Improved metabolic regulation is associated with retinoblastoma protein gene haploinsufficiency in mice.

Abstract: Retinoblastoma protein (pRb) is involved in the control of energy metabolism, and its inactivation protects mice against high-fat diet-induced diabesity. Here, we tested the hypothesis that partial deficiency in the Rb gene could confer metabolic advantages in front of acute challenges to metabolism and as mice age on a regular diet. Rb haploinsufficient (Rb(+/-)) mice and wild-type (WT) littermates were studied from weaning and characterized at 1.5-2.5 mo of age (young adults) and 6-7.5 mo of age (mature adults). Whereas no differences in body weight or composition were observed at young age, mature adult Rb(+/-) mice were leaner than WT littermates, displaying 36% reduced body fat content. At both ages studied, Rb(+/-) mice displayed improved blood lipids, enhanced sensitivity to the blood glucose-lowering effect of insulin and to the anorectic effect of leptin, and a reduced respiratory exchange ratio, indicative of an increased use of fatty acids as a fuel. Insulin sensitivity and oral fat tolerance were better maintained with age in the Rb(+/-) than the WT mice. Mature adult Rb(+/-) mice displayed gene expression changes consistent with increased fatty acid oxidation in white adipose tissue and skeletal muscle and paramount signs of browning in the inguinal white adipose tissue. In conclusion, Rb haploinsufficiency provides metabolic advantages in front of acute metabolic stressors and ameliorates body fat gain and metabolic impairments that normally accompany transition from young to mature adult age.

Petrov|Petar D|PD|
Ribot|Joan|J|
Palou|Andreu|A|
Bonet|M Luisa|ML|

retinoblastoma
insulin sensitivity
fat tolerance
browning


Searching the H. pylori; serology & PCR in children with adenoid hypertrophy and rhino sinusitis: a cross sectional study, Tehran, Iran.

Abstract:
OBJECTIVE
Searching the H. pylori -DNAs in adenoid and IgA, IgG antibodies in serum of children.

METHODS
A cross- sectional study had done upon 53 children (Mean age 8 ±1.9 years) with adenoid surgery in ENT and Pediatric Department of Rasul Akram Hospital (2008-2010). Of 53 cases with adenoid surgery, 40 cases had rhino sinusitis (in sinus CT scan). The resected adenoid tissues (n=40) centrifuged and homogenized and its DNAs extracted and searched for H. pylori- DNAs by qualitative PCR. Serum H. pylori antibodies (IgG &IgA ELISA) calculated quantitatively. Chi square values (p < 0.05) calculated for all categorical variables. The agreement between serologic test and PCR was assessed by the calculation of kappa statistic.

RESULTS
Positive PCR for H. pylori detected in 15%of cases; regardless of sex and age of cases. Positive IgA: 17.5% (7/40) and IgG: 20% (8/40) respectively. All cases with positive H. pylori- IgG were female; p=0.003 and meaningful differences in mean age of cases observed for positive IgA (p=0.001) and IgG (p=0.01). Poor agreement observed between positive PCR and serum IgG&IgA (Fisher's Exact test=0.3; 0.5).

CONCLUSION
Positive PCR in adenoid tissue (15%) was very close to positive serum IgA (15%) but without any agreement for each case. The H. pylori infection may have a relative role at least in 15% of children with adenoid surgery. Chronic sinusitis and ear infection might be added to infected adenoid tissue as a reservoir for bacteria. The search by specific culture may elucidate better the role of H. pylori infections in both gastric and adenoid tissues. The decision for use of antibiotics to eradicate the H. pylori infection in recurrent or chronic adenotonsillar infections (with rhinosinusitis) before adenoid surgery needs Randomized Control Trial (RCT) studies. Drug of choice for eradication of H. pylori dependent to antibiotic sensitivity test in each country.

H. pylori
PCR
IgA
IgG
Adenoid surgery
Adenoid tissue


Educational attainment of children born to mothers with epilepsy.

Abstract:
OBJECTIVE
Small prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance.

METHODS
We used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects.

RESULTS
We identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (-12.7% less than the control group), mathematics (-12.1%), language (-10.4%) and in science (-12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by -20.7% less than the control group), mathematics (-21.9%), language (-19.3%) and science (-19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group.

CONCLUSIONS
In utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.

Lacey|Arron S|AS|
Pickrell|William Owen|WO|
Thomas|Rhys H|RH|0000-0003-2062-8623
Kerr|Mike P|MP|
White|Cathy P|CP|
Rees|Mark I|MI|

D011297:Prenatal Exposure Delayed Effects

educational attainment
epilepsy
antiepileptic drugs
case-control study
clinical decision support


The Standardised Mensendieck Test as a tool for evaluation of movement quality in patients with nonspecific chronic low back pain.

Abstract:
BACKGROUND AND AIMS
Nonspecific chronic low back pain is a multifactorial biopsychosocial health problem where accurate assessments of pain, function and movement are vital. There are few reliable and valid assessment tools evaluating movement quality, hence the aim was to investigate nonspecific chronic low back pain patients' movement patterns with the Standardised Mensendieck Test.

METHODS
Twenty patients (mean age=41, SD=9.02) with nonspecific chronic low back pain were examined with the Standardised Mensendieck Test whilst being videotaped and compared with 20 healthy controls. A physiotherapist, blinded to participant's group belonging, scored Standardised Mensendieck Test videos according to the standardised manual. Associations between movement quality, fear of movement and re(injury) i.e. kinesiophobia and pain intensity were also investigated.

RESULTS
Patients scored significantly poorer than the controls in all 5 Standardised Mensendieck Test domains (p<0.001). The biggest difference was observed with regard to movement pattern domain. In women we also found a difference in the respiration pattern domain.

CONCLUSIONS
The Standardised Mensendieck Test was able to detect significant differences in quality of movement between patients and healthy controls. These results indicate that the Standardised Mensendieck Test may be a valuable examination tool in assessment and treatment of nonspecific chronic low back pain patients. Further, longitudinal studies should investigate whether poor movement and respiration patterns are important factors in nonspecific chronic low back pain, e.g. as predictors and/or mediators of therapeutic effects.

Kaarbø|Mette Bøymo|MB|
Haugstad|Gro Killi|GK|
Stubhaug|Audun|A|
Wojniusz|Slawomir|S|

Standardised Mensendieck Test
movement quality
low back pain
kinesiophobia
respiration


Rates and determinants of incidence and clearance of cervical HPV genotypes among HIV-seropositive women in Pune, India.

Abstract:
BACKGROUND
Several studies in recent years have documented the genotype-specific prevalence of HPV infection and wide diversity and multiplicity of HPV genotypes among HIV-seropositive women. Yet, information on changes in HPV genotype-specific incidence and clearance rates over time, and their correlation with clinical or immunologic factors among HIV-seropositive women is scarce.

OBJECTIVES
We conducted a prospective study to investigate the incidence and clearance rates of cervical HPV genotypes among HIV-seropositive women in India and expand the evidence base in this area of research.

STUDY DESIGN
Cervical samples were collected from n=215 HIV-seropositive women in Pune, India who underwent two screening visits separated by a median of 11-months (interquartile range: 8-18 months). HPV genotypes were determined by Roche Linear Array HPV assay. Individual genotype-specific and carcinogenicity-grouping-specific HPV incidence and clearance rates were calculated and the associations between incidence/clearance and age and HIV-related metrics were explored.

RESULTS
Incidence and clearance rates for 'any HPV' and 'carcinogenic HPV' genotypes were 11.1 and 18.3, and 6.7 and 33.8, per 100 person-years, respectively. Incidence and clearance rates for HPV genotypes of alpha-9 species (HPV16, HPV31, HPV33, HPV35, HPV52 and HPV58) and alpha-7 species (HPV18, HPV39, HPV45, HPV59 and HPV68) were 5.8 and 2.04, and 32.1 and 53.5, per 100 person-years, respectively. Clearance of any HPV type was associated with increasing age of participants (odds ratio: 1.08, 95%CI: 1.004-1.17), although the association marginally lost its statistical significance when adjusted for CD4 counts and antiretroviral therapy status.

CONCLUSIONS
Genotype-specific clearance rates of HPV were higher than corresponding incidence rates. The suggestion of a positive associations of increasing age with HPV clearance points to the need for etiologic studies on age-related hormonal changes on clearance of cervical HPV infection.

Mane|Arati|A|
Sahasrabuddhe|Vikrant V|VV|
Nirmalkar|Amit|A|
Risbud|Arun R|AR|
Sahay|Seema|S|
Bhosale|Ramesh A|RA|
Vermund|Sten H|SH|
Mehendale|Sanjay M|SM|

Incidence
Clearance
HPV
Genotypes
HIV
Natural history


Quantifying colloid fate and transport through dense vegetation and soil systems using a particle-plugging tempered fractional-derivative model.

Abstract: Colloid contaminants are widely distributed in surface runoff from crop land and can be effectively removed by vegetative filter strips (VFS), whose quantification however proves difficult. Standard mechanism-based models contain many unknown parameters with intrinsic uncertainty, limiting their applicability and potential extension for other environmental conditions and colloid contaminant types. To remedy this limitation and capture the complex dynamics of colloids through the soil-vegetation system, this study proposes a parsimonious, particle-plugging tempered fractional advection-dispersion eq. (P-TFADE) with a few empirical parameters, which is built upon the promising fractional calculus engine. The P-TFADE model extends the promising tempered fractional derivative model by incorporating a plugging term, which is then proved to be able to capture both the plugging dynamics and tailing behavior of colloids under various hydrologic and geochemical conditions. Applications also show that the two critical parameters in the P-TFADE model, the time index (α) and plugging coefficient (Kp), can efficiently characterize the impact of the flowrate and ionic condition on transport of different sized colloids observed in our laboratory. In addition, the vegetation type determines the overall structure of the soil-vegetation system, whose impact on the colloid removal efficiency can be quantified by adding a parameter λ in the physical model. Therefore, the novel P-TFADE model can reduce the model uncertainty and help us further understand the nature of colloid dynamics through dense vegetation and soil systems.

Yu|Congrong|C| Wei|Song|S| Zhang|Yong|Y| Zheng|Yi|Y| Yu|Zhongbo|Z| Donahoe|Rona|R| Wei|Hui|H|

Soil-vegetation system
Tailing behavior
Removal efficiency
Colloid transport
Plugging process
Tempered fractional model


Profiling the Mismatch Tolerance of Argonaute 2 through Deep Sequencing of Sliced Polymorphic Viral RNAs.

Abstract: Low allelic and clonal variability among endogenous RNAi targets has focused mismatch tolerance studies to RNAi-active guide strands. However, the inherent genomic instability of RNA viruses such as hepatitis C virus (HCV) gives rise to quasi-species mutants within discrete clones: this facilitates mismatch tolerance studies from a target perspective. We recently quantified the slicing imprecision of Argonaute 2 using small interfering RNA (siRNA) analogs of the DNA-directed RNAi drug TT-034 and next-generation sequencing of 5' RNA ligase-mediated rapid amplification of cDNA ends (RACE-SEQ). Here, we present an open-source, customizable, and computationally light RACE-SEQ bioinformatic pipeline, describing adaptations that semiquantitatively report the impact of RNAi hybridization site mismatches from the target perspective. The analysis shows that Argonaute 2 has a substitution-specific, 3- to 5-log activity window between fully complementary targets and targets with mismatches across positions 10-11. It further focuses the endonucleotic Slicer imprecision around positions 13-17, demonstrating its dependence on guide strand central region complementarity, and potentiation by even a single mismatch. We further propose pharmacogenomics value in testing endogenous targets using recombinant replicon systems and RACE-SEQ to report the pharmacodynamics of sequence-specific oligonucleotide therapeutics against all possible polymorphisms in a population, in a minimally biased, patient-free manner.

Theotokis|Pantazis I|PI|
Usher|Louise|L|
Kortschak|Christopher K|CK|
Schwalbe|Ed|E|
Moschos|Sterghios A|SA|

RNAi
siRNA
RACE-SEQ
bioinformatics
oligonucleotides
SNP susceptibility
mechanism of action
personalized medicine
pharmacology
shRNA


Cerebral involvement in systemic vasculitides: Extracts from the guideline of the German neurological society.

Abstract: Cerebral vasculitis is a rare disorder but plays a major role in the differential diagnosis of stroke, encephalopathy and headache. This guideline was developed in order to support clinicians in the diagnosis and treatment of cerebral manifestations of systemic vasculitides and rheumatic diseases. It is based on a medline research and was developed in a modified Delphi process and approved by the involved societies. This article is an abridged and translated version of the guideline published in DGNeurologie: Berlit, P. & Krämer, M. DGNeurologie (2018) 1: 17. 10.1007/s42451-018-0001-y.

Eosinophilic granulomatosis with polyangiitis (EGPA)


Natural Parasitism in Fruit Fly (Diptera: Tephritidae) Populations in Disturbed Areas Adjacent to Commercial Mango Orchards in Chiapas and Veracruz, Mexico.

Abstract: To determine the natural parasitism in fruit fly populations in disturbed areas adjacent to commercial mango orchards in the states of Chiapas and Veracruz, Mexico, we recorded over one year the fruit fly-host associations, fly infestation, and parasitism rates in backyard orchards and patches of native vegetation. We also investigated the relationship between fruit size, level of larval infestation, and percent of parasitism, and attempted to determine the presence of superparasitism. The most recurrent species in trap catches was Anastrepha obliqua (Macquart), followed by Anastrepha ludens (Loew), in both study zones. The fruit infestation rates were higher in Chiapas than in Veracruz, with A. obliqua again being the most conspicuous species emerging from collected fruits. The diversity of parasitoids species attacking fruit fly larvae was greater in Chiapas, with a predominance of Doryctobracon areolatus (Szépligeti) in both sites, although the exotic Diachasmimorpha longicaudata (Ashmead) was well established in Chiapas. Fruit size was positively correlated with the number of larvae per fruit, but this relationship was not observed in the level of parasitism. The number of oviposition scars was not related to the number of immature parasitoids inside the pupa of D. areolatus emerging from plum fruits. Mass releases of Di. longicaudata seem not to affect the presence or prevalence of the native species. Our findings open new research scenarios on the role and impact of native parasitoid species attacking Anastrepha flies that can contribute to the development of sound strategies for using these species in projects for augmentative biological control.

Montoya|Pablo|P|
Ayala|Amanda|A|
López|Patricia|P|
Cancino|Jorge|J|
Cabrera|Héctor|H|
Cruz|Jassmin|J|
Martinez|Ana Mabel|AM|
Figueroa|Isaac|I|
Liedo|Pablo|P|

superparasitism
Anastrepha obliqua
Anastrepha ludens
fruit infestation
Doryctobracon areolatus


State of Art of Cancer Pharmacogenomics in Latin American Populations.

Abstract: Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations.

López-Cortés|Andrés|A|
Guerrero|Santiago|S|
Redal|María Ana|MA|
Alvarado|Angel Tito|AT|
Quiñones|Luis Abel|LA|

cancer
pharmacogenomics
Latin America
pharmacogenetics
precision medicine
single nucleotide polymorphism


Current Practices Regarding Perioperative Management of Patients With Fracture on Antiplatelet Therapy: A Survey of Orthopedic Surgeons.

Abstract:
OBJECTIVE
There continues to be controversy over whether operative delay is necessary for patients on antiplatelet therapy, particularly for elderly patients with hip fractures. This study sought to assess current clinical practices of orthopedic surgeons regarding perioperative management of these patients.

METHODS
A 12-question, Web-based survey was distributed to orthopedic surgeons via e-mail. Questions regarding timing of surgery assumed patients were on antiplatelet therapy and assessed attitudes toward emergent and nonemergent orthopedic cases as well as operative delay for specific closed fracture types. Responses were compared using unpaired, 2-tailed Student t tests for continuous variables and Pearson chi-square tests with odds ratios (ORs) and 95% confidence intervals (CIs) for categorical variables. Statistical significance was defined as a P value <.05.

RESULTS
Overall 67 orthopedic surgeons responded. Fifty-two percent (n = 35) of the respondents described their practice as academic. Thirty-nine percent (n = 25) of the surgeons indicated that no delay was acceptable for urgent but nonemergent surgery, and 78% (n = 50) reported no delay for emergent surgery was acceptable. Sixty-eight percent (n = 46) of respondents felt patients on antiplatelet therapy with closed hip fractures did not require operative delay. Surgeons who opted for surgical delay in hip fractures were more likely to delay surgery in other lower extremity fracture types (OR = 16.4, 95% CI 4.48-60.61, P < .001). Sixty-four percent (n = 41) of the surgeons indicated there was no protocol in place at their institution.

CONCLUSIONS
There continues to be wide variability among orthopedic surgeons with regard to management of patients with fracture on antiplatelet therapy. Over a quarter of surgeons continue to opt for surgical delay in patients with hip fracture. This survey highlights the need to formulate and better disseminate practice management guidelines for patients with fracture on antiplatelet therapy, particularly given the aging population in the United States.

Pean|Christian A|CA|
Goch|Abraham|A|
Christiano|Anthony|A|
Konda|Sanjit|S|
Egol|Kenneth|K|

antiplatelet therapy
orthopedics
operative delay
hip fracture
clopidogrel
fragility fractures
geriatric trauma


Inhibitor development after liver transplantation in congenital factor VII deficiency.

Abstract: Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.

See|W-S Q|WS|
Chang|K-O|KO|
Cheuk|D K-L|DK|
Leung|Y-Y R|YY|
Chan|G C-F|GC|
Chan|S-C|SC|
Ha|S-Y|SY|

D002675:Child, Preschool
D005167:Factor VII
D005168:Factor VII Deficiency
D005260:Female
D006801:Humans
D007223:Infant
D007231:Infant, Newborn
D020300:Intracranial Hemorrhages
D016031:Liver Transplantation
D011994:Recombinant Proteins

inhibitor
liver transplant
congenital Factor VII deficiency


Fatal pancreatic fistula after laparoscopic distal pancreatectomy for intraductal papillary mucinous carcinoma with pancreaticobiliary maljunction and sphincterotomized papilla: a case report.

Abstract:
BACKGROUND
Pancreatic juice is constantly activated by contaminated bile in patients with pancreaticobiliary maljunction (PBM). Here, we report a case of laparoscopic distal pancreatectomy for a patient with PBM and sphincterotomized papilla, resulting in fatal pancreatic fistula.

CASE PRESENTATION
A 79-year-old man was diagnosed with pancreatic intraductal papillary mucinous neoplasm and common bile duct stones. Endoscopic sphincterotomy was performed prior to surgery. The pancreatic duct was simultaneously visualized when the contrast agent was injected into the common bile duct. Sudden bleeding was observed from the abdominal drain on postoperative day (POD) 6. Emergent stent graft placement and coil embolization were performed for bleeding from the splenic artery. On POD 9, the drainage fluid changed to yellowish in color with bile contamination. For internal drainage of the digestive fluid, endoscopic retrograde biliary tube and pancreatic drainage tube were placed. On POD 24, second emergent coil embolization was performed for bleeding from the left gastric artery. On POD 25, open abdominal drainage was performed. On POD 32, third emergent coil embolization was performed for bleeding from the gastroduodenal artery. Subsequently, remnant pancreatic resection was performed. On POD 39, massive bleeding was again observed from the abdominal drain. Emergency arterial portography revealed bleeding in the right wall of the superior mesenteric vein. The patient died of hemorrhagic shock on the same day.

CONCLUSIONS
The extreme risk of severe pancreatic fistula after distal pancreatectomy should be considered in patients with PBM and sphincterotomized papilla. In this extraordinary situation, surgeons should promptly decide whether to resect the remnant pancreas to prevent losing the patient.

Fatal pancreatic fistula
Distal pancreatectomy
Pancreaticobiliary maljunction
Intraductal papillary mucinous neoplasm
Endoscopic sphincterotomy


Identification of transcription factors from NF-Y, NAC, and SPL families responding to osmotic stress in multiple tomato varieties.

Abstract: Identifying osmotic stress-responsive transcription factors (TFs) can facilitate discovery of master regulators mediating salt and/or drought tolerance. To date, few RNA-seq datasets for high resolution time course of salt or drought stress treatments are publicly available for certain crop species. However, such datasets may be available for other crops, and in combination with orthology analysis may be used to infer candidate osmotic stress regulators across distantly related species. Here, we demonstrate the utility of this approach for identification and validation of osmotic stress-responsive transcription factors in tomato. First, we developed physiologically calibrated salt and dehydration-responsive systems for tomato cultivars using real time measurements of transpiration rate and photosynthetic efficiency. Next, we identified differentially expressed TFs in rice using raw RNA-seq datasets for a publicly available salt stress time course. Putative salt stress-responsive TFs in tomato were then inferred based on their orthology with the transcription factors upregulated by salt in rice. Finally, using our osmotic stress system, we experimentally validated stress-responsive expression of predicted tomato candidates representing NUCLEAR FACTOR Y, SQUAMOSA PROMOTER BINDING, and NAC domain TF families. Quantification of transcript copy numbers confirmed that mRNAs encoding all three TFs were strongly upregulated not only by salt but also by drought stress. Induction by both salt and dehydration occurred in a temporal manner across diverse tomato cultivars, suggesting that the identified TFs may play important roles in regulating osmotic stress responses.

Filichkin|Sergei A|SA|
Ansariola|Mitra|M|
Fraser|Valerie N|VN|
Megraw|Molly|M|

D023081:CCAAT-Binding Factor
D018556:Crops, Agricultural
D055864:Droughts
D018551:Lycopersicon esculentum
D009997:Osmotic Pressure
D010940:Plant Proteins
D054712:Salinity
D012492:Salts
D013312:Stress, Physiological
D014157:Transcription Factors

Transcription factors
Drought stress
Tomato cultivars
Salt stress
Solanum lycopersicum


The patient's agenda: nurses' experience of learning and using guided self-determination.

Abstract:
OBJECTIVES
Health care has seen a shift towards person-centred care to encompass the entirety of a person's needs and preferences, but research is sparse on healthcare professionals learning and using person-centred care.

AIM
To investigate nurses' experiences of learning and using the person-centred method guided self-determination (GSD) in three different gynaecological settings and to determine whether, and potentially, how new tasks introduced by the GSD method influence their professional identity.

DESIGN
A qualitative interview study conducted between January 2019 and January 2020.

METHOD
We conducted 16 semi-structured interviews with nurses educated in using GSD. Applying inductive and deductive reasoning, we analysed the interviews using thematic analysis. The study was registered with the Danish Data Protection Agency (file no.: VD-2018-445, I-Suite no.: 6700).

RESULTS
The analysis generated three main themes with two subthemes each: (a) prerequisites and barriers to learning and using GSD in terms of personal factors and organisational and method-related factors; (b) new knowledge and understanding of illness with the subthemes expanded understanding of illness and a different relationship; and (c) nursing undergoing change with the subthemes, a new role and a professional self shaped through interaction with other professions.

CONCLUSIONS
Although other professionals may have either supported or challenged the use of GSD, most nurses indicated that it supplemented their professional role and identity as they gained new knowledge about person-centred challenges and felt more confident. When introducing GSD in nursing, the organisation must not only consider individual characteristics, multidisciplinary collaboration and communication but also plan individual education and supervision. This is necessary because all these factors affect how a new professional role is constructed and adopted, not to mention how it influences the nurses' perception of their professional identity and use of GSD. Establishing a helpful person-centred environment must also be considered.

guided self-determination
person-centred care
nursing role


What people share about the COVID-19 outbreak on Twitter? An exploratory analysis.

Abstract:
BACKGROUND
The recent outbreak of respiratory illness caused by COVID-19 in Wuhan, China, has received global attention as it has infected thousands of individuals there, and later it has also been reported from other countries internationally. This study aims at performing an exploratory study on Twitter to understand the information shared among the community regarding the COVID-19 outbreak.

METHODS
COVID-19 related tweets were collected from Twitter using keywords from 18 January to 25 January 2020. Top-ranking tweets were taken as samples and then categorised based on the content. Expressions or opinion tweets were analysed qualitatively to understand the mindset of the people regarding the outbreak. Theme wise reachability evaluation of the messages was also performed.

RESULTS
Based on the content of the tweets, five themes were evolved: (1) general information; (2) health information; (3) expressions; (4) humour and (5) others. 57.42% of messages are general information followed by expressive tweets (24.12%). Humorous messages were liked the most, whereas health information tweets were retweeted the maximum. Fear was the predominant emotion expressed in the messages.

CONCLUSION
The results of the study would be useful to focus on the dissemination of the right information and effective communication on Twitter related to health and outbreak management.


Quantifying adhesive thickness and adhesion parameters using higher-order SH guided waves.

Abstract: A method to quantify the interface shear stiffness, adhesive shear modulus and adhesive thickness in an aluminium-epoxy-aluminium joint is presented. Shear horizontal guided waves are considered to infer the properties. A numerical model that employs spring stiffness boundary conditions at the aluminium-epoxy interface was developed to generate dispersion curves. The sensitivity of the first four SH-like modes to epoxy thickness, interface shear stiffness, and adhesive shear modulus are analyzed. The dispersion analysis reveals that higher-order anti-symmetric modes are sensitive to all three parameters, whereas the symmetric modes are sensitive only to adhesive thickness. Hence to prevent false alarms that might arise while assessing the bond conditions, symmetric and anti-symmetric modes should be simultaneously generated. Periodic permanent magnet (PPM) electromagnetic acoustic transducers (EMATs) are used to generate and detect SH-like modes. Utilizing the constant wavelength property of PPM-EMATs, SH2-like and SH3-like modes are generated. Short-time Fourier transform (STFT) is used to separate the modes merged in the received time response. By overlaying the dispersion curves of SH2-like mode on STFT, the thickness of epoxy is quantified. The dispersion curves of SH3-like mode are generated using the measured thickness and overlaid on STFT to measure the interface shear stiffness and epoxy shear modulus. The proposed method is experimentally demonstrated on aluminium-epoxy-aluminium samples of different surface treatments. The study demonstrates a reliable nondestructive evaluation of adhesive bonds that reduces possible false alarms.

PPM-EMATs
Adhesive bonds
Bond stiffness
Interface weakness
SH-guided waves
Viscoelastic damping


Modeling and control approach to a distinctive quadrotor helicopter.

Abstract: The referenced quadrotor helicopter in this paper has a unique configuration. It is more complex than commonly used quadrotors because of its inaccurate parameters, unideal symmetrical structure and unknown nonlinear dynamics. A novel method was presented to handle its modeling and control problems in this paper, which adopts a MIMO RBF neural nets-based state-dependent ARX (RBF-ARX) model to represent its nonlinear dynamics, and then a MIMO RBF-ARX model-based global LQR controller is proposed to stabilize the quadrotor's attitude. By comparing with a physical model-based LQR controller and an ARX model-set-based gain scheduling LQR controller, superiority of the MIMO RBF-ARX model-based control approach was confirmed. This successful application verified the validity of the MIMO RBF-ARX modeling method to the quadrotor helicopter with complex nonlinearity.

Wu|Jun|J| Peng|Hui|H| Chen|Qing|Q| Peng|Xiaoyan|X|

Quadrotor helicopter
RBF-ARX model
ARX model
Nonlinear system
Physical model


Arsenic resistance genes of As-resistant purple nonsulfur bacteria isolated from As-contaminated sites for bioremediation application.

Abstract: This study aimed to identify arsenic resistant mechanisms in As-resistant purple nonsulfur bacteria (PNSB) by screening them for presence of As-resistance genes and related enzymes. Resistance to As(III) and As(V) of four As-resistant PNSB determined in terms of median inhibition concentration (IC50 values) were in the order of strains Rhodopseudomonas palustris C1 > R. palustris AB3 > Rubrivivax benzoatilyticus C31 > R. palustris L28 which corresponded to the presence of As-resistance genes in these bacteria. The strain C1 showed all As-marker genes; arsC, arsM, aioA, and acr3, while aioA was not detected in strain AB3. Strains C31 and L28 had only Arsenite-transporter gene, acr3. Translation of all these detected gene sequences of strain C1 to amino acid sequences showed that these proteins have vicinal cysteine; Cys126, Cys105, and Cys178 of Acr3, ArsC, AioA, respectively. Tertiary structure of proteins Acr3, ArsC, AioA, and ArsM showed strain C1 exhibits the high activities of arsenite oxidase and arsenate reductase enzymes that are encoded by aioA and arsC genes, respectively. Moreover, strain C1 with arsM gene produced volatile-methylated As-compounds; monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and arsenobetaine (AsB) in the presence of either As(III) or As(V). In conclusion, the strain C1 has great potential for its application in bioremediation of As-contaminated sites.

Nookongbut|Phitthaya|P| Kantachote|Duangporn|D| Krishnan|Kannan|K| Megharaj|Mallavarapu|M|

D015964:Gene Expression Regulation, Bacterial

purple nonsulfur bacteria
As-resistance genes
arsenite oxidase
arsenate reductase
As-methylation


Antioxidant properties of HDL.

Abstract: High-density lipoprotein (HDL) provides a pathway for the passage of lipid peroxides and lysophospholipids to the liver via hepatic scavenger receptors. Perhaps more importantly, HDL actually metabolizes lipid hydroperoxides preventing their accumulation on low-density lipoprotein (LDL), thus impeding its atherogenic structural modification. A number of candidates have been suggested to be responsible for HDL's antioxidant function, with paraoxonase-1 (PON1) perhaps the most prominent. Here we review the evidence for HDL anti-oxidative function and the potential contributions of apolipoproteins, lipid transfer proteins, paraoxonases and other enzymes associated with HDL.

Soran|Handrean|H|
Schofield|Jonathan D|JD|
Durrington|Paul N|PN|

high-density lipoprotein
apolipoprotein A1
glycated low-density lipoprotein
oxidized low-density lipoprotein
paraoxonase 1


Stress shielding in periprosthetic bone following a total knee replacement: Effects of implant material, design and alignment.

Abstract: Periprosthetic bone strain distributions in some of the typical cases of total knee replacement (TKR) were studied with regard to the selection of material, design and the alignments of tibial components to examine which conditions are more forgiving than the others to stress shielding post a TKR. Four tibial components with two implant designs (cruciate sacrificing and cruciate retaining) and material properties (metal-backed (MB) and all-polyethylene (AP)) were considered in a specimen-specific finite element tibia bone model loaded in a neutral position. The influence of tibial material and design on the periprosthetic bone strain response was investigated under the peak loads of walking and stair descending/ascending. Two of the models were also modified to examine the effect of selected implant malalignment conditions (7° posterior, 5° valgus and 5° varus) on stress shielding in the bone, where the medio-lateral load share ratios were adjusted accordingly. The predicted increases of bone density due to implantation for the selected cases studied were also presented. For the cases examined, the effect of stress shielding on the periprosthetic bone seems to be more significantly influenced by the implant material than by the implant geometry. Significant stress shielding is found in MB cases, as opposed to increase in bone density found in AP cases, particularly in the bones immediately beneath the baseplate. The effect of stress shielding is reduced somewhat for the MB components in the malaligned positions compared with the neutral case. In AP cases, the effect of stress shielding is mostly low except in the varus position, possibly due to off-loading of lateral condyle. Increases in bone density are found in both MB and AP cases for the malaligned conditions.

D019645:Arthroplasty, Replacement, Knee
D001696:Biomechanical Phenomena
D020342:Finite Element Analysis
D006801:Humans
D011474:Prosthesis Design
D013314:Stress, Mechanical
D013977:Tibia

Stress shielding
Periprosthetic
Total knee replacement
Tibial component
Finite element
Malalignment


Comparative Analysis of bla KPC Expression in Tn4401 Transposons and the Tn3-Tn4401 Chimera.

Abstract: Two basic structures that carry the bla KPC gene, the Tn4401 transposon and the Tn3-Tn4401 chimera, have been identified within and outside China. However, the different bla KPC expression levels and promoter activities of these two structures are not completely understood. We constructed Tn4401a, Tn4401b, and Tn3-Tn4401 chimera recombinants and found that the imipenem (IPM) and meropenem (MEM) MICs for the Escherichia coli transformants carrying the chimera were 2-fold higher than for those carrying Tn4401b but 2-fold lower than for those carrying Tn4401a In addition to the promoter P1, we characterized a novel potential promoter sequence (PX) in the chimera using 5' rapid amplification of cDNA ends (5' RACE), of which the -35 and -10 sequences were TTCAAA and TGAGACAAT, respectively. Although mutation of P1, P2, or PX significantly downregulated bla KPC mRNA expression in each structure (P < 0.05), the P2 mutation resulted in 2- and 3-fold greater decreases than the P1 mutation in Tn4401a and Tn4401b, respectively. Similarly, despite no significant difference in the PX and P1 mutations in the chimera, the carbapenem MIC and Klebsiella pneumoniae carbapenemase (KPC) production resulting from P2 mutations were significantly lower than those of P1 (P < 0.01) in the Tn4401 transposons. These studies indicate that the Tn3-Tn4401 chimera contains a novel potential bla KPC promoter, PX, and that its carbapenem resistance falls in between those of Tn4401a and Tn4401b.

Huang|Jiansheng|J| Hu|Xiaolei|X| Zhao|Yunan|Y| Shi|Yang|Y| Ding|Hui|H| Wu|Rongzhen|R| Zhao|Zhigang|Z| Ji|Jiansong|J|


Targeted nanoparticles for tumour radiotherapy enhancement-the long dawn of a golden era?

Abstract: Despite considerable progress in (I) our understanding of the aetiopathology of head and neck cancer and (II) the precise delivery of radiotherapy, long-term survival rates for many patients with head and neck cancer remain disappointingly low. Over the past years, gold nanoparticles (NP) have emerged as promising radiation dose enhancers. In a recent study published in Nanoscale, Popovtzer et al. have used gold NP coated with an antibody against the epidermal growth factor receptor (EGFR) in an attempt to enhance radiation-induced tumour cell killing in a head and neck cancer xenograft model. They report a significant impact of the combined treatment with radiation and gold NP on tumour growth and suggest an involvement of apoptosis, inhibition of angiogenesis and diminished tissue repair. In this perspective, we illustrate the underlying radiobiophysical concepts and discuss some of the challenges associated with this and related nanoparticle-radiotherapy studies from a physics, chemistry, biology and therapy angle. We conclude that strong interdisciplinary collaborations spanning all these areas are crucially important to proceed towards effective cancer treatment with gold NP "from bench to bedside".

Gargioni|Elisabetta|E| Schulz|Florian|F| Raabe|Annette|A| Burdak-Rothkamm|Susanne|S| Rieckmann|Thorsten|T| Rothkamm|Kai|K|

radiotherapy
Head and neck cancer
dose enhancement
epidermal growth factor receptor (EGFR)
nanomaterials


A novel portable extra-corporeal life support system for the treatment of cardio-pulmonary failure under controlled hypothermia. Preliminary study in experimental animals.

Abstract:
UNLABELLED
Abstract

PURPOSE
several therapeutic options are used in emergency situations, when heart and/or lung functions acutely fail. Because of the poor results of conventional treatments, the use of an extra-corporeal life support (ECLS) systems able to completely assume the heart and lung functions in emergency situations is becoming a viable alternative. We have developed a unique ECLS system for patients needing extended respiratory and/or circulatory support and controlled hypothermia.

METHODS
the ECLS apparatus is portable and easy to handle by incorporating a disposable centrifugal blood pump, a membrane oxygenator, a waterless heating/cooling device. A sensor's system is integrated in the equipment for continuous monitoring/displaying of several parameters.

RESULTS
the system was tested in bench laboratory studies and in large experimental animals to check feasibility, functionality, durability, consistency and safety. Adult sheep were used, after cannulation of large vessels in the neck, either to test the apparatus in normal physiologic conditions, or under controlled mild hypothermia (33 to 34° C). Two modes of vascular access were tested:  veno-arterial (V-A) and veno-venous (V-V). Vital parameters and systolic blood pressures were continuously monitored up to 48 hours.

DISCUSSION
initial laboratory experiment of the He-Art apparatus indicated that the system was safe and able to control and stabilize the hemodynamic conditions. The device represented a second generation ECLS system, by adding the protective effect of moderate to mild hypothermia against ischemic cardiac and brain injuries.

Benassi|Filippo|F| Giuliani|Enrico|E| Corticelli|Davide|D| Parravicni|Roberto|R|


Highly Efficient Pure-Blue Light-Emitting Diodes Based on Rubidium and Chlorine Alloyed Metal Halide Perovskite.

Abstract: Perovskite light-emitting diodes (PeLEDs) are promising candidates for display and solid-state lighting, due to their tunable colors, high conversion efficiencies, and low cost. However, the performance of blue PeLEDs is far inferior to that of the near-infrared, red, and green counterparts. Here, the fabrication of pure-blue PeLEDs with an emission peak at 475 nm, a peak external quantum efficiency of 10.1%, and a maximum luminance of 14 000 cd m-2 is demonstrated by tailoring the compositions of perovskites. The pure-blue electroluminescence is achieved by simultaneous addition of rubidium and chlorine ions into CsPbBr3 and incorporation of phenylethylammonium chloride forms quasi-2D hybrid perovskites. The combination of these composition engineering results in blueshifted emissions without reducing the quantum yield. The judicious alloying is shown to be critical to result in the better morphology with suppressed current leakage and enhanced light outcoupling.

perovskites
light-emitting devices
mixed halides
rubidium-alloying


Cluster-determinant 36 (CD36) impacts on vitamin E postprandial response.

Abstract:
SCOPE
A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma α-tocopherol concentration, suggesting a possible role of this protein in vitamin E intestinal absorption or tissue uptake.

METHODS AND RESULTS
To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on α- and γ-tocopherol transmembrane uptake and efflux using transfected HEK cells. γ-Tocopherol postprandial response was then assessed in CD36-deficient mice compared with wild-type mice, after the mice had been fully characterized for their α-tocopherol, vitamin A and lipid plasma, and tissue contents. Both α- and γ-tocopherol uptake was significantly increased in cells overexpressing CD36 compared with control cells. Compared with wild-type mice, CD36-deficient mice displayed a significantly decreased cholesterol hepatic concentration, and males exhibited significantly higher triacylglycerol contents in liver, brain, heart, and muscle. Although tissue α-tocopherol concentration after adjustment for lipid content was not modified, γ-tocopherol postprandial response was significantly increased in CD36-deficient mice compared with controls, likely reflecting the postprandial hypertriglyceridemia observed in these mice.

CONCLUSION
Our findings show for the first time that CD36 participates-directly or indirectly-in vitamin E uptake, and that CD36 effect on postprandial lipid metabolism in turn modifies vitamin E postprandial response.

Goncalves|Aurélie|A| Roi|Stéphanie|S| Nowicki|Marion|M| Niot|Isabelle|I| Reboul|Emmanuelle|E|

CD36
α-Tocopherol
Intestinal absorption
γ-Tocopherol
Bioavailability
Transgenic mice


Progressive Muscular Atrophy.

Abstract: Progressive muscular atrophy (PMA) is a rare, sporadic, adult-onset motor neuron disease, clinically characterized by isolated lower motor neuron features; however, clinically evident upper motor neuron signs may emerge in some patients. Subclinical upper motor neuron involvement is identified pathologically, radiologically, and neurophysiologically in a substantial number of patients with PMA. Patients with subclinical upper motor neuron involvement do not fulfill the revised El Escorial criteria to participate in amyotrophic lateral sclerosis clinical trials. Intravenous immunoglobulin therapy is only marginally beneficial in a small subgroup of patients with lower motor neuron syndrome without conduction block.

D003937:Diagnosis, Differential
D019468:Disease Management
D006801:Humans
D016756:Immunoglobulins, Intravenous
D016472:Motor Neuron Disease
D009134:Muscular Atrophy, Spinal
D059906:Neuroimaging
D012720:Severity of Illness Index

Progressive muscular atrophy
PMA
Lower motor neuron syndrome
Lower motor neuron-onset ALS


Biosynthesis and expression of a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats-15: a novel versican-cleaving proteoglycanase.

Abstract: The proteoglycanase clade of the ADAMTS superfamily shows preferred proteolytic activity toward the hyalectan/lectican proteoglycans as follows: aggrecan, brevican, neurocan, and versican. ADAMTS15, a member of this clade, was recently identified as a putative tumor suppressor gene in colorectal and breast cancer. However, its biosynthesis, substrate specificity, and tissue expression are poorly described. Therefore, we undertook a detailed study of this proteinase and its expression. We report propeptide processing of the ADAMTS15 zymogen by furin activity, identifying RAKR(212)↓ as a major furin cleavage site within the prodomain. ADAMTS15 was localized on the cell surface, activated extracellularly, and required propeptide processing before cleaving V1 versican at position (441)E↓A(442). In the mouse embryo, Adamts15 was expressed in the developing heart at E10.5 and E11.5 days post-coitum and in the musculoskeletal system from E13.5 to E15.5 days post-coitum, where it was co-localized with hyaluronan. Adamts15 was also highly expressed in several structures within the adult mouse colon. Our findings show overlapping sites of Adamts15 expression with other members of ADAMTS proteoglycanases during embryonic development, suggesting possible cooperative roles during embryogenesis, consistent with other ADAMTS proteoglycanase combinatorial knock-out mouse models. Collectively, these data suggest a role for ADAMTS15 in a wide range of biological processes that are potentially mediated through the processing of versican.

Dancevic|Carolyn M|CM|
Fraser|Fiona W|FW|
Smith|Adam D|AD|
Stupka|Nicole|N|
Ward|Alister C|AC|
McCulloch|Daniel R|DR|

D018507:Gene Expression Regulation, Developmental

D015971:Gene Expression Regulation, Enzymologic

Proteoglycan
Embryo
Development
Extracellular Matrix
Extracellular Matrix Proteins
Metalloprotease
Skeletal Muscle


Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.

Abstract: The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2 R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39-CD73-A2 R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.

immunosuppressive regimens - minimization/withdrawal


Effects of pressure and strain on physical properties of VI3.

Abstract: The van der Waals ferromagnetic material VI3is a magnetic Mott insulator. In this work, we investigate the effects of isotropic and anisotropic pressure on the atomic structure and the electronic structure of VI3using the first-principles method. The in-plane strain induces structural distortion and breaks the three-fold rotational symmetry of the lattice. Both the in-plane and out-of-plane strain widen the conduction and the valence bands, reduce the energy band gap and drive VI3from a semiconductor to a three-dimensional metal. The structural distortion is not the cause of insulator-to-metal transition. Calculations of the magnetocrystalline anisotropy energy indicate an easy-axis to easy-plane transition when the pressure is higher than 2 GPa. The ferromagnetic Curie temperature falls from 63 K at 0 GPa to 25 K at 6 GPa.

ferromagnetism
insulator-to-metal transition
first-principles calculation
strain engineering


Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis- a systematic review of global literature with focus on South Africa.

Abstract:
INTRODUCTION
Tuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains. The inclusion of HRQOL PROs in trials and clinical practice can provide additional information beyondclinical and microbiological parameters. Furthermore, HRQOL may be associated with medication adherence. This review focuses on patient-reported HRQOL and its association with medication adherence in TB patients in South Africa.

METHODS
A comprehensive search strategy was developed focusing on the impact of TB on patient-reported HRQOL,the existence of a conceptual framework of TB-specific HRQOL, determinants of medication adherence and the association of HRQOL with medication adherence. Data were extracted from all identified articles and additionaldata extraction was performed by two independent reviewers with special focus on longitudinal studies in order to understand changes of HRQOL and adherence over time. Research gaps were identified with regard to patient-reported HRQOL and medication adherence.

RESULTS
A total of 66 articles met the eligibility criteria. Ten HRQOL studies and one adherence study used a longitudinal design, none of these in South Africa. A variety of different generic and disease-specific HRQOL measures were identified in the articles. In South Africa four HRQOL and five adherence studies (non-longitudinal) were published. Similar factors (socio-demographic, socio-economic, disease-related, therapy-related and psycho-social aspects) affect HRQOL and adherence. Although standard TB treatment improved all health domains, psychological well-being and social functioning remained impaired in microbiologically cured patients after treatment.

CONCLUSION
While evidence of TB impact on HRQOL and medication adherence and their association exists, it is verylimited for the South African situation. No valid and reliable TB-specific HRQOL measures were identified in this systematicreview. An assessment of HRQOL in TB patients in South Africa is required as this may assist with improving current disease management programmes, medication adherence and national treatment guidelines.

Kastien-Hilka|Tanja|T| Abulfathi|Ahmed|A| Rosenkranz|Bernd|B| Bennett|Bryan|B| Schwenkglenks|Matthias|M| Sinanovic|Edina|E|

Health-related quality of life
Medication adherence
South Africa
Tuberculosis
Patient-reported outcomes


How resilient is health financing policy in Europe to economic shocks? Evidence from the first year of the COVID-19 pandemic and the 2008 global financial crisis.

Abstract: The COVID-19 pandemic triggered an economic shock just ten years after the shock of the 2008 global financial crisis. Economic shocks are a challenge for health systems because they reduce government revenue at the same time as they increase the need for publicly financed health care. This article explores the resilience of health financing policy to economic shocks by reviewing policy responses to the financial crisis and COVID-19 in Europe. It finds that some health systems were weakened by responses to the 2008 crisis. Responses to the pandemic show evidence of lessons learnt from the earlier crisis but also reveal weaknesses in health financing policy that limit national preparedness to face economic shocks, particularly in countries with social health insurance schemes. These weaknesses highlight where permanent changes are needed to strengthen resilience in future: countries will have to find ways to reduce cyclicality in coverage policy and revenue-raising; increase the priority given to health in allocating public spending; and ensure that resources are used to meet equity and efficiency goals. Although many health systems are likely to face budgetary pressure in the years ahead, the experience of the 2008 crisis shows that austerity is not an option because it undermines resilience and progress towards universal health coverage.

Thomson|Sarah|S|
García-Ramírez|Jorge Alejandro|JA|
Akkazieva|Baktygul|B|
Habicht|Triin|T|
Cylus|Jonathan|J|
Evetovits|Tamás|T|

Resilience
Health financing
COVID-19
Global financial crisis
Austerity


Uveal Melanoma: GNAQ and GNA11 Mutations in a Greek Population.

Abstract:
BACKGROUND/AIM
Uveal melanoma is the most common primary adult intraocular malignancy. It is known to have a strong metastatic potential, fatal for the vast majority of patients. In recent years, meticulous cytogenetic and molecular profiling has led to precise prognostication, that unfortunately is not matched by advancements in adjuvant therapies. G Protein subunits alpha Q (GNAQ) and alpha 11 (GNA11) are two of the major driver genes that contribute to the development of uveal melanoma. Understanding their prognostic significance can allow tailored management and facilitate their use in the on-going quest of targeted uveal melanoma therapies.

MATERIALS AND METHODS
Formalin-fixed, paraffin-embedded specimens were obtained from 47 patients of Greek origin, with uveal melanoma. GNAQ and GNA11 genes were screened for mutations in exons 4 and 5, by polymerase chain reaction and Sanger sequencing.

RESULTS
The overall mutation frequency of GNAQ/GNA11 genes was 42.4%. A novel mutation c.625_626delinsGC was identified in GNA11. No correlation was observed between the mutation status and metastasis occurrence or overall survival time of patients.

CONCLUSION
Mutations in GNAQ and GNA11 genes in this Greek population present frequencies that qualify them as potential targets for customized therapy.

Psinakis|Filippos|F| Katseli|Anastasia|A| Koutsandrea|Chryssanthy|C| Frangia|Konstantina|K| Florentin|Lina|L| Apostolopoulou|Despina|D| Dimakopoulou|Konstantina|K| Papakonstantinou|Dimitrios|D| Georgopoulou|Eleni|E| Brouzas|Dimitrios|D|

D044385:GTP-Binding Protein alpha Subunits

D043802:GTP-Binding Protein alpha Subunits, Gq-G11

D020022:Genetic Predisposition to Disease

Uveal melanoma
GNAQ
GNA11
Sanger-sequencing


Clinical outcome of AO/OTA type C fracture of the distal humerus using the expanded paratricipital approach and cadaveric comparison of the exposure of the paratricipital and expanded paratricipital approaches to the distal humerus.

Abstract:
BACKGROUND
We investigated the overall clinical outcome of the expanded paratricipital approach in complex articular fractures of the distal humerus and the effect of lack of visualization in the surgical field. In addition, we performed a cadaveric study to investigate the expansion or limitation of articular access in the expanded paratricipital approach.

METHODS
Forty-one AO/OTA type 13C fracture cases treated using the expanded paratricipital approach at a single trauma center from 2013 to 2017 were enrolled in this study. We evaluated the overall clinical outcome and analyzed the effect of lack of visualization in the surgical field with the expanded paratricipital approach by comparing outcomes between 2 groups classified by the location of the main articular fracture (group 1, limited visualization; group 2, without limited visualization). The length of inaccessible and accessible articular segments were analyzed using 40 matched-pair elbows.

RESULTS
The average duration of follow-up was 15.1 months. All fractures (type C1 in 11 cases, type C2 in 21, and type C3 in 9) were radiologically healed at 3.2 months after surgery. No cases required additional surgery because of implant irritation. The average Mayo Elbow Performance Score was 90.5. The mean Disabilities of the Arm, Shoulder and Hand score was 18.5. Among the 41 cases, the limited visualization group (group 1, n = 21) had a longer surgical time and higher percentage of nonanatomic reduction than group 2. Although the expanded paratricipital approach allowed more articular exposure than the conventional approach, there was still a 20mm inaccessible articular segment (30% of transepicondylar width) in cadaveric dissection.

CONCLUSIONS
The expanded paratricipital approach can be used in type C1, type C2, and selective type C3 articular fractures of the distal humerus with favorable results. Relative to surgical times and achieving anatomic reduction, it is more successful in a fracture with a main articular fragment and with good visualization.

Cho|Jae-Woo|JW|
Kim|Beom-Soo|BS|
Yeo|Do-Hyun|DH|
Kang|Seong Hyun|SH|
Lim|Eic Ju|EJ|
Sakong|Seungyeob|S|
Cho|Won-Tae|WT|
Oh|Jong-Keon|JK|

outcome
Distal humerus
expanded paratricipital
complex articular fracture
fracture fixation
surgical approach


A new threat to bees? Entomopathogenic nematodes used in biological pest control cause rapid mortality in Bombus terrestris.

Abstract: There is currently a great deal of concern about population declines in pollinating insects. Many potential threats have been identified which may adversely affect the behaviour and health of both honey bees and bumble bees: these include pesticide exposure, and parasites and pathogens. Whether biological pest control agents adversely affect bees has been much less well studied: it is generally assumed that biological agents are safer for wildlife than chemical pesticides. The aim of this study was to test whether entomopathogenic nematodes sold as biological pest control products could potentially have adverse effects on the bumble bee Bombus terrestris. One product was a broad spectrum pest control agent containing both Heterorhabditis sp. and Steinernema sp., the other product was specifically for weevil control and contained only Steinernema kraussei. Both nematode products caused ≥80% mortality within the 96 h test period when bees were exposed to soil containing entomopathogenic nematodes at the recommended field concentration of 50 nematodes per cm(2) soil. Of particular concern is the fact that nematodes from the broad spectrum product could proliferate in the carcasses of dead bees, and therefore potentially infect a whole bee colony or spread to the wider environment.

Dutka|Alexandrea|A|
McNulty|Alison|A|
Williamson|Sally M|SM|

Bees
Entomopathogenic nematodes
Biological pest control
Pollinator health


Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson's disease.

Abstract: While people are often aware of the motor symptoms in Parkinson's disease (PD), few know of the many non-motor symptoms, which patients report have a greater impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the most common non-motor symptoms, which can occur at any stage of PD, even years prior to diagnosis, and can affect all sections along the GI tract causing a range of symptoms including drooling, gastroparesis and constipation. We have investigated whether a neurotoxin model of PD induced by rotenone, a mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction seen clinically. Sprague-Dawley rats were administered 2.75 mg/kg rotenone, 5 days/week for 4 weeks, via intraperitoneal injection. Rats underwent behavioural testing, including the one-hour stool and gastric emptying tests before GI contents and tissues were collected for microbiota and histological analysis. Rats exposed to rotenone had more days with evidence of diarrhoea and significantly delayed gastric emptying, reproducing the clinical symptom of gastroparesis. Microbiota analysis revealed alterations in the small intestine and colon of rotenone-treated rats, relatively consistent with changes described in PD patients. Histological analysis demonstrated mucosal thickening and goblet cell hyperplasia in the colon of rotenone rats, which may be an adaptive response to the toxin or changes in GI microbiota. Our results indicate that rotenone may be a good model for investigating the mechanisms involved with Parkinson's GI symptoms and for screening potential therapeutic options as it is capable of recapitulating some key GI changes that occur during PD progression.

Johnson|Michaela E|ME|
Stringer|Andrea|A|
Bobrovskaya|Larisa|L|

Rotenone
Gastrointestinal
Microbiota
Gastroparesis
Diarrhea
Parkinson’s disease


Suppression of NLRP3 Inflammasome, Pyroptosis, and Cell Death by NIM811 in Rotenone-Exposed Cells as an in vitro Model of Parkinson's Disease.

Abstract:
BACKGROUND
Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra. Recently, NLRP3 inflammasome and pyroptosis were found to be associated with PD. Cyclosporine A (CsA), an immunosuppressant, reduces neuronal death in PD. However, CsA could hardly pass through the blood-brain barrier (BBB) and high dose is associated with severe side effects and toxicity. N-methyl-4-isoleucine-cyclosporine (NIM811) is a CsA derivate that can pass through the BBB. However, little is known about its effect on PD.

OBJECTIVE
The objectives of this study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of NIM811 on the neurotoxicity of a Parkinson-like in vitro model induced by rotenone.

METHODS
Murine hippocampal HT22 cells were cultured with the mitochondrial complex I inhibitor rotenone, a widely used pesticide that has been used for many years as a tool to induce a PD model in vitro and in vivo and proven to be reproducible. NIM811 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by resazurin assay, reactive oxygen species (ROS) production by dihydroethidine (DHE), and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). TUNEL and caspase-1 immunofluorescent double staining was used to detect pyroptosis. NLRP3, caspase-1, pro-caspase-1, GSDMD, and interleukin-18 (IL-18) were measured using Western blotting after 24 h of rotenone incubation. The reactivity of interleukin-1β (IL-1β) was determined by ELISA.

RESULTS
Our results demonstrated that rotenone caused more than 40% of cell death, increased ROS production, and reduced mitochondrial membrane potential, while NIM811 reversed these alterations. Immunofluorescent double staining showed that rotenone increased the percentage of caspase-1 and TUNEL double-labelled cells, an indication of pyroptosis, after 24 h of incubation. The protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-18, and IL-1β was significantly increased after 24 h of rotenone incubation. NIM811 suppressed rotenone-induced pyroptosis and downregulated the protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-1β, and IL-18.

CONCLUSION
These results provide evidence that rotenone activates the NLRP3 inflammomere and induces pyroptosis. NIM811 protects the cell from rotenone-induced damage and inhibits NLRP3 inflammasome and pyroptosis. NIM811 might serve as a potential therapeutic drug in the treatment of PD.

Zhang|Minghao|M|
He|Qingping|Q|
Chen|Guisheng|G|
Li|P Andy|PA|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein


Understanding Youth Perceptions of Neighborhood Disorder: The Role of Conduct Problems.

Abstract: While research addresses neighborhood disorder as leading to conduct problems, the role of individual-level differences in shaping adolescent perceptions of neighborhood has been overlooked. Data on youth, over-selected for childhood conduct problems (N = 744, 58% childhood conduct problems, 47% girls), were used to examine the link between conduct problems (time 1: Mean age = 12.23) and perceived neighborhood disorder (time 3: M = 14.30). The mediating role of delinquent friends, peer victimization, depressive symptoms, and observer-rated neighborhood disorder (time 2: M = 13.23) were also tested. Conduct problems were associated with higher levels of perceived neighborhood disorder, via delinquent peers and peer victimization. These findings offer new insight into the consequences of perceived neighborhood disorder for health and wellbeing.

Neighborhood disorder
Conduct problems
Peer victimization
Delinquent peers
Longitudinal


Human CD4+ T-Cell Clone Expansion Leads to the Expression of the Cysteine Peptidase Inhibitor Cystatin F.

Abstract: The existence of CD4+ cytotoxic T cells (CTLs) at relatively high levels under different pathological conditions in vivo suggests their role in protective and/or pathogenic immune functions. CD4+ CTLs utilize the fundamental cytotoxic effector mechanisms also utilized by CD8+ CTLs and natural killer cells. During long-term cultivation, CD4+ T cells were also shown to acquire cytotoxic functions. In this study, CD4+ human T-cell clones derived from activated peripheral blood lymphocytes of healthy young adults were examined for the expression of cytotoxic machinery components. Cystatin F is a protein inhibitor of cysteine cathepsins, synthesized by CD8+ CTLs and natural killer cells. Cystatin F affects the cytotoxic efficacy of these cells by inhibiting the major progranzyme convertases cathepsins C and H as well as cathepsin L, which is involved in perforin activation. Here, we show that human CD4+ T-cell clones express the cysteine cathepsins that are involved in the activation of granzymes and perforin. CD4+ T-cell clones contained both the inactive, dimeric form as well as the active, monomeric form of cystatin F. As in CD8+ CTLs, cysteine cathepsins C and H were the major targets of cystatin F in CD4+ T-cell clones. Furthermore, CD4+ T-cell clones expressed the active forms of perforin and granzymes A and B. The levels of the cystatin F decreased with time in culture concomitantly with an increase in the activities of granzymes A and B. Therefore, our results suggest that cystatin F plays a role in regulating CD4+ T cell cytotoxicity. Since cystatin F can be secreted and taken up by bystander cells, our results suggest that CD4+ CTLs may also be involved in regulating immune responses through cystatin F secretion.

D015496:CD4-Positive T-Lymphocytes
D018414:CD8-Positive T-Lymphocytes
D020789:Cathepsin C
D056668:Cathepsin L
D045744:Cell Line, Tumor
D002999:Clone Cells
D003545:Cysteine
D053804:Granzymes
D006801:Humans
D019169:Jurkat Cells
D007694:Killer Cells, Natural
D008213:Lymphocyte Activation
D011480:Protease Inhibitors
D013602:T-Lymphocytes, Cytotoxic

peptidases
cystatin F
granzymes
CD4+ T helper cells
cytotoxic lymphocytes


Aestuariibius insulae gen. nov., sp. nov., isolated from a tidal flat sediment.

Abstract: A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-13T, which was isolated from a tidal flat sediment of the Yellow Sea in South Korea, was characterized taxonomically. Strain DBTF-13T grew optimally at 25-30 °C and pH 7.0-8.0, and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-13T formed an evolutionary lineage independent of other genera, including the genera Pseudooctadecabacter and Octadecabacter. Strain DBTF-13T exhibited 16S rRNA gene sequence similarity values of 96.9 % to the type strain of Pseudooctadecabacter jejudonensis, and of 95.8-96.5 % to the type strains of Octadecabacter species. Strain DBTF-13T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c and C16 : 0 as the major fatty acids. The major polar lipids of strain DBTF-13T were phosphatidylcholine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G+C content of strain DBTF-13T was 61.6 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to differentiate strain DBTF-13T from the genera Pseudooctadecabacter and Octadecabacter. On the basis of the data presented, strain DBTF-13T constitutes a new genus and species within the class Alphaproteobacteria, for which the name Aestuariibius insulae gen. nov., sp. nov. is proposed. The type strain is DBTF-13T (=KACC 19432T=NBRC 113038T).

Park|Sooyeon|S| Choi|Jeehyun|J| Won|Sung-Min|SM| Park|Ji-Min|JM| Yoon|Jung-Hoon|JH|

Aestuariibius insulae
tidal flat sediment
novel genus
novel species
polyphasic taxonomy


Facile synthesis of strontium ferrite nanorods/graphene composites as advanced electrode materials for supercapacitors.

Abstract: The exploration of efficient and stable electrode materials is important for supercapacitors. Composite electrode materials are promising candidates for supercapacitors since single component materials cannot satisfy the dual needs of high energy density and power density. In this study, uniform strontium ferrite nanorods are grown on graphene by a facile surfactant assisted hydrothermal method. The resultant SrFe12O19 nanorods/graphene (SrFe12O19 NR/G) composites combine the merits of both SrFe12O19 and graphene, and the SrFe12O19 NR/G based supercapacitors exhibit specific capacitances of 681.2 and 450.9 F g-1 at 1 and 20 A g-1, respectively, and 95.5% of capacitance retention after 10,000 cycles at 1 A g-1. Moreover, they exhibit outstanding energy density and power density characteristics (47.3 Wh kg-1 at 500.9 W kg-1 and 31.3 Wh kg-1 at 10247.7 W kg-1). In addition, the influence of component ratio on the electrochemical performances of SrFe12O19 NR/G composites is thoroughly studied. Finally, the energy storage behavior and mechanism of as-obtained SrFe12O19 NR/G composites are investigated to further understand their enhanced capacitive performances. This work not only provides a new supercapacitor electrode material, but also offers an idea that can be used for the construction of composite electrode materials.

Fu|Min|M| Zhang|Zhihao|Z| Zhu|Zitong|Z| Zhuang|Qingru|Q| Chen|Wei|W| Yu|Hao|H| Liu|Qingyun|Q|

Graphene
Composite electrode materials
Energy storage
SrFe(12)O(19) nanorods


Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves.

Abstract: During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM+ cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.SIGNIFICANCE STATEMENT Cortical slow waves are a defining feature of non-rapid eye-movement (NREM) sleep and are thought to be important for many of its restorative benefits. Yet, the mechanism by which cortical neurons abruptly and synchronously cease firing, the neuronal basis of the slow wave, remains unknown. Using chemogenetic and optogenetic approaches, we provide the first evidence that links a specific class of inhibitory interneurons-somatostatin-positive cells-to the generation of slow waves during NREM sleep in freely moving mice.

Funk|Chadd M|CM|0000-0001-6399-7803
Peelman|Kayla|K|
Bellesi|Michele|M|
Marshall|William|W|0000-0002-4779-6734
Cirelli|Chiara|C|0000-0003-2563-677X
Tononi|Giulio|G|


Human disease/clinical medical sciences for dentistry in early-years dental graduates: Transition from undergraduate study to clinical practice.

Abstract:
INTRODUCTION
Dental bodies across Europe have published curricula aiming to guide the development of a graduating dentist who is safe and competent, and which also contain direction on what knowledge and understanding of patient's health, drugs and disease a recent graduate should have.

MATERIALS, METHODS AND AIM
A questionnaire to survey Foundation Dentists in Wales regarding their undergraduate teaching and assessment in human disease/clinical medical science for dentistry and how this translates to their knowledge, attitudes and confidence in the dental management of patients who may have chronic disease or disability.

RESULTS
A 97% response rate to the questionnaire from Foundation Dentists graduating from schools across the UK showed that the large majority felt their teaching and learning in human disease/clinical medical science for dentistry was appropriately delivered and assessed, and that they were well prepared for independent dental practice and to plan and safely manage treatments for all their patients.

DISCUSSION
This survey of newly qualified dentists representing graduates from different types of dental courses and both newer and long-established schools across the UK reports the foundation dentists felt that they are competent and safe to care for all patients, including those with complex medical histories.

CONCLUSIONS
The foundation dentists surveyed have completed dental undergraduate courses containing the appropriate education and assessment for human health and disease, such that they are prepared to manage their patient population safely, and are well placed to serve their patients as the population continues to age and the amount of medical morbidity increases.

D007722:Health Knowledge, Attitudes, Practice

human disease
dental practice
HD/CMSD
clinical medical science in dentistry
early years graduates


Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer.

Abstract:
BACKGROUND
The thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer.

METHODS AND RESULTS
TP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer.

CONCLUSION
Higher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging.

Lindskog|Elinor B|EB|
Wettergren|Yvonne|Y|
Odin|Elisabeth|E|
Gustavsson|Bengt|B|
Derwinger|Kristoffer|K|

thymidine phosphorylase
colorectal cancer
lymph nodes
prognosis
differentiation grade


Patient-specific functional electrical stimulation strategy based on muscle synergy and walking posture analysis for gait rehabilitation of stroke patients.

Abstract:
OBJECTIVE
To evaluate a novel multi-channel functional electrical stimulation (FES) rehabilitation method based on the evaluation of patient-specific walking dysfunction.

METHODS
This study investigated a novel multi-channel FES-based rehabilitation method that analysed the patient's muscle synergy and walking posture. A patient-specific FES profile was produced in the pre-evaluation stage by comparing the muscle synergy and walking posture of the patient with those of healthy control subjects. During the rehabilitation phase, this profile was used to determine an appropriate FES pulse width and amplitude for stimulating the patient's muscles as they walked across a flat surface.

RESULTS
Two stroke patients with hemiplegic symptoms participated in a clinical evaluation of the proposed method involving a 4-week course of rehabilitation. An evaluation of the rehabilitation results based on a comparison of the pre- and post-rehabilitation muscle synergy and walking posture revealed that the rehabilitation enhanced the muscle synergy similarity between the patients and healthy control subjects and their quantitative walking performance, as measured by a 10-m walk test and walking speed, by up to 23.38% and 30.00%, respectively.

CONCLUSION
These results indicated that the proposed rehabilitation method improved walking ability by improving muscle coordination and adequately supporting weakened muscles in stroke patients.

functional electrical stimulation
muscle synergy
Stroke rehabilitation


Ibrutinib in association with venetoclax for the treatment of mantle-cell lymphoma: a multicenter case series.

Abstract:
INTRODUCTION
Mantle-cell lymphoma (MCL) with relapsed/refractory (R/R) disease after intensive chemotherapy have few effective treatment options. Ibrutinib showed a promising median progression-free survival (PFS) with manageable toxicity. The BCL2 inhibitor venetoclax showed encouraging results in R/R MCL patients and preclinical models suggest a potential synergistic effect of dual BTK and BCL2 inhibition. Ibrutinib in association with venetoclax was successfully investigated in a phase II trial.

CASE REPORT
We have retrospectively analyzed 4 patients with R/R MCL receiving daily oral ibrutinib in association with venetoclax. All patients received oral ibrutinib 560 mg per day as monotherapy and subsequently added venetoclax with an initial dose of 50 mg per day, with weekly rump-up until a full dose of 400 mg per day until disease progression. All patients achieved a response, the CR rate was 50%. The aim was to perform an allogeneic SCT (allo-SCT). One patient experienced an early relapse and died because of PD. Allo-SCT was successfully performed in the other 3 patients; ibrutinib and venetoclax were discontinued before allo-SCT. One patient died because of transplant-related complications, while the other 2 cases are alive and in CR. No tumor lysis syndrome occurred.

DISCUSSION
Ibrutinib plus venetoclax represents a promising and feasible treatment option for R/R MCL patients outside clinical trials.

Fabbri|Alberto|A|
Cencini|Emanuele|E|
Congiu|Angela Giovanna|AG|
Miglino|Maurizio|M|
Rigacci|Luigi|L|
Bocchia|Monica|M|

ibrutinib
venetoclax
Mantle-cell lymphoma


Morphoelasticity in the development of brown alga Ectocarpus siliculosus: from cell rounding to branching.

Abstract: A biomechanical model is proposed for the growth of the brown alga Ectocarpus siliculosus Featuring ramified uniseriate filaments, this alga has two modes of growth: apical growth and intercalary growth with branching. Apical growth occurs upon the mitosis of a young cell at one extremity and leads to a new tip cell followed by a cylindrical cell, whereas branching mainly occurs when a cylindrical cell becomes rounded and swells, forming a spherical cell. Given the continuous interplay between cell growth and swelling, a poroelastic model combining osmotic pressure and volumetric growth is considered for the whole cell, cytoplasm and cell wall. The model recovers the morphogenetic transformations of mature cells: transformation of a cylindrical shape into spherical shape with a volumetric increase, and then lateral branching. Our simulations show that the poro-elastic model, including the Mooney-Rivlin approach for hyper-elastic materials, can correctly reproduce the observations. In particular, branching appears to be a plasticity effect due to the high level of tension created after the increase in volume of mature cells.

Jia|Fei|F|
Ben Amar|Martine|M|0000-0001-9132-2053
Billoud|Bernard|B|
Charrier|Bénédicte|B|

growth
poroelasticity
bioelasticity
cell division
morphogenesis
seaweed


Crystal structure of (2-methyl-4-phenyl-4H-benzo[4,5]thia-zolo[3,2-a]pyrimidin-3-yl)(phen-yl)methanone.

Abstract: In the title compound, C24H18N2OS, the pyrimidine ring has a flat envelope conformation with the methine C atom as the flap. The attached phenyl and benzoyl rings are inclined to the mean plane of the pyrimidine ring by 84.87 (8) and 75.33 (9)°, respectively. The benzo-thia-zolo group is planar (r.m.s. deviation = 0.009 Å) and inclined to the mean plane of the pyrimidine ring by 3.27 (6)°. In the crystal, mol-ecules are linked by pairs of C-H⋯N hydrogen bonds, forming inversion dimers.

Sankar|T|T|
Naveen|S|S|
Lokanath|N K|NK|
Gunasekaran|K|K|

crystal structure
pyrimidine
C—H⋯N hydrogen bonding
benzo
thiazolo


Cell-Based Versus Enzyme-Linked Immunosorbent Assay for the Detection of Acetylcholine Receptor Antibodies in Chinese Juvenile Myasthenia Gravis.

Abstract:
BACKGROUND
Patients in China with juvenile-onset myasthenia gravis present early, with a high prevalence of purely ocular symptoms, spontaneous remission rates, and low antibody seropositivity. Antibody detection using a cell-based assay has been reported to increase the diagnostic sensitivity in adult-onset myasthenia gravis. However, this method in patients with juvenile-onset myasthenia gravis has not been investigated.

METHODS
Patients with juvenile-onset myasthenia gravis who had not received prednisone or immunosuppressive therapy were recruited between June 2015 and April 2018 at the Huashan Hospital. Clinical information was collected. Serum anti-acetylcholine receptor antibodies were detected via cell-based assay with HEK293T cells expressing acetylcholine receptor subunits and rapsyn. Additionally, the IgG antibody subclass was identified.

RESULTS
Eighty-two patients with juvenile-onset myasthenia gravis were enrolled in the current study. Among them, 48 patients were anti-acetylcholine receptor positive (58.5%) and 34 were seronegative (41.5%), as assessed via enzyme-linked immunosorbent assay. Cell-based assay yielded 63 positive subjects (76.8%) and 19 seronegative subjects (23.2%). All the enzyme-linked immunosorbent assay-positive samples showed robust immunofluorescence in the cell-based assay, whereas 15 of 34 enzyme-linked immunosorbent assay-negative patients (44.1%) were found to have low-affinity acetylcholine receptor antibodies. Among all the cell-based assay-positive patients, 41 were positive for both adult and fetal acetylcholine receptor antibodies (50.0%), 18 were found positive for only adult acetylcholine receptor antibodies (21.9%), and four were found to possess only fetal acetylcholine receptor antibodies (4.9%). Fifteen antibody-positive samples underwent subclassification and were confirmed to be IgG1 subclass predominant (n = 15, including eight adult and fetal acetylcholine receptor antibody positive, five only adult acetylcholine receptor antibody positive, and two only fetal acetylcholine receptor antibody positive). There were no significant differences in clinical features among patients with different antibody profiles.

CONCLUSIONS
The cell-based assay showed increased sensitivity in acetylcholine receptor antibody detection in Chinese patients with juvenile-onset myasthenia gravis, and most cases of Chinese juvenile-onset myasthenia gravis are still acetylcholine receptor autoantibody mediated. Furthermore, the antibodies detected are predominately of the IgG1 subclass.

Yan|Chong|C| Li|Wenhui|W| Song|Jie|J| Feng|Xuelin|X| Xi|Jianying|J| Lu|Jiahong|J| Zhou|Shuizhen|S| Zhao|Chongbo|C|

Acetylcholine receptor
Juvenile myasthenia gravis
cell-based assay
Diagnosis
ELISA


Effect of early feed restriction on physiological responses, performance and ascites incidence in broiler chickens raised in normal or cold environment.

Abstract: Intensive selection of broilers for faster growth and better feed efficiency resulted in greater susceptibility to metabolic disorders such as ascites syndrome, which is one of the major causes of mortality and economic loss in broiler industry. Whereas cool temperature is one of the primary triggers for ascites, early feed restriction (FDR) significantly alleviates its incidence and mortality. However, little is known about effects of FDR, cold environmental temperature and their interaction on physiological responses in broiler chickens. For this purpose, 320 one-day-old male broilers were divided into two treatment groups of Ad libitum (Ad) and feed restricted (FR) with eight pen replicates each. Chickens in FR group underwent feed access limitation from days 7 to 14 of age. On day 21 half of the birds (four pens) in each group exposed to the cold temperature (CT) and the other half (four pens) continued at normal temperature (NT). Average daily feed intake, average daily weight gain and feed conversion ratio (FCR) were measured at days 7, 14, 21, 28 and 42. At 39 and 46 days of age two chicks with a BW around the pen average were selected from each pen and slaughtered after collecting blood samples. Then, relative weight of internal organs and right ventricle weight per total ventricle weight (RV : TV) ratio were calculated. Compared with NT group, CT birds had higher daily feed intake and FCR (P<0.05) from day 28 to 42. Cumulative ascites mortality in CT chickens was higher (P<0.001) than NT chicks. Within the CT group, ascites mortality in FR chickens was reduced (P<0.001) to 1.25% compared with 8.75% in Ad chicks. Birds in CT group had significantly (P<0.05) thicker right ventricle and greater relative weight of heart, hematocrit and triiodothyronine concentration. However, none of these parameters were affected by FDR. Under cold stress conditions, FDR reduced activity of alanine aminotransferase and aspartate aminotransferase (P<0.05). Serum triglyceride, cholesterol, high-density lipoprotein and total protein were not influenced by either temperature or feeding regimen. In conclusion, these findings suggest that FDR reduces ascites incidence mainly by allowing better development of internal organs, which helps them to cope with the high metabolic pressure and suffer less damage.

Mohammadalipour|R|R|
Rahmani|H R|HR|
Jahanian|R|R|
Riasi|A|A|
Mohammadalipour|M|M|
Nili|N|N|

D000824:Animal Nutritional Physiological Phenomena

feed restriction
ascites
cold temperature
blood biochemistry
thyroid hormone


Efficient synthesis of new antiproliferative steroidal hybrids using the molecular hybridization approach.

Abstract: A series of steroidal hybrids with different terminal bioactive scaffolds were synthesized using the molecular hybridization approach and further evaluated for their antiproliferative activity against several cancer cell lines of different origins using the MTT assay. The preliminary results indicated that compounds 12a-h with the terminal isatin motif were remarkably sensitive to SH-SY5Y cells, thereby exerting potent growth inhibition in vitro. This selectivity is possibly attributed to LSD1 inactivation (IC50 = 3.18 μM). Besides, we also found that the chloro atom at the 7-position on the isatin core was beneficial for the activity through the SARs studies. Among this series, compound 12g showed the best inhibitory activity (IC50 = 4.06 μM) against SH-SY5Y cells, which was comparable to that of 5-FU. Compound 12g arrested cell cycle at G2/M phase, induced apoptosis accompanied with decrease of mitochondrial membrane potential, and inhibited LSD1 potently (IC50 = 3.18 μM). Docking studies showed that compound 12g formed interactions with surrounding amino acid residues and the steroid nucleus occupied the tubular hydrophobic cavity of the active site. Compounds 13-18 represented weak to moderate activity against the tested cancer cell lines. The steroidal dimer 20 and the structurally simplified non-steroidal dimer 21 were found to be devoid of the inhibitory activity.

Yu|Bin|B| Qi|Ping-Ping|PP| Shi|Xiao-Jing|XJ| Huang|Ruilei|R| Guo|Hao|H| Zheng|Yi-Chao|YC| Yu|De-Quan|DQ| Liu|Hong-Min|HM|

D004354:Drug Screening Assays, Antitumor

Steroids
Molecular hybridization
Antiproliferative activity
LSD1 inactivation
Apoptosis
Cell cycle arrest
Docking simulations


Phobos LIFE (Living Interplanetary Flight Experiment).

Abstract: The Planetary Society's Phobos Living Interplanetary Flight Experiment (Phobos LIFE) flew in the sample return capsule of the Russian Federal Space Agency's Phobos Grunt mission and was to have been a test of one aspect of the hypothesis that life can move between nearby planets within ejected rocks. Although the Phobos Grunt mission failed, we present here the scientific and engineering design and motivation of the Phobos LIFE experiment to assist with the scientific and engineering design of similar future experiments. Phobos LIFE flew selected organisms in a simulated meteoroid. The 34-month voyage would have been the first such test to occur in the high-radiation environment outside the protection of Earth's magnetosphere for more than a few days. The patented Phobos LIFE "biomodule" is an 88 g cylinder consisting of a titanium outer shell, several types of redundant seals, and 31 individual Delrin sample containers. Phobos LIFE contained 10 different organisms, representing all three domains of life, and one soil sample. The organisms are all very well characterized, most with sequenced genomes. Most are extremophiles, and most have flown in low Earth orbit. Upon return from space, the health and characteristics of organisms were to have been compared with controls that remained on Earth and have not yet been opened.

Betts|Bruce H|BH|
Warmflash|David|D|
Fraze|Raymond E|RE|
Friedman|Louis|L|
Vorobyova|Elena|E|
Lilburn|Timothy G|TG|
Smith|Amy|A|
Rettberg|Petra|P|
Jönsson|K Ingemar|KI|
Ciftcioglu|Neva|N|
Fox|George E|GE|
Svitek|Tomas|T|
Kirschvinck|Joseph L|JL|
Moeller|Ralf|R|
Wassmann|Marko|M|
Berger|Thomas|T|

Phobos LIFE
Lithopanspermia.
Panspermia
Spaceflight experiments
Transpermia


Acquisition of cognitive and communication milestones in infants with Down syndrome.

Abstract:
BACKGROUND
Understanding the timing of developmental milestones in typical and clinical populations facilitates intervention planning and the early detection of risk for co-occurring conditions. Normative timing of developmental milestone achievement has been established for typically developing children. However, there is little information regarding the timing of cognitive and communication skill acquisition in young children with Down syndrome (DS). The objectives of this study are to (1) provide foundational information regarding the timing of cognitive and communication skill acquisition in infants with DS and (2) facilitate the early identification of infants with risk for co-occurring conditions.

METHOD
Seventy-four infants with DS (age range: 4-18 months) completed the Bayley Scales of Infant Development-III (Bayley 2006). Individual items from the cognitive and communication scales were selected for analysis. Parents provided information regarding their infant's developmental and family history.

RESULTS
The percentage of infants who attained each skill was calculated within 2-month age bands. For infants who did not show skill acquisition within each age band, the rates of prematurity, heart defects, corrective heart surgery and significant illness were calculated as well.

CONCLUSIONS
This study provides foundational information that can contribute to the formulation of a developmental schedule for cognitive and language milestone acquisition in infants with DS.

cognition
communication
milestones
Down syndrome
early intervention
precursors


Review: comparison of PET rubidium-82 with conventional SPECT myocardial perfusion imaging.

Abstract: Nuclear cardiology has for many years been focused on gamma camera technology. With ever improving cameras and software applications, this modality has developed into an important assessment tool for ischaemic heart disease. However, the development of new perfusion tracers has been scarce. While cardiac positron emission tomography (PET) so far largely has been limited to centres with on-site cyclotron, recent developments with generator produced perfusion tracers such as rubidium-82, as well as an increasing number of PET scanners installed, may enable a larger patient flow that may supersede that of gamma camera myocardial perfusion imaging.

Ghotbi|Adam A|AA|
Kjaer|Andreas|A|
Hasbak|Philip|P|

myocardial perfusion imaging
cardiology
cardiac PET
cardiac SPECT
rubidium


Data supporting the elemental composition, the morphological and thermal properties of MnPhos/waterborne poly(urethane)(WPU) coatings for carbon steel.

Abstract: The data set presented here offers evidence of the elemental composition related to a SEM micrograph of [Mn5(PO3(OH))2(PO4)2⋅4H2O] (MnPhos) powders, known as hurealite, and synthesized by the reflux method. In addition, it contains additional information of the glass transition, melting and decomposition temperatures and their weight loss percent of coatings based on MnPhos incorporated into waterborne poly(urethane) (WPU). These data are complementing of the article "Corrosion investigation of new hybrid organic/inorganic coatings for carbon steel substrates: electrochemical and surface characterizations".

Salazar-Bravo|P|P|
Torres-Huerta|A M|AM|
Del Angel-López|D|D|
Domínguez-Crespo|M A|MA|
Palma-Ramírez|D|D|
López-Oyama|A B|AB|

Elemental composition
SEM micrographs
Hureaulite
MnPhos/WPU coatings
Thermograms