Assistance Dogs for Persons with Hearing Impairment: A Review.

Abstract: The use of dogs to help people with disabilities has been known for a long time. Assistance dogs carry out a variety of practical tasks for disabled people with appropriate and targeted training, including assisting deaf persons or people with profound hearing loss. The benefits of assistance dogs for persons with hearing impairment (hearing dogs) include a) improved ability to carry out daily tasks through the codified reporting of sounds proper of everyday life and/or of dangerous situations and b) psychosocial aspects such as companionship and sense of protection. The benefits derived from the use of assistance dogs for persons with hearing impairment are less studied compared to those of assistance dogs employed for other disabilities. Moreover, the role of hearing dogs may appear rather controversial considering technological advances in the field of surgical or prosthetic rehabilitation for people with hearing impairment. This article aims to review features and training of hearing dogs, the effects of their employment and legislative aspects for their owners.

Martellucci|Salvatore|S|
Belvisi|Valeria|V|
Ralli|Massimo|M|
Stadio|Arianna Di|AD|
Musacchio|Angela|A|
Greco|Antonio|A|
Gallo|Andrea|A|
Vincentiis|Marco de|M|
Attanasio|Giuseppe|G|

D019986:Persons With Hearing Impairments

Assistance dogs
deafness
hearing loss
hearing dogs
vestibular loss


Abstract:
BACKGROUND
Activation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome.

METHODS
We included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein - LBP and sCD14) were measured in blood samples taken at day 1 (within 24h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score>2.

RESULTS
Compared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32EU/mL, P=0.03) as well as higher LBP (median: 18.7 vs 11.5μg/mL, P<0.01) and sCD14 level (median: 1330 vs 1070ng/mL, P<0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03-15.02, P=0.04, adjusted for age and stroke severity).

CONCLUSIONS
Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

Klimiec|Elzbieta|E| Pera|Joanna|J| Chrzanowska-Wasko|Joanna|J| Golenia|Aleksandra|A| Slowik|Agnieszka|A| Dziedzic|Tomasz|T|

Endotoxin
Ischemic stroke
Outcome
Inflammation


Kmt2c mutations enhance HSC self-renewal capacity and convey a selective advantage after chemotherapy.

Abstract: The myeloid tumor suppressor KMT2C is recurrently deleted in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly therapy-related MDS/AML (t-MDS/t-AML), as part of larger chromosome 7 deletions. Here, we show that KMT2C deletions convey a selective advantage to hematopoietic stem cells (HSCs) after chemotherapy treatment that may precipitate t-MDS/t-AML. Kmt2c deletions markedly enhance murine HSC self-renewal capacity without altering proliferation rates. Haploid Kmt2c deletions convey a selective advantage only when HSCs are driven into cycle by a strong proliferative stimulus, such as chemotherapy. Cycling Kmt2c-deficient HSCs fail to differentiate appropriately, particularly in response to interleukin-1. Kmt2c deletions mitigate histone methylation/acetylation changes that accrue as HSCs cycle after chemotherapy, and they impair enhancer recruitment during HSC differentiation. These findings help explain why Kmt2c deletions are more common in t-MDS/t-AML than in de novo AML or clonal hematopoiesis: they selectively protect cycling HSCs from differentiation without inducing HSC proliferation themselves.

Chen|Ran|R|
Okeyo-Owuor|Theresa|T|
Patel|Riddhi M|RM|
Casey|Emily B|EB|
Cluster|Andrew S|AS|
Yang|Wei|W|
Magee|Jeffrey A|JA|


Insect prophenoloxidase: the view beyond immunity.

Abstract: Insect prophenoloxidase (PPO) is an important innate immunity protein due to its involvement in cellular and humoral defense. It belongs to a group of type-3 copper-containing proteins that occurs in almost all organisms. Insect PPO has been studied for over a century, and the PPO activation cascade is becoming clearer. The insect PPO activation pathway incorporates several important proteins, including pattern-recognition receptors (PGRP, β GRP, and C-type lectins), serine proteases, and serine protease inhibitors (serpins). Due to their complexity, PPO activation mechanisms vary among insect species. Activated phenoloxidase (PO) oxidizes phenolic molecules to produce melanin around invading pathogens and wounds. The crystal structure of Manduca sexta PPO shows that a conserved amino acid, phenylalanine (F), can block the active site pocket. During activation, this blocker must be dislodged or even cleaved at the N-terminal sequence to expose the active site pockets and allow substrates to enter. Thanks to the crystal structure of M. sexta PPO, some domains and specific amino acids that affect PPO activities have been identified. Further studies of the relationship between PPO structure and enzyme activities will provide an opportunity to examine other type-3 copper proteins, and trace when and why their various physiological functions evolved. Recent researches show that insect PPO has a relationship with neuron activity, longevity, feces melanization (phytophagous insects) and development, which suggests that it is time for us to look back on insect PPO beyond the view of immunity in this review.

Lu|Anrui|A| Zhang|Qiaoli|Q| Zhang|Jie|J| Yang|Bing|B| Wu|Kai|K| Xie|Wei|W| Luan|Yun-Xia|YX| Ling|Erjun|E|

insect
prophenoloxidase
type-3 copper proteins
melanization
protein structure


Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice.

Abstract: Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design  Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results  20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression ( p  < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated ( p  < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls ( p  = 0.001). Conclusion  Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.

Grace|Matthew R|MR|
Dotters-Katz|Sarah K|SK|
Zhou|Chunxiao|C|
Manuck|Tracy|T|
Boggess|Kim|K|
Bae-Jump|Victoria|V|


A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly.

METHODS
This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60-80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks.

RESULTS
VAS for xerostomia was decreased by 22.04±22.76 in the YMJ group and 23.58±23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37kg/m(2) showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant.

CONCLUSION
A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD.

Han|Gajin|G| Ko|Seok-Jae|SJ| Kim|Juyeon|J| Oh|Ja-Young|JY| Park|Jae-Woo|JW| Kim|Jinsung|J|

5-hydroxymethyl-2-furaldehyde (PubChem CID: 237332)


Histogram Analysis of Diffusion-Weighted Magnetic Resonance Imaging as a Biomarker to Predict Lymph Node Metastasis in T3 Stage Rectal Carcinoma.

Abstract:
Purpose
This study investigated the predictive value of apparent diffusion coefficient (ADC) histogram parameters of the primary tumor for regional lymph node metastasis (LNM) in pathological T3 stage rectal cancer.

Patients and Methods
We retrospectively studied 175 patients with T3 stage rectal cancer who underwent preoperative MRI, including diffusion-weighted imaging, between January 2015 and October 2017. Based on pathological analysis of surgical specimens, 113 patients were classified into the LN- group and 62 in the LN+ group. We analyzed clinical data, radiological characteristics and histogram parameters derived from ADC maps. Then, receiver operating characteristic curve (ROC) analyses were generated to determine the best diagnostic performance.

Results
The mean (p=0.002, cutoff=1.08×10-3 s/mm2), coefficient of variation (CV) (p=0.040, cutoff=0.249) of the ADC map, carbohydrate antigen 199, and N stage with magnetic resonance (mrN stage) were independent factors for LNM. Combining these factors yielded the best diagnostic performance, with the area under the ROC curve of 0.838, 72.9% sensitivity, 79.1% specificity, 65.2% positive predictive value, and 84.5% negative predictive value.

Conclusion
With the mean >1.08×10-3 s/mm2 and CV <0.249, the ADC improved the diagnostic performance of LNM in T3 stage rectal cancer, which could assist surgeons with neoadjuvant chemoradiotherapy.

Li|Jin|J| Zhou|Yang|Y| Wang|Xinxin|X| Yu|Yanyan|Y|0000-0003-2839-0541 Zhou|Xueyan|X| Luan|Kuan|K|

diffusion-weighted magnetic resonance imaging


Caffeine and Selective Adenosine Receptor Antagonists as New Therapeutic Tools for the Motivational Symptoms of Depression.

Abstract: Major depressive disorder is one of the most common and debilitating psychiatric disorders. Some of the motivational symptoms of depression, such anergia (lack of self-reported energy) and fatigue are relatively resistant to traditional treatments such as serotonin uptake inhibitors. Thus, new pharmacological targets are being investigated. Epidemiological data suggest that caffeine consumption can have an impact on aspects of depressive symptomatology. Caffeine is a non-selective adenosine antagonist for A1/A2A receptors, and has been demonstrated to modulate behavior in classical animal models of depression. Moreover, selective adenosine receptor antagonists are being assessed for their antidepressant effects in animal studies. This review focuses on how caffeine and selective adenosine antagonists can improve different aspects of depression in humans, as well as in animal models. The effects on motivational symptoms of depression such as anergia, fatigue, and psychomotor slowing receive particular attention. Thus, the ability of adenosine receptor antagonists to reverse the anergia induced by dopamine antagonism or depletion is of special interest. In conclusion, although further studies are needed, it appears that caffeine and selective adenosine receptor antagonists could be therapeutic agents for the treatment of motivational dysfunction in depression.

López-Cruz|Laura|L|
Salamone|John D|JD|
Correa|Mercè|M|

caffeine
adenosine receptors
anergia
fatigue
antidepressants
dopamine
anxiety


Effect of metal primers and tarnish treatment on bonding between dental alloys and veneer resin.

Abstract:
PURPOSE
The aim of this study was to evaluate the effect of metal primers on the bonding of dental alloys and veneer resin. Polyvinylpyrrolidone solution's tarnish effect on bonding strength was also investigated.

MATERIALS AND METHODS
Disk-shape metal specimens (diameter 8 mm, thickness 1.5 mm) were made from 3 kinds of alloy (Co-Cr, Ti and Au-Ag-Pd alloy) and divided into 4 groups per each alloy. Half specimens (n=12 per group) in tarnished group were immersed into polyvinylpyrrolidone solution for 24 hours. In Co-Cr and Ti-alloy, Alloy Primer (MDP + VBATDT) and MAC-Bond II (MAC-10) were applied, while Alloy Primer and V-Primer (VBATDT) were applied to Au-Ag-Pd alloys. After surface treatment, veneering composite resin were applied and shear bond strength test were conducted.

RESULTS
Alloy Primer showed higher shear bond strength than MAC-Bond II in Co-Cr alloys and Au-Ag-Pd alloy (P<.05). However, in Ti alloy, there was no significant difference between Alloy Primer and MAC-Bond II. Tarnished Co-Cr and Au-Ag-Pd alloy surfaces presented significantly decreased shear bond strength.

CONCLUSION
Combined use of MDP and VBATDT were effective in bonding of the resin to Co-Cr and Au-Ag-Pd alloy. Tarnish using polyvinylpyrrolidone solution negatively affected on the bonding of veneer resin to Co-Cr and Au-Ag-Pd alloys.

Choo|Seung-Sik|SS| Huh|Yoon-Hyuk|YH| Cho|Lee-Ra|LR| Park|Chan-Jin|CJ|

Metal primer
Tarnish
Resin
Polyvinylpyrrolidone solution
Shear bond strength


Chronic Constipation: a Review of Current Literature.

Abstract: Chronic constipation is a common health condition representing a substantial proportion of primary care visits and referrals to specialist providers. Chronic constipation can have a significant negative effect on health-related quality of life and has been associated with psychological distress in severely affected patients. It has the potential to cause patients to curtail work, school, and social activities. While different pathophysiological mechanisms have been implicated in the development of chronic constipation, in some instances, the causes of chronic constipation are not easily determined. Expenditures for the evaluation and management of chronic constipation represent a significant burden on patients and payers, and it is important for clinicians to have a clear understanding of the different pathophysiological mechanisms associated with constipation, understand the different testing modalities and treatments that are available including their appropriateness and limitations, and tailor that knowledge to the management of individual patients.

Chronic constipation
Constipation
Management of chronic constipation
Dyssynergic defecation
Pelvic floor dysfunction
Types of constipation


A novel toti-like virus from a plant pathogenic oomycete Globisporangium splendens.

Abstract: We investigated virus infection in the plant pathogenic oomycete Globisporangium splendens, formerly classified as Pythium splendens, in Japan. From 12 strains investigated, three strains contained virus-like double-stranded (dsRNA). Next-generation sequencing revealed that the G. splendens strain MAFF 425508 and MAFF 305867 contained a virus related to toti-like viruses, that we named Pythium splendens RNA virus 1 (PsRV1). PsRV1 has a ca. 5700 nt-length genome encoding two overlapping open reading frames (ORFs). The ORF2 encodes an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis with deduced RdRp amino acid sequences indicated that PsRV1 was closely related to Pythium polare RNA virus 1 (PpRV1) from G. polare infecting mosses in the Arctic. PsRV1 was vertically transmitted through the hyphal swellings, vegetative organs of G. splendens, in a temperature-dependent manner. Also, we showed that PsRV1 infected in a symptomless manner.

Shiba|Kazuki|K|
Hatta|Chiharu|C|
Sasai|Shinsaku|S|
Tojo|Motoaki|M|
Ohki|Satoshi T|ST|
Mochizuki|Tomofumi|T|

Globisporangium splendens
Pythium
Next generation sequencing
Oomycete virus
Totivirus
Vertical transmission


Synthesis and Pin1 inhibitory activity of thiazole derivatives.

Abstract: Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis-trans isomerase (PPIase) which specifically catalyze the conformational conversion of the amide bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising anticancer target. A series of new thiazole derivatives were designed and synthesized, and their inhibitory activities were measured against human Pin1 using a protease-coupled enzyme assay. Of all the tested compounds, a number of thiazole derivatives bearing an oxalic acid group at 4-position were found to be potent Pin1 inhibitors with IC50 values at low micromolar level. The detailed structure-activity relationships were analyzed and the binding features of compound 10b (IC50 5.38μM) was predicted using CDOCKER program. The results of this research would provide informative guidance for further optimizing thiazole derivatives as potent Pin1 inhibitors.

Zhao|Hailong|H| Cui|Guonan|G| Jin|Jing|J| Chen|Xiaoguang|X| Xu|Bailing|B|

Pin1
Thiazole derivatives
PPIase
Pin1 inhibitor
Anti-cancer agents


Hydrothermal carbonisation of mechanically dewatered digested sewage sludge-Energy and nutrient recovery in centralised biogas plant.

Abstract: This study aimed to assess the role of hydrothermal carbonisation (HTC) in digestate processing in centralised biogas plants receiving dewatered sludge from regional wastewater treatment plants and producing biomethane and fertilisers. Chemically conditioned and mechanically dewatered sludge was used as such (total solids (TS) 25%) or as diluted (15% TS) with reject water in 30 min or 120 min HTC treatments at 210 °C, 230 °C or 250 °C, and the produced slurry was filtered to produce hydrochars and filtrates. The different hydrochars contributed to 20-55% of the original mass, 72-88% of the TS, 74-87% of the energy content, 71-92% of the carbon, above 86% of phosphorous and 38-64% of the nitrogen present in the original digestates. The hydrochars' energy content (higher heating values were 11.3-12.2 MJ/kg-TS) were similar to that of the digestates, while the ash contents increased (from 43% up to 57%). HTC treatments produced filtrates in volumes of 42-76% of the dewatered digestate, having a soluble chemical oxygen demand (SCOD) of 28-44 g/L, of which volatile fatty acids (VFAs) contributed 10-34%, and methane potentials of 182-206 mL-CH4/g-SCOD without any major indication of inhibition. All 32 pharmaceuticals detected in the digestates were below the detection limit in hydrochars and filtrates, save for ibuprofen and benzotriazole in filtrate, while heavy metals were concentrated in the hydrochars but below the national limits for fertiliser use, save for mercury. The integration of HTC to a centralised biogas plant was extrapolated to enhance the annual biogas production by 5% and ammonium recovery by 25%, and the hydrochar was estimated to produce 83 GJ upon combustion or to direct 350 t phosphorous to agriculture annually.

Hämäläinen|Anna|A| Kokko|Marika|M| Kinnunen|Viljami|V| Hilli|Tuomo|T| Rintala|Jukka|J|

Hydrothermal carbonisation
Nutrient recovery
Hydrochar
Phosphorous
Energy recovery
Sewage sludge digestate


Biodegradation of decabromodiphenyl ether (BDE 209) by a newly isolated bacterium from an e-waste recycling area.

Abstract: Polybrominated diphenyl ethers (PBDEs) have become widespread environmental pollutants all over the world. A newly isolated bacterium from an e-waste recycling area, Stenotrophomonas sp. strain WZN-1, can degrade decabromodiphenyl ether (BDE 209) effectively under aerobic conditions. Orthogonal test results showed that the optimum conditions for BDE 209 biodegradation were pH 5, 25 °C, 0.5% salinity, 150 mL minimal salt medium volume. Under the optimized condition, strain WZN-1 could degrade 55.15% of 65 μg/L BDE 209 under aerobic condition within 30 day incubation. Moreover, BDE 209 degradation kinetics was fitted to a first-order kinetics model. The biodegradation mechanism of BDE 209 by strain WZN-1 were supposed to be three possible metabolic pathways: debromination, hydroxylation, and ring opening processes. Four BDE 209 degradation genes, including one hydrolase, one dioxygenase and two dehalogenases, were identified based on the complete genome sequencing of strain WZN-1. The real-time qPCR demonstrated that the expression level of four identified genes were significantly induced by BDE 209, and they played an important role in the degradation process. This study is the first to demonstrate that the newly isolated Stenotrophomonas strain has an efficient BDE 209 degradation ability and would provide new insights for the microbial degradation of PBDEs.

Wu|Zhineng|Z| Xie|Miaomiao|M| Li|Yao|Y| Gao|Guanghai|G| Bartlam|Mark|M| Wang|Yingying|Y|

Biodegradation
BDE 209
Stenotrophomonas
Genome sequencing
Real-time qPCR


Significance of multiple preoperative laboratory abnormalities as prognostic indicators in patients with urothelial carcinoma of the upper urinary tract following radical nephroureterectomy.

Abstract:
BACKGROUND
The aim of this study was to investigate the prognostic significance of multiple preoperative laboratory abnormalities in upper urinary tract urothelial carcinoma (UUTUC) patients.

METHODS
This study included a total of 135 consecutive patients with clinically localized UUTUC who underwent radical nephroureterectomy (RNU). The impact of several preoperative blood-based markers in addition to conventional clinical factors on extravesical recurrence-free survival (eRFS) in these patients was retrospectively evaluated.

RESULTS
Despite the lack of a significant correlation between conventional clinical factors and any of the postoperative pathologic parameters, preoperative laboratory abnormalities were shown to have a significant impact on some pathological factors reflecting an aggressive phenotype as follows-C-reactive protein (CRP) level on pathological stage, De Ritis (aspartate transaminase/alanine transaminase) ratio on nodal involvement, and neutrophil-lymphocyte ratio (NLR) on pathological stage. During the observation period of this study (median 36.1 months), extravesical disease recurrence was detected in 44 (32.6%) of the 135 patients with a 5-year eRFS rate of 62.1%. Of several factors examined, the CRP level, De Ritis ratio, and NRL were significantly correlated with eRFS on univariate analysis. Of these significant factors, the De Ritis ratio and NRL were identified as independent predictors of eRFS on multivariate analysis. Moreover, there were significant differences in eRFS according to the positive numbers of these two independent risk factors.

CONCLUSIONS
These findings suggest that it is important to consider laboratory abnormalities, particularly the De Ritis ratio and NLR, to predict disease recurrence following RNU in patients with clinically localized UUTUC.

Nishikawa|Masatomo|M| Miyake|Hideaki|H| Kurahashi|Toshifumi|T| Fujisawa|Masato|M|

Upper urinary tract urothelial carcinoma


Outcomes after helicopter versus ground emergency medical services for major trauma--propensity score and instrumental variable analyses: a retrospective nationwide cohort study.

Abstract:
BACKGROUND
Because of a lack of randomized controlled trials and the methodological weakness of currently available observational studies, the benefits of helicopter emergency medical services (HEMS) over ground emergency medical services (GEMS) for major trauma patients remain uncertain. The aim of this retrospective nationwide cohort study was to compare the mortality of adults with serious traumatic injuries who were transported by HEMS and GEMS, and to analyze the effects of HEMS in various subpopulations.

METHODS
Using the Japan Trauma Data Bank, we evaluated all adult patients who had an injury severity score ≥ 16 transported by HEMS or GEMS during the daytime between 2004 and 2014. We compared in-hospital mortality between patients transported by HEMS and GEMS using propensity score matching, inverse probability of treatment weighting and instrumental variable analyses to adjust for measured and unmeasured confounding factors.

RESULTS
Eligible patients (n = 21,286) from 192 hospitals included 4128 transported by HEMS and 17,158 transported by GEMS. In the propensity score-matched model, there was a significant difference in the in-hospital mortality between HEMS and GEMS groups (22.2 vs. 24.5%, risk difference -2.3% [95% confidence interval, -4.2 to -0.5]; number needed to treat, 43 [95% confidence interval, 24 to 220]). The inverse probability of treatment weighting (20.8% vs. 23.9%; risk difference, -3.9% [95% confidence interval, -5.7 to -2.1]; number needed to treat, 26 [95% confidence interval, 17 to 48]) and instrumental variable analyses showed similar results (risk difference, -6.5% [95% confidence interval, -9.2 to -3.8]; number needed to treat, 15 [95% confidence interval, 11 to 27]). HEMS transport was significantly associated with lower in-hospital mortality after falls, compression injuries, severe chest injuries, extremity (including pelvic) injuries, and traumatic arrest on arrival to the emergency department.

CONCLUSIONS
HEMS was associated with a significantly lower mortality than GEMS in adult patients with major traumatic injuries after adjusting for measured and unmeasured confounders.

Ground emergency medical service
Instrumental variable
Helicopter emergency medical service
Trauma
Mortality
Japan Trauma Data Bank
Propensity score


Phenotypic characterization of MCP-1 expressing neurons in the rat cerebral cortex.

Abstract: Chemokines are small, secreted molecules that mediate inflammatory reactions. Neurons and astrocytes constitutively express chemokines implicated in the process of neuroinflammation associated with neurodegenerative diseases. The monocyte chemoattractant protein-1 (MCP-1) has been widely related to this process. However, the constitutive expression of this molecule by neurons has not been elucidated so far. In this study, we set out to characterize the neurochemical phenotype of MCP-1-expressing neurons in the rat neocortex to infer its role in basal conditions. We observed the presence of two populations of neurons expressing MCP-1: One population of cells with weak expression of MCP-1 corresponding to principal neurons (Tbr-1 positive) and a second population with high expression of MCP-1 corresponding to inhibitory neurons (GAD-67 positive), in particular to CCK/CBR1 interneurons. Moreover, high MCP-1-expressing neurons were metabolically active (pCREB positive). The population of CCK interneurons that co-localizes with MCP-1 corresponds to the regular-spiking basket cells and is co-responsible for the perisomatic inhibition of principal pyramidal neurons. Previous studies have demonstrated that MCP-1 can alter the electric properties of neurons and a tonic function for this molecule has been postulated. As CCK-inhibitory neurons are affected in mood disorders, whether the expression of MCP-1 was maintained in humans could be part of the link between inflammatory responses and observed changes in mood state.

Mulet|Maria|M|
Blasco-Ibáñez|José Miguel|JM|
Kirstein|Martina|M|
Crespo|Carlos|C|
Nacher|Juan|J|
Varea|Emilio|E|

Phenotypic characterization
MCP-1
Rat
Neocortex
Interneuron
CCL2


Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India.

Abstract:
AIM
Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting.

METHODS
The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated.

RESULTS
One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively.

CONCLUSION
Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.

biologics
tuberculosis
rheumatic diseases
disease modifying anti-rheumatic drugs
rheumatoid arthritis


Increasing the response rate of text messaging data collection: a delayed randomized controlled trial.

Abstract:
OBJECTIVE
To test the effectiveness of multiple interventions on increasing the response rate of text messaging for longitudinal data collection.

METHODS
Our cohort included 283 caregivers of children aged 6-12 months who were participating in an anemia program in rural China. Using text messages to collect data on anemia medication adherence, we conducted a delayed randomized controlled trial to test multiple interventions (an additional four reminders; a ¥5.0 (US$0.79) credit reward for replying; and a feedback text message). After a 6-week pilot study with week 7 as the baseline measurement, we randomly allocated all participants into two groups: group 1 (n = 142) and group 2 (n = 141). During weeks 8-11, we introduced the interventions to group 1, and in weeks 12-15 the intervention was introduced to both groups. We compared the response rates between groups and explored factors affecting the response rate.

RESULTS
During weeks 8-11, the response rates in group 1 increased and were significantly higher than in group 2 (p<0.05). During weeks 12-15, the response rate increased significantly in group 2 (p>0.05) and slightly decreased in group 1. Younger participants or participants who had children with lower hemoglobin concentration were more likely to reply (p = 0.02). Sending four reminders on the second day contributed to only 286 (11.7%) extra text messages.

DISCUSSION
Our study showed that multiple interventions were effective in increasing response rate of text messaging data collection in rural China.

CONCLUSIONS
Larger multi-site studies are needed to find the most effective way of using these interventions to allow usage of text messaging data collection for health research.

Li|Ye|Y|
Wang|Wei|W|
Wu|Qiong|Q|
van Velthoven|Michelle Helena|MH|
Chen|Li|L|
Du|Xiaozhen|X|
Zhang|Yanfeng|Y|
Rudan|Igor|I|
Car|Josip|J|

randomized controlled trial
nutrition surveys
program evaluation


From Machining Chips to Raw Material for Powder Metallurgy-A Review.

Abstract: Chips are obtained by subtractive processes such as machining workpieces and until recently considered as waste. However, in recent years they are shown to have great potential as sustainable raw materials for powder technologies. Powder production from metal chips, through the application of solid-state processes, seems to be an alternative to conventional atomization from liquid cooled with different fluids. However, chip material and processing have an essential role in the characteristics of powder particles, such as particle size, shape, size distribution and structure (4S's), which are essential parameters that must be considered having in mind the powder process and the metallurgy applications. Moreover, different approaches refereed in the application of this new "powder process" are highlighted. The goal is to show how the actual research has been transforming subtractive processes from a contributor of wastes to clean technologies.

Fernandes|Adriana André Martins das Neves de Pinho|AAMDNP|

metal chips
additive manufacturing
milling
powder characteristics
sintering


A Method to Investigate Astrocyte and Microglial Morphological Changes in the Aging Brain of the Rhesus Macaque.

Abstract: With a rapidly aging population, studies of neuroinflammation and degeneration associated with eugeric aging are becoming critical. Using the unique archive at the Tulane National Primate Research Center as a resource, we have developed tools to quantify morphological changes in astrocytes and microglia across the life span of monkeys. This method can be used for morphometric studies of multiple parameters simultaneously in an unbiased manner.

Chiu|Kevin B|KB|
Lee|Kim M|KM|
Robillard|Katelyn N|KN|
MacLean|Andrew G|AG|

Astrocyte Aging Neuroinflammation Eugeric Microglia Neurodegeneration


Distinct effect of CacyBP/SIP on the ERK1/2-CREB-BDNF pathway in undifferentiated and differentiated neuroblastoma NB2a cells.

Abstract: CacyBP/SIP, a protein expressed to high extent in the brain, has been shown to act as ERK1/2 phosphatase in vitro and in cultured cells. It has been demonstrated recently that CacyBP/SIP can modulate the activity of some transcription factors in neurons and glioma cells. In the present work we have examined the effect of CacyBP/SIP overexpression and silencing on the phosphorylation/activity of ERK1/2 (pERK1/2) and CREB (pCREB) and on the level of BDNF mRNA in differentiated and undifferentiated neuroblastoma NB2a cells. We have shown that in undifferentiated cells the amount of pERK1/2 decreased upon CacyBP/SIP overexpression. Further studies have shown that the activity of CREB and the level of BDNF mRNA, downstream effectors of the ERK1/2 signaling pathway, also depended on the CacyBP/SIP level and strictly matched the level of pERK1/2. Interestingly, in differentiated NB2a cells, overexpression of CacyBP/SIP appeared to have a distinct effect on the pERK1/2 level from that observed in undifferentiated cells. Subsequent studies have revealed that distinct function of CacyBP/SIP in undifferentiated and differentiated NB2a cells might be due to changes in its posttranslational modifications and protein ligands. Altogether, our studies suggest that CacyBP/SIP is involved in the ERK1/2-CREB-BDNF pathway and that it might regulate this pathway depending on the stage of NB2a cell differentiation.

D017362:Cyclic AMP Response Element-Binding Protein

CacyBP/SIP
NB2a cells
ERK1/2
CREB
BDNF
Cell differentiation


Examining how and why to Engage Practitioners from across the Learning Landscape in the Research Enterprise: Proposal for Phronêtic Research on Education.

Abstract: Educational practitioners are often reluctant, if not actively resistant, to their participation in production and consumption of educational research. Based on my research experience with educational practitioners, I try to deconstruct this phenomenon using dialogic Bakhtinian and Aristotelian sociocultural frameworks. I consider two major related breakdowns in the educational practice: 1) a lack of self-correcting process in the educational practice, while reliance on accountability policy to achieve the practice quality, and 2) a breakdown between educational research and educational practice. I argue that the first breakdown is caused by viewing teaching as poiesis, aiming at preset curricular endpoints, and not as praxis, critically defining its own values, goals, and virtues. As to the second breakdown, I argue that current mainstream and even innovative research is defined through the technê and epistêmê ways of knowing, which correspond to a poiesic vision of educational practice. I suggest that educational practice primarily involves the phronêtic and sophic ways of knowing, which correspond to a praxis vision of educational practice. I describe phronêtic research of teaching through a case of my students, preservice teachers, working on revisions of their lessons that they conducted at an urban afterschool program. Finally, I consider recommendations for institutional support for phronêtic research on teaching.

Praxis
Technê
Epistêmê
Agency
Aristotle
Bakhtin
Dialogue
Phronêsis
Poïesis
Self-correcting practice
Sophia
Standards


Glutamine Cooperatively Upregulates Lipopolysaccharide-Induced Nitric Oxide Production in BV2 Microglial Cells through the ERK and Nrf-2/HO-1 Signaling Pathway.

Abstract: Glutamine (Gln) is a nonessential α-amino acid for protein biosynthesis. However, the mechanism through which Gln regulates NO production in microglial cells is still unclear. In this study, we investigated whether the presence or absence of Gln affects NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our data revealed that Gln depletion decreased cell viability accompanied by mild cytotoxicity, and blocked LPS-induced NO production concomitant with a significant decrease in inducible NO synthase (iNOS) expression. Additionally, Gln depletion for 24 h blocked the restoration of LPS-mediated NO production in the presence of Gln, suggesting that Gln depletion caused long-term immune deprivation. In particular, sodium-coupled amino acid transporter 1 and 2 (SNAT1 and SNAT2), which are the main Gln transporters, were highly upregulated in LPS-stimulated BV2 microglial cells, in the presence of Gln accompanied by NO production. Regardless of the presence of Gln, LPS positively stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and transient Nrf2 knockdown and HO-1 inhibition stimulated LPS-induced NO production and iNOS expression; however, transient Nrf2 knockdown did not affect SNAT1 and SNAT2 expression, indicating that Gln transporters, SNAT1 and SNAT2, were not regulated by Nrf2, which downregulated the HO-1-mediated NO production. Moreover, Gln depletion significantly reduced LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation; furthermore, a specific ERK inhibitor, PD98059, and transient ERK knockdown attenuated LPS-stimulated NO production and iNOS expression, in the presence of Gln, accompanied by downregulation of SNAT1 and SNAT2, suggesting that the ERK signaling pathway was related to LPS-mediated NO production via SNAT1 and SNAT2. Altogether, our data indicated that extracellular Gln is vital for NO production from microglia in inflammatory conditions.

Jayasooriya|Rajapaksha Gedara Prasad Tharanga|RGPT|

nuclear factor-erythroid 2-related factor 2


Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats.

Abstract: This study investigated neuroendocrine, autonomic, and cardiovascular changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in 60-days-old female normotensive Wistar rats and female spontaneously hypertensive rats (SHR). Both strains of rats were exposed for 10 consecutive days to either the homotypic stressor repeated restraint stress (RRS) or the heterotypic stressor chronic unpredictable stress (CUS). As expected, SHR had higher baseline blood pressure values and impaired baroreflex activity in relation to normotensive animals. Besides, SHR presented higher plasma corticosterone levels and decreased thymus weight. Both RRS and CUS increased baseline plasma corticosterone concentration and decreased body weight gain in both normotensive and SHR rats. In addition, both stress protocols caused hypertrophy of adrenal glands in normotensive rats. Regarding the cardiovascular effects, RRS increased basal heart rate in both rat strains, which was mediated by an increase in sympathetic tone to the heart. Besides, RRS increased baroreflex-mediated tachycardia in SHR animals, while CUS increased cardiac parasympathetic activity and pacemaker activity in normotensive rats. Taken together, these results indicate a stress type-specific effect, as identified by a vulnerability of both strains to the deleterious cardiovascular effects evoked by the homotypic stressor and a resilience to the impact of the heterotypic stressor. Vulnerability of hypertensive rats was evidenced by the absence of CUS-evoked adaptive cardiovascular responses and an increase of baroreflex tachycardia in SHR animals subjected to RRS. The somatic and HPA axis changes were overall independent of the chronic stress regimen and pre-existing hypertension.

Vieira|Jonas O|JO|
Duarte|Josiane O|JO|
Costa-Ferreira|Willian|W|
Crestani|Carlos C|CC|

Female
SHR
Restraint stress
Autonomic activity
Chronic variable stress
Glucocorticoids


Cytokines in the Treatment of Melanoma.

Abstract:
PURPOSE OF REVIEW
The use of cytokines in harnessing the immune system to eradicate cancer has been an important treatment modality. However, the dose-limiting toxicities of these cytokines limited their usage in clinic. Here, we review the basic biology of cytokines involved in the treatment of melanoma and discuss their therapeutic applications. Moreover, we describe several innovative technological approaches that have been developed to improve the pharmacokinetics, safety, and efficacy of these cytokines.

RECENT FINDINGS
The safety and the anti-tumor activity of newly engineered cytokines including PEGylated IL-2 (NKTR-214), PEGylated IL-10 (AM0010), and IL-15 super agonist (ALT-803) have been evaluated in clinical trials with encouraging clinical activity and acceptable safety profile, both as single agents and in combination with immuno-oncology agents. A greater understanding of the mechanisms of action and effective dosing of these newly engineered cytokine together with determination of optimum combination therapy regimens may yield greater clinical benefits in the future.


The association between polymorphisms near TMEM18 and the risk of obesity: a meta-analysis.

Abstract:
BACKGROUND
Many studies have proposed that the pathogenesis of obesity has a genetic basis, with an important risk factor being the presence of polymorphisms in the region of the TMEM18 gene, which plays a significant role in feeding behaviour; however, subsequent studies among different ethnic populations and age groups have shown inconsistent results. Therefore, this present meta-analysis examines the relationship between TMEM18 polymorphisms with the risk of obesity with regard to age group and ethnic population.

METHODS
A literature database search was conducted for available relevant studies investigating the association between obesity risk and the presence of rs6548238, rs4854344, rs11127485, rs2867125 and rs7561317 polymorphisms in TMEM18. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were calculated by either a fixed-effects model or random effect model based on a heterogeneity test. The meta-analysis of rs6548238 and its surrogates examined the relationships between 53 395 obesity cases and 123 972 healthy controls from 27 studies and published data from the POPULOUS collection (Poland).

RESULTS
A significant association is observed between rs6548238 (and surrogate) and obesity risk, with OR = 1.25 (95% CI: 1.08-1.45). Regarding population type, a significant association was revealed among groups of Europeans with OR = 1.32 (1.10-1.59) and Mexicans with OR = 1.39 (1.13-1.73). However, a lack of statistical significance was noticed in groups in Asia with OR = 1.11 (95% CI: 0.86-1.42). Regarding age, a significant association was observed among children with OR = 1.28 (95% CI: 1.18-1.39) but not in adults OR = 1.21 (95% CI: 0.92-1.58).

CONCLUSIONS
The polymorphisms near TMEM18 appear to play a role in the development of obesity. Our findings indicate that differences exist between ethnic populations and age groups, supporting those of a previous study showing the various effects of genetic factors on age and ethnic groups.


A dowel exercise tool to improve finger range of motion.

Abstract: A new clinical and home dowel exercise tool to reduce joint stiffness of the fingers is introduced, along with the fabrication and the exercises that are used with it. Patients may utilize it to improve their finger joint range of motion, and facilitate tendon glide by isolating the targeted stiff joints of the fingers.


Observing the Effect of Soil-Applied Insecticides on Wireworm (Coleoptera: Elateridae) Behavior and Mortality Using Radiographic Imaging.

Abstract: Radiographic imaging was used to study corn wireworm, Melanotus communis (Gyllenhal) (Coleoptera: Elateridae), behavior in the soil relative to Irish potato, Solanum tuberosum L. (Solanales: Solanaceae), placed above a barrier of insecticide-treated soil. Behavioral response to three insecticides was evaluated by 1) calculating the percentage of wireworms that breached the zone of insecticide-treated soil, 2) comparing the variability in the mean distance between each wireworm and the center of the tuber in each arena compartment, 3) comparing the cumulative distance of wireworm travel, and 4) comparing incidence and severity of wireworm-inflicted tuber injury. The percentage of wireworms that breached the insecticide zone was significantly lower in the bifenthrin treatment than the untreated check, but not different from clothianidin or fipronil. Limited difference between treatments in relation to the cumulative distance traveled was observed where bifenthrin inhibited travel distance more than other insecticides tested. No difference in variability of movement in relation to the food source was observed between treatments. Bifenthrin and fipronil treatments resulted in the greatest reduction in wireworm injury incidence and severity compared to the untreated check. While bifenthrin suppressed wireworm movement and feeding more than other insecticides tested, exposure to fipronil resulted in higher wireworm mortality at all sample dates.

Langdon|Kevin W|KW|
Colee|James|J|
Abney|Mark R|MR|

wireworm
Elateridae
radiograph
Irish potato


Polycystic ovary syndrome and mitochondrial dysfunction.

Abstract: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.

Polycystic ovary syndrome
Hyperandrogenism
Oxidative stress
Abnormal follicular development
And inflammation
Insulin resistance
Obesity


No detectable effect of Wolbachia wMel on the prevalence and abundance of the RNA virome of Drosophila melanogaster.

Abstract: Wolbachia is an endosymbiotic bacterium that can block viral infections in arthropods, generating interest in its potential to control the spread of mosquito-borne disease. Drosophila melanogaster is model organism for Wolbachia infection, and the wMel strain of Wolbachia can improve host survival following viral infection. However, it is unclear whether wMel induces anti-viral blocking against the broader native virome of D. melanogaster, or whether the major effect of Wolbachia is a reduction in viral abundance rather than viral clearance. We examined the effect of Wolbachia on viral abundance by comparing the total transcriptome of wMel-positive and wMel-negative D. melanogaster populations sampled from six locations in Australia. In addition, we examined the impact of wMel on individual flies by obtaining transcriptome data from 20 wMel-positive and 20 wMel-negative D. melanogaster from the location (Melbourne) with highest density of wMel. These data revealed high viral abundance in both Wolbachia-positive and -negative populations and individuals. Notably, none of the viral species identified, representing RNA viruses from at least nine families/floating genera, showed evidence of protection by wMel. Although the viral loads of picorna-like viruses are reduced by wMel under experimental conditions, we observed no such effect here. These data show that D. melanogaster can harbour abundant RNA viruses regardless of its Wolbachia status and imply that the interaction between Wolbachia and viruses in nature is more complex than simple blocking.

Shi|Mang|M|
White|Vanessa L|VL|
Schlub|Timothy|T|
Eden|John-Sebastian|JS|
Hoffmann|Ary A|AA|
Holmes|Edward C|EC|0000-0001-9596-3552

Wolbachia Drosophila transcriptomics evolution virus


A blinded, randomized, controlled trial assessing conservative management strategies for frozen shoulder.

Abstract:
BACKGROUND
There is little evidence for the optimal form of nonoperative treatment in the management of frozen shoulder. This study assesses the efficacy of current physiotherapy strategies.

METHODS
All primary care referrals of frozen shoulder to our physiotherapy department were included during a 12-month period. Of these referrals, 17% met the inclusion criteria for primary idiopathic frozen shoulder. The 75 patients were randomly assigned to 1 of 3 groups: group exercise class, individual physiotherapy, and home exercises alone. A single independent physiotherapist, who was blinded to the treatment groups, made all assessments. Range of motion, Constant score, Oxford Shoulder Score, Short Form 36, and Hospital Anxiety and Disability Scale (HADS) outcome measures were performed at baseline, 6 weeks, 6 months, and 1 year.

RESULTS
The exercise class group improved from a mean Constant score of 39.8 at baseline to 71.4 at 6 weeks and 88.1 at 1 year. There was a significant improvement in shoulder symptoms on Oxford and Constant scores (P < .001). This improvement was greater than with individual physiotherapy or home exercises alone (P < .001). The improvement in range of motion was significantly greater in both physiotherapy groups over home exercises (P < .001). HADS scores significantly improved during the course of treatment (P < .001). The improvement in HADS anxiety score was significantly greater in both physiotherapy intervention groups than in home exercises alone.

CONCLUSIONS
A hospital-based exercise class can produce a rapid recovery from a frozen shoulder with a minimum number of visits to the hospital and is more effective than individual physiotherapy or a home exercise program.

Russell|Sarah|S| Jariwala|Arpit|A| Conlon|Robert|R| Selfe|James|J| Richards|Jim|J| Walton|Michael|M|

frozen shoulder
Shoulder
physiotherapy
anxiety
HADS
SF-36
adhesive capsulitis


The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: A systematic review and meta-analysis of 5507 patients.

Abstract:
BACKGROUND
The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT).

METHODS
Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference.

RESULTS
Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40years, pooled HR 0.30 (95% CI 0.11-0.82).

CONCLUSIONS
Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients.

O'Rorke|M A|MA|
Murray|L J|LJ|
Brand|J S|JS|
Bhoo-Pathy|N|N|

D064726:Triple Negative Breast Neoplasms

Radiotherapy
Survival
Recurrence
Meta-analysis
Triple negative breast cancer
Surgery


A passage retrieval method based on probabilistic information retrieval model and UMLS concepts in biomedical question answering.

Abstract:
BACKGROUND AND OBJECTIVE
Passage retrieval, the identification of top-ranked passages that may contain the answer for a given biomedical question, is a crucial component for any biomedical question answering (QA) system. Passage retrieval in open-domain QA is a longstanding challenge widely studied over the last decades. However, it still requires further efforts in biomedical QA. In this paper, we present a new biomedical passage retrieval method based on Stanford CoreNLP sentence/passage length, probabilistic information retrieval (IR) model and UMLS concepts.

METHODS
In the proposed method, we first use our document retrieval system based on PubMed search engine and UMLS similarity to retrieve relevant documents to a given biomedical question. We then take the abstracts from the retrieved documents and use Stanford CoreNLP for sentence splitter to make a set of sentences, i.e., candidate passages. Using stemmed words and UMLS concepts as features for the BM25 model, we finally compute the similarity scores between the biomedical question and each of the candidate passages and keep the N top-ranked ones.

RESULTS
Experimental evaluations performed on large standard datasets, provided by the BioASQ challenge, show that the proposed method achieves good performances compared with the current state-of-the-art methods. The proposed method significantly outperforms the current state-of-the-art methods by an average of 6.84% in terms of mean average precision (MAP).

CONCLUSION
We have proposed an efficient passage retrieval method which can be used to retrieve relevant passages in biomedical QA systems with high mean average precision.

Sarrouti|Mourad|M|
Ouatik El Alaoui|Said|S|

D016247:Information Storage and Retrieval

Probabilistic information retrieval model


Wound Closure After Posterior Multi-level Lumbar Spine Surgery: An Anatomical Cadaver Study and Technical Note.

Abstract: Meticulous attention to wound closure in posterior lumbar spine surgery is an important principle in reducing surgical site infections. We detail standardized wound closure used for posterior lumbar spine surgery at a tertiary care referral center and illustrate this as a step-by-step cadaveric dissection. The lumbar spine of a cadaveric specimen (male, 73 years at death) was used for dissection. Standardizing wound closure in posterior lumbar spine surgery may help limit wound complications and infection. Some key points of our technique, as demonstrated on a cadaveric specimen, include separating fascial compartments, avoiding suture abscesses, and creating a tension-free wound.

Yilmaz|Emre|E|
Tawfik|Tamir|T|
O'Lynnger|Thomas M|TM|
Iwanaga|Joe|J|
Blecher|Ronen|R|
Abdul-Jabbar|Amir|A|
Tubbs|R Shane|RS|
Schmidt|Cameron K|CK|
Oskouian|Rod J|RJ|
Chapman|Jens|J|

wound closure
lumbar
spine surgery
technique
fascia
subcutaneous


Growth and fluctuating asymmetry of human newborns: influence of inbreeding and parental education.

Abstract: Historically, medical concerns about the deleterious effects of closely inbred marriages have focused on the risk posed by recessive Mendelian disease, with much less attention to developmental instability. We studied the effects of inbreeding (first-cousin marriage) on growth and fluctuating asymmetry of 200 full-term infants (101 inbred and 99 outbred) whose parents were of similar socioeconomic status in Sivas Province, Turkey. In addition to differences in their mean inbreeding coefficients (f = 1/16 for first cousins and f < 1/1,024 for unrelated parents), the consanguineous parents were less well educated (3 years, on average for both husbands and wives). We measured weight, height, head circumference, and chest circumference of the newborns, as well as four bilateral traits (ear width, ear length, and second and fourth digit lengths). After taking education into account, none of the measures of size (weight, height, head circumference, and chest circumference) and fluctuating asymmetry differed between the inbred and outbred groups. Male children of well-educated parents, however, were larger and had less fluctuating asymmetry. Female children of well-educated parents weighed more than those of less well-educated parents, but were otherwise indistinguishable for height, head circumference, chest circumference, and fluctuating asymmetry. We conclude that inbreeding depression causes neither an increase in fluctuating asymmetry of full-term newborns, nor a decrease in body size. Unmeasured variables correlated with education appear to have an effect on fluctuating asymmetry and size of male children and only a weak effect on size (weight) of female children.

developmental instability
first-cousin marriage
inbreeding depression
birth weight


Capsid Structure of Leishmania RNA Virus 1.

Abstract: Leishmania parasites cause a variety of symptoms, including mucocutaneous leishmaniasis, which results in the destruction of the mucous membranes of the nose, mouth, and throat. The species of Leishmania carrying Leishmania RNA virus 1 (LRV1), from the family Totiviridae, are more likely to cause severe disease and are less sensitive to treatment than those that do not contain the virus. Although the importance of LRV1 for the severity of leishmaniasis was discovered a long time ago, the structure of the virus remained unknown. Here, we present a cryo-electron microscopy reconstruction of the virus-like particle of LRV1 determined to a resolution of 3.65 Å. The capsid has icosahedral symmetry and is formed by 120 copies of a capsid protein assembled in asymmetric dimers. RNA genomes of viruses from the family Totiviridae are synthetized, but not capped at the 5' end, by virus RNA polymerases. To protect viral RNAs from degradation, capsid proteins of the L-A totivirus cleave the 5' caps of host mRNAs, creating decoys to overload the cellular RNA quality control system. Capsid proteins of LRV1 form positively charged clefts, which may be the cleavage sites for the 5' cap of Leishmania mRNAs. The putative RNA binding site of LRV1 is distinct from that of the related L-A virus. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative decapping site. Such inhibitors may be developed into a treatment for mucocutaneous leishmaniasis caused by LRV1-positive species of Leishmania IMPORTANCE Twelve million people worldwide suffer from leishmaniasis, resulting in more than 30 thousand deaths annually. The disease has several variants that differ in their symptoms. The mucocutaneous form, which leads to disintegration of the nasal septum, lips, and palate, is caused predominantly by Leishmania parasites carrying Leishmania RNA virus 1 (LRV1). Here, we present the structure of the LRV1 capsid determined using cryo-electron microscopy. Capsid proteins of a related totivirus, L-A virus, protect viral RNAs from degradation by cleaving the 5' caps of host mRNAs. Capsid proteins of LRV1 may have the same function. We show that the LRV1 capsid contains positively charged clefts that may be sites for the cleavage of mRNAs of Leishmania cells. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative mRNA cleavage site. Such inhibitors may be used as treatments for mucocutaneous leishmaniasis.

D002213:Capsid
D036022:Capsid Proteins
D020285:Cryoelectron Microscopy
D016679:Genome, Viral
D019199:Leishmaniavirus
D012367:RNA, Viral

capsid
structure
Leishmania
RNA
virus
parasite
leishmaniasis
LRV1
Totiviridae
cryo-electron microscopy
genome
mRNA
decapping
CAP-4
Viannia
uncoating
virion


Design, synthesis, biological evaluation, and molecular modeling of coumarin-piperazine derivatives as acetylcholinesterase inhibitors.

Abstract: Acetylcholinesterase (AChE) is an important drug target for the treatment of Alzheimer's disease. A novel series of coumarin-piperazine derivatives were synthesized and their potency to inhibit human AChE enzyme (hAChE) was studied. All the final compounds were characterized by infrared, (1)H NMR, (13)C NMR, and elemental analysis. Docking experiments of the designed coumarin-piperazine derivatives were carried out in order to compare the theoretical and experimental binding affinities toward hAChE, to delineate the inhibitory mechanism. Subsequently, a structure-activity relationship (SAR) study using the molecular field method showed that the hydrophobic field and positive charge center conferred by the coumarin and piperazine moieties demonstrated an inhibitory mechanism. Among the compounds tested, 3f, 3j, and 3m were found to be the most potent inhibitors of hAChE.

Modh|Rahul P|RP|
Kumar|Sivakumar Prasanth|SP|
Jasrai|Yogesh T|YT|
Chikhalia|Kishor H|KH|

D057927:Hydrophobic and Hydrophilic Interactions

Alzheimer's disease
hAChE
Docking
Coumarin
Piperazine
Field-based activity model


Reliability of automated versus handheld breast ultrasound examinations of suspicious breast masses.

Abstract:
PURPOSE
The purpose of this study was to assess the reliability of automated breast ultrasound (ABUS) examinations of suspicious breast masses in comparison to handheld breast ultrasound (HHUS) with regard to Breast Imaging Reporting and Data System (BI-RADS) category assessment, and to investigate the factors affecting discrepancies in categorization.

METHODS
A total of 135 masses that were assessed as BI-RADS categories 4 and 5 on ABUS that underwent ultrasound (US)-guided core needle biopsy from May 2017 to December 2017 were included in this study. The BI-RADS categories were re-assessed using HHUS. Agreement of the BI-RADS categories was evaluated using kappa statistics, and the positive predictive value of each examination was calculated. Logistic regression analysis was performed to identify the mammography and US findings associated with discrepancies in the BI-RADS categorization.

RESULTS
The overall agreement between ABUS and HHUS in all cases was good (79.3%, kappa=0.61, P<0.001). Logistic regression analysis revealed that accompanying suspicious microcalcifications on mammography (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.83 to 11.71; P=0.001) and an irregular shape on US (OR, 5.59; 95% CI, 1.43 to 21.83; P=0.013) were associated with discrepancies in the BI-RADS categorization.

CONCLUSION
The agreement between ABUS and HHUS examinations in the BI-RADS categorization of suspicious breast masses was good. The presence of suspicious microcalcifications on mammography and an irregular shape on US were factors associated with ABUS yielding a lower level of suspicion than HHUS in terms of the BI-RADS category assessment.

Yun|Gabin|G|
Kim|Sun Mi|SM|
Yun|Bo La|B|
Ahn|Hye Shin|HS|
Jang|Mijung|M|


VA mental health clinician experiences and attitudes toward OpenNotes.

Abstract:
OBJECTIVE
To describe Department of Veterans Affairs (VA) mental health clinician attitudes toward and experiences with OpenNotes (also known as Blue Button), which provides patients direct access to clinical notes online.

METHOD
A 35-item online survey was administered to 263 mental health clinicians and nurses from one VA Medical Center.

RESULTS
Seventy-nine percent of eligible subjects participated. Most respondents agreed or somewhat agreed that OpenNotes is a good idea in general, but only half agreed that making mental health notes available online is a good idea. Most believed that patients will better remember plans of care and be better prepared for visits. Most also felt that patients will worry more and request changes in notes. Many clinicians reported being less detailed and changing the tone of their notes.

CONCLUSION
As a group, mental health clinicians are positive about OpenNotes in general but ambivalent about the use of OpenNotes in mental health care. The results call for research on outcomes of OpenNotes use in mental health and to develop education and support to help clinicians adapt to OpenNotes.

Dobscha|Steven K|SK|
Denneson|Lauren M|LM|
Jacobson|Laura E|LE|
Williams|Holly B|HB|
Cromer|Risa|R|
Woods|Susan|S|

D014493:United States Department of Veterans Affairs

Mental health
Veterans
Attitude of health personnel
Electronic health records
Health services research


Understanding and Increasing Influenza Vaccination Acceptance: Insights from a 2016 National Survey of U.S. Adults.

Abstract: Background: The percentage of adults in the U.S. getting seasonal influenza vaccination has not changed significantly since 2013 and remains far below the federal government's 70% target. Objective: This study assessed and identified characteristics, experiences, and beliefs associated with influenza vaccination using a nationally representative survey of 1005 U.S. adults 19 years old and older. Methods: The sample was drawn from the National Opinion Research Center's AmeriSpeak Panel, a probability-based panel designed to be representative of the U.S. household population. Results: Overall, 42.3% received an influenza vaccination in the past 12 months, with rates highest for non-Hispanic Whites and Blacks and those 65 years old and older. Hispanic respondents and those under 64 years old were much less likely to get an influenza vaccination. They were also less aware of the recommendation, less informed about influenza and the benefits of vaccination, and least confident in the vaccine. Conclusions: Increasing influenza vaccination coverage in the U.S. requires a greater focus on 19-64 year-olds, particularly those 50 to 64, Hispanics and continued focus on those with diabetes and asthma. Efforts need to increase awareness of influenza vaccination recommendations, foster a sense of being well informed about influenza vaccination benefits and the risks associated with non-vaccination, and increase confidence that there are meaningful benefits from receiving an influenza vaccination.

Nowak|Glen J|GJ|0000-0002-9153-2189
Cacciatore|Michael A|MA|
Len-Ríos|María E|ME|

D010342:Patient Acceptance of Health Care

influenza
influenza vaccination
vaccine acceptance
adult vaccination


Traditional Chinese medicine for lipid metabolism disorders.

Abstract: Dyslipidemia significantly contributes to the development of cardiovascular disease (CVD), which is the most common cause of morbidity and mortality in China. Statins are the first-line therapy for reducing LDL-C serum levels. However, they have adverse effects, which restrict their clinical application. Traditional Chinese medicine (TCM) preparations have been increasingly described for their beneficial effects in hyperlipidemic patients. Existing data show that the lipid-regulating effects of TCM may be related to: (1) inhibiting intestinal absorption of lipids; (2) reducing endogenous cholesterol synthesis; (3) regulating cholesterol transport; (4) promoting the excretion of cholesterol in the liver; (5) regulating transcription factors related to lipid metabolism. This study provides an overview of recent studies and elaborates the underlying mechanisms of lipid-regulation by TCM.

traditional Chinese medicine
Dyslipidemia
underlying mechanisms


Mathematical modeling of COD removal via the combined treatment of domestic wastewater and landfill leachate based on the PACT process.

Abstract: The experiments performed in this study consisted of 16 batch reactors fed different mixtures of landfill leachate combined with synthetic wastewater treated using the Powdered Activated Carbon Treatment (PACT) process. The objective was to measure the COD mass removal per liter each day for each reactor using two models: the first model combined the variables PAC concentration (0 g·L(-1), 2 g·L(-1), 4 g·L(-1), and 6 g·L(-1)) and leachate rate in the wastewater (0%, 2%, 5%, and 10%), and the second model combined the PAC concentration and the influent COD. The Response Surface Methodology with Central Composite Design was used to describe the response surface of both models considered in this study. Domestic wastewater was produced under controlled conditions in the laboratory where the experiments were performed. The results indicated that the PAC effect was null when the influent did not contain leachate; however, as the concentration of leachate applied to the mixture was increased, the addition of a higher PAC concentration resulted in a better COD mass removal in the reactors. The adjusted R(2) values of the two models were greater than 0.95, and the predicted R(2) values were greater than 0.93. The models may be useful for wastewater treatment companies to calculate PAC requirements in order to meet COD mass removal objectives in combined treatment.

Fernández Bou|Ángel S|ÁS|
Nascentes|Alexandre Lioi|AL|
Costa Pereira|Barbara|B|
Da Silva|Leonardo Duarte Batista|LD|
Alberto Ferreira|João|J|
Campos|Juacyara Carbonelli|JC|

D057919:Biological Oxygen Demand Analysis

D052918:Environmental Restoration and Remediation

Combined treatment of landfill leachate and sewage

mathematical model of COD removal from leachate


Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study.

Abstract:
BACKGROUND
Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.

METHODS
A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.

RESULTS
Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).

CONCLUSIONS
In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Dalfino|Lidia|L|
Puntillo|Filomena|F|
Ondok|Maria Josephine Mura|MJ|
Mosca|Adriana|A|
Monno|Rosa|R|
Coppolecchia|Sara|S|
Spada|Maria Luigia|ML|
Bruno|Francesco|F|
Brienza|Nicola|N|

acute kidney injury
critically ill
colistin
ascorbic acid
colistimethate sodium


Feelings of depression, pain and walking difficulties have the largest impact on the quality of life of people with multiple sclerosis, irrespective of clinical phenotype.

Abstract:
BACKGROUND
The symptoms that have the largest impact on health-related quality of life (HRQoL) in people with multiple sclerosis (MS) may vary by MS phenotype (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)). Knowing these symptoms assists in symptom management.

OBJECTIVE
To examine the associations between 13 common MS symptoms and HRQoL in the total sample and stratified by MS phenotype.

METHOD
The study included 1985 participants. HRQoL was measured with two multi-attribute utility instruments: assessment of quality of life with eight dimensions (AQoL-8D) and European quality of life with five dimensions and five levels for each dimension (EQ-5D-5L). Multivariable linear regression was used to identify the symptoms that had the largest impact on the HRQoLs.

RESULTS
Feelings of depression, pain, fatigue, and feelings of anxiety were most strongly associated with AQoL-8D and EQ-5D-5L. Walking difficulties additionally contributed to reduced EQ-5D-5L. The strongest single predictors in the multivariable analyses were feelings of depression or pain for AQoL-8D and walking difficulties for EQ-5D-5L, irrespective of MS phenotype.

CONCLUSION
The strongest single predictors for the AQoL-8D and EQ-5D-5L were feelings of depression, pain and walking difficulties, irrespective of MS phenotype. Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS.

Zhang|Yan|Y|
Taylor|Bruce V|BV|
Simpson|Steve|S|
Blizzard|Leigh|L|
Campbell|Julie A|JA|
Palmer|Andrew J|AJ|
van der Mei|Ingrid|I|


Molasses melanoidin-like products enhance phytoextraction of lead through three Brassica species.

Abstract: Previously, it has been suggested that melanoidin-like products (MLP) from sugarcane molasses may accelerate copper phytoextraction. In this study, we evaluated the facilitatory effect of MLP on phytoextraction in a medium including cadmium or lead, the concentrations of which were adjusted around the regulation values of the Soil Contamination Countermeasures Act in Japan. Three Brassica species were tested based on their fast growth, high biomass productivity, and high heavy metal absorption. Both biomass and lead uptake in the nutrient medium with 1 mM lead nitrate were significantly increased by the addition of MLP, and almost all of the lead was accumulated in the root tissue. Therefore, MLP were able both to detoxify lead ions and to improve their bioavailability in Brassica species. In contrast, only these species with MLP or citric acid survived in the nutrient medium with 1 mM cadmium sulfate. The phytoextraction of cadmium using these species was therefore impractical under the Act.

Brassica species
sugarcane molasses
melanoidin


Detection of pregnancy-associated glycoproteins in milk and blood as a test for early pregnancy in dairy cows.

Abstract: The objective of our study was to evaluate 2 pregnancy-associated glycoprotein (PAG)-based enzyme-linked immunosorbent assays (ELISAs) for use with either blood or milk. From 12 dairy farms, 116 Montbéliarde or Holstein cows were selected that had either undergone artificial insemination (AI; n = 102) or had calved (n = 14) 2-3 months earlier and had not undergone any further AI. Serum, plasma, and milk were obtained from all cows; serum and plasma were analyzed using the blood pregnancy test and milk using the milk pregnancy test. No false-positive results were observed when samples of the 14 noninseminated cows were tested. Cows undergoing AI were sampled at ~16, 30, and 41 days post-AI. An additional milk sample was taken at ~53 days post-AI. To establish whether the inseminated cows were pregnant, the cows were subjected to transrectal ultrasonography (TU) on or around day 41. Of the 102 inseminated cows, 63 were confirmed pregnant by TU. By day 30, the serum, plasma, and milk ELISAs demonstrated 100%, 100%, and 98.1% sensitivity and 88.6%, 88.9%, and 90.3% specificity, respectively, with potential pregnancy losses 30-41 days post-AI. Accuracy obtained on serum, plasma, and milk at ~41 days post-AI and on milk at ~53 days post-AI ranged from 97.4% to 100%. There were no differences of practical significance in performance between the blood and milk ELISAs for the sampling dates chosen. This new diagnostic capability with milk samples offers a major improvement in bovine reproductive management.

Commun|Loïc|L| Velek|Katherine|K| Barbry|Jean-B|JB| Pun|San|S| Rice|Anna|A| Mestek|Anton|A| Egli|Christoph|C| Leterme|Serge|S|

pregnancy-associated glycoproteins
Dairy cows
pregnancy detection


Intra-Operative Neural Response Telemetry and Acoustic Reflex Assessment using an Advance-In-Stylet Technique and Modiolus-Hugging: A prospective cohort study.

Abstract:
OBJECTIVES
The development of cochlear implant (CI) electrode arrays has focused on the use of a minimally invasive technique involving a modiolus-hugging placement of the electrode. The aim of this study was to evaluate the "advance-in-stylet" (AIS) technique compared to the advance-off-stylet (AOS) technique recommended for the current cochlear Nucleus(®) device. In the AIS technique, the stylet is not removed. We evaluated the electrical auditory thresholds measured when the stylet was removed (modiolus-hugging) compared to measurements taken with the stylet in place (lateral wall cochlea electrode placement).

METHODS
In this prospective cohort study, 30 consecutive patients received unilateral Nucleus Freedom(®) CIs using AIS insertion. Measurement of the acoustic reflex (AR) and neural response telemetry (NRT) were performed with the stylet in place (lateral wall placement of the electrodes) and then removed (perimodiolar placement), and the results compared. The responses were measured in the basal, middle and apical turns in both groups-with and without stylet.

RESULTS
The AIS surgery was completed without complication in 30 patients (16 males and 14 females, age range 3-54 years [mean 11]). Based on neural response telemetry, only apical electrodes showed statistically significant differences in thresholds, but the AR was not significantly different before or after stylet removal in any of the electrode groups tested.

CONCLUSIONS
The effects of modiolus-hugging do not seem to result in a large difference in electrical stimulation thresholds so, in difficult cases, the stylet may be left in place without significantly changing the thresholds, except perhaps at the apical turn.


Synthesis of some steroidal mitocans of nanomolar cytotoxicity acting by apoptosis.

Abstract: Several steroids (abiraterone, prednisone, testosterone, cholesterol) and the BCL-2 inhibitor bexarotene were used as starting materials to synthesize iperazinyl-spacered rhodamine B conjugates. The conjugates were screened for their cytotoxicity in SRB assays against several human tumor cell lines and found to be active in a low μM to nM range. The conjugate derived from testosterone held an EC50 = 59 nM against MCF-7 tumor cells and acted mainly by necrosis. The prednisone conjugate, however, was less cytotoxic but acted mainly by apoptosis and held a moderate selectivity against MCF-7 tumor cells.

D004354:Drug Screening Assays, Antitumor

Synthesis
Steroids
Cytotoxicity
Apoptosis
Prednisone
Rhodamine B


Robust Visual Tracking Based on Adaptive Multi-Feature Fusion Using the Tracking Reliability Criterion.

Abstract: Multi-resolution feature fusion DCF (Discriminative Correlation Filter) methods have significantly advanced the object tracking performance. However, careless choice and fusion of sample features make the algorithm susceptible to interference, leading to tracking failure. Some trackers embed the re-detection module to remedy tracking failures, yet distinguishing ability and stability of the sample features are scarcely considered when training the detector, resulting in low effectiveness detection. Firstly, this paper proposes a criterion of feature tracking reliability and conduct a novel feature adaptive fusion framework. The feature tracking reliability criterion is proposed to evaluate the robustness and distinguishing ability of the sample features. Secondly, a re-detection module is proposed to further avoid tracking failures and increase the accuracy of target re-detection. The re-detection module consists of multiple SVM detectors trained by different sample features. When the tracking fails, the SVM detector trained by the most reliable sample feature will be activated to recover the target and adjust the target position. Finally, comparison experiments on OTB2015 and UAV123 databases demonstrate the accuracy and robustness of the proposed method.

Zhou|Lin|L|0000-0002-2700-834X Wang|Han|H| Jin|Yong|Y| Hu|Zhentao|Z| Wei|Qian|Q| Li|Junwei|J| Li|Jifang|J|

correlation filter
feature tracking reliability criterion
adaptive feature fusion
multiple online detectors
visual object tracking


Tagging of individual embryos with electronic p-Chips.

Abstract: Collecting information about biochemical processes occurring inside a single cell or embryo is traditionally done either using fluorescent dyes with microscopy or via microelectrode voltage-clamp techniques. This paper demonstrates that a more direct method - transmission of information using an electronic chip implanted in an embryo - is feasible. A light-activated microtransponder with dimensions 250 μm × 250 μm × 100 μm (a "p-Chip") was implanted into a blastula-stage frog (Xenopus laevis) embryo. To implant the chip, a small slit is made in the blastocoel roof with an electrolytically-sharpened tungsten needle, and the p-Chip is inserted using fine forceps. The chip is activated when illuminated by a 60 mW focused laser beam, which causes the p-Chip to send its numeric ID to a nearby receiver. At no time during signal transmission does a wire or other type of object come in contact with or penetrate the epidermal layer covering the p-Chip. The embryo survives the procedure, extruding the chip after approximately 3 h. The method shows promise for studies including voltage potential, pH and other parameters.

Mandecki|Wlodek|W|
Rodriguez|Efrain Frank|EF|
Drawbridge|Julie|J|

D055615:Electrical Equipment and Supplies

Single cell
Microtransponder
Xenopus laevis
Identification
Microchip
RFID


Age-induced changes in the lower limb muscle activities during uphill walking at steep grades.

Abstract:
BACKGROUND
Uphill walking is particularly challenging for elderly persons. However, there is a lack of age-differentiated studies investigating the underlying differences in muscle activation when walking on sloped surfaces. These studies are needed, e.g., for planning of evacuations of large modern cruise ships with long walking distances on often inclined surfaces.

METHODS
An age-differentiated, gender-balanced study with 26 young (20-30 years) and 26 elderly people (60-77 years) was therefore conducted, investigating uphill walking at 7° and at 14° contrasted to level walking on a treadmill. EMG signals of musculus gluteus maximus (GMAX), m. biceps femoris (BF), m. rectus femoris (RF), m. vastus medialis (VM), m. gastrocnemius medialis (GAS) and m. soleus (SOL) were analysed with regard to mean and maximum muscle activities and timing during the gait cycle.

RESULTS
The results showed that walking uphill at 14° was highly strainful for elderly people. In line with previous research, young people mostly "pushed" themselves uphill with the GAS and SOL. In contrast, elderly people not only used the known compensatory ability of hip muscles to propel the trailing leg, but also showed a high level of BF activation prolonged until the mid-stance phase at the steepest uphill gradient of 14°.

SIGNIFICANCE
The strikingly long activation of the BF until the mid-stance phase in elderly people at steep gradients is an unexpected, new finding. It suggests that, instead of pushing, elderly people "pull" themselves uphill. In cases of evacuations, the lower physical fitness levels of elderly passengers and their increased need for assistance on inclined surfaces have to be planned for in advance. Considering the findings in (home) training programmes might help elderly people to strengthen lower limb muscles and to enhance the efficiency of muscle activation patterns enabling them to manage steep inclinations more easily.

Kwee-Meier|Sonja Th|ST|
Mertens|Alexander|A|
Jeschke|Sabina|S|

Uphill walking
Elderly
Incline
EMG
Gait cycle


Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens.

Abstract: House dust mites (HDMs) are sources of an extensive repertoire of allergens responsible for a range of allergic conditions. Technological advances have accelerated the identification of these allergens and characterized their putative roles within HDMs. Understanding their functional bioactivities is illuminating how they interact with the immune system to cause disease and how interrelations between them are essential to maximize allergic responses. Two types of allergen bioactivity, namely proteolysis and peptidolipid/lipid binding, elicit IgE and stimulate bystander responses to unrelated allergens. Much of this influence arises from Toll-like receptor (TLR) 4 or TLR2 signalling and, in the case of protease allergens, the activation of additional pleiotropic effectors with strong disease linkage. Of related interest is the interaction of HDM allergens with common components of the house dust matrix, through either their binding to allergens or their autonomous modulation of immune receptors. Herein, we provide a contemporary view of how proteolysis, lipid-binding activity and interactions with polysaccharides and polysaccharide molecular recognition systems coordinate the principal responses which underlie allergy. The power of the catalytically competent group 1 HDM protease allergen component is demonstrated by a review of disclosures surrounding the efficacy of novel inhibitors produced by structure-based design.

D000069452:Pathogen-Associated Molecular Pattern Molecules

polysaccharide
house dust mite
Toll-like receptors
protease allergen
lipid-binding protein


Anti-leukemia activity of PVP-coated silver nanoparticles via generation of reactive oxygen species and release of silver ions.

Abstract: Silver nanoparticles (AgNPs) have anti-cancer effect. However, whether and how these particles could inhibit the growth of acute myeloid leukemia (AML) cells is unclear. In the present study, we prepared AgNPs with various sizes and investigated their cytotoxic effect on AML cells. We found that AgNPs could inhibit the viability of AML cells including the isolates from AML patients. AgNPs caused the production of reactive oxygen species (ROS), losses of mitochondrial membrane potential (MMP), DNA damage and apoptosis. Both vitamin C (Vit C) and N-acetyl-L-cysteine (NAC) could completely reverse the generation of ROS upon AgNPs, however only NAC but not Vit C could protect the cells from losses of MMP, DNA damage and apoptosis thoroughly. Similar results were obtained when cells were treated with silver ions alone. As NAC was not only an antioxidant to scavenge ROS but also a silver ion chelator, these data supported the model that both generation of ROS and release of silver ions played critical roles in the AgNPs-induced cytotoxic effect against AML cells. Taken together, this work elucidated the cytotoxic effect of AgNPs on AML cells and their underlying mechanism and might have significant impact on AML treatment.

Guo|Dawei|D| Zhu|Lingying|L| Huang|Zhihai|Z| Zhou|Haixia|H| Ge|Yue|Y| Ma|Wenjuan|W| Wu|Jie|J| Zhang|Xiuyan|X| Zhou|Xuefeng|X| Zhang|Yu|Y| Zhao|Yun|Y| Gu|Ning|N|

Silver nanoparticles
Reactive oxygen species
Silver ions
Acute myeloid leukemia
Cytotoxicity


Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A.

Abstract: CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, CD44s levels correlate with EGFR signature and predict poor prognosis in glioblastomas. Because Rab7A facilitates trafficking of many RTKs to lysosomes, our findings identify CD44s as a Rab7A regulator to attenuate RTK degradation.

Wang|Wei|W|
Zhang|Honghong|H|
Liu|Sali|S|
Kim|Chung Kwon|CK|
Xu|Yilin|Y|
Hurley|Lisa A|LA|
Nishikawa|Ryo|R|
Nagane|Motoo|M|
Hu|Bo|B|
Stegh|Alexander H|AH|
Cheng|Shi-Yuan|SY|
Cheng|Chonghui|C|

D002460:Cell Line
D011992:Endosomes
D066246:ErbB Receptors
D005909:Glioblastoma
D057809:HEK293 Cells
D006801:Humans
D018960:Hyaluronan Receptors
D008247:Lysosomes
D020033:Protein Isoforms
D021381:Protein Transport
D015398:Signal Transduction
D020691:rab GTP-Binding Proteins
D000090802:rab7 GTP-Binding Proteins


WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes.

Abstract: Adiponectin, an adipokine with insulin-sensitizing effect, is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW adiponectin oligomers possess the most potent insulin-sensitizing activity. WSF-P-1(N-methyl-1,2,3,4,5,6-hexahydro-1,1,5,5-tetramethyl-7H-2,4α-methanonaphthalen-7-amine) is derived from natural sesquiterpene longifolene by chemical modifications. We found that WSF-P-1 activates AMPK in both 3T3-L1 adipocytes and 293T cells in this study. Activation of AMPK by WSF-P-1 promotes the assembly of HMW adiponectin and increases the HMW/total ratio of adiponectin in 3T3-L1 adipocytes. We demonstrated that the Ca2+-dependent CaMKK signaling pathway is involved in WSF-P-1-induced AMPK activation and adiponectin multimerization. WSF-P-1 also activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes, making it a potential drug candidate for the treatment of type 2 diabetes, obesity, and other obesity-related metabolic diseases.

D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase

AMPK
adiponectin
CaMKK
glucose uptake
insulin sensitivity


Diagnostic utility of CT in differentiating between ruptured ovarian corpus luteal cyst and ruptured ectopic pregnancy with hemorrhage.

Abstract:
BACKGROUND
To evaluate the performance of computed tomography (CT) as a diagnostic aid to differentiate between ruptured ovarian corpus luteal cyst (ROCLC) and ruptured ectopic pregnancy with hemorrhage (REPWH).

METHODS
A total of 36 patients treated at our hospitals for ROCLC and REPWH from June 2014 to August 2017 were included in this study. Based on the diagnosis, the study population was divided into ROCLC group (n = 21) and REPWH group (n = 15). CT scans were performed for all patients prior to treatment. The size of the cystic shadows and the depth of the pelvic effusion were analyzed and compared with independent sample Student's t test and Fisher's exact test.

RESULTS
Cystic shadows with maximum diameters ≥3.0 cm presented in 16 patients with ROCLC and 1 patient with REPWH, while 4 patients with ROCLC and 9 patients with REPWH exhibited cystic shadows with maximum diameters <3.0 cm. The mean diameters along the major and minor axes in the two groups were 3.76 ± 1.11 cm and 2.93 ± 0.98 cm, 1.96 ± 0.65 cm and 1.60 ± 0.55 cm, respectively (p < 0.001). The mean depth of the pelvic effusion in patients with ROCLC and REPWH were 5.20 ± 2.47 cm and 6.96 ± 2.07 cm, respectively (p = 0.038).

CONCLUSION
The cystic shadow of ROCLC is larger than that of the REPWH. The depth of the pelvic effusion of REPWH is deeper than that of the ROCLC. CT can help differentiate between ROCLC and REPWH based on the size of the cystic shadow and the depth of pelvic effusion in the adnexal area.

Ruptured ovarian corpus luteal cyst (ROCLC)

Ruptured ectopic pregnancy with hemorrhage (REPWH)


Delirium risk of histamine-2 receptor antagonists and proton pump inhibitors: A study based on the adverse drug event reporting database in Japan.

Abstract:
OBJECTIVE
Although histamine-2 receptor antagonists (H2RAs) have been shown to be more likely to cause delirium than proton pump inhibitors (PPIs), these results were not adjusted for potential confounding factors. Accordingly, we investigated whether H2RAs and PPIs are risk factors for delirium, even when adjusting for other risk factors by analyzing adverse drug event reports compiled in the post-marketing stages of drugs provided by the Japanese regulatory authorities.

METHOD
We analyzed 577,431 reports in the Japanese Adverse Drug Event Report database from April 2004 to July 2020.

RESULTS
Of all reports analyzed, 2532 described delirium, and 574,899 described other adverse events. Delirium was associated with H2RAs (crude reporting odds ratio, ROR, 4.17; 95% CI, 3.34-5.22) but not PPIs (crude ROR 0.62; 95% CI 0.43-0.90). Even with adjustment for age, sex, history of dementia or depression, and concomitant drugs reported as risk factors for delirium, the use of H2RAs showed a significantly higher adjusted ROR than that of PPIs (H2RAs: adjusted ROR 3.99; 95% CI 3.18-5.01 and PPIs: adjusted ROR 0.58; 95%CI 0.40-0.84).

CONCLUSIONS
These results suggest that, from a cognitive perspective, PPIs may be preferable to H2RAs for patients with or at risk for delirium.

Kikkawa|Nao|N| Sogawa|Rintaro|R| Monji|Akira|A| Sumi|Shintaro|S| Murakawa-Hirachi|Toru|T| Kubo|Toshiki|T| Eguchi|Yuko|Y| Miyamoto|Yuki|Y| Kamo|Masahiro|M| Tobita|Shuko|S| Yukawa|Misako|M| Uchida|Rina|R| Egoshi|Masayoshi|M| Shimanoe|Chisato|C|

Delirium
Histamine-2 receptor antagonist
Proton pump inhibitor


Chlorophyll b degradation by chlorophyll b reductase under high-light conditions.

Abstract: The light-harvesting chlorophyll a/b binding protein complex of photosystem II (LHCII) is the main antenna complex of photosystem II (PSII). Plants change their LHCII content depending on the light environment. Under high-light conditions, the content of LHCII should decrease because over-excitation damages the photosystem. Chlorophyll b is indispensable for accumulating LHCII, and chlorophyll b degradation induces LHCII degradation. Chlorophyll b degradation is initiated by chlorophyll b reductase (CBR). In land plants, NON-YELLOW COLORING 1 (NYC1) and NYC1-Like (NOL) are isozymes of CBR. We analyzed these mutants to determine their functions under high-light conditions. During high-light treatment, the chlorophyll a/b ratio was stable in the wild-type (WT) and nol plants, and the LHCII content decreased in WT plants. The chlorophyll a/b ratio decreased in the nyc1 and nyc1/nol plants, and a substantial degree of LHCII was retained in nyc1/nol plants after the high-light treatment. These results demonstrate that NYC1 degrades the chlorophyll b on LHCII under high-light conditions, thus decreasing the LHCII content. After the high-light treatment, the maximum quantum efficiency of the PSII photochemistry was lower in nyc1 and nyc1/nol plants than in WT and nol plants. A larger light-harvesting system would damage PSII in nyc1 and nyc1/nol plants. The fluorescence spectroscopy of the leaves indicated that photosystem I was also damaged by the excess LHCII in nyc1/nol plants. These observations suggest that chlorophyll b degradation by NYC1 is the initial reaction for the optimization of the light-harvesting capacity under high-light conditions.

Chlorophyll b reductase
High-light conditions
Arabidopsis
Light-harvesting complex