk. The results of experimental, epidemiological and observational studies are not univocal and a number of biases and confounders affect the interpretation of data. The aim of this review is to critically review the data linking GH therapy during childhood with cancer risk, highlighting strengths and weaknesses of the available evidence.

Cancer
Growth hormone
Insulin-like growth factor


Five patients with a chromosome 1q21.1 triplication show macrocephaly, increased weight and facial similarities.

Abstract: Recurrent rearrangements of chromosome 1q21.1 that occur as a consequence of non-allelic homologous recombination (NAHR) show considerable variability in phenotypic expression and penetrance. Chromosome 1q21.1 deletions (OMIM 612474) have been associated with microcephaly, intellectual disability, autism, schizophrenia, cardiac abnormalities and cataracts. Phenotypic features in individuals with 1q21.1 duplications (OMIM 612475) include macrocephaly, learning difficulties, developmental delay, intellectual disability and mild dysmorphic features. Half of these patients show autistic behavior. For the first time, we describe five patients, including monozygotic twins, with a triplication of the 1q21.1 chromosomal segment. Facial features common to all patients include a high, broad forehead; a flat and broad nasal bridge; long, downslanted palpebral fissures and dysplastic, low-set ears. Likely associated features include macrocephaly and increased weight. We observed that the triplications arose through different mechanisms in the patients: it was de novo in one patient, inherited from a triplication carrier in two cases, while the father of the twins is a 1q21.1 duplication carrier. The de novo triplication contained copies of both maternal alleles, suggesting it was generated by a combination of inter- and intrachromosomal recombination.

Van Dijck|Anke|A|
van der Werf|Ilse M|IM|
Reyniers|Edwin|E|
Scheers|Stefaan|S|
Azage|Meron|M|
Siefkas|Kiana|K|
Van der Aa|Nathalie|N|
Lacroix|Amy|A|
Rosenfeld|Jill|J|
Argiropoulos|Bob|B|
Davis|Kellie|K|
Innes|A Micheil|AM|
Mefford|Heather C|HC|
Mortier|Geert|G|
Meuwissen|Marije|M|
Kooy|R Frank|RF|

1q21.1 triplication
Macrocephaly
Recurrent rearrangements
Genomic disorder
Overweight


Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites.

Abstract:
BACKGROUND & AIMS
Intestinal hyperpermeability, impaired peritoneal macrophages (PMs) phagocytosis, and bacterial translocation (BT), resulting in increased systemic and local infection/inflammation such as spontaneous bacterial peritonitis (SBP) together with increased tumor necrosis factor-α (TNFα) levels, are all implicated in the pathogenesis of cirrhosis-related complications. Manipulation of the cannabinoid receptors (CB1R and CB2R), which are expressed on the gut mucosa and PMs, has been reported to modulate intestinal inflammation and systemic inflammatory cytokine release. Our study aims to explore the effects of chronic CB1R/CB2R agonist/antagonist treatments on relevant abnormalities in cirrhotic ascitic rats.

METHODS
Vehicle, archidonyl-2-chloroethylamide (ACEA, CB1R agonist), JWH133 (CB2R agonist), and AM630 (CB2R antagonist) were given to thioacetamide (TAA) and common bile duct ligation (BDL) cirrhotic rats with ascites for two weeks and various measurement were performed.

RESULTS
Compared to sham rats, CB2Rs were downregulated in cirrhotic rat intestines and PMs. The two-week JWH133 treatment significantly decreased systemic/intestinal oxidative stress, TNFα and inflammatory mediators, infection, intestinal mucosal damage and hyperpermeability; the JWH133 treatment also decreased bacterial overgrowth/adhesion, BT and SBP, upregulated intestinal tight junctions and downregulated the PM TNFα receptor/NFκBp65 protein expression in cirrhotic rats. Acute and chronic JWH133 treatment corrected the TNFα-induced suppression of phagocytosis of cirrhotic rat PMs, which then could be reversed by concomitant AM630 treatment.

CONCLUSIONS
Our study suggests that CB2R agonists have the potential to treat BT and various relevant abnormalities through inhibition of systemic/intestinal oxidative stress, inflammatory cytokines and TNFα release in cirrhosis. Overall, the chronic CB2R agonist treatment affects multiple approach mechanisms, and its direct effect on the hyperdynamic circulation is only minor.

Yang|Ying-Ying|YY| Hsieh|Shie-Liang|SL| Lee|Pei-Chang|PC| Yeh|Yi-Chen|YC| Lee|Kuei-Chuan|KC| Hsieh|Yun-Cheng|YC| Wang|Ying-Wen|YW| Lee|Tzung-Yan|TY| Huang|Yi-Hsiang|YH| Chan|Che-Chang|CC| Lin|Han-Chieh|HC|

Bacterial translocation
Intestinal hyperpermeability
Peritoneal macrophages
Spontaneous bacterial peritonitis
Cannabinoid receptors


Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target Cell Wall Integrity.

Abstract: Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2Δ and bck1Δ (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2Δ and bck1Δ showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAΔ, mpkCΔ) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention.

Kim|Jong H|JH|
Chan|Kathleen L|KL|
Mahoney|Noreen|N|

monoterpenoids
cell wall integrity
antimycotic
benzaldehydes
chemosensitization
Saccharomyces cerevisiae
filamentous fungi
mycotoxins
signal transduction
synergism


Food Insecurity Is Associated with Depression, Anxiety, and Stress: Evidence from the Early Days of the COVID-19 Pandemic in the United States.

Abstract: Purpose: To understand associations between food insecurity and depression, anxiety, and stress during the COVID-19 pandemic among low-income adults in the United States. Methods: During March 19-24, 2020, we fielded a national, web-based survey (53% response rate) among low-income adults (<250% of the federal poverty line) in the United States (N=1,476). Food security status was measured using the 18-question USDA Household Food Security Module. Multivariable-adjusted logistic regression models examined the association between food insecurity and psychological distress outcomes and COVID-19-specific worries. Qualitative data from an open-response question were also analyzed. Results: More than one-third of low-income adults screened positive for depression (33%), anxiety (39%), and high stress (39%). Greater food insecurity was associated with a dose-response relationship with all psychological distress outcomes (all outcomes p-trend <0.001) and COVID-19-specific worries (all outcomes p-trend <0.001). Compared to food-secure adults, adults with very low food security were more likely to screen positive for depression (odds ratio [OR] 7.72; 95% confidence interval [CI]: 5.52-10.80), anxiety (OR 6.19; 95% CI: 4.51-8.51), and high perceived stress (OR 10.91; 95% CI: 7.78-15.30). Very low food security was also associated with increased worries about the effect of COVID-19 on one's health (OR 2.56; 95% CI: 1.90-3.45), income (OR 5.18; 95% CI: 3.78-7.06), and ability to feed one's family (OR 9.24; 95% CI: 6.61-12.92). Conclusions: The COVID-19 pandemic is negatively associated with the mental health of low-income adults in the United States, with disproportionate associations among adults experiencing food insecurity. These disparities have the potential to increase mental health disparities over the long term.

Wolfson|Julia A|JA|
Garcia|Travertine|T|
Leung|Cindy W|CW|

food insecurity
depression
anxiety
stress
low-income
psychological distress
mental health
disparities


Lymphocyte modulation by tofacitinib in patients with rheumatoid arthritis.

Abstract: Tofacitinib is an oral small molecule targeting the intracellular Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways approved for the treatment of active rheumatoid arthritis (RA). We investigated the effects of tofacitinib on the response of RA lymphocytes to B and T cell collagen epitopes in their native and post-translationally modified forms. In particular, peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy subjects were cultured with type II collagen peptides (T261-273, B359-369, carT261-273, citB359-369) or with phorbol myristate acetate (PMA)/ionomycin/CD40L in the presence or absence of 100 nM tofacitinib for 20 h and analyzed by fluorescence activated cell sorter (FACS). Cultures without brefeldin A were used for cytokine supernatant enzyme-linked immunosorbent assay (ELISA) analysis. Tofacitinib down-regulated inflammatory cytokines by stimulated B [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and T [interferon (IFN)-γ, IL-17 or TNF-α] cells in the short term, while a significant reduction of IL-17 and IL-6 levels in peripheral blood mononuclear cell (PBMC) supernatant was also observed. IL-10 was significantly reduced in collagen-stimulated B cells from patients with RA and increased in controls, thus mirroring an altered response to collagen self-epitopes in RA. Tofacitinib partially prevented the IL-10 down-modulation in RA B cells stimulated with collagen epitopes. In conclusion, the use of tofacitinib exerts a rapid regulatory effect on B cells from patients with RA following stimulation with collagen epitopes while not reducing inflammatory cytokine production by lymphocytes.

Isailovic|Natasa|N|
Ceribelli|Angela|A|
Cincinelli|Gilberto|G|
Vecellio|Matteo|M|
Guidelli|Giacomo|G|
Caprioli|Marta|M|
Luciano|Nicoletta|N|
Motta|Francesca|F|
Selmi|Carlo|C|0000-0002-0323-0376
De Santis|Maria|M|0000-0002-3196-1336

collagen epitope
regulatory effect
Janus kinase
acquired immunity
post-translational modifications
targeted synthetic DMARDs


Rapid and Sensitive Detection of Mycobacterium tuberculosis by an Enhanced Nanobiosensor.

Abstract: Tuberculosis (TB) mostly spreads from person to person through Mycobacterium tuberculosis (MTB). However, the majority of conventional detection methods for MTB cannot satisfy the requirements for actual TB detection. As one of the most promising powerful platforms, a silicon nanowire field-effect transistor (SiNW-FET) biosensor shows good prospect in TB detection. In this study, an enhanced SiNW-FET biosensor was developed for the rapid and sensitive detection of MTB. The surface functional parameters of the biosensor were explored and optimized. The SiNW-FET biosensor has good sensitivity with a detection limit of 0.01 fg/mL toward protein. The current change value shows a linear upward trend with the increase in protein concentration in the range of 1 fg/mL to 100 μg/mL. One whole test cycle can be accomplished within only 30 s. More importantly, a good distinction was realized in the sputum without pretreatment between normal people and TB patients, which greatly shortened the TB detection time (only 2-5 min, considering the dilution of sputum). Compared with other methods, the SiNW-FET biosensor can detect MTB with a remarkably broad dynamic linear range in a shorter time.

Mycobacterium tuberculosis
silicon nanowire
field-effect transistor
biosensor
sputum


Reaching 200-ps timing resolution in a time-of-flight and depth-of-interaction positron emission tomography detector using phosphor-coated crystals and high-density silicon photomultipliers.

Abstract: Current research in the field of positron emission tomography (PET) focuses on improving the sensitivity of the scanner with thicker detectors, extended axial field-of-view, and time-of-flight (TOF) capability. These create the need for depth-of-interaction (DOI) encoding to correct parallax errors. We have proposed a method to encode DOI using phosphor-coated crystals. Our initial work using photomultiplier tubes (PMTs) demonstrated the possibilities of the proposed method, however, a major limitation of PMTs for this application is poor quantum efficiency in yellow light, corresponding to the wavelengths of the converted light by the phosphor coating. In contrast, the red-green-blue-high-density (RGB-HD) silicon photomultipliers (SiPMs) have a high photon detection efficiency across the visible spectrum. Excellent coincidence resolving time (CRT; [Formula: see text]) was obtained by coupling RGB-HD SiPMs and [Formula: see text] lutetium fine silicate crystals coated on a third of one of their lateral sides. Events were classified in three DOI bins ([Formula: see text] width) with an average sensitivity of 83.1%. A CRT of [Formula: see text] combined with robust DOI encoding is a marked improvement in the phosphor-coated approach that we pioneered. For the first time, we read out these crystals with SiPMs and clearly demonstrated the potential of the RGB-HD SiPMs for this TOF-DOI PET detector.

Kwon|Sun Il|SI|
Ferri|Alessandro|A|
Gola|Alberto|A|
Berg|Eric|E|
Piemonte|Claudio|C|
Cherry|Simon R|SR|
Roncali|Emilie|E|

time-of-flight
depth-of-interaction
positron emission tomography
silicon photomultiplier
phosphor coating
coincidence timing resolution


Sinus thrombectomy for purulent cerebral venous sinus thrombosis utilizing a novel combination of the Trevo stent retriever and the Penumbra ACE aspiration catheter: the stent anchor with mobile aspiration technique.

Abstract: Intracranial complications of sinusitis are rare but life threatening. We present a case of a 17-year-old woman with sinusitis who deteriorated over the course of 12 days from subdural empyema and global purulent cerebral venous sinus thrombosis. The patient was managed with surgery and mechanical thrombectomy utilizing a novel 'stent anchor with mobile aspiration technique', in which a Trevo stent retriever (Stryker) was anchored in the superior sagittal sinus (SSS) while a 5 MAX ACE reperfusion catheter (Penumbra) was passed back and forth from the SSS to the sigmoid sinus with resultant dramatic improvement in venous outflow. The patient was extubated on postoperative day 3 and was discharged with minimal lower extremity weakness on postoperative day 11. This is the first report using the Trevo stent retriever for sinus thrombosis. It is important to keep these rare complications in mind when evaluating patients with oral and facial infections.

Mascitelli|Justin R|JR|
Pain|Margaret|M|
Zarzour|Hekmat K|HK|
Baxter|Peter|P|
Ghatan|Saadi|S|
Mocco|J|J|

Stent Infection Device Intervention Vein


Simultaneous determination of skimmin, apiosylskimmin, 7-hydroxycoumarin and 7-hydroxycoumarin glucuronide in rat plasma by liquid chromatography-Orbitrap mass spectrometry and its application to pharmacokinetics.

Abstract: The effective fraction of coumarin glycosides from Hydrangea paniculata Sieb (HP) has been under development for the treatment of chronic kidney disease for years. Skimmin and apiosylskimmin are the main coumarin glycosides of HP, and the major metabolites in rats are 7-hydroxycoumarin (7-HC) and 7-hydroxycoumarin glucuronide (7-HCG). In this study, a sensitive and reliable liquid chromatography-Orbitrap mass spectrometry method was developed for the simultaneous determination of skimmin, apiosylskimmin, 7-HC and 7-HCG in rat plasma. The chromatographic separation was performed on a Zobax SB C18 column (2.1 × 100 mm, 3.5 μm) at a flow rate of 0.3 ml/min with a gradient mobile phase of water and acetonitrile containing 0.2% formic acid. Skimmin, apiosylskimmin and 7-HCG were detected in targeted-selected-ion-monitoring mode at positive ions m/z of 325.0911, 457.1331 and 339.0703, respectively. 7-HC and the internal standard were detected in parallel-reaction-monitoring mode at m/z 163.0387 → 119.0492 and 260.1641 → 116.1071 to overcome the carryover of 7-HC. Linearity was obtained for the analytes within the ranges 20-2,000 ng/ml for skimmin, 5-500 ng/ml for apiosylskimmin and 7-HC and 100-10,000 ng/ml for 7-HCG. Validation parameters were all in line with the criteria of international guidance. The method has been applied to the pharmacokinetic study of HP in rats.

Skimmin
Skimmin
7-hydroxycoumarin
7-hydroxycoumarin glucuronide
pharmacokinetics
apiosyl
skimmin


TAVI and the future of aortic valve replacement.

Abstract: Aortic valve stenosis (AS) is the most common valvular pathology and has traditionally been managed using surgical aortic valve replacement (SAVR). A large proportion of affected patient demographics, however, are unfit to undergo major surgery given underlying comorbidities. Since its introduction in 2002, transcatheter aortic valve implantation (TAVI) has gained popularity and transformed the care available to different-risk group patients with severe symptomatic AS. Specific qualifying criteria and refinement of TAVI techniques are fundamental in determining successful outcomes for intervention. Given the successful applicability in high-risk patients, TAVI has been further developed and trialed in intermediate and low-risk patients. Within intermediate-risk patient groups, TAVI was shown to be noninferior to SAVR evaluating 30-d mortality and secondary endpoints such as the risk of bleeding, development of acute kidney injury, and length of admission. The feasibility of expanding TAVI procedures into low-risk patients is still a controversial topic in the literature. A number of trials have recently been published which demonstrate TAVI as noninferior and even superior over SAVR for primary study endpoints.

D065467:Transcatheter Aortic Valve Replacement

TAVI
aortic valve
valve replacement
surgery


Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response.

Abstract:
AIMS/HYPOTHESIS
A European Phase III trial of GAD formulated with aluminium hydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response.

METHODS
In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD65-induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum.

RESULTS
GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was ≥210 days (p < 0.05). In the group that received two doses of GAD-alum, levels of several GAD65-induced cytokines were higher in participants who received the H1N1 vaccination and the first GAD-alum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum.

CONCLUSIONS/INTERPRETATION
In individuals who received two doses of GAD-alum, receiving the Pandemrix vaccine closer to the first GAD-alum injection, i.e. <150 days, seemed to affect both GAD65-induced immune response and C-peptide preservation.

TRIAL REGISTRATION
ClinicalTrials.gov NCT00723411.

Tavira|Beatriz|B| Cheramy|Mikael|M| Axelsson|Stina|S| Åkerman|Linda|L| Ludvigsson|Johnny|J| Casas|Rosaura|R|

Vaccine
H1N1
GAD
Type 1 diabetes
Children
Immune intervention


Optical imaging of resting-state functional connectivity in a novel arterial stiffness model.

Abstract: This study aims to assess the impact of unilateral increases in carotid stiffness on cortical functional connectivity measures in the resting state. Using a novel animal model of induced arterial stiffness combined with optical intrinsic signals and laser speckle imaging, resting state functional networks derived from hemodynamic signals are investigated for their modulation by isolated changes in stiffness of the right common carotid artery. By means of seed-based analysis, results showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Furthermore, a graph analysis indicated a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex lateral to the treated carotid, which however did not translate in differentiated metabolic activity.

Guevara|Edgar|E| Sadekova|Nataliya|N| Girouard|Hélène|H| Lesage|Frédéric|F|

(110.4234) Multispectral and hyperspectral imaging


Standard Neoadjuvant Treatment in Early/Locally Advanced Breast Cancer.

Abstract: Neoadjuvant treatment allows us to improve surgical results and test new drugs. In recent years, there have been significant advances in the field of neoadjuvant treatment, including hormonal neoadjuvant therapy in luminal tumors, double blockade in HER2-positive tumors, and the use of platinum salts in triple-negative tumors.

Neoadjuvant treatment
Breast cancer
Pathological complete response


Gender-Specific Risk Factors of Physical Activity-Related Injuries among Middle School Students in Southern China.

Abstract: This cross-sectional study was carried out to explore the potential risk factors of physical activity-related injuries (PARI) among middle-school students of different genders. Selected by the random cluster sampling method, students aged from 12 to 16 years old in grades 7-8 from six middle schools in Shantou, southern China, were recruited for this investigation in November 2017. Information about socio-demographics, physical activity (PA) exposure time, individual exercise behaviors, risk-taking behaviors, and PARI experiences in the past 12 months was collected. A multivariate logistic regression model was used to explore the risk factors of PARI. A total of 1270 students completed valid questionnaires, with an overall injury incidence of 33.6% (boys: 42.0%; girls: 25.0%), an injury risk of 0.68 injuries/student/year, and an injury rate of 1.43 injuries per 1000 PA exposure hours. For boys, living in a school dormitory, participating in sports teams, exercising on a wet floor, rebellious behavior, and having longer PA exposure time were the risk factors of PARI. For girls, those who were sports team members, whose parents were divorced or separated, and those with longer PA exposure time were more vulnerable to suffer from PARI. In conclusion, PARI was a health problem among middle school students in southern China. Boys and girls differed in PARI occurrence and were affected by different risk factors, which provides a basis for targeted gender-specific intervention programs to reduce the occurrence of PARI among middle-school students.

risk factors
middle school
physical activity
adolescents
sports injury


Carcinogenic potential of polypropylene mid-urethral slings: what do we know so far?

Abstract:
INTRODUCTION AND HYPOTHESIS
Polypropylene (PP) mesh has come under increased scrutiny owing to previous FDA safety communications regarding the risks of mesh in trans-vaginal surgery and ensuing class action litigation for post-operative complications. Additional concerns have been raised regarding a possible link between implanted PP mesh and the long-term development of malignancy. Until recently, no research was specifically committed to the exploration of such a link. Our objective was to provide an overview of the recent literature focusing on any association between the use of PP mesh for midurethral sling procedures and the development of malignancy.

METHODS
Multiple online research databases were searched for information related to any possible carcinogenic potential of PP mesh.

RESULTS
There was no increased incidence in the development of malignancy after midurethral sling procedures using PP mesh in any of the studies.

CONCLUSION
Given the scarcity of evidence suggesting otherwise, the likelihood of PP mesh causing malignancy is exceptionally low. However, with few studies and an unknown latency period between exposure and diagnosis, more observational data would prove useful to exclude causality.

Polypropylene
Sling
Mesh
Carcinogenesis
Foreign body
Stress incontinence


Isosteviol Sodium Inhibits Astrogliosis after Cerebral Ischemia/Reperfusion Injury in Rats.

Abstract: Previous reports have indicated that isosteviol sodium (STVNa) has neuroprotective effects against acute focal cerebral ischemia in rats; however, the exact underlying mechanisms and ideal treatment paradigm are not known. To find a reasonable method for STVNa administration and to determine its possible therapeutic mechanisms, we characterized the protective effects of single-dose and multiple-dose STVNa in cerebral ischemic/reperfusion (I/R) injury in rats. Single and multiple treatments with 10 mg/kg STVNa were administered intraperitoneally after injury to investigate its neuroprotective effects. Neurobehavioral deficits and infarct volume were assessed 7 d after ischemia. Both STVNa treatments reduced infarct volumes, improved neurological behaviors, preserved cellular morphology, enhanced neuronal survival, and suppressed cell apoptosis. Multiple treatments performed better than single treatment. Reactive astrogliosis was apparent at 7 d after injury and was significantly inhibited by multiple STVNa treatments but not single treatment. These results indicate that STVNa exerts neuroprotection by different mechanisms in the acute and delayed phases of I/R. Specifically, STVNa neuroprotection in the delayed phase of injury was found to be accompanied with the inhibition of astrogliosis.

Zhang|Hao|H| Sun|Xiaoou|X| Xie|Yanxiang|Y| Tian|Fang|F| Hu|Hui|H| Tan|Wen|W|

isosteviol sodium
astrogliosis
rat
cerebral ischemic/reperfusion injury


The Mutation of the Ap3b1 Gene Causes Uterine Hypoplasia in Pearl Mice.

Abstract: The pearl (pe) mouse mutant has been identified as a model for Hermansky-Pudlak syndrome and bears a mutation in the beta3A subunit of the AP-3 complex, which has a core function in the biogenesis and function of various lysosomal-related organelles. Through large-scale mating, we found that female pearl mice also displayed reduced fertility with a smaller litter size. Abnormal uteri in both 1-month-old and 3-month-old mice were observed as having short and thin uterine horns, indicating abnormal development. Histological studies revealed that the endometrial epithelium and endometrial stoma of the uterus were both thinner than those in the normal controls. We examined some key factors in uterine development, including the Hoxa10, Hoxa11, and Wnt5a genes, and found that they all presented lower mRNA and protein levels. The pearl mouse could serve as a model for uterine hypoplasia, a common problem in female infertility.

Jing|Renwei|R| Kong|Yu|Y| Han|Gang|G| Zhang|Jingye|J| Li|Kailin|K| Dong|Xuan|X| Yan|Jie|J| Zhang|Haiqing|H| Han|Jia|J| Feng|Lijun|L|

D033966:Adaptor Protein Complex beta Subunits

Uterine hypoplasia
Pearl mouse
Uterine endometrium


Sensor Based on Molecularly Imprinted Polymer Membranes and Smartphone for Detection of Fusarium Contamination in Cereals.

Abstract: The combination of the generic mobile technology and inherent stability, versatility and cost-effectiveness of the synthetic receptors allows producing optical sensors for potentially any analyte of interest, and, therefore, to qualify as a platform technology for a fast routine analysis of a large number of contaminated samples. To support this statement, we present here a novel miniature sensor based on a combination of molecularly imprinted polymer (MIP) membranes and a smartphone, which could be used for the point-of-care detection of an important food contaminant, oestrogen-like toxin zearalenone associated with Fusarium contamination of cereals. The detection is based on registration of natural fluorescence of zearalenone using a digital smartphone camera after it binds to the sensor recognition element. The recorded image is further processed using a mobile application. It shows here a first example of the zearalenone-specific MIP membranes synthesised in situ using "dummy template"-based approach with cyclododecyl 2, 4-dihydroxybenzoate as the template and 1-allylpiperazine as a functional monomer. The novel smartphone sensor system based on optimized MIP membranes provides zearalenone detection in cereal samples within the range of 1-10 µg mL-1 demonstrating a detection limit of 1 µg mL-1 in a direct sensing mode. In order to reach the level of sensitivity required for practical application, a competitive sensing mode is also developed. It is based on application of a highly-fluorescent structural analogue of zearalenone (2-[(pyrene-l-carbonyl) amino]ethyl 2,4-dihydroxybenzoate) which is capable to compete with the target mycotoxin for the binding to zearalenone-selective sites in the membrane's structure. The competitive mode increases 100 times the sensor's sensitivity and allows detecting zearalenone at 10 ng mL-1. The linear dynamic range in this case comprised 10-100 ng mL-1. The sensor system is tested and found effective for zearalenone detection in maize, wheat and rye flour samples both spiked and naturally contaminated. The developed MIP membrane-based smartphone sensor system is an example of a novel, inexpensive tool for food quality analysis, which is portable and can be used for the "field" measurements and easily translated into the practice.

molecularly imprinted polymer membranes
zearalenone
fluorescence
mycotoxins
biosensors
smartphone-based sensors


COVID-19 related fear and mental health in Indian sample: The buffering effect of support system.

Abstract: The scientific world witnessed a surge of researches, from all corners of the world, regarding the humanitarian crisis precipitated by COVID-19 pandemic, more specifically its impact on people's mental health. However, researchers exploring the association between COVID-19 related fear and mental health are yet to understand the conditions through which potential benefits may occur. Many factors could buffer the effects of COVID-19 related fear on mental health; support system is probably the predominant one. Thus, the present study examined the moderating effects of support system in the association between COVID-19 related fear and mental health outcomes - somatic symptoms, generalized anxiety disorder (GAD), and depression. Using a web-based cross-sectional survey, we collected data from 163 volunteers assessed with demographic information, COVID-19 related fear, support system, and mental health outcomes. Hierarchical multiple regression analysis and simple effect tests revealed that high levels of support from family, friends, and significant others might buffer/lessen the psychological sequelae (e.g., somatic symptoms, anxiety, and depression during public health emergencies, such as COVID-19 pandemic. Given the potential for negative mental health outcomes following pandemics, such as COVID-19, efforts to enhance peoples' support system may be especially important.

Covid-19 related fear
Support system
Somatic symptoms
Anxiety
Depression


Structurally Constrained Insulin Analogs by Directed Stepwise Crosslinking.

Abstract:
BACKGROUND
Research has been directed at the optimization of insulin for medicinal purposes. An insulin analog that could be reversibly activated might provide more precise pharmacokinetic control and broaden the inherent therapeutic index of the hormone. The prospect of using intramolecular structural constraint to reversibly inactive insulin might constitute the first step to achieving such an optimized analog. Chemically crosslinked insulin analogs have been reported where two amines are covalently linked by reaction with symmetrical bifunctional active esters. There is little selectivity in this synthetic approach to molecular constraint with multiple derivatives being formed.

OBJECTIVE
To systematically evaluate the synthesis of covalently crosslinked insulin analogs by asymmetric methods and the biological consequences.

METHOD
We report synthesis of amine crosslinked insulin analogs via a two-step procedure. The stepwise approach was initiated by amide bond formation and followed by second site alkylation to produce site-specific, cross-linked insulin analogs.

RESULTS
A set of unique insulin analogs crosslinked at the two of the three native amines were synthesized. They were chemical characterized and assessed by in vitro bioanalysis to result in a significant and reasonably consistent reduction in biological potency.

CONCLUSION
We achieved an unambiguous two-step synthesis of several crosslinked insulin analogs differing in location of the chemical tether. Bioanalysis demonstrated the ability of the molecular constraint to reduce bioactivity. The results set the stage for in vivo assessment of whether such a reduction in potency can be used pharmacologically to establish a constrained hormone upon which reversible tethering might be subsequently introduced.

Zhang|Fa|F|
Mayer|John P|JP|
Gelfanov|Vasily|V|
Liu|Fa|F|
DiMarchi|Richard D|RD|

Insulin analogs
amide bond
biological potency
bioactivity
peptide hormone
reversible tethering.


Identification of candidate biomarkers associated with apoptosis in melanosis coli: GNG5, LPAR3, MAPK8, and PSMC6.

Abstract: Purpose: Melanosis coli (MC) is a disorder of pigmentation of the wall of the colon, often identified at the time of colonoscopy. The aim of the present study is to identify candidate biomarkers for MC. Methods: The transcriptome data for MC (GSE78933) with five MC tissues and five corresponding normal tissues is obtained from the NCBI Gene Expression Omnibus (GEO) database. R/Bioconductor package limma was used to screen differently expressed genes (DEGs). ClueGO of cytoscape was applied for Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Based on STRING V10 database, protein-protein interaction (PPI) network was constructed. The pathological tissue and normal tissue from 23 MC patients and 23 controls were collected, respectively. The relative expression of hub nodes was detected by qRT-PCR and Western blot. For regulating the expression of these genes, overexpression vector was constructed or siRNA transfection was used. Finally, apoptosis was detected by flow cytometry. Results: Total 1342 DEGs were screened, including 786 up-regulated and 556 down-regulated genes. These genes were mainly enriched in stimulatory C-type lectin receptor signaling pathway, polysaccharide biosynthetic process, intracellular, and oxidative phosphorylation. PPI network was then constructed with 426 DEGs and 895 interactions. Thereinto, G-protein subunit γ 5 (GNG5), lysophosphatidic acid receptor 3 (LPAR3), mitogen-activated protein kinase 8 (MAPK8), NHP2L1, proteasome 26S subunit, ATPase 6 (PSMC6), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit β (PIK3CB) were hub nodes with higher degree. RT-PCR and Western blot results showed that GNG5, LPAR3, MAPK8, and PSMC6 were differently expressed with significance. The expression of these screened genes is also related with cell apoptosis. Conclusion: GNG5, LPAR3, MAPK8, and PSMC6 might be candidate biomarkers associated with apoptosis in MC.

D000074183:ATPases Associated with Diverse Cellular Activities

D044388:GTP-Binding Protein gamma Subunits

D048055:Mitogen-Activated Protein Kinase 8

biomarkers
Melanosis coli
differently express
cell apoptosis
protein-protein interaction network


The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa.

Abstract: The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent.

Benke|Amalia|A|
Williams|Alford Joseph|AJ|
MacNeil|Adam|A|

polio data Immunization surveillance workforce


Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal areas, Pakistan: evaluation for human and ecological risk assessment.

Abstract: Potentially toxic elements (PTEs) contaminations in the soil ecosystem are considered as extremely hazardous due to toxicity, persistence and bioaccumulative nature. Therefore, this study was aimed to summarize the results of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan. Results were evaluated for the pollution quantification factors, including contamination factor (CF), pollution load index (PLI), ecological risk index (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35) values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations were used to calculate the human exposure for the risk assessment, including chronic or non-carcinogenic risks such as the hazard quotient (HQ) and carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI, HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the mining activities, weathering and erosion of mafic and ultramafic bedrocks hosting ophiolites. This study strongly recommends that best control measures need to be taken for soil PTEs with the intent to alleviate any continuing potential threat to the human health, property and environment, which otherwise could enter ecosystem and ultimately the living beings. Further studies are recommended to combat the soil PTEs concentrations and toxicity in the Tribal areas for a best picture of understanding the element effects on human, and environment can be achieved that will lead to a sustainable ecological harmony.

Saddique|Umar|U|
Muhammad|Said|S|
Tariq|Mohsin|M|
Zhang|Hua|H|
Arif|Mohammad|M|
Jadoon|Ishtiaq A K|IAK|
Khattak|Nimat Ullah|NU|

Ecological risk assessment
Human health risk assessment
Ophiolites
Mining, mafic and ultramafic rocks


The predicting roles of carcinoembryonic antigen and its underlying mechanism in the progression of coronavirus disease 2019.

Abstract:
BACKGROUND
The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known.

OBJECTIVE
The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism.

METHODS
The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively.

RESULTS
In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.020). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication.

CONCLUSION
This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and type II pneumocyte.

Huang|Runzhi|R| Meng|Tong|T| Zha|Qiongfang|Q| Cheng|Kebin|K| Zhou|Xin|X| Zheng|Junhua|J| Zhang|Dingyu|D| Liu|Ruilin|R|0000-0001-5498-9131

Carcinoembryonic antigen-related cell adhesion molecules


Comprehensive analysis of machine learning models for prediction of sub-clinical mastitis: Deep Learning and Gradient-Boosted Trees outperform other models.

Abstract: Sub-clinical bovine mastitis decreases milk quality and production. Moreover, sub-clinical mastitis leads to the use of antibiotics with consequent increased risk of the emergence of antibiotic-resistant bacteria. Therefore, early detection of infected cows is of great importance. The Somatic Cell Count (SCC) day-test used for mastitis surveillance, gives data that fluctuate widely between days, creating questions about its reliability and early prediction power. The recent identification of risk parameters of sub-clinical mastitis based on milking parameters by machine learning models is emerging as a promising new tool to enhance early prediction of mastitis occurrence. To develop the optimal approach for early sub-clinical mastitis prediction, we implemented 2 steps: (1) Finding the best statistical models to accurately link patterns of risk factors to sub-clinical mastitis, and (2) Extending this application from the farms tested to new farms (method generalization). Herein, we applied various machine learning-based prediction systems on a big milking dataset to uncover the best predictive models of sub-clinical mastitis. Data from 364,249 milking instances were collected by an electronic automated in-line monitoring system where milk volume, lactose concentration, electrical conductivity (EC), protein concentration, peak flow and milking time for each sample were measured. To provide a platform for the application of the models developed to other farms, the Z transformation approach was employed. Following this, various prediction systems [Deep Learning (DL), Naïve Bayes, Generalized Liner Model, Logistic Regression, Decision Tree, Gradient-Boosted Tree (GBT) and Random Forest] were applied to the non-transformed milking dataset and to a Z-standardized dataset. ROC (Receiver Operating Characteristics Curve), AUC (Area Under The Curve), and high accuracy demonstrated the high sensitivity of GBT and DL in detecting sub-clinical mastitis. GBT was the most accurate model (accuracy of 84.9%) in prediction of sub-clinical bovine mastitis. These data demonstrate how these models could be applied for prediction of sub-clinical mastitis in multiple bovine herds regardless of the size and sampling techniques.

Ebrahimi|Mansour|M|
Mohammadi-Dehcheshmeh|Manijeh|M|
Ebrahimie|Esmaeil|E|
Petrovski|Kiro R|KR|


Associations Between Nicotine Knowledge and Smoking Cessation Behaviors among U.S. Adults Who Smoke.

Abstract:
INTRODUCTION
Misperceptions about nicotine's contribution to smoking-related health harms could complicate efforts to reduce the public health burden of smoking. Study goals were to describe nicotine knowledge among adults who smoke and investigate whether misperceiving nicotine as a source of health harm was associated with beneficial health behaviors, or lower uptake of using less harmful sources of nicotine to support smoking cessation attempts.

METHOD
This study used longitudinal data from 9,140 adults who participated in four waves of the Population Assessment of Tobacco and Health Study and were current smokers during the first wave. Logistic regressions estimated odds ratios for correct responses across six aspects of nicotine knowledge assessed in Wave 4. Longitudinal models estimated associations between misperceptions and cigarette consumption, and odds of making a quit attempt; self-reported cessation; e-cigarette use; and use of NRT or e-cigarettes to support quit attempts.

RESULTS
Participants who were non-White, older, and had lower educational attainment or income tended to be least knowledgeable about nicotine. Misperceiving nicotine as harmful to health was associated with increased odds of quit attempts (AOR: 1.12, 95% CI: 1.03, 1.23), lower odds of cessation success (AOR: 0.84, 95% CI: 0.73, 0.98) and e-cigarette use (AOR: 0.79, 95% CI: 0.72, 0.86), and lower odds of using NRT (AOR: 0.84, 95% CI: 0.71, 0.99) or e-cigarettes to support quit attempts (AOR: 0.59, 95% CI: 0.49, 0.71).

CONCLUSION
Harm reduction efforts may be impeded by misperceptions about nicotine. Further work should evaluate the effects of correcting such misperceptions through public education.

IMPLICATIONS
This study provides longitudinal evidence that among adult smokers, misperceiving nicotine as a primary cause of smoking-related diseases may be associated with reduced cessation success and lower likelihood of using less harmful nicotine products. These misperceptions may therefore impede efforts to encourage smokers ready to quit to use evidence-based cessation support such as nicotine replacement during quit attempts and limit the success of policies designed to shift smokers to less harmful sources of nicotine. Further work should evaluate the longitudinal effects of correcting nicotine misperceptions through public education targeted toward adults who smoke.

Snell|L M|LM|
Colby|S M|SM|
DeAtley|T|T|
Cassidy|R|R|
Tidey|J W|JW|


Harnessing the power of theta: natural manipulations of cognitive performance during hippocampal theta-contingent eyeblink conditioning.

Abstract: Neurobiological oscillations are regarded as essential to normal information processing, including coordination and timing of cells and assemblies within structures as well as in long feedback loops of distributed neural systems. The hippocampal theta rhythm is a 3-12 Hz oscillatory potential observed during cognitive processes ranging from spatial navigation to associative learning. The lower range, 3-7 Hz, can occur during immobility and depends upon the integrity of cholinergic forebrain systems. Several studies have shown that the amount of pre-training theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning. Our lab has used a brain-computer interface (BCI) that delivers eyeblink conditioning trials contingent upon the explicit presence or absence of hippocampal theta. A behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to four-fold increase in learning speed. This behavioral effect is accompanied by enhanced amplitude and synchrony of hippocampal local field potential (LFP)s, multi-unit excitation, and single-unit response patterns that depend on theta state. Additionally, training in the presence of hippocampal theta has led to increases in the salience of tone-induced unit firing patterns in the medial prefrontal cortex, followed by persistent multi-unit activity during the trace interval. In cerebellum, rhythmicity and precise synchrony of stimulus time-locked LFPs with those of hippocampus occur preferentially under the theta condition. Here we review these findings, integrate them into current models of hippocampal-dependent learning and suggest how improvement in our understanding of neurobiological oscillations is critical for theories of medial temporal lobe processes underlying intact and pathological learning.

Hoffmann|Loren C|LC|
Cicchese|Joseph J|JJ|
Berry|Stephen D|SD|

theta
neurobiological oscillations
brain-computer interface
local field potential
hippocampus
cognitive enhancement
eyeblink classical conditioning


Development and validation of a liquid chromatography-tandem mass spectrometry analytical method for the therapeutic drug monitoring of eight novel anticancer drugs.

Abstract: To support therapeutic drug monitoring of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at -20°C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile. An equal amount of 10 mm NH4 CO3 was added to the supernatant to yield the final extract. A 2 μL aliquot of this extract was injected onto a C18 -column, gradient elution was applied and triple-quadrupole mass spectrometry in positive-ion mode was used for detection. All results were within the acceptance criteria of the latest US Food and Drug Administration guidance and European Medicines Agency guidelines on method validation, except for the carry-over of ceritinib and crizotinib. These were corrected for by the injection order of samples. Additional stability tests were carried out for axitinib and dabrafenib in relation to their reported photostability. In conclusion, the described method to simultaneously quantify the eight selected anticancer drugs in human plasma was successfully validated and applied for therapeutic drug monitoring in cancer patients treated with these drugs.

D000970:Antineoplastic Agents
D002853:Chromatography, Liquid
D016903:Drug Monitoring
D006801:Humans
D057230:Limit of Detection
D016014:Linear Models
D015203:Reproducibility of Results
D053719:Tandem Mass Spectrometry

validation
therapeutic drug monitoring
anticancer drugs
LC-MS/MS
clinical application


Improvement of lung ischemia-reperfusion injury by inhibition of microRNA-155 via reductions in neuroinflammation and oxidative stress of vagal afferent nerve.

Abstract: Lung ischemia-reperfusion injury (LIRI) is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine the effects of inhibiting microRNA-155 on the levels of proinflammatory cytokines and products of oxidative stress in the pulmonary vagal afferent nerves and the commissural nucleus of the solitary tract (cNTS) after LIRI. A rat model of LIRI was used. ELISA method was employed to examine proinflammatory cytokines, namely, IL-1β, IL-6 and TNF-α; and key biomarkers of oxidative stress, 8-isoprostaglandin F2α (8-iso PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). In results, in the process of LIRI, the levels of microRNA-155 were amplified in the vagal afferent nerves and cNTS, and this was accompanied with increases of IL-1β, IL-6 and TNF-α; and 8-iso PGF2α and 8-OHdG. Application of microRNA-155 inhibitor, but not its scramble, attenuated the elevation of proinflammatory cytokines and amplification of 8-iso PGF2α and 8-OHdG in those nerve tissues. In conclusion, we observed the abnormalities in the pulmonary afferent pathways at the levels of the peripheral nerves and brainstem, which is likely to affect respiratory functions as LIRI occurs. Our data suggest that blocking microRNA-155 signal pathways plays a beneficial role in regulating LIRI via inhibiting responses of neuroinflammation and oxidative stress signal pathways to LIRI.

Zhou|Yan|Y| Zhang|Lianjie|L| Guan|Jingjing|J| Yin|Xin|X|

neuroinflammation
oxidative stress
brainstem
lung ischemia
miRNA-155
vagal nerves


Impaired Femoral Vascular Compliance and Endothelial Dysfunction in 30 Healthy Male Soccer Players: Competitive Sports and Local Detrimental Effects.

Abstract:
BACKGROUND
Despite beneficial effects of physical activity on cardiovascular risk, discordant data on elite athletes (high atherosclerotic damage in activity comprising strenuous exertion) and retired sportsmen are reported in the literature.

HYPOTHESIS
We hypothesize that long-lasting daily physical activity could affect the morphology and function of the carotid and femoral vessel walls differently, as assessed in elite male athletes aged 20 to 30 years compared with age- and sex-matched healthy controls.

STUDY DESIGN
Retrospective case-control study.

LEVEL OF EVIDENCE
Level 3.

METHODS
Sixty male subjects (30 athletes and 30 controls) underwent medical examination for ankle brachial index, augmentation index (AIX) and AIX corrected for heart rate (AIXr), peripheral arterial tonometry (PAT), and intima media thickness and pulse wave velocity assay at common carotid (carotid-intima media thickness [c-IMT], carotid-pulse wave velocity [c-PWv]) and femoral arteries (femoral-intima media thickness [f-IMT], femoral-pulse wave velocity [f-PWv]) assessed by ultrasonography using Doppler ultrasound.

RESULTS
Athletes showed a significantly lower heart rate (HR) at rest and a better lipid profile than controls. In athletes, c-PWv (5.87 ± 0.80 vs 6.62 ± 1.02 m/s, P = 0.001) and f-PWv (8.96 ± 1.29 vs 7.89 ± 1.39, P = 0.002) were, respectively, significantly lower and higher than values found in controls; accordingly, carotid AIX (4.03 ± 6.21 vs 7.81 ± 5.21, P = 0.003) and femoral AIX (8.56 ± 10.21 vs 6.09 ± 7.95, P = 0.042) were lower and higher than control values, even after correction for heart rate (P = 0.03). On the other hand, IMT values were significantly higher in controls than in athletes (c-IMT, P < 0.0001; f-IMT, P < 0.0001). A positive significant correlation between HR and c-IMT and f-IMT (r = 0.527, P < 0.001 and r = 0.539, P < 0.0001, respectively) and between HR and c-PWv (r = 0.410, P = 0.01) was found when controls and athletes were considered as a whole group. Soccer players showed lower PAT values in comparison with controls (P = 0.002).

CONCLUSION
Elite sports positively affect c-IMT, f-IMT, and carotid PWv and AIX but not femoral PWv, AIX, AIXr, or PAT.

CLINICAL RELEVANCE
Physical activity affects vascular beds in elite athletes differentially, depending on the rate of superior or inferior limb involvement in different sports. In soccer players, physical activity has a protective effect on carotid and femoral vessel walls but worsens femoral arterial and endothelial function. These findings highlight how different results can be shown on carotid and femoral districts, when these vascular districts are differently stressed during sport activity.

Cioni|Gabriele|G|
Berni|Andrea|A|
Gensini|Gian Franco|GF|
Abbate|Rosanna|R|
Boddi|Maria|M|

peripheral arterial tonometry
intima media thickness
arterial stiffness


Evaluation of the antioxidant and melanogenesis inhibitory properties of pracparatum mungo (lu-do huang).

Abstract: Pracparatum mungo (Lu-Do Huang) is a traditional Chinese functional medicine made from the natural fermentation of mung bean (Lǜ Dòu) mixed with other Chinese medicines. It has been recognized as having liver protecting and detoxifying effects. As mung beans have been verified to possess anti-inflammatory, antioxidant, antipyretic, and whitening actions, the present research utilized the in vitro, ex vivo, and in vivo experimental models to investigate the antioxidant and melanin inhibiting effects of P. mungo on the skin. The in vitro experiment revealed that P. mungo methanol extract (PMME) and P. mungo ethanol extract (PMEE) possess the capacity to clear α,α-diphenyl-2-picrylhydrazyl (DPPH) radicals and inhibit tyrosinase activity. The ex vivo experiment indicated that PMEE can promote the growth of MDCK cells and increase the enzymatic activities of superoxide dismutase (SOD) and catalase in MDCK cells. On the other hand, PMME and PMEE can suppress the proliferation of A375 cells, and PMEE can reduce the enzymatic activities of SOD and catalase in A375 cells. The in vivo results showed that P. mungo can enhance the enzymatic performance of SOD, Catalase, and glutathione peroxidase (GPx) in the liver. The results also showed that P. mungo has antioxidant characteristics and can inhibit tyrosinase activity, thereby promoting the growth of skin tissues and suppressing the proliferation of A375 cells, and thus enhancing the effects that the antioxidant enzymatic performance has on the liver. These results can be applied in the development of tyrosinase inhibitors or antioxidants used for the inhibition of melanin biosynthesis or for auto-oxidation in further industrial applications, particularly those relating to functional food or cosmetic compositions.

Kao|Yu-Yu|YY| Chuang|Tien-Fu|TF| Chao|Shiou-Huei|SH| Yang|Jo-Hsuan|JH| Lin|Yu-Chuan|YC| Huang|Hui-Yu|HY|

Antioxidant
Pracparatum mungo
Tyrosinase inhibitor
Anti-melanogenesis


Validation of Thermal Lethality against Salmonella enterica in Poultry Offal during Rendering.

Abstract: Recent outbreaks of human disease following contact with companion animal foods cross-contaminated with enteric pathogens, such as Salmonella enterica, have resulted in increased concern regarding the microbiological safety of animal foods. Additionally, the U.S. Food and Drug Administration Food Safety Modernization Act and its implementing rules have stipulated the implementation of current good manufacturing practices and food safety preventive controls for livestock and companion animal foods. Animal foods and feeds are sometimes formulated to include thermally rendered animal by-product meals. The objective of this research was to determine the thermal inactivation of S. enterica in poultry offal during rendering at differing temperatures. Raw poultry offal was obtained from a commercial renderer and inoculated with a mixture of Salmonella serovars Senftenberg, Enteritidis, and Gallinarum (an avian pathogen) prior to being subjected to heating at 150, 155, or 160°F (65.5, 68.3, or 71.1°C) for up to 15 min. Following heat application, surviving Salmonella bacteria were enumerated. Mean D-values for the Salmonella cocktail at 150, 155, and 160°F were 0.254 ± 0.045, 0.172 ± 0.012, and 0.086 ± 0.004 min, respectively, indicative of increasing susceptibility to increased application of heat during processing. The mean thermal process constant (z-value) was 21.948 ± 3.87°F. Results indicate that a 7.0-log-cycle inactivation of Salmonella may be obtained from the cumulative lethality encountered during the heating come-up period and subsequent rendering of raw poultry offal at temperatures not less than 150°F. Current poultry rendering procedures are anticipated to be effective for achieving necessary pathogen control when completed under sanitary conditions.

Jones-Ibarra|Amie-Marie|AM|
Acuff|Gary R|GR|
Alvarado|Christine Z|CZ|
Taylor|T Matthew|TM|

Poultry offal
Rendering
Thermal processing
Animal food safety
Pet food
Salmonella lethality


Human tularemia in Italy. Is it a re-emerging disease?

Abstract: Tularemia is a contagious infectious disease due to Francisiella tularensis that can cause serious clinical manifestations and significant mortality if untreated. Although the frequency and significance of the disease has diminished over the last decades in Central Europe, over the past few years, there is new evidence suggesting that tularemia has re-emerged worldwide. To know the real epidemiology of the disease is at the root of correct control measures. In order to evaluate whether tularemia is re-emerging in Italy, data on mortality and morbidity (obtained by the National Institute of Statistics; ISTAT), Italian cases described in the scientific literature and data concerning hospitalizations for tularemia (obtained by the National Hospital Discharge Database) were analysed. From 1979 to 2010, ISTAT reported 474 cases and no deaths. The overall number of cases obtained from the literature review was at least 31% higher than that reported by ISTAT. Moreover, the number of cases reported by ISTAT was 3·5 times smaller than hospitalized cases. In Italy tularemia is sporadic, rarely endemic and self-limiting; but, although the trend of reported tularemia does not support the hypothesis of a re-emerging disease, the study demonstrates a wide underreporting of the disease. The real frequency of the disease should be carefully investigated and taken into account in order to implement specific prevention measures.

D'Alessandro|D|D| Napoli|C|C| Nusca|A|A| Bella|A|A| Funari|E|E|

tularemia
Italy
epidemiology
Compulsory reporting
discharge forms


Cerebrospinal Fluid Rhinorrhea and Subsequent Bacterial Meningitis due to an Atypical Clival Fracture.

Abstract: Cases of cerebrospinal fluid (CSF) rhinorrhea due to clival fracture are rare. We present a case of bacterial meningitis with CSF rhinorrhea after a clival fracture. Heavily T2-weighted images showed a bone flap in the thinned clivus and fluid collection in the sphenoid sinus. CSF rhinorrhea developed at 1 month after mild trauma. The fracture may have been caused by the trauma and/or by the pressure gradient between the intracranial CSF space and the sphenoid sinus. A detailed history to identify trauma and an examination to detect bone defects in the skull base are necessary when patients present with bacterial meningitis and persistent rhinorrhea.

cerebrospinal fluid
rhinorrhea
bacterial meningitis
clival fracture


Differential Ultra-Wideband Microwave Imaging: Principle Application Challenges.

Abstract: Wideband microwave imaging is of interest wherever optical opaque scenarios need to be analyzed, as these waves can penetrate biological tissues, many building materials, or industrial materials. One of the challenges of microwave imaging is the computation of the image from the measurement data because of the need to solve extensive inverse scattering problems due to the sometimes complicated wave propagation. The inversion problem simplifies if only spatially limited objects—point objects, in the simplest case—with temporally variable scattering properties are of interest. Differential imaging uses this time variance by observing the scenario under test over a certain time interval. Such problems exist in medical diagnostics, in the search for surviving earthquake victims, monitoring of the vitality of persons, detection of wood pests, control of industrial processes, and much more. This paper gives an overview of imaging methods for point-like targets and discusses the impact of target variations onto the radar data. Because the target variations are very weak in many applications, a major issue of differential imaging concerns the suppression of random effects by appropriate data processing and concepts of radar hardware. The paper introduces related methods and approaches, and some applications illustrate their performance.

Sachs|Jürgen|J| Ley|Sebastian|S| Just|Thomas|T| Chamaani|Somayyeh|S|0000-0003-2077-599X Helbig|Marko|M|

ultra-wideband
microwave imaging
M-sequence
medical imaging
pulse radar
target localization
through-wall radar
vital data capturing
wooden pest detection


The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients.

Abstract:
HYPOTHESIS
Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China.

MATERIALS AND METHODS
T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively.

RESULTS
There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls.

CONCLUSIONS
Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.


Malignant Pilomatricoma: A Report of Two Cases and Review of Literature.

Abstract: Malignant pilomatricoma is an extremely rare tumour arising from the hair follicle. About 80 known cases are reported in literature till date. Presented herewith are two cases of malignant pilomatricoma, occurring in young female patients, each with a different clinical presentation and outcome. It is important to be aware of this entity as malignant pilomatricoma, though, initially locally aggressive, can recur if incompletely excised and also can metastasize to lungs, bones and lymph nodes.

Flynn|Anita|A|
Agastyaraju|Anuradha Durga|AD|
Sunitha|N|N|
Harrison|Aradhana|A|

Metastases
Anaplasia
Basaloid cells
Tumours of epidermal appendages


Self-care and postoperative dressing management.

Abstract: As the increasing burden on healthcare costs continues to rise, posing clinical and financial challenges for all healthcare providers attempting to provide optimal, evidence-based wound care, the situation appears to be reaching the tipping point with regard to reduced resources, increasing patient groups with complex wounds and financial restraints. It is clearly time for action and new ways of working that include empowering patients and carers to take appropriate ownership within their personal wound-care journey. This observational evaluation explores 10 community-based patients presenting with postoperative acute surgical wounds; it examines and evaluates the patients' experience with regard to self-care satisfaction, Leukomed Control product satisfaction and actual traditional/personal costs incurred up to a 4-week period. The evaluation highlights not only an overall positive improvement within patient satisfaction and experience, alongside optimised wound progression and related cost savings, but also offers a valuable insight into the promotion and success of patients taking ownership of their wound-care journey.

Self-care
Acute post-surgical wounds
Cost-effectiveness
Optimised wound healing
Positive patient experience