Efficient removal and long-term sequestration of cadmium from aqueous solution using ferrous sulfide nanoparticles: Performance, mechanisms, and long-term stability.

Abstract: Cadmium (Cd) is one of the most commonly detected toxic heavy metals in the environment. Ferrous sulfide (FeS) nanoparticles were prepared using sodium carboxymethyl cellulose (CMC) as a stabilizer and tested for removal of Cd from aqueous solutions. Effects of CMC concentration, initial Cd concentration, pH, humic acid (HA) and dissolved oxygen were examined. Fully stabilized FeS (100 mg/L) nanoparticles were obtained using 0.01 wt% CMC. Batch kinetic tests showed that the nanoparticles at 100 mg/L as FeS rapidly removed 93% of 1 mg/L Cd within 4 h at pH 7.0, and the kinetic data were well interpreted by a pseudo-second-order rate model with a rate constant of 6.68 g·mg-1·hr-1. Sorption isotherm was well simulated by a dual-mode isotherm model with a maximum Langmuir sorption capacity of 497.5 mg/L at pH 7.0. Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffraction (XRD) analyses suggested that chemical precipitation and surface complexation between Cd and FeS were dominant immobilization mechanisms. Increasing pH from 4.0 to 8.0 enhanced Cd removal rate from 73.0% to 98.8%, whereas addition of 3 mg/L HA (as total organic matter) inhibited the removal rate by 2.7% and the presence of molecular oxygen had negligible effect. Increasing NaCl or CaCl2 from 0 to 10 mM suppressed Cd removal by 10.1% and 27.7%, respectively. The immobilized Cd remained insoluble when aged for 717 days under anoxic or oxic conditions. This study demonstrated that CMC-stabilized FeS nanoparticles can facilitate long-term immobilization of cadmium in contaminated water.

Tian|Shuting|S| Gong|Yanyan|Y| Ji|Haodong|H| Duan|Jun|J| Zhao|Dongye|D|

Sequestration
Cadmium
Long-term stability
Heavy metal
Chemical stabilization
Iron sulfide nanoparticles


Relation between total shock energy and mortality in patients with implantable cardioverter-defibrillator.

Abstract:
BACKGROUND
Implantable Cardioverter-Defibrillator (ICD) shocks have been associated with mortality. However, no study has examined the relation between total shock energy and mortality. The aim of this study is to assess the association of total shock energy with mortality, and to determine the patients who are at risk of this association.

METHODS
Data from 316 consecutive patients who underwent initial ICD implantation in our hospital between 2000 and 2011 were retrospectively studied. We collected shock energy for 3 years from the ICD implantation, and determined the relation of shock energy on mortality after adjusting confounding factors.

RESULTS
Eighty-seven ICD recipients experienced shock(s) within 3 years from ICD implantation and 43 patients had died during the follow-up. The amount of shock energy was significantly associated with all-cause death [adjusted hazard ratio (HR) 1.26 (per 100 joule increase), p < 0.01] and tended to be associated with cardiac death (adjusted HR 1.30, p = 0.08). The survival rate of patients with high shock energy accumulation (≥182 joule) was lower (p < 0.05), as compared to low shock energy accumulation (<182 joule), likewise to no shock. Besides, the relation between high shock energy accumulation and all-cause death was remarkable in the patients with low left ventricular ejection fraction (LVEF ≤40%) or atrial fibrillation (AF).

CONCLUSIONS
Increase of shock energy was related to mortality in ICD recipients. This relation was evident in patients with low LVEF or AF.

Tenma|Taro|T| Yokoshiki|Hisashi|H| Mitsuyama|Hirofumi|H| Watanabe|Masaya|M| Mizukami|Kazuya|K| Kamada|Rui|R| Takahashi|Masayuki|M| Sasaki|Ryo|R| Maeno|Motoki|M| Okamoto|Kaori|K| Chiba|Yuki|Y| Anzai|Toshihisa|T|

Total shock energy
Mortality
Implantable cardioverter-defibrillator
Low left ventricular ejection fraction
Atrial fibrillation
Shock accumulation


A new method to assay hypoxia-inducible factor-1 based on small molecule binding DNA.

Abstract: Hypoxia-inducible factor-1 (HIF-1) is among the most important indicators of hypoxia in evaluating severity of many diseases. In this work, a novel method for HIF-1 detection is proposed by using electrochemical techniques based on small molecule binding DNA. In this method, since the designed DNA sequence can specifically bind with either an electroactive small molecule or HIF-1, the signal readout is inversely proportional to HIF-1 concentration, thus a simple and easily-operated method for HIF-1 detection can be developed. With the proposed method, HIF-1 can be determined in a linear range from 5 to 25nM with a detection limit of 2.8nM. Furthermore, the proposed method can be directly used to assay HIF-1 in placenta tissue, and the assay results can reliably reflect the severity of preeclampsia, a very dangerous condition during pregnancy. The proposed method also shows desirable sensitivity, high selectivity and excellent reproducibility, so this method can have potential applications in clinical practice.

Yang|Nana|N| Li|Hao|H| Yin|Tingting|T| Huang|Yue|Y| Sun|Lizhou|L| Li|Genxi|G|

Hypoxia-inducible factor-1
Preeclampsia
Biosensor
Echinomycin
Electroanalysis


Is a midwife's continuous presence during childbirth a matter of course? Midwives' experiences and thoughts about factors that may influence their continuous support of women during labour.

Abstract:
OBJECTIVE
to gain an understanding about midwives' experiences of providing a continuous supportive presence in the delivery room during childbirth, and to learn about factors that may affect this continuous support.

DESIGN/SETTING
qualitative study at a maternity unit in Norway, where about 4000 births take place each year. In-depth interviews were conducted with ten midwives working in two different maternity wards. The qualitative data were analysed using systematic text condensation.

FINDINGS
the analysis generated three main themes: relational competence, the midwife's ideology, the culture and philosophy of the maternity unit. The midwives identified being mentally present and actively developing mutual trust with the woman in labour as two very important factors for building a relationship with her. They suggested that the midwife's first encounter with the woman is a key opportunity for establishing rapport during labour. Successfully providing a continuous presence during labour fostered the midwives' perception of themselves as a 'good midwife'; this was considered a feature of holistic care and health promotion. The workload in the unit sometimes made it difficult for them to provide a continuous presence in the delivery room. The midwives experienced feelings of inadequacy when they felt that they had too little time available for the woman in labour.

KEY CONCLUSIONS
midwives' skill in building a relationship with the woman in labour combined with their values and understanding of the midwifery profession are important factors influencing their decision to provide a continuous presence during childbirth. If it is policy that maternity units should provide continuous support to women in labour, managers should ensure that it is actually provided.

Aune|Ingvild|I|
Amundsen|Hanne Hvaal|HH|
Skaget Aas|Lene Christina|LC|

Continuous presence
Health promotion
Continuity of care
Midwifery ideology


Factors associated with do-not-resuscitate document completion among patients hospitalized in geriatric ward.

Abstract:
BACKGROUND
With a rapidly aging population, there is an increasing need for do-not-resuscitate (DNR) and advance care planning (ACP) discussions. This study investigated the factors associated with signing DNR documents of older patients in the geriatric ward.

METHODS
We conducted a retrospective cohort study at a geriatric ward in a tertiary hospital in Southern Taiwan. Three hundred and thirty-seven hospitalized older patients aged ≥65 years in the geriatric ward from 2018 to 2019. The Hospital Information System and electronic medical records were accessed to obtain details regarding patients' demographics, daily living activities, serum albumin level, nutrition screening score, intensive care unit transferal, resuscitation procedure, days of hospital stay, and survival status on discharge, and DNR status was recorded retrospectively. Patients were classified into DNR and non-DNR groups, with t-tests and Chi-square tests applied to compare the differences between groups. Logistic regression was performed to predict factors related to the DNR documents.

RESULTS
A total of 337 patients were included, 66 of whom had signed a DNR during hospitalization. After multivariate logistic regression, age 85 or more compared to age 65-74 (adjusted odds ratio, aOR 5.94), poor nutrition with screening score two or more (aOR 2.71), albumin level less than 3 (aOR 3.24), Charlson Comorbidity Index higher than 2 (aOR 2.46) and once transferred to ICU (aOR 5.11) were independently associated with DNR documentation during hospitalization.

CONCLUSIONS
Several factors related to DNR documents for geriatric patients were identified which could provide clinical information for physicians, patients, and their families to discuss DNR and ACP.

Wu|Chien-Yi|CY| Jen|Chun-Hao|CH| Chuang|Yun-Shiuan|YS| Fang|Tzu-Jung|TJ| Wu|Yu-Hsuan|YH| Wu|Ming-Tsang|MT|

Do-not-resuscitate
Advance care planning
Geriatric care
Older people


Temporal variation in the deposition of different types of collagen within a porous biomaterial implant.

Abstract: The deposition of new collagen in association with a medical implant has been studied using expanded polytetrafluoroethylene vascular replacement samples implanted subcutaneously in sheep, for up to 28 days. New type I collagen mRNA synthesis was followed by in situ hybridization, while the accumulation of new collagen types III, V, VI, XII, and XIV was followed by immunohistochemistry. All the collagen detected in the pores of the implant were newly deposited at various times after implantation and were not due to any pre-existing dermal collagen that may have been present around the implant. Collagen deposition was seen initially surrounding the implant and, with time, was seen to infiltrate within its pores. In situ hybridization showed that the majority of infiltrating cells had switched on mRNA that coded for type I collagen production. Histology showed that cellular infiltration increased with time, accompanied by increasing collagen deposition. The deposition of different collagen types happened at different rates. The type V and VI collagens preceded the major interstitial collagens in the newly deposited tissue, although at longer time points, detection of type V collagen appeared to decrease. After disruption of the interstitial collagens with enzyme, the "masked" type V collagen was clearly still visible by immunohistochemistry. Little type XII collagen could be seen within the porous mesh, although it was seen in the surrounding tissues. By contrast, type XIV was seen throughout the porous structure of the implanted mesh, with less being visible outside the material where type XII was more abundant.

White|Jacinta F|JF|
Werkmeister|Jerome A|JA|
Bisucci|Teresa|T|
Darby|Ian A|IA|
Ramshaw|John A M|JA|

collagen
in situ hybridization
immunohistochemistry
cell
material interaction
porous material


Role of Porous Carriers in the Biopharmaceutical Performance of Solid SMEDDS of Canagliflozin.

Abstract:
OBJECTIVE
The aim of the present investigation entails the development of solid SMEDDS for improving the oral bioavailability of canagliflozin using porous carriers. The previous patent (WO2017046730A1) was based on enhanced solubility of canagliflozin through co-crystal formation.

METHODS
Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and hydrophobic carriers. The prepared solid SMEDDS were characterized for various parameters to determine the optimized formulation. In vitro, ex vivo and in vivo studies were carried out to determine drug release kinetics, permeation and absorption rate, respectively. Stability of the formulation was investigated at 45°C/75% RH.

RESULTS
The solid preconcentrates prepared with hydrophobic carriers exhibited desired attributes in a uniform range. Neusilin adsorbed solid SMEDDS (S(N)SMEDDS) portrayed enhanced amorphization in XRD and DSC studies and found to be physically compatible in FTIR studies. SEM revealed colloidal particles having spherical morphology with negligible aggregation. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.72, 5.85, 4.51 and 3.0-fold, respectively, as compared to pure drug. TEM of reconstituted SMEDDS indicated nano-sized globules with negligible coalescence. Enhanced in vitro dissolution rate of optimized solid SMEDDS manifested in bioavailability enhancement of 167.54% and 188.98%, as compared to pure drug and marketed product. These studies further substantiate the lymphatic uptake of SMEDDS through chylomicron flow blocking approach. Establishment of Level A IVIVC showed a uniform correlation between the in vitro dissolution efficiency and in vivo pharmacokinetic parameters.

CONCLUSION
The present investigation reveals the immense potential of solid SMEDDS in augmenting the oral bioavailability profile of poorly water-soluble drug canagliflozin.

Singh|Dilpreet|D|
Tiwary|Ashok K|AK|
Bedi|Neena|N|

canagliflozin
bioavailability
Solubility
lymphatic uptake
microemulsion
solid carriers.


Aberrant glycosaminoglycan biosynthesis by tumor suppressor EXTL2 deficiency promotes liver inflammation and tumorigenesis through Toll-like 4 receptor signaling.

Abstract: Certain proteoglycans, consisting of a core protein and glycosaminoglycan (GAG) chains, are among the many types of biomolecules that can function as damage-associated molecular pattern molecules (DAMPs). We, therefore, hypothesized that the expression level and structural alteration of GAGs affect inflammation. We have previously reported that the effects on GAG biosynthesis caused by loss of the tumor suppressor gene exostosin-like 2 (Extl2) influence liver injury and regeneration processes. To examine how altered GAG biosynthesis may underscore the relationship between inflammation and tumorigenesis, we assessed its role in non-alcoholic steatohepatitis and hepatocarcinoma (HCC) induced by dietary obesity and insulin-resistance. We demonstrated that GAGs produced in the absence of EXTL2 act as DAMPs and directly input signals into cells via the Toll-like 4 receptor. In addition, the subsequent transcriptional activation of inflammatory and tumor-promoting cytokines by NF-κB contributes to injury- and inflammation-driven tumor promotion. Thus, dysregulated biosynthesis of GAGs is considered to increase the risk of HCC in a background of obesity and diabetes.

D065626:Non-alcoholic Fatty Liver Disease

glycosaminoglycan
inflammation
NF-kappaB (NF-κB)
liver cancer
proteoglycans (PG)


Statistical and practical considerations in designing of immuno-oncology trials.

Abstract: The novel mechanism of action of immunotherapy agents, in treatment of various types of cancer, poses unique challenges during the designing of clinical trials. It is important to account for possibility of a delayed treatment effect and adjust sample size accordingly. This paper provides an analytical approach for computing sample size in the presence of a delayed effect using a piece-wise proportional hazards model. Failing to account for an anticipated treatment delay may result in considerable loss in power. The overall hazard ratio (HR), which now represents the average HR across the entire treatment period, can remain a meaningful measure of average benefit to patients in the trial. We show that, special consideration needs to be given for the designing of interim analyses related to futility, so as not to increase the probability of incorrectly stopping an effective agent. It is shown that the weighted log-rank test, using the Fleming-Harrington class of weights, can be used as supportive analysis to better reflect the impact of a delayed effect and possible long-term benefit in a subset of the overall population.

Mukhopadhyay|Pralay|P| Huang|Wenmei|W| Metcalfe|Paul|P| Öhrn|Fredrik|F| Jenner|Mary|M| Stone|Andrew|A|

Delayed treatment effect
piece-wise proportional hazards model
futility
weighted log-rank test
interim analysis


A UHPLC-MS/MS Method for the Detection of Meat Substitution by Nine Legume Species in Emulsion-Type Sausages.

Abstract: Meat substitution by legume proteins in various types of meat products is a common practice. A reliable detection and quantification of these additives is required to control food specifications, especially regarding food fraud. Consequently, a UHPLC-MS/MS method for the simultaneous detection of alfalfa (Medicago sativa), broad bean (Vicia faba), chickpea (Cicer arietinum), lentil (Lens culinaris), lupine (Lupinus albus and Lupinus angustifolius), pea (Pisum sativum), peanut (Arachis hypogaea), and soy (Glycine max) proteins in meat products was developed. After protein extraction and tryptic digestion, three marker peptides for each legume species were measured by multiple reaction monitoring (MRM) using an optimized extraction protocol. To the best of our knowledge, the marker peptides for alfalfa, broad bean, chickpea, and lentil have not been reported previously. Emulsion-type sausages with 0.1, 0.4, 0.7, 1.0, 1.3, 1.6, 1.9, 2.2, and 2.5% meat substitution by each legume species, representing the concentration range between inadvertently transferred cross-contaminations and the conscious use for meat substitution, were produced for matrix calibration. No false-positive results were recorded in blank samples. In the quantification of alfalfa, broad bean, chickpea, lentil, pea, peanut, and soy, 673 of 756 measuring data of the recovery rate in unknown sausages were in the accepted range of 80-120%.

meat substitution
legumes
food fraud
marker peptides
allergens
food adulteration
food safety
foreign protein
mass spectrometry


Third trimester cortisol status is associated with offspring sex and polycystic ovary syndrome status: Odense Child Cohort.

Abstract:
OBJECTIVE
To determine predictors of maternal serum (S) and urinary (U) cortisol and cortisone levels during the third trimester and to examine associations between maternal cortisol status, offspring sex, and maternal polycystic ovary syndrome (PCOS) status.

DESIGN
Prospective observational study.

SETTING
The study is part of the prospective Odense Child Cohort.

PATIENT(S)
The study cohort included 1,489 women (with PCOS, n = 145; without PCOS, n = 1,344).

INTERVENTION(S)
Fasting blood samples, 24-hour urinary samples.

MAIN OUTCOME MEASURE(S)
Fasting morning S-cortisol and 24-hour U-cortisol/U-cortisone (24-hour U-C/C) were collected at gestational week 28 and measured by liquid chromatography-tandem mass spectrometry.

RESULT(S)
Maternal S-cortisol levels were significantly higher in women pregnant with girls (n = 702) vs. boys (n = 787): mean (mean - SD; mean + SD) 833 (643; 1,079) vs. 799 (588; 1,083) nmol/L. In multiple regression analyses, maternal S-cortisol was positively associated with female offspring and inversely associated with maternal age and parity. When women were divided according to PCOS status, 24-hour U-cortisone was higher: 467 (334; 652) vs. 415 (286; 604) nmol/24 hours; and 24-hour U-C/C was lower in women with PCOS compared with women without PCOS.

CONCLUSION(S)
Maternal third trimester S-cortisol levels were positively associated with female offspring. Cortisol metabolism was higher in women with PCOS vs. women without PCOS.

Andersen|Marianne Skovsager|MS|
Jensen|Richard Christian|RC|
Schmedes|Anne Vibeke|AV|
Brandslund|Ivan|I|
Kyhl|Henriette Boye|HB|
Jensen|Tina Kold|TK|
Glintborg|Dorte|D|


Modifying the Interface Edge to Control the Electrical Transport Properties of Nanocontacts to Nanowires.

Abstract: Selecting the electrical properties of nanomaterials is essential if their potential as manufacturable devices is to be reached. Here, we show that the addition or removal of native semiconductor material at the edge of a nanocontact can be used to determine the electrical transport properties of metal-nanowire interfaces. While the transport properties of as-grown Au nanocatalyst contacts to semiconductor nanowires are well-studied, there are few techniques that have been explored to modify the electrical behavior. In this work, we use an iterative analytical process that directly correlates multiprobe transport measurements with subsequent aberration-corrected scanning transmission electron microscopy to study the effects of chemical processes that create structural changes at the contact interface edge. A strong metal-support interaction that encapsulates the Au nanocontacts over time, adding ZnO material to the edge region, gives rise to ohmic transport behavior due to the enhanced quantum-mechanical tunneling path. Removal of the extraneous material at the Au-nanowire interface eliminates the edge-tunneling path, producing a range of transport behavior that is dependent on the final interface quality. These results demonstrate chemically driven processes that can be factored into nanowire-device design to select the final properties.

Lord|Alex M|AM|0000-0002-6258-2187
Ramasse|Quentin M|QM|
Kepaptsoglou|Despoina M|DM|
Evans|Jonathan E|JE|
Davies|Philip R|PR|0000-0003-4394-766X
Ward|Michael B|MB|
Wilks|Steve P|SP|


Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae.

Abstract: Polybrominated diphenyl ethers (PBDEs) are distributed throughout the environment. Despite a moratorium on their use, concentrations of PBDEs in the atmosphere and in residential environments remain high due to their persistence. The environmental health risks remain concerning and one of the major adverse effects is neurodevelopmental toxicity. However, the early response and effects of PBDEs exposure on the developing brain remain unknown. In the present study, we investigated the impacts of 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) on vascular growth and vascular barrier function with an emphasis on cerebral blood vessels, in the early life stages, using a zebrafish model. No general toxicity was observed in exposing zebrafish larvae to 0-0.5 μM BDE-99 at 72 hpf. BDE-99 exposure resulted in neither general toxicity nor pronounced developmental impairment in somatic blood vessels, including intersegmental vessels (ISV) and common cardinal veins (CCV). Meanwhile, both 0.05 μM and 0.5 μM of BDE-99 reduced cerebrovascular density as well as down-regulation of VEGFA and VEGFR2 in the head. In addition, BDE-99 exposure increased vascular leakage, both in cerebral and truncal vasculature at 72 hpf. The accentuated vascular permeability was observed in the head. The mRNA levels of genes encoding tight junction molecules decreased in the BDE-99-exposed larvae, and more robust reductions in Cldn5, Zo1 and Jam were detected in the head than in the trunk. Moreover, proinflammatory factors including TNF-α, IL-1β and ICAM-1 were induced, and the expression of neurodevelopment-related genes was suppressed in the head following BDE-99 exposure. Taken together, these results reveal that developmental exposure to BDE-99 impedes cerebrovascular growth and disturbs vascular barrier formation. The cerebral vasculature in developing zebrafish, a more sensitive target for BDE-99, may be a promising tool for the assessment of the early neurodevelopmental effects due to PBDEs exposure.

Zhong|Xiali|X| Kang|Jianmeng|J| Qiu|Jiahuang|J| Yang|Wenhan|W| Wu|Jingwei|J| Ji|Di|D| Yu|Yuejin|Y| Ke|Weijian|W| Shi|Xiongjie|X| Wei|Yanhong|Y|

D018507:Gene Expression Regulation, Developmental

D042461:Vascular Endothelial Growth Factor A

D040301:Vascular Endothelial Growth Factor Receptor-2

Vascular barrier
Zebrafish
Polybrominated diphenyl ethers
Cerebrovasculature
Developmental toxicity
Vascular toxicity


Lysosomal two-pore channel subtype 2 (TPC2) regulates skeletal muscle autophagic signaling.

Abstract: Postnatal skeletal muscle mass is regulated by the balance between anabolic protein synthesis and catabolic protein degradation, and muscle atrophy occurs when protein homeostasis is disrupted. Autophagy has emerged as critical in clearing dysfunctional organelles and thus in regulating protein turnover. Here we show that endolysosomal two-pore channel subtype 2 (TPC2) contributes to autophagy signaling and protein homeostasis in skeletal muscle. Muscles derived from Tpcn2(-/-) mice exhibit an atrophic phenotype with exacerbated autophagy under starvation. Compared with wild types, animals lacking TPC2 demonstrated an enhanced autophagy flux characterized by increased accumulation of autophagosomes upon combined stress induction by starvation and colchicine treatment. In addition, deletion of TPC2 in muscle caused aberrant lysosomal pH homeostasis and reduced lysosomal protease activity. Association between mammalian target of rapamycin and TPC2 was detected in skeletal muscle, allowing for appropriate adjustments to cellular metabolic states and subsequent execution of autophagy. TPC2 therefore impacts mammalian target of rapamycin reactivation during the process of autophagy and contributes to maintenance of muscle homeostasis.

Lin|Pei-Hui|PH|
Duann|Pu|P|
Komazaki|Shinji|S|
Park|Ki Ho|KH|
Li|Haichang|H|
Sun|Mingzhai|M|
Sermersheim|Mathew|M|
Gumpper|Kristyn|K|
Parrington|John|J|
Galione|Antony|A|
Evans|A Mark|AM|
Zhu|Michael X|MX|
Ma|Jianjie|J|

Lysosome
Muscle Atrophy
Autophagy
Protein Turnover
Calcium Channel


Phase I/II Study of Docetaxel and S-1 in Previously-Treated Patients with Advanced Non-Small Cell Lung Cancer: LOGIK0408.

Abstract:
BACKGROUND
As docetaxel plus S-1 may be feasible for cancer treatment, we conducted a phase I/II trial to determine the recommended docetaxel dose and the fixed S-1 dose (phase I), as well as confirm the regimen's efficacy and safety (phase II) for previously-treated patients with advanced non-small cell lung cancer.

METHODS
Patients ≤75 years with performance status ≤1 and adequate organ function were treated at three-week intervals with docetaxel on day 1 and 80 mg/m2 oral S-1 from days 1-14. The starting docetaxel dose was 45 mg/m2 and this was escalated to a maximum of 70 mg/m2. In phase II, response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed.

RESULTS
The recommended doses were 50 mg/m2 docetaxel (day 1) and 80 mg/m2 S-1 (days 1-14). Grades 3 and 4 leukocytopenia and neutropenia occurred in 44% and 67% of patients, respectively. Nonhematologic toxicities were generally mild. Overall response to chemotherapy was 7.7% (95% confidence interval (CI), 1.6-20.9%), and median PFS and OS were 18.0 weeks (95% CI; 11.3-22.9 weeks) and 53.0 weeks, respectively.

CONCLUSION
Fifty mg/m2 docetaxel plus 80 mg/m2 oral S-1 had a lower response rate than anticipated; however, the survival data were encouraging. A further investigation is warranted to select the optimal patient population.

Takayama|Koichi|K| Uchino|Junji|J|0000-0003-0651-7767 Fujita|Masaki|M| Tokunaga|Shoji|S| Imanaga|Tomotoshi|T| Morinaga|Ryotaro|R| Ebi|Noriyuki|N| Saeki|Sho|S| Matsukizono|Kazuya|K| Wataya|Hiroshi|H| Yamada|Tadaaki|T|0000-0002-6945-281X Nakanishi|Yoichi|Y|0000-0001-7813-3469

docetaxel
S-1
non-small cell lung cancer
phase I/II trial
chemotherapy
previously treated patients


The role of clinical nurse specialists in the implementation and sustainability of a practice change.

Abstract:
AIM
This project's purpose was to promote and sustain a practice change focusing on delirium utilising the clinical nurse specialist (CNS) in a leadership role.

BACKGROUND
Delirium is an altered state of consciousness accompanied by an acute change in cognition that tends to have a fluctuating course. Delirium is strongly associated with negative outcomes and is often unrecognised.

METHOD
A policy was implemented stating that the RNs will screen patients for delirium with the confusion assessment method (CAM). Interdisciplinary delirium education was offered prior to the practice change and repeated at 3, 6 and 12 months after implementation. The documentation, completion and CAM accuracy screening were determined by the CNS.

RESULTS
The CAM documentation and completion audit goal was met and sustained by week 21, and screenings were accurate 83% of the time.

CONCLUSIONS
The CNS has an opportunity to take a leadership role when instituting an innovative practice change. Successful implementation of a new practice requires that patient care units are divided into cohorts with systematic roll-out of the initiative.

IMPLICATIONS FOR NURSING MANAGEMENT
In addition to leadership, CNS availability on the patient care units is imperative to staff acceptance and sustainability of a practice change.

Babine|Rhonda L|RL|
Honess|Cindy|C|
Wierman|Heidi R|HR|
Hallen|Sarah|S|

D003693:Delirium
D006801:Humans
D007857:Leadership
D008403:Mass Screening
D009720:Nurse Clinicians
D024802:Nurse's Role
D009936:Organizational Innovation
D063868:Patient Outcome Assessment
D011050:Policy Making
D015397:Program Evaluation

nursing
delirium
leadership
education
continuing
staff development


Crack nucleation and propagation in microcrystalline-cellulose based granules subject to uniaxial and triaxial load.

Abstract: Cracking patterns in four kinds of granules, based on the common pharmaceutical excipient microcrystalline cellulose (MCC) and subject to compressive load, were examined. The initial pore structure and the location of initial failure under uniaxial compression were assessed using X-ray micro-computed tomography, whereas contact force development and onset of cracking under more complex compressive load were examined using a triaxial testing apparatus. Smoothed particle hydrodynamics (SPH) simulations were employed for numerical analysis of the stress distributions prior to cracking. For granules subject to uniaxial compression, initial cracking always occurred along the meridian and the precise location of the crack depended on the pore structure. Likewise, for granules subject to triaxial compression, the fracture plane of the primary crack was generally parallel to the dominant loading direction. The occurrence of cracking was highly dependent on the triaxiality ratio, i.e. the ratio between the punch displacements in the secondary and dominant loading directions. Compressive stresses in the lateral directions, induced by triaxial compression, prevented crack opening and fragmentation of the granule, something that could be verified by simulations. These results provide corroboration as well as further insights into previously observed differences between confined and unconfined compression of granular media.

Jonsson|Henrik|H| Öhman-Mägi|Caroline|C| Alderborn|Göran|G| Isaksson|Per|P| Frenning|Göran|G|

D002482:Cellulose
D019245:Compressive Strength
D055595:Mechanical Phenomena
D013314:Stress, Mechanical
D013718:Tensile Strength
D055114:X-Ray Microtomography

Cracking Granule Uniaxial Triaxial Fragmentation


Decoupling Between Pulmonary Artery Diastolic and Wedge Pressure Following Transcatheter Aortic Valve Replacement.

Abstract:
BACKGROUND
Coexistent pulmonary hypertension with severe aortic stenosis confers a greater risk of mortality for patients undergoing transcatheter aortic valve replacement (TAVR). In this patient population, the impact of significant decoupling between pulmonary artery diastolic and pulmonary capillary wedge, as it relates to clinical risk, remained uncertain.Methods and Results:Patients with severe aortic stenosis who underwent TAVR and completed pre-procedural and post-procedural invasive hemodynamic assessments with right heart catheterization were retrospectively assessed. The impact of post-TAVR decoupling, defined as a pressure difference ≥3 mmHg, on 2-year all-cause mortality or risk of heart failure admission was analyzed. Among 77 included patients (median age 86 years, 23 men), 16 had post-TAVR decoupling. The existence of post-TAVR decoupling was associated with a higher cumulative incidence of the primary endpoint (44% vs. 7%, P=0.001), with an adjusted hazard ratio of 5.87 (95% confidence interval 1.58-21.9, P=0.008).

CONCLUSIONS
A greater risk of worse outcomes in those with post-TAVR decoupling was observed. A therapeutic strategy for post-TAVR decoupling and its clinical implication need to be created and investigated in the future.

Imamura|Teruhiko|T| Narang|Nikhil|N| Sobajima|Mitsuo|M| Tanaka|Shuhei|S| Ushijima|Ryuichi|R| Fukuda|Nobuyuki|N| Ueno|Hiroshi|H| Kinugawa|Koichiro|K|

Hemodynamics
Heart failure
Aortic valve disease


Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo.

Abstract: While the aggregate differentiation of the hematopoietic stem cell (HSC) population has been extensively studied, little is known about the lineage commitment process of individual HSC clones. Here, we provide lineage commitment maps of HSC clones under homeostasis and after perturbations of the endogenous hematopoietic system. Under homeostasis, all donor-derived HSC clones regenerate blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system has been perturbed by irradiation or by an antagonistic anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiate. Some of these clones dominantly expand and exhibit lineage bias. We identified the cellular origins of clonal dominance and lineage bias and uncovered the lineage commitment pathways that lead HSC clones to different levels of self-renewal and blood production under various transplantation conditions. This study reveals surprising alterations in HSC fate decisions directed by conditioning and identifies the key hematopoiesis stages that may be manipulated to control blood production and balance.

Lu|Rong|R|0000-0002-5151-9246
Czechowicz|Agnieszka|A|
Seita|Jun|J|
Jiang|Du|D|
Weissman|Irving L|IL|

lineage commitment
hematopoietic stem cell
clonal tracking
radiation
transplantation preconditioning


The heparan sulfate proteoglycan syndecan-1 regulates colon cancer stem cell function via a focal adhesion kinase-Wnt signaling axis.

Abstract: In colon cancer, downregulation of the transmembrane heparan sulfate proteoglycan syndecan-1 (Sdc-1) is associated with increased invasiveness, metastasis, and dedifferentiation. As Sdc-1 modulates signaling pathways relevant to stem cell function, we tested the hypothesis that it may regulate a tumor-initiating cell phenotype. Sdc-1 small-interfering RNA knockdown in the human colon cancer cell lines Caco2 and HT-29 resulted in an increased side population (SP), enhanced aldehyde dehydrogenase 1 activity, and higher expression of CD133, LGR5, EPCAM, NANOG, SRY (sex-determining region Y)-box 2, KLF2, and TCF4/TCF7L2. Sdc-1 knockdown enhanced sphere formation, cell viability, Matrigel invasiveness, and epithelial-to-mesenchymal transition-related gene expression. Sdc-1-depleted HT-29 xenograft growth was increased compared to controls. Decreased Sdc-1 expression was associated with an increased activation of β1-integrins, focal adhesion kinase (FAK), and wingless-type (Wnt) signaling. Pharmacological FAK and Wnt inhibition blocked the enhanced stem cell phenotype and invasive growth. Sequential flow cytometric SP enrichment substantially enhanced the stem cell phenotype of Sdc-1-depleted cells, which showed increased resistance to doxorubicin chemotherapy and irradiation. In conclusion, Sdc-1 depletion cooperatively enhances activation of integrins and FAK, which then generates signals for increased invasiveness and cancer stem cell properties. Our findings may provide a novel concept to target a stemness-associated signaling axis as a therapeutic strategy to reduce metastatic spread and cancer recurrence. DATABASES: The GEO accession number of the Affymetrix transcriptomic screening is GSE58751.

Kumar Katakam|Sampath|S|
Tria|Valeria|V|
Sim|Wey-Cheng|WC|
Yip|George W|GW|
Molgora|Stefano|S|
Karnavas|Theodoros|T|
Elghonaimy|Eslam A|EA|
Pelucchi|Paride|P|
Piscitelli|Eleonora|E|
Ibrahim|Sherif Abdelaziz|SA|
Zucchi|Ileana|I|
Reinbold|Rolland|R|
Greve|Burkhard|B|
Götte|Martin|M|0000-0003-2360-2496

D000080924:Aldehyde Dehydrogenase 1 Family

D000071858:Epithelial Cell Adhesion Molecule

D015972:Gene Expression Regulation, Neoplastic

D051876:Sex-Determining Region Y Protein

D058118:Transcription Factor 7-Like 2 Protein

D023041:Xenograft Model Antitumor Assays

tumor-initiating cells
xenograft
extracellular matrix
glycosaminoglycan
syndecans


Predictors of Oral Feeding Resumption after Stroke in a Rehabilitation Hospital: A Retrospective Study.

Abstract:
BACKGROUND
Dysphagia is common after stroke, requiring exclusive enteral feeding in 20% of patients. Recovery of oral feeding is associated with increased quality of life, better functional outcomes, and decreased mortality rates. However, evidence is heterogeneous and not conclusive on which factors are predictive of oral feeding recovery for stroke patients in rehabilitation units.

AIM
To investigate predictors of complete oral feeding recovery.

DESIGN
Retrospective study.

SETTING
Intensive inpatient rehabilitation hospital.

POPULATION
Poststroke dysphagic individuals with enteral feeding.

METHODS
Retrospective chart review of demographic, clinical, rehabilitation, and swallowing factors. Univariate analysis and multivariate regression analysis were used to compare variables between the oral feeding recovery group and the enteral feeding group at discharge.

RESULTS
One hundred thirty-nine patients were included in the analysis. A total of 61.9% of the sample population resumed complete oral intake at discharge. There were statistically significant differences between the 2 groups in Functional Independence Measure cognitive score, clinical swallow evaluation, and instrumental swallow evaluation at admittance, and dysphagia rehabilitation. Multiple logistic regression analysis identified the absence of aspiration signs with liquids associated with a higher probability of the resumption of complete oral feeding (odds ratio [OR] 3.57; 95% confidence interval [CI] 1.07-11.89). Age between 73 and 79 years (OR .96; 95% CI .01-.58), the presence of aspiration and/or penetration (OR .22; 95% CI .07-.72), and the presence of residue (OR .14; 95%CI .04-.43) during fiberoptic endoscopic evaluation of swallowing presented lower probability of returning to complete oral feeding.

CONCLUSION
Several demographic and swallowing characteristics predicted oral feeding recovery. Absence of dysphagia signs documented on fiberoptic endoscopic evaluation of swallowing was the strongest predictor of complete oral feeding resumption.

Calvo|Irene|I| Pizzorni|Nicole|N| Gilardone|Giulia|G| Mayer|Flavia|F| Vanacore|Nicola|N| Buraschi|Valentina|V| Gilardone|Marco|M| Corbo|Massimo|M|

oral feeding
stroke
rehabilitation
Dysphagia
enteral feeding


Oligodendroglia Are Particularly Vulnerable to Oxidative Damage after Neurotrauma In Vivo.

Abstract: Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-Ethynyl-2'-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 d after injury. Injury led to increases in DNA, protein, and lipid damage in oligodendrocyte progenitor cells and mature oligodendrocytes at 3 d, regardless of proliferative state, associated with a decline in the numbers of oligodendrocyte progenitor cells at 7 d. O4+ preoligodendrocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8-hydroxyguanosine immunoreactivity were more likely to be caspase3+ By day 28, newly derived mature oligodendrocytes had significantly reduced myelin regulatory factor gene mRNA, indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+ oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochemistry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivoSIGNIFICANCE STATEMENT Injury to the CNS is characterized by oxidative damage in areas adjacent to the injury. However, the cellular subpopulations and structures most vulnerable to this damage remain to be elucidated. Here we use powerful NanoSIMS techniques to show increased oxidative damage in oligodendroglia and axons and to demonstrate that cells early in the oligodendroglial lineage are the most vulnerable to DNA oxidation. Further immunohistochemical and in situ hybridization investigation reveals that mature oligodendrocytes derived after injury are more vulnerable to oxidative damage than their counterparts existing at the time of injury and have reduced myelin regulatory factor gene mRNA, yet preexisting oligodendrocytes are more likely to die.

oligodendroglia
NanoSIMS
myelin regulatory factor gene
oligodendrocyte precursor cell
oxidative stress
proliferation and differentiation


Small ruminant lentiviruses in goats in southern Italy: Serological evidence, risk factors and implementation of control programs.

Abstract: Small ruminant lentiviruses (SRLVs) can drastically affect milk production in goat flocks and only an early detection can control and prevent their spread. Since SRLVs are responsible for persistent infections, antibody screening is the most valuable tool to identify infected animals. ELISA is recommended as the election test both for its sensitivity and for its ability to detect low antibody titers, thus identifying infected animals earlier than agar gel immunodiffusion (AGID). In the present study, an investigation was conducted to assess the SRLV seroprevalence in goat flocks in southern Italy and a transversal comparative study was carried out through the analysis of the possible risk factors influencing SRLV spread. A total of 4800 sera from 1060 flocks were analyzed and overall seroprevalences of 18,64% and 51,69% at animal and herd levels, respectively, were observed. Both the region and the herd production systems were able to affect seroprevalence, differently from the herd size, probably because the mean number of goats per herd is low and the semi-intensive management is similar regardless of the dimensional class of each herd. In particular, meat producing herds showed the higher seroprevalence, as a result of the poor sanitation and low animal monitoring in comparison to milk producing herds, where animals are managed twice daily and the relationship between dams and kids is checked to guarantee an adequate quantitative/qualitative milk yield. In the absence of vaccines or effective treatments, health preventive management and seroepidemiological investigations are the only successful approach to restrict SRLV spread as observed in countries were official/voluntary control programs are carried out.

Cirone|Francesco|F|
Maggiolino|Aristide|A|
Cirilli|Margie|M|
Sposato|Alessio|A|
De Palo|Pasquale|P|
Ciappetta|Giacinto|G|
Pratelli|Annamaria|A|

Lentiviruses
Goats
Risk factors
Control
Antibodies


Young adolescents with autism show abnormal joint attention network: A gaze contingent fMRI study.

Abstract: Behavioral research has revealed deficits in the development of joint attention (JA) as one of the earliest signs of autism. While the neural basis of JA has been studied predominantly in adults, we recently demonstrated a protracted development of the brain networks supporting JA in typically developing children and adolescents. The present eye-tracking/fMRI study now extends these findings to adolescents with autism. Our results show that in adolescents with autism JA is subserved by abnormal activation patterns in brain areas related to social cognition abnormalities which are at the core of ASD including the STS and TPJ, despite behavioral maturation with no behavioral differences. Furthermore, in the autism group we observed increased neural activity in a network of social and emotional processing areas during interactions with their mother. Moreover, data indicated that less severely affected individuals with autism showed higher frontal activation associated with self-initiated interactions. Taken together, this study provides first-time data of JA in children/adolescents with autism incorporating the interactive character of JA, its reciprocity and motivational aspects. The observed functional differences in adolescents ASD suggest that persistent developmental differences in the neural processes underlying JA contribute to social interaction difficulties in ASD.

Oberwelland|E|E|
Schilbach|L|L|
Barisic|I|I|
Krall|S C|SC|
Vogeley|K|K|
Fink|G R|GR|
Herpertz-Dahlmann|B|B|
Konrad|K|K|
Schulte-Rüther|M|M|

D001289:Attention Deficit Disorder with Hyperactivity

Eye-tracking
Social interaction
Familiarity
Functional magnetic resonance imaging
Superior temporal sulcus
Temporoparietal junction


Determination and classification of intraoral phosphor storage plate artifacts and errors.

Abstract:
Purpose
The aim of this study was to determine the reasons and solutions for intraoral phosphor storage plate (PSP) image artifacts and errors, and to develop an appropriate classification of the artifacts.

Materials and Methods
This study involved the retrospective examination of 5,000 intraoral images that had been obtained using a phosphor plate system. Image artifacts were examined on the radiographs and classified according to possible causative factors.

Results
Artifacts were observed in 1,822 of the 5,000 images. After examination of the images, the errors were divided into 6 groups based on their causes, as follows: images with operator errors, superposition of undesirable structures, ambient light errors, plate artifacts (physical deformations and contamination), scanner artifacts, and software artifacts. The groups were then re-examined and divided into 45 subheadings.

Conclusion
Identification of image artifacts can help to improve the quality of the radiographic image and control the radiation dose. Knowledge of the basic physics and technology of PSP systems could aid to reduce the need for repeated radiography.

Artifacts
Diagnostic Imaging
Radiography, Dental


Photovoltage response of (XZn)Fe2O4-BiFeO3 (X=Mg, Mn or Ni) interfaces for highly selective Cr3+, Cd2+, Co2+ and Pb2+ ions detection.

Abstract: High-photostability fluorescent (XZn)Fe2O4 (X=Mg, Mn or Ni) embedded in BiFeO3 spinel-perovskite nanocomposites were successfully fabricated via a novel bio-induced phase transfer method using shewanella oneidensis MR-1. These nanocomposites have the near-infrared fluorescence response (XZn or Fe)-O-O-(Bi) interfaces (785/832nm), and the (XZn)Fe2O4/BiFeO3 lattices with high/low potentials (572.15-808.77meV/206.43-548.1meV). Our results suggest that heavy metal ion (Cr3+, Cd2+, Co2+ and Pb2+) d↓ orbitals hybridize with the paired-spin X-Zn-Fe d↓-d↓-d↑↓ orbitals to decrease the average polarization angles (-29.78 to 44.71°), qualitatively enhancing the photovoltage response selective potentials (39.57-487.84meV). The fluorescent kinetic analysis shows that both first-order and second-order equilibrium adsorption isotherms are in line and meet the Langmuir and Freundlich modes. Highly selective fluorescence detection of Co2+, Cr3+ and Cd2+ can be achieved using Fe3O4-BiFeO3 (Langmuir mode), (MgZn)Fe2O4-BiFeO3 and (MnZn)Fe2O4-BiFeO3 (Freundlich mode), respectively. Where the corresponding max adsorption capacities (qmax) are 1.5-1.94, 35.65 and 43.7 multiple, respectively, being more competitive than that of other heavy metal ions. The present bio-synthesized method might be relevant for high-photostability fluorescent spinel-perovskite nanocomposites, for design of heavy metal ion sensors.

Bian|Liang|L| Li|Yu-Jin|YJ| Li|Jing|J| Nie|Jia-Nan|JN| Dong|Fa-Qin|FQ| Song|Mian-Xin|MX| Wang|Li-Sheng|LS| Dong|Hai-Liang|HL| Li|Hai-Long|HL| Nie|Xiao-Qin|XQ| Zhang|Xiao-Yan|XY| Li|Xin-Xi|XX| Xie|Lei|L|

Photovoltage response
Interface
Heavy metal ion
Ferrite-bismuth ferrite
Selective fluorescence probe


Gender intersections identified whilst transitioning mass vitamin A supplementation into an integrated reproductive and child health programme in Sierra Leone.

Abstract: Since 2006, Sierra Leone has achieved high rates of vitamin A supplementation (VAS) coverage (>88%) during mass campaigns. In 2017, campaigns started transitioning to routine VAS within a six-monthly contact point for integrated reproductive and child health (RCH) services. This contact point included improved counselling and provision of modern contraceptives; throughout this transition high VAS coverage (>85%) has been maintained. VAS programmes have traditionally operated on the assumption that they are gender-neutral, but recent research suggests these programmes should re-examine how they interact with gender. This qualitative study examined intersections between gender and Sierra Leone's integrated VAS programming by conducting 32 individual interviews with parents, district health management and national staff, and six focus group discussions with health workers and community health workers (CHWs) in three pilot program districts. The study found that most senior health positions are held by males, and the lower cadres of majority female health workers often felt unsupported/disrespected by their male superiors and male CHW supervisees, or that their years of experience were overlooked in favour of the academic qualifications of less experienced male colleagues. Gender was not included in program training, and most staff did not have a good understanding of gender intersections; however, health workers actively engaged in awareness raising with male stakeholders to increase male involvement in RCH. Routine delivery requires mothers to invest time and money to access health facilities, where most mothers felt that better qualified staff were able to offer better advice and more services. Health workers felt that outreach services utilizing CHWs could decrease this time/money burden; however, CHWs are unqualified to provide counselling and provision of modern contraception, and there are fewer female CHWs. Records kept in health facilities record VAS by sex, but monthly reports submitted to the district and onwards to the national Health Management Information System are not disaggregated by sex. Programme and policymakers should consider improving the representation by females in senior, decision-making positions, integrating gender information into all trainings, supporting female health workers, training and recruiting more female CHWs, and reporting VAS coverage by sex.

Bauck|Aubrey|A|
Jalloh|Umu H|UH|
Kargbo|Anita|A|
Hodges|Mary H|MH|
Doledec|David|D|

vitamin A supplementation
reproductive and child health
Sierra Leone
modern contraception
community health workers
Gender equity


Self-Selected Versus Standardised Warm-Ups; Physiological Response on 500 m Sprint Kayak Performance.

Abstract: This study investigated the effectiveness of a self-selected (SS) warm-up on 500 m sprint kayak performance (K500) compared to continuous (CON) and intermittent high intensity (INT)-type warm-ups. Twelve nationally ranked sprint kayakers (age 17.7 ± 2.3 years, mass 69.2 ± 10.8 kg) performed CON (15 min at the power at 2 m·mol-1), INT (10 min at 2 m·mol-1, followed by 5 × 10 s sprints at 200% power at VO2max with 50 s recovery at 55% power at VO2max), and SS (athlete's normal competition warm-up) warm-ups in a randomised order. After a five-minute passive recovery, K500 performance was determined on a kayak ergometer. Heart rate and blood lactate (BLa) were recorded before and immediately after each warm-up and K500 performance. Ratings of perceived exertion (RPE) were recorded at the end of the warm-up and K500. BLa, heart rate, and RPE were generally higher after the INT than CON and SS warm-ups (p < 0.05). No differences in these parameters were found between the conditions for the time trial (p > 0.05). RPE and changes in BLa and heart rate after the K500 were comparable. There were no differences in K500 performance after the CON, SS, or INT warm-ups. Applied practitioners can, therefore, attain similar performance independent of warm-up type.

kayakers
continuous
acute performance
autoregulation
intermittent high-intensity
water sport


"Inside-in" or "inside-out"? The membrane topology of SLC41A1.

Abstract: Membrane topology is an important parameter for understanding the function and regulation of any integral protein. This aspect of the NME SLC41A1 is currently under debate. The most probable model, which has been computer-predicted, exhibits ten TMh with both termini being oriented intracellularly. However, other freely accessible online prediction programs predict that SLC41A1 possesses eleven ("outside-in" configuration), nine ("outside-in" configuration), or eight ("inside-in" configuration) TMh. The consensus based on published experimental data acquired by independent research teams is that the N-terminal flanking region is located intracellularly. However, controversy remains about the orientation of the C-terminus, which has lately been proposed to be extracellular in peer-reviewed bibliography. Here, we performed split-ubiquitin functional assays with transgenic SLC41A1 fused N- or C-terminally to a Cub-LexA-VP16 reporter cassette. The bait constructs were co-expressed in S. cerevisiae st. NMY51 with positive recombinant membrane markers (Ost1, Fur4, Alg5, Tom20) tagged with NubI (or NubG). Ubiquitin could only be reconstituted if the reporter moiety was exposed to the cytosol. Functional reconstitution of ubiquitin was observed when SLC41A1 C-terminally tagged with Cub was co-expressed with NubI-tagged membrane markers, thereby, indicating a cytosolic orientation of the C-terminus of SLC41A1. Thus, our experimental data are in favor of the - the in silico analyses being strongly preferred - ten TMh model of SLC41A1 topology, with both termini being oriented intracellularly.

D027682:Cation Transport Proteins
D002462:Cell Membrane
D011487:Protein Conformation
D011993:Recombinant Fusion Proteins
D012441:Saccharomyces cerevisiae
D025801:Ubiquitin

split-ubiquitin functional assay
Na+/Mg2+ exchanger
transmembrane helix


Obstructive sleep apnea, CPAP therapy and Parkinson's disease motor function: A longitudinal study.

Abstract:
INTRODUCTION
We aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment.

METHODS
Data were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities.

RESULTS
We studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA+ compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA+CPAP-. However, in OSA+CPAP+, mUPDRS change was significantly lower compared to OSA- (β = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [β = 0.39]) and TUG change was lower compared to OSA+CPAP- (β = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [β = 0.02]).

CONCLUSIONS
In this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.

Meng|Lingrui|L|
Benedetti|Andrea|A|
Lafontaine|Anne-Louise|AL|
Mery|Victoria|V|
Robinson|Ann Ross|AR|
Kimoff|John|J|
Gros|Priti|P|
Kaminska|Marta|M|

D045422:Continuous Positive Airway Pressure

Obstructive sleep apnea
Continuous positive airway pressure
TUG
Neurodegenerative disorders
Parkinson disease
Sleep disorders
UPDRS


Analysis of behind the armor ballistic trauma.

Abstract: The impact response of body armor composed of a ceramic plate with an ultrahigh molecular weight polyethylene (UHMWPE) fiber-reinforced composite and layers of UHMWPE fibers shielding a block of ballistic gelatin has been experimentally and numerically analyzed. It is a surrogate model for studying injuries to human torso caused by a bullet striking body protection armor placed on a person. Photographs taken with a high speed camera are used to determine deformations of the armor and the gelatin. The maximum depth of the temporary cavity formed in the ballistic gelatin and the peak pressure 40mm behind the center of the gelatin front face contacting the armor are found to be, respectively, ~34mm and ~15MPa. The Johnson-Holmquist material model has been used to simulate deformations and failure of the ceramic. The UHMWPE fiber-reinforced composite and the UHMWPE fiber layers are modeled as linear elastic orthotropic materials. The gelatin is modeled as a strain-rate dependent hyperelastic material. Values of material parameters are taken from the open literature. The computed evolution of the temporary cavity formed in the gelatin is found to qualitatively agree with that seen in experiments. Furthermore, the computed time histories of the average pressure at four points in the gelatin agree with the corresponding experimentally measured ones. The maximum pressure at a point and the depth of the temporary cavity formed in the gelatin can be taken as measures of the severity of the bodily injury caused by the impact; e.g. see the United States National Institute of Justice standard 0101.06-Ballistic Resistance of Body Armor.

Wen|Yaoke|Y|
Xu|Cheng|C|
Wang|Shu|S|
Batra|R C|RC|

Ultrahigh molecular weight polyethylene (UHMWPE) composite


Characteristics of DNMT3A mutations in acute myeloid leukemia.

Abstract:
Background
DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.

Methods
A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.

Results
We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8-23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.

Conclusion
We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.

Park|Dong Jin|DJ|
Kwon|Ahlm|A|
Cho|Byung-Sik|BS|
Kim|Hee-Je|HJ|
Hwang|Kyung-Ah|KA|
Kim|Myungshin|M|
Kim|Yonggoo|Y|


Abstract: Development of the salivary gland is characterized by extensive branching morphogenesis and lumen formation, the latter of which is closely associated with differentiation into acinar and ductal cells. Although various molecules, including signaling and cell adhesion molecules, have been implicated in salivary gland development, transcription factors (TFs) regulating the expression of those molecules and morphological development of the gland are largely unknown. Here we show that knockdown of the epithelial TF, Grainyhead-like 2 (Grhl2), with siRNA in developing mouse submandibular salivary gland (SMG) cultured ex vivo resulted in retardation of epithelial development. This retardation was concomitant with suppression of gene expression for the cell adhesion molecules, such as E-cadherin and the extracellular protease inhibitor SPINT1, and with the disorganized deposition of the basal lamina protein laminin. ChIP-PCR demonstrated the binding of Grhl2 protein to the Spint1 gene in the SMG. Notably, addition of recombinant SPINT1 protein in cultured SMG overcame the suppressive effects of Grhl2 siRNA on epithelial development and laminin deposition. These findings show that Grhl2 regulation of SPINT1 expression controls salivary gland development.

Matsushita|Takumi|T| Sakai|Manabu|M| Yoshida|Hiroaki|H| Morita|Shousuke|S| Hieda|Yohki|Y| Sakai|Takayoshi|T|

D053491:Proteinase Inhibitory Proteins, Secretory


Influence of moisture source dynamics and weather patterns on stable isotopes ratios of precipitation in Central-Eastern Africa.

Abstract: We report the first δ18O and δ2H data of Virunga rainfall in the Eastern Democratic Republic of the Congo, situated on the limit between Central and Eastern Africa. The dataset is from 13 rain gauges deployed at Mount Nyiragongo and its surroundings sampled monthly between December 2013 and October 2015. The δ18O and δ2H vary from -6.44 to 6.16‰, and -32.53 to 58.89‰ respectively, and allowed us to define a LMWL of δ2H = 7.60δ18O + 16.18. Three main wind directions, i.e. NE, E and SE, were identified in the upper atmosphere corresponding to three major moisture source regions. On the contrary, lower atmospheric winds are weaker in nature and originate mainly from the S and SW, creating a topographically-driven, more local moisture regime. The latter is due to the accumulation in the floor of the rift of water vapor from Lake Kivu forming a layer of isotopically enriched vapor that mediates the isotope enrichment of the falling raindrops. A strong seasonality is observed in both δ18O and δ2H data, and is primarily driven by combined seasonal and spatial variation in the moisture sources. The δ18O and δ2H seasonality is thus correlated to weather patterns, as the latter control the wet to dry season shifting, and vice versa. The key characteristic of seasonality is the variation of monthly precipitation amounts, since the mean monthly air temperature is nearly constant on an annual scale. Two regionally relevant hydrological processes contribute to the isotopic signature: namely moisture uptake from the isotopically enriched surface waters of East African lakes and from the depleted soil-water and plants. Consequently, the proportion of water vapor from each of these reservoirs in the atmosphere drives the enrichment or depletion of δ2H and δ18O in the precipitation. Thus, during wet periods the vapor from soil-plants evapotranspiration dominates yielding isotopically depleted precipitation, contrary to dry periods when vapor from lakes surface evaporation dominates, yielding isotopically enriched precipitation. At the global scale, our dataset reduces gaps in this region that has been poorly studied for δ18O and δ2H in precipitation. At the regional scale, the improved understanding of the ways land cover, moisture source seasonal and spatial dynamics, and atmospheric patterns impact precipitation spatial and temporal variabilities in Central-East African will contribute to the ongoing research on mitigating the impacts of ongoing climate change in Sub-Saharan Africa. The reduction of gaps and uncertainties in δ2H and δ18O of precipitation, and the understanding of their interrelation with weather patterns are essential for a better past, present and future environmental and climatic modelling at both local and regional scales.

Balagizi|Charles M|CM|
Kasereka|Marcellin M|MM|
Cuoco|Emilio|E|
Liotta|Marcello|M|

East African Lakes stable isotopes
Moisture source for Virunga
Virunga Local Meteoric Water Line
Virunga precipitation stable isotopes
Virunga precipitation variability


Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

Abstract:
BACKGROUND
Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node-negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection.

METHODS
Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids (99m Tc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan.

RESULTS
Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%.

CONCLUSION
This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.

sentinel lymph node biopsy
superparamagnetic iron oxide
magnetic probe
breast cancer


Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma.

Abstract: Treatment response assessment in multiple myeloma (MM) relies on the detection of paraprotein in serum and/or urine, bone marrow morphology and immunohistochemistry. With remarkable advances in therapy, particularly in the newly diagnosed setting, achievement of complete remission became frequent, creating the need to identify smaller amounts of residual disease and understand their prognostic and therapeutic implications. Measurable residual disease (MRD) can be assessed primarily by flow cytometry and next generation sequencing and state-of-the-art assays have sensitivity approaching 1 in 106 cells. This review discusses the existing challenges in utilizing MRD to inform management of MM and highlights open research questions and opportunities as MRD is more routinely incorporated into clinical practice for patients with MM.

Bal|Susan|S|
Weaver|Allison|A|
Cornell|Robert F|RF|0000-0002-2011-1475
Costa|Luciano J|LJ|0000-0001-5362-2469

multiple myeloma
flow cytometry
deep sequencing
residual neoplasm
surrogate end point


The eversible tentacle organs of Polyommatus caterpillars (Lepidoptera, Lycaenidae): Morphology, fine structure, sensory supply and functional aspects.

Abstract: In their late (3rd and 4th) larval stages, caterpillars of the myrmecophilous lycaenid (Lepidoptera) species Polyommatus coridon and Polyommatus icarus, possess on their 8th abdominal segment two eversible so called tentacle organs (TOs). Previous histological and behavioural results have proposed that the TOs may release a volatile substance that elicits "excited runs" in attendant ants. In our study we investigated for the first time the temporal in- and eversion pattern of TOs. Using nerve tracing, Micro-CT, light- and electron microscopy techniques we studied (i) the histology of the 8th abdominal segment, (ii) the fine structure of the cuticular and cellular apparatus of the TOs, (iii) the attachment sites of the retractor muscle of each TO and (iv) the fine structure of the long slender tentacle hairs which are exposed to the outside, when the TOs are everted and fold back into the TO-sac during inversion. Our data show that the tentacle hairs are typical insect mechanoreceptors, each innervated by a small bipolar sensory cell with a tubular body in the tip of the outer dendritic segment. The latter is enclosed by a cuticular sheath previously called the "internal cuticular duct" and misinterpreted in earlier studies as the space, where the tentacle hairs actively secrete fluids. However, we found no glandular structures nearby or in the wall of the TO-sac. Also we did not reveal any conspicuous signs of secretory activity in one of the enveloping cells belonging to a tentacle hair. Although highly unusual features for an insect mechanoreceptor are: (a) the hair-shaft lumen of tentacle hairs contains flocculent material as well small vesicles and (b) the thin cuticular wall of the hair-shaft and its spines possess few tiny pores. Our data do not support the assumption of previous studies that volatile substances are released via the tentacle organs during their interactions with ants which in turn are supposed to cause excited runs in ants.

Gnatzy|W|W|
Jatho|M|M|
Kleinteich|T|T|
Gorb|S N|SN|
Hustert|R|R|

Tentacle organ
Morphology
Polyommatus coridon
Polyommatus icarus
Mechanoreceptors
Sensilla
Tentacle motion
Ultrastructure


Baseline markers of inflammation, lipids, glucose, and Dietary Inflammatory Index scores do not differ between adults willing to participate in an intensive inflammation reduction intervention and those who do not.

Abstract:
BACKGROUND:
Chronic inflammation is associated with numerous chronic diseases and can be managed with diet.

AIM:
The purpose of this study was to examine differences in baseline characteristics and plasma inflammation levels between two groups of participants that participated in an intensive, lifestyle intervention or a remotely delivered intervention. This work also assessed the association between Dietary Inflammatory Index (DII)® scores and participants' inflammatory and metabolic biomarkers at baseline.

METHOD:
Ninety-five participants (61 intervention, 34 control) chose to enroll in either a 12-month intervention consisting of a face-to-face nutrition, physical activity, and stress management intervention or a remotely-delivered intervention (control group) focusing on general cancer prevention. The intervention group met at the University of South Carolina for classes and the control group had materials emailed to them. A quantile regression was used to compare participants' high-sensitivity C-reactive protein and interleukin-6 levels. Multiple linear regression was used to determine the association between DII scores and biomarkers.

RESULTS:
There were significant differences in age, body mass index, body fat percentage, and blood pressure between groups, but there were no differences in levels of inflammatory biomarkers. Values of interleukin-6 at the 90th percentile of its distribution were 8.31 pg/ml higher among those in DII quartile 4 compared with quartile 1 ( p = 0.02). All other outcomes were not significant.

CONCLUSION:
Given similar levels of inflammatory biomarkers, participants opting for the control group would also have benefited from a more intensive lifestyle intervention focusing on reducing inflammation.

Inflammation
Dietary Inflammatory Index
stress
self-selection trial
vegetarian diet


Polymorphisms of transcription factor-7-like 2 (TCF7L2) gene in Tunisian women with polycystic ovary syndrome (PCOS).

Abstract:
BACKGROUND AND AIMS
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in their child-bearing age, and is often associated with insulin resistance and type 2 diabetes (T2DM). Given the overlap between PCOS and T2DM, we investigated the association of transcription factor-7-like 2 (TCF7L2) variants rs4506565, rs7903146, rs12243326, and rs12255372 with the susceptibility to PCOS.

SUBJECTS AND METHODS
Study subjects comprised 119 Tunisian women with PCOS (mean age 29.8±4.7years), and 150 control women (mean age 30.6±5.9years). TCF7L2 genotyping was done by the allelic discrimination/real-time PCR method.

RESULTS
Minor allele frequencies (MAFs) of rs4506565 (P=0.61), rs7903146 (P=0.68), rs12243326 (P=0.56), and rs12255372 (P=0.60) were comparable between PCOS cases and control subjects. As the four tested TCF7L2 variants were in linkage disequilibrium, 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 2111 was initially negatively associated with PCOS [P=0.035; OR (95% CI)=0.13 (0.02-0.85)], which was later lost upon correcting for multiple comparisons [Pc=0.248].

CONCLUSION
Our data suggest that there is weak or no contribution of TCF7L2 gene polymorphism to PCOS in Tunisian women. Further studies with larger samples are necessary to confirm this observation.

Ben-Salem|A|A|
Ajina|M|M|
Suissi|M|M|
Daher|H S|HS|
Almawi|W Y|WY|
Mahjoub|T|T|

D020022:Genetic Predisposition to Disease

homeostasis model assessment for insulin resistance


Overlap and Mutual Distinctions Between Clinical Recovery and Personal Recovery in People With Schizophrenia in a One-Year Study.

Abstract: Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P = .026, OR = 4.94 [1.30-23.0]; baseline clinical recovery for stable personal recovery at one year; P = .016, OR = 3.64 [1.31-11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery.

Dubreucq|Julien|J|0000-0003-4079-4194 Gabayet|Franck|F| Godin|Ophélia|O| Andre|Myrtille|M| Aouizerate|Bruno|B| Capdevielle|Delphine|D| Chereau|Isabelle|I| Clauss-Kobayashi|Julie|J| Coulon|Nathalie|N| D'Amato|Thierry|T| Dorey|Jean-Michel|JM| Dubertret|Caroline|C| Faraldo|Mégane|M| Laouamri|Hakim|H| Leigner|Sylvain|S| Lancon|Christophe|C| Leboyer|Marion|M| Llorca|Pierre-Michel|PM| Mallet|Jasmina|J| Misdrahi|David|D| Passerieux|Christine|C| Rey|Romain|R| Pignon|Baptiste|B|0000-0003-0526-3136 Schorr|Benoit|B| Urbach|Mathieu|M| Schürhoff|Franck|F| Szoke|Andrei|A| ||| Fond|Guillaume|G|0000-0003-3249-2030 Berna|Fabrice|F|

clinical recovery
personal recovery
schizophrenia
full recovery
psychosocial treatment


Polyamines alleviate the inhibitory effect of the DNA cross-linking agent mitomycin C on root growth.

Abstract: Polyamines (putrescine, spermidine and spermine) are ubiquitously present in various types of cells of living organisms. They are involved in a variety of cellular processes, including cell proliferation and cell differentiation, and are required for abiotic stress tolerances in plants. However, it is still not understood whether polyamines are involved in the plant growth inhibition caused by DNA-damaging agents. In this study, we examined the effects of polyamines on the inhibition of plant root growth and gene expression in Arabidopsis thaliana treated with mitomycin C (MMC), a genotoxic agent that induces DNA interstrand crosslinks. We found that polyamines alleviated the inhibitory effect caused by MMC on root growth. In addition, we also found that polyamines alleviated the increased expression of AtBRCA1 and AtRAD51 genes induced by MMC treatment. Our study provides the first evidence that polyamines contribute to tolerance against plant-growth inhibition caused by a DNA-damaging chemical.

D018506:Gene Expression Regulation, Plant

Polyamine
mitomycin C
root growth
Arabidopsis thaliana
DNA damage


Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas.

Abstract:
AIM
To study the effect of vasoactive intestinal peptide (VIP) on wound healing in experimental alkali burns of the cornea.

METHODS
Twenty-seven albino rabbits, weighing 3.2±0.75 kg were used. Alkali burns were induced on corneas by applying 10 mm Whatman paper No:50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows: 1) control group given no treatment (n=5); 2) VIP given subconjunctivally (n=6); 3) VIP injected into anterior chamber (n=6); 4) NaCl 0.9% given subconjunctivally (n=5); 5) NaCl 0.9% given into the anterior chamber (n=5). All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 a.m. to 6 p.m.

RESULTS
VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes (PMNL) infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 (P<0.05).

CONCLUSION
We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenases and this might prevent the extracellular amorphous substance loss.

Tuncel|Nese|N| Yildirim|Nilgun|N| Gurer|Firdevs|F| Basmak|Hikmet|H| Uzuner|Kubilay|K| Sahinturk|Varol|V| Gursoy|Huseyin|H|

vasoactive intestinal peptide
wound healing
alkali-burned cornea
alkali burn
rabbit


How academically productive are endocrine surgeons in the United States?

Abstract:
BACKGROUND
Many surgical departments in the United States lack endocrine surgery faculty. Although endocrine surgeons can provide worthwhile clinical services, it is unclear how they contribute to the overall academic mission of the department. The present study aims to evaluate the academic productivity of endocrine surgeons, as defined by the American Association of Endocrine Surgeons (AAES) membership, when compared with other academic surgical faculty.

MATERIALS AND METHODS
An established database of 4081 surgical department faculty was used for this study. This database includes surgical faculty of the top 50 National Institutes of Health (NIH) funded universities and faculty from five outstanding hospital-based surgical departments. Academic metrics including publication, citations, H-index, and NIH funding were obtained using publically available data from websites. The AAES membership status was gathered from the online membership registry.

RESULTS
A total of 110 AAES members were identified in this database, accounting for 2.7% of this population. Overall, the AAES members outperformed other academic surgical faculty with respect to publications (66 ± 94 versus 28 ± 91, P < 0.001), publication citations (1430 ± 3432 versus 495 ± 2955, P < 0.001), and H-index (19 ± 18 versus 10 ± 13, P < 0.001). In addition, the AAES members were more likely to have former/current NIH funding and hold divisional or departmental leadership positions than their non-AAES member colleagues.

CONCLUSIONS
Based on these data, the AAES members excelled with respect to publications, citations, and research funding compared with nonendocrine surgical faculty. These results demonstrate that endocrine surgeons can contribute enormously to the overall academic mission. Therefore, more surgical departments in the United States should consider establishing an endocrine surgery program.

Garner|Evan F|EF|
Valsangkar|Nakul P|NP|
Wang|Thomas N|TN|
Porterfield|John R|JR|
Koniaris|Leonidas G|LG|
Chen|Herbert|H|

Academic productivity
Endocrine surgery
AAES
H-index
Bibliometrics


Effects of Cr and Zr Addition on Microstructures, Compressive Properties, and Abrasive Wear Behaviors of In Situ TiB₂/Cu Cermets.

Abstract: In situ micro-TiB₂/Cu cermets with a different TiB₂ content (40, 50, and 60 vol %) were successfully fabricated by combustion synthesis (CS) and hot press consolidation in Cu-Ti-B systems. In addition, different contents of Cr and Zr were added to the Cu-Ti-B systems. The microstructure, mechanical properties, and abrasive wear properties of the TiB₂/Cu cermets were investigated. As the ceramic content increased, the yield strength and compressive strength of the cermets were found to increase, while the strain decreased. An increase in load and abrasive particle size caused the wear volume loss of the TiB₂/Cu cermets to increase. When the ceramic content was 60 vol %, the wear resistance of the TiB₂/Cu cermets was 3.3 times higher than that of pure copper. The addition of the alloying elements Zr and Cr had a significant effect on the mechanical properties of the cermets. When the Cr content was 5 wt %, the yield strength, ultimate compressive strength, and microhardness of the cermets reached a maximum of 997 MPa, 1183 MPa, and 491 Hv, respectively. Correspondingly, when the Zr content was 5 wt %, those three values reached 1764 MPa, 1967 MPa, and 655 Hv, respectively, which are 871 MPa, 919 MPa, and 223 Hv higher than those of the unalloyed cermets. The wear mechanism of the in-situ TiB₂/Cu cermets, and the mechanisms by which the strength and wear resistance were enhanced by the addition of Zr, were preliminarily revealed.

Qiu|Feng|F|0000-0003-4741-7906 Duan|Xiangzheng|X| Dong|Baixin|B| Yang|Hongyu|H| Lu|Jianbang|J| Li|Xiujuan|X|0000-0002-4972-3088

compression property
abrasive wear
in situ
cermets
combustion


The order of concurrent training affects mTOR signaling but not mitochondrial biogenesis in mouse skeletal muscle.

Abstract: Concurrent training involves a combination of two different modes of training. In this study, we conducted an experiment by combining resistance and endurance training. The purpose of this study was to investigate the influence of the order of concurrent training on signal molecules in skeletal muscle. The phosphorylation levels of p70 S6 kinase, S6 ribosomal protein, and 4E-binding protein 1, which are related to hypertrophy signaling, increased significantly in the resistance-endurance order group as compared with in control group not the endurance-resistance order group. The gene expressions related to metabolism were not changed by the order of concurrent training. The mitochondrial respiratory chain complex was evaluated by western blot. Although both groups of concurrent training showed a significant increase in MTCO1, UQCRC2, and ATP5A protein levels, we could not detect a difference based on the order of concurrent training. In conclusion, a concurrent training approach involving resistance training before endurance training on the same day is an effective way to activate both mTOR signaling and mitochondria biogenesis.

D000818:Animals
D008297:Male
D051379:Mice
D008813:Mice, Inbred ICR
D008931:Mitochondria, Muscle
D018482:Muscle, Skeletal
D001678:Organelle Biogenesis
D010766:Phosphorylation
D010805:Physical Conditioning, Animal
D051057:Proto-Oncogene Proteins c-akt
D055070:Resistance Training
D058570:TOR Serine-Threonine Kinases

concurrent training
mTOR signaling
mitochondrial biogenesis
skeletal muscle


Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis.

Abstract: We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: -0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD), n = 14)) from those without osteoporosis (δ44/42CaBlood: -0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations ([Ca]Blood) were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were - 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis.

Eisenhauer|A|A|
Müller|M|M|
Heuser|A|A|
Kolevica|A|A|
Glüer|C-C|CC|
Both|M|M|
Laue|C|C|
Hehn|U V|UV|
Kloth|S|S|
Shroff|R|R|
Schrezenmeir|J|J|

Calcium isotopes
Osteoporosis
Bone biomarkers
Bone mineral density (BMD)
Dual energy x-ray absorptiometry (DXA)
Mass-spectrometry


Long-term persistence of anti-β2 glycoprotein I in treated leprosy patients.

Abstract: β2 glycoprotein I (β2GPI) is a phospholipid binding protein that plays an important role in endothelial stability, blood coagulation, clearance of apoptotic debris and other physiologic processes. Anti-β2GPI antibodies occur in normal individuals and transiently during the course of infections, but are also associated with thrombotic events in autoimmune disease: the antiphospholipid syndrome (APS). A total of 31 out of 37 treated leprosy patients previously found to present high titers of IgM anti-β2GPI and/or anticardiolipin antibodies (aCL) remained positive for IgM antiphospholipid antibodies (aPL), and exhibited high titers of anti-β2GPI. The 37 patients were part of the 77 aPL-positive patients from a previous study that evaluated 158 leprosy patients. The median time elapsed between the first and second sample was 66 months. None of the 37 patients had any thrombotic event and 24 had a reactional state and were still requiring the use of prednisone, thalidomide or both. None of them fulfilled World Health Organization criteria for leprosy recurrence.

Ribeiro|S L E|SL|
Pereira|H L A|HL|
Silva|N P|NP|
Sato|E I|EI|
Passos|L F S|LF|
Dos-Santos|M C|MC|

antiphospholipid syndrome
Anticardiolipin antibodies
anticoagulation


The levels, sources and reactivity of volatile organic compounds in a typical urban area of Northeast China.

Abstract: Air concentrations of volatile organic compounds (VOCs) were continually measured at a monitoring site in Shenyang from 20 August to 16 September 2017. The average concentrations of alkanes, alkenes, aromatics and carbonyls were 28.54, 6.30, 5.59 and 9.78 ppbv, respectively. Seven sources were identified by the Positive Matrix Factorization model based on the measurement data of VOCs and CO. Vehicle exhaust contributed the most (36.15%) to the total propene-equivalent concentration of the measured VOCs, followed by combustion emission (16.92%), vegetation emission and secondary formation (14.33%), solvent usage (10.59%), petrochemical industry emission (9.89%), petrol evaporation (6.28%), and liquefied petroleum gas (LPG) usage (5.84%). Vehicle exhaust, solvent usage and combustion emission were found to be the top three VOC sources for O3 formation potential, accounting for 34.52%, 16.55% and 11.94%, respectively. The diurnal variation of the total VOCs from each source could be well explained by their emission characteristics, e.g., the two peaks of VOC concentrations from LPG usage were in line with the cooking times for breakfast and lunch. Wind rose plots of the VOCs from each source could reveal the possible distribution of the sources around the monitoring site. The O3 pollution episodes during the measurement period were found to be coincident with the elevation of VOCs, which was mainly due to the air parcel from the southeast direction where petrochemical industry emission was found to be dominant, suggesting that the petrochemical industry emission from the southeast was probably a significant cause of O3 pollution in Shenyang.

Ma|Zhuobiao|Z| Liu|Chengtang|C| Zhang|Chenglong|C| Liu|Pengfei|P| Ye|Can|C| Xue|Chaoyang|C| Zhao|Di|D| Sun|Jichen|J| Du|Yiming|Y| Chai|Fahe|F| Mu|Yujing|Y|

Volatile organic compounds
Field measurement
Photochemical ozone formation
Source apportionment


Students report more positive attitudes toward older adults following an interprofessional service-learning course.

Abstract: The aim of this study was to assess undergraduate students' perceptions of older adults over the semester in an interprofessional service-learning course that implemented a health promotion program called Bingocize® at community facilities for older adults. Students were surveyed at the beginning of the semester, at midterm, and at the conclusion of the course. Quantitative and qualitative data were collected to assess the students' perceptions and experiences. Results suggest that a course on aging that includes interprofessional service-learning in geriatric settings is associated with a significant increase in positive perceptions of the older adult population. Further research, however, is warranted to validate the findings.

Neils-Strunjas|Jean|J|
Crandall|K Jason|KJ|
Shackelford|Jo|J|
Dispennette|Kathryn|K|
Stevens|Lauren Rene|LR|
Glascock|Allison|A|

Service-learning
attitudes toward aging
undergraduate education


Redox Coenzyme F420 Biosynthesis in Thermomicrobia Involves Reduction by Stand-Alone Nitroreductase Superfamily Enzymes.

Abstract: Coenzyme F420 is a redox cofactor involved in hydride transfer reactions in archaea and bacteria. Since F420-dependent enzymes are attracting increasing interest as tools in biocatalysis, F420 biosynthesis is being revisited. While it was commonly accepted for a long time that the 2-phospho-l-lactate (2-PL) moiety of F420 is formed from free 2-PL, it was recently shown that phosphoenolpyruvate is incorporated in Actinobacteria and that the C-terminal domain of the FbiB protein, a member of the nitroreductase (NTR) superfamily, converts dehydro-F420 into saturated F420 Outside the Actinobacteria, however, the situation is still unclear because FbiB is missing in these organisms and enzymes of the NTR family are highly diversified. Here, we show by heterologous expression and in vitro assays that stand-alone NTR enzymes from Thermomicrobia exhibit dehydro-F420 reductase activity. Metabolome analysis and proteomics studies confirmed the proposed biosynthetic pathway in Thermomicrobium roseum These results clarify the biosynthetic route of coenzyme F420 in a class of Gram-negative bacteria, redefine functional subgroups of the NTR superfamily, and offer an alternative for large-scale production of F420 in Escherichia coli in the future.IMPORTANCE Coenzyme F420 is a redox cofactor of Archaea and Actinobacteria, as well as some Gram-negative bacteria. Its involvement in processes such as the biosynthesis of antibiotics, the degradation of xenobiotics, and asymmetric enzymatic reductions renders F420 of great relevance for biotechnology. Recently, a new biosynthetic step during the formation of F420 in Actinobacteria was discovered, involving an enzyme domain belonging to the versatile nitroreductase (NTR) superfamily, while this process remained blurred in Gram-negative bacteria. Here, we show that a similar biosynthetic route exists in Thermomicrobia, although key biosynthetic enzymes show different domain architectures and are only distantly related. Our results shed light on the biosynthesis of F420 in Gram-negative bacteria and refine the knowledge about sequence-function relationships within the NTR superfamily of enzymes. Appreciably, these results offer an alternative route to produce F420 in Gram-negative model organisms and unveil yet another biochemical facet of this pathway to be explored by synthetic microbiologists.


Effectiveness of a school-based intervention on physical activity and screen time among adolescents.

Abstract:
OBJECTIVES
To evaluate the effectiveness of a multi-component school-based intervention on physical activity (PA) and screen time (ST) among urban adolescents in Bangladesh.

DESIGN
Cluster-randomised controlled trial.

METHODS
Eight high schools were randomly assigned to either intervention group (IG) or control group (CG). Participants (n = 160 per group, 40 school) were in grades 8-9. A 12-week multi-component intervention was developed based on the WHO's Health-Promoting Schools framework. The IG received weekly supervised circuit exercise (30 min/week), health education session (10 min/week) with health educational materials, and lunchtime sports activities (20 min/week). The main outcome measures included self-reported PA, ST, knowledge on PA and SB, which were assessed at baseline, 8 and 12 weeks. Repeated measures ANCOVA was used to evaluate the intervention effects.

RESULTS
Total PA (MET-min/week) was increased from baseline to 8 and 12 weeks in the IG (3%-5%) but decreased in the CG (5%-3%) and significantly improved in the IG compared to the CG (p < 0.001) over time. Average ST (min/day) reduced from baseline to 8 and 12 weeks in the IG (28%-35%), while remained unchanged in the CG (6%-5%). The IG had a significantly lower average ST than the CG at 12 weeks. The average knowledge scores on PA and SB were significantly higher in the IG than the CG at 12 weeks (p < 0.001).

CONCLUSIONS
Our intervention has demonstrated some promising effects on increasing PA, reducing ST, and improving PA and SB knowledge. This study underscores the need for a scaled-up evaluation in other locations including rural settings.

Ahmed|Kazi Rumana|KR|
Kolbe-Alexander|Tracy|T|
Khan|Asaduzzaman|A|

Intervention
Physical activity
Screen time
Adolescent
Schools