Urban snow indicates pollution originating from road traffic.

Abstract: Traffic is a major source of pollutants in cities. In this well-replicated study we analysed a broad array of contaminants in snowpacks along roads of different traffic intensities. The majority of pollutants showed a similar pattern with respect to traffic intensity: pH and conductivity as well as concentrations of PAHs, total suspended solids, phosphorus and most heavy metals were higher next to high intensity roads compared to low intensity roads. These pollutant levels also decreased considerably up to 5 m distance from the roads. Furthermore, apart from nitrogen, these variables increased in concentration from control sites in urban forest patches to road bank sites next to roads of low, intermediate and high traffic intensities. The deposition pattern of various traffic-derived pollutants--whether gaseous or particle-bound--was the same. Such information can be useful for the purposes of managing pollutants in urban areas.

Kuoppamäki|Kirsi|K|
Setälä|Heikki|H|
Rantalainen|Anna-Lea|AL|
Kotze|D Johan|DJ|

Urban Snow Traffic PAH Phosphorus Metals Nitrogen


Advanced Surface Ablation in Mild (Fruste) Keratoconus: A Case Report.

Abstract: Corneal ectasia is a complication of refractive surgery, and keratoconus is a contraindication to this type of procedure. Surface ablation may be an option for selected cases of mild keratoconus, with patient education being fundamental to this treatment as well as a complete evaluation of the cornea and optical properties of the patient. Here we report the clinical outcome of a patient 15 years after advanced surface ablation in a case of mild (fruste) keratoconus.

Esporcatte|Louise P G|LPG|
Salomão|Marcella Q|MQ|
Sena|Nelson B|NB|
Lopes|Bernardo T|BT|
Ambrósio|Renato|R|

Keratoconus
Corneal ectasia
Photorefractive keratectomy


Oxidative stress and DNA damage in agricultural workers after exposure to pesticides.

Abstract:
BACKGROUND
Recent epidemiological studies on workers describe that exposure to pesticides can induce oxidative stress by increased production of free radicals that can accumulate in the cell and damage biological macromolecules, for example, RNA, DNA, DNA repair proteins and other proteins and/or modify antioxidant defense mechanisms, as well as detoxification and scavenger enzymes. This study aimed to assess oxidative stress and DNA damage among workers exposed to pesticides.

METHODS
For this purpose, 52 pesticide exposed workers and 52 organic farmers were enrolled. They were assessed: the pesticide exposure, thiobarbituric acid reactive substances (TBARS), total glutathione (TG), oxidized glutathione levels (GSSG), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), levels.

RESULTS
Correlation between pesticide exposure was positively associated with high TBARS and 8-oxodG levels (p <  0.001). A negative association was founded with TG and GSSG and pesticide exposure.

CONCLUSIONS
The present investigation results seem to indicate a mild augment in oxidative stress associated with pesticide exposure, followed by an adaptive response to increase the antioxidant defenses to prevent sustained oxidative adverse effects stress.

Agricultural workers
Pesticides
Biomonitoring
Cancer
Disease
ROS


Assessment of Diabetic Polyneuropathy in Inpatient Care: Fasting Blood Glucose, HbA1c, Electroneuromyography and Diabetes Risk Factors.

Abstract:
CONFLICT OF INTEREST
NONE DECLARED.

GOAL
THE GOALS OF THIS STUDY ARE TO: a) determine the prevalence of diabetic polyneuropathy (DPNP) in hospitalized patients with diabetes mellitus (DM) type 2; b) determine the frequency of DPNP in hospitalized patients with type 2 DM in relation to gender, duration of diabetes, fasting blood glucose and HbA1c; c) identify the dominant DPNP symptoms and the presence of variable risk factors in hospitalized patients; and d) determine the frequency and motor nerve conduction velocity of n. peroneus (electroneuromyography) in relation to the treatment of type 2 DM in hospitalized patients with DPNP.

MATERIAL AND METHODS
The study was conducted on 141 patients diagnosed with type 2 diabetes who were hospitalized at the Neurological clinic of Clinical Center of Sarajevo University in the period from June 1 2009 to June 1 2010. All patients included in the study were older than 18. Values determined for all subjects are: age, sex, dominant symptoms, duration of type 2 DM, fasting blood glucose, HbA1c, motor conduction velocity of n. peroneus, diabetes risk factors (hyperlipidemia, hypertension, smoking, alcoholism, obesity) and DM treatment type.

RESULTS
Of 141 patients with type 2 DM, DPNP was confirmed in 50 patients (35.5%). Men were slightly more represented in the total sample (51.8%). In a sample of patients with DPNP, there were slightly more male patients (n=26; 52%). The average age of patients with DPNP was higher in men (58.3±12.5) (p<0.05). The average age of the patients with DPNP was 55.1± 13.2. Average values of fasting glucose was higher in the group of patients with DPNP (11.032±5.4 mmol/l) compared to patients without DPNP (9.7±2.8 mmol/l) (p<0.05). Mean values of HbA1C were higher in patients with DPNP (8.212±3.3%) compared to patients without DPNP (6.9±2.6%) (p<0.05). Analysis of DM duration between patients with and without DPNP did not show statistically significant difference (chi-square=3.858, p>0.05). In both groups, most of the patients had duration of DM over 10 years, with a minimum duration of DM of 12 months. There are statistically significant differences in applied DM therapy by gender (chi-square=11.939, p<0.05). Hypertension was more frequent in women (79.2%:69.2%), hyperlipidemia was equally presented in both sexes (50%:50%), obesity was more prevalent among women (25%:7.7%), while alcoholism and smoking were more frequent in men (7.7%:0%; 34.6%:8.3%). There are statistically significant differences in the prevalence of risk factors by gender (chi-square=10.013, p<0.05).

CONCLUSIONS
The DPNP incidence was higher in patients with longer duration of the disease, but without significant gender differences. Fasting blood glucose and HbA1c were significantly higher in patients with DPNP compared to patients without DPNP (p<0.05). The dominant symptoms of DPNP were paresthesia (44%) and hypoesthesia (28%). Regarding variable risk factors, the most common were hypertension and hyperlipidemia, without statistical significance in gender distribution, while smoking was significantly more common in men than women (34.6%:8.3%). DPNP was present in 43.2% of men who use insulin therapy, while 54.2% of women with DPNP used oral therapy. The lowest frequency of DPNP was found in patients treated with combined therapy. Motor conduction velocity of n. peroneus was significantly lower in men using insulin therapy and/or combined therapy (p<0.05), whereas in patients on oral therapy there was no significant gender difference. Timely DM type 2 diagnosis with proper treatment and electromyoneurographic monitoring (especially in older men) can prevent onset of diabetic polyneuropathy and contribute to its successful treatment.

diabetic polyneuropathy
inpatient
fasting blood glucose
HbA1c
electroneuromyography
diabetes mellitus
ENMG


Complete chloroplast genome of Prunus yedoensis Matsum.(Rosaceae), wild and endemic flowering cherry on Jeju Island, Korea.

Abstract: The complete chloroplast genome sequences of the wild flowering cherry, Prunus yedoensis Matsum., which is native and endemic to Jeju Island, Korea, is reported in this study. The genome size is 157 786 bp in length with 36.7% GC content, which is composed of LSC region of 85 908 bp, SSC region of 19 120 bp and two IR copies of 26 379 bp each. The cp genome contains 131 genes, including 86 coding genes, 8 rRNA genes and 37 tRNA genes. The maximum likelihood analysis was conducted to verify a phylogenetic position of the newly sequenced cp genome of P. yedoensis using 11 representatives of complete cp genome sequences within the family Rosaceae. The genus Prunus exhibited monophyly and the result of the phylogenetic relationship agreed with the previous phylogenetic analyses within Rosaceae.

Cho|Myong-Suk|MS|
Hyun Cho|Chung|C|
Yeon Kim|Su|S|
Su Yoon|Hwan|H|
Kim|Seung-Chul|SC|

D001482:Base Composition
D018742:DNA, Chloroplast
D019143:Evolution, Molecular
D059646:Genome Size
D054628:Genome, Chloroplast
D010802:Phylogeny
D027861:Prunus
D012335:RNA, Ribosomal
D012343:RNA, Transfer
D056910:Republic of Korea
D000073336:Whole Genome Sequencing

Prunus yedoensis
wild flowering cherry
Cerasus, endemic species
natural hybrid


Minimal changes in telomere length after a 12-week dietary intervention with almonds in mid-age to older, overweight and obese Australians: results of a randomised clinical trial.

Abstract: Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50-80 years) were randomised to an AED (n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in samples of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD - 14·3 %; P < 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (-12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.

Telomere length
Almonds
Diet
Diet quality
Ageing


Neural Entrainment to the Beat: The "Missing-Pulse" Phenomenon.

Abstract: Most humans have a near-automatic inclination to tap, clap, or move to the beat of music. The capacity to extract a periodic beat from a complex musical segment is remarkable, as it requires abstraction from the temporal structure of the stimulus. It has been suggested that nonlinear interactions in neural networks result in cortical oscillations at the beat frequency, and that such entrained oscillations give rise to the percept of a beat or a pulse. Here we tested this neural resonance theory using MEG recordings as female and male individuals listened to 30 s sequences of complex syncopated drumbeats designed so that they contain no net energy at the pulse frequency when measured using linear analysis. We analyzed the spectrum of the neural activity while listening and compared it to the modulation spectrum of the stimuli. We found enhanced neural response in the auditory cortex at the pulse frequency. We also showed phase locking at the times of the missing pulse, even though the pulse was absent from the stimulus itself. Moreover, the strength of this pulse response correlated with individuals' speed in finding the pulse of these stimuli, as tested in a follow-up session. These findings demonstrate that neural activity at the pulse frequency in the auditory cortex is internally generated rather than stimulus-driven. The current results are both consistent with neural resonance theory and with models based on nonlinear response of the brain to rhythmic stimuli. The results thus help narrow the search for valid models of beat perception.SIGNIFICANCE STATEMENT Humans perceive music as having a regular pulse marking equally spaced points in time, within which musical notes are temporally organized. Neural resonance theory (NRT) provides a theoretical model explaining how an internal periodic representation of a pulse may emerge through nonlinear coupling between oscillating neural systems. After testing key falsifiable predictions of NRT using MEG recordings, we demonstrate the emergence of neural oscillations at the pulse frequency, which can be related to pulse perception. These findings rule out alternative explanations for neural entrainment and provide evidence linking neural synchronization to the perception of pulse, a widely debated topic in recent years.

oscillations
pulse
neural resonance theory
MEG
auditory rhythm


Outcome after PORT in ypN2 or R1/R2 versus no PORT in ypN0 Stage III-N2 NSCLC after Induction Chemotherapy and Resection.

Abstract:
INTRODUCTION
We investigated patients with contemporarily staged and treated stage III-N2 NSCLC treated with induction chemotherapy and surgery with or without postoperative radiotherapy (PORT). We focused on survival and toxicity and investigated what additional PORT may offer in patients with ypN2 status or incomplete resection.

METHODS
We identified 161 patients with pathologically proven, resectable stage III-N2 NSCLC from our prospective database who were treated between 1998 and 2012. Of these patients, 150 without progressive disease after chemotherapy underwent resection. Patients with ypN2 status or R1/2 resection received three-dimensional PORT (n = 70) to a dose of 50 to 66 Gy in 2-Gy fractions.

RESULTS
The mean follow-up time was 49 months. The 5-year overall survival (OS) rate was 35.1% in intention-to-treat analysis; relapse-free survival was 31.8%, the cumulative local recurrence (LR) rate was 50.9%, and the distant metastasis rate was 63.4%. The 5-year OS, relapse-free survival, and cumulative LR and distant metastasis rates were 32.0%, 32.9%, 47.0%, and 63.9% in the PORT group versus 38.1%, 30.7%, 54.1%, and 63.2% in the non-PORT group. These results were not significantly different, even though patients in the PORT group had worse prognostic features. Cardiac toxicity was higher in the non-PORT group (p = 0.02), but pulmonary toxicity was similar (p = 0.15). There was no difference between the two groups regarding dyspnea (p = 0.32), cough (p = 0.37), forced expiratory volume in 1 second (p = 0.30), and diffusing capacity of the lung for carbon monoxide (p = 0.61).

CONCLUSIONS
A similar outcome (OS, LR, and toxicity) was seen in both patient groups (PORT versus non-PORT group). Despite the limitations of this retrospective study, PORT can be both effective and safe for patients with stage III-N2 NSCLC with an R1/R2 resection or yN2 after induction chemotherapy and surgery.

Billiet|Charlotte|C|
Peeters|Stéphanie|S|
Decaluwé|Herbert|H|
Vansteenkiste|Johan|J|
Dooms|Christophe|C|
Deroose|Christophe M|CM|
Hendrikx|Marc|M|
De Leyn|Paul|P|
Bulens|Paul|P|
Karim|Rezaul|R|
Le Péchoux|Cécile|C|
Mebis|Jeroen|J|
De Ruysscher|Dirk|D|

NSCLC
Postoperative radiotherapy
Survival
Local tumor control
Stage III
Toxicity N2


The role of visfatin in pathogenesis of gestational diabetes (GDM).

Abstract: Gestational diabetes (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. Two major metabolic disorders: insulin resistance and β-cells dysfunction, play currently major role in pathogenesis of GDM. Adipose tissue is an organ involved in production of adipokines, which have various influence on metabolism of glucose and lipids. Visfatin is an adipokine mainly produced and secreted by the fat tissue. It exerts an insulin-like effect by binding to the insulin receptor-1 and have hypoglycemic effect. Visfatin appears to be an important factor in the pathophysiology of GDM. The aim of this article is to review the literature concerning the relationship between the adipokine mentioned above and GDM, and to clarify its role in the pathophysiology of GDM.

Radzicka|Sandra|S| Pietryga|Marek|M| Iciek|Rafal|R| Brązert|Jacek|J|

visfatin
GDM
NAMPT
adipocytokines
gestational diabetes mellitus


Multiple mathematical models of diffusion-weighted magnetic resonance imaging combined with prognostic factors for assessing the response to neoadjuvant chemotherapy and radiation therapy in locally advanced rectal cancer.

Abstract:
PURPOSE
To investigate whether the apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) based on histogram analyses derived from the whole-tumor volume combined with prognostic factors can be used to assess the response to chemotherapy and radiation therapy (CRT) in locally advanced rectal cancer (LARC).

MATERIALS AND METHODS
This study included 60 patients with LARC who underwent diffusion-weighted imaging with 9b values (0-1000s/mm2) before CRT. Histograms derived from the whole-tumor volume were used to obtain the ADC, IVIM (Dslow, Dfast, and f), and SEM parameters (distributed diffusion coefficient (DDC) and α). The histogram metrics and prognostic factors before CRT were compared between pathological complete response (pCR) and non-pCR patients. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were generated to analyze the histogram metrics and prognostic factors.

RESULTS
A significant difference was only found in the tumor volume between the pCR and non-pCR groups (p = 0.033, AUC = 0.740). The ADC mean, DDC median, and most of the histogram metrics were significantly lower in the pCR group than the non-pCR group (p = 0.000-0.025), and AUC was highest for the ADC mean (0.890). Only the Dslow median differed significantly between the two groups (p = 0.023, AUC = 0.721). However, the Dfast, f, and α histogram metrics did not differ significantly between the pCR and non-pCR groups. The AUC for the ADC mean combined with the tumor volume was 0.908, with a sensitivity of 100% and specificity of 81%. The inter-observer agreements were good or excellent for the ADC and SEM histogram parameters but generally fair for IVIM.

CONCLUSION
The whole-tumor ADC mean combined with the tumor volume was highly accurate for predicting pCR. The IVIM models were inferior to ADC and SEM at predicting pCR.

Liang|Chun-Yi|CY| Chen|Mao-Dong|MD| Zhao|Xi-Xi|XX| Yan|Cheng-Gong|CG| Mei|Ying-Jie|YJ| Xu|Yi-Kai|YK|

D038524:Diffusion Magnetic Resonance Imaging

Multiple mathematical models
Locally advanced rectal cancer
Whole-tumor volume
DWI
Histogram analysis
Response prediction


The use of a custom-made mouthguard stabilizes the electromyographic activity of the masticatory muscles among Karate-Dō athletes.

Abstract:
AIMS
To analyze and compare the electromyographic activity of the temporal (anterior portion) and masseter muscles among Karate-Dō athletes before and after training, with and without the use of a mouthguard.

METHODS
Twenty athletes (14 males and 6 females) with a mean age of 23.7 ± 7.5 years participated. They had surface electromyography recordings taken of their bilateral temporal and masseter muscles before and after training under the following conditions: no mouthguard, with a ready-made mouthguard, and with a custom-made mouthguard. Activity was examined at mandibular rest, while clenching, and at maximum voluntary contraction. The data were normalized using the mean maximum voluntary contraction.

RESULTS
The right (p = 0.005) and left (p = 0.015) temporal muscles showed significantly lower electromyographic activity with a custom-made mouthguard compared with no mouthguard after training while clenching. The electromyographic activity of the temporal and masseter muscles did not show significant differences when tested at mandibular rest and while clenching before or after training with a custom-made mouthguard (p > 0.05).

CONCLUSION
The use of a custom-made mouthguard preserved participants' electromyographic profiles before and after training; thus, they allow for stable muscle activity during the training of Karate-Dō athletes.

Raquel|Gilsane|G|
Namba|Eli Luis|EL|
Bonotto|Daniel|D|
Ribeiro Rosa|Edvaldo Antônio|EA|
Trevilatto|Paula Cristina|PC|
Naval Machado|Maria Ângela|MÂ|
Vianna-Lara|Michelle Santos|MS|
Azevedo-Alanis|Luciana Reis|LR|

Facial injuries
Injury prevention
Martial arts


Manifesto on united airways diseases (UAD): an Interasma (global asthma association - GAA) document.

Abstract:
OBJECTIVE
The large amount of evidence and the renewed interest in upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD).

METHODS
Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members.

RESULTS
The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refers to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life.

CONCLUSIONS
Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and home based continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.

manifesto
United Airways Diseases
Interasma
consensus


Primary aneurysmal bone cyst of talus.

Abstract: Aneurysmal bone cyst (ABC) of the talus is an extremely rare lesion; less than 20 cases have been reported in PubMed till 2012. We report a primary ABC of the talus in a 20-year-old male that was managed by extended intralesional curettage with phenol as an adjuvant and autologous cancellous iliac crest bone grafting. The patient had excellent functional outcome and there was no recurrence at 2 years of follow-up.

Sharma|Siddhartha|S| Gupta|Parikshaa|P| Sharma|Sarthak|S| Singh|Manjeet|M| Singh|Dara|D|


Lactate dehydrogenase as a prognostic marker in neoplastic meningitis.

Abstract: This study aimed to establish the prognostic utility of lactate dehydrogenase (LDH) levels in the cerebrospinal fluid (CSF) of patients with neoplastic meningitis (NM). Patients with a confirmed diagnosis of NM at a cancer referral center were included. Data on demographic and oncological background, clinical symptoms, diagnostic tests, treatment, and survival were analyzed. In total, 119 patients were included, 74% of whom were females. The mean age was 44.2 years at the time of cancer diagnosis and 46.6 years at the time between NM diagnosis. Primary cancers were mostly breast cancer, lung cancer, or hematologic malignancies. The mean Karnofsky performance score (KPS) was 65. Frequent clinical symptoms were visual complaints, headache, cranial neuropathy, focal weakness, and decreased awareness. Diagnosis was made based on clinical symptoms, cytological CSF analysis results, and/or magnetic resonance imaging findings. The median overall survival (OS) was 4 months (95% CI 2.48-5.52). Prognostic variables associated with a better OS were hematopoietic malignancies, KPS ≥ 70, absence of meningeal signs, receiving any form of treatment, normal CSF glucose levels, and normal CSF LDH levels. After bivariate analysis, high LDH in the CSF remained statistically significant as a poor prognostic indicator. The LDH level is a useful parameter to assess the prognosis of patients with NM. Other factors associated with the prognosis of these patients were tumor type, CSF glucose levels, performance status, and receiving any form of treatment.

Cacho-Díaz|Bernardo|B|
Lorenzana-Mendoza|Nydia A|NA|
Reyes-Soto|Gervith|G|
Hernández-Estrada|Allan|A|
Monroy-Sosa|Alejandro|A|
Guraieb-Chahin|Paola|P|
Cantu-de-León|David|D|

Lactate dehydrogenase
Neoplastic meningitis
Survival
Prognosis
Meningeal carcinomatosis


Veterinary Compounding: Regulation, Challenges, and Resources.

Abstract: The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies. The scope of veterinary compounding is broad and focused primarily on meeting the therapeutic needs of companion animals and not food-producing animals in order to avoid human exposure to drug residues. As beneficial as compounded medical therapies may be to animal patients, these therapies are not without risks, and serious adverse events may occur from poor quality compounds or excipients that are uniquely toxic when administered to a given species. Other challenges in extemporaneous compounding for animals include significant regulatory variation across the global veterinary community, a relative lack of validated compounding formulas for use in animals, and poor adherence by compounders to established compounding standards. The information presented in this article is intended to provide an overview of the current landscape of compounding for animals; a discussion on associated benefits, risks, and challenges; and resources to aid compounders in preparing animal compounds of the highest possible quality.

veterinary
compounding
veterinary pharmacy


Quantification of Liver Iron Overload: Correlation of MRI and Liver Tissue Biopsy in Pediatric Thalassemia Major Patients Undergoing Bone Marrow Transplant.

Abstract: Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5 Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7 years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p < 0.001). Also, there was a significant correlation between serum ferritin levels and liver R2* MRI (r = 0.5647; p < 0.01). Two patients had high variance in serum ferritin levels (2100 and 4100 mg/g) while their LIC was around 24 mg/g, whereas the difference was not seen in T2* MRI. Hence, the liver T2* MRI is a better modality for assessing LIC. Serum ferritin is less reliable than quantitative MRI. The liver T2* MRI is a safe, reliable, feasible and cost-effective method compared to liver tissue biopsy for LIC assessment.

Bafna|Varun|V|
Bhat|Sunil|S|
Raj|Vimal|V|
Badiger|Shobha|S|
Annapandian|Vellaichamy Muthupandi|VM|
Nataraj|K S|KS|
Damodar|Sharat|S|0000-0003-2374-8655

Thalassemia
Bone marrow transplant
Liver iron concentration
Magnetic resonance image
T2* MRI
R2* MRI


The immunogenicity and protection effect of the BPL-inactivated CA16 vaccine in different animal systems.

Abstract: We evaluated the effect of a β-propiolactone (BPL)-inactivated coxsackievirus A16 (CA16) vaccine, using three immunogenicity evaluation and two animal challenge systems. A CA16 virus strain, named 419, was used as the production strain. Another CA16 strain, named 1131, was isolated and used as the challenge strain in intracerebral inoculation of neonatal mice for the calculation of median lethal dose (LD 50). In the passive and maternal antibody-protection challenge systems, all results indicated that the vaccine could protect mouse pups from lethal challenge with the CA16 virus. In the immunogenicity systems, three types of animal (mouse, rat, and cynomolgus monkey), were immunized with the 419/CA16 vaccine. The dose-effect relationship and the antibody-generation routine were described. The CA16 vaccine induced a more potent serum antibody effect in rat than in mouse. The serum antibody titer was detectable more than 63 days after the initial vaccination. We also identified tools to evaluate the effect of the BPL-inactivated CA16 vaccine.

Qi An|Wen|W|
Guo Su|Zhi|Z|
Wen Pan|Ruo|R|
Ping Yang|Bao|B|
Chao Zhang|Yong|Y|
Shi|Liang|L|
Li|Qing|Q|

immunogenicity
vaccine
coxsackievirus A16
challenge systems
enterovirus


Evaluation of polar organic chemical integrative and hollow fibre samplers for the determination of a wide variety of organic polar compounds in seawater.

Abstract: The calibration of two passive samplers for the determination of 20 emerging organic compounds in seawater is described in this work: i) a new version of polar organic chemical integrative sampler (POCIS) containing 100 mg of mixed-mode anion exchanger (Strata X-AW) and 100 mg of polymeric HLB (Plexa) sorbent materials and using a highly porous Nylon membrane (30-μm pore size) and ii) polyethersulfone (PES) hollow fibre. Among the studied contaminants, herbicides, hormones, life style products (stimulants and artificial sweeteners), industrial chemicals (corrosion inhibitor and fluorinated compounds), personal care products and several pharmaceuticals were included. In the case of POCIS, both the sorbents and the Nylon membranes were extracted and analysed independently. The calibration set up consisted on a continuous-flow tank that was fed with a continuous flow of seawater (2 L/h) and a stock mixture of contaminants (20 mL/h), assuring a nominal concentration of ~ 600 ng/L (each analyte) in the tank. The uptake was linear in POCIS sorbent and Nylon membranes but exponential for PES hollow fibres. Furthermore, the highest sampling rates (Rs) values were obtained in POCIS sorbent (between 2.7 for acetaminophen and 491 mL/day for perfluoro-n-octanoic acid, PFOA) followed by Nylon membranes (between 3.6 for OBT and 50 mL/day for telmisartan) and the lowest were those from PES fibres (between 1.7 for bezafibrate and 157 mL/day for butylparaben). Additionally, five deuterated compounds ([2H5]-atrazine, [2H3]-amitriptyline, [2H7]-irbesartan, [2H3]-ketoprofen and [2H9]-progesterone) were studied as candidates for performance reference compounds (PRCs) in both POCIS and PES, and though [2H5]-atrazine, [2H9]-progesterone and [2H3]-amitriptyline showed acceptable results in the case of POCIS, only [2H5]-atrazine provided a good validation. In the case of PES fibres, the PRC corrections did not provide acceptable results due to a low dissipation of the PRCs. Finally, POCIS were deployed in two sites of the low part of the estuary of Bilbao (northern Spain) from where water samples were also taken and analysed. As a result, in addition to the overall good agreement between the passive and active samplings, passive samplers allowed the determination of several compounds that were below the detection limits in the active sampling.

Mijangos|Leire|L| Ziarrusta|Haizea|H| Prieto|Ailette|A| Zugazua|Oihane|O| Zuloaga|Olatz|O| Olivares|Maitane|M| Usobiaga|Aresatz|A| Paschke|Albrecht|A| Etxebarria|Nestor|N|

Polar organic chemical integrative sampler


Precise breakpoint detection in a patient with 9p- syndrome.

Abstract: We present a case of 9p- syndrome with a complex chromosomal event originally characterized by the classical karyotype approach as 46,XX,der(9)t(9;13)(p23;q13). We used advanced technologies (Bionano Genomics genome imaging and 10× Genomics sequencing) to characterize the location of the translocation and accompanying deletion on Chromosome 9 and duplication on Chromosome 13 with single-nucleotide breakpoint resolution. The translocation breakpoint was at Chr 9:190938 and Chr 13:50850492, the deletion at Chr 9:1-190938, and the duplication at Chr 13:50850492-114364328. We identified genes in the deletion and duplication regions that are known to be associated with this patient's phenotype (e.g., ZIC2 in dysmorphic facial features, FOXD4 in developmental delay, RNASEH2B in developmental delay, and PCDH9 in autism). Our results indicate that clinical genomic assessment of individuals with complex karyotypes can be refined to a single-base-pair resolution when utilizing Bionano and 10× Genomics sequencing. With the 10× Genomics data, we were also able to characterize other variation (e.g., loss of function) throughout the remainder of the patient's genome. Overall, the Bionano and 10× technologies complemented each other and provided important insight into our patient with 9p- syndrome. Altogether, these results indicate that newer technologies can identify precise genomic variants associated with unique patient phenotypes that permit discovery of novel genotype-phenotype correlations and therapeutic strategies.

Ng|Jeffrey|J|
Sams|Eleanor|E|
Baldridge|Dustin|D|
Kremitzki|Milinn|M|
Wegner|Daniel J|DJ|
Lindsay|Tina|T|
Fulton|Robert|R|
Cole|F Sessions|FS|
Turner|Tychele N|TN|

congenital sensorineural hearing impairment


Bootstrap ARDL on Health Expenditure, CO2 Emissions, and GDP Growth Relationship for 18 OECD Countries.

Abstract: Using annual time-series data over the period 1975-2017, the researcher applied the bootstrap autoregressive-distributed lag (ARDL) cointegration model developed by McNown et al. (1) to examine whether there is a long run relationship among health expenditure, CO2 emissions, and gross domestic product (GDP) per capita in 18 Organization for Economic Cooperation and Development (OECD) countries. We find cointegration exists in Netherlands when real GDP per capita serves as a dependent variable, in New Zealand when health expenditure is the dependent variable, and in the United States when CO2 emissions are dependent variables. The main results show evidence of a short run relationship between the three variables. The empirical results support that there is a bidirectional causality between health expenditure and GDP growth for Germany and the United States, between CO2 emissions and GDP growth for Canada, Germany, and the United States, and between health expenditure and CO2 emissions for New Zealand and Norway. The results also indicate that there are unidirectional causality in other countries.

Wang|Chien-Ming|CM| Hsueh|Hsin-Pei|HP| Li|Fangjhy|F| Wu|Cheng-Feng|CF|

bootstrap ARDL
health expenditure
CO2 emissions
GDP growth
long run relation


Essential Oil from Bark of Aniba parviflora (Meisn.) Mez (Lauraceae) Reduces HepG2 Cell Proliferation and Inhibits Tumor Development in a Xenograft Model.

Abstract: Aniba parviflora (Meisn.) Mez (Lauraceae) is an aromatic plant of the Amazon rainforest, which has a tremendous commercial value in the perfumery industry; it is popularly used as flavoring sachets and aromatic baths. In Brazilian folk medicine, A. parviflora is used to treat victims of snakebites. Herein, we analyzed the chemical composition of A. parviflora bark essential oil (EO) and its effect on the growth of human hepatocellular carcinoma HepG2 cells in vitro and in vivo. EO was obtained by hydrodistillation and characterized by GC-MS and GC-FID. The main constituents of EO were linalool (16.3±3.15), α-humulene (14.5±2.41 %), δ-cadinene (10.2±1.09 %), α-copaene (9.51±1.12 %) and germacrene B (7.58±2.15 %). Initially, EO's cytotoxic effect was evaluated against five cancer cell lines (HepG2, MCF-7, HCT116, HL-60 and B16-F10) and one non-cancerous one (MRC-5), using the Alamar blue method after 72 h of treatment. The calculated IC50 values were 9.05, 22.04, >50, 15.36, 17.57, and 30.46 μg/mL, respectively. The best selectivity was for HepG2 cells with a selective index of 3.4. DNA Fragmentation and cell cycle distribution were quantified in HepG2 cells by flow cytometry after a treatment period of 24 and 48 h. The effect of EO on tumor development in vivo was evaluated in a xenograft model using C.B-17 SCID mice engrafted with HepG2 cells. In vivo tumor growth inhibition of HepG2 xenograft at the doses of 40 and 80 mg/kg were 12.1 and 62.4 %, respectively.

de Lima|Emilly J S P|EJSP|http://orcid.org/0000-0001-9866-6342

da Silva|Felipe M A|FMA|http://orcid.org/0000-0002-1809-1372

D004354:Drug Screening Assays, Antitumor

Aniba parviflora
Lauraceae
HepG2
cytotoxicity
antitumor agents


Sensing of hydrophobic cavity of serum albumin by an adenosine analogue: fluorescence correlation and ensemble spectroscopic studies.

Abstract: Adenosine is a naturally occurring purine nucleoside that plays important role in various biochemical processes. We have studied the binding of TNP-Ado (trinitrophenylated-adenosine), a fluorescent analogue of adenosine (which itself is a weak fluorophore), with a model transport protein, bovine serum albumin (BSA). The binding affinity was determined using Fluorescence correlation spectroscopy (FCS) and compared with its value obtained from macroscopic fluorescence spectroscopic studies. Fluorescence and circular dichroism (CD) spectroscopies were employed together with molecular docking study to locate the probable binding site of TNP-Ado on BSA and its effect on the conformation and stability of BSA. Fluorescence studies showed that TNP-Ado binds to BSA in 1:1 stoichiometry via an entropically favoured process. Induced CD spectra revealed that a chiro-optical switching of TNP-Ado occurs upon binding to BSA. Results on urea-induced denaturation of BSA and docking study suggested that the binding site for the ligand is in the hydrophobic subdomain IIA of BSA, consistent with the results of other measurements. This study establishes TNP-Ado as a sensor of hydrophobic regions in proteins like serum albumin, having the capability of detecting a minimum concentration of 140ng/ml protein. FCS measurement of binding interaction of rhodamine-labeled TNP-Ado (RTNP-Ado) with BSA yielded an association constant of KFCS=(1.03±0.06) × 10(4)M(-1). The association constants (Ka) obtained for binding of BSA with rhodamine-free (i.e. TNP-Ado) and rhodamine-labeled (RTNP-Ado) ligands, obtained using the ensemble spectroscopic technique, were (2.3±0.06) × 10(5)M(-1) and (3.4±0.03) × 10(4)M(-1), respectively. The difference between the values of Ka for the free and labeled ligands suggests that fluorescent labeling of small molecules perceptibly interferes with the binding process. On the other hand, the difference in Ka obtained by FCS and ensemble techniques is due to the fact that while the former measures the change in the diffusion constant (i.e. size) of RTNP-Ado upon binding to BSA, the latter focuses on the change of tryptophan emission properties of BSA due to the presence of bound RTNP-Ado.

Nag|Moupriya|M| Bera|Kallol|K| Chakraborty|Sandipan|S| Basak|Soumen|S|

D057927:Hydrophobic and Hydrophilic Interactions

Hydrophobic
Adenosine analogue
Fluorescence correlation spectroscopy
Molecular docking study
Chiro-optical switching


Effects of different roughage sources and feeding levels on adipogenesis of ovine adipocytes.

Abstract: The objective of the present study was to conduct an adipogenic evaluation of different roughage sources and feeding levels during ruminant adipocyte differentiation in vitro. Six wether sheep were divided into a timothy hay feeding group (TFG, n = 3) and an Italian ryegrass straw feeding group (IFG, n = 3). The sheep were fed high-roughage (HR), medium roughage (MR) and low-roughage (LR) diets in a one-way layout design each over a 6-day period. Sheep serum samples collected on the last day of each dietary treatment were added to an adipogenic induction medium for differentiation of preadipocytes derived from sheep subcutaneous adipose tissue. The cytoplasmic lipid accumulations in the TFG serum-treated preadipocytes were significantly higher than those of the IFG-serum treated preadipocytes on day 12. Messenger RNA expression of CCAAT/enhancer-binding protein (C/EBP)-α, C/EBP-β, C/EBP-δ, fatty-acid-binding protein (aP2) and stearoyl-coenzyme A desaturase (SCD) were regulated by each serum treatment. This study shows that different roughage source diets and roughage-to-concentrate ratio diets can regulate adipocyte differentiation via ruminant blood composition.

Kim|Da-Hye|DH| Choi|Ki-Choon|KC| Ichinohe|Toshiyoshi|T| Song|Sang-Houn|SH|

adipocyte differentiation
lipid accumulation
serum treatment


A randomized controlled trial of two mail-based lifestyle interventions for breast cancer survivors.

Abstract:
PURPOSE
Although breast cancer survivors' lifestyle choices affect their subsequent health, a majority do not engage in healthy behaviors. Because treatment end is a "teachable moment" for potentially altering lifestyle change for breast cancer survivors, we developed and tested two mail-based interventions for women who recently completed primary treatment.

METHODS
One hundred seventy-three survivors were randomly assigned to (1) Targeting the Teachable Moment (TTMI, n = 57), (2) Standard Lifestyle Management (SLM, n = 58), or (3) usual care (UC, n = 58) control group. Participants who were assigned to TTMI and SLM received relevant treatment materials biweekly for 4 months. Participants were assessed at baseline (T1, before randomization), post-treatment (T2, 4 months), and follow-up (T3, 7 months). Fruit and vegetable (F/V) intake, fat intake, and moderate-to-vigorous physical activity (MVPA) were assessed.

RESULTS
Results showed promise for these mail-based interventions for changes in health behaviors: Survivors in TTMI (+.47) and SLM (+.45) reported increased F/V intake, whereas those in UC (-.1) reported decreased F/V intake from T1 to T2. Changes in minutes of MVPA from T1 to T2 were higher in SLM than UC and marginally higher in TTMI than UC. However, these differences were due to decreased MVPA in UC rather than increased MVPA in the intervention groups. There were no group differences regarding fat intake. Survivors reported high satisfaction and preference for mail-based interventions, supporting feasibility.

CONCLUSIONS
Mail-based lifestyle interventions for breast cancer survivors may benefit F/V intake and physical activity. Further testing and optimizing of these interventions is warranted.

Park|Crystal L|CL|
Cho|Dalnim|D|
Salner|Andrew L|AL|
Dornelas|Ellen|E|

Teachable moment
Mail-based intervention
Physical activity
Dietary behaviors


Estimation of co-variance components, genetic parameters, and genetic trends of reproductive traits in community-based breeding program of Bonga sheep in Ethiopia.

Abstract:
OBJECTIVE
The objectives of the study were to evaluate reproductive performance and selection response through genetic trend of community-based breeding programs (CBBPs) of Bonga sheep.

METHODS
Reproduction traits data were collected between 2012 and 2018 from Bonga sheep CBBPs. Phenotypic performance was analyzed using the general linear model procedures of Statistical Analysis System. Genetic parameters were estimated by univariate animal model for age at first lambing (AFL) and repeatability models for lambing interval (LI), litter size (LS), and annual reproductive rate (ARR) traits using restricted maximum likelihood method of WOMBAT. For correlations bivariate animal model was used. Best model was chosen based on likelihood ratio test. The genetic trends were estimated by the weighted regression of the average breeding value of the animals on the year of birth/ lambing.

RESULTS
The overall least squares mean±standard error of AFL, LI, LS, and ARR were 375± 12.5, 284±9.9, 1.45±0.010, and 2.31±0.050, respectively. Direct heritability estimates for AFL, LI, LS, and ARR were 0.07±0.190, 0.06±0.120, 0.18±0.070, and 0.25±0.203, respectively. The low heritability for both AFL and LI showed that these traits respond little to selection programs but rather highly depend on animal management options. The annual genetic gains were -0.0281 days, -0.016 days, -0.0002 lambs and 0.0003 lambs for AFL, LI, LS, and ARR, respectively.

CONCLUSION
Implications of the result to future improvement programs were improving management of animals, conservation of prolific flocks and out scaling the CBBP to get better results.

Areb|Ebadu|E|
Getachew|Tesfaye|T|
Kirmani|M A|MA|
G Silase|Tegbaru|T|
Haile|Aynalem|A|

Genetic Parameter
Genetic Trend
Bonga Sheep
Reproductive Performance
Recording


Assessing the evidence for weight loss strategies in people with and without type 2 diabetes.

Abstract: This review will examine topical issues in weight loss and weight maintenance in people with and without diabetes. A high protein, low glycemic index diet would appear to be best for 12-mo weight maintenance in people without type 2 diabetes. This dietary pattern is currently being explored in a large prevention of diabetes intervention. Intermittent energy restriction is useful but no better than daily energy restriction but there needs to be larger and longer term trials performed. There appears to be no evidence that intermittent fasting or intermittent severe energy restriction has a metabolic benefit beyond the weight loss produced and does not spare lean mass compared with daily energy restriction. Meal replacements are useful and can produce weight loss similar to or better than food restriction alone. Very low calorie diets can produce weight loss of 11-16 kg at 12 mo with persistent weight loss of 1-2 kg at 4-6 years with a very wide variation in long term results. Long term medication or meal replacement support can produce more sustained weight loss. In type 2 diabetes very low carbohydrate diets are strongly recommended by some groups but the long term evidence is very limited and no published trial is longer than 12 mo. Although obesity is strongly genetically based the microbiome may play a small role but human evidence is currently very limited.

Protein
Glycemic index
Intermittent energy restriction
Very low calorie diet
Very low carbohydrate diet
Alternate day fasting
Low fat diets


Prognosis for Cutaneous Melanoma by Clinical and Pathological Profile: A Population-Based Study.

Abstract:
Introduction
Among white people, the incidence of cutaneous malignant melanoma (CMM) has been increasing steadily for several decades. Meanwhile, there has also been a significant improvement in 5-year survival among patients with melanoma. This population-based cohort study investigates the five-year melanoma-specific survival (MSS) for all melanoma cases recorded in 2015 in the Veneto Tumor Registry (North-Est Italian Region), taking both demographic and clinical-pathological variables into consideration.

Methods
The cumulative melanoma-specific survival probabilities were calculated with the Kaplan-Meier method, applying different sociodemographic and clinical-pathological variables. Cox's proportional hazards model was fitted to the data to assess the association between independent variables and MSS, and also overall survival (OS), calculating the hazard ratios (HR) relative to a reference condition, and adjusting for sex, age, site of tumor, histotype, melanoma ulceration, mitotic count, tumor-infiltrating lymphocytes (TIL), and stage at diagnosis.

Results
Compared with stage I melanoma, the risk of death was increased for stage II (HR 3.31, 95% CI: 0.94-11.76, p=0.064), almost ten times higher for stage III (HR 10.51, 95% CI: 3.16-35.02, p<0.001), and more than a hundred times higher for stage IV (HR 117.17, 95% CI: 25.30-542.62, p<0.001). Among the other variables included in the model, the presence of mitoses and histological subtype emerged as independent risk factors for death.

Conclusions
The multivariable analysis disclosed that older age, tumor site, histotype, mitotic count, and tumor stage were independently associated with a higher risk of death. Data on survival by clinical and morphological characteristics could be useful in modelling, planning, and managing the most appropriate treatment and follow-up for patients with CMM.

Buja|Alessandra|A|
Bardin|Andrea|A|
Damiani|Giovanni|G|
Zorzi|Manuel|M|
De Toni|Chiara|C|
Fusinato|Riccardo|R|
Spina|Romina|R|
Vecchiato|Antonella|A|
Del Fiore|Paolo|P|
Mocellin|Simone|S|
Baldo|Vincenzo|V|
Rugge|Massimo|M|
Rossi|Carlo Riccardo|CR|

melanoma
survival
cancer survival
clinical characteristics
epidemiology


Transcriptome analysis of seed dormancy after rinsing and chilling in ornamental peaches (Prunus persica (L.) Batsch).

Abstract:
BACKGROUND
Ornamental peaches cv. 'Yaguchi' (Prunus persica (L.) Batsch) can be propagated via seeds. The establishment of efficient seed treatments for early germination and seedling growth is required to shorten nursery and breeding periods. It is important, therefore, to identify potential candidate genes responsible for the effects of rinsing and chilling on seed germination. We hypothesized that longer rinsing combined with chilling of seeds can alter the genes expression in related to dormancy and then raise the germination rate in the peach. To date, most molecular studies in peaches have involved structural genomics, and few transcriptome studies of seed germination have been conducted. In this study, we investigated the function of key seed dormancy-related genes using next-generation sequencing to profile the transcriptomes involved in seed dormancy in peaches. De novo assembly and analysis of the transcriptome identified differentially expressed and unique genes present in this fruit.

RESULTS
De novo RNA-sequencing of peach was performed using the Illumina Miseq 2000 system. Paired-end sequence from mRNAs generated high quality sequence reads (9,049,964, 10,026,362 and 10,101,918 reads) from 'Yaguchi' peach seeds before rinsed (BR) and after rinsed for 2 or 7 days with a chilling period of 4 weeks (termed 2D4W and 7D4W), respectively. The germination rate of 7D4W was significantly higher than that of 2D4W. In total, we obtained 51,366 unique sequences. Differential expression analysis identified 7752, 8469 and 506 differentially expressed genes from BR vs 2D4W, BR vs 7D4W and 2D4W vs 7D4W libraries respectively, filtered based on p-value and an adjusted false discovery rate of less than 0.05. This study identified genes associated with the rinsing and chilling process that included those associated with phytohormones, the stress response and transcription factors. 7D4W treatment downregulated genes involved in ABA synthesis, catabolism and signaling pathways, which eventually suppressed abscisic acid activity and consequently promoted germination and seedling growth. Stress response genes were also downregulated by the 7D4W treatment, suggesting that this treatment released seeds from endodormancy. Transcription factors were upregulated by the BR and 2D4W treatment, suggesting that they play important roles in maintaining seed dormancy.

CONCLUSIONS
This work indicated that longer rinsing combined with chilling affects gene expression and germination rate, and identified potential candidate genes responsible for dormancy progression in seeds of 'Yaguchi' peach. The results could be used to develop breeding programs and will aid future functional genomic research in peaches and other fruit trees.

Kanjana|Worarad|W| Suzuki|Tomohiro|T| Ishii|Kazuo|K| Kozaki|Toshinori|T| Iigo|Masayuki|M| Yamane|Kenji|K|0000-0003-0255-0842

D018506:Gene Expression Regulation, Plant

Transcriptome
Rinsing
Chilling
Ornamental peach
Seed germination


Transcriptional regulation of OCT4 by the ETS transcription factor ESE-1 in NCCIT human embryonic carcinoma cells.

Abstract: The epithelium-specific ETS transcription factor-1 (ESE-1) is physiologically important in the pathogenesis of various diseases. Recently, OCT4, a transcription factor involved in stem cell pluripotency, has been implicated in tumorigenesis. In this study, we invested the molecular mechanism by which ESE-1 regulates transcription of OCT4 in NCCIT human embryonic carcinoma cells. Real-time PCR analysis revealed that OCT4 levels were high in undifferentiated NCCIT cells but significantly decreased upon retinoic acid-mediated differentiation, concomitant with up-regulation of ESE-1 expression. OCT4 mRNA level rose following shRNA-mediated knockdown of ESE-1, but declined when ESE-1 was overexpressed, suggesting that the expression levels of OCT4 and ESE-1 may be coordinated in an opposite manner. Promoter-reporter assays revealed that induced OCT4 promoter activity in NCCIT cells was significantly down-regulated by ESE-1 overexpression in a dose-dependent manner. The inhibitory effect of ESE-1 on OCT4 promoter activity was relieved by co-expression of an ESE-1 mutant lacking the transactivation domain, but not by mutants lacking other domains. Serial deletion and site-directed mutagenesis of the OCT4 promoter revealed that a potential ETS binding site (EBS) is present in the conserved region 2 (CR2). ESE-1 interacted with the EBS element in CR2 and enrichment of CR2 significantly increased upon RA-mediated differentiation of NCCIT cells, suggesting that this binding is likely to be involved in ESE-1-mediated repression of OCT4 promoter activity upon differentiation. Taken together, the results of this study reveal the molecular details of the mechanism by which the oncogenic factor ESE-1 regulates expression of the stem cell transcription factor OCT4 in pluripotent NCCIT cells.

Park|Sung-Won|SW|
Do|Hyun-Jin|HJ|
Ha|Woo Tae|WT|
Han|Mi-Hee|MH|
Yang|Heung-Mo|HM|
Lee|Soo-Hong|SH|
Song|Hyuk|H|
Kim|Nam-Hyung|NH|
Kim|Jae-Hwan|JH|

D002454:Cell Differentiation
D004268:DNA-Binding Proteins
D054278:Embryonal Carcinoma Stem Cells
D055785:Gene Knockdown Techniques
D006801:Humans
D009154:Mutation
D050814:Octamer Transcription Factor-3
D039904:Pluripotent Stem Cells
D011401:Promoter Regions, Genetic
D050783:Proto-Oncogene Proteins c-ets
D014157:Transcription Factors
D014158:Transcription, Genetic
D015533:Transcriptional Activation

Transcription
ESE-1
NCCIT cells
OCT4 promoter


Elution of High-affinity (>10-9 KD) Antibodies from Tissue Sections: Clues to the Molecular Mechanism and Use in Sequential Immunostaining.

Abstract: Inconsistent results obtained with published methods for the elution of antibodies from tissue sections prompted the assessment of both old and new methods in combination with monoclonal rabbit antibodies of known, increased affinity (above 1×10(-9) KD). We tested an acidic (pH 2) glycine buffer, a 6 M urea hot buffer and a 2-Mercaptoethanol, SDS buffer (2-ME/SDS). Some antibodies were not removed by the glycine pH 2 or 6 M urea hot buffers, indicating that antibodies survive much harsher conditions than previously believed. We found that the elution is dependent upon the antibody affinity and is reduced by species-specific crosslinking via a dimeric or Fab fragments of a secondary antibody. The high affinity bond of exogenous streptavidin with the endogenous biotin can be removed by 6 M urea but not by the other buffers. 2-ME/SDS buffer is superior to glycine pH 2 and 6 M urea hot elution buffers for all antibodies because of its irreversible effect on the structure of the antibodies. It also has a mild retrieving effect on some antigens present on routinely treated sections and no detrimental effect on the immunoreactivity of the tissue. Therefore, 2-ME/SDS buffer is the method of choice to perform multiple rounds of immunostaining on a single routine section.

Gendusa|Rossella|R|
Scalia|Carla Rossana|CR|
Buscone|Serena|S|
Cattoretti|Giorgio|G|

elution
antibody
affinity
multiple immunostaining
stripping


Surface Replacement Arthroplasty of the Humeral Head in Young, Active Patients: Midterm Results.

Abstract:
BACKGROUND
The treatment of glenohumeral arthritis in young, active patients remains controversial. Standard total shoulder arthroplasty in this patient group has not obtained the same satisfaction rate as in older patients. One surgical option that has emerged is humeral resurfacing.

HYPOTHESIS
Humeral head surface replacement arthroplasty (SRA) would provide satisfactory clinical outcomes in active patients, allowing them to maintain their normal lifestyle without activity restrictions.

STUDY DESIGN
Case series; Level of evidence, 4.

METHODS
From 2004 to 2007, all consecutive surface replacement arthroplasties of the humerus performed at the authors' institution were identified and retrospectively reviewed, and 118 patients who underwent SRA during this time were identified. This study included patients younger than 60 years who wished to maintain an active lifestyle; 52 of the 118 patients met the inclusion criteria. University of California at Los Angeles (UCLA) shoulder scores and subjective shoulder value (SSV) scores were used to measure clinical outcomes at an average follow-up of 6 years (range, 4-8 years). Of the 52 patients meeting the inclusion criteria, 48 were contacted and examined for the study, with 4 patients lost to follow-up.

RESULTS
The mean postoperative UCLA score was 28.03, with 1 patient requiring revision because of pain and glenoid wear. The mean SSV was 92% (range, 0%-100%), with 3 patients restricting their activity because of the shoulder. Forty-seven of the 48 contacted patients stated that, given the option, they would have the same surgery again. One patient required revision surgery because of pain.

CONCLUSION
Surface replacement arthroplasty provided reasonable results in patients younger than 60 years with high activity demands with a low rate of revision at midterm follow-up.

Iagulli|Nicholas D|ND|
Field|Larry D|LD|
Hobgood|E Rhett|ER|
Hurt|James A|JA|
Charles|Ryan|R|
O'Brien|Michael J|MJ|
Savoie|Felix H|FH|

surface replacement arthroplasty
glenohumeral arthritis
humeral head surface replacement
shoulder arthritis
young patients


Muscle group dependent responses to stimuli in a grasshopper model for tonic immobility.

Abstract: Tonic Immobility (TI) is a prolonged immobile condition exhibited by a variety of animals when exposed to certain stimuli, and is thought to be associated with a specific state of arousal. In our study, we characterize this state by using the reliably inducible TI state of the grasshopper (Hieroglyphus banian) and by monitoring abdominal pulsations and body movements in response to visual and auditory stimuli. These pulsations are present during the TI and 'awake', standing states, but not in the CO2 anesthetized state. In response to the stimuli, animals exhibited a suppression in pulsation and a startle response. The suppression of pulsation lasted longer than the duration of stimulus application. During TI, the suppression of pulsation does not habituate over time, whereas the startle response does. In response to the translating visual stimulus, the pulsations are suppressed at a certain phase independent of the time of stimulus application. Thus, we describe TI in Hieroglyphus banian as a state more similar to an 'awake' state than to an anesthetized state. During TI, the circuitry to the muscle outputs controlling the abdomen pulsation and the startle response are, at least in some part, different. The central pattern generators that maintain the abdomen pulsation receive inputs from visual and auditory pathways.

Tonic immobility
Habituation
Stimulus response


Testing independence of bivariate interval-censored data using modified Kendall's tau statistic.

Abstract: In this paper, we study a nonparametric procedure to test independence of bivariate interval censored data; for both current status data (case 1 interval-censored data) and case 2 interval-censored data. To do it, we propose a score-based modification of the Kendall's tau statistic for bivariate interval-censored data. Our modification defines the Kendall's tau statistic with expected numbers of concordant and disconcordant pairs of data. The performance of the modified approach is illustrated by simulation studies and application to the AIDS study. We compare our method to alternative approaches such as the two-stage estimation method by Sun et al. (Scandinavian Journal of Statistics, 2006) and the multiple imputation method by Betensky and Finkelstein (Statistics in Medicine, 1999b).

Testing independence
Kendall's tau
Current status data
Case 2 interval-censored data
Bivariate failure time data


DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition.

Abstract: The discovery of incretin-based medications represents a major therapeutic advance in the pharmacological management of type 2 diabetes mellitus (T2DM), as these agents avoid hypoglycemia, weight gain, and simplify the management of T2DM. Dipeptidyl peptidase-4 (CD26, DPP4) inhibitors are the most widely used incretin-based therapy for the treatment of T2DM globally. DPP4 inhibitors are modestly effective in reducing HbA1c (glycated hemoglobin) (≈0.5%) and while these agents were synthesized with the understanding of the role that DPP4 plays in prolonging the half-life of incretins such as glucagon-like peptide-1 and gastric inhibitory peptide, it is now recognized that incretins are only one of many targets of DPP4. The widespread expression of DPP4 on blood vessels, myocardium, and myeloid cells and the nonenzymatic function of CD26 as a signaling and binding protein, across a wide range of species, suggest a teleological role in cardiovascular regulation and inflammation. Indeed, DPP4 is upregulated in proinflammatory states including obesity, T2DM, and atherosclerosis. Consistent with this maladaptive role, the effects of DPP4 inhibition seem to exert a protective role in cardiovascular disease at least in preclinical animal models. Although 2 large clinical trials suggest a neutral effect on cardiovascular end points, current limitations of performing trials in T2DM over a limited time horizon on top of maximal medical therapy must be acknowledged before rendering judgment on the cardiovascular efficacy of these agents. This review will critically review the science of DPP4 and the effects of DPP4 inhibitors on the cardiovascular system.

Zhong|Jixin|J|
Maiseyeu|Andrei|A|
Davis|Stephen N|SN|
Rajagopalan|Sanjay|S|

diabetes mellitus
incretins
glucagon-like peptide-1
cardiovascular diseases
DPP4 protein, mouse


Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

Abstract: The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

Beattie|James|J|
Al-Khafaji|Hasanain|H|
Noer|Pernille R|PR|
Alkharobi|Hanaa Esa|HE|
Alhodhodi|Aishah|A|
Meade|Josephine|J|
El-Gendy|Reem|R|
Oxvig|Claus|C|

insulin-like growth factor-binding protein-4

insulin-like growth factor-binding protein-5


Optimisation of double-enzymatic extraction of arabinoxylan from fresh corn fibre.

Abstract: Enzymatic extraction of arabinoxylans (AXs) is an attractive and environmentally friendly extraction option, in which technical considerations (yield and purity) have been coupled with environmental concerns. Amano HC 90 and Cellulase were combined to evaluate their interactive effects on AX extraction from destarched, deproteinised bran (DSDPB). A response surface methodology was used to obtain the optimal extraction conditions. The experimental data fit well with the predicted values and the model adequately represented the actual relationship among the measured parameters. The extraction yield and AX content in the extract under optimal conditions (double-enzyme dose of 920 U/g, pH of 3.0, extraction temperature of 35.0 °C; extraction time of 6 h; and DSDPB to liquid ratio of 1:30) were 40.73 ± 0.09% and 75.88 ± 0.11%, respectively. The double-enzymatic extraction method of AX from fresh corn fibre was more efficient than the chemical method.

Ma|Fumin|F| Li|Xiaolei|X| Yin|Jiayu|J| Ma|Lin|L| Li|Dan|D|

Arabinoxylan
Fresh corn fibre
Enzymatic
Central composite rotatable design


Circ_0000526 Blocks the Progression of Breast Cancer by Sponging miR-492.

Abstract: Breast cancer is one of the leading causes of cancer-associated death. This work aimed to explore the expression, function, and mechanism of circ_0000526 on the progression of breast cancer.  The expressions of circ_0000526, miR-492, and suppressor of cytokine signaling 2 (SOCS2) in breast cancer samples were measured using quantitative real-time polymerase chain reaction. The correlation between pathological indexes of patients and the expression of circ_0000526 was also analyzed. Human breast cancer cell lines MCF-7 and MDA-MB-231 were applied to investigate the associated mechanism. Cell counting kit-8 assays were used to assess the effect of circ_0000526 on proliferation, and together with the wound healing assay, transwell assay was conducted to detect the effects of circ_0000526 on migration and invasion. Furthermore, luciferase reporter assay was used to verify the targeting relationship between miR-492 and circ_0000526. In addition, Western blot was performed to detect the regulatory effects of circ_0000526 on SOCS2.  Circ_0000526 expression in breast cancer samples was downregulated, which was correlated with unfavorable pathological indexes. It significantly inhibited the proliferation and metastasis of breast cancer cells, and facilitated apoptosis. The overexpression of circ_0000526 remarkably inhibited the expression of miR-492 by sponging it, and in turn promoted the expression of SOCS2.  Circ_0000526 served as a tumor suppressor, which could function as the sponge of miR-492, an oncogenic microRNA, in breast cancer, and enhance the expression of tumor suppressor SOCS2 indirectly.

Wang|Wen-Bin|WB| Ren|Ping|P| Ren|Fei-Hua|FH| Huang|Ming|M| Cheng|Xing|X|


Advanced alveolar soft part sarcoma responds to apatinib.

Abstract: Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). The patient was subsequently treated with apatinib (500 mg/day), a specific VEGFR-2 inhibitor. Treatment was well tolerated, and the patient exhibited a partial response, with the lung metastases reduced in size and number after one month of therapy. To date, 12-month progression-free survival has been achieved. Apatinib may provide an additional treatment option for metastatic ASPS, particularly in cases resistant to other chemotherapeutic options. Furtherstudies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib for treatment of ASPS.

Zhou|Yong|Y| Tang|Fan|F| Wang|Yiying|Y| Min|Li|L| Luo|Yi|Y| Zhang|Wenli|W| Shi|Rui|R| Duan|Hong|H| Tu|Chongqi|C|

vascular endothelial growth factor receptor-2


Antimycobacterial activity of pyrazinoate prodrugs in replicating and non-replicating Mycobacterium tuberculosis.

Abstract: Tuberculosis (TB) is an important infectious disease caused by Mycobacterium tuberculosis (Mtb) and responsible for thousands of deaths every year. Although there are antimycobacterial drugs available in therapeutics, just few new chemical entities have reached clinical trials, and in fact, since introduction of rifampin only two important drugs had reached the market. Pyrazinoic acid (POA), the active agent of pyrazinamide, has been explored through prodrug approach to achieve novel molecules with anti-Mtb activity, however, there is no activity evaluation of these molecules against non-replicating Mtb until the present. Additionally, pharmacokinetic must be preliminary evaluated to avoid future problems during clinical trials. In this paper, we have presented six POA esters as prodrugs in order to evaluate their anti-Mtb activity in replicating and non-replicating Mtb, and these showed activity highly influenced by medium composition (especially by albumin). Lipophilicity seems to play the main role in the activity, possibly due to controlling membrane passage. Novel duplicated prodrugs of POA were also described, presenting interesting activity. Cytotoxicity of these prodrugs set was also evaluated, and these showed no important cytotoxic profile.

Segretti|Natanael Dante|ND|
Simões|Cristina Kortstee|CK|
Corrêa|Michelle Fidelis|MF|
Felli|Veni Maria Andres|VMA|
Miyata|Marcelo|M|
Cho|Sang Hyun|SH|
Franzblau|Scott Gary|SG|
Fernandes|João Paulo Dos Santos|JPDS|

Duplicated prodrug
Antimycobacterial prodrug
LORA assay
Pyrazinoate ester


Socioenvironmental adversity and risk of prostate cancer in non-Hispanic black and white men.

Abstract: Non-Hispanic black (NHB) men experience higher risk of prostate cancer than other racial/ethnic groups, and it is possible that socioenvironmental (SE) adversity and resulting stress may contribute to this disparity. Data from the Southern Community Cohort Study were used to evaluate associations between SE adversity and perceived stress in relation to prostate cancer risk, overall and by race/ethnicity and grade. Between 2002 and 2009, 26,741 men completed a questionnaire, from which an 8-item SE adversity composite was created (covering socioeconomic status, residential environment, and social support/buffers). Two items from the Perceived Stress Scale were assessed. With follow-up through 2011, 527 prostate cancer cases were diagnosed. In multivariable models, each one-unit increase in the SE adversity composite was associated with increased prostate cancer risk among non-Hispanic white (NHW) men (HR 1.23; 95% CI 1.02-1.48) and reduced risk among NHB men (HR 0.89; 95% CI 0.82-0.95) (p interaction: 0.001). This pattern held for low grade, but not high grade, cancers although power was limited for the latter. Perceived stress variables were associated with increased risk of prostate cancer among NHW men, but not among NHB men. Results do not support the hypothesis that SE adversity my underlay the racial disparity in prostate cancer, over and above that of covariates, including healthcare utilization.

Prostate cancer
African Americans
Life stress
Minority health
Psychological stress


Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models.

Abstract: Despite the growing importance of the cerebellum as a region highly vulnerable to accumulating molecular errors in schizophrenia, limited information is available regarding altered molecular networks with potential therapeutic targets. To identify altered networks, we conducted one-shot liquid chromatography-tandem mass spectrometry in postmortem cerebellar cortex in schizophrenia and healthy individuals followed by bioinformatic analysis (PXD024937 identifier in ProteomeXchange repository). A total of 108 up-regulated proteins were enriched in stress-related proteins, half of which were also enriched in axonal cytoskeletal organization and vesicle-mediated transport. A total of 142 down-regulated proteins showed an enrichment in proteins involved in mitochondrial disease, most of which were also enriched in energy-related biological functions. Network analysis identified a mixed module of mainly axonal-related pathways for up-regulated proteins with a high number of interactions for stress-related proteins. Energy metabolism and neutrophil degranulation modules were found for down-regulated proteins. Further, two double-hit postnatal stress murine models based on maternal deprivation combined with social isolation or chronic restraint stress were used to investigate the most robust candidates of generated networks. CLASP1 from the axonal module in the model of maternal deprivation was combined with social isolation, while YWHAZ was not altered in either model. METTL7A from the degranulation pathway was reduced in both models and was identified as altered also in previous gene expression studies, while NDUFB9 from the energy network was reduced only in the model of maternal deprivation combined with social isolation. This work provides altered stress- and mitochondrial disease-related proteins involved in energy, immune and axonal networks in the cerebellum in schizophrenia as possible novel targets for therapeutic interventions and suggests that METTL7A is a possible relevant altered stress-related protein in this context.

networks
schizophrenia
pathways
postmortem brain
proteomics


Growth Potential of Listeria monocytogenes in Chef-Crafted Ready-to-Eat Fresh Cheese-Filled Pasta Meal Stored in Modified Atmosphere Packaging.

Abstract: This study evaluated the growth of lactic acid bacteria (LAB) in a fresh, filled-pasta meal, stored in modified atmosphere packaging and the influence of lactic acid (LA) and pH on the growth of Listeria monocytogenes (Lm). Samples were taken from three lots manufactured by a local catering company and stored at both 6 and 14°C. LAB numbers, LA concentration, pH, and the presence of Lm were evaluated at 1, 4, 6, 8, 10, 12, and 14 days of shelf life and the undissociated LA concentration ([LA]) was calculated. The LAB maximum cell density was greater in the products stored at 14°C than those stored at 6°C (10.1 ± 1.1 versus 5.6 ± 1.5 log CFU/g) and [LA] at 14 days was 9 to 21 ppm at 6°C and 509 to 1,887 ppm at 14°C. Challenge tests were made to evaluate the interference of LAB and [LA] on Lm growth. Aliquots of the samples (25 g) were inoculated at 1 to 10 days of shelf life and incubated at 9°C for 7 days, and the difference between Lm numbers at the end and at the beginning of the test (δ) was calculated. Logistic regression was used to model the probability of growth of Lm as a function of LAB and [LA]. The products inoculated at 1 day of shelf life had δ values between 4.2 and 5.6 log CFU/g, but the growth potential was progressively reduced during the shelf life. Lm growth was never observed in the products stored at 14°C. In those stored at 6°C, it grew only in the samples with LAB <5.7 log CFU/g. LAB interaction might thus inhibit the growth of Lm in temperature-abused products and limit its growth in refrigerated products. Logistic regression estimated that the probability of Lm growth was <10% if LAB was >6.6 log CFU/g or log[LA] was >2.2 ppm. The growth or inactivation kinetic of Lm was investigated with a homogenate of three samples with LAB numbers close to the maximum population density. After an initial growth, a subsequent reduction in the number of Lm was observed. This means that the maximum numbers of Lm might not be detected at the end of the product shelf life.

Trevisani|Marcello|M|
Cesare|Alessandra DE|A|
Vitali|Silva|S|
Mancusi|Rocco|R|
Bovo|Federica|F|
Manfreda|Gerardo|G|

Growth potential
Modified atmosphere packaging
Lactic acid bacteria
Filled pasta


Proceedings of the Working Group Session on Fertility Preservation for Individuals with Gender and Sex Diversity.

Abstract: Children and adolescents with gender and sex diversity include (1) gender-nonconforming and transgender individuals for whom gender identity or expression are incongruent with birth-assigned sex (heretofore, transgender) and (2) individuals who have differences in sex development (DSD). Although these are largely disparate groups, there is overlap in the medical expertise necessary to care for individuals with both gender and sex diversity. In addition, both groups face potential infertility or sterility as a result of desired medical and surgical therapies. The Ann & Robert H. Lurie Children's Hospital of Chicago (Lurie Children's) gender and sex development program (GSDP) provides specialized multidisciplinary care for both transgender and DSD patients. In response to patient concerns that recommended medical treatments have the potential to affect fertility, the Lurie Children's GSDP team partnered with experts from the Oncofertility Consortium at Northwestern University to expand fertility preservation options to gender and sex diverse youth. This article summarizes the results of a meeting of experts across this field at the annual Oncofertility Consortium conference with thoughts on next steps toward a unified protocol for this patient group.

Finlayson|Courtney|C|
Johnson|Emilie K|EK|
Chen|Diane|D|
Dabrowski|Elizabeth|E|
Gosiengfiao|Yasmin|Y|
Campo-Engelstein|Lisa|L|
Rosoklija|Ilina|I|
Jacobson|Jill|J|
Shnorhavorian|Margarett|M|
Pavone|Mary Ellen|ME|
Moravek|Molly B|MB|
Bonifacio|Herbert J|HJ|
Simons|Lisa|L|
Hudson|Janella|J|
Fechner|Patricia Y|PY|
Gomez-Lobo|Veronica|V|
Kadakia|Rachel|R|
Shurba|Angela|A|
Rowell|Erin|E|
Woodruff|Teresa K|TK|

fertility
transgender
disorders of sex development
gender dysphoria
intersex


SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis.

Abstract:
OBJECTIVE
To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes.

METHODS
This nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use.

RESULTS
The study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users.

CONCLUSIONS
ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.

TRIAL REGISTRATION NUMBER
EUPAS34887.

clinical epidemiology
critical care
respiratory infection
viral infection


Elemental concentration and migratability in bioplastics derived from organic waste.

Abstract: In line with the Circular Economy approach, the production of polyhydroxyalkanoate (PHA) with organic waste as the feedstock may a biotechnological application to reduce waste and recover high-value materials. The potential contaminants that could transfer from bio-waste to a PHA include inorganic elements, such as heavy metals. Hence, the total content and migratability of certain elements were evaluated in several PHA samples produced from different origins and following different methods. The total content of certain elements in PHA ranged between 0.0001 (Be) and 49,500 mg kg-1 (Na). The concentrations of some alkaline (Na and K) and alkaline earth (Ca and Mg) metals were highest, which are of little environmental concern. The feedstock type and PHA stabilisation and extraction procedures affected the element contents. Several sets of experiments were conducted to evaluate the migration of elements from the PHA samples under different storage times, temperatures, and pH levels. The total contents of some heavy metals (As, Cd, Fe, Hg, Ni, Pb, and Zn) in PHA produced from fruit waste or crops (commercial PHA) were lower than those in the PHA samples produced from the mixture of the organic fraction of municipal waste and sludge from wastewater treatment. Both the PHA obtained by extraction from wet biomass (acid storage) with aqueous phase extraction reagents and commercial PHA were below the migration limits stipulated by the current Toy Safety Directive and by Commission Regulation (EU) October 2011 on plastic materials and articles intended to come into contact with food under frozen and refrigerated conditions.

Astolfi|Maria Luisa|ML|
Marconi|Elisabetta|E|
Lorini|Laura|L|
Valentino|Francesco|F|
Silva|Fernando|F|
Ferreira|Bruno Sommer|BS|
Canepari|Silvia|S|
Majone|Mauro|M|

Cold vapour generation atomic fluorescence spectrometry

Inductively coupled plasma mass spectrometry


Queer binge: harmful alcohol use among sexual minority young people in Australia.

Abstract:
OBJECTIVES
The literature suggests that sexual minority young people (SMYP) use alcohol at disproportionate levels when compared with their heterosexual counterparts. Little is known about alcohol dependency symptoms and correlations between high-risk alcohol use/dependency symptoms and minority stress in this population in general and between subgroups.

STUDY DESIGN
Cross-sectional study.

METHODS
Descriptive statistics, adjusted odds ratios, and analysis of covariance were used to determine high-risk alcohol use, dependency symptoms, differences between subgroups, and correlations between alcohol use, dependency symptoms, and minority stress.

RESULTS
A total of 1556 Australian SMYPs aged 18 to 35 years completed the survey. Fifty percent of the participants reported high-risk alcohol consumption with significant differences between subgroups. Typical dependency symptoms such as 'health, social, legal or financial problems due to alcohol consumption' (16.8%, n = 247) were identified in large parts of the sample. High-risk consumption and dependency symptoms were significantly correlated with minority stress.

CONCLUSION
High levels of high-risk alcohol use and dependency symptoms were found, largely consistent with existing literature. However, disparities are not distributed equally in this population, suggesting that future health promotion interventions should focus on SMYP subgroups. Significant correlations between minority stress and dependency symptoms/high-risk use suggest a potential route for future interventions in these populations.

D044468:Native Hawaiian or Other Pacific Islander

Alcohol use
Minority stress
Binge drinking
Gender identity
Health disparities
LGBT health
Sexual identity


Ultrasound risk stratification for malignancy using the 2015 American Thyroid Association Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Abstract:
BACKGROUND
The 2015 American Thyroid Association (ATA) Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer provides selection criteria for nodules prior to ultrasound-guided fine-needle aspiration biopsy.

OBJECTIVE
To evaluate the diagnostic performance of pediatric thyroid nodule risk stratification for predicting malignancy when applying the ultrasound (US) criteria recommended.

MATERIALS AND METHODS
US characteristics of 39 thyroid nodules in 33 pediatric patients who underwent US fine-needle aspiration biopsy were reviewed by two radiologists. Based on the aggregated US criteria from the ATA Guidelines, each nodule was assigned a level of malignancy risk. Kappa coefficients were estimated to assess intra- and interobserver reliability. Using each patient's largest nodule observation (n = 33), univariable exact logistic regression analyses of US parameters were then conducted to estimate the odds of a malignant pathology diagnosis. A penalized Firth correction was employed in the univariable models analyzing composition, shape and level of suspicion due to quasi-complete data separation.

RESULTS
Twenty-seven nodules in 21 patients (median age: 16 years; 17 female) were benign and 12 nodules in 12 patients (median age: 16.5 years; 11 female) were malignant. Intraobserver agreement was substantial to almost perfect for composition, echogenicity, shape and margins. Interobserver agreement was almost perfect for composite level of suspicion. High level of suspicion was assigned to all 12 malignant nodules versus 9/21 (43%) of the benign nodules. Level of suspicion, solid/predominantly solid composition, irregular margins and echogenic foci emerged as significant predictors of malignancy with odds ratios (OR) of 8.5 (95% confidence interval [CI]: 1.7-1,130, P = 0.001), 10.5 (95% CI: 1.1-1,417, P = 0.04), 53.2 (95% CI: 5.1-2,988, P < 0.0001) and 3.5 (95% CI: 1.1-23.2, P = 0.03), respectively.

CONCLUSION
The composite, US-based risk stratification criteria from the 2015 ATA Guidelines may provide an appropriate and reproducible method for estimating risk of malignancy for pediatric thyroid nodules.

Lim-Dunham|Jennifer E|JE|
Erdem Toslak|Iclal|I|
Alsabban|Khalid|K|
Aziz|Amany|A|
Martin|Brendan|B|
Okur|Gokcan|G|
Longo|Katherine C|KC|

D000293:Adolescent
D003937:Diagnosis, Differential
D005260:Female
D006801:Humans
D008297:Male
D017410:Practice Guidelines as Topic
D015203:Reproducibility of Results
D018570:Risk Assessment
D012680:Sensitivity and Specificity
D012955:Societies, Medical
D013961:Thyroid Gland
D016606:Thyroid Nodule
D018084:Ultrasonography, Interventional
D014481:United States

Ultrasound
Malignancy
Thyroid
Children
Nodule
Fine-needle aspiration


Transcriptome Analysis of Clinopodium chinense (Benth.) O. Kuntze and Identification of Genes Involved in Triterpenoid Saponin Biosynthesis.

Abstract: Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is an important herb in traditional Chinese medicine. Triterpenoid saponins are a major class of active compounds in C. chinense with broad pharmacological activities and hemostatic, antitumor, and anti-hyperglycemic effects. To identify genes involved in triterpenoid saponin biosynthesis, transcriptomic analyses of leaves, stems, and roots from C. chinense were performed. A total of 135,968 unigenes were obtained by assembling the leaf, stem, and root transcripts, of which 102,154 were annotated in public databases. Differentially expressed genes were determined based on expression profile analysis and analyzed for differential expression of unique genes related to triterpenoid saponin biosynthesis. Multiple unigenes encoding crucial enzymes or transcription factors involved in triterpenoid saponin synthesis were identified and analyzed. The expression levels of unigenes encoding enzymes were experimentally validated using quantitative real-time PCR. This study greatly broadens the public transcriptome database for this species and provides a valuable resource for identifying candidate genes involved in the biosynthesis of triterpenoid saponins and other secondary metabolites.

Shi|Yuanyuan|Y| Zhang|Shengxiang|S| Peng|Daiyin|D| Wang|Chenkai|C| Zhao|Derui|D| Ma|Kelong|K| Wu|Jiawen|J| Huang|Luqi|L|

transcriptome
Clinopodium chinense (Benth.) O. Kuntze
triterpenoid saponin biosynthesis
differentially expressed genes
RNA sequencing


The Clinical Significance of Separate Measurements of Carotid Arterial Wall to Assess the Risk Factor for Atherosclerosis.

Abstract:
BACKGROUND
Carotid intima-media thickness (CIMT) is associated with several risk factors for atherosclerosis and has been consistently linked to cardiovascular and cerebrovascular disease. The clinical significance of separate measurements of CIMT, which is the sum of the intima (IT) and media thickness (MT), to use as an assessment of risk for atherosclerosis has not yet been fully established.

METHODS
Among 3377 patients who underwent B-mode ultrasound of carotid arteries and coronary angiography in the Medical Department of St. Mary's Hospital from September 2003 to March 2009, 1146 subjects (M:F = 616:530; mean age, 57.7 ± 12.1 years) who were diagnosed with normal coronary arteries were enrolled in this study. IT, MT, and CIMT of the enrolled patients were manually measured using high-frequency ultrasonography (15 MHz linear array transducer).

RESULTS
In multivariate logistic regression analysis, age (β = 0.063, p < 0.0001), body mass index (BMI) (β = 0.028, p = 0.018), and hypertension (HTN) (β = 0.046, p = 0.0002) were associated with MT (R(2) = 0.256) and the IT/MT ratio (R(2) = 0.209). Age (β = 0.065, p < 0.0001), BMI (β = 0.025, p = 0.038), hemoglobin A1c (β = 0.045, p = 0.045), and HTN (β = 0.043, p = 0.0006) correlated with mean CIMT (R(2) = 0.230). Age (β = -0.071, p < 0.0001) and BMI (β = -0.046, p = 0.002) were associated with the IT/MT ratio (R(2) = 0.219) on the left side. Age (β = 0.093, p < 0.0001) was related to MT (R(2) = 0.265) and mean CIMT (R(2) = 0.243) on the left side.

CONCLUSION
We noted different atherosclerotic risk factors were related to measurements of the arterial wall in different ways. Therefore, separate measurements of CIMT might be a useful method to assess the risk for atherosclerosis.

Kim|Ji-Hoon|JH| Youn|Ho-Joong|HJ| Kim|Gee-Hee|GH| Moon|Keon-Woong|KW| Yoo|Ki-Dong|KD| Kim|Chul-Min|CM|

Separate measurement
Atherosclerosis
Carotid intima and media thickness


Modern trends in diuretics development.

Abstract: Diuretics are the first-line therapy for widespread cardiovascular and non-cardiovascular diseases. Traditional diuretics are commonly prescribed for treatment in patients with hypertension, edema and heart failure, as well as with a number of kidney problems. They are diseases with high mortality, and the number of patients suffering from heart and kidney diseases is increasing year by year. The use of several classes of diuretics currently available for clinical use exhibits an overall favorable risk/benefit balance. However, they are not devoid of side effects. Hence, pharmaceutical researchers have been making efforts to develop new drugs with a better pharmacological profile. High-throughput screening, progress in protein structure analysis and modern methods of chemical modification have opened good possibilities for identification of new promising agents for preclinical and clinical testing. In this review, we provide an overview of the medicinal chemistry approaches toward the development of small molecule compounds showing diuretic activity that have been discovered over the past decade and are interesting drug candidates. We have discussed promising natriuretics/aquaretics/osmotic diuretics from such classes as: vasopressin receptor antagonists, SGLT2 inhibitors, urea transporters inhibitors, aquaporin antagonists, adenosine receptor antagonists, natriuretic peptide receptor agonists, ROMK inhibitors, WNK-SPAK inhibitors, and pendrin inhibitors.

Titko|Tetiana|T| Perekhoda|Lina|L| Drapak|Iryna|I| Tsapko|Yevgen|Y|

Diuretics
ROMK
Aquaporin (AQP)
SGLT2 inhibitors (gliflozins)
Small molecular drugs
Urea transporter (UT)


Dynamic evaluation of a trilobal capillary-channeled polymer fiber shape for reversed phase protein separations and comparison to the eight-channeled form.

Abstract: A new, trilobal-shaped capillary-channeled polymer fiber is under development to address the issues of poor A-term performance of the previous eight-channeled form. The trilobal geometry should provide better packing homogeneity due to the fewer potential orientations of the symmetric fiber geometry. Comparisons of separation efficiency and peak shape were made between the two fiber shapes through several dynamic parameters. Column hydrodynamics were investigated with two marker compounds, uracil and bovine serum albumin, with van Deemter plots of those two compounds revealing differences in the packing qualities between the different fiber shapes. Parametric fitting to the van Deemter, Knox, and Giddings equations provides insights into the column physical structures. Separation quality for both shapes was evaluated across differences in fiber packing density, gradient rate, and mobile phase linear velocity for the reversed phase separation of a four protein mixture, containing ribonuclease A, cytochrome c, lysozyme, and myoglobin. The results of this study lay the ground work for future efforts in the use of trilobal fibers for the separation of biomacromolecules.

capillary-channeled polymer fiber
reversed phase
proteins
liquid chromatography
polypropylene


Morphological features of the internal carotid artery: advantages of combining linear and convex probes in duplex ultrasonography.

Abstract:
RATIONALE AND OBJECTIVES
Previous research has determined that carotid abnormalities (CAs) are partly located >3 cm above the carotid bifurcation. However, identifying CAs occurring in this location using high-frequency linear probes is difficult. The aim of this study was to explore the efficacy of a combination of high-frequency and low-frequency probes in duplex ultrasonography for identifying morphologic features of the internal carotid artery (ICA).

MATERIALS AND METHODS
A total of 1055 ICAs from 532 patients were analyzed. CAs were classified prospectively according to the criteria of Wain et al, Weibel and Fields, and Metz et al. The diagnostic rates of high-frequency ultrasonography alone and a combination of high-frequency and low-frequency ultrasonography were compared. The distances from the carotid bifurcation to the initial point of the CA and to the mandibular angle were also measured.

RESULTS
High-frequency ultrasonography detected 23.2% of CAs, and the combination detected 32.2% of CAs (P < .001) in the 1055 ICAs. Of these CAs, 32.4% and 16.8% began >2.5 and >3 cm above the carotid bifurcation, respectively. The distance between the carotid bifurcation and the mandibular angle was <1.5 cm in 100 arteries (9.48%). The diameter of the distal ICA was larger in patients with CAs than in those without CAs (4.33 ± 0.52 vs 4.13 ± 0.49 mm, P < .001).

CONCLUSIONS
Combining high-frequency and low-frequency probes is better than high-frequency probes alone to assess morphologic features of the ICA in duplex ultrasonography. Low-frequency convex probes should be added to traditional ultrasonography for the evaluation of morphologic features of the ICA before carotid endarterectomy, carotid artery stenting, and CA angioplasty.

Xiong|Jian-Qun|JQ| Yu|Chen|C| Shi|Yu-Wen|YW| Li|Ying-Hua|YH|

morphologic
Internal carotid artery
convex probes
ultrasonography


lncRNA SNHG6 promotes hepatocellular carcinoma progression by interacting with HNRNPL/PTBP1 to facilitate SETD7/LZTFL1 mRNA destabilization.

Abstract: The lncRNA SNHG6 (small nucleolar RNA host gene 6) plays vital roles in tumorigenesis and the progression of hepatocellular carcinoma (HCC). However, the regulatory mechanisms of SNHG6 are largely unknown. In this study, we identified, via quantitative proteomics, specific cytoskeleton-associated proteins and enzyme modulators to be potential targets of SNHG6. SNHG6 reduced the mRNA levels of lysine methyltransferase, SET domain containing 7 (SETD7) and leucine zipper transcription factor-like 1 (LZTFL1) by posttranscriptional destabilization. Silencing of SETD7 or LZTFL1 reversed the suppressive effects of SNHG6 knockdown on HCC progression. Heterogeneous nuclear ribonucleoprotein L (HNRNPL) and polypyrimidine tract binding protein 1 (PTBP1) were identified as SNHG6-interacting proteins that bind to SETD7 or LZTFL1 mRNA. Forced expression of SNHG6 led to HNRNPL being competitively adsorbed by SNHG6, thereby removing its stabilizing effect on SETD7. Concurrently, the functional SNHG6-PTBP1 complex facilitated the degradation of LZTFL1 mRNA in hepatoma cells. These results indicated that SNHG6 promotes HCC progression by functioning as a "decoy plus guide" for HNRNPL and PTBP1 to facilitate mRNA decay of SETD7 and LZTFL1, thereby serving as a novel therapeutic target for HCC.

Wang|Haitao|H| Ma|Pei|P| Liu|Pengpeng|P| Guo|Deliang|D| Liu|Zhisu|Z| Zhang|Zhonglin|Z|