A multiplex PCR system for 13 RM Y-STRs with separate amplification of two different repeat motif structures in DYF403S1a.

Abstract: In forensic science and human genetics, Y-chromosomal short tandem repeats (Y-STRs) have been used as very useful markers. Recently, more Y-STR markers have been analyzed to enhance the resolution power in haplotype analysis, and 13 rapidly mutating (RM) Y-STRs have been suggested as revolutionary tools that can widen Y-chromosomal application from paternal lineage differentiation to male individualization. We have constructed two multiplex PCR sets for the amplification of 13 RM Y-STRs, which yield small-sized amplicons (<400bp) and a more balanced PCR efficiency with minimum PCR cycling. In particular, with the developed multiplex PCR system, we could separate three copies of DYF403S1a into two copies of DYF403S1a and one of DYF403S1b1. This is because DYF403S1b1 possesses distinguishable sequences from DYF403S1a at both the front and rear flanking regions of the repeat motif; therefore, the locus could be separately amplified using sequence-specific primers. In addition, the other copy, defined as DYF403S1b by Ballantyne et al., was renamed DYF403S1b2 because of its similar flanking region sequence to DYF403S1b1. By redefining DYF403S1 with the developed multiplex system, all genotypes of four copies could be successfully typed and more diverse haplotypes were obtained. We analyzed haplotype distributions in 705 Korean males based on four different Y-STR subsets: Yfiler, PowerPlex Y23, Yfiler Plus, and RM Y-STRs. All haplotypes obtained from RM Y-STRs were the most diverse and showed strong discriminatory power in Korean population.

Lee|Eun Young|EY|
Lee|Hwan Young|HY|
Kwon|So Yeun|SY|
Oh|Yu Na|YN|
Yang|Woo Ick|WI|
Shin|Kyoung-Jin|KJ|

D060885:Multiplex Polymerase Chain Reaction

Haplotype
DYF403S1
Koreans
Discriminatory power
Rapidly mutating Y-STR


Demographic Risk Factors for Suicide among Youths in The Netherlands.

Abstract: In 2000 to 2016 the highest number of suicides among Dutch youths under 20 in any given year was 58 in 2013. In 2017 this number increased to 81 youth suicides. To get more insight in what types of youths died by suicide, particularly in recent years (2013-2017) we looked at micro-data of Statistics Netherlands and counted suicides among youths till 23, split out along gender, age, regions, immigration background and place in household and compared this to the general population of youths in the Netherlands. We also compared the demographics of young suicide victims to those of suicide victims among the population as a whole. We found higher suicide rates among male youths, older youths, those of Dutch descent and youths living alone. These differences were generally smaller than in the population as a whole. There were also substantial geographical differences between provinces and healthcare regions. The method of suicide is different in youth compared to the population as a whole: relatively more youth suicides by jumping or lying in front of a moving object and relatively less youth suicides by autointoxication or drowning, whereas the most frequent method of suicide among both groups is hanging or suffocation.


Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4-12 Years.

Abstract:
BACKGROUND
Few studies have examined the efficacy or safety of a transdermal β2 agonist as add-on medicationto long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients.

METHODS
In this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2 mg daily) or oral sustained-release theophylline (usual dose, 4-5 mg_kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events.

RESULTS
Thirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group.

CONCLUSIONS
These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy.

Katsunuma|Toshio|T| Fujisawa|Takao|T| Mizuho|Nagao|N| Akira|Akasawa|A| Nomura|Ichiro|I| Yamaoka|Akiko|A| Kondo|Hisashi|H| Masuda|Kei|K| Yamaguchi|Koichi|K| Terada|Akihiko|A| Ikeda|Masanori|M| Nishioka|Kenji|K| Adachi|Yuichi|Y| Kurihara|Kazuyuki|K|

tulobuterol
asthma
theophylline
child
preschool
transdermal patch


Age at menarche and epithelial ovarian cancer risk: A meta-analysis and Mendelian randomization study.

Abstract: Age at menarche (AAM) was found to be associated with ovarian cancer risk in previous observational studies. However, the causality of this association remains unclear. Here, after systematic meta-analyses, we performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of AAM in epithelial ovarian cancer (EOC) etiology. We performed meta-analyses including 11 410 cases and 1 163 117 noncases to quantitatively evaluate the association between AAM and ovarian cancer risk. In MR analyses, we used 25 single nucleotide polymorphisms (SNPs) associated with AAM for Chinese and 390 SNPs for Europeans as instrumental variables. MR estimates were calculated using inverse-variance weighted methods from 1044 cases and 1172 controls in a Chinese genome-wide association study and validated by the Ovarian Cancer Association Consortium and Consortium of Investigators of Modifiers of BRCA1/2 studies with 29 396 cases and 68 502 controls of European ancestry. In meta-analyses, we observed an inverse association (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.93 to 1.00, P = 0.036) between per year older AAM and ovarian cancer risk in case-control studies, but no association was observed in cohort studies. In MR analyses, the OR of EOC risk per year increase in AAM was 0.81 (95% CI = 0.67 to 0.97, P = 0.026) in Chinese and 0.94 (95% CI = 0.90 to 0.98, P = 0.003) in Europeans, respectively. Our study supports a causal association between AAM and EOC risk.

menarche
ovarian cancer
meta-analysis
Mendelian randomization analysis


The Relationship Between Dissociation and Symptoms of Psychosis: A Meta-analysis.

Abstract: Evidence suggests that dissociation is associated with psychotic experiences, particularly hallucinations, but also other symptoms. However, until now, symptom-specific relationships with dissociation have not been comprehensively synthesized. This is the first prospectively registered (CRD42017058214) meta-analysis to quantify the magnitude of association between dissociative experiences and all symptoms of psychosis. MEDLINE, PsycINFO, PubMed, and Scopus databases were searched using exhaustive terms denoting dissociation and psychotic symptoms. We included both nonclinical (58 studies; 16 557 participants) and clinical (46 studies; 3879 patient participants) samples and evaluated study quality. Ninety-three eligible articles considering 20 436 participants were retained for analysis. There was a robust association between dissociation and clinical and nonclinical positive psychotic symptoms (r = .437; 95%CI: .386 -.486), with the observed effect larger in nonclinical studies. Symptom-specific associations were also evident across clinical and nonclinical studies, and included significant summary effects for hallucinations (r = .461; 95%CI: .386 -.531), delusions (r = .418; 95%CI: .370 -.464), paranoia (r = .447; 95%CI: .393 -.499), and disorganization (r = .346; 95%CI: .249 -.436). Associations with negative symptoms were small and, in some cases, not significant. Overall, these findings confirm that dissociative phenomena are not only robustly related to hallucinations but also to multiple positive symptoms, and less robustly related to negative symptoms. Our findings are consistent with proposals that suggest certain psychotic symptoms might be better conceptualized as dissociative in nature and support the development of interventions targeting dissociation in formulating and treating psychotic experiences.

Longden|Eleanor|E| Branitsky|Alison|A| Moskowitz|Andrew|A| Berry|Katherine|K| Bucci|Sandra|S| Varese|Filippo|F|

dissociation
psychosis
meta-analysis
childhood trauma


A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development.

Abstract: During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown. In this study, ADAM12 was localized to anchoring trophoblast columns in first trimester placentas and to highly invasive extracellular matrix-degrading trophoblasts in placental villous explants. The importance of ADAM12 in directing trophoblast invasion was tested using loss-of and gain-of-function strategies, where siRNA-directed knockdown of ADAM12 inhibited trophoblast cell invasion while over-expression promoted migration and invasion in two trophoblastic cell models. In placental villous explant cultures, siRNA-directed loss of ADAM12 significantly dampened trophoblast column outgrowth. Additionally, we provide functional evidence for the ADAM12S variant in promoting trophoblast invasion and column outgrowth through a mechanism requiring its catalytic activity. This is the first study to assign a function for ADAM12 in trophoblast biology, where ADAM12 may play a central role regulating the behavior of invasive trophoblast subsets in early pregnancy. This study also underlines the importance of ADAM12L and ADAM12S in directing cell motility in normal developmental processes outside of cancer, specifically highlighting a potentially important function of ADAM12S in directing early placental development.

Aghababaei|M|M|
Perdu|S|S|
Irvine|K|K|
Beristain|A G|AG|

D018507:Gene Expression Regulation, Developmental

A Disintegrin and Metalloproteinase 12
trophoblast
cell invasion
placenta
protease


Promoting attachment between parents and neonates despite the COVID-19 pandemic.

Abstract: Social distancing is the only option available during the COVID-19 pandemic until a vaccine is developed. However, this is having a major impact on human relationships and bonding between parents and neonates is a major concern. Separation during this health emergency could have lifelong consequences for offspring, and there are even greater concerns if newborn infants are sick or vulnerable and need intensive care. We look at how bonding can be safely supported and maintained without risking infecting neonates, by comparing the international guidelines and proposing safe actions within those frameworks.

COVID-19 pandemic bonding separation guidelines


Why does Existential Threat Promote Intergroup Violence? Examining the Role of Retributive Justice and Cost-Benefit Utility Motivations.

Abstract: The current research examined the role of retributive justice and cost-benefit utility motivations in the process through which mortality salience increases support for violent responses to intergroup conflict. Specifically, previous research has shown that mortality salience often encourages political violence, especially when perceptions of retributive justice are activated. The current research examined whether mortality salience directly activates a justice mindset over a cost-benefit utility mindset, and whether this justice mindset is associated with support for political violence. In Study 1 (N = 209), mortality salience was manipulated among Israeli participants who then read about a Hamas attack on Israel with either no casualties or many casualties, after which justice and utility motivations for retribution were assessed. Study 2 (N = 112), examined whether the link between death primes and support for an Israeli preemptive strike on Iran's nuclear facilities is mediated by justice or cost-benefit utility considerations. Results of both studies revealed that primes of death increased justice-related motivations, and these motives, rather than utility motives, were associated with support for violence. Findings suggest that existential concerns often fuel violent intergroup conflict because they increase desire for retributive justice, rather than increase belief that violence is an effective strategy. These findings expand our knowledge on the motivations for intergroup violence, and shed experimental light on real-life eruptions of violent conflict indicating that when existential concerns are salient, as they often are during violent conflict, the decision to engage in violence often disregards the utility of violence, and leads to the preference for violent solutions to political problems - even when these solutions make little practical sense.

intergroup conflict
support for violence
cost-benefit analysis
justice beliefs
terror management


Single Cell Proteomics Using Multiplexed Isobaric Labeling for Mass Spectrometric Analysis.

Abstract: Single cell proteomics is an emerging field of bioanalysis allowing one to capture proteome profiles of isolated single cells, which is expected to yield additional biological information in comparison with bulk cell analysis. Mass spectrometry-based methods provide unbiased analysis of detectable proteins limited only by technical parameters, such as sensitivity, which necessitates the development of best-practice workflows. Here, we describe the entire experimental design of single cell proteome analysis, exemplified by cultured A549 lung adenocarcinoma cells treated with an anti-cancer drug (methotrexate) and utilizing tandem mass tag (TMTpro™) labeling strategy for mass spectrometric data acquisition.

Végvári|Ákos|Á|
Rodriguez|Jimmy E|JE|
Zubarev|Roman A|RA|

Single cell proteomics
Methotrexate
A549 human cell line
Chemical proteomics
Clean sample preparation
Mass spectrometry
TMT-labeling


Prognostic value of on admission arterial PCO2 in hospitalized patients with community-acquired pneumonia.

Abstract:
BACKGROUND
There is little data about the correlation between the outcome of community acquired pneumonia (CAP) and the hypercapnic type respiratory failure. In this study we prospectively investigated the prognostic significance of first arterial CO2 tension in patients hospitalized with CAP.

METHODS
In this prospective study patients with CAP, admitted to a general hospital were included. PaCO2 was measured for each subject in an arterial blood sample drawn in the first 2 hours and its correlations with three major outcomes were evaluated: intensive care unit (ICU) admission, duration of admission and mortality in 30 days.

RESULTS
A total of 114 patients (mean age: 60.9±18.3; male: 51.8%) diagnosed with CAP were included. Significant relationship was not found between PaCO2 and mortality (P=0.544) or ICU admission (P=0.863). However advanced age, associated CHF, high BUN levels, high CURB-65 scores, associated pleural effusion in chest X-ray and being admitted to the ICU (P=0.012, 0.004, 0.003, <0.001, 0.045 and <0.001 respectively) were all significant prognostic factors of higher mortality risks. Prognostic factors for ICU admission were a history of malignancy (P=0.004), higher CURB-65 (P<0.001) scores and concomitant pleural effusion (P=0.028) in chest X-ray. Hypercapnic patients hospitalized for longer duration compared with normocapnic subjects. Furthermore, patients with lower pH (P=0.041) and pleural effusions (P=0.002) were hospitalized longer than the others.

CONCLUSIONS
There was less prominent prognostic value regarding on-admission PaCO2 in comparison to other factors such as CURB-65. Considering the inconsistent results of surveys conducted on prognostic value of PaCO2 for CAP outcomes, further investigations are required to reach a consensus on this matter.

Yassin|Zeynab|Z|
Saadat|Mohammad|M|
Abtahi|Hamidreza|H|
Rahimi Foroushani|Abbas|A|
Peiman|Soheil|S|

intensive care unit (ICU)
mortality
Community-acquired pneumonia (CAP)
arterial blood gases (ABGs)
arterial carbon dioxide tension


Differences in apoptotic signaling and toxicity between dimethylmonothioarsinic acid (DMMTAV) and its active metabolite, dimethylarsinous acid (DMAIII), in HepaRG cells: Possibility of apoptosis cascade based on diversity of active metabolites of DMMTAV.

Abstract: Dimethylmonothioarsinical acid (DMMTAV), a metabolite of arsenosugars (AsSug) and arsenolipids (AsLP), which are major organoarsenicals contained in seafoods, has been a focus of our attention due to its toxicity. It has been reported that the toxicity of DMMTAV differs according to the host cell type and that dimethylarsinous acid (DMAIII), which is a higher active metabolite of inorganic and organo arsenic compounds, may be the ultimate substance. To further elucidate the details of the mechanisms of DMMTAV, we carried out toxicological characterization by comparing DMMTAV and DMAIII using HepaRG cells, which are terminally differentiated hepatic cells derived from a human hepatic progenitor cell line that retains many characteristics, e.g, primary human hepatocytes including the morphology and expression of key metabolic enzymes (P450 s and GSTs, etc.) and complete expression of all nuclear receptors. HepaRG cells were induced to undergo differentiation by DMSO, which result red in increased levels of metabolic enzymes such as P450 and GST, in non-differentiated cells the cellular toxicities of DMMTAV and DMAIII were reduced and the induction of toxicity by DMMTAV was increased by GSH but not by DMAIII. Both DMAIII and DMMTAV induce apoptosis and increase caspase 3/7 activity. DMAIII exposure increased the activity of caspase-9. On the contrary, DMMTAV exposure resulted in markedly elevated activity of caspase-8 as well as caspase-9. These results suggest there are differences between the signaling pathways of apoptosis in DMAIII and DMMTAV and that between their active metabolites. Consequently, the ultimate metabolic substance of toxicity induction of DMMTAV may not only be DMAIII, but may also be partly due to other metabolic substances produced through the activation mechanism by GSH.

Shimoda|Yasuyo|Y| Kato|Koichi|K| Asami|Satoru|S| Kurita|Masahiro|M| Kurosawa|Hidetoshi|H| Toriyama|Masaharu|M| Miura|Motofumi|M| Hata|Akihisa|A| Endo|Yoko|Y| Endo|Ginji|G| An|Yan|Y| Yamanaka|Kenzo|K|

Dimethylmonothioarsinic acid
Dimethylarsinic acid
Dimethylarsinic acid
Apoptosis
Caspase
Dimethylarsinous acid
Glutathione


Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug-naïve type 2 diabetic patients.

Abstract:
BACKGROUND
The weight-reducing effect of exenatide has been proved, but too much weight loss in normal-weight patients may concern physicians. This study evaluated the effects of exenatide monotherapy on glycemic control and weight change in normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes (T2D).

METHODS
In this multicenter prospective study, 29 normal-weight, 54 overweight, and 27 obese newly diagnosed and drug-naïve patients with T2D were treated with exenatide for 48 weeks. The primary efficacy endpoint was the effect of baseline body mass index (BMI) on glycemic control, measured as the change in HbA1c from baseline to Week 48 compared among different BMI groups. Other endpoints included comparisons of the effects of exenatide on fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body weight, and other metabolic indices.

RESULTS
After 48-week treatment, the estimated mean changes in HbA1c in normal-weight, overweight, and obese patients were -1.9%, -1.8%, and -1.5%, respectively (P = 0.290 among groups after adjustment for baseline values). There were similar declines in FPG and 0.5- and 2-hour PPG among groups. There were non-significant trends from normal-weight to overweight to obese patients for increased weight reduction (decreases of 2.2, 3.9, and 4.0 kg, respectively; P = 0.104) and changes in waist circumference (decreases of 2.2, 3.2, and 5.6 cm, respectively; P = 0.078).

CONCLUSIONS
Baseline BMI had no effect on glycemic control, weight change, or other metabolic indices with exenatide monotherapy. Normal-weight patients with T2D would benefit from exenatide as much as overweight or obese patients on glucose control, without increased risk of excess weight loss.

Deng|Hongrong|H| Lin|Shuo|S| Yang|Xubin|X| Lv|Jing|J| Luo|Sihui|S| Zeng|Longyi|L| Weng|Jianping|J| Xu|Wen|W| |||

exenatide
type 2 diabetes
body weight
2型糖尿病
体重
艾塞那肽


Ritonavir-boosted paritaprevir, ombitasvir plus ribavirin could improve eGFR in patients with renal impairment and HCV: an Egyptian cohort.

Abstract:
BACKGROUND
The present study aimed at evaluation of changes in estimated glomerular filtration rate (eGFR) among chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) Stages 3-5 who were treated with 12 weeks of ritonavir-boosted paritaprevir, ombitasvir plus ribavirin.

METHODS
Changes in renal functions were compared across follow up time points (baseline, SVR4, and SVR8). Data on on-treatment adverse events (AEs), serious AEs, laboratory abnormalities, treatment discontinuation were collected.

RESULTS
171 patients were included (females 35%, mean age 53 years). 29 patients had liver cirrhosis. The most common etiologies of CKD were diabetes and/or hypertension (n = 67). All included patient reached the end of treatment (EOT) with no treatment discontinuations. The overall EOT response was 100%. 122/122 (100%) patients who reached 4 weeks post-treatment have achieved SVR4, and 80/80 (100%) have achieved SVR12. No reported SAEs. Ribavirin therapy was interrupted in 25% (43/171) of patients due to anemia; 16 patients required blood transfusions. The median eGFR improved from 33.5 (15) mL/min/1.73 m2 at baseline to 35 (36) mL/min/1.73 m2 at SVR8 (p = 0.0003).

CONCLUSIONS
The use of ombitasvir, paritaprevir, and ritonavir for treatment of HCV-infected patients with advanced renal disease was safe and effective, moreover, it was associated with significantly improved eGFR.

ritonavir-boosted paritaprevir
ombitasvir
eGFR
HCV
chronic kidney disease
genotype 4
real-world


Prognostic factors and incidence of primary mucosal melanoma: a population-based study in France.

Abstract: Few population-based studies on the incidence and prognosis of primary mucosal melanoma (PMM) are available. The first objective was to evaluate disease-specific survival of PMM, overall and according to specific locations, and to identify prognostic factors. The second objective was to assess the global incidence of PMM compared to cutaneous melanoma and to specify the relative frequency of each affected location. A retrospective population-based study of incident PMM diagnosed between 2004 and 2014 was conducted, relying on the regional melanoma registry of the French Champagne-Ardenne region (1.34 million inhabitants). Thirty-nine cases were identified, including 17 head and neck (13 sinonasal and four oral), 12 vulvovaginal, six conjunctival, and four anorectal PMMs. Some 76.9% of cases were revealed by late symptoms. The median disease-specific survival time was 23.9 months and the five-year disease-specific survival rate was 31.8%. Univariate and multivariate analyses led to identification of primary tumour size and the presence of nodal or visceral macrometastases at diagnosis as adverse prognostic factors, while Breslow thickness and ulceration were unreported in 41% of cases and failed to display any prognostic value. Compared to other locations, conjunctival PMMs had a smaller tumour size and better prognosis. The annual incidence rate was 0.18/100,000 and the incidence ratio between PMM and cutaneous melanoma was 1/50. This population-based study confirms the rarity, delayed diagnosis, and severity of PMM, suggesting that improving prognosis will require specific, targeted therapies.

Beaudoux|Olivia|O| Riffaud|Laurence|L| Barbe|Coralie|C| Grange|Florent|F|

incidence
primary mucosal melanoma
prognosis


Bisphosphonate Use in Pediatric Oncology for Pain Management.

Abstract: The use of bisphosphonates for pain control in children with cancer is not extensively studied. We retrospectively evaluated 35 children with cancer treated with intravenous bisphosphonates for pain management at a single institution from 1998 through 2015. We analyzed pain scores and opioid and adjuvant medication consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and 4 weeks after administration. We also determined the time interval between diagnosis and first administration of bisphosphonates and duration of life after bisphosphonate administration. Mean pain scores were 2.45 (±2.96) and 0.75 (±1.69) before and 14 days after bisphosphonate administration, respectively ( P = .25), and morphine equivalent doses of opioids were 5.52 (±13.35) and 5.27 (±9.77), respectively ( P = .07). Opioid consumption was significantly decreased at days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration. The median duration of life after first bisphosphonate administration was 80 days, indicating its use late in the course of treatment. Bisphosphonates did not significantly improve pain outcomes at 2 weeks, but opioid consumption was reduced at several time points during the first 3 weeks. The use of bisphosphonates earlier in the course of pediatric oncological disease should be evaluated in prospective investigations.

bisphosphonate
pain management
pain scores
opioid consumption
adjuvant pain medication
pediatric cancer


Mobility Analysis of AmpuTees (MAAT I): Quality of life and satisfaction are strongly related to mobility for patients with a lower limb prosthesis.

Abstract:
BACKGROUND
While rehabilitation professionals are historically trained to place emphasis on the restoration of mobility following lower limb amputation, changes in healthcare dynamics are placing an increased emphasis on the limb loss patient's quality of life and general satisfaction. Thus, the relationship between these constructs and mobility in the patient with lower limb loss warrants further investigation.

OBJECTIVES
To determine the relationship between mobility of the patient with lower limb loss and both (1) general satisfaction and (2) quality of life.

STUDY DESIGN
Retrospective chart analysis.

METHODS
A retrospective chart review of the Prosthetic Limb Users Survey of Mobility and the Prosthesis Evaluation Questionnaire-Well-Being subsection. Pearson correlations were used to test relationships.

RESULTS
Data from 509 patients with a lower limb prosthesis were included. Mobility was found to be positively correlated with quality of life ( r = 0.511, p < 0.001, 95% confidence interval (0.443, 0.569)) and general satisfaction ( r = 0.475, p < 0.001, 95% confidence interval (0.403, 0.542)), as well as their arithmetic mean (i.e. Prosthesis Evaluation Questionnaire-Well-Being) ( r = 0.533, p < 0.001, 95% confidence interval (0.466, 0.592)).

CONCLUSION
This study provides evidence of a strong positive correlation between mobility and both quality of life and general satisfaction. Thus, in the holistic care of a patient with lower limb loss, maximizing mobility would correlate with greater quality of life and general satisfaction. Clinical relevance There is growing emphasis on the quality of life and general satisfaction experienced by patients undergoing prosthetic rehabilitation. The results of this study underscore the importance of providing prosthetic rehabilitation that maximizes the patient's mobility, noting that these individuals also report greater quality of life and general satisfaction.

Wurdeman|Shane R|SR|
Stevens|Phillip M|PM|
Campbell|James H|JH|

mobility
MAAT
quality of life
amputation
prosthetics


Correlating soil nutrient test lead with bioaccessible lead in highly-contaminated soils receiving lead-immobilizing amendments.

Abstract: Lead (Pb) is one of the most common metals exceeding human health risk guidelines for soil concentrations worldwide. Pb bioaccessibility is known to vary depending on soil physiochemical characteristics and, as a result, in vitro and in vivo tests exist that are used to estimate bioaccessible Pb in contaminated soils. Although in vitro tests such as the relative bioaccessibility leaching procedure (RBALP) present simpler and more cost-effective risk assessments than in vivo methods, soil tests such as Mehlich-3, Modified Morgan, and ammonium bicarbonate-diethylenetriamine pentaacetate (AB-DTPA) extractions are extremely routine and even more cost-effective. Currently, there are few comparisons examining the viability of common soil nutrient tests for assessing Pb bioaccessibility in soils from contaminated sites with extremely high total Pb concentrations or for sites that have received amendments, such as those containing compost, iron, and/or phosphorus, intended to immobilize Pb. Here, we examine the correlation between RBALP Pb and Pb as determined using three commonly utilized soil tests, Mehlich-3, Modified Morgan, and AB-DTPA, in archived samples from one Pb-contaminated site receiving compost amendment (Seattle, WA, USA) and one extremely Pb-contaminated site receiving mixtures of compost, P, and Fe (Joplin, MO, USA). At both the Seattle and Joplin sites separately, RBALP Pb was significantly correlated with all three soil nutrient test values, regardless of soil amendment. However, RBALP was only significantly correlated with Modified Morgan and total Pb when examining the Joplin and Seattle data together, likely resulting from different factors controlling Pb solubility at the two sites. These findings suggest that a diverse suite of relatively inexpensive and accessible soil nutrient test methods correlate with bioaccessible Pb at a specific site, regardless of whether Pb-immobilizing amendments have been used.

Judy|Jonathan D|JD|
Sarchapone|Jennifer|J|
Gravesen|Caleb|C|
Hettiarachchi|Ganga|G|
Buchanan|Caroline|C|
LaMontagne|Derek|D|
Pachon|Julio|J|

Lead
Bioavailability
E-waste
Mitigation
Urban soils


Invasive Insects: Management Methods Explored.

Abstract: Invasive insect species can act as a plague across the globe, capable of vast expansion and rapid, proliferate reproduction. The spread of pathogens of serious diseases such as malaria and Zika virus and damages to agricultural crops number some of the afflictions invasive insects provide to humans alone. Additionally, an escape from predators can fail to keep invasive insects in check, providing potential threats such as extra resource competition to native species when insects invade. A variety of methods are employed to combat these invasive species, each with their own varying levels of success. Here, we explore the more traditional methods of invasive insect pest control, such as pesticides and biological control. In lieu of several unintended consequences resulting from such practices, we suggest some should be abandoned. We evaluate the potential of new techniques, in particular, those with a genetic component, regarding the costs, benefits and possible consequences of implementing them. And finally, we consider which techniques should be the focus of future research, if we truly wish to manage or even eradicate invasive insects in their introduced lands.

McLaughlin|Gemma M|GM|
Dearden|Peter K|PK|

invasive insect
pesticide
RNA interference
biocontrol
gene editing


Assessing the potential value and mechanism of Ginkgo biloba L. On coal-fired arsenic-induced skin damage: In vitro and human evidence.

Abstract: Exposure through arsenic-contaminated air and food caused by the burning of coal is a major environmental public health concern in Guizhou Province of China. Previous studies have shown that immunological dysfunction is involved in the pathogenesis and carcinogenesis of arsenic; however, knowledge regarding effective prevention measures have not been fully examined. The effect of Ginkgo biloba extract (EGb761) on arsenic-induced skin damage of human immortalized keratinocyte cells (HaCaT) was first evaluated in this study. The results showed that 200 μg/mL EGb761 can reduce the expression of miR-155-5p, and the indicators reflecting arsenic-induced skin damage (Krt1, Krt6c and Krt10) in arsenic-exposed cells (P < 0.05), the expression levels of NF-AT1; the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) in cells; and the levels of secreted IL-2 and IFN-γ in cell supernatants were significantly increased (P < 0.05). Further randomized controlled double-blind experiments showed that compared to the placebo control group, the expression level of miR-155-5p in the plasma of the Ginkgo biloba intervention group, the indicators in the serum reflecting arsenic-induced skin damage (Krt1, Krt6c, and Krt10) and the epithelial-mesenchymal transformation (EMT) vimentin were significantly reduced (P < 0.05), but the levels of NF-AT1 and the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) and EMT (E-cadherin) in serum were significantly increased (P < 0.05). Our study provides some limited evidence that Ginkgo biloba L. can increase the expression of NF-AT1 by downregulating the level of miR-155-5p, alleviating immunological dysfunction, and decreasing the expression of EMT biomarkers, thus indirectly improving arsenic-induced skin damage.

Ginkgo biloba L.
skin damage
immunological dysfunction
Arsenic


Research on Current Curative Expenditure among Lung Cancer Patients Based on the "System of Health Accounts 2011": Insights into Influencing Factors.

Abstract:
PURPOSE
To investigate the total current curative expenditure (CCE) of lung cancer in Hunan Province, China under the framework of the System of Health Accounts 2011 (SHA 2011) and explore the effect of insurance status, surgery and length of stay on the hospitalization expenses of patients with lung cancer.

METHODS
Through multistage stratified cluster random sampling, a total of 46,214 patients with lung cancer were enrolled from 1,072 medical institutions in Hunan Province in 2016. Under the SHA 2011 framework, the lung cancer CCE was analyzed. The relationships between hospitalization expenditure and the following factors (surgery, type of hospital, insurance status, length of stay, institution level, age and sex) were analyzed using Spearman's correlation analyses, and how these factors influenced hospital expenditure was explored through multiple stepwise regression analysis and structural equation modelling.

RESULTS
The CCE for lung cancer patients was 8063.75 million CNY. In total, 96.03% of the CCE for lung cancer occurred in hospitals and 58.88% of the expenditure flowed to general hospitals. The highest expenditures were incurred in the group aged 55-74 y, which accounted for 61.58% of the CCE. Drugs accounted for the greatest share expenditure to lung cancer patients at 34.31% of the CCE. Surgery, insurance status, institution level, sex and hospital type explained 57.5% of the variance in hospital expenses. The hospitalization expenses were related to surgery, insurance status, institution level and sex (rs = 0.033-0.688, p < 0.001). Surgery, insurance status and length of stay had direct effects on hospitalization expenses. Length of stay mediated the relationship between surgery and hospitalization expenses for lung cancer patients. Surgery mediated the relationship between insurance status and hospitalization expenses. All of these variables can explain 45% of the variance in hospitalization expenses.

CONCLUSIONS
The CCE of lung cancer is extremely high. The problems related to treatment efficiency and equity are serious for lung cancer patients in China. It is essential to expand health insurance coverage and reduce the curative expenditure of lung cancer.

Zang|Shuang|S| Zhan|Huan|H| Zhou|Liangrong|L| Wang|Xin|X|

current curative expenditure
lung cancer
System of Health Accounts 2011


Ferritin H gene deletion in the choroid plexus and forebrain results in hydrocephalus.

Abstract: Ferritin H, the major iron storage protein, has essential functions in early embryonic development as well as in adult liver and intestine. To address the question whether ferritin H has similarly essential functions in the brain we used the Cre/loxP system to generate mice with a forebrain-specific inactivation of the ferritin H gene. Ferritin H deficiency in most cells of the forebrain including cells of the choroid plexus caused accumulation of cerebrospinal fluid in the lateral ventricles and the subarachnoid space. Brain tissue iron content was unchanged.

Schweizer|Claude|C|
Fraering|Patrick C|PC|
Kühn|Lukas C|LC|

Ferritin H
Iron
Brain
Mice
Blood brain barrier


Real-time skin chromophore estimation from hyperspectral images using a neural network.

Abstract:
BACKGROUND
Hyperspectral imaging for in vivo human skin study has shown great potential by providing non-invasive measurement from which information usually invisible to the human eye can be revealed. In particular, maps of skin parameters including oxygen rate, blood volume fraction, and melanin concentration can be estimated from a hyperspectral image by using an optical model and an optimization algorithm. These applications, relying on hyperspectral images acquired with a high-resolution camera especially dedicated to skin measurement, have yielded promising results. However, the data analysis process is relatively expensive in terms of computation cost, with calculation of full-face skin property maps requiring up to 5 hours for 3-megapixels hyperspectral images. Such a computation time prevents punctual previewing and quality assessment of the maps immediately after acquisition.

METHODS
To address this issue, we have implemented a neural network that models the optimization-based analysis algorithm. This neural network has been trained on a set of hyperspectral images, acquired from 204 patients and their corresponding skin parameter maps, which were calculated by optimization.

RESULTS
The neural network is able to generate skin parameter maps that are visually very faithful to the reference maps much more quickly than the optimization-based algorithm, with computation times as short as 2 seconds for a 3-megapixel image representing a full face and 0.5 seconds for a 1-megapixel image representing a smaller area of skin. The average deviation calculated on selected areas shows the network's promising generalization ability, even on wide-field full-face images.

CONCLUSION
Currently, the network is adequate for preview purposes, providing relatively accurate results in a few seconds.

hyperspectral
imaging
in vivo
non-invasive
machine learning


Optimization of soya lecithin and Tween 80 based novel vitamin D nanoemulsions prepared by ultrasonication using response surface methodology.

Abstract: Vitamin D nanoemulsions were fabricated using ultrasonic homogenization approach. Response surface methodology (RSM) was used to optimize the preparation conditions for mixed surfactants (Soya lecithin and Tween 80; 2:3) based nanoemulsions. The effects of homogenization time (3.5-6.5 min), surfactant to oil ratio (0.43-0.78) and disperse phase volume (7-9%) on response variables were studied. Response Surface Methodology analysis results depicted that the polynomial model (second-order) can be used to predict response values. The coefficients of determinations were more than 0.90 for each response. The optimum emulsifying conditions for vitamin D nanoemulsions were 4.35 min homogenization time, 0.62 surfactant to oil ratio (S/O) and 7% disperse phase volume (DPV). Whereas, the experimental values for droplet size, droplet growth ratio (DGR) and vitamin D retention were 112.36 ± 3.6 nm, 0.141 ± 0.07 and 76.65 ± 1.7% respectively. This research will be useful for the food and pharmaceutical industry to develop soya lecithin and Tween 80 based vitamin D delivery system for food additives and nutraceutical components.

Mehmood|Tahir|T|
Ahmed|Anwaar|A|
Ahmed|Zaheer|Z|
Ahmad|Muhammad Sheeraz|MS|

Soya lecithin
Vitamin D
Nanoemulsions
RSM
Droplet size


Tularemia as a waterborne disease: a review.

Abstract: Francisella tularensis is a Gram-negative, intracellular bacterium causing the zoonosis tularemia. This highly infectious microorganism is considered a potential biological threat agent. Humans are usually infected through direct contact with the animal reservoir and tick bites. However, tularemia cases also occur after contact with a contaminated hydro-telluric environment. Water-borne tularemia outbreaks and sporadic cases have occurred worldwide in the last decades, with specific clinical and epidemiological traits. These infections represent a major public health and military challenge. Human contaminations have occurred through consumption or use of F. tularensis-contaminated water, and various aquatic activities such as swimming, canyoning and fishing. In addition, in Sweden and Finland, mosquitoes are primary vectors of tularemia due to infection of mosquito larvae in contaminated aquatic environments. The mechanisms of F. tularensis survival in water may include the formation of biofilms, interactions with free-living amoebae, and the transition to a 'viable but nonculturable' state, but the relative contribution of these possible mechanisms remains unknown. Many new aquatic species of Francisella have been characterized in recent years. F. tularensis likely shares with these species an ability of long-term survival in the aquatic environment, which has to be considered in terms of tularemia surveillance and control.

Tularemia
waterborne diseases
mosquitoes
aquatic environment
amoeba
species
bacterial biofilms


Report of the Korean Association of Lung Cancer Registry (KALC-R), 2014.

Abstract:
PURPOSE
The aim of this study was to investigate epidemiology, clinical characteristics and sex differences of patients with lung cancer using nationwide registry in Korea.

Materials and Methods
The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry, and surveyed about 10% of lung cancer cases. For this first survey of cases diagnosed in 2014, cases were selected through a systematic sampling method.

RESULTS
Total 2,621 lung cancer patients were surveyed, and the median patient age was 70 years. During the study period, adenocarcinoma was the most frequent histologic type, the proportion of female patients was 28.4%, and women had a better prognosis (median survival, not reached vs. 13 months; p<0.001) than did men for non-small cell lung cancer. The proportion of never-smokers was 36.4%, and never-smoking was more prevalent in women than in men (87.5 vs. 16.0%, p<0.001). Epidermal growth factor receptor (EGFR) mutations were found in 36.8% of stage IV adenocarcinoma patients, and higher in female compared to male patients (51.2 vs. 26.6%, p<0.001). In addition, patients with EGFR mutation showed better survival (median survival, 18 vs. 8 months; p<0.001) than patients without EGFR mutation in these patients.

CONCLUSION
This is the first survey to gather unbiased nationwide lung cancer statistics in Korea. More than one-third of lung cancer patients had no smoking history. Female had a high proportion of non-smoker, more adenocarcinoma with EGFR mutation and generally better prognosis than male.

Choi|Chang-Min|CM|
Kim|Ho Cheol|HC|
Jung|Chi Young|CY|
Cho|Deog Gon|DG|
Jeon|Jae Hyun|JH|
Lee|Jeong Eun|JE|
Ahn|Jin Seok|JS|
Kim|Seung Joon|SJ|
Kim|Yeongdae|Y|
Choi|Yoo-Duk|YD|
Suh|Yang-Gun|YG|
Kim|Jung-Eun|JE|
Lee|Boram|B|
Won|Young-Joo|YJ|
Kim|Young-Chul|YC|

Epidemiology
Korea
Never-smokers
Epidermal growth factor receptor
Lung neoplasms


Using word embedding technique to efficiently represent protein sequences for identifying substrate specificities of transporters.

Abstract: Membrane transport proteins and their substrate specificities play crucial roles in various cellular functions. Identifying the substrate specificities of membrane transport proteins is closely related to protein-target interaction prediction, drug design, membrane recruitment, and dysregulation analysis, thus being an important problem for bioinformatics researchers. In this study, we applied word embedding approach, the main cause for natural language processing breakout in recent years, to protein sequences of transporters. We defined each protein sequence based on the word embeddings and frequencies of its biological words. The protein features were then fed into machine learning models for prediction. We also varied the lengths of protein sequence's constituent biological words to find the optimal length which generated the most discriminative feature set. Compared to four other feature types created from protein sequences, our proposed features can help prediction models yield superior performance. Our best models reach an average area under the curve of 0.96 and 0.99, respectively on the 5-fold cross validation and the independent test. With this result, our study can help biologists identify transporters based on substrate specificities as well as provides a basis for further research that enriches a field of applying natural language processing techniques in bioinformatics.

Nguyen|Trinh-Trung-Duong|TT| Le|Nguyen-Quoc-Khanh|NQ| Ho|Quang-Thai|QT| Phan|Dinh-Van|DV| Ou|Yu-Yen|YY|

D000595:Amino Acid Sequence
D019295:Computational Biology
D006801:Humans
D026901:Membrane Transport Proteins
D009323:Natural Language Processing
D013379:Substrate Specificity
D060388:Support Vector Machine

Word embeddings
Substrate specificities
Transporter
Natural language processing
Feature extraction
Protein function prediction
Support vector machine


Novel spectrophotometric determination of flumethasone pivalate and clioquinol in their binary mixture and pharmaceutical formulation.

Abstract: This work is concerned with development and validation of three simple, specific, accurate and precise spectrophotometric methods for determination of flumethasone pivalate (FP) and clioquinol (CL) in their binary mixture and ear drops. Method A is a ratio subtraction spectrophotometric one (RSM). Method B is a ratio difference spectrophotometric one (RDSM), while method C is a mean center spectrophotometric one (MCR). The calibration curves are linear over the concentration range of 3-45 μg/mL for FP, and 2-25 μg/mL for CL. The specificity of the developed methods was assessed by analyzing different laboratory prepared mixtures of the FP and CL. The three methods were validated as per ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits.

Abdel-Aleem|Eglal A|EA|
Hegazy|Maha A|MA|
Sayed|Nour W|NW|
Abdelkawy|M|M|
Abdelfatah|Rehab M|RM|

Flumethasone
Clioquinol
Binary mixture
Ratio subtraction
Ratio difference
Mean centering


Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale.

Abstract: The objective of the study was to develop an amorphous solid dispersion (ASD) for an insoluble compound X by hot melt extrusion (HME) process. The focus was to identify material-sparing approaches to develop bioavailable and stable ASD including scale up of HME process using minimal drug. Mixtures of compound X and polymers with and without surfactants or pH modifiers were evaluated by hot stage microscopy (HSM), polarized light microscopy (PLM), and modulated differential scanning calorimetry (mDSC), which enabled systematic selection of ASD components. Formulation blends of compound X with PVP K12 and PVP VA64 polymers were extruded through a 9-mm twin screw mini-extruder. Physical characterization of extrudates by PLM, XRPD, and mDSC indicated formation of single-phase ASD's. Accelerated stability testing was performed that allowed rapid selection of stable ASD's and suitable packaging configurations. Dissolution testing by a discriminating two-step non-sink dissolution method showed 70-80% drug release from prototype ASD's, which was around twofold higher compared to crystalline tablet formulations. The in vivo pharmacokinetic study in dogs showed that bioavailability from ASD of compound X with PVP VA64 was four times higher compared to crystalline tablet formulations. The HME process was scaled up from lab scale to clinical scale using volumetric scale up approach and scale-independent-specific energy parameter. The present study demonstrated systematic development of ASD dosage form and scale up of HME process to clinical scale using minimal drug (∼500 g), which allowed successful clinical batch manufacture of enabled formulation within 7 months.

Agrawal|Anjali M|AM|
Dudhedia|Mayur S|MS|
Zimny|Ewa|E|

hot melt extrusion
amorphous solid dispersion
bioavailability
dissolution
process scale up


Highly sensitive LC-MS/MS methods for urinary biological monitoring of occupational exposure to cyclophosphamide, ifosfamide, and methotrexate antineoplastic drugs and routine application.

Abstract: Highly sensitive ESI-LC-MS/MS methods were developed for urinary biological monitoring of occupational exposure to cyclophosphamide (CP), ifosfamide (IF), and methotrexate (MTX), which are hazardous antineoplastic drugs frequently handled by healthcare professionals. Extraction methods consisted of liquid/liquid extraction for simultaneous urinary CP and IF assays, and of solid phase extraction for the urinary MTX assay. A good linearity (r2>0.997), precision (CV<14.6%), and accuracy (bias<9.9%) were achieved for all compounds. The limit of detection (LOD) was 10pg/ml and the lower limit of quantification (LOQ) was 20pg/ml for all three drugs. Applying these methods in routine, more than 116 healthcare professionals occupationally exposed to antineoplastic drugs were monitored and 635 urines were analysed. Eleven healthcare professionals (9.5%) were found to be contaminated to at least one of the three antineoplastic drugs. Among analysed urines, 22 samples were found positives. The measured concentrations ranged from 20.1 to 1850pg/ml and, for six samples, concentrations were at CP trace level, between the LOD and LOQ values (10-20pg/ml). Such efficient analytical tools combining high specificity with high sensitivity are essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to these widely used antineoplastic drugs. These methods allow to monitor the healthcare professionals exposure to antineoplastic drugs in the aim to assess the effectiveness of collective and individual protective measures.

Canal-Raffin|Mireille|M| Khennoufa|Karim|K| Martinez|Béatrice|B| Goujon|Yves|Y| Folch|Celia|C| Ducint|Dominique|D| Titier|Karine|K| Brochard|Patrick|P| Verdun-Esquer|Catherine|C| Molimard|Mathieu|M|

Biological monitoring
Occupational exposure
Antineoplastic drugs
Healthcare professionals
Urine
LC–MS/MS


Travelling abroad with cystic fibrosis: Assessment of risks and healthcare requirements.

Abstract: There is limited information on the risks and healthcare requirements of patients with cystic fibrosis (CF) undertaking travel abroad. Of 100 patients (mean age 24.7 years, mean FEV1 57.3 %predicted) attending a UK adult CF Centre, 96% had travelled abroad but 14% now limited travel on medical advice. They travelled frequently and widely, often undertaking adventurous activities on holidays, but because of the costs involved, 18% travelled without travel insurance and 23% with insurance which did not cover CF. Of those who had ever had an illness abroad 10% had a CF-related illness (7 chest infection, 2 dehydration, 1 pancreatitis) and 12% a non-CF-related illness (4 sunburn, 3 gastroenteritis, 3 ear infection, 1 fall, 1 gastro-oesophageal reflux). There is a wide range of disease severity and assessment of the medical risks and the travel insurance premium to be charged should be based on the individual's health status rather than generically on the basis of a diagnosis of CF.

Miller|Rachel|R|
Blanch|Laura|L|
Lenaghan|Sarah|S|
Anderson|Alan|A|
Doe|Simon|S|
Bourke|Stephen J|SJ|

Travel
Cystic fibrosis
Healthcare requirements
Travel insurance
Risk assessment


Transcatheter aortic valve implantation in patients with a reduced left ventricular ejection fraction: a single-centre experience in 2000 patients (TAVIK Registry).

Abstract:
BACKGROUND
Previous studies into the effect of a reduced left ventricular ejection fraction (EF) on the short- and long-term prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) have reported conflicting findings. We analysed data from the Karlsruhe TAVI registry with the aim of addressing this question.

METHODS AND RESULTS
Patients with aortic stenosis undergoing TAVI were divided into sub-groups according to EF: severely reduced (<30%; n = 109), reduced (≥30 and ≤40%; n = 201), and mid-range/preserved (>40%; n = 1690). VARC complications at 30 days for the population with severely reduced EF did not differ in comparison to the patients with mid-range/preserved EF. Patients with severely reduced EF had a significantly lower survival at 48 h (91.7 vs. 99.0%; p < 0.001), at 30 days (84.4 vs. 95.8%; p < 0.001) and at 1 year (66.1 vs. 85.0%, p < 0.001) compared to those with mid-range/preserved EF. The risk of death increased with age, peripheral arterial disease, poor self-care and chronic renal failure in patients with severely reduced EF.

CONCLUSIONS
Mortality post-TAVI was higher for patients with a reduced EF, although the excess comorbidity burden likely contributed to this. A reduced EF should not be considered a contraindication for TAVI per se, but the additional presence of comorbidity indicates increased risk for these patients.

Schymik|Gerhard|G|
Tzamalis|Panagiotis|P|
Herzberger|Valentin|V|
Bergmann|Jens|J|
Bramlage|Peter|P|
Würth|Alexander|A|
Conzelmann|Lars Oliver|LO|
Luik|Armin|A|
Schröfel|Holger|H|

D065467:Transcatheter Aortic Valve Replacement

Ejection fraction
TAVI
Aortic stenosis
Risk
Mortality
Surgery


Exploring views of orthopaedic surgeons, rheumatologists and general practitioners about osteoarthritis management.

Abstract:
BACKGROUND
Delivery of recommended treatments for hip and knee osteoarthritis (OA) is known to be discordant with guideline recommendations. However, professional views related to OA management across medical and surgical disciplines are not well understood. The aim of this study was to explore the views of medical professionals about management of hip and knee OA.

METHODS
Qualitative study. Semistructured individual interviews were conducted with orthopaedic surgeons, rheumatologists and general practitioners routinely involved in the management of OA. Interviews were audiotaped, transcribed, member-checked, coded and thematically analysed.

RESULTS
Fifteen medical professionals were interviewed. Three main themes were: (i) recognition of the importance of nonsurgical management of hip and knee OA, focussed on self-management, exercise-therapy, weight management and analgesia; (ii) joint replacement being considered the 'last resort' for end stage disease not responding to nonsurgical management; and (iii) determination of management 'success' through patient perceptions was more common than the use of validated instruments. Views on management broadly converged across disciplines, except for the role of joint replacement, considered an adjunct in the overall management of OA by rheumatologists and as a definitive cure by orthopaedic surgeons.

CONCLUSIONS
Aligning with current guidelines, medical professionals recognised the importance of nonsurgical management focussed on exercise-therapy for hip and knee OA, and concurred that joint replacement surgery should be a last resort. A focus on patient education was less prominent, which along with implementation of validated outcome measures in routine medical practice, may require greater health system support.

surgeon
osteoarthritis management
hip
knee
qualitative
doctor


Widespread covariation of early environmental exposures and trait-associated polygenic variation.

Abstract: Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R2 = 0.008; P = 5e-13), parental smacking (R2 = 0.01; P = 4e-15), household income (R2 = 0.032; P = 1e-22), watching television (R2 = 0.034; P = 5e-47), and maternal education (R2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

Krapohl|E|E|0000-0002-6809-7908
Hannigan|L J|LJ|
Pingault|J-B|JB|
Patel|H|H|
Kadeva|N|N|
Curtis|C|C|
Breen|G|G|
Newhouse|S J|SJ|
Eley|T C|TC|
O'Reilly|P F|PF|
Plomin|R|R|

D020022:Genetic Predisposition to Disease

environmental risk
prediction
gene–environment correlation
human complex traits
polygenic scores


Transfer and retention effects of gait training with anterior-posterior perturbations to postural responses after medio-lateral gait perturbations in older adults.

Abstract:
BACKGROUND
Gait perturbations, occurring in any direction in daily life, may result in a fall. In fall prevention, gait perturbation training is a promising approach. Treadmill perturbations in anterior-posterior direction can easily be applied by accelerations or decelerations of the belt, but it is unknown whether training effects transfer to reactive recovery in medio-lateral direction. We aimed to evaluate the transfer and retention effects of gait training with treadmill perturbations in anterior-posterior direction to medio-lateral reactive recovery.

METHODS
30 community dwelling older adults (>65 years) participated in this study. They were randomly assigned to a treadmill training session either with 16 anterior-posterior perturbations or with treadmill walking. The assessments contained a walking trial with 4 anterior-posterior and 4 medio-lateral perturbations. Deviations in trunk velocity from unperturbed walking were summed over the first three strides after perturbation as a measure of recovery.

FINDINGS
An exposure to gait perturbations during the baseline assessment led to significant improvement of recovery responses. For anterior-posterior perturbations, both groups showed better recovery immediately and 1-week post-intervention, and no group x time interaction was found.. For medio-lateral perturbations, both groups showed better recovery immediately and 1-week post-intervention, and again no group × time interaction.

INTERPRETATION
Baseline assessment with perturbations in anterior-posterior and medio-lateral directions caused significant improvements that were retained. Short-term training can be effective in dynamic stabilization of one's trunk, but our findings do not exclude that multi-directional perturbations may be needed.

Rieger|M M|MM|
Papegaaij|S|S|
Pijnappels|M|M|
Steenbrink|F|F|
van Dieën|J H|JH|

Treadmill
Walking
Accidental falls
Aging
Exercise test
Postural balance


Rapid Method for the Determination of the Stable Oxygen Isotope Ratio of Water in Alcoholic Beverages.

Abstract: This paper demonstrates the first successful application of an online pyrolysis technique for the direct determination of oxygen isotope ratios (δ(18)O) of water in alcoholic beverages. Similar water concentrations in each sample were achieved by adjustment with absolute ethyl alcohol, and then a fixed GC split ratio can be used. All of the organic ingredients were successfully separated from the analyte on a CP-PoraBond Q column and subsequently vented out, whereas water molecules were transferred into the reaction furnace and converted to CO. With the system presented, 15-30 μL of raw sample was diluted and can be analyzed repeatedly; the analytical precision was better than 0.4‰ (n = 5) in all cases, and more than 50 injections can be made per day. No apparent memory effect was observed even if water samples were injected using the same syringe; a strong correlation (R(2) = 0.9998) was found between the water δ(18)O of measured sample and that of working standards. There was no significant difference (p > 0.05) between the mean δ(18)O value and that obtained by the traditional method (CO2-water equilibration/isotope ratio mass spectrometry) and the newly developed method in this study. The advantages of this new method are its rapidity and straightforwardness, and less test portion is required.

Wang|Daobing|D| Zhong|Qiding|Q| Li|Guohui|G| Huang|Zhanbin|Z|

D000434:Alcoholic Beverages
D013058:Mass Spectrometry
D010103:Oxygen Isotopes
D014867:Water

stable oxygen isotope ratio
water
alcoholic beverage
pyrolysis


Factors associated with respiratory symptoms among herbicide applicators and assistant applicators in maize field.

Abstract: A cross-sectional study was conducted with 3,291 maize farmers enrolled whose main roles were herbicide applicators and assistant applicators. This study aimed to compare the prevalence of respiratory symptoms and the use of personal protective equipment (PPE) between herbicide applicators and assistant applicators, and determine factors associated with respiratory symptoms. Our results suggest that wheeze and dyspnea were associated with the task on the farm (adj. OR = 10.33 for wheeze and 24.13 for dyspnea), amount of herbicide use (adj. OR = 1.95 for wheeze and 1.41 for dyspnea), frequency of herbicide use (adj. OR = 2.87 for wheeze and 4.08 for dyspnea), not always wearing a mask (adj. OR = 1.49 for wheeze and 3.17 for dyspnea), not always wearing gloves (adj. OR = 2.63 for wheeze and 2.44 for dyspnea), and not always wearing goggles (adj.OR = 2.01 for dyspnea) after adjusting for confounding factors.

respiratory symptoms
herbicide
Farmer
pesticides


Long-Term Cardiovascular Risk Associated With Stage 1 Hypertension Defined by the 2017 ACC/AHA Hypertension Guideline.

Abstract:
BACKGROUND
Systolic/diastolic blood pressure (BP) of 130 to 139/80 to 89 mm Hg has been recently defined as stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association hypertension guideline. To what extent this BP stratum affects cardiovascular risk needs to be quantified in considering its adoption in China.

OBJECTIVES
The purpose of this study was to assess the relative risk and population-attributable risk of cardiovascular disease (CVD) associated with stage 1 hypertension and age-specific differences.

METHODS
In total, 21,441 participants age ≥35 years and free of CVD at baseline were followed for up to 20 years in the Chinese Multi-provincial Cohort Study. The adjusted hazard ratio (HR) and population-attributable risk for CVD associated with stage 1 hypertension were calculated.

RESULTS
Participants with stage 1 hypertension accounted for 25.8% of the cohort. Among participants age 35 to 59 years, the HR comparing stage 1 hypertension to BP <120/<80 mm Hg for CVD incidence was 1.78 (95% confidence interval [CI]: 1.50 to 2.11), coronary heart disease incidence was HR: 1.77 (95% CI: 1.33 to 2.36), stroke incidence was HR: 1.79 (95% CI: 1.45 to 2.22), and CVD mortality was HR: 2.50 (95% CI: 1.66 to 3.77). The proportions of cardiovascular deaths and events attributable to stage 1 hypertension were 26.5% and 13.4% among participants age 35 to 59 years, respectively. Among participants age ≥60 years, however, stage 1 hypertension was not related to increased risk compared with BP <120/<80 mm Hg, and population-attributable risk associated with this stratum was not found. Over a 15-year period, 65.0% of participants age 35 to 59 years with stage 1 hypertension experienced an increase in BP to 140/90 mm Hg or higher, and they had a 3.01-fold increased cardiovascular risk compared with those who maintained BP <130/<80 mm Hg.

CONCLUSIONS
The effect of 2017 American College of Cardiology/American Heart Association stage 1 hypertension on cardiovascular risk is evidenced in young and middle-aged Chinese adults, but not in those age ≥60 years.

Qi|Yue|Y| Han|Xueyu|X| Zhao|Dong|D| Wang|Wei|W| Wang|Miao|M| Sun|Jiayi|J| Liu|Jun|J| Li|Yan|Y| Gao|Shen|S| Hao|Yongchen|Y| Deng|Qiuju|Q| Liu|Jing|J|

hypertension
cardiovascular disease
cohort study
incidence
mortality


Comparison of neuropathic pain characteristics associated with total brachial plexus injury before and after surgical repair: A retrospective study.

Abstract:
OBJECTIVES
The goal of this study was to compare clinical characteristics of neuropathic pain associated with total brachial plexus injury before and after surgeries and to correlate possible contributing factors concerning to the pain prognosis.

PATIENTS AND METHODS
Thirty patients with both total brachial plexus injury and neuropathic pain were included. Neuropathic pain was evaluated in terms of pain intensities, symptoms and regions. Pain intensities were evaluated by a visual analogue scale. The Neuropathic Pain Symptoms Inventory questionnaire and body maps were used to compare the pain symptoms and regions. Demographic data, injury and repair information were evaluated to analyze the possible factors influencing the prognosis.

RESULTS
The average pain score of all participants was 7.13 ± 2.46 preoperatively and 5.40 ± 2.08 postoperatively. All patients were divided into Pain Relief Group and Pain Aggravation Group. Older age (p = 0.042), machine traction injury (p = 0.019)and nerve transplantation(p = 0.015) seemed to be related with pain aggravation. Paroxysmal pain was aggravated after surgical repairs (p = 0.041), while paresthesia/dysesthesia improved after surgery (p = 0.003). The permanent component of the pain (spontaneous pain) did not show any significant change (p = 0.584). Pain in C5 (p < 0.001) and C6 (p = 0.031) dermatomes got relieved after surgery.

CONCLUSION
This study revealed the neuropathic pain of most patients with total brachial plexus injury was alleviated after neurosurgery, and the pain prognosis of different symptoms and regions varied after the nerve repair.

Guo|Jinding|J| Gao|Kaiming|K| Zhou|Yingjie|Y| Zhao|Xin|X| Lao|Jie|J|

D000055:Accessory Nerve
D000328:Adult
D001917:Brachial Plexus
D020516:Brachial Plexus Neuropathies
D018450:Disease Progression
D005260:Female
D006801:Humans
D007367:Intercostal Nerves
D008297:Male
D008875:Middle Aged
D016067:Nerve Transfer
D009437:Neuralgia
D019635:Neurosurgical Procedures
D010147:Pain Measurement
D010292:Paresthesia
D059348:Peripheral Nerve Injuries
D010791:Phrenic Nerve
D011379:Prognosis
D012189:Retrospective Studies
D013127:Spinal Nerves
D013497:Sural Nerve
D016896:Treatment Outcome
D055815:Young Adult

Neuropathic pain
Brachial plexus
Neurosurgery
Prognostic factors
Surgical outcomes


Immunogloboulin E-Mediated Food Sensitization in Children with Celiac Disease: A Single-Center Experience.

Abstract:
Purpose
Celiac disease (CD) is an autoimmune disorder of the small intestine caused by an abnormal immune response to gluten proteins and is often characterized by gastrointestinal symptoms. Food allergy (FA) is an adverse immune sensitivity to ingested food proteins leading to inflammation in various organs including the gastrointestinal tract. The relationship between CD and FA remains unclear. This study aimed to assess the prevalence and clinical relevance of immunoglobulin E (IgE)-mediated food sensitization in children with CD.

Methods
Fifty-nine children diagnosed with CD were reviewed for clinical symptoms and evidence of IgE-sensitization to food and airborne allergens using the PolyCheck method.

Results
IgE-mediated sensitization has been diagnosed in 20.3% of children with CD (CD/ A). In the CD/A group, 58.3% of children were sensitized to food and 66.7% to airborne allergens. Further, 41.7% of patients with CD and allergy reported gastrointestinal tract symptoms associated with the ingestion of sensitizing foods. Analysis of the clinical status revealed that the incidence of other allergic disorders in the CD/A group was as follows: atopic dermatitis (33.3%), asthma (25.0%), and allergic rhinitis (16.7%). The percentage of eosinophils was significantly higher in the CD/A group than in the CD group (0.33±0.25 vs. 0.11±0.09; p=0.006).

Conclusion
The diagnosis of CD does not exclude FA. The gastrointestinal symptoms in children with CD may be the result of both CD and FA; therefore, children with CD should be evaluated for the presence of FA regardless of age.

Celiac disease
Child
Food hypersensitivity


Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses.

Abstract: Dendritic cells are powerful antigen-presenting cells that are essential for the priming of T cell responses. In addition to providing T-cell-receptor ligands and co-stimulatory molecules for naive T cell activation and expansion, dendritic cells are thought to also provide signals for the differentiation of CD4+ T cells into effector T cell populations. The mechanisms by which dendritic cells are able to adapt and respond to the great variety of infectious stimuli they are confronted with, and prime an appropriate CD4+ T cell response, are only partly understood. It is known that in the steady-state dendritic cells are highly heterogenous both in phenotype and transcriptional profile, and that this variability is dependent on developmental lineage, maturation stage, and the tissue environment in which dendritic cells are located. Exposure to infectious agents interfaces with this pre-existing heterogeneity by providing ligands for pattern-recognition and toll-like receptors that are variably expressed on different dendritic cell subsets, and elicit production of cytokines and chemokines to support innate cell activation and drive T cell differentiation. Here we review current information on dendritic cell biology, their heterogeneity, and the properties of different dendritic cell subsets. We then consider the signals required for the development of different types of Th immune responses, and the cellular and molecular evidence implicating different subsets of dendritic cells in providing such signals. We outline how dendritic cell subsets tailor their response according to the infectious agent, and how such transcriptional plasticity enables them to drive different types of immune responses.

D000818:Animals
D017951:Antigen Presentation
D002454:Cell Differentiation
D003713:Dendritic Cells
D006801:Humans
D008954:Models, Biological
D006377:T-Lymphocytes, Helper-Inducer
D014158:Transcription, Genetic

dendritic cells
CD4+ T cells
Th effector responses


Emotion and sex of facial stimuli modulate conditional automaticity in behavioral and neuronal interference in healthy men.

Abstract: Our surrounding provides a host of sensory input, which we cannot fully process without streamlining and automatic processing. Levels of automaticity differ for different cognitive and affective processes. Situational and contextual interactions between cognitive and affective processes in turn influence the level of automaticity. Automaticity can be measured by interference in Stroop tasks. We applied an emotional version of the Stroop task to investigate how stress as a contextual factor influences the affective valence-dependent level of automaticity. 120 young, healthy men were investigated for behavioral and brain interference following a stress induction or control procedure in a counter-balanced cross-over-design. Although Stroop interference was always observed, sex and emotion of the face strongly modulated interference, which was larger for fearful and male faces. These effects suggest higher automaticity when processing happy and also female faces. Supporting behavioral patterns, brain data show lower interference related brain activity in executive control related regions in response to happy and female faces. In the absence of behavioral stress effects, congruent compared to incongruent trials (reverse interference) showed little to no deactivation under stress in response to happy female and fearful male trials. These congruency effects are potentially based on altered context- stress-related facial processing that interact with sex-emotion stereotypes. Results indicate that sex and facial emotion modulate Stroop interference in brain and behavior. These effects can be explained by altered response difficulty as a consequence of the contextual and stereotype related modulation of automaticity.

Emotion Sex Interference Stress Stereotype FMRI


Dendrites In Vitro and In Vivo Contain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation.

Abstract:
UNLABELLED
In cultured vertebrate neurons, axons have a uniform arrangement of microtubules with plus-ends distal to the cell body (plus-end-out), whereas dendrites contain mixed polarity orientations with both plus-end-out and minus-end-out oriented microtubules. Rather than non-uniform microtubules, uniparallel minus-end-out microtubules are the signature of dendrites in Drosophila and Caenorhabditis elegans neurons. To determine whether mixed microtubule organization is a conserved feature of vertebrate dendrites, we used live-cell imaging to systematically analyze microtubule plus-end orientations in primary cultures of rat hippocampal and cortical neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neurons in the somatosensory cortex of living mice. In vitro and in vivo, all microtubules had a plus-end-out orientation in axons, whereas microtubules in dendrites had mixed orientations. When dendritic microtubules were severed by laser-based microsurgery, we detected equal numbers of plus- and minus-end-out microtubule orientations throughout the dendritic processes. In dendrites, the minus-end-out microtubules were generally more stable and comparable with plus-end-out microtubules in axons. Interestingly, at early stages of neuronal development in nonpolarized cells, newly formed neurites already contained microtubules of opposite polarity, suggesting that the establishment of uniform plus-end-out microtubules occurs during axon formation. We propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization.

SIGNIFICANCE STATEMENT
Live-cell imaging was used to systematically analyze microtubule organization in primary cultures of rat hippocampal neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neuron in somatosensory cortex of living mice. In vitro and in vivo, all microtubules have a plus-end-out orientation in axons, whereas microtubules in dendrites have mixed orientations. Interestingly, newly formed neurites of nonpolarized neurons already contain mixed microtubules, and the specific organization of uniform plus-end-out microtubules only occurs during axon formation. Based on these findings, the authors propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization.

dendrites
polarity
neuron
development
cytoskeleton
microtubule dynamics


Engineered Maturation Approaches of Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes.

Abstract: Heart diseases such as myocardial infarction and myocardial ischemia are paroxysmal and fatal in clinical practice. Cardiomyocytes (CMs) differentiated from human pluripotent stem cells provide a promising approach to myocardium regeneration therapy. Identifying the maturity level of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is currently the main challenge for pathophysiology and therapeutics. In this review, we describe current maturity indicators for cardiac microtissue and microdevice cultivation technologies that accelerate cardiac maturation. It may provide insights into regenerative medicine, drug cardiotoxicity testing, and preclinical safety testing.

Ge|Feixiang|F|
Wang|Zetian|Z|
Xi|Jianzhong Jeff|JJ|

D000818:Animals
D002454:Cell Differentiation
D006801:Humans
D032383:Myocytes, Cardiac
D039904:Pluripotent Stem Cells
D033581:Stem Cell Transplantation
D013234:Stem Cells
D020257:Ventricular Remodeling

maturation
ventricular
cardiomyocytes
human pluripotent stem cell
cardiac tissue engineering


Ultrasound assessment of soft tissue augmentation around implants in the aesthetic zone using a connective tissue graft and xenogeneic collagen matrix - 1-year randomised follow-up.

Abstract:
PURPOSE
A comparative, ultrasound evaluation of the thickness of keratinized mucosa (TKT) around implants one year after gingival augmentation (GA) by means of a connective tissue graft (CTG) and the xenogeneic collagen matrix (CMX).

MATERIALS AND METHODS
A total of 75 bone level tapered implants (Conelog® Camlog) were inserted in 57 patients in the aesthetic area of both jaws. The patients were divided into 3 groups: control group I- without GA; group II- GA 3 months before implantation, and group III- GA 3 months after implantation. Groups II and III were divided into two subgroups depends on type of material used for GA: (a) CMX (Mucograft®, Geistlich Pharma AG) and (b) CTG. The patients underwent a clinical and ultrasound examination before, then after 3 and 12 months following GA respectively to evaluate TKT at two points using ultrasound equipment (Pirop®, Echoson). Point 1 was considered to be in the middle of the line connecting the cemento-enamel junction (CEJ) to the adjacent teeth, and point 2 on the mucogingival junction (MGJ).

RESULTS
Three months after GA, the highest increase in gingival thickness was noted in group IIIb (point 1 - 0.95mm, 2 - 1.01mm). However, 12 months after GA the highest gingival thickness was observed in group IIb (point 1 - 1.76mm, 2 - 1.36m) and next IIIb (point 1 - 1.52mm, 2 - 1.15mm).

CONCLUSIONS
Both CTG and Geistlich Mucograft® increased TKT, but higher values were noted using CTG augmentation before implantation. An ultrasonic device can be used as a non-invasive, reliable, and reproducible method for evaluating TKT.

Puzio|Monika|M| Błaszczyszyn|Artur|A| Hadzik|Jakub|J| Dominiak|Marzena|M|

Connective tissue graft
Mucograft(®)
Thickness keratinized gingiva
Ultrasound measurements


Modulation of Visible Room Temperature Phosphorescence by Weak Magnetic Fields.

Abstract: Magnetic control over excited states of molecules presents interest for many applications. Here we show for the first time that visible room temperature phosphorescence in multichromophoric donor-acceptor systems can be modulated by weak magnetic fields (<1 T) via magnetic field effects (MFE) on the spin dynamics in photogenerated radical pairs (RPs). The studied compounds comprise Pt porphyrin (PtP)-Rosamine B (RosB) dyads, which possess strong visible absorption bands and phosphoresce at room temperature. The observed MFE is unique in that it occurs upon direct excitation of the PtP in the dyads, whereby ultrafast quantitative formation of the local PtP triplet state precedes the occurrence of radical intermediates. A model explaining the effect is proposed, which is based on reversible electron transfer between the local triplet state and a long-lived RP. External magnetic field modulates spin dynamics in the RP, affecting contribution of the singlet RP recombination channel and thereby influencing phosphorescence.

Mani|Tomoyasu|T|
Tanabe|Mana|M|
Yamauchi|Seigo|S|
Tkachenko|Nikolai V|NV|
Vinogradov|Sergei A|SA|

phosphorescence
magnetic field effects
spin dynamics
porphyrin
triplet state
radical pair mechanism


Oral relative bioavailability of Dichlorodiphenyltrichloroethane (DDT) in contaminated soil and its prediction using in vitro strategies for exposure refinement.

Abstract: In this study, the bioavailability of DDTr (sum of DDT, DDD and DDE isomers) in pesticide-contaminated soil was assessed using an in vivo mouse model. DDTr relative bioavailability (RBA) ranged from 18.7±0.9 (As35) to 60.8±7.8% (As36) indicating that a significant portion of soil-bound DDTr was not available for absorption following ingestion. When DDTr bioaccessibility was assessed using the organic Physiologically Based Extraction Test (org-PBET), the inclusion of a sorption sink (silicone cord) enhanced DDTr desorption by up to 20-fold (1.6-3.8% versus 18.9-56.3%) compared to DDTr partitioning into gastrointestinal fluid alone. Enhanced desorption occurred as a result of the silicone cord acting as a reservoir for solubilized DDTr to partition into, thereby creating a flux for further desorption until equilibrium was achieved. When the relationship between in vivo and in vitro data was assessed, a strong correlation was observed between the mouse bioassay and the org-PBET+silicone cord (slope=0.94, y-intercept=3.5, r(2)=0.72) suggesting that the in vitro approach may provide a robust surrogate measure for the prediction of DDTr RBA in contaminated soil.

Juhasz|Albert L|AL|
Herde|Paul|P|
Smith|Euan|E|

Relative bioavailability
DDT
Bioaccessibility
Sorption Sink
Correlation


Isolation and expression features of hexose kinase genes under various abiotic stresses in the tea plant (Camellia sinensis).

Abstract: Hexokinases (HXKs, EC 2.7.1.1) and fructokinases (FRKs, EC 2.7.1.4) play important roles in carbohydrate metabolism and sugar signaling during the growth and development of plants. However, the HXKs and FRKs in the tea plant (Camellia sinensis) remain largely unknown. In this manuscript, we present the molecular characterization, phylogenetic relationships, conserved domains and expression profiles of four HXK and seven FRK genes of the tea plant. The 11 deduced CsHXK and CsFRK proteins were grouped into six main classes. All of the deduced proteins, except for CsFKR7, possessed putative ATP-binding motifs and a sugar recognition region. These genes exhibited tissue-specific expression patterns, which suggests that they play different roles in the metabolism and development of source and sink tissues in the tea plant. There were variations in CsHXKs and CsFRKs transcript abundance in response to four abiotic stresses: cold, salt, drought and exogenous abscisic acid (ABA). Remarkably, CsHXK3 and CsHXK4 were significantly induced in the leaves and roots under cold conditions, CsHXK1 was apparently up-regulated in the leaves and roots under salt and drought stresses, and CsHXK3 was obviously stimulated in the leaves and roots under short-term treatment with exogenous ABA. These findings demonstrate that CsHXKs play critical roles in response to abiotic stresses in the tea plant. Our research provides a fundamental understanding of the CsHXK and CsFRK genes of the tea plant and important information for the breeding of stress-tolerant tea cultivars.

Li|Na-Na|NN| Qian|Wen-Jun|WJ| Wang|Lu|L| Cao|Hong-Li|HL| Hao|Xin-Yuan|XY| Yang|Ya-Jun|YJ| Wang|Xin-Chao|XC|

D018506:Gene Expression Regulation, Plant

Abiotic stress
Tea plant
Hexokinase
Fructokinase
Gene expression


Effects of minocycline on expression of bcl-2, bax in early retinal neuropathy of diabetes in rats.

Abstract:
AIM
To study the effect of the minocycline (MNC) on expression of bcl-2, bax in retinal nerve cells of rat with diabetes.

METHODS
Male SD rats were randomly divided into negative control group, model control group and MNC treated group. Diabetes model was established by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The protein expressions of bcl-2 and bax in retina were detected by immunohistochemistry method.

RESULTS
Compared with the negative control group, bax immunoreactive neurons in retina were increased significantly (P<0.01) in model control group. However, bax immunoreactive neurons in retina in MNC treated group were significantly decreased (P<0.01). Compared with the model control group, bcl-2 immunoreactive neurons in retina were increased significantly(P<0.01) in MNC treated group.

CONCLUSION
MNC can obviously decreased expression of bax and increased expression of bcl-2 in retina with DR. It is one of path of inhibiting impairment on retinal nerve cells with DR.


Wnt7a regulates high autophagic and inflammatory response of epidermis in high-glucose environment.

Abstract: Type 2 diabetes mellitus (T2DM) is an important reason to cause chronic wound healing or even amputation to patients. A common characteristic of T2DM is the presence of hyperglycemia. Autophagy, a cellular pathway which related to protein and organelle degradation, is relevant to many types of cellular homeostasis change and human diseases including diabetes. However, the relationship between high glucose and autophagy in keratinocytes remains unclear. Previously in our research, wnt7a was proved to accelerate healing process by promoting angiogenesis and ameliorating local inflammation, while little is known about its role in epithelial cells, namely keratinocytes. We hypothesized that reduced expression of wnt7a may contribute to the increment of autophagy. We then compared the expression of autophagic markers such as nlrp3, LC3A/B and bip by high glucose-cultured HaCaT cells, with or without wnt7a treatment. Then we examined the expression levels of TNF-α, TLR-4 and p62 to assess inflammatory statement. High glucose induced a significant increasement in the expression of both autophagic markers and inflammatory markers and these elevated protein levels were reversed after the use of wnt7a. Therefore, these results showed that wnt7a regulates overwhelmed autophagy and inflammation promoted under high glucose condition.

Wang|Wei|W| Zhang|Fang|F| Yan|Xin|X| Tan|Qian|Q|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

Wnt7a Autophagy Keratinocytes Inflammation


ACES: a machine learning toolbox for clustering analysis and visualization.

Abstract:
BACKGROUND
Studies that aim at explaining phenotypes or disease susceptibility by genetic or epigenetic variants often rely on clustering methods to stratify individuals or samples. While statistical associations may point at increased risk for certain parts of the population, the ultimate goal is to make precise predictions for each individual. This necessitates tools that allow for the rapid inspection of each data point, in particular to find explanations for outliers.

RESULTS
ACES is an integrative cluster- and phenotype-browser, which implements standard clustering methods, as well as multiple visualization methods in which all sample information can be displayed quickly. In addition, ACES can automatically mine a list of phenotypes for cluster enrichment, whereby the number of clusters and their boundaries are estimated by a novel method. For visual data browsing, ACES provides a 2D or 3D PCA or Heat Map view. ACES is implemented in Java, with a focus on a user-friendly, interactive, graphical interface.

CONCLUSIONS
ACES has been proven an invaluable tool for analyzing large, pre-filtered DNA methylation data sets and RNA-Sequencing data, due to its ease to link molecular markers to complex phenotypes. The source code is available from https://github.com/GrabherrGroup/ACES .

Gao|Jiangning|J|
Sundström|Görel|G|
Moghadam|Behrooz Torabi|BT|
Zamani|Neda|N|
Grabherr|Manfred G|MG|

D016000:Cluster Analysis
D019175:DNA Methylation
D003922:Diabetes Mellitus, Type 1
D006801:Humans
D000077230:Internet Access
D025341:Principal Component Analysis
D012313:RNA
D014584:User-Computer Interface

Clustering
Centroid detection
Data visualization
Discriminative power prediction


Comparison between movement pattern training and strengthening on muscle volume, muscle fat, and strength in patients with hip-related groin pain: An exploratory analysis.

Abstract: The purpose of this exploratory analysis was to compare the impact of movement pattern training (MoveTrain) and standard strength and flexibility training (Standard) on muscle volume, strength and fatty infiltration in patients with hip-related groin pain (HRGP). We completed a secondary analysis of data collected during an assessor-blinded randomized control trial. Data were used from 27 patients with HRGP, 15-40 years, who were randomized into MoveTrain or Standard groups. Both groups participated in their training protocol (MoveTrain, n = 14 or Standard, n = 13) which included 10 supervised sessions over 12 weeks and a daily home exercise program. Outcome measures were collected at baseline and immediately after treatment. Magnetic resonance images data were used to determine muscle fat index (MFI) and muscle volume. A hand-held dynamometer was used to assess isometric hip abductor and extensor strength. The Standard group demonstrated a significant posttreatment increase in gluteus medius muscle volume compared to the MoveTrain group. Both groups demonstrated an increase in hip abductor strength and reduction in gluteus minimus and gluteus maximus MFI. The magnitude of change for all outcomes were modest. Statement of Clinical Significance: Movement pattern training or a program of strength/flexibility training may be effective at improving hipabductor strength and reducing fatty infiltration in the gluteal musculature among those with HRGP. Further research is needed to betterunderstand etiology of strength changes and impact of muscle volume and MFI in HRGP and the effect of exercise on muscle structure andfunction.

volume
strength
hip-related groin pain
fatty infiltration
buttocks


Evidence for critical role of Tie2/Ang1 interaction in metastatic oral cancer.

Abstract: Angiopoietin-1 (Ang1) is a binding partner of endothelial cell-specific tyrosine-protein kinase receptor (Tie2), which serves important roles in vascular development and angiogenesis. Tie2 is closely associated with the metastasis of oral squamous cell carcinomas (OSCCs) however, little is known about the correlation between Tie2 and Ang1. In the present study, the functional mechanisms of the Tie2/Ang1 interaction were investigated using Tie2 overexpressed (oeTie2) OSCC cells and recombinant Ang1 protein. oeTie2 cells had increased cell-cell and cell-extracellular matrix adhesions compared with the control cells. Additionally, the adhesive activities increased following treatment with exogenous Ang1, indicating that Ang1 directly enhances Tie2 functions. In the clinical OSCC data from 10 cases positive for regional lymph node metastasis, all cases were negative for Tie2 expression and eight cases (80%) were negative for Ang1 expression. These results suggest that Tie2 and Ang1 serve important roles in cancer metastasis and may be potential biomarkers and therapeutic targets for OSCC metastasis.

Kitajima|Daisuke|D| Kasamatsu|Atsushi|A| Nakashima|Dai|D| Miyamoto|Isao|I| Kimura|Yasushi|Y| Endo-Sakamoto|Yosuke|Y| Shiiba|Masashi|M| Tanzawa|Hideki|H| Uzawa|Katsuhiro|K|

Tie2
Ang1
oral squamous cell carcinoma
cell-extracellular matrix adhesion
regional lymph node metastasis
cell-cell adhesion


Economic Evaluations Comparing a Trial of Labor with an Elective Repeat Cesarean Delivery: A Systematic Review.

Abstract:
BACKGROUND
For women who have had a previous low transverse cesarean delivery, the decision to undergo a trial of labor after cesarean (TOLAC) or an elective repeat cesarean delivery (ERCD) has important clinical and economic ramifications.

OBJECTIVES
To evaluate the cost-effectiveness of the alternative choices of a TOLAC and an ERCD for women with low-risk, singleton gestation pregnancies.

METHODS
We searched EMBASE, MEDLINE, CINAHL, Cochrane Library, EconLit, and the Cost-Effectiveness Analysis Registry with no language, publication, or date restrictions up until October 2015. Studies were included if they were primary research, compared a TOLAC with an ERCD, and provided information on the relative cost of the alternatives. Abstracts and partial economic evaluations were excluded.

RESULTS
Of 310 studies initially reviewed, 7 studies were included in the systematic review. In the base-case analyses, 4 studies concluded that TOLAC was dominant over ERCD, 1 study found ERCD to be dominant, and 2 studies found that although TOLAC was more costly, it offered more benefits and was thus cost-effective from a population perspective when considering societal willingness to pay for better outcomes. In sensitivity analyses, cost-effectiveness was found to be dependent on a high likelihood of TOLAC success, low risk of uterine rupture, and low relative cost of TOLAC compared with ERCD.

CONCLUSIONS
For women who are likely to have a successful vaginal delivery, routine ERCD may result in excess morbidity and cost from a population perspective.

Rogers|Anna Joy|AJ|
Rogers|Nathaniel G|NG|
Kilgore|Meredith L|ML|
Subramaniam|Akila|A|
Harper|Lorie M|LM|

D017604:Cesarean Section, Repeat
D003362:Cost-Benefit Analysis
D005260:Female
D006801:Humans
D017059:Models, Econometric
D011247:Pregnancy
D015203:Reproducibility of Results
D014219:Trial of Labor
D016064:Vaginal Birth after Cesarean

economics
trial of labor
cesarean delivery
cost
effectiveness
elective surgical procedures
pregnancy complications
probability
quality-adjusted life-years
utility
vaginal birth after cesarean


Self-perceptions about the profession of dentistry-comparisons between Lithuanian and Polish University graduating students.

Abstract:
AIM
To examine the perceptions and overall satisfaction about the dental profession amongst the final-year student cohorts from the Lithuanian and Polish universities.

MATERIAL AND METHODS
For the Lithuanian cohort, the response rate was 95% (N = 143) and for the Polish cohort it was 99% (N = 123). The survey included a pre-tested questionnaire with multiple questions from three domains: (a) Sociodemographic, (b) Influences of others and (c) Dentistry Profession.

RESULTS
Polish university students were older (25.3 ± 2.6 years) than Lithuanian students (23.5 ± 1.6 years), more Lithuanian (83.1%) students were single compared to Polish cohort (34.7%), and more students graduating in Poland (43.4%) were males compared to the Lithuanian students (26.6%). In both countries, students were mostly influenced towards their choice of dentistry by their parents/relatives and positive experiences. Similar profession-related dimensions were identified for student from both countries: (a) the prestige of the profession, (b) job-related security, and (c) self-realisation. Satisfaction with a profession differed substantially between the two student cohorts, but none of the sociodemographic predictors explained this variation satisfactorily.

CONCLUSIONS
Sociodemographic differences were found between the students from Lithuanian and Polish universities. Yet, both student cohorts were similarly influenced towards choosing dentistry. The profession's prestige, job security and self-realisation were the most important profession-related dimensions. Polish university students were more satisfied with the profession than Lithuanian students.

perceptions
dentistry
dental students
medical profession


Ileosigmoid knot at week 13 of pregnancy: report of a case.

Abstract: The ileosigmoid knot (ISK) is a rare cause of intestinal obstruction. ISK is a condition in which the ileum wraps around the base of the sigmoid colon and forms a knot, leading to high mortality with rapid progression to bowel gangrene. We herein report a rare case of ISK at week 13 of pregnancy. The ISK was diagnosed by computed tomography, and the patient underwent emergency surgery for acute abdomen. Laparotomy showed segmental gangrenous change in the sigmoid colon, which was twisted around the distal ileal loop. The gangrenous bowel was resected, and primary anastomosis was performed. To our knowledge, the present case involves the first and earliest pregnancy in which a preoperative diagnosis of ISK was made and successful treatment was performed with surgery. A radiologic approach should be undertaken for prompt diagnosis and optimal management, even in early pregnancy.

Shimizu|Riha|R| Hoshino|Yoshinori|Y| Irie|Haruko|H| Ito|Homare|H| Terauchi|Toshiaki|T| Kimata|Masaru|M| Furukawa|Junji|J| Shinozaki|Hiroharu|H| Kobayashi|Kenji|K| Ogata|Yoshiro|Y|

Ileosigmoid knot
Pregnancy
Emergency surgery
Small bowel obstruction
Strangulation