Tissue distribution of polystyrene nanoplastics in mice and their entry, transport, and cytotoxicity to GES-1 cells.

Abstract: With the widespread use of plastics and nanotechnology products, nanoplastics (NPs) have become a potential threat to human health. It is of great practical significance to study and evaluate the distribution of NPs in mice as mammal models and their entry, transport, and cytotoxicity in human cell lines. In this study, we detected the tissue distribution of fluorescent polystyrene nanoplastics (PS-NPs) in mice and assessed their endocytosis, transport pathways, and cytotoxic effects in GES-1 cells. We found that PS-NPs were clearly visible in gastric, intestine, and liver tissues of mice and in GES-1 cells treated with PS-NPs. Entry of PS-NPs into GES-1 cells decreased with the inhibition of caveolae-mediated endocytosis (nystatin), clathrin-mediated endocytosis (chlorpromazine HCl), micropinocytosis (ethyl-isopropyl amiloride), RhoA (CCG-1423), and F-actin polymerization (lantrunculin A). Rac1 inhibitors (NSC 23766) had no significant effect on PS-NPs entering GES-1 cells. F-actin levels significantly decreased in CCG-1423-pretreated GES-1 cells exposed to PS-NPs. GES-1 cell ultrastructural features indicated that internalized PS-NPs can be encapsulated in vesicles, autophagosomes, lysosomes, and lysosomal residues. RhoA, F-actin, RAB7, and LAMP1 levels in PS-NPs-treated GES-1 cells were remarkably up-regulated and the Rab5 level was significantly down-regulated compared to levels in untreated cells. PS-NPs treatment decreased cell proliferation rates and increased cell apoptosis. The formation of autophagosomes and autolysosomes and levels of LC3II increased with the length of PS-NPs treatment. The results indicated that cells regulated endocytosis in response to PS-NPs through the RhoA/F-actin signaling pathway and internalized PS-NPs in the cytoplasm, autophagosomes, or lysosomes produced cytotoxicity. These results illustrate the potential threat of NPs pollution to human health.

Ding|Yunfei|Y| Zhang|Ruiqing|R| Li|Boqing|B| Du|Yunqiu|Y| Li|Jing|J| Tong|Xiaohan|X| Wu|Yulong|Y| Ji|Xiaofei|X| Zhang|Ying|Y|

Nanoplastics Endocytosis Proliferation Apoptosis Autophagy


Genome-Wide Association Mapping Identifies Novel Panicle Morphology Loci and Candidate Genes in Sorghum.

Abstract: Panicle morphology is an important trait in racial classification and can determine grain yield and other agronomic traits in sorghum. In this study, we performed association mapping of panicle length, panicle width, panicle compactness, and peduncle recurving in the sorghum mini core panel measured in multiple environments with 6,094,317 single nucleotide polymorphism (SNP) markers. We mapped one locus each on chromosomes 7 and 9 to recurving peduncles and eight loci for panicle length, panicle width, and panicle compactness. Because panicle length was positively correlated with panicle width, all loci for panicle length and width were colocalized. Among the eight loci, two each were on chromosomes 1, 2, and 6, and one each on chromosomes 8 and 10. The two loci on chromosome 2, i.e., Pm 2-1 and Pm 2-2, were detected in 7 and 5 out of 11 testing environments, respectively. Pm 2-2 colocalized with panicle compactness. Candidate genes were identified from both loci. The rice Erect Panicle2 (EP2) ortholog was among the candidate genes in Pm 2-2. EP2 regulates panicle erectness and panicle length in rice and encodes a novel plant-specific protein with unknown functions. The results of this study may facilitate the molecular identification of panicle morphology-related genes and the enhancement of yield and adaptation in sorghum.

Wang|Lihua|L|
Upadhyaya|Hari D|HD|
Zheng|Jian|J|
Liu|Yanlong|Y|
Singh|Shailesh Kumar|SK|
Gowda|C L L|CLL|
Kumar|Rajendra|R|
Zhu|Yongqun|Y|
Wang|Yi-Hong|YH|
Li|Jieqin|J|

association mapping
panicle morphology
candidate genes
sorghum
mini core


Mineralogical dataset of natural zeolites from Lessini Mounts, Northern Italy: Analcime, natrolite, phillipsite and harmotome chemical composition.

Abstract: This dataset article contains mineralogical and chemical data of some natural zeolites such as analcime, natrolite, phillipsite and harmotome. These minerals were found as secondary phases within vesicles and veins in the basaltic rocks of the Lessini Mounts, Northern Italy. Methods for obtaining the datasets include optical microscopy, X-ray diffraction, scanning electron microscopy and electron probe microanalysis. Analcime forms well-developed, transparent to milky crystals with a typical icositetrahedron habit. The average composition of analcime is calculated as Na13.79Ca0.01K0.03Ba0.03[Al14.28Si33.82O96] 16H2O, with all of the extra-framework sites occupied by sodium. Natrolite usually forms hemispherical aggregates with glassy, colourless to white thin prismatic crystals, which generally radiate from a central point. The average chemical composition of natrolite is Na14.28Ca0.14K0.01[Al15.60Si24.59O80] 16H2O. Crystals of phillipsite-harmotome serie occur in a variety of forms and display a highly variable chemical composition, from almost pure compositions to intermediate values. Phillipsite is more common and its average chemical composition is Ca1.40Na0.29K1.08Ba0.27[Al4.68Si11.28O32] 12H2O, while harmotome is rare and has an average chemical composition of Ca0.97Na0.20K0.36Ba0.91[Al4.60Si11.46O32] 12H2O. The obtained dataset can be used for various purposes: it can be used by other authors to compare morphological features and chemical compositions of similar zeolites crystals discovered in other parts of the world, it can be compared with those obtained from similar geologic environments encouraging studies on hydrothermal processes, and it could represent the starting point for a potential exploration of zeolites from an industrial point of view.

Zeolites
Lessini Mounts
Basalts
Secondary minerals
Veneto Volcanic Province


Analgesic and Antidepressant Effects of the Clinical Glutamate Modulators Acetyl-L-Carnitine and Ketamine.

Abstract: Pain and depression are leading causes of disability and of profound social and economic burden. Their impact is aggravated by their chronicity and comorbidity and the insufficient efficacy of current treatments. Morphological and functional metabolism studies link chronic pain and depressive disorders to dysfunctional neuroplastic changes in fronto-limbic brain regions that control emotional responses to painful injuries and stressful events. Glutamate modulators are emerging new therapies targeting dysfunctional brain areas implicated in the generation and maintenance of chronic pain and depression. Here, we report the effects of two clinically approved glutamate modulators: acetyl-L-carnitine (ALCAR) and S, R(±)ketamine (KET). ALCAR is a natural neurotrophic compound currently marketed for the treatment of neuropathies. KET is the prototypical non-competitive antagonist at N-methyl-D-aspartate glutamate receptors and a clinically approved anesthetic. Although they differ in pharmacological profiles, ALCAR and KET both modulate aminergic and glutamatergic neurotransmissions and pain and mood. We assessed in rats the effects of ALCAR and KET on cerebral metabolic rates for glucose (rCMRglc) and assessed clinically the effects of ALCAR in chronic pain and of KET in post-operative pain. ALCAR and KET increased rCMRglc at similar degrees in prefrontal, somatosensory, and cingulate cortices, and KET increased rCMRglc at a different, much larger, degree in limbic and dopaminergic areas. While rCMRglc increases in prefrontal cortical areas have been associated with analgesic and antidepressant effects of ALCAR and KET, the marked metabolic increases KET induces in limbic and dopaminergic areas have been related to its psychotomimetic and abuse properties. In patients with chronic neuropathic pain, ALCAR (1,000 mg/day) yielded to a fast (2 weeks) improvement of mood and then of pain and quality of life. In day-surgery patients, KET improved dischargeability and satisfaction. In obese patients undergoing bariatric surgery, a single, low dose of KET (0.5 mg/kg) at induction of anesthesia determined a very fast (hours) amelioration of post-operative depression and pain and an opioid-sparing effect. These findings indicate that ALCAR and KET, two non-selective glutamate modulators, still offer viable therapeutic options in comorbid pain and depression.

Freo|Ulderico|U| Brugnatelli|Viola|V| Turco|Fabio|F| Zanette|Gastone|G|

regional cerebral metabolic rates for glucose


Prior knowledge snake segmentation of ultrasound images denoised by J-divergence anisotropy diffusion.

Abstract:
BACKGROUND
Applying transrectal ultrasound to robot-assisted laparoscopic radical prostatectomy has attracted attention in recent years, and it is considered as a proper method to provide real-time subsurface anatomic features. A precise registration between the ultrasound equipment and robotic surgical system is necessary, which usually requires a fast and accurate recognition of the registration tool in the ultrasound image.

METHODS
Tissue forceps are chosen as the registration tool. J-divergence anisotropy diffusion and prior knowledge snake segmentation are proposed for the automatic recognition of forceps in ultrasound images.

RESULTS
Simulation, gel tissue phantom experiments and in vitro experiments are carried out. Several evaluation indices are calculated to compare results under different methods.

CONCLUSIONS
The proposed methods are proved to be practicable, reliable and superior to existing ones, with reduced calculation time and higher accuracy.

prior knowledge snake segmentation
ultrasound image
anisotropy diffusion denoising


Magnetic nanoparticles coated with cyclodextrins and citrate for irinotecan delivery.

Abstract: In the present work, we study the role of different components in the formation of more stable iron oxide magnetic nanoparticles (MNPs): β-cyclodextrin (BCD), 2-hydroxypropyl-β-cyclodextrin (HP) and citrate anion. MNPs formulations were characterized by FTIR, particles size measurements, zeta potential based on dynamic light scattering principle technique, X-ray powder pattern diffraction, XPS spectroscopy, transmission electron microscopy and thermogravimetric analysis. The results showed that cyclodextrins and citrate plays a key role in order to obtain a lower size of coated MNPs and proved to be an efficient strategy to obtain a more stable colloidal dispersion, avoiding the nanoparticles oxidation, enhancing the irinotecan incorporation and release. Furthermore, citrate-coated BCD-MNPs showed the same cytotoxicity of the free IRI.

Monteiro|Ana P F|APF|
Caminhas|Larissa D|LD|
Ardisson|José D|JD|
Paniago|Roberto|R|
Cortés|Maria E|ME|
Sinisterra|Rubén D|RD|

Magnetic nanoparticle
Cyclodextrin
Citrate
Irinotecan
Cancer


Open-label study of long-term administration of dotinurad in Japanese hyperuricemic patients with or without gout.

Abstract:
BACKGROUND
Dotinurad is a novel selective urate reabsorption inhibitor (SURI) which reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). This study was intended to verify the efficacy and safety of dotinurad following treatment for 34 or 58 weeks in hyperuricemic patients with or without gout.

METHODS
This long-term study had an open-label design with dose escalation. The dose of dotinurad started at 0.5 mg/day and was increased progressively to 2 mg/day. If the serum uric acid level of patients did not reach ≤ 6 mg/dL at week 14, the dose was increased to 4 mg/day. The primary endpoint was the percent change in serum uric acid level from the baseline to each visit.

RESULTS
At a dose of 2 mg, serum uric acid levels at week 34 and 58 were reduced from the baseline by 46.73% and 47.17%, respectively; at 4 mg, the respective values were 54.92% and 57.35%. At week 34 and 58, the percentages of patients achieving a serum uric acid levels ≤ 6.0 mg/dL with 2-mg dose were 89.11% and 91.30%, respectively; with 4 mg, the respective rates were 97.50% and 100.00%. In addition, the incidences of adverse events and adverse drug reactions were 65.2% and 21.8%, respectively.

CONCLUSION
Dotinurad at doses of 2-4-mg sufficiently reduced serum uric acid levels in hyperuricemic patients with or without gout, and its efficacy and safety were verified for long-term administration. ClinicalTrials.gov Identifier: NCT03006445.

Hosoya|Tatsuo|T| Fushimi|Masahiko|M| Okui|Daisuke|D| Sasaki|Tomomitsu|T| Ohashi|Tetsuo|T|

D027701:Organic Cation Transport Proteins

Dotinurad
Gout
Selective urate reabsorption inhibitor
FYU-981
Hyperuricemia
URAT1 inhibitor


Development and characterization of an allergoid of cat dander for immunotherapy.

Abstract:
BACKGROUND
Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice.

METHODS
The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD was characterized in protein profile by SDS-PAGE, size exclusion chromatography (SEC) and peptide footprint. The allergenic profile of ACD was determined by immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen content in NCD was obtained by the ELISA sandwich protocol and was extrapolated to ACD.

RESULTS
The control process determined the optimal development of the allergoid. The ACD obtained contains 182.28μg/mg of protein and 11.90μg/mg of Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel d 7. The high degree of polymerization was evidenced with the determination of the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD showed a significant loss of allergenicity respect to NCD, while the IgG-binding capacity was maintained.

CONCLUSIONS
The ACD obtained presents a good safety profile, so would be a good alternative for treatment of cat allergy.

Sola|J P|JP|
Pedreño|Y|Y|
Cerezo|A|A|
Peñalver-Mellado|M|M|

Allergoid
Cat dander
Immunotherapy
Safety
Allergen-specific IgE


Protein Acetylation and Its Role in Bacterial Virulence.

Abstract: Protein acetylation is a universal post-translational modification which is found in both eukaryotes and prokaryotes. This process is achieved enzymatically by the protein acetyltransferase Pat, and nonenzymatically by metabolic intermediates (e.g., acetyl phosphate) in bacteria. Protein acetylation plays a role in bacterial chemotaxis, metabolism, DNA replication, and other cellular processes. Recently, accumulating evidence has suggested that protein acetylation might be involved in bacterial virulence because a number of bacterial virulence factors are acetylated. In this review, we summarize the progress in understanding bacterial protein acetylation and discuss how it mediates bacterial virulence.

Ren|Jie|J| Sang|Yu|Y| Lu|Jie|J| Yao|Yu-Feng|YF|


Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules.

Abstract: For many years, bile acids were thought to only function as detergents which solubilize fats and facilitate the uptake of fat-soluble vitamins in the intestine. Many early observations; however, demonstrated that bile acids regulate more complex processes, such as bile acids synthesis and immune cell function through activation of signal transduction pathways. These studies were the first to suggest that receptors may exist for bile acids. Ultimately, seminal studies by many investigators led to the discovery of several bile acid-activated receptors including the farnesoid X receptor, the vitamin D receptor, the pregnane X receptor, TGR5, α5 β1 integrin, and sphingosine-1-phosphate receptor 2. Several of these receptors are expressed outside of the gastrointestinal system, indicating that bile acids may have diverse functions throughout the body. Characterization of the functions of these receptors over the last two decades has identified many important roles for these receptors in regulation of bile acid synthesis, transport, and detoxification; regulation of glucose utilization; regulation of fatty acid synthesis and oxidation; regulation of immune cell function; regulation of energy expenditure; and regulation of neural processes such as gastric motility. Through these many functions, bile acids regulate many aspects of digestion ranging from uptake of essential vitamins to proper utilization of nutrients. Accordingly, within a short time period, bile acids moved beyond simple detergents and into the realm of complex signaling molecules. Because of the important processes that bile acids regulate through activation of receptors, drugs that target these receptors are under development for the treatment of several diseases, including cholestatic liver disease and metabolic syndrome. In this review, we will describe the various bile acid receptors, the signal transduction pathways activated by these receptors, and briefly discuss the physiological processes that these receptors regulate.

D018160:Receptors, Cytoplasmic and Nuclear

Bile acids
Farnesoid X receptor
Vitamin D receptor
Pregnane X receptor
TGR5
Sphingosine-1-phosphate receptor 2


ECMPride: prediction of human extracellular matrix proteins based on the ideal dataset using hybrid features with domain evidence.

Abstract: Extracellular matrix (ECM) proteins play an essential role in various biological processes in multicellular organisms, and their abnormal regulation can lead to many diseases. For large-scale ECM protein identification, especially through proteomic-based techniques, a theoretical reference database of ECM proteins is required. In this study, based on the experimentally verified ECM datasets and by the integration of protein domain features and a machine learning model, we developed ECMPride, a flexible and scalable tool for predicting ECM proteins. ECMPride achieved excellent performance in predicting ECM proteins, with appropriate balanced accuracy and sensitivity, and the performance of ECMPride was shown to be superior to the previously developed tool. A new theoretical dataset of human ECM components was also established by applying ECMPride to all human entries in the SwissProt database, containing a significant number of putative ECM proteins as well as the abundant biological annotations. This dataset might serve as a valuable reference resource for ECM protein identification.

Liu|Binghui|B| Leng|Ling|L| Sun|Xuer|X| Wang|Yunfang|Y| Ma|Jie|J| Zhu|Yunping|Y|

Extracellular matrix proteins
Prediction tool
Proteomics
Random forest
Under-sampling ensemble method


Tomography of anthropogenic nitrate contribution along a mesoscale river.

Abstract: Elevated nitrate concentrations are a thread for water supply and ecological integrity in surface water. Nitrate fluxes obtained by standard monitoring protocols at the catchment outlet strongly integrate spatially and temporally variable processes such as mobilization and turnover. Consequently, inference of dominant nitrate sources is often problematic and challenging in terms of effective river management and prioritization of measures. Here, we combine a spatially highly resolved assessment of nitrate concentration and fluxes along a mesoscale catchment with four years of monitoring data at two representative sites. The catchment is characterized by a strong land use gradient from pristine headwaters to lowland sub-catchments with intense agricultural land use and wastewater sources. We use nitrate concentrations in combination with hydrograph separation and isotopic fingerprinting methods to characterize and quantify nitrate source contribution. The hydrological analysis revealed a clear dominance of base flow during both campaigns. However, the absolute amounts of discharge differed considerably from one another (outlet: 1.42m3s-1 in 2014, 0.43m3s-1 in 2015). Nitrate concentrations are generally low in the pristine headwaters (<3mgL-1) and increase downstream (15 to 16mgL-1) due to the contribution of agricultural and wastewater sources. While the agricultural contribution did not vary in terms of nitrate concentration and isotopic signature between the years, the wastewater contribution strongly increased with decreasing discharge. Wastewater-borne nitrate load in the entire catchment ranged between 19% (2014) and 39% (2015). Long-term monitoring of nitrate concentration and isotopic composition in two sub-catchment exhibits a good agreement with findings from spatially monitoring. In both datasets, isotopic composition indicates that denitrification plays only a minor role. The spatially highly resolved monitoring approach helped to pinpoint hot spots of nitrate inputs into the stream while the long-term information allowed to place results into the context of intra-annual variability.

Müller|Christin|C| Musolff|Andreas|A| Strachauer|Ulrike|U| Brauns|Mario|M| Tarasova|Larisa|L| Merz|Ralf|R| Knöller|Kay|K|

Surface water
Meso-scale isotope pattern
Nitrate pollution
Nitrogen isotope of nitrate
Water quality


Frequent Epigenetic Inactivation of DIRAS-1 and DIRAS-2 Contributes to Chemo-Resistance in Gliomas.

Abstract: We previously reported that DIRAS-3 is frequently inactivated in oligodendrogliomas due to promoter hypermethylation and loss of the chromosomal arm 1p. DIRAS-3 inactivation was associated with better overall survival. Consequently, we now investigated regulation and function of its family members DIRAS-1 and DIRAS-2. We found that DIRAS-1 was strongly downregulated in 65% and DIRAS-2 in 100% of analyzed glioma samples compared to non-neoplastic brain tissue (NNB). Moreover, a significant down-regulation of DIRAS-1 and -2 was detected in glioma data obtained from the TCGA database. Mutational analyses did not reveal any inactivating mutations in the DIRAS-1 and -2 coding regions. Analysis of the DIRAS-1 and -2 promoter methylation status showed significantly higher methylation in IDH-mutant astrocytic and IDH-mutant and 1p/19q-codeleted oligodendroglial tumors compared to NNB. Treatment of U251MG and Hs683 glioblastoma cells lines with 5-azacytidine led to significant re-expression of DIRAS-1 and -2. For IDH-wild-type primary gliomas, however, we did not observe significantly elevated DIRAS-1 and -2 promoter methylation levels, but still detected strong downregulation of both DIRAS family members. Additional analyses revealed that DIRAS-1 and -2 expression was also regulated by histone modifications. We observed a shift towards promoter heterochromatinization for DIRAS-1 and less promoter euchromatinization for DIRAS-2 in IDH-wild-type glioblastomas compared to controls. Treatment of the two glioblastoma cell lines with a histone deacetylase inhibitor led to significant re-expression of DIRAS-1 and -2. Functionally, overexpression of DIRAS-1 and -2 in glioblastoma cells translated into significantly higher sensitivity to lomustine treatment. Analyses of DNA damage markers revealed that DIRAS-1 and -2 may play a role in p53-dependent response to alkylating chemotherapy.

methylation
glioblastoma
histone modification
lomustine
chromatin
p53


The efficacy and safety of simultaneous integrated dose reduction in clinical target volume with intensity-modulated radiotherapy for patients with locally advanced esophageal squamous cell carcinoma.

Abstract:
Background
Compelling research to explore the effectiveness of simultaneous integrated dose reduction in clinical target volume (CTV) with intensity-modulated radiotherapy (SIR-IMRT) for locally advanced esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare the clinical efficacy and treatment-related toxicity between SIR-IMRT and conventional IMRT (C-IMRT) in the treatment of ESCC.

Methods
From March 2010 to September 2016, the clinical data of 257 patients with ESCC who received definitive IMRT in the Tianjin Medical University Cancer Institute and Hospital were collected and retrospectively analyzed. Among these patients, 137 patients received C-IMRT with a prescribed dose of 60 Gy in 30 fractions for planning target volume (PTV), while 120 patients received SIR-IMRT with a prescribed dose of 60 Gy in 30 fractions for the planning gross tumor volume (PGTV) and a prescribed dose of 54 Gy in 30 fractions for PTV. All of the patients received definitive IMRT with elective nodal irradiation. Locoregional control, survival, treatment toxicity and dose to organs at risk (OAR) were compared between the groups.

Results
Patients who received SIR-IMRT showed a similar locoregional failure rate compared to the C-IMRT group (27.5% versus 29.9%, P=0.668). The 1-, 2- and 3-year overall survival (OS) rates were 71.5%, 44.3%, 44.3% vs. 77.9%, 52.1%, 32.9% in the C-IMRT and SIR-IMRT groups, respectively (P=0.825). No significant differences were observed in PFS and LRRFS between the two groups (P=0.880 and P=0.216, respectively). The dose of lung V30 and the maximum dose of spinal cord in the C-IMRT group were significantly higher than those in the SIR-IMRT group (P=0.013, P=0.047). The incidence of acute radiation esophagitis was significantly lower in the SIR-IMRT group (P=0.046), although no statistical difference was observed in the incidence of acute severe adverse events between the two groups.

Conclusions
SIR-IMRT offers an effective and safe option for patients with unresectable ESCC who receive definitive RT. Further prospective and larger sample size studies are warranted to confirm our results.

Zhao|Jingjing|J| Lei|Tongda|T| Zhang|Tian|T| Chen|Xi|X| Dong|Jie|J| Guan|Yong|Y| Wang|Jing|J| Wei|Hui|H| Er|Puchun|P| Han|Dong|D| Wei|Xiaoying|X| Guo|Zhoubo|Z| Du|Qingwu|Q| Wang|Jun|J| Liu|Ningbo|N| Song|Yongchun|Y| Yuan|Zhiyong|Z| Zhao|Lujun|L| Zhang|Wencheng|W| Pang|Qingsong|Q| Wang|Ping|P|

Esophageal squamous cell carcinoma (ESCC)


Which Aspects of Professional Commitment Can Effectively Retain Nurses in the Nursing Profession?

Abstract:
PURPOSE
This study examined which aspects of professional commitment can effectively retain nurses in the nursing profession.

DESIGN, SETTINGS, AND PARTICIPANTS
This study used a longitudinal design, simple random sampling, and two-wave data collection to survey and follow up a representative sample of 579 nurses for 1 year in a major medical center in northern Taiwan.

METHODS
Items measuring each aspect of professional commitment came from Meyer et al.'s scale. In the second wave, administrative data were culled to determine whether these nurses remain employed as nurses. Structural equation modeling is used to analyze the data.

RESULTS
Analytical results indicate that continuance commitment predicts nurse retention in the nursing profession (path coefficient = 0.34, p < .01).

CONCLUSIONS
Institutional efforts to improve continuance commitment (e.g., improved salary structures and enhanced professional development opportunities) likely retain nurses in the nursing profession.

CLINICAL RELEVANCE
The findings of this study indicate the importance of continuance intention in retaining nurses. Nursing managers who face staff retention issues may consider making efforts to improve nurse salary and employer-sponsored benefits.

Chang|Hao-Yuan|HY|
Shyu|Yea-Ing Lotus|YI|
Wong|May-Kuen|MK|
Friesner|Daniel|D|
Chu|Tsung-Lan|TL|
Teng|Ching-I|CI|

professional commitment
continuance commitment
nurse retention
Affective commitment
normative commitment


Different influences on mitochondrial function, oxidative stress and cytotoxicity of antibiotics on primary human neuron and cell lines.

Abstract: Although antibiotics are generally well tolerated, their toxic effects on the central nervous system have been gained attention. In this study, we systematically investigated the neuron toxicity of antibiotics from six different classes. We show that clinically relevant concentrations of metronidazole, tigecycline, azithromycin and clindamycin but not ampicillin or sulfamethoxazole induce apoptosis of human primary neuron cells and lines. Notably, tigecycline, azithromycin and clindamycin cause neuron cell oxidative damage whereas metronidazole has no effect on reactive oxygen species (ROS) production, suggesting that metronidazole induces neuron death via ROS-independent mechanism. Tigecycline, azithromycin and clindamycin induce mitochondrial dysfunctions via targeting different mitochondrial respiratory complexes, leading to mitochondrial membrane potential disruption and energy crisis. The deleterious effects of antibiotics are reversed by pretreatment of neuron cells with antioxidant. Our work highlights the different influences of antibiotics on mitochondrial dysfunction, oxidative damage and cytotoxicity in neuron cells. We also provide a strategy to prevent the neurotoxicity.

antibiotics
oxidative damage
mitochondrial dysfunction
neuron disease


Immunity to rubella: an Italian retrospective cohort study.

Abstract:
BACKGROUND
International guidelines recommend that healthcare workers (HCWs) have presumptive evidence of immunity to rubella and that susceptible HCWs and doubt cases receive two doses of the MMR vaccine. However, a small percentage of the fully immunized will remain unprotected against wild viruses. Moreover, protective levels of antibodies induced by the vaccine have been shown to decline over time, but a formal recommendation regarding the testing of immunized HCWs for the persistence of IgG against rubella is lacking.

METHODS
The aim of this study was to evaluate the long-term immunogenicity conferred by rubella vaccination and the effectiveness of a strategy for the management of immunized individuals in whom IgG against rubella could not be demonstrated (non-responders). The study enrolled students and medical residents who attended the Hygiene Department of Bari Policlinico University Hospital for biological risk assessment (April 2014 to June 2018).

RESULTS
Two thousand students and residents with documented immunization (≥2 doses of rubella or MMR vaccine) were tested. In 181 (9%), IgG against rubella was not detectable. The seronegative rate was higher among participants vaccinated at age < 2 years (89.6%) and lower among those immunized at age ≥ 2 years (93.6%; p < 0.0001). The administration of a single MMR booster dose resulted in a seroconversion rate of 98% in the seronegative group. The seroconversion rate after a second booster dose was 100%. No serious adverse events in the re-immunized were recorded.

CONCLUSIONS
An important proportion of individuals immunized for rubella or MMR do not have a protective titer for the disease(s). Our management strategy (booster followed by re-test and, for those who are still negative, a second booster and re-test) is consistent with the goal of achieving immunological memory.

Healthcare workers
MMR vaccine
Booster dose
Duration of immunization


Barbed sutures reduce arthrotomy closure duration and suture utilisation compared to interrupted conventional sutures for primary total hip arthroplasty: a randomised controlled trial.

Abstract:
INTRODUCTION
The broad aim of this study was to compare the safety and efficacy of using barbed sutures and running closure versus interrupted placement of standard of care sutures for closure of the arthrotomy during total hip arthroplasty (THA). Specifically, we compared duration of arthrotomy closure, the number of sutures utilised for arthrotomy closure, and 90-day outcomes including wound-related readmission, reoperation, and complications.

METHODS
A total of 60 patients undergoing 60 THAs were enrolled in a prospective, single-blinded trial and randomised to receive either running closure of the arthrotomy with barbed sutures (n = 30) or interrupted closure with standard of care sutures (n = 30). Patients were eligible if they were undergoing primary THA for osteoarthritis and excluded if they had a BMI > 45 kg/m2 or age > 80 years or <18 years.

RESULTS
Arthrotomy closure duration was significantly shorter in the barbed suture group (3 minutes ± 9 seconds) versus the standard of care group (8 minutes ± 26 seconds, p < 0.001). The suture utilisation for arthrotomy closure was 1 suture in the barbed sutured group 28/30 (93%) patients versus 2-4 sutures in 27/30 (90%) in the standard of care group (p < 0.001). The overall number of wound-related complications in the barbed suture group was 1/30 (3%) versus 1/30 (3%) in the standard of care group (p = 1.00). The rate of suture abscesses was 1/30 (3%) in barbed suture group versus the standard of care (p = 1.00). There was trochanter bursitis 1/30 (3%) in the standard of care group versus zero in the barbed suture group (p = 1.00).

CONCLUSIONS
These results suggest that barbed suture utilisation may be faster and more resource efficient than use of standard of care sutures for arthrotomy closure in THA.ClinicalTrials.gov Identifier: NCT03285555.

D000369:Aged, 80 and over
D019644:Arthroplasty, Replacement, Hip
D019645:Arthroplasty, Replacement, Knee
D006801:Humans
D011446:Prospective Studies
D013536:Suture Techniques
D013537:Sutures
D016896:Treatment Outcome

Barbed suture
total hip arthroplasty
total hip replacement
wound closure


Life at the Margins: Marginality and Race in Undergraduate Students and Faculty.

Abstract: The United States has become increasingly diverse, but this same rise in diversity is not reflected in the nursing profession. The purpose of this study was to investigate the relationship between marginality and minority status for nursing students in two states with very different racial/ethnic minority profiles. Marginality was measured using the Koci Marginality Index. When comparing students by geographical region, there were statistically significant differences between the two groups with regard to the marginality subconcepts of intermediacy, differentiation, power, secrecy, voice, liminality, and reflectiveness. Data were also collected from nurse faculty at each of the universities in Texas and Wisconsin. Findings suggest that there are significant differences between the two faculty samples with regard to advising, tutoring, and mentoring activities, as well as referral of minority students to campus resources. Marginalization is a complicated, deeply entrenched issue that continues to significantly impact minority nursing students across the nation.

marginalization
faculty
diversity
nursing students


Prevalence, characteristics, and distribution of HPV genotypes in women from Zhejiang Province, 2016-2020.

Abstract:
OBJECTIVE
To evaluate and understand the prevalence of HPV genotypes and characteristics of female populations in specific areas and the relationship with cervical lesions, which can effectively guide cervical cancer screening and formulate HPV vaccine prevention strategies.

METHODS
A total of 77,443 women who visited gynecological clinics and underwent health examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine during 2016-2020 were enrolled in this survey. Cervical samples were collected for HPV DNA genotyping and cervical cytology testing. Cervical biopsies were performed for patients with visible cervical abnormality or abnormal cytological results.

RESULTS
The results showed the 5-year overall positive rate was 22.3%, of which the gynecology clinic group had significantly more positive results compared with the health examination group (P < 0.001). The five most common genotypes in Zhejiang Province were HPV 52, 58, CP8304, 16, and 51 (23.9%, 12.7%, 11.7%, 11.7% and 9.3%). HPV infection was age-specific, with the highest infection rate in the age group ≤ 20 compared to other age groups (P < 0.001). HPV infection was also season-specific, with the highest infection rate in spring or winter. The main HPV infection mode was single infection (P = 0.004), but patients ≤ 20 years old were more likely to develop multiple infections (51.0%). HPV 16, 52 and 58 were the main genotypes that caused cytological abnormalities and HPV16, 18, 56, 58 and 66 were independent risk factors for cervical lesions (OR = 2.352, 1.567, 2.000, 1.694, 1.889; all P < 0.05). Further analysis found HPV 16 and 18 were the main genotypes that cause cervical cancer histological abnormalities and were independent risk factors for cervical cancer (OR = 5.647, P < 0.001; OR = 3.495, P = 0.036).

CONCLUSION
This article analyzed the prevalence of distribution characteristics of HPV infection and revealed the corelation between HPV infection and cytological and histological abnormalities. Comprehensive results of this survey will help Zhejiang Province to formulate public health policies and provide evidence for future selection of specific HPV vaccines.


Hepatitis E virus infection and waste pickers: A case-control seroprevalence study.

Abstract: Whether waste pickers are a risk group for hepatitis E virus (HEV) infection is largely unknown. This study aimed to determine the association between HEV exposure and the occupation of waste pickers and the work characteristics of waste pickers. An age-and gender-matched case-control seroprevalence study of 86 waste pickers and 86 control subjects of the general population was performed. We determined anti-HEV IgG antibodies in sera of cases and controls using a commercially available enzyme-linked immunoassay. The McNemar's test was used to assess the association between HEV seropositivity and the occupation of waste picker. The association between HEV seropositivity and work characteristics of waste pickers was assessed by bivariate and logistic regression analyses. Anti-HEV IgG antibodies were detected in 14 (16.3%) of the 86 waste pickers and in 8 (9.3%) of the 86 control subjects (McNemar's pair test: odds ratio (OR) = 13.0; 95% confidence interval (CI): 0.73-230.77; p = .02). Bivariate analysis showed that HEV exposure was associated with an ill status (p = .01) and reflexes impairment (p = .009). Logistic regression analysis showed that HEV seropositivity was associated with increasing age (OR = 6.52; 95% CI: 1.95-21.78; p = .002) and raising pigs (OR = 12.01; 95% CI: 1.48-97.26; p = .02). This is the first age- and gender-matched case-control study on the association between HEV infection and the occupation of waste picker. Waste pickers represent a risk group for HEV infection. Factors associated with HEV seropositivity found in this study may help in the design of optimal planning to avoid HEV infection.

Hepatitis E virus
waste pickers
case-control study
Mexico
epidemiology


Gait Retraining With Real-Time Biofeedback to Reduce Knee Adduction Moment: Systematic Review of Effects and Methods Used.

Abstract:
OBJECTIVE
To review the current literature regarding methods and effects of real-time biofeedback used as a method for gait retraining to reduce knee adduction moment (KAM), with intended application for patients with knee osteoarthritis (KOA).

DATA SOURCES
Searches were conducted in MEDLINE, Embase, CINAHL, SPORTDiscus, Web of Science, and Cochrane Central Register of Controlled Trials with the keywords gait, feedback, and knee osteoarthritis from inception to May 2015.

STUDY SELECTION
Titles and abstracts were screened by 1 individual for studies aiming to reduce KAM. Full-text articles were assessed by 2 individuals against predefined criteria.

DATA EXTRACTION
Data were extracted by 1 individual according to a predefined list, including participant demographics and training methods and effects.

DATA SYNTHESIS
Electronic searches resulted in 190 potentially eligible studies, from which 12 met all inclusion criteria. Within-group standardized mean differences (SMDs) for reduction of KAM in healthy controls ranged from .44 to 2.47 and from .29 to .37 in patients with KOA. In patients with KOA, improvements were reported in pain and function, with SMDs ranging from .55 to 1.16. Methods of implementation of biofeedback training varied between studies, but in healthy controls increased KAM reduction was noted with implicit, rather than explicit, instructions.

CONCLUSIONS
This review suggests that biofeedback gait training is effective primarily for reducing KAM but also for reducing pain and improving function in patients with KOA. The review was limited by the small number of studies featuring patients with KOA and the lack of controlled studies. The results suggest there is value and a need in further researching biofeedback training for reducing KAM. Future studies should include larger cohorts of patients, long-term follow-up, and controlled trials.

Richards|Rosie|R|
van den Noort|Josien C|JC|
Dekker|Joost|J|
Harlaar|Jaap|J|

D001676:Biofeedback, Psychology
D005684:Gait
D006801:Humans
D007719:Knee Joint
D020370:Osteoarthritis, Knee
D026741:Physical Therapy Modalities

Gait
Osteoarthritis, knee
Rehabilitation


Finding the right mix: a framework for selecting seeding rates for cover crop mixtures.

Abstract: Cover crop mixtures have the potential to provide more ecosystem services than cover crop monocultures. However, seeding rates that are typically recommended (i.e. seeding rate of monoculture divided by the number of species in the mixture) are non-optimized and often result in the competitive species dominating the mixture, and therefore limiting the amount of ecosystem services that are provided. We created an analytical framework for selecting seeding rates for cover crop mixtures that maximize multifunctionality while minimizing seed costs. The framework was developed using data from a field experiment, which included six response surface designs of two-species mixtures, as well as a factorial replacement design of three-species and four-species mixtures. We quantified intraspecific and interspecific competition among two grasses and two legume cover crop species with grass and legume representing two functional groups: pearl millet [Pennisetum glaucum (L.) R.Br.], sorghum sudangrass [Sorghum bicolor (L.) Moench × Sorghum sudanense (Piper) Stapf], sunn hemp (Crotalaria juncea L.), and cowpea [Vigna unguiculata (L.) Walp]. Yield-density models were fit to estimate intraspecific and interspecific competition coefficients for each species in biculture. The hierarchy from most to least competitive was sorghum sudangrass > sunn hemp > pearl millet > cowpea. Intraspecific competition of a less competitive species was the greatest when the biculture was composed of two species in the same functional group. Competition coefficients were used to build models that estimated the biomass of each cover crop species in three-species and four-species mixtures. The competition coefficients and models were validated with an additional nine site-years testing the same cover crop mixtures. The biomass of a species in a site-year was accurately predicted 69% of the time (low root mean square error, correlation > 0.5, not biased, r2 > 0.5). Applying the framework, we designed three-species and four-species mixtures by identifying relative seeding rates that produced high biomass with high species evenness (i.e. high multifunctionality) at low seed costs based on a Pareto front analysis of 10,418 mixtures. Accounting for competition when constructing cover crop mixtures can improve the ecosystem services provided, and such an advancement is likely to lead to greater farmer adoption.

cover crops
mixtures
competition
multifunctionality
response surface design
yield-density model
Pareto front
optimization


Cholinergic system and exploratory behavior are changed after weekly-binge ethanol exposure in zebrafish.

Abstract: Binge drinking is characterized by excessive alcohol consumption in a short period of time and is associated with a poor quality of life. Zebrafish are commonly used to investigate neurochemical, behavioral, and genetic parameters associated with ethanol (EtOH) exposure. However, few studies have used zebrafish as a model to investigate binge EtOH exposure. In order to elucidate the potential neurobehavioral impairments evoked by binge EtOH exposure in zebrafish, animals were immersed in 1.4% EtOH for 30 min three consecutive times with intervals of one week. Neurobehavioral parameters were analyzed immediately following the third exposure, as well as 2 and 9 days later. Brain choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were reduced 9 days after the treatment. Thiobarbituric acid-reactive species and dichlorodihydrofluorescein levels were increased immediately after the treatment, but both returned to normal levels 2 days after the treatment. Catalase and glutathione reductase were impaired 2 and 9 days after the treatment. No alteration was observed in superoxide dismutase and glutathione peroxidase activities. EtOH treatment did not alter brain expression of inflammatory genes such as il-1β, il-10, and tnf-α. Zebrafish displayed anxiolytic-like behavior immediately after the last exposure, though there was no behavioral alteration observed 9 days after the treatment. Therefore, binge EtOH exposure in zebrafish leads to long lasting brain cholinergic alteration, probably related to oxidative stress immediately after the exposure, which is independent of classical inflammatory markers.

Bernardo|Henrique Teza|HT|
Agostini|Jotele Fontana|JF|
Toé|Helena Cristina Zuehl Dal|HCZD|
Vieira|Karine Medeiros|KM|
Baldin|Samira Leila|SL|
Schuck|Patrícia Fernanda|PF|
Uribe-Cruz|Carolina|C|
Longo|Larisse|L|
da Silveira|Themis Reverbel|TR|
Rosemberg|Denis Broock|DB|
Rico|Eduardo Pacheco|EP|

Cholinergic
Behavior
Zebrafish
Binge EtOH
Oxidative stress


Measurement of Neighborhood Context in an Urban Cohort of HIV-infected or at risk Low-Income Women.

Abstract: The study of neighborhood disadvantage and health relies on census socioeconomic data but would benefit from reliable survey measures of factors that influence health within low income communities. The Perceptions of Neighborhood Environment Scale (PNES) was developed for use in the general U.S. population, and its measurement properties in a cohort of low-income urban women living with or at risk for HIV are described. The scale and all but one subscale have good psychometric and ecometric reliability, as well as convergent, construct, and concurrent validity, and are not collinear with household and community area income in low-income urban neighborhoods.

Burke-Miller|Jane K|JK|
Weber|Kathleen|K|
Cohn|Susan E|SE|
Hershow|Ronald C|RC|
Sha|Beverly|B|
French|Audrey L|AL|
Cohen|Mardge H|MH|

HIV/AIDS
HLM
gender
poverty measurement
survey research


Reconfiguration of DNA methylation in aging.

Abstract: A complex interplay between multiple biological effects shapes the aging process. The advent of genome-wide quantitative approaches in the epigenetic field has highlighted the effective impact of epigenetic deregulation, particularly of DNA methylation, on aging. Age-associated alterations in DNA methylation are commonly grouped in the phenomenon known as "epigenetic drift" which is characterized by gradual extensive demethylation of genome and hypermethylation of a number of promoter-associated CpG islands. Surprisingly, specific DNA regions show directional epigenetic changes in aged individuals suggesting the importance of these events for the aging process. However, the epigenetic information obtained until now in aging needs a re-consideration due to the recent discovery of 5-hydroxymethylcytosine, a new DNA epigenetic mark present on genome. A recapitulation of the factors involved in the regulation of DNA methylation and the changes occurring in aging will be described in this review also considering the data available on 5 hmC.

Zampieri|Michele|M| Ciccarone|Fabio|F| Calabrese|Roberta|R| Franceschi|Claudio|C| Bürkle|Alexander|A| Caiafa|Paola|P|


Critical factors in the recovery of pathogenic microorganisms in blood.

Abstract:
BACKGROUND
The critical factors for optimal recovery of microbial pathogens from blood are not only the basis for how we perform blood cultures on a daily basis, but are also important for development of all current blood-culture systems. Because much of this research was conducted and published between 1975 and 2010 there is a general sense that many physicians and scientists may not be familiar with it, but it is critical for performing and interpreting blood cultures.

OBJECTIVES
To review the critical factors in the laboratory recovery and isolation of pathogenic microorganisms in blood.

SOURCES
Literature review of published papers, select reviews and updated guidelines.

CONTENT
This review focuses on the critical factors that affect the recovery isolation of pathogenic microorganisms from individuals with bloodstream infections. Contemporary blood-culture systems, and current methods for blood-culture collection, have been designed to incorporate these critical factors so as to optimize recovery and isolation of pathogens while minimizing contamination.

IMPLICATIONS
It is important for microbiologists and practitioners to understand how and why these critical factors affect current blood-culture practices to improve patient management. Future research should emphasize which of these critical factors will still play a role in the era of molecular diagnostic tests, which will no longer be relevant, and which new critical factors have yet to be defined.

Blood culture
Bloodstream infection
Bacteraemia
Fungaemia
Sepsis


Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors.

Abstract: Increased interest in marine resources has led to increased screening of marine fungi for novel bioactive compounds and considerable effort is being invested in discovering these metabolites. For compound discovery, small-scale cultures are adequate, but agitated bioreactors are desirable for larger-scale production. Calcarisporium sp. KF525 has recently been described to produce calcaride A, a cyclic polyester with antibiotic activity, in agitated flasks. Here, we describe improvements in the production of calcaride A in both flasks (13-fold improvement) and stirred bioreactors (200-fold improvement). Production of calcaride A in bioreactors was initially substantially lower than in shaken flasks. The cultivation pH (reduced from 6.8 to <5.4), carbon source (sucrose replacing glucose), C/N ratio and nature of mycelial growth (pellets or filaments) were important in improving calcaride A production. Up to 4.5 mg·g-1 biomass (85 mg·L-1) calcaride A were produced in the bioreactor, which was only slightly less than in shaken flasks (14 mg·g-1, 100 mg·L-1). The results demonstrate that a scalable process for calcaride A production could be developed using an iterative approach with flasks and bioreactors.

Tamminen|Anu|A|
Wang|Yanming|Y|
Wiebe|Marilyn G|MG|

calcaride A
Calcarisporium
marine fungi
pH
macrocylic polyester
stirred tank bioreactor


Fabrication and Mechanism Study of Cerium-Based P, N-Containing Complexes for Reducing Fire Hazards of Polycarbonate with Superior Thermostability and Toughness.

Abstract: A superior comprehensive performance is essential for the extensive utilization of polymers. Current flame-retardant strategies for polycarbonates (PCs) usually realize satisfied fire resistance at the cost of thermostability, toughness, and/or mechanical robustness. Thus, we report a rare-earth-based P, N-containing complex with a lamellar aggregated structure [Ce(DPA)3] by a coordination reaction between a tailored ligand and cerium(III) nitrate. The results indicate that incorporating 3 wt % Ce(DPA)3 enables the resultant PC composite to achieve UL-94 V-0 rating, with a 55% reduction in the peak heat release rate. Besides, the initial (T5) and maximum (Tmax1 and Tmax2) decomposition temperatures are significantly increased by 21, 19, and 27 °C, respectively, in an air atmosphere. Moreover, the impact strength and elongation at break of the PC composite containing 3 wt % Ce(DPA)3 are greatly increased by 20 and 59%, respectively, relative to pristine PC, while its tensile strength (57 MPa) is still close to that of bulk PC (60 MPa). Notably, this work provides a novel methodology for revealing the evolution mechanisms of chemical structures of vapor and residual products during thermal decomposition, which is conducive to guiding fire and heat resistance modification of PC in the future.

polycarbonate
fire-retardant mechanisms
rare-earth complexes
thermal resistance
toughen


Bacterial Min proteins beyond the cell division.

Abstract: Min system in Escherichia coli is one of the well-studied phenomena of self-organization and spatial distribution of proteins. Several multidisciplinary approaches were used to study the oscillation phenomena of the Min system. The focus of most of these studies was to understand the role of Min system in placement of the Z-ring to the mid-cell and to characterize its interaction with divisome proteins. The involvement of Min system in other cellular processes is poorly characterized. Few recent studies have suggested that Min proteins play an important role in various cellular processes such as bacterial motility, colonization, and virulence. Similarly, MinD is reported to interact with RNaseE, which suggests the association of the Min system with RNA decay. Our Protein-Protein Interaction network analysis shows that MinD interacts with proteins from diverse cellular processes such as protein secretory pathway, chaperone system, and bacterial adhesion. These studies suggest that apart from its role in cell division, Min system also plays a key role in other essential cellular processes. In this review, we have discussed the role of the Min system in cellular processes other than the cell division, such as RNA decay, bacterial motility, and virulence.

Taviti|Ashoka Chary|AC|
Beuria|Tushar Kant|TK|

D000251:Adenosine Triphosphatases
D001422:Bacterial Adhesion
D002455:Cell Division
D004926:Escherichia coli
D029968:Escherichia coli Proteins
D011485:Protein Binding
D060066:Protein Interaction Maps
D021381:Protein Transport

Min System
virulence
RNaseE
bacterial adhesion
FlhG


Properties of Slo1 K+ channels with and without the gating ring.

Abstract: High-conductance Ca(2+)- and voltage-activated K(+) (Slo1 or BK) channels (KCNMA1) play key roles in many physiological processes. The structure of the Slo1 channel has two functional domains, a core consisting of four voltage sensors controlling an ion-conducting pore, and a larger tail that forms an intracellular gating ring thought to confer Ca(2+) and Mg(2+) sensitivity as well as sensitivity to a host of other intracellular factors. Although the modular structure of the Slo1 channel is known, the functional properties of the core and the allosteric interactions between core and tail are poorly understood because it has not been possible to study the core in the absence of the gating ring. To address these questions, we developed constructs that allow functional cores of Slo1 channels to be expressed by replacing the 827-amino acid gating ring with short tails of either 74 or 11 amino acids. Recorded currents from these constructs reveals that the gating ring is not required for either expression or gating of the core. Voltage activation is retained after the gating ring is replaced, but all Ca(2+)- and Mg(2+)-dependent gating is lost. Replacing the gating ring also right-shifts the conductance-voltage relation, decreases mean open-channel and burst duration by about sixfold, and reduces apparent mean single-channel conductance by about 30%. These results show that the gating ring is not required for voltage activation but is required for Ca(2+) and Mg(2+) activation. They also suggest possible actions of the unliganded (passive) gating ring or added short tails on the core.

Budelli|Gonzalo|G|
Geng|Yanyan|Y|
Butler|Alice|A|
Magleby|Karl L|KL|
Salkoff|Lawrence|L|

D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits

BK channel
Kv1.4
iberiotoxin
tetraethylammonium
β1 subunit


One-pot synthesis of biocompatible superparamagnetic iron oxide nanoparticles/hydrogel based on salep: characterization and drug delivery.

Abstract: This work describes synthesis of biocompatible magnetic iron oxide nanoparticles/hydrogel based on salep (MION-salep hydrogel) by a facile one-pot strategy. The prepared sample was characterized by techniques like scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDAX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), and vibrating sample magnetometer (VSM). The obtained MION had an 8 nm diameter with a narrow size distribution and was superparamagnetic with large saturation magnetization at room temperature. The most attractive feature of the obtained sample was its swelling properties under external magnetic field (EMF), different temperatures, and pHs. Moreover, MION-salep hydrogel showed ability to deferasirox release at pH=7 with non-Fickian diffusion mechanism. An in vitro cytotoxicity study implied that the as-synthesized sample is nontoxic.

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Hydrogel
Salep
Drug delivery
Magnetic iron oxide nanoparticles


Investigating the oxidation state of Fe from LiFePO4 -based lithium ion battery cathodes via capillary electrophoresis.

Abstract: A capillary electrophoresis (CE) method with ultraviolet/visible (UV-Vis) spectroscopy for iron speciation in lithium ion battery (LIB) electrolytes was developed. The complexation of Fe2+ with 1,10-phenantroline (o-phen) and of Fe3+ with ethylenediamine tetraacetic acid (EDTA) revealed effective stabilization of both iron species during sample preparation and CE measurements. For the investigation of small electrolyte volumes from LIB cells, a sample buffer with optimal sample pH was developed to inhibit precipitation of Fe3+ during complexation of Fe2+ with o-phen. However, the presence of the conducting salt lithium hexafluorophosphate (LiPF6 ) in the electrolyte led to the precipitation of the complex [Fe(o-phen)3 ](PF6 )2 . Addition of acetonitrile (ACN) to the sample successfully re-dissolved this Fe2+ -complex to retain the quantification of both species. Further optimization of the method successfully prevented the oxidation of dissolved Fe2+ with ambient oxygen during sample preparation, by previously stabilizing the sample with HCl or by working under counterflow of argon. Following dissolution experiments with the positive electrode material LiFePO4 (LFP) in LIB electrolytes under dry room conditions at 20°C and 60°C mainly revealed iron dissolution at elevated temperatures due to the formation of acidic electrolyte decomposition products. Despite the primary oxidation state of iron in LFP of +2, both iron species were detected in the electrolytes that derive from oxidation of dissolved Fe2+ by remaining molecular oxygen in the sample vials during the dissolution experiments.

Hanf|Lenard|L| Diehl|Marcel|M| Kemper|Lea-Sophie|LS| Winter|Martin|M| Nowak|Sascha|S|0000-0003-1508-6073

Lithium ion battery
Cathode
Capillary electrophoresis
Iron speciation
Electrolytes
Transition metal dissolution


Development and Application of Cochlear Implant-Based Electric-Acoustic Stimulation of Spiral Ganglion Neurons.

Abstract: Cochlear implants are currently the most effective treatment for profound sensorineural hearing loss. However, their therapeutic effect is limited by the survival and proper physiological function of spiral ganglion neurons (SGNs), which are targeted by the cochlear implant. It is therefore critical to explore the mechanism behind the effect of electric-acoustic stimulation (EAS) on the targeted SGNs. In this work, a biocompatible cochlear implant/graphene EAS system was created by combining a cochlear implant to provide the electrically transformed sound stimulation with graphene as the conductive neural interface. SGNs were cultured on the graphene and exposed to EAS from the cochlear implant. Neurite extension of SGNs was accelerated with long-term stimulation, which might contribute to the development of growth cones. Our system allows us to study the effects of cochlear implants on SGNs in a low-cost and time-saving way, and this might provide profound insights into the use of cochlear implants and thus be of benefit to the populations suffering from sensorineural hearing loss.

electric-acoustic stimulation
spiral ganglion neurons
cochlear implant
graphene
neurites


Surface Finish Analysis in Single Point Incremental Sheet Forming of Rib-Stiffened 2024-T3 and 7075-T6 Alclad Aluminium Alloy Panels.

Abstract: The article presents the results of the analysis of the interactions between the single point incremental forming (SPIF) process parameters and the main roughness parameters of stiffened ribs fabricated in Alclad aluminium alloy panels. EN AW-7075-T6 and EN AW-2024-T3 Alclad aluminium alloy sheets were used as the research material. Panels with longitudinal ribs were produced with different values of incremental vertical step size and tool rotational speed. Alclad is formed of high-purity aluminium surface layers metallurgically bonded to aluminium alloy core material. The quality of the surface roughness and unbroken Alclad are key problems in SPIF of Alclad sheets destined for aerospace applications. The interactions between the SPIF process parameters and the main roughness parameters of the stiffened ribs were determined. The influence of forming parameters on average roughness Sa and the 10-point peak-valley surface roughness Sz was determined using artificial neural networks. The greater the value of the incremental vertical step size, the more prominent the ridges found in the inner surface of stiffened ribs, especially in the case of both Alclad aluminium alloy sheets. The predictive models of ANNs for the Sa and the Sz were characterised by performance measures with R2 values lying between 0.657 and 0.979. A different character of change in surface roughness was found for sheets covered with and not covered with a soft layer of technically pure aluminium. In the case of Alclad sheets, increasing the value of the incremental vertical step size increases the value of the surface roughness parameters Sa and Sz. In the case of the sheets not covered by Alclad, reduction of the tool rotational speed increases the Sz parameter and decreases the Sa parameter. An obvious increase in the Sz parameter was observed with an increase in the incremental vertical step size.

surface finish
incremental sheet forming
2024-T3
aluminium alloy
surface roughness
load-carrying capacity


Multiple components in direction learning in smooth pursuit eye movements of monkeys.

Abstract: We analyzed behavioral features of smooth pursuit eye movements to characterize the course of acquisition and expression of multiple neural components of motor learning. Monkeys tracked a target that began to move in an initial "pursuit" direction and suddenly, but predictably, changed direction after a fixed interval of 250 ms. As the trial is repeated, monkeys learn to make eye movements that predict the change in target direction. Quantitative analysis of the learned response revealed evidence for multiple, dynamic, parallel processes at work during learning. 1) The overall learning followed at least two trial courses: a fast component grew and saturated rapidly over tens of trials, and a slow component grew steadily over up to 1,000 trials. 2) The temporal specificity of the learned response within each trial was crude during the first 100 trials but then improved gradually over the remaining trials. 3) External influences on the gain of pursuit initiation modulate the expression but probably not the acquisition of learning. The gain of pursuit initiation and the expression of the learned response decreased in parallel, both gradually through a 1,000-trial learning block and immediately between learning trials with different gains in the initiation of pursuit. We conclude that at least two distinct neural mechanisms drive the acquisition of pursuit learning over 100 to 1,000 trials (3 to 30 min). Both mechanisms generate underlying memory traces that are modulated in relation to the gain of pursuit initiation before expression in the final motor output. NEW & NOTEWORTHY We show that cerebellum-dependent direction learning in smooth pursuit eye movements grows in at least two components over 1,100 behavioral learning repetitions. One component grows over tens of trials and the other over hundreds. Within trials, learned temporal specificity gradually improves over hundreds of trials. The expression of each learning component on a given trial can be modified by external factors that do not affect the underlying memory trace.

acquisition of motor learning
cerebellum
expression of motor learning
floccular complex
learned timing
sensory-motor adaptation


Development and Evaluation of a Train-the-Trainer Workshop for Hong Kong Community Social Service Agency Staff.

Abstract:
INTRODUCTION
Capacity building approaches are useful in large-scale community-based health promotion interventions. However, models to guide and evaluate capacity building among social service agency staff in community settings are rare in the literature. This paper describes the development and evaluation of a 1-day (7 h) train-the-trainer (TTT) workshop for the "Enhancing Family Well-Being Project". The workshop aimed at equipping staff from different community agencies with the knowledge and skills to design, implement, and evaluate positive psychology-based interventions for their clients in Sham Shui Po, an over-crowded and low-income district in Hong Kong.

METHODS
The current TTT extended and improved on our previous successful model by adding research and evaluation methods (including the Logic Model, process evaluation, and randomized controlled trial), which are important to plan and evaluate the community interventions. Evaluation of the TTT was guided by the Integrated Model of Training Evaluation and Effectiveness (IMTEE), with quantitative and qualitative methods. Quantitative data were collected from pretraining (T1), post-training (T2), and 6-month (T3) and 12-month (T4) follow-up surveys. Qualitative data were collected from four focus groups of agency staff after the intervention.

RESULTS
Ninety-three staff from 30 community agencies attended the training, and 90 completed the baseline survey. Eighty-eight, 63, and 57 staff performed the evaluations at T2, T3, and T4, respectively. Agency staff were satisfied with the TTT. Immediate enhancement of knowledge, self-efficacy, and positive attitudes toward the training content was found at T2 (Cohen's d ranged from 0.24 to 1.22, all p < 0.05). Enhancement of knowledge of all training contents persisted at T3 and T4 (Cohen's d ranged from 0.34 to 0.63, all p < 0.05). Enhancement of self-efficacy in the use of positive psychology in intervention design persisted at T3 (Cohen's d = 0.22, p = 0.04). The skills learned were utilized to plan and develop subsequent interventions. Twenty-nine interventions were successfully designed and implemented by the agency staff, and delivered to 1,586 participants. The agency staff indicated their intention to utilize the skills they had learned for other interventions (score ≥4 out of 6) and to share these skills with their colleagues. Qualitative feedbacks from 23 agency staff supported the quantitative results.

CONCLUSION
Our brief TTT was effectively delivered to a large number of agency staff and showed effects that persisted up to 12 months. Our training and evaluation models may offer a template for capacity building among social service agency staff for community brief, universal family health promotion interventions in diverse settings.

Zhou|Qianling|Q|
Stewart|Sunita M|SM|
Wan|Alice|A|
Leung|Charles Sai-Cheong|CS|
Lai|Agnes Y|AY|
Lam|Tai Hing|TH|
Chan|Sophia Siu-Chee|SS|

train-the-trainer
social service agency staff
capacity building
training evaluation
positive psychology
community-based intervention
social work


Intraspecific variation shapes community-level behavioral responses to urbanization in spiders.

Abstract: Urban areas are an extreme example of human-changed environments, exposing organisms to multiple and strong selection pressures. Adaptive behavioral responses are thought to play a major role in animals' success or failure in such new environments. Approaches based on functional traits have proven especially valuable to understand how species communities respond to environmental gradients. Until recently, they have, however, often ignored the potential consequences of intraspecific trait variation (ITV). When ITV is prevalent, it may highly impact ecological processes and resilience against stressors. This may be especially relevant in animals, in which behavioral traits can be altered very flexibly at the individual level to track environmental changes. We investigated how species turnover and ITV influenced community-level behavioral responses in a set of 62 sites of varying levels of urbanization, using orb web spiders and their webs as models of foraging behavior. ITV alone explained around one-third of the total trait variation observed among communities. Spider web structure changed according to urbanization, in ways that increase the capture efficiency of webs in a context of smaller urban prey. These trait shifts were partly mediated by species turnover, but ITV increased their magnitude, potentially helping to buffer the effects of environmental changes on communities. The importance of ITV varied depending on traits and on the spatial scale at which urbanization was considered. Despite being neglected from community-level analyses in animals, our results highlight the importance of accounting for intraspecific trait variation to fully understand trait responses to (human-induced) environmental changes and their impact on ecosystem functioning.

human-induced recent environmental changes


Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis.

Abstract: Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the VEGFA, IL-1β, IL-1α and IL-6 genes with the early-stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I-II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine VEGFA, IL-1β, IL-1α and IL-6 polymorphisms were analysed. The VEGFA and IL-6 haplotypes were inferred using Phase software. Patients were prospectively followed-up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between IL-1α rs1800587 C allele and larger primary tumour size; IL-6 rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, IL-6 (rs1800797-re1800795) AC diplotype and hormonal receptor-positive disease; IL-6 rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, IL-1α rs1800587 CC and IL-6 rs1800797 GG genotype carriers exhibited worse disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS). The IL-6 rs1800795 GG genotype was associated with worse OS. IL-6 (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the IL-1α rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the IL-1α and IL-6 genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early-stage patients with BC.

Korobeinikova|Erika|E| Ugenskiene|Rasa|R| Insodaite|Ruta|R| Rudzianskas|Viktoras|V| Jaselske|Evelina|E| Poskiene|Lina|L| Juozaityte|Elona|E|

angiogenesis
breast cancer
prognosis
single nucleotide polymorphisms
VEGFA
IL-1β
IL-1α
IL-6
inflammation


A computational model of the effect of symplastic growth on cell mechanics in a linear leaf blade.

Abstract: The epidermis of a linear leaf, as in Poaceae, is established by parallel files of cells originating from the leaf base. Their feature is symplastic growth where neighboring cell walls adhere and do not slide along each other. We developed a simple mechanical cell-based model for symplastic growth of linear leaf blade. The challenge is to determine what restrictions on cell size symplastic growth creates compared to the free growing cells. We assume an unidirectional growing cell ensemble starting from a meristem-like layer of generative cells and then generating parallel cell rows from every cell of the initial layer. Each cell is characterized by its growth function, and growth of the whole leaf blade is accompanied by mutual adjustment between all the cells. Cells divide once they have reached a threshold area. A mathematical model and its implementation are proposed for computational simulation of 1D symplastic growth of tissues. The question analyzed is how a cell grows in a plant tissue if there is a mechanism for regulating the growth of an isolated growing cell and the behavior of the cell wall matter is elastoplastic. The results of the simulation of linear leaf blade growth are compared to those for a free-growing cell population.

Zubairova|Ulyana|U| Golushko|Sergey|S| Penenko|Aleksey|A| Nikolaev|Sergey|S|

D048708:Cell Growth Processes
D048429:Cell Size
D018519:Meristem
D008954:Models, Biological
D008962:Models, Theoretical
D009997:Osmotic Pressure
D018515:Plant Leaves

Symplastic growth
cell mechanics
linear leaf
computer simulation
L-systems


Identifying accessible prognostic factors for breast cancer relapse: a case-study on 405 histologically confirmed node-negative patients.

Abstract:
BACKGROUND
Histologically, node-negative breast cancer generally have a good prognosis. However, 10 to 30% of the cases present local relapses or metastasis. This group of people has high chances of remission if detected early. The aim of this study is to identify financial affordability for developing countries to adjust treatment.

METHODS
We selected 405 patients with histologically confirmed node-negative breast cancer in our institution between January 2001 and December 2003. Patients with metastasis were excluded. The statistical analysis was conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois).

RESULTS
The medial age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41% of cases. In the histologic examination, the medial size was 30 mm. Grade III tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%. The mean number of lymph nodes was 14. Eight patients had neoadjuvant chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal therapy. The follow-up showed 17.7% cases of relapse either locally or in a metastatic way in a mean time of 57.4 months. The disease-free survival at 5 years was 82.1%, and the overall survival for the same period was 91.5%. The histologic tumor size and the grade and number of lymph node dissected were shown to be influencing the disease-free survival. Radiation therapy and hormone therapy showed improved disease-free survival and overall survival.

CONCLUSION
Our study found interesting results that may help personalize the treatment especially for patient living in underdeveloped countries, but further studies are needed to evaluate those and more accessible prognostic factors for a more accessible healthcare.

Zemni|Ines|I|
Ghalleb|Montassar|M|
Jbir|Ichraf|I|
Slimane|Maher|M|
Ben Hassouna|Jamel|J|
Ben Dhieb|Tarek|T|
Bouzaiene|Hatem|H|
Rahal|Khaled|K|

D018931:Antineoplastic Agents, Hormonal
D001940:Breast
D001943:Breast Neoplasms
D017024:Chemotherapy, Adjuvant
D018572:Disease-Free Survival
D005260:Female
D005500:Follow-Up Studies
D017048:Health Care Costs
D006801:Humans
D008198:Lymph Nodes
D008207:Lymphatic Metastasis
D008408:Mastectomy
D008875:Middle Aged
D020360:Neoadjuvant Therapy
D060787:Neoplasm Grading
D009364:Neoplasm Recurrence, Local
D009367:Neoplasm Staging
D057285:Precision Medicine
D011379:Prognosis
D018714:Radiotherapy, Adjuvant
D012189:Retrospective Studies
D015996:Survival Rate

Breast cancer
Early stage
Node negative
Prognoses


Brain cell apoptosis inhibition by butylphthalide in Alzheimer's disease model in rats.

Abstract: The present study was designed to test the hypothesis that butylphthalide protects the brain of Alzheimer's disease (AD) model rats by inhibiting apoptosis. Ninety Sprague-Dawley rats were randomly divided into drug, control and blank groups of 30 rats in each. The rats in the drug and control groups were treated to induce AD. Then, the rats in the drug group were administered with butylphthalide daily, the rats in the AD control group were given normal saline, and the rats in the healthy group were fed routinely. All rats were sacrificed after 30 days; the brain tissues were used for testing for apoptosis by the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) staining method, for determining mitogen-activated protein kinase (MAPK), ERK and P21 protein by western blot analysis, and their cognate mRNA levels by RT-PCR. The results of the TUNEL staining indicated that apoptosis of the brain tissues of rats in the drug group was significantly less than that in the control group and blank group. The protein expression levels of MAPK in the drug group were significantly lower than that in the control group, but higher than that in the normal healthy group (P<0.05). The mRNA expression levels of MAPK in the drug group were significantly lower than those in the control group, but higher than those in the normal healthy group (P<0.05). Based on these results, butylphthalide showed a protective apoptosis-inhibition effect on the brain tissues of the AD rats and this seems to be a consequence of its inhibition of the expressions of MAPK mRNA and MAPK protein in the brain of the rat.

Song|Fu-Xia|FX| Wang|Li|L| Liu|Hong|H| Wang|Ying-Li|YL| Zou|Yong|Y|

apoptosis
butylphthalide
Alzheimer
mitogen-activated protein kinase


Hypoglossal Nerve Stimulation in Veterans with Obstructive Sleep Apnea.

Abstract:
OBJECTIVES
The hypoglossal nerve stimulator (HNS) is an effective treatment for obstructive sleep apnea (OSA) in a relatively healthy subset of the population. Our aim was to determine the efficacy of HNS in a veteran population with a high incidence of chronic disease and mental health disorders. Our secondary aim was to compare subjective outcomes and adherence between veterans with and without mental health disorders.

METHODS
We included all patients who underwent HNS at our institution to date. Veterans were divided into two groups based on whether or not they carried a diagnosis of anxiety, depression, and/or post-traumatic stress disorder. Demographics, comorbidities, previous OSA treatments, adverse events, and adherence to therapy were recorded. Baseline and treatment outcome data were collected and analyzed including polysomnographic parameters, Epworth sleepiness scale score (ESS), and body mass index.

RESULTS
Thirty-one patients were identified: 93.5% male, median age = 63.0 years. Median apnea hypopnea index (AHI) decreased from 30.0 to 3.0 events/hour (P < .001) and median ESS dropped from 11.0 to 6.5 (P < .001). There was no difference between groups with regard to change in AHI or ESS (P = .31 and .61). Twenty-six (89.7%) patients achieved surgical success (decrease in AHI > 50% and AHI < 20 events/hour) and 21 (72.4%) had AHI < 5 events/hour. The mean device usage was 5.4 hours/night which was not significantly different between groups (P = .55).

CONCLUSION
Our cohort exhibited similar declines in AHI and ESS compared to published studies with adequate adherence to HNS. There were no significant differences in ESS or adherence to therapy between veterans with and without mental health disorders.

LEVEL OF EVIDENCE
4 Laryngoscope, 130:2275-2280, 2020.

hypoglossal nerve stimulator
veterans
Obstructive sleep apnea
mental health
surgery for obstructive sleep apnea


Adsorption of micronutrient metal ion onto struvite to prepare slow release multielement fertilizer: Copper(II) doped-struvite.

Abstract: In this study, struvite (MgNH4PO4.6H2O) sample was prepared by precipitation. Synthetic struvite was used as an adsorbent to remove Cu(II) from aqueous solution. Struvite was characterized by X-ray diffraction, FTIR, particle size analysis, SEM-EDX, surface area and true density. Solubility of struvite in water and acid solutions was investigated. Batch adsorption experiments were carried out by changing the initial Cu(II) concentration, contact time, struvite dosage and temperature. Cu(II) adsorption was found to be highly pH-dependent, and maximum adsorption was observed in the basic pH range. Equilibrium data were applied to Langmuir, Freundlich and D-R adsorption isotherms. Kinetic data were also analyzed for pseudo-first, pseudo-second and intraparticle diffusion models. Langmuir adsorption isotherm and pseudo-second kinetic models fit best to the data. Maximum adsorption capacity was found to be 158.73 mg g-1 at 20 °C, pH of 6 and adsorbent dosage of 1 g L-1 for a contact time of 240 min. Activation energy, mean adsorption energy (from D-R isotherm) and thermodynamic parameters were evaluated, and the nature of adsorption was found to be physical, endothermic and spontaneous. On the basis of characterization upon struvite before and after adsorption, it was found that the electrostatic attraction supported the ion sorption on struvite surface, and the transformation of Cu(II) ion into copper phosphate and copper hydroxide occurred on struvite surface. After its adsorption, solubility study was carried out. Release of P, N, Mg and Cu into extracts was studied. Phosphorus, nitrogen, magnesium and copper solubility in pure water was lower than about 1%.

Struvite
Cu(II) adsorption
Isotherm
Kinetics
Thermodynamic parameters
Dissolution


Coprosma kawaikiniensis (Rubiaceae) a new species from the Dubautia-Sadleria shrubland-fernland community on Kaua'i, Hawaiian Islands.

Abstract: Coprosma kawaikiniensis K.R. Wood, Lorence & Kiehn (Rubiaceae), a rare endemic tree from Kaua'i, Hawaiian Islands, is described and illustrated along with a previously undescribed endemic plant community, the Dubautia-Sadleria shrubland-fernland (DSSF). The new species differs from Hawai'i congeners by its combination of opposite, long, elliptic to narrowly elliptic or ovate-elliptic leaves with revolute margins; caducous stipules 7-10 mm long, externally glabrous, densely hirtellous-pilose near the margins of the inner surface; unbranched inflorescences with peduncles 20-28 mm long; flowers 6-8 per cluster; and persistent calyx tube with 4-8 irregular dentate lobes. Known only from the windward slopes and ridges of southeastern Kaua'i below the Kawaikini summit, Coprosma kawaikiniensis falls into the IUCN Critically Endangered (CR) Red List category.

Wood|Kenneth R|KR|
Lorence|David H|DH|
Kiehn|Michael|M|

Coprosma
Rubiaceae
new species
Dubautia-Sadleria shrubland-fernland
Hawaiian Islands
Critically Endangered
Kaua‘i
high endemism


DNA Methylation Profiling for the Diagnosis and Prognosis of Patients with Nontuberculous Mycobacterium Lung Disease.

Abstract: The incidence of nontuberculous Mycobacterium (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis (n = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the "pathfinder" package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and p < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and p < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. TGFBr1 was significantly less methylated, whereas HLA-DR1 and HLA-DR5 were more methylated in patients with poor prognosis (compared to those with good prognosis). LRP5, E2F1, and ADCY3 were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1-cell differentiation, such as TGFBr1 and HLA-DR, may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.

Oh|Jee Youn|JY|
Ko|Young Kyung|YK|
Gim|Jeong-An|JA|

DNA methylation
nontuberculous Mycobacterium
tuberculosis


European hospital managers' perceptions of patient-centred care.

Abstract:
PURPOSE
The spotlight has recently been placed on managers' responsibility for patient-centred care as a result of Mid Staffordshire NHS Foundation Trust failings. In previous research, clinicians reported that managers do not have an adequate structured plan for implementing patient-centred care. The purpose of this paper is to assess the perceptions of European hospital management with respect to factors affecting the implementation of a patient-centred approach.

DESIGN/METHODOLOGY/APPROACH
In total, 15 semi-structured interviews were conducted with hospital managers (n=10), expert country informants (n=2), patient organisations (n=2) and a user representative (n=1) from around Europe. Participants were purposively and snowball sampled. Interviews were analysed using framework analysis.

FINDINGS
Most participants felt that current levels of patient-centred care are inadequate, but accounted that there were a number of macro, meso and micro challenges they faced in implementing this approach. These included budget constraints, political and historical factors, the resistance of clinicians and other frontline staff. Organisational culture emerged as a central theme, shaped by these multi-level factors and influencing the way in which patient-centred care was borne out in the hospital. Participants proposed that the needs of patients might be better met through increasing advocacy by patient organisations and greater staff contact with patients.

ORIGINALITY/VALUE
This study is the first of its kind to obtain management views from around Europe. It offers an insight into different models of how patient-centred care is realised by management. It indicates that managers see the value of a patient-centred approach but that they feel restricted by a number of factors at multiple levels.

D001291:Attitude of Health Personnel
D003431:Cross-Cultural Comparison
D005060:Europe
D006739:Hospital Administration
D006740:Hospital Administrators
D006801:Humans
D007407:Interviews as Topic
D007857:Leadership
D015279:Organizational Culture
D017060:Patient Satisfaction
D018802:Patient-Centered Care
D036301:Qualitative Research

Hospital managers
Patient-centred care
Europe
Organizational culture
Qualitative
Quality improvement


The impact of telemedicine in the postoperative care of the neurosurgery patient in an outpatient clinic: a unique perspective of this valuable resource in the developing world--an experience of more than 3000 teleconsultations.

Abstract: Telemedicine has always been used as a teleconsultation tool in neurological emergencies (e.g., triage in head injuries, stroke, and cerebrovascular accidents). At Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore, India, we have been operating two teleconsultation sessions per week for the postoperative patient population, addressing routine follow-up and semiemergent conditions in this cohort of patients. At our center more than 80% of the neurosurgical procedures are conducted in patients traveling more than 1500 km. Telemedicine as a routine tool in clinical medicine has significant financial and psychosocial benefits versus routine outpatient clinics. There are very few reports of telemedicine use in routine outpatient teleconsultations in the available neurosurgical literature; those that are present do not differentiate or analyze the use in routine versus emergency neurosurgery. We discuss the role of this underused resource in the developing countries and retrospectively analyze the clinical data in more than 1500 patients and 3000 teleconsultations during a period of 6 years. We address the financial implications, psychosocial factors, and several other factors that could make this relatively modest technology an indispensible tool in current neurosurgical practice, especially in a developing country like India.

Dadlani|Ravi|R|
Mani|Subramaniyan|S|
A U|Jai Ganesh|JG|
Mohan|Dilip|D|
Rajgopalan|Niranjana|N|
Thakar|Sumit|S|
Aryan|Saritha|S|
Hegde|Alangar S|AS|

Telemedicine Postoperative Neurosurgery Outpatient Teleconsultation Socioeconomic


Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.

Abstract: The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter's syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison's disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.

Panimolle|Francesca|F| Tiberti|Claudio|C| Granato|Simona|S| Semeraro|Antonella|A| Gianfrilli|Daniele|D| Anzuini|Antonella|A| Lenzi|Andrea|A| Radicioni|Antonio|A|

Autoimmunity
Type 1 diabetes
Hypogonadism
Klinefelter’s syndrome


Dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer.

Abstract: To quantitatively evaluate dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer. Overall, 11 lung SBRT patients (8 female and 3 male; mean age: 75.0 years) with medially located tumors were included. Treatment plans with simulated rotational offsets of 1°, 3°, and 5° in roll, yaw, and pitch were generated and compared with the original plans. Both clockwise and counterclockwise rotations were investigated. The following dosimetric metrics were quantitatively evaluated: planning target volume coverage (PTV V100%), max PTV dose (PTV Dmax), percentage prescription dose to 0.35cc of cord (cord D0.35cc), percentage prescription dose to 0.35cc and 5cc of esophagus (esophagus D0.35cc and D5cc), and volume of the lungs receiving at least 20Gy (lung V20). Statistical significance was tested using Wilcoxon signed rank test at the significance level of 0.05. Overall, small differences were found in all dosimetric matrices at all rotational offsets: 95.6% of differences were < 1% or < 1Gy. Of all rotational offsets, largest change in PTV V100%, PTV Dmax, cord D0.35cc, esophagus D0.35cc, esophagus D5cc, and lung V20 was - 8.36%, - 6.06%, 11.96%, 8.66%, 6.02%, and - 0.69%, respectively. No significant correlation was found between any dosimetric change and tumor-to-cord/esophagus distances (R(2) range: 0 to 0.44). Larger dosimetric changes and intersubject variations were observed at larger rotational offsets. Small dosimetric differences were found owing to rotational offsets up to 5° in lung SBRT for medially located tumors. Larger intersubject variations were observed at larger rotational offsets.

Yang|Yun|Y|
Catalano|Suzanne|S|
Kelsey|Chris R|CR|
Yoo|David S|DS|
Yin|Fang-Fang|FF|
Cai|Jing|J|


Effect of intravenous administration of romifidine on intraocular pressure in clinically normal horses.

Abstract:
OBJECTIVE
To evaluate the effect of intravenous administration of romifidine on the intraocular pressure (IOP) in horses.

ANIMALS STUDIED
Twenty-four horses with no ocular abnormalities.

PROCEDURE
Horses were randomly assigned into two equal groups (treatment and control). All horses in the treatment group received an intravenous (IV) injection of romifidine (40 μg/kg). The horses in the control group were administrated an intravenous injection of 0.9% saline (0.4 mL/100 kg). In both groups, the IOP values were measured immediately (T0 ) pre-administration and at 5 (T5 ), 15 (T15 ), 30 (T30 ), 45 (T45 ), 60 (T60 ), 90 (T90 ), and 120 (T120 ) min after drug administration.

RESULTS
The pre-treatment values (T0 ) of IOP for right and left eyes were 24.25 ± 3.5 and 25.16 ± 3.4 mmHg, respectively. A significant decrease in IOP values was observed in both right and left eyes of the horses in treatment group at T5 , T15 , T30 , T45 , T60 , and T90 in comparison with the baseline values (P < 0.05). The lowest level of IOP in romifidine-treated groups was recorded at T45 for the right and left eyes (10.25 ± 2.3 and 11.25 ± 3.5 mmHg, respectively).

CONCLUSION
Romifidine significantly decreased IOP in clinically normal horses and may be used safely for surgery or diagnostic ocular procedures in horses when specific control of IOP is required.

Marzok|Mohamed A|MA|
El-Khodery|Sabry A|SA|
Oheida|Aiman H|AH|

romifidine
intraocular pressure
horse
applanation tonometry


A Queer Theorist's Critique of Online Domestic Violence Advocacy: Critically Responding to the National Coalition Against Domestic Violence Web Site.

Abstract: Since the foundations of the contemporary anti-violence movement in the 1960s and 1970s, advocates have sought to establish a critical understanding of domestic violence that we can use to direct our efforts for social change. Yet many advocates and advocacy organizations continue to rely on a problematic narrative of sameness that marginalizes and erases diverse victims' experiences and needs. In this article, I conduct a critical discourse analysis of the National Coalition Against Domestic Violence Web site to identify outcomes of this narrative for the inclusivity of advocacy efforts. I argue that despite the organization's numerous claims to represent diverse victims' experiences, Web site content reveals that its purportedly general account of domestic violence normalizes the experiences of a small group of victims-namely, heterosexual, cisgender women. Further, the Web site's content greatly limits the potential for thinking about and discussing violence across difference. I conclude with recommendations for changes in advocacy practices.

national coalition against domestic violence