Increased subclinical atherosclerosis in patients with chronic plaque psoriasis.

Abstract:
BACKGROUND
Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls.

METHODS
Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors.

RESULTS
Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls.

CONCLUSION
The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.

Evensen|Kristin|K|
Slevolden|Ellen|E|
Skagen|Karolina|K|
Rønning|Ole Morten|OM|
Brunborg|Cathrine|C|
Krogstad|Anne-Lene|AL|
Russell|David|D|

Atherosclerosis
Psoriasis
Carotid stenosis
Carotid IMT
Carotid plaques
Carotid ultrasound
Co-morbidity


Mentoring in Global Cancer Research Training.

Abstract: This manuscript illustrates general concepts of mentoring in low- and middle-income countries (LMICs). The focus of this manuscript is on public health research based on our experiences with the Cancer Epidemiology Education in Special Populations (CEESP) Program which is further illustrated in this Supplement. While the CEESP Program provides research training in global and US minority settings, this manuscript is focused on the global aspects of the program. We describe the process of selecting students into the CEESP Program, the process of mentoring them, and the preparation of the mentoring sites. We emphasize the review of the CEESP mentors in LMICs and put forward recommendations for enhancing their mentoring skills and disseminating the experience to other US and global institutions interested in global cancer education.

Soliman|Amr S|AS|
Chamberlain|Robert M|RM|
Michalek|Arthur|A|
O'Donnell|Joseph F|JF|
Gallagher|Richard|R|

Mentoring
Global
Research training
Low- and middle-income countries
Cancer education


Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis.

Abstract: Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca(2+) release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca(2+) imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca(2+) ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca(2+) imaging, we found that the depletion of ER Ca(2+) stores by TG elicited a transient rise in cytoplasmic Ca(2+), followed by sustained increase depending on extracellular Ca(2+). But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na(+)/Ca(2+) exchanger inhibitor), inhibited the relatively high [Ca(2+)]i. NPS R-568 also resulted in the same effect, and the duration of [Ca(2+)]i increase was eliminated completely by U73122 and was reduced in the absence of [Ca(2+)]o. NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis.

Wu|Qiu-yue|QY| Sun|Ming-rui|MR| Wu|Chun-li|CL| Li|Yang|Y| Du|Jing-jing|JJ| Zeng|Jing-ya|JY| Bi|Hai-liang|HL| Sun|Yi-hua|YH|

D000818:Animals
D017209:Apoptosis
D020013:Calcium Signaling
D005110:Extracellular Space
D005434:Flow Cytometry
D015544:Inositol 1,4,5-Trisphosphate
D042541:Intracellular Space
D015640:Ion Channel Gating
D017208:Rats, Wistar
D044169:Receptors, Calcium-Sensing
D018805:Sepsis
D013601:T-Lymphocytes
D050052:TRPC Cation Channels
D019284:Thapsigargin
D010738:Type C Phospholipases

Calcium-sensing receptor
Lymphocytes
Sepsis
Cytokine
Transient receptor potential channel


Interaction mechanism of kafirin with ferulic acid and tetramethyl pyrazine: Multiple spectroscopic and molecular modeling studies.

Abstract: Ferulic acid (FA) and tetramethyl pyrazine (TMP) are intrinsic bioactive compounds in baijiu, and kafirin is the major protein of sorghum, which is the raw material of baijiu. In this study, the interactions of kafirin-FA and kafirin-TMP were investigated by multiple spectroscopic and molecular modeling techniques. Fluorescence spectra showed that intrinsic fluorescence of kafirin drastically quenched because of the formations of kafirin-FA and kafirin-TMP complexes. The CD studies indicated that the combination with FA or TMP decreased the α-helix content of kafirin slightly. The shifts and intensity changes of UV-Vis, FTIR and fluorescence spectra confirmed the formations of complexes. Moreover, the molecular docking and molecular dynamics studies showed that hydrophobic interactions and hydrogen bonds played major roles in the formations of kafirin-FA and kafirin-TMP complexes, and the formations of complexes made kafirin structures more compact. This work is of great importance for further quality improvement in baijiu and alcoholic beverages.

Zhu|Lin|L| Song|Xuebo|X| Pan|Fei|F| Tuersuntuoheti|Tuohetisayipu|T| Zheng|Fuping|F| Li|Qing|Q| Hu|Siqi|S| Zhao|Feifei|F| Sun|Jinyuan|J| Sun|Baoguo|B|

Tetramethyl pyrazine (Pub Chem CID: 14296)


The prognostic role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

Abstract:
BACKGROUND
Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be prognostic markers in various types of cancers. In this study, we retrospectively investigated the prognostic role of NLR and PLR in stage III non-small cell lung cancer patients (NSCLC) treated with concurrent chemoradiotherapy (CCRT).

MATERIALS AND METHODS
Seventy-nine stage III NSCLC patients treated with definitive CCRT were retrospectively evaluated. All patients received conformal RT with a total dose of 60-66 Gy with CCRT. The optimal cutoff values identified by receiver operating characteristic curve were 155 for PLR and 3.21 for NLR for overall survival (OS) and 142 and 3.21, respectively, for progression-free survival (PFS).

RESULTS
Median age of the study population was 58 years with 72 (91%) males. Stages IIIA, IIIB, and IIIC were found in 21 (26.6%), 48 (60.8%), and 10 (12.7%) patients, respectively. Patients with a PLR <155 had a significantly longer OS (P = 0.038) compared with patients who had a higher PLR. The NLR and other parameters were not found to be in correlation with OS. In multivariable analysis, the PLR and lymphocyte count were significantly associated with OS (hazard ratio [HR]: 2.29, 95% confidence interval [CI]: 1.29-4.08, P = 0.005 and HR: 2.00, 95% CI: 1.17-3.42, P = 0.011, respectively). The PLR and lymphocyte count were identified as independent prognostic factors of poor PFS (HR: 2.08, 95% CI: 1.17-3.69, P = 0.012 and HR: 1.83, 95% CI: 1.08-3.08, P = 0.024, respectively).

CONCLUSION
Our results support the prognostic role of pretreatment PLR and lymphocyte count in stage III NSCLC patients treated with concurrent radiotherapy.

Yılmaz|Ufuk|U| Ozdemir|Ozer|O| Batum|Ozgur|O| Ermin|Sinem|S|

neutrophil-lymphocyte ratio
platelet-lymphocyte ratio
Lung cancer
prognosis


Emergency Department Changes to Combat COVID-19 in Oman.

Abstract: Our hospital is one of the tertiary care hospitals in Oman receiving coronavirus disease (COVID-19; C19) patients. To meet the expected surge of patients, a number of changes was made to the emergency department (ED), especially regarding capacity building and patient flow. At first, few changes were made to the main ED, which mainly includes the addition of a COVID suspect room with the use of a separate resuscitation area. The major drawback of the abovementioned system was the inability to see more than 2 patients simultaneously. A later separate COVID emergency department (CED) was used. In the CED, pending admissions was the major problem, as the C19 ward and C19 intensive care unit were becoming full; this problem was solved through central command help. In the normal ED, the main problem was the presentation of C19-positive patients sometimes hiding their symptoms and reaching inside the main ED, exposing the staff and patients. In order to combat this problem, all patients with an acute respiratory problem, even if C19 is not suspected, were taken to the corner cubicle. In this report, the changes made in the ED to combat C19 spread are discussed.

emergency
COVID-19
Oman
pandemics
personal protective equipment


Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture.

Abstract: This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete-event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision-making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E-factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium-sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed-batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision-making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854-866, 2017.

antibody manufacture
process economics
fed-batch
continuous chromatography
perfusion culture


A 2D finite element model for shear wave propagation in biological soft tissues: Application to magnetic resonance elastography.

Abstract: Dynamic elastography is a virtual palpation tool that aims at investigating the mechanical response of biological soft tissues in vivo. The objective of this study is to develop a finite element model (FEM) with low computational cost for reproducing realistically wave propagation for magnetic resonance elastography in heterogeneous soft tissues. Based on the first-order shear deformation theory for moderately thick structures, this model is developed and validated through comparison with analytical formulations of wave propagating in heterogeneous, viscoelastic infinite medium. This 2D-FEM is then compared to experimental data and a 3D-FEM using a commercial software. Our FEM is a powerful promising tool for investigations of magnetic resonance elastography.

finite element model
shear wave propagation
magnetic resonance elastography
heterogeneity
shear deformation theory
viscoelasticity


An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in an Extended Flexible Non-homologous End Joining Complex.

Abstract: DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). Yet, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcs (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.

D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase

DNA-dependent serine/threonine protein kinase (DNA-PK)


Investigation of low-temperature performances of hybrid catalysts with different chain length OHC reductants.

Abstract: In the present work, NO conversion efficiency of the hybrid catalysts at low temperatures was investigated. ANP-TVM and ANP-TVC-TVM hybrid catalysts for OHC-SCR performance were prepared by the impregnation method. The properties of catalysts were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) and X-ray diffraction (XRD) analyses. The NO conversion ratios with real diesel exhaust gases were performed using oxygenated hydrocarbon reductants such as ethanol, propanol, n-butanol and n-penthanol. Performances of the hybrid catalysts at different engine loads and low temperatures were investigated. It was determined that ANP-TVC-TVM gave better results at all temperatures and loads. In general, the performance of ANP-TVC-TVM hybrid catalyst was superior with ethanol reductant except for at 1 kW engine load. The maximum NO conversion ratio was 90.6% on the ANP-TVC-TVM hybrid catalyst with n-butanol at 1 kW engine load and 300°C.

catalyst
reductant
OHC-SCR
NOx
diesel engine


A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Abstract: Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology.

Kamp|Marcel A|MA|
Lieshout|Jasper H van|JHV|
Dibué-Adjei|Maxine|M|
Weber|Jasmin K|JK|
Schneider|Toni|T|
Restin|Tanja|T|
Fischer|Igor|I|
Steiger|Hans-Jakob|HJ|

Mortality
Mouse
Mouse model
Delayed cerebral ischemia
Subarachnoid hemorrhage
SAH
DCI


Levels of Serum Brain-Derived Neurotropic Factor in Individuals at Ultra-High Risk for Psychosis-Findings from the Longitudinal Youth at Risk Study (LYRIKS).

Abstract:
BACKGROUND
Identifying biomarkers to enrich prognostication and risk predictions in individuals at high risk of developing psychosis will enable stratified early intervention efforts. Brain-derived neurotrophic factor has been widely studied in schizophrenia and in first-episode psychosis with promising results. The aim of this study was to examine the levels of serum brain-derived neurotrophic factor between healthy controls and individuals with ultra-high risk of psychosis.

METHODS
A sample of 106 healthy controls and 105 ultra-high risk of psychosis individuals from the Longitudinal Youth at Risk Study was included in this study. Ultra-high risk of psychosis status was determined using the Comprehensive Assessment of At-Risk Mental State at recruitment. Calgary Depression Scale for Schizophrenia was used to assess the severity of depression. All participants were followed up for 2 years, and ultra-high risk of psychosis remitters were defined by ultra-high risk of psychosis individuals who no longer fulfilled Comprehensive Assessment of At-Risk Mental State criteria at the end of the study period. Levels of brain-derived neurotrophic factor were measured in the serum by enzyme-linked immunosorbent assay method.

RESULTS
The ultra-high risk of psychosis group had significantly higher baseline levels of serum brain-derived neurotrophic factor compared with the control group (3.7 vs 3.3 ng/mL, P=.018). However, baseline levels of serum brain-derived neurotrophic factor did not predict the development of psychosis (OR=0.64, CI=0.40-1.02) or remission (OR=0.83, CI=0.60-1.15) from ultra-high risk of psychosis status.

CONCLUSION
Findings from our study did not support a role for serum brain-derived neurotrophic factor in predicting outcomes in ultra-high risk of psychosis individuals. However, the finding of higher levels of serum brain-derived neurotrophic factor in ultra-high risk of psychosis individuals deserves further study.

Yee|Jie Yin|JY|
Lee|Tih-Shih|TS|
Lee|Jimmy|J|

brain-derived neurotrophic factor
ultra-high risk of psychosis
peripheral markers


Effects of Dietary Exposure to Sulfamethazine on the Hematological Parameters and Hepatic Oxidative Stress Biomarkers in Nile Tilapia (Oreochromis niloticus).

Abstract: Sulfamethazine (SMZ) is one of the most commonly used sulfonamide compounds in fish farming, and its physiological effects on fish are unknown. SMZ was administered to juvenile Nile tilapia (Oreochromis niloticus) at a dose level of 422 mg kg(-1) body weight, for a period of 11 days, via medicated feed. Fish were divided into two groups, the control group (CG) and the group fed with SMZ in feed. The administration of SMZ did not alter the erythrograms and leukograms of the Nile tilapia. The SMZ-fed group showed the same hepatic lipid peroxidation (LPO) concentration as the CG. Nonetheless, the oral administration of SMZ raised the hepatic catalase (CAT) and glutathione S-transferase (GST) activities, the increase probably being sufficient to prevent hepatic LPO production. The oral administration of SMZ affects the hepatic GST and CAT activities of Nile tilapia.

do Nascimento de Queiroz|Sonia Claudia|SC|

Sulfamethazine
Antibiotics
Antioxidant defense
Toxicology


Identification of Two Novel Modifications at Tryptophan Residues.

Abstract: Protein post-translational modifications (PTMs) play important roles in cellular physiology. Mass spectrometry (MS) has been developed into a powerful tool to identify all possible protein modifications. Herein, we describe our efforts to deduce the structures of two unknown modifications at tryptophan (Trp) residues (W + 92 Da and W + 108 Da). The two modifications were further confirmed by aligning the MS/MS fragmentation of synthetic peptide with in-vivo peptide identified. Finally, the mimic experiment elucidated how two Trp modifications occur. This study, therefore, expands current knowledge of Trp modifications.

Zheng|Shuzhen|S| Zhang|Kai|K| Tian|Shanshan|S| He|Xiwen|X| Zhang|Yukui|Y|

Post-translational modifications
Mass spectrometry
Proteomics
Tryptophan modifications


Effects of total flavones from Acanthopanax senticosus on L-type calcium channels, calcium transient and contractility in rat ventricular myocytes.

Abstract: Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge-detection system. Exposure to TFAS resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current-voltage relationship but also shifted the activation and inactivation curves of ICa-L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat ventricular myocytes and consequent negative effect on myocardial contractility.

Guan|Shengjiang|S| Ma|Juanjuan|J| Chu|Xi|X| Gao|Yonggang|Y| Zhang|Ying|Y| Zhang|Xuan|X| Zhang|Fenghua|F| Liu|Zhenyi|Z| Zhang|Jianping|J| Chu|Li|L|

total flavones
L-type calcium channel
calcium transient
myocyte shortening
calcium overload
patch clamp


Simultaneous antagonism of dopamine D1/D2/D3 receptor in the NAc reduces 50-kHz ultrasonic calls in response to rhythmic tactile stroking.

Abstract: Tactile stimulation such as rhythmic stroking elicits 50-kHz ultrasonic vocalizations (USVs) in rats that are thought to reflect positive affective states. Dopaminergic neurotransmission in the nucleus accumbens (NAc) is required for tactile reward-induced 50-kHz USVs; however, it is still unknown whether the accumbal dopaminergic system differentially modulates 50-kHz USV call subtypes induced by rhythmic stroking. We therefore examined both total and categorized 50-kHz USV rate, peak frequency, and duration under dopamine (DA) receptor antagonism in the NAc shell. Bilateral injection of the D1 receptor antagonist SCH 23390 (500 ng/side) plus the D2/D3 receptor antagonist raclopride (25 μg/side) significantly reduced the number of predominantly flat calls with harmonics during stimulation and the number of frequency-modulated (FM) calls after stimulation. In contrast, there were no substantial changes in total and categorized 50-kHz USVs mean peak frequencies and call durations. Therefore, emission of different subtypes of 50-kHz USVs may be differently regulated by dopaminergic transmission. The 50-kHz harmonics and FM USVs induced by rhythmic stroking may be useful behavioral markers for tactile reward in rats.

SCH 23390
Raclopride
Reward
50-kHz calls
Acoustic features
Positive emotion


Prevalence of pterygium in Iran: a systematic review and meta-analysis study.

Abstract:
Background and aim
Pterygium is one of the most prevalent pathologies involving the cornea, which can lead to various vision signs and even reduction in eyesight. No accurate estimate has been reported about the prevalence of pterygium in Iran. Hence, this study aimed to determine the pterygium prevalence in Iran by meta-analysis method.

Methods
Searching for data of the last eleven years (from 2004 to 2015) was conducted using the keywords of pterygium, eye, and Iran in International and domestic indexing services and databases including Iranmedex, Scientific Information Database (SID), Magiran, Irandoc, Medlib, IranPsych, Science Direct, Web of Science (Thomson Reuters), PubMed, and Scopus. The data were analyzed using the meta-analysis method (the random effects model). The disharmony of the studies was investigated using the I2 index. The data were analyzed by STATA Ver.11 software.

Results
In 5 studies conducted in Iran, with a sample size of 10,838 people between 2004 and 2015, the extent of the prevalence was estimated to be 11% (95% CI: 3 to 18%). Also, the prevalence of pterygium in women and men was 18% and 13%, respectively.

Conclusion
According to the published reports from Iran and its comparison with other points in the world, the prevalence of pterygium in Iran is high, especially among women.

Yasemi|Masoud|M|
Bamdad|Shahram|S|
Sarokhani|Diana|D|
Sarokhani|Mandana|M|
Sayemiri|Kourosh|K|
Ahmadi|Nayeb Ali|NA|


Overlapping Surgery Increases Operating Room Efficiency Without Adversely Affecting Outcomes in Total Hip and Knee Arthroplasty.

Abstract:
BACKGROUND
Several recent studies have demonstrated that overlapping surgeries in total hip (THA) and knee (TKA) arthroplasty do not increase the rates of complications, but whether this practice is cost-effective has yet to be addressed in the literature. The purpose of this study is to determine the effect of overlapping surgery on procedural costs and surgical productivity during THA and TKA.

METHODS
We identified all patients undergoing primary THA or TKA from 2015 to 2018 by 18 surgeons at a single orthopedic specialty hospital. Procedural and personnel costs were calculated for each case using a time-driven activity-based costing algorithm. Overlap of surgical time by at least 30 minutes was used to define an overlapping procedure. We compared costs and outcomes between overlapping and nonoverlapping procedures, standardizing all costs to 8-hour time blocks. A multivariate regression analysis was performed to determine independent effect of overlapping procedures on costs and outcomes.

RESULTS
Of the 4786 consecutive procedures, 968 (20.2%) overlapped by at least 30 minutes. Although overlapping rooms increased mean operative time by 8.3 minutes (P < .0001) and operating room personnel costs by $80 per case (<.0001), overlapping surgeons could perform significantly more procedures per 8 hours (7.6 vs 6.4; P < .0001), increasing total 8-hour profit margin by $1215 per procedure. There was no difference in 90-day readmission rate, length of stay, or rates of discharge home between the groups.

CONCLUSION
Overlapping noncritical portions of procedures in primary THA and TKA appear to be both a safe practice and an effective strategy.

Zachwieja|Erik|E|
Yayac|Michael|M|
Wills|Bradley W|BW|
Wilt|Zachary|Z|
Austin|Matthew S|MS|
Courtney|P Maxwell|PM|

D019644:Arthroplasty, Replacement, Hip
D019645:Arthroplasty, Replacement, Knee
D006801:Humans
D007902:Length of Stay
D009873:Operating Rooms
D010351:Patient Discharge
D012189:Retrospective Studies

overlapping surgery
complications
surgical productivity
total hip arthroplasty
total knee surgery


Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system.

Abstract: The blood-brain barrier (BBB) is involved in the pathogeneses of ischemic stroke (IS). Geniposide (GEN), an iridoid glycoside isolated from Gardenia jasminoides Ellis, has been used for the treatment of IS. However, the effects of GEN on the BBB are poorly understood. In vitro disease models of the BBB could be very helpful for the elucidation of underlying mechanisms and the development of novel therapeutic strategies. Therefore, we established an in vitro BBB model composed of primary cultures of brain microvascular endothelial cells and astrocytes. We then used this in vitro model to investigate the effect of GEN on the function of the BBB. Oxygen glucose deprivation and reoxygenation (OGD/R) significantly increased permeability and cell apoptosis in this in vitro BBB model. Notably, GEN pretreatment effectively improved the BBB function by decreasing the permeability of the BBB, promoting expression of tight junction proteins (zonula occludens-1, claudin-5, and occludin) and gamma-glutamyl transpeptidase, increasing transendothelial electrical resistance, mitigating oxidative stress damage and the release of inflammatory cytokines, downregulating the expression levels of matrix metallopeptidases-9 (MMP-9) and MMP-2, and increasing the release of brain derived neurotrophic factor and glial cell derived neurotrophic factor. Therefore, GEN can ameliorate the BBB dysfunction induced by OGD/R conditions through multiple protective mechanisms. The findings suggest that GEN may be an appropriate drug for restoring the barrier function of the BBB.

Li|Changxiang|C| Wang|Xueqian|X| Cheng|Fafeng|F| Du|Xin|X| Yan|Juntang|J| Zhai|Changming|C| Mu|Jie|J| Wang|Qingguo|Q|


Association between metabolic syndrome components and chronic kidney disease among 37,533 old Chinese individuals.

Abstract:
BACKGROUND
Chronic kidney disease (CKD) has become a worldwide health problem among aging populations. However, epidemiological information on Chinese elderly people with CKD is still lacking. This study aimed to investigate the epidemiological features and associated risk factors of CKD in aging population in China.

METHODS
In this cross-sectional study, a total of 37,533 individuals aged ≥ 65 years were enrolled in Binhai from January to December 2018. The crude and standardized prevalence of CKD were calculated. Associations of metabolism-related indicators with CKD were examined using univariate and multivariate analyses.

RESULTS
The overall prevalence of CKD was 17.7% (95% confidence interval 17.3-18.1%) in this Chinese elderly population. The prevalence was 17.5% among men (95% CI 17.0-18.1%) and 17.8% among women (95% CI 17.3-18.4%). The mean eGFR was 84.22 (SD ± 12.87) mL/min/1.73 m2, with the median value higher for women than for men.

CONCLUSION
Our study shows a high prevalence of CKD among Chinese elderly population. Aging, pre-HTN, HTN, elevated triglyceride, and FBG were associated with the risk of CKD. More attention should be paid to metabolic diseases to prevent CKD in the elderly.

Xu|Lingling|L| Liu|Jin|J| Li|Dongling|D| Yang|Hua|H| Zhou|Yang|Y| Yang|Junwei|J|

Chronic kidney disease (CKD)
Elderly
Prevalence
Metabolic risk factors


Planned cesarean delivery compared to induction of labor in women with class III obesity: a cost-minimization analysis (.).

Abstract:
OBJECTIVE
To compare the costs between planned cesarean delivery (CD) and induction of labor (IOL) in women with class III obesity.

METHODS
We conducted a cost-minimization analysis using data from a previous study of women with a BMI ≥40 kg/m(2) delivering term singletons via planned CD or after IOL. Decision trees were built with branches for two "treatments": planned CD and IOL (probabilities derived from parent study). Direct and total costs were obtained for each mother-infant pair. Sensitivity analyses for probability of successful IOL were performed.

RESULTS
A total of 661 mother-infant pairs were included - 399 IOLs and 262 planned CDs. Of 399 IOLs, 236 (59%) delivered vaginally and 163 (41%) had a CD. IOL was slightly less costly. For IOL and planned CD, respectively, direct costs were $7416 versus $7474, and total costs were $11 545 versus $11 665. Sensitivity analyses indicated that IOL was the least costly strategy if the probability of vaginal delivery after IOL was >57% (0.575 for direct costs; 0.570 for total costs). There was, however, a slight cost advantage to planned CD in women with a prior cesarean.

CONCLUSIONS
In women with class III obesity, IOL is less costly than planned CD if the probability of vaginal delivery after IOL in an individual patient is greater than 57%.

Subramaniam|Akila|A|
Corvey|Kathryn J|KJ|
Kilgore|Meredith L|ML|
Edwards|Rodney K|RK|

D000328:Adult
D002585:Cesarean Section
D017046:Cost Savings
D003365:Costs and Cost Analysis
D003663:Decision Trees
D005260:Female
D006801:Humans
D007751:Labor, Induced
D009767:Obesity, Morbid
D011247:Pregnancy
D011248:Pregnancy Complications
D016064:Vaginal Birth after Cesarean
D055815:Young Adult

planned cesarean delivery
induction of labor
Class III obesity
costs


Metastatic undifferentiated pleomorphic sarcoma causing intraoperative stroke.

Abstract: Malignant Fibrous Histiocytoma was historically the most commonly diagnosed soft tissue sarcoma of adults. In 2002, the World Health Organization declassified malignant fibrous histiocytoma as a formal diagnostic entity. They recommended renaming the disease "Pleomorphic Undifferentiated Sarcoma". Current thoughts about the origin of this tumor are being debated. We report a case of a dedifferentiated liposarcoma that metastasized to the lung within one year. The histologic morphology of the metastasis was more aggressive than the primary lesion, and was consistent with a pleomorphic undifferentiated sarcoma. Following surgical resection of the metastatic pulmonary lesion, the patient never fully regained consciousness. He expired the day following his surgery. At autopsy, the patient was found to have died from a massive hemorrhagic stroke involving almost the entire left cerebrum. Tumor emboli from the pulmonary metastasis were seen in the left middle cerebral artery, causing the cerebral infarct. The embolic lesion was consistent with a pleomorphic undifferentiated sarcoma. This case illustrates the evolution that soft tissue sarcomas can undergo as they metastasize and become increasingly undifferentiated, and confirms the surgical risk of resecting such lesions.

Spaulding|Reed|R|
Koumoundouros|Theodoros|T|
Parker|Joseph C|JC|

malignant fibrous histiocytoma
Pleomorphic undifferentiated sarcoma
liposarcoma
embolus


Phospholipid-Coated Hydrophobic Mesoporous Silica Nanoparticles Enhance Thrombectomy by High-Intensity Focused Ultrasound with Low Production of Embolism-Inducing Clot Debris.

Abstract: Here we report the efficacy of a nanoparticle-assisted high-intensity focused ultrasound (HIFU) treatment that selectively destroys blood clots while minimizing generation of microparticles, or microemboli, that can cause further complications postsurgery. Treatment of malignant blood clots (thrombi) and the resulting emboli are critical problems for numerous patients, and treatments addressing these conditions would benefit from advancements in noninvasive procedures such as HIFU. While recanalization of occlusive blood clots is currently addressed with surgical intervention that seeks to minimize formation of large emboli, there is a danger of microemboli (micrometer-size particles) that have been theorized to be responsible for the poor correlation between apparent surgical success and patient outcome. Here, the addition of phospholipid-coated hydrophobically modified silica nanoparticles (P@hMSNs) improved the efficacy of HIFU treatment by serving as cavitation nuclei for mechanical disruption of thrombi. This treatment was evaluated for the ability to clear the HIFU focal area of a thick and dense thrombus within 10 min. Moreover, it was found that the use of P@hMSN+HIFU treatment generated a significantly smaller microembolic load as compared to comparison techniques, including a HIFU + microbubble contrast agent, HIFU alone, and direct mechanical disruption. This reduction in the microembolic load can occur either with primary removal of the clot by P@hMSN+HIFU or by insonation of the clot fragments after mechanical thrombectomy. Lastly, this method was evaluated in a flow model, where nonocclusive model thrombi and model emboli were mechanically ablated within the focal area within 15 s. Together, these results represent a combination therapy capable of resolving thrombi and microembolisms resulting from thrombectomy through localized destruction of clotted material.

D057086:High-Intensity Focused Ultrasound Ablation

D057927:Hydrophobic and Hydrophilic Interactions

nanoparticle ultrasound cavitation atherosclerosis thrombosis


Bioactive Phenolic Compounds of Two Medicinal Mushroom Species Trametes versicolor and Stereum subtomentosum as Antioxidant and Antiproliferative Agents.

Abstract: Medicinal mushrooms have tremendous potential in production of bioactive compounds with diverse bioactivities while the biochemical potential of some specific mushroom strains (autochthonous for the region) in production of specific bioactive agents may be of the main importance in a continuous search for novel strains with supreme activities all over the world. In this study, the ethanolic (EtOH) and water (H2 O) extracts of wild-growing polypore mushroom species were investigated: Trametes versicolor (L.) Lloyd and Stereum subtomentosum Pouzar. This study was designed to determine total phenol (TP), flavonoid (TF) and protein content (TPR) as well as LC/MS/MS phenolic profile related to in vitro antioxidant, antiproliferative (MTT assay) (AP) and DNA fragmentation properties. The H2 O extracts expressed better antioxidant scavenging potential than EtOH showing the highest activity for the T. versicolor (IC50 =5.6 μg/mL, IC50 =0.6 μg/mL for DPPH. and OH. , respectively) while O2 .- activity achieved the best activity for S. subtomentosum (IC50 =4.1 μg/mL). In contrary, the highest AP activity was obtained for the EtOH extracts of S. subtomentosum (IC50 =141.1 μg/mL). The EtOH extracts of both species showed the highest TP, TF and TPR content. Obtained results of DNA degradation indicate genotoxicity potential of the extracts at high concentration. The LC/MS/MS detection showed that the majority of analyzed extracts contained phenolic acids, p-hydroxybenzoic and protocatechuic acid. The obtained results suggest that analyzed medicinal mushroom species, T. versicolor and S. subtomentosum, could be of potential interest as new sources of strong natural antioxidants as well as antiproliferative agents in the future.

D002851:Chromatography, High Pressure Liquid

phenolic compounds
Trametes versicolor
Stereum subtomentosum
antiproliferative
DNA fragmentation
scavenging activity


Cell internalization of 7-ketocholesterol-containing nanoemulsion through LDL receptor reduces melanoma growth in vitro and in vivo: a preliminary report.

Abstract: Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a cellular model the murine melanoma cell line B16F10 was used. The nanoparticle (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of melanoma cells. In addition, it was observed dissipation of the transmembrane potential, evidenced with flow cytometry; presence of autophagic vacuoles, visualized and quantified with flow cytometry and acridine orange; and presence of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired cytokenesis was accompanied by changes in cellular morphology into a fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown by the increased actin polymerization. 7KCLDE was injected into B16 melanoma tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor 7KCLDE promoted a >50% size reduction, enlarged the necrotic area, and reduced intratumoral vasculature. 7KCLDE increased the survival rates of animals, without hematologic or liver toxicity. Although more pre-clinical studies should be performed, our preliminary results suggested that 7KCLDE is a promising novel preparation for cancer chemotherapy.

Favero|Giovani M|GM|
Paz|Jessica L|JL|
Otake|Andréia H|AH|
Maria|Durvanei A|DA|
Caldini|Elia G|EG|
de Medeiros|Raphael S S|RSS|
Deus|Debora F|DF|
Chammas|Roger|R|
Maranhão|Raul C|RC|
Bydlowski|Sergio P|SP|

nanoemulsion
LDL receptor
melanoma
7-ketocholesterol
cell death


Characterization of Nine Compounds Isolated from the Acid Hydrolysate of Lonicera fulvotomentosa Hsu et S. C. Cheng and Evaluation of Their In Vitro Activity towards HIV Protease.

Abstract: In this study, we isolated nine compounds from the acid hydrolysate of the flower buds of Lonicera fulvotomentosa Hsu et S. C. Cheng and characterized their chemical structures using 1H-NMR, 13C-NMR, and electron ionization mass spectroscopy (EI-MS). These compounds were identified as β-sitosterol (1), 5,5'-dibutoxy-2,2'-bifuran (2), nonacosane-10-ol (3), ethyl (3β)-3,23-dihydroxyolean-12-en-28-oate (4), oleanolic acid (5), ethyl caffeate (6), caffeic acid (7), isovanillin (8), and hederagenin (9), with 4 as a new triterpene compound. Inhibitory activity against human immunodeficiency virus (HIV) protease was also evaluated for the compounds, and only ethyl caffeate, caffeic acid, and isovanillin (6, 7, and 8) exhibited inhibitory effects, with IC50 values of 1.0 μM, 1.5 μM, and 3.5 μM, respectively. Molecular docking with energy minimization and subsequent molecular dynamic (MD) simulation showed that ethyl caffeate and caffeic acid bound to the active site of HIV protease, while isovanillin drifted out from the active site and dissociated into bulk water during MD simulations, and most of the binding residues of HIV protease have been previously identified for HIV protease inhibitors. These results suggest that caffeic acid derivatives may possess inhibitory activities towards HIV protease other than previously reported inhibitory activities against HIV integrase, and thus ethyl caffeate and caffeic acid could be used as lead compounds in developing potential HIV protease inhibitors, and possibly even dual-function inhibitors against HIV.

Wang|Xia|X|
Wei|Ying|Y|
Tian|Wei-Yi|WY|
Sakharkar|Meena Kishore|MK|
Liu|Qing|Q|
Yang|Xin|X|
Zhou|Yan-Zi|YZ|
Mou|Cheng-Li|CL|
Cai|Gui-Lan|GL|
Yang|Jian|J|

D020134:Catalytic Domain
D016333:HIV Protease
D017320:HIV Protease Inhibitors
D015497:HIV-1
D031239:Lonicera
D013058:Mass Spectrometry
D062105:Molecular Docking Simulation
D056004:Molecular Dynamics Simulation
D015394:Molecular Structure
D064209:Phytochemicals
D010936:Plant Extracts


Total Synthesis and Structural Assignment of (-)-Fusaequisin A.

Abstract: (-)-Fusaequisin A is an irregularly assembled polyketide isolated from the ascomycete Fusarium equiseti. Fusaequisin A shares a carbon backbone with curvicollide C from the ascomycete Podospora curvicolla but its absolute configuration remained hitherto unsettled. Herein, we document the total synthesis of (-)-fusaequisin A and its 4-O-desmethyl derivative following a central-to-lateral building block strategy. Catalytic asymmetric Claisen rearrangement, Julia-Kocienski olefination and olefin cross-metathesis served as key C/C-connecting transformations. The constitution and absolute configuration of (-)-fusaequisin A was deduced and the original structural assignment was adjusted.

total synthesis
polyketides
asymmetric synthesis
natural products
structural elucidation


Spread of Water-Borne Pollutants at Traffic Accidents on Roads.

Abstract: Traffic accidents sometimes lead to the spread of hazardous compounds to the environment. Accidental spills of hazardous compounds on roads in the vicinity of vulnerable objects such as water supplies pose a serious threat to water quality and have to be assessed. This study compared three different assessment methods, electrical resistivity measurements, analytical flow calculations, and 1D and 2D dynamic flow modeling, to describe rapid transport processes in the road shoulder and roadside verge after a major spill. The infiltration and flow paths of water-borne substances were described during simulated discharge of pollutants on different road types. Full-scale tracer tests using sodium chloride were carried out at nine different road locations in Sweden. Analysis of grain size distribution and infiltrometer tests were carried out at the road shoulder and verges. The pathways and travel times were traced using resistivity measurements and 3D inverse modeling. The resistivity measurements were compared to analytical flow calculations and 1D and 2D dynamic modeling. All measurement sites were highly heterogeneous, which caused preferential flow. Vertical flow velocities of 1.4-8.6 × 10-4 m/s were measured. The results of the analytical calculations and flow modeling were of the same order of magnitude. The measurements showed that almost all infiltration goes directly into the road embankment, hence the composition and structure of the built-up road must be considered. The non-destructive resistivity measurements and 3D modeling provided useful information for clarifying the infiltration and flow pattern of water-borne compounds from road runoff.

Pollution
Road
Electrical resistivity
Modeling
Infiltration


Functional connectivity of dorsal and ventral frontoparietal seed regions during auditory orienting.

Abstract: Our ability to refocus auditory attention is vital for even the most routine day-to-day activities. Shifts in auditory attention can be initiated "voluntarily," or triggered "involuntarily" by unexpected novel sound events. Here we employed psychophysiological interaction (PPI) analyses of auditory functional MRI data, to compare functional connectivity patterns of distinct frontoparietal cortex regions during cued voluntary vs. novelty-driven involuntary auditory attention shifting. Overall, our frontoparietal seed regions exhibited significant PPI increases with auditory cortex (AC) areas during both cued and novelty-driven orienting. However, significant positive PPI patterns associated with voluntary auditory attention (cue>novel task regressor), but mostly absent in analyses emphasizing involuntary orienting (novel>cue task regressor), were observed with seeds within the frontal eye fields (FEF), superior parietal lobule (SPL), and right supramarginal gyri (SMG). In contrast, significant positive PPIs associated selectively with involuntary orienting were observed between ACs and seeds within the bilateral anterior interior frontal gyri (IFG), left posterior IFG, SMG, and posterior cingulate cortices (PCC). We also found indices of lateralization of different attention networks: PPI increases selective to voluntary attention occurred primarily within right-hemispheric regions, whereas those related to involuntary orienting were more frequent with left-hemisphere seeds. In conclusion, despite certain similarities in PPI patterns across conditions, the more dorsal aspects of right frontoparietal cortex demonstrated wider connectivity during cued/voluntary attention shifting, whereas certain left ventral frontoparietal seeds were more widely connected during novelty-triggered/involuntary orienting. Our findings provide partial support for distinct attention networks for voluntary and involuntary auditory attention.

Rossi|Stephanie|S|
Huang|Samantha|S|
Furtak|Sharon C|SC|
Belliveau|John W|JW|
Ahveninen|Jyrki|J|

Auditory attention
Psychophysiological interaction
Auditory cortex
Involuntary attention
Voluntary orienting
fMRI


Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity.

Abstract:
BACKGROUND & AIMS
Sustained c-Jun N-terminal kinase (JNK) activation by saturated fatty acids plays a role in lipotoxicity and the pathogenesis of non-alcoholic steatohepatitis (NASH). We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes.

METHODS
Primary mouse hepatocytes (PMH) from adeno-shlacZ or adeno-shSab treated mice and HuH7 cells were used.

RESULTS
In PMH, PA dose-dependently up to 1mM stimulated oxygen consumption rate (OCR) due to mitochondrial β-oxidation. At ⩾1.5mM, PA gradually reduced OCR, followed by cell death. Inhibition of JNK, caspases or treatment with antioxidant butylated hydroxyanisole (BHA) protected PMH against cell death. Sab knockdown or a membrane permeable Sab blocking peptide prevented PA-induced mitochondrial impairment, but inhibited only the late phase of both JNK activation (beyond 4h) and cell death. In PMH, PA increased p-PERK and its downstream target CHOP, but failed to activate the IRE-1α arm of the UPR. However, Sab silencing did not affect PA-induced PERK activation. Conversely, specific inhibition of PERK prevented JNK activation and cell death, indicating a major role upstream of JNK activation.

CONCLUSIONS
The effect of p-JNK on mitochondria plays a key role in PA-mediated lipotoxicity. The interplay of p-JNK with mitochondrial Sab leads to impaired respiration, ROS production, sustained JNK activation, and apoptosis.

Win|Sanda|S|
Than|Tin Aung|TA|
Le|Bao Han Allison|BH|
García-Ruiz|Carmen|C|
Fernandez-Checa|Jose C|JC|
Kaplowitz|Neil|N|

D048868:Adaptor Proteins, Signal Transducing

D048031:JNK Mitogen-Activated Protein Kinases

D065626:Non-alcoholic Fatty Liver Disease

Palmitic acid
Hepatocytes
Reactive oxygen species
Mitochondria
Apoptosis


Our experience in the management of prostate cancer in renal transplant recipients.

Abstract:
INTRODUCTION AND OBJECTIVES
The management of Prostate cancer (PCa) in renal transplant recipients (RTR) is challenging and remain controversial. Currently there is no consensus about this condition. The aim of the study was to analyse our experience in the diagnosis and management of PCa in RTR.

METHOD
Retrospective monocentric study of a prospective and consecutive database from 2003-2017. Inclusion of RTR diagnosed of PCa. Staging and treatment in agreement with the contemporary guidelines. The main outcome measures included clinical staging, type of treatment, oncological outcomes and follow-up.

RESULTS
1,330 renal transplants were performed (787 males), diagnosed of PCa in 33 RTR (4.2%), mean age 66years±6.3 (51-78). Median PSA was 8.8ng/ml and PSA ratio 0.19. Mean time between renal transplantation and PCa diagnosis 130months±90 (2-236).

TREATMENTS
Radical prostatectomy (RP) (n=22; 66.7%), Radiation therapy (RT) with Androgen deprivation therapy (ADT) (n=7; 21.2%), Active surveillance (n=3; 9.1%), ADT (n=1; 3%). No graft loss neither impaired renal function due to PCa treatment was reported. After RP two patients (9.1%) presented biochemical recurrence treated with RT. Remission of the 100%. Mean follow-up was 61months±37 (6-132).

CONCLUSIONS
PCa in renal transplant patients can be managed with the same therapeutic options as in the general population. Active surveillance should also be provided in RTR despite being under immunosuppressive therapy.

Narváez|A|A| Suarez|J|J| Riera|L|L| Castells-Esteve|M|M| Cocera|R|R| Vigués|F|F|

D000368:Aged
D006801:Humans
D016030:Kidney Transplantation
D008297:Male
D008875:Middle Aged
D011183:Postoperative Complications
D011471:Prostatic Neoplasms
D012189:Retrospective Studies
D016896:Treatment Outcome

Prostate cancer
Renal transplant
Radical prostatectomy
Active surveillance
Biochemical recurrence
Cáncer de próstata
Prostatectomía radical
Recidiva bioquímica
Trasplante renal
Vigilancia activa


Current role of rituximab in systemic lupus erythematosus.

Abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by periods of flares and remission, resulting in organ damage over time caused by persistent disease activity and treatment-related complications. Conventional therapies are not ideal in terms of efficacy and safety. Novel biological therapies are being developed to enhance therapeutic efficacy, minimize disease exacerbation and reduce toxicities. As dysregulation of B cells is the hallmark of SLE, B-cell targeted therapies are the focus of recent clinical research. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used with success in recalcitrant lupus manifestations. However, randomized controlled trials have failed to reveal its benefit in renal and non-renal SLE when combined with conventional immunosuppressive protocols. Although heterogeneity of SLE manifestations, pitfalls in study design and the limitations of the assessment tools for various clinical end points may have contributed to the discouraging results, rituximab remains an option in patients who are refractory or intolerant to conventional therapies. Recently, a regimen consisting of rituximab and mycophenolate mofetil without oral corticosteroids was reported to be effective in lupus nephritis. While the efficacy of this regimen has to be confirmed, future controlled trials should focus on the efficacy of rituximab in refractory lupus manifestations and its synergistic effect with other immunosuppressive agents such as cyclophosphamide. In short-term randomized controlled trials, a non-significant increase in serious adverse events was observed in SLE patients treated with rituximab. Long-term safety data of rituximab in SLE, in particular the incidence of hypogammaglobulinemia and serious/opportunistic infections, have to be continuously surveyed.

D064420:Drug-Related Side Effects and Adverse Reactions

D016032:Randomized Controlled Trials as Topic

lupus therapy novel biologics therapeutics anti-CD20


Quantifying Uncertainty in the Ratio of Two Measured Variables: A Recap and Example.

Abstract: Estimating uncertainty in the ratio of 2 measured variables can be achieved via 2 seemingly different approaches: by determining the variance of the first-order Taylor approximation to the ratio, or by the so-called "Propagation of Error" approach. This Lesson Learned shows that the 2 approaches are mathematically equivalent, and provides an example of the approach.

Shackleford|David M|DM|
Jamsen|Kris M|KM|

ADME
bioavailability
caco-2 cells
in vitro models
pharmacokinetics


Maternal depression and warmth during childhood predict age 20 neural response to reward.

Abstract:
OBJECTIVE
Early parenting experiences likely shape children's brain development, with consequences potentially extending into adulthood. Parents' affective disorders and expressions of positive affect could exert an influence on affect-related circuitry. The current study evaluated how maternal depression and maternal warmth assessed in early childhood and early adolescence were related to boys' reward function during early adulthood.

METHOD
Participants were 120 boys at socioeconomic risk for emotional problems. Mothers' history of depression during the child's lifetime was measured when boys were 42 months old and 10 and 11 years old. Maternal warmth was observed during mother-child interactions at 18 and 24 months and at 10 and 11 years.

RESULTS
Maternal warmth during early childhood was associated with less activation in the medial prefrontal cortex (mPFC) when anticipating and experiencing reward loss. Maternal warmth during early adolescence was associated with less activation in the mPFC when winning rewards and greater activation in the caudate when experiencing loss. The association between maternal warmth during early childhood and early adolescence and reward function in the striatum and mPFC was stronger for boys exposed to maternal depression relative to boys who were not.

CONCLUSIONS
The experience of warmth and affection from mothers may be a protective factor for reward function in boys exposed to maternal depression, possibly by engaging vulnerable neural reward systems through affiliation.

Morgan|Judith K|JK|
Shaw|Daniel S|DS|
Forbes|Erika E|EE|


Methylthiouracil, a new treatment option for sepsis.

Abstract: The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as an attractive therapeutic strategies in the management of severe sepsis or septic shock. Here, we examined the effects of methylthiouracil (MTU), used as antithyroid drug, by monitoring the effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1, and on the modulation of HMGB1-mediated inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice. MTU inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. MTU also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with MTU reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury. Our results indicate that MTUs could be candidate therapeutic agents for various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Kwak|Soyoung|S| Ku|Sae-Kwang|SK| Kang|Hyejin|H| Baek|Moon-Chang|MC| Bae|Jong-Sup|JS|

D061307:Human Umbilical Vein Endothelial Cells

Methylthiouracil
Sepsis
HMGB1
Drug repositioning


A Semiquantitative Non-invasive Measurement of PcomA Patency in C57BL/6 Mice Explains Variance in Ischemic Brain Damage in Filament MCAo.

Abstract: Numerous studies on experimental ischemic stroke use the filament middle cerebral artery occlusion (fMCAo) model in C57BL/6 mice, but lesion sizes in this strain are highly variable. A known contributor is variation in the posterior communicating artery (PcomA) patency. We therefore aimed to provide a semiquantitative non-invasive in vivo method to routinely assess PcomA patency. We included 43 male C57BL/6 mice from four independent studies using a transient 45 min fMCAo model. Edema-corrected lesion sizes were measured by magnetic resonance (MR) imaging 24 h after reperfusion. Time-of-flight MR angiography was performed 7 days before and 24 h after fMCAo. Scores of PcomA size measured 24 h after, but not scores measured 7 days before fMCAo were negatively correlated with lesion size. Variability in PcomA patency explained 30% of the variance in our cohort (p < 0.0001, coefficient of determination r 2 = 0.3). In a simulation using parameters typical for experimental stroke research, the power to detect a true effect of d = 1 between two groups increased by 15% when an according covariate was included in the statistical model. We have demonstrated that in vivo measurement of PcomA size is feasible and can lead to increased accuracy in assessing the effect of treatments.

Knauss|Samuel|S|
Albrecht|Carolin|C|
Dirnagl|Ulrich|U|
Mueller|Susanne|S|
Harms|Christoph|C|
Hoffmann|Christian Johannes|CJ|
Koch|Stefan Paul|SP|
Endres|Matthias|M|
Boehm-Sturm|Philipp|P|

stroke
lesion size
posterior communicating artery
angiography
MRI
mouse


Surgical management of competing pulmonary blood flow affects survival before Fontan/Kreutzer completion in patients with tricuspid atresia type I.

Abstract:
OBJECTIVES
To determine the association between surgical management of pulmonary blood flow (PBF) at initial and staged procedures with survival to Fontan/Kreutzer operation (Fontan) in patients with tricuspid atresia.

METHODS
Infants aged <3 months with tricuspid atresia type I (n = 303) were enrolled from 34 institutions (1999-2013). Among those who underwent surgical intervention (n = 302), initial procedures were: systemic to pulmonary artery shunt (SPS; n = 189; 62%); pulmonary artery banding (PAB; n = 50; 17%); and superior cavopulmonary connection (SCPC; n = 63; 21%). Multiphase parametric-hazard models were used to analyze competing outcomes.

RESULTS
Risk-adjusted 6-year survival was lower after SPS (85%; P = .04) versus PAB (93%) or SCPC (93%). Survival after SPS when the main pulmonary artery (MPA) was closed (n = 21) or banded (n = 4) was 60%, versus 93% without MPA intervention (P = .02). After SPS, survival before SCPC was lower with an open ductus arteriosus (n = 7; 76% vs 97%; P = .02). Similarly, after SPS, risk-adjusted survival was similar to that for patients who had an initial PAB or SCPC when MPA intervention was avoided and the ductus arteriosus either closed spontaneously before SPS, or was closed during SPS. For all patients reaching SCPC (n = 277), survival to Fontan was not significantly influenced by whether PBF persisted through the MPA.

CONCLUSIONS
Tricuspid atresia patients with SPS represent a high-risk subgroup. Avoiding an open ductus arteriosus and concomitant MPA intervention during SPS may help mitigate the risk associated with SPS. The presence of antegrade PBF through the MPA, at initial and staged operations, did not significantly influence survival to Fontan operation.

Wilder|Travis J|TJ|
Ziemer|Gerhard|G|
Hickey|Edward J|EJ|
Gruber|Peter J|PJ|
Karamlou|Tara|T|
Kirshbom|Paul M|PM|
Blackstone|Eugene H|EH|
DeCampli|William M|WM|
Williams|William G|WG|
McCrindle|Brian W|BW|

D002170:Canada
D018729:Fontan Procedure
D006801:Humans
D007223:Infant
D053208:Kaplan-Meier Estimate
D011183:Postoperative Complications
D011446:Prospective Studies
D011651:Pulmonary Artery
D011652:Pulmonary Circulation
D012307:Risk Factors
D013997:Time Factors
D016896:Treatment Outcome
D018785:Tricuspid Atresia
D014261:Tricuspid Valve
D014481:United States

tricuspid atresia
systemic to pulmonary artery shunt
accessory pulmonary blood flow
congenital heart disease


Influence of drug-drug interactions on effectiveness and safety of direct-acting antivirals against hepatitis C virus.

Abstract:
OBJECTIVES
Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug-drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug-drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients.

METHODS
Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug-drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug-drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug-drug interactions related to the effectiveness of direct-acting antivirals.

RESULTS
Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug-drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug-drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug-drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841).

CONCLUSIONS
Drug-drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug-drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals.

Margusino-Framiñán|Luis|L| Cid-Silva|Purificación|P| Giménez-Arufe|Victor|V| Mondelo-García|Cristina|C| Fernández-Oliveira|Carla|C| Mena-de-Cea|Álvaro|Á| Martín-Herranz|Isabel|I| Castro-Iglesias|Ángeles|Á|

direct-acting antivirals
pharmaceutical care
clinical pharmacist
antiviral agents
chronic hepatitis c
drug interactions


Sprouty2 is involved in the control of osteoblast proliferation and differentiation through the FGF and BMP signaling pathways.

Abstract: Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified. In this study, we investigated the involvement of Sprouty2 in osteoblast proliferation and differentiation. We examined Sprouty2 expression in MC3T3-E1 cells, and found that high levels of Sprouty2 expression were induced by basic FGF stimulation. Overexpression of Sprouty2 in MC3T3-E1 cells resulted in suppressed proliferation compared with control cells. Sprouty2 negatively regulated the phosphorylation of ERK1/2 after basic FGF stimulation, and of Smad1/5/8 after BMP stimulation. Furthermore, Sprouty2 suppressed the expression of osterix, alkaline phosphatase, and osteocalcin mRNA, which are markers of osteoblast differentiation. Additionally, Sprouty2 inhibited osteoblast matrix mineralization. These results suggest that Sprouty2 is involved in the control of osteoblast proliferation and differentiation by downregulating the FGF-ERK1/2 and BMP-Smad pathways, and suppresses the induction of markers of osteoblast differentiation.

Taketomi|Takaharu|T| Onimura|Tomohiro|T| Yoshiga|Daigo|D| Muratsu|Daichi|D| Sanui|Terukazu|T| Fukuda|Takao|T| Kusukawa|Jingo|J| Nakamura|Seiji|S|

D047908:Intracellular Signaling Peptides and Proteins

osteoblast
fibroblast growth factor
bone morphogenetic protein
sprouty


Age Differences in Work-Disability Duration Across Canada: Examining Variations by Follow-Up Time and Context.

Abstract: Purpose This study aimed to understand age differences in wage-replacement duration by focusing on variations in the relationship across different periods of follow-up time. Methods We used administrative claims data provided by six workers' compensation systems in Canada. Included were time-loss claims for workers aged 15-80 years with a work-related injury/illness during the 2011 to 2015 period (N = 751,679 claims). Data were coded for comparability across cohorts. Survival analysis examined age-related differences in the hazard of transitioning off (versus remaining on) disability benefits, allowing for relaxed proportionality constraints on the hazard rates over time. Differences were examined on the absolute (hazard difference) and relative (hazard ratios [HR]) scales. Results Older age groups had a lower likelihood of transitioning off wage-replacement benefits compared to younger age groups in the overall models (e.g., 55-64 vs. 15-24 years: HR 0.62). However, absolute and relative differences in age-specific hazard rates varied as a function of follow-up time. The greatest age-related differences were observed at earlier event times and were attenuated towards a null difference across later follow-up event times. Conclusions Our study provides new insight into the workplace injury/illness claim and recovery processes and suggests that older age is not always strongly associated with worse disability duration outcomes. The use of data from multiple jurisdictions lends external validity to our findings and demonstrates the utility of using cross-jurisdictional data extracts. Future work should examine the social and contextual determinants that operate during various recovery phases, and how these factors interact with age.

Fan|Jonathan K|JK|0000-0002-7750-881X
Macpherson|Robert A|RA|
Smith|Peter M|PM|
Harris|M Anne|MA|
Gignac|Monique A M|MAM|
McLeod|Christopher B|CB|

D000293:Adolescent
D002170:Canada
D006233:Disabled Persons
D005500:Follow-Up Studies
D006801:Humans
D008875:Middle Aged
D060051:Occupational Injuries
D014942:Workers' Compensation
D055815:Young Adult

Age
Survival analysis
Return to work
Work injury
Workers’ compensation


Seedling response to environmental variability: The relationship between phenotypic plasticity and evolutionary history in closely related Eucalyptus species.

Abstract:
PREMISE OF THE STUDY
Phenotypic plasticity is an important means through which organisms cope with environmental variability. We investigated seedling plasticity in the green ash eucalypts within a phylogenetic framework to examine the relationship between plasticity and evolutionary history. The green ashes are a diverse group, which include the tallest flowering plant in the world (Eucalyptus regnans) and a rare mallee less than 1 m tall (E. cunninghamii).

METHODS
Seedlings of 12 species were exposed to high and low nutrient and water availability in a factorial experiment. Leaf trait and total plant plasticity were evaluated using the phenotypic plasticity index. A phylogeny of the species was estimated using genome-wide scans.

KEY RESULTS
We found significant differences in functional traits across species, growth forms, and substrates in response to changes in resource availability. Many traits (e.g., leaf width) were highly plastic for most species. Interspecific differences in leaf-level plasticity was significant, however plasticity was not correlated with phylogeny. Species with broader environmental niches had higher leaf-level plasticity than species with narrower environmental ranges.

CONCLUSIONS
Plastic responses to environmental variability can differ widely among closely related species, and plasticity is therefore likely to be associated with many factors, including habitat and range size, as well as evolutionary history. Our results provided insights for species delimitation in Eucalyptus, which have management implications. Because of the high number of rare species and that other species are commercially important, a more comprehensive understanding of plasticity is essential for predicting their response to changing climates.

Rutherford|Susan|S|
Bonser|Stephen P|SP|
Wilson|Peter G|PG|
Rossetto|Maurizio|M|

nutrients
Australia
BayesTraits
Diversity Arrays Technology (DArT)
Myrtaceae
climate change
conservation
phylogenetic relationships
phylogenetic signal
water treatments


Seed handling by primary frugivores differentially influence post-dispersal seed removal of Chinese yew by ground-dwelling animals.

Abstract: Seed handling by primary frugivores can influence secondary dispersal and/or predation of post-dispersal seeds by attracting different guilds of ground-dwelling animals. Many studies have focused on seeds embedded in feces of mammals or birds; however, less is known about how ground-dwelling animals treat seeds regurgitated by birds (without pulp and not embedded in feces). To compare the effect of differential seed handling by primary dispersers on secondary seed removal of Chinese yew (Taxus chinensis var. mairei), we conducted a series of exclosure experiments to determine the relative impact of animals on the removal of defecated seeds (handled by masked palm civet), regurgitated seeds (handled by birds) and intact fruits. All types of yew seeds were consistently removed at a higher rate by rodents than by ants. Regurgitated seeds had the highest removal percentage and were only removed by rodents. These seeds were probably eaten in situ without being secondarily dispersed. Defecated seeds were removed by both rodents and ants; only ants might act as secondary dispersers of defecated seeds, whereas rodents ate most of them. We inferred that seeds regurgitated by birds were subjected to the highest rates of predation, whereas those dispersed in the feces of masked palm civets probably had a higher likelihood of secondary dispersal. Seeds from feces attracted ants, which were likely to transport seeds and potentially provided a means by which the seeds could escape predation by rodents. Our study highlighted that primary dispersal by birds might not always facilitate secondary dispersal and establishment of plant populations.

Pan|Yang|Y| Bai|Bing|B| Xiong|Tianshi|T| Shi|Peijian|P| Lu|Changhu|C|

Taxus chinensis
defecated seeds
regurgitated seeds
arils
secondary seed dispersal


An Evaluation Approach of Cell Viability Based on Cell Detachment Assay in a Single-Channel Integrated Microfluidic Chip.

Abstract: Due to the heterogeneity of cancer cell populations, the traditional evaluation approach of cell viability based on the cell counting assay is quite inaccurate for the dose-response test of anticancer drugs, cell toxicology assays, and other biochemical stimulations. In this paper, an evaluation approach of cell viability based on the cell detachment assay in a single-channel integrated microfluidic chip is proposed to improve the accuracy of cell viability assessment. The electrodes are coated by fibronectin for specific cell adhesion, and it is biologically significant to study the cell detachment assay in vitro. The maximum number of cells that can be detected by this sensor is about 105 cells (overgrowing), while the minimum is about 100 cells. This method is calibrated with the half-maximal inhibitory concentration assay, and the results show that the cell viability calculated by adhesion strength is more accurate than that evaluated using the cell counting assay. Meanwhile, the shear rate is transformed into shear stress for the comparability among the results in other papers. The most sensitive frequency is also determined as 1 kHz according to normalized impedance. Besides, the impedance of cell adhesion affected by different shear stresses is monitored to study the optimized plan for long-term culture of cells in the integrated microfluidic chip prepared for the cell detachment assay. Adhesion strength τ25, which is the magnitude of shear stress needed to detach 75% of cell population, is introduced to describe the cell adhesion forces. It is calculated and normalized based on the cell detachment assay to evaluate cell viability. The relative errors of the cell detachment method compared with those of the cell counting method decrease by 0.637 (0% FBS), 0.586 (0.5% FBS), and 0.342 (2% FBS).

Wei|Mingji|M|0000-0002-6733-2670 Zhang|Rongbiao|R| Zhang|Fei|F| Zhang|Yecheng|Y| Li|Guoxiao|G| Miao|Renjie|R| Shao|Shihe|S|

Cell viability
Integrated microfluidic chip
Adhesion strength
Shear stress
Electrochemical impedance spectroscopy


Effect on Chemical and Physical Properties of Soil Each Peat Moss, Elemental Sulfur, and Sulfur-Oxidizing Bacteria.

Abstract: Peat moss is an organic substance corroded by sphagnum moss and has a pH of 3.0-4.0. Elemental sulfur is sulfated and oxidized by the action of bacteria to become sulfuric acid. These biological factors can alter the soil environment. Blueberries require soil with a pH of 4.5-5.2 and high organic matter content. In this experiment, we investigated whether different treatment rates of peat moss, elemental sulfur, and sulfur-oxidizing bacteria affect changes in soil pH, physicochemical properties, and electrical conductivity. We detected strong changes in soil pH as a reaction to the supply of peat moss, elemental sulfur, and sulfur-oxidizing bacteria. The pH of the soil when peat moss and elemental sulfur each were supplied was reduced. In addition, the pH decreased faster when elemental sulfur and sulfur-oxidizing bacteria were supplied together than elemental sulfur alone, satisfying an acidic soil environment suitable for blueberry cultivation. In this experiment, it is shown that peat moss, elemental sulfur, and sulfur-oxidizing bacteria are suitable for lowering soil pH. It was demonstrated that when elemental sulfur and sulfur-oxidizing bacteria were treated together, the pH decreased faster than when treated with peat moss. It could be economically beneficial to farmers to use elemental sulfur and sulfur-oxidizing bacteria, which are cheaper than peat moss, to reduce the pH of the soil.

pH
blueberry
organic matter content
physicochemical property
acidic soil


Ocular Dominance Plasticity of Areas 17 and 21a in the Cat.

Abstract: The visual system is organized in a parallel and hierarchical architecture. However, the plasticity in hierarchical neural networks is controversial across different response features and at different levels. In this study, we recorded areas 17 and 21a, earlier and intermediate stages of the visual cortex in the cat, respectively, by single-unit recording and intrinsic-signal optical imaging. We found that ocular dominance (OD) plasticity evoked by monocular deprivation (MD) was stronger in area 21a than in area 17 in the critical period (CP), and this plasticity became weaker but still persisted in area 21a while it disappeared in area 17 beyond the CP. These results suggest a diversified functional plasticity along the visual information processing pathways in a hierarchical neural network.

Wang|Jian|J| Ni|Zheyi|Z| Jin|Anqi|A| Yu|Tiandong|T| Yu|Hongbo|H|

ocular dominance plasticity
hierarchical neural network
optical imaging
area 21a
critical period


The Interplay Between Systemic Inflammatory Factors and MicroRNAs in Age-Related Macular Degeneration.

Abstract: We aimed to explore the expression of systemic inflammatory factors and selected intracellular miRNAs that regulate inflammatory signaling pathways potentially involved in age-related macular degeneration (AMD) pathogenesis. A total of 179 patients with wet AMD, 175 with dry AMD and 121 controls were enrolled in the study. Soluble inflammatory factors were analyzed in plasma samples using Luminex technology. Expression of selected miRNAs was analyzed in isolated nucleated peripheral blood cells (PBNCs) using real-time qPCR. Wet AMD was an independent factor associated with higher concentrations of IL-6 (β = +0.24, p = 0.0004), GM-CSF (β = +0.31, p < 0.001), IFN-γ (β = +0.58, p < 0.001), higher expression of miRNA-23a-3p (β = +0.60, p < 0.0001), miRNA-30b (β = +0.32, p < 0.0001), miRNA-191-5p (β = +0.28, p < 0.0001) and lower concentration of IL-1β (β = -0.25, p = 0.0003), IL-5 (β = -0.45, p < 0.001), IL-10 (β = -0.45, p < 0.001), IL-12 (β = -0.35, p < 0.001), lower expression of miRNA-16-5p (β = -0.31, p < 0.0001), miRNA-17-3p (β = -0.18, p = 0.01), miRNA-150-5p (β = -0.18, p = 0.01) and miRNA-155-5p (β = -0.47, p < 0.0001). Multivariate analysis revealed that dry AMD was an independent factor associated with higher concentration of GM-CSF (β = +0.34, p < 0.001), IL-6 (β = +0.13, p = 0.05), higher expression of miRNA-23a-3p (β = +0.60, p < 0.0001), miRNA-126-3p (β = +0.23, p = 0.0005), miRNA-126-5p (β = +0.16, p = 0.01), miRNA 146a (β = +0.14, p = 0.03), and mRNA191-5p (β = +0.15, p = 0.03) and lower concentrations of TNF-α (β = +0.24, p = 0.0004), IL-1β (β = -0.39, p < 0.001), IL-2 (β = -0.20, p = 0.003), IL-5 (β = -0.54, p < 0.001), IL-10 (β = -0.56, p < 0.001), IL-12 (β = -0.51, p < 0.001), lower expression of miRNA-16-5p (β = -0.23, p = 0.0004), miRNA-17-3p (β = -0.20, p = 0.003) and miRNA-17-5p (β = -0.19, p = 0.004). Negative correlations between visual acuity and WBC, lymphocyte count, TNF-α, IL-1 β, IL-2, IL-4, IL-6, IL-10 concentrations and miRNA-191-5p, as well as positive correlations between visual acuity and miRNA-126-3p, -126-5p, and -155-5p PBNCs expression were found in AMD patients. No such correlations were found in the control group. Our results may suggest the role of both intra- and extracellular mechanisms implicated in inflammatory response regulation in multifactorial AMD pathogenesis.

Litwińska|Zofia|Z|
Sobuś|Anna|A|
Łuczkowska|Karolina|K|
Grabowicz|Aleksandra|A|
Mozolewska-Piotrowska|Katarzyna|K|
Safranow|Krzysztof|K|
Kawa|Miłosz Piotr|MP|
Machaliński|Bogusław|B|
Machalińska|Anna|A|

macular degeneration
miRNA
cytokines
inflammation
interleukin


Insights into the photo-induced formation of reactive intermediates from effluent organic matter: The role of chemical constituents.

Abstract: In the present study, the formation of triplet states of organic matters (3OM∗) from effluent organic matter (EfOM) under simulated solar irradiation was investigated. EfOM was separated into hydrophobic (HPO), transphilic (TPI), and hydrophilic (HPI) components. The quantum yield coefficients (ƒTMP) of 3OM∗ were measured for each component and compared to those of reference natural organic matter (NOM). NaBH4 reduction was performed on the EfOM, and the effect of aromatic ketones moieties on triplet formation was also determined. Furthermore, the apparent quantum yield of 1O2 (Φ1O2) and O2•- (ΦO2•-) was measured. Our results suggested that the HPI fraction acted as a sink for 3OM∗. A linear correlation was observed between ƒTMP and Φ1O2 for NOM/EfOM, except for NaBH4-reduced effluent and HPI components. Both ƒTMP and Φ1O2 were positively correlated with the contribution rates of NaBH4-reducible moieties (aromatic ketones) toward 3OM∗. Aromatic ketones were primarily responsible for the production of 3OM∗ from EfOM, whereas quinone moieties played a key role in the production of 3OM∗ in NOM-enriched solutions. Understanding the role of chemical constituents on the photo activity of EfOM/NOM is essential for providing useful insights on their photochemical effects in aquatic systems.

Zhou|Huaxi|H| Lian|Lushi|L| Yan|Shuwen|S| Song|Weihua|W|

Effluent organic matter
Triplet states of organic matters
Photochemical transformation
Reactive oxygen species


Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats.

Abstract: Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. The complexity of SCI suggests that a concerted multi-targeted therapeutic approach is warranted to optimally improve function. Damage to spinal cord is complicated by an increased detrimental response from secondary injury factors mediated by activated glial cells and infiltrating macrophages. While elevation of enolase especially neuron specific enolase (NSE) in glial and neuronal cells is believed to trigger inflammatory cascades in acute SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown. This study measured NSE expression levels and key inflammatory mediators after acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor of enolase, in a male Sprague-Dawley (SD) rat SCI model. Serum NSE levels as well as cytokines/chemokines and metabolic factors were evaluated in injured animals following treatment with vehicle alone or ENOblock using Discovery assay. Spinal cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers by Western blotting. The results indicated a significant decrease in serum inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and expression of MMPs in spinal cord tissues after treatment with ENOblock (100 µg/kg, twice). These results support the hypothesis that activation of glial cells and inflammation status can be modulated by regulation of NSE expression and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed that ENOblock decreased gliosis which may have occurred through reduction of elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes extracellular degradation and production of inflammatory cytokines/chemokines and metabolic factors which activates glia and damages neurons. Thus, reduction of NSE by ENOblock may have potential therapeutic implications in acute SCI.

Haque|Azizul|A|
Capone|Mollie|M|
Matzelle|Denise|D|
Cox|April|A|
Banik|Naren L|NL|

Enolase
Spinal cord injury
Glia
Cytokines and chemokines
Matrix metalloproteinases


Impact of space flight on bacterial virulence and antibiotic susceptibility.

Abstract: Manned space flight induces a reduction in immune competence among crew and is likely to cause deleterious changes to the composition of the gastrointestinal, nasal, and respiratory bacterial flora, leading to an increased risk of infection. The space flight environment may also affect the susceptibility of microorganisms within the spacecraft to antibiotics, key components of flown medical kits, and may modify the virulence characteristics of bacteria and other microorganisms that contaminate the fabric of the International Space Station and other flight platforms. This review will consider the impact of true and simulated microgravity and other characteristics of the space flight environment on bacterial cell behavior in relation to the potential for serious infections that may appear during missions to astronomical objects beyond low Earth orbit.

International Space Station
microgravity
Staphylococcus aureus
bacterial phenotypes
low-shear modeled microgravity
spacecraft contamination


Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response.

Abstract:
BACKGROUND
Immune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune cells (TIIs) in primary oral squamous cell carcinoma (OSCC) and develop immune features-derived models for prognostication and therapeutic prediction.

METHODS
A total number of 392 patients with OSCC receiving ablative surgery at three independent centers were retrospectively enrolled and defined as training, testing and validation cohorts. Detailed features of 12 types of TIIs at center of tumor and invasive margin were assessed by immunohistochemistry coupled with digital quantification. TIIs abundance in OSCC was also estimated by bioinformatics approaches using multiple publicly available data sets. Prognostic models based on selected immune features were trained via machine learning approach, validated in independent cohorts and evaluated by time-dependent area under the curves and concordance index (C-index). Immune types of OSCC were further identified by consensus clustering and their associations with genetic, molecular features and patient survival were clarified.

RESULTS
Patterns of TIIs infiltration varied among patients and dynamically evolved along with tumor progression. Prognostic models based on selected TIIs were identified as efficient and sensitive biomarkers to stratify patients into subgroups with favorable or inferior survival as well as responders or non-responders to postoperative radiotherapy or immunotherapy. These models outperformed multiple conventional biomarkers and immune-related scores in prognostic prediction. Furthermore, we identified two main immune subtypes of OSCC (immune-hot and immune-cold) which harbored characteristic TIIs infiltrations and genomic and molecular features, and associated with patient survival.

CONCLUSIONS
Our results delineated immune landscape and subtypes in OSCC, consolidated their clinical values as robust biomarkers to predict patient survival and therapeutic benefits and reinforced key roles of TIIs and tumor-immune interactions underlying oral tumorigenesis, ultimately facilitating development of tailed immunotherapeutic strategies.

Diao|Pengfei|P| Jiang|Yue|Y| Li|Yuanyuan|Y| Wu|Xiang|X| Li|Jin|J| Zhou|Chen|C| Jiang|Lei|L| Zhang|Wei|W| Yan|Enshi|E| Zhang|Ping|P| Ding|Xu|X| Wu|Heming|H| Yuan|Hua|H| Ye|Jinhai|J| Song|Xiaomeng|X| Wan|Linzhong|L| Wu|Yunong|Y| Jiang|Hongbing|H| Wang|Yanling|Y| Cheng|Jie|J|0000-0001-9068-4271


The effect of Baby-friendly status on exclusive breastfeeding in U.S. hospitals.

Abstract: In 2014, a leading hospital accreditation agency, mandated hospitals publicly report their exclusive breastfeeding (EBF) rates. This new regulation provided an opportunity to explore differences in EBF outcomes using a standardized definition across a large hospital sample in the United States. The purpose of this study was to examine the relationships between population demographics and the Baby-friendly (BF) hospital designation on EBF rates in hospitals throughout the United States. We obtained EBF rates from 121 BF hospitals and 1,608 hospitals without the BF designation. Demographic variables were computed using census tract data for the population surrounding each hospital. Relationships were explored using linear regression. We found that EBF rates were positively correlated with a bachelor's degree, log income, and those who identified as White or Asian and negatively correlated with those without college attendance, individuals living below the poverty line, and those who identified as African American or Hispanic. For all models, the BF designation of a hospital was associated with higher EBF rates (p < 0.01; effect sizes, 0.11-0.49) with the exception of the model containing log income. Using a multiple linear regression model that was allowed to contain more than one independent variable, we were able to explain 22% of the variability in EBF rates. The BF hospital designation was associated with significantly higher EBF rates independent of demographic variables. Support for hospitals to attain the BF hospital designation is a meaningful public health goal.

breastfeeding
Baby-friendly hospital initiative
breastfeeding disparities
breastfeeding promotion
exclusive breastfeeding rates
joint commission


Synthesis of a new magnetic-MIP for the selective detection of 1-chloro-2,4-dinitrobenzene, a highly allergenic compound.

Abstract: Molecularly imprinted polymers (MIPs) in combination with magnetic nanoparticles, in a core@shell format, were studied for selective detection of 1-chloro-2,4-dinitrobenzene (CDNB), a powerful allergenic substance. Magnetic nanoparticles were prepared by the co-precipitation method and mixed with oleic acid (OA). This material was then encapsulated in three types of hydrophobic polymeric matrix, poly-(MA-co-EDGMA), poly-(AA-co-EDGMA), and poly-(1-VN-co-EDGMA), by the mini-emulsion method. These matrices were used due to their ability to interact specifically with the functional groups of the analyte. Finally, the MIP-CDNB was obtained on the magnetic-hydrophobic surfaces using precipitation polymerization in the presence of the analyte. XRD diffraction patterns suggested the presence of magnetite in the composite and SEM analysis revealed a nanoparticle size between 10 and 18nm. Under the optimized adsorption conditions, the magnetic-MIP material showed a higher adsorption capacity (5.1mgg-1) than its non-magnetic counterpart (4.2mgg-1). In tests of the selectivity of the magnetic-MIP towards CDNB, α-values of 2.5 and 10.4, respectively, were obtained for dichlorophenol and o-nitrophenol, two structurally similar compounds, and no adsorption was observed for any other non-analogous analyte. The magnetic-MIP and magnetic-NIP were applied using water enriched with 0.5mgL-1 of CDNB, achieving recovery values of 83.8(±0.8)% and 66(±1)%, respectively, revealing the suitability of the material for detection of CDNB.

Uzuriaga-Sánchez|Rosario Josefina|RJ|
Wong|Ademar|A|
Khan|Sabir|S|
Pividori|Maria I|MI|
Picasso|Gino|G|
Sotomayor|Maria D P T|MDPT|

Magnetic-MIP
1-Chloro-2,4-dinitrobenzene
Allergenic substances
Biomimetic polymers
Environmental control
Plastic antibodies


Education, APOE ε4, and Cognition in Individuals with Subjective Cognitive Decline with Worry in the SILCODE Study.

Abstract:
BACKGROUND
Education could offer a protective effect on cognition in individuals with Subjective Cognitive Decline (SCD), which is considered to be the early stage of Alzheimer's Disease (AD). However, the effect of education on cognition in SCD individuals with SCD-plus features is not clear.

OBJECTIVE
The aim of the study was to explore the effect of education on cognition in SCD individuals with SCD-plus features.

METHODS
A total of 234 individuals with SCD were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Cognition was assessed across 4 domains (memory, executive, language, and general cognitive functions). Multiple linear regression models were constructed to examine the effect of education on cognitive scores in individuals without worry (n=91) and with worry (n=143). Furthermore, we assessed differences in effects between APOE ε4 noncarriers and APOE ε4 carriers in both groups.

RESULTS
Multiple linear regression analysis showed a positive effect of education on memory, executive, and language cognition in individuals without worry and all cognitive domains in individuals with worry. Furthermore, we found a positive effect of education on executive cognition in APOE ε4 noncarriers without worry and language and general cognition in APOE ε4 carriers without worry. Meanwhile, education had a positive effect on all cognitive domains in APOE ε4 noncarriers with worry and executive, language, and general cognition in APOE ε4 carriers with worry.

CONCLUSION
This study indicates that education has the potential to delay or reduce cognitive decline in SCD individuals with SCD-plus features.

Chen|Guanqun|G| Lin|Li|L| Yang|Kun|K| Han|Ying|Y|

education
subjective cognitive decline
Alzheimer's disease
apolipoprotein E
cognitive reserve
prevention.


Influence of molecular characteristics in the prognosis of methicillin-resistant Staphylococcus aureus prosthetic joint infections: beyond the species and the antibiogram.

Abstract: We have explored the relationship of phenotypic (antibiogram, β-haemolysis, agr functionality, biofilm formation) and genotypic characteristics on the prognosis of 18 cases of methicillin-resistant S. aureus prosthetic joint infection (2005-2015). All isolates belonged to CC5, and had agr type II. This pilot study suggests that phage-borne genes belonging to the immune evasion cluster (chp, sak and scn) were more frequent among episodes with treatment failure (80.0 vs. 37.5%).

Muñoz-Gallego|Irene|I| Lora-Tamayo|Jaime|J| Pérez-Montarelo|Dafne|D| Brañas|Patricia|P| Viedma|Esther|E| Chaves|Fernando|F|

Joint infections
Biofilms
Bone infections
DAIR
MRSA


Responsive neurostimulation for regional neocortical epilepsy.

Abstract:
OBJECTIVE
Surgical resection of seizure-producing brain tissue is a gold standard treatment for drug-resistant focal epilepsy. However, several patient-specific factors can preclude resective surgery, including a spatially extensive ("regional") seizure-onset zone (SOZ). For such patients, responsive neurostimulation (RNS) represents a potential treatment, but its efficacy has not been investigated in this population.

METHODS
We performed a multicenter retrospective cohort study of patients (N = 30) with drug-resistant focal epilepsy and a regional neocortical SOZ delineated by intracranial monitoring who were treated with the RNS System for at least 6 months. RNS System leads were placed at least 1-cm apart over the SOZ, and most patients were treated with a lead-to-lead stimulation pathway. Five patients underwent partial resection of the SOZ concurrent with RNS System implantation. We assessed change in seizure frequency relative to preimplant baseline and evaluated correlation between clinical outcome and stimulation parameters.

RESULTS
Median follow-up duration was 21.5 months (range 6-52). Median reduction in clinical seizure frequency was 75.5% (interquartile range [IQR] 40%-93.9%). There was no significant difference in outcome between patients treated with and without concurrent partial resection. Most patients were treated with low charge densities (1-2.5 µC/cm2 ), but charge density, interlead distance, and duration of treatment were not significantly correlated with outcome.

SIGNIFICANCE
RNS is a feasible and effective treatment in patients with drug-resistant regional neocortical seizures. Prospective studies in larger cohorts are necessary to determine optimal lead configuration and stimulation parameters, although our results suggest that lead-to-lead stimulation and low charge density may be effective in some patients.

responsive neurostimulation
RNS System
regional neocortical seizures
drug-resistant epilepsy