Correction

Bauer C, Sauer BG. Growing and retaining an endoscopy nurse. Clin Gastroenterol Hepatol 2019;17:5–7.

http://bit.ly/2Sqc1ly

Correction

Singh S, Brill JV, Proudfoot JA, Metcalfe L, Vu L, Sandborn WJ, Kosinski LR. Project Sonar: a community practice-based intensive medical home for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2018;16:1847–1850.

http://bit.ly/2GjLJuY

Correction

El-Serag HB, Kao JY, Kanwal F, Gilger M, LoVecchio F, Moss SF, Crowe S, Elfant A, Haas T, Hapke RJ, Graham DY. Houston consensus conference on testing for Helicobacter pylori infection in the United States. Clin Gastroenterol Hepatol 2018;16:992–1002.

http://bit.ly/2Slg1E4

Double-Blind Clinical Trial of Arginine Supplementation in the Treatment of Adult Patients with Sickle Cell Anaemia

Background. Sickle cell anaemia (SCA) is the most prevalent monogenic disease in Brazil. In SCA, haemoglobin S (HbS) is formed, which modifies red blood cell morphology. Intravascular haemolysis occurs, in which free Hb and free radicals degrade nitric oxide (NO) and release arginase, which reduces arginine levels. Because arginine is a substrate for NO formation, this decrease leads to reduced NO (vasodilator) synthesis. SCA treatment uses hydroxyurea (HU) to maintain high foetal haemoglobin (HbF) levels and reduces HbS to avoid haemolytic episodes. Objective. To analyse the efficacy of L-arginine as an adjuvant in the treatment of SCA patients. Setting. The State Blood Centre of Ceará, Brazil. Methods. This was a randomized double-blind clinical study of adults with SCA with continuous use of HU at the State Blood Centre of Ceará. The clinical study enrolled 25 patients receiving HU + L-arginine (500 mg) and 25 patients receiving HU + placebo. The treatment was carried out over four months. Laboratory tests were performed to determine the levels of the following: (1) complete blood count; (2) nitrite + nitrate; (3) HbF; and (4) reticulocytes. The clinical experiments were performed by a haematologist. The main outcome measures were nitrite and pain. Results. Statistical analysis showed that the levels of NO were increased in the study group, and there was also a reduction in pain frequency using a pain frequency scale by day, week, and month. The levels of nitrite plus nitrate in the group receiving placebo plus HU did not change among the times evaluated (38.27 ± 17.27 mg/L, 39.49 ± 12.84 mg/L, 34.45 ± 11.25 mg/L, p >0.05), but in the patients who received supplementation with L-arginine plus HU, a significant increase in nitrite plus nitrate levels was observed between M0 and M4 (36.55 ± 20.23 mg/L versus 48.64 ± 20.63 mg/L, p =0.001) and M2 and M4 (35.71 ± 15.11 mg/L versus 48.64 ± 20.63 mg/L, p

http://bit.ly/2GnWHQd

Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor

Journal Name: Biological Chemistry
Issue: Ahead of print


http://bit.ly/2S9xdgj

Presentation of Ocular Syphilis in a HIV-Positive Patient with False-Negative Serologic Screening

Purpose. The ocular sequelae of syphilis are devastating and may cause blindness. The ambiguous nature of its ocular manifestations makes syphilis difficult to detect. Though uncommon, the rise of syphilis in the United States requires a renewed understanding of its ophthalmic presentation to prevent devastating outcomes. We present this case to raise awareness for the increasing prevalence of ocular syphilis and appropriate serologic testing. Observations. We describe a 65-year-old HIV-positive male with worsening retinitis, uveitis, and rapid visual loss. Initial lab results showed a nonreactive rapid plasma reagin (RPR) for syphilis. However, subsequent Treponema pallidum antibody testing was positive 48 hours after initial false-negative serologic screening. The patient had a rapid and successful recovery following treatment with penicillin. Conclusions and Importance. The incidence of syphilis is on the rise once again, and patients living with HIV are at increased risk. Ocular syphilis should be considered in susceptible populations in the clinical setting of retinitis, uveitis, and worsening visual loss with unknown cause. In addition, retesting for syphilis will decrease the prevalence of false-negative results, especially in patients with high clinical suspicion.

http://bit.ly/2TukYYi

Misdiagnosis: Acute Chest Syndrome That Evolved into Acute Respiratory Distress Syndrome in a Patient without a Documented History of Hemoglobinopathy

Acute chest syndrome (ACS) is a feared complication of sickle cell disease. Here is a case of a patient who presented with symptoms suggestive of acute chest syndrome yet had a delayed diagnosis presumably due to the lack of documented history of sickle cell disease of the patient, consequently evolving into acute respiratory distress syndrome (ARDS). He was subsequently diagnosed with heterozygous sickle cell SC disease on hemoglobin electrophoresis. After appropriate management with mechanical ventilator, broad-spectrum empiric intravenous antibiotics, exchange transfusion, and intravenous fluid resuscitation, the patient was medically optimized and safely discharged home, with significant improvement noted on successive follow-up visits.

http://bit.ly/2GhAPpq

Safflower Yellow B Protects Brain against Cerebral Ischemia Reperfusion Injury through AMPK/NF-kB Pathway

Inflammation had showed its important role in the pathogenesis of cerebral ischemia and secondary damage. Safflower yellow B (SYB) had neuroprotective effects against oxidative stress-induced brain injuries, but the mechanisms were still largely unknown to us. In this study, we tried to investigate the anti-inflammation effects of SYB and the possible roles of AMPK/NF-κB signaling pathway on these protective effects. In vivo, brain ischemia/reperfusion (I/R) was induced by transient middle cerebral artery occlusion for 2 h and reperfusion for 20 h. Neurofunctional evaluation, infarction area, and brain water contents were measured. Brain injury markers and inflammatory cytokines levels were measured by ELISA kits. In vitro, cell viability, apoptosis, and LDH leakage were measured after I/R in PC12 cells. The expression and phosphorylation levels of AMPK, NF-κB p65, and P-IκB-α in cytoplasm and nuclear were measured by Western blotting. SiRNA experiment was performed to certify the role of AMPK. The results showed SYB reduced infarct size, improved neurological outcomes, and inhibited brain injury after I/R. In vitro test, SYB treatment alleviated PC12 cells injury and apoptosis and inhibited the inflammatory cytokines (IL-1, IL-6, TNF-α, and COX-2) in a dose-dependent manner. SYB treatment induced AMPK phosphorylation and inhibited NF-κB p65 nuclear translocation both in brain and in PC12 cells. Further studies also showed that the inhibition of NF-κB activity of SYB was through AMPK. In conclusion, SYB protected brain I/R injury through reducing expression of inflammatory cytokines and this effect might be partly due to the inhibition of NF-κB mediated by AMPK.

http://bit.ly/2G6BBGG

The Efficacy and Safety of a Herbal Toothpaste in Reducing Gingivitis: A Double-Blind, Randomized, Placebo-Controlled, Parallel Allocation Clinical Trial

Aim. To examine the efficacy and safety of the toothpaste containing Rhizoma Chuanxiong and Rhizoma Imperatae extracts in reducing gingivitis. Method. A double-blind clinical trial was conducted, in which 120 volunteers were randomly assigned to the test group ( = 60) or the control group ( = 60). Tetramethylpyrazine, senkyunolide A, ferulic acid, and ligustilide are the main effective components of Rhizoma Chuanxiong and Rhizoma Imperatae contains the main components of cylindrin, carotene, 5-hydroxytryptamine, potassium, and calcium. The control group used placebo toothpaste containing neither Rhizoma Chuanxiong extract nor Rhizoma Imperatae extract. Plaque, gingivitis, and bleeding were assessed at the baseline, prior to the supragingival scaling, and at 4, 8, and 12 weeks. Results. During the trial, both test and control groups showed a decreasing trend compared to the baseline. At the end of 12 weeks, with respect to Gingival Index (GI), Bleeding Index (BI), and Bleeding on Probing percentage (BOP%) scores, there were significant differences between test and control groups (GI, P

http://bit.ly/2UwX52k

Antidepressant Effect of Tetragonia tetragonoides (Pall.) Kuntze Extract on Serotonin Turnover

Tetragonia tetragonoides (Pall.) Kuntze (TTK) is a groundcover found along coastal areas of the Korean peninsula. TTK is traditionally used to improve women's health and treat gastrointestinal diseases. Use of herbal medicines in the treatment of mood disorders has recently been suggested as an alternative therapeutic strategy. In the present study, we determined that consumption of TTK extract ameliorated progression of depressive-like symptoms in ovariectomized (OVX) rats and further examined the mechanisms involved, i.e., synthesis, release, and reuptake(s) of serotonin (also known as 5-HT). We assessed the mRNA expression levels of tryptophan hydroxylases (TPH-1 and TPH-2) and serotonin transporter (SERT) as well as the reuptake activity of serotonin in RBL-2H3 cells. We also determined whether or not TTK extract regulates the serum level of serotonin and improves depressive-like symptoms in 0.5, 1, and 2% TTK-fed OVX female rats in a forced swimming test. Our results show that the mRNA levels of TPH-1 and SERT were significantly reduced, whereas the mRNA level of TPH-2 was dose-dependently elevated by TTK (50 and 100 μg/mL) in RBL-2H3 cells. TTK significantly inhibited LPS- (lipopolysaccharide-) induced serotonin uptake in RBL-2H3 cells in a dose-dependent manner. The serum level(s) of serotonin was elevated by 1% and 2% TTK treatment in OVX female rats. Moreover, immobility time in the forced swimming test was reduced by 1% and 2% TTK treatment but not altered by 0.5% TTK treatment in OVX female rats. Taken together, these results indicate that TTK may significantly inhibit depressive-like symptoms due to upregulation of serotonin level(s) and regulation of serotonin reuptake activity. Thus, TTK may exert beneficial effects on depression during pre- or/and postmenopausal periods via modulation of serotonin synthesis and metabolism.

http://bit.ly/2G5AJly

A Randomized Controlled Trial of Chuanhutongfeng Mixture for the Treatment of Chronic Gouty Arthritis by Regulating miRNAs

Background. We investigated whether Chuanhutongfeng mixture has actions on chronic gouty arthritis (CGA) by regulating miRNAs. Methods. A total of 255 patients with CGA and 30 controls were enrolled. miRNA expression profiles and cluster analysis were preformed; RT-qPCR was used to detect miRNAs associated with CGA. Patients were allocated into Chuanhutongfeng mixture, allopurinol (positive control), and control (etoricoxib) groups. Expression of plasma miRNAs was measured before and after treatments; expression of chemokine 2 (CCL2) and interleukin 8 (CXCL8) was determined by ELISA. Results. 48 miRNAs were differentially expressed and compared to controls. 36 miRNAs expression levels were > 1.5 times and 12 miRNAs

http://bit.ly/2UC2ZiK

Identification of Traditional Chinese Medicine Constitutions and Physiological Indexes Risk Factors in Metabolic Syndrome: A Data Mining Approach

Objective. In order to find the predictive indexes for metabolic syndrome (MS), a data mining method was used to identify significant physiological indexes and traditional Chinese medicine (TCM) constitutions. Methods. The annual health check-up data including physical examination data; biochemical tests and Constitution in Chinese Medicine Questionnaire (CCMQ) measurement data from 2014 to 2016 were screened according to the inclusion and exclusion criteria. A predictive matrix was established by the longitudinal data of three consecutive years. TreeNet machine learning algorithm was applied to build prediction model to uncover the dependence relationship between physiological indexes, TCM constitutions, and MS. Results. By model testing, the overall accuracy rate for prediction model by TreeNet was 73.23%. Top 12.31% individuals in test group (n=325) that have higher probability of having MS covered 23.68% MS patients, showing 0.92 times more risk of having MS than the general population. Importance of ranked top 15 was listed in descending order . The top 5 variables of great importance in MS prediction were TBIL difference between 2014 and 2015 (D_TBIL), TBIL in 2014 (TBIL 2014), LDL-C difference between 2014 and 2015 (D_LDL-C), CCMQ scores for balanced constitution in 2015 (balanced constitution 2015), and TCH in 2015 (TCH 2015). When D_TBIL was between 0 and 2, TBIL 2014 was between 10 and 15, D_LDL-C was above 19, balanced constitution 2015 was below 60, or TCH 2015 was above 5.7, the incidence of MS was higher. Furthermore, there were interactions between balanced constitution 2015 score and TBIL 2014 or D_LDL-C in MS prediction. Conclusion. Balanced constitution, TBIL, LDL-C, and TCH level can act as predictors for MS. The combination of TCM constitution and physiological indexes can give early warning to MS.

http://bit.ly/2G5AFCk

Efficacy of Danshen Class Injection in the Treatment of Acute Cerebral Infarction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Introduction. As a common chronic disease with high morbidity and recurrent rate, acute cerebral infarction (ACI) affects the life quality of patients and gives them heavy psychological burden. And Danshen class injections (DSCIs) are commonly adopted in treating ACI. So, this network meta-analysis (NMA) was designed to assess the clinical efficacy of eight kinds of DSCIs. Methods. A systematic literature search was performed in PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure Database, the China Biomedical Literature Service System, the Chinese Scientific Journals Full-text Database, and Wanfang database from their inception to Dec. 2017 aiming to collect related randomized controlled trials (RCTs). And then data were analyzed through Stata and WinBUGS software based on the Bayesian statistical model. The results were reported as odds ratio (OR) and mean difference (MD) with 95% credible intervals (CIs). The consistency test between direct and indirect comparisons was also evaluated and inconsistency factor was presented to manifest the heterogeneity among them. Meanwhile, the surface under the cumulative ranking probabilities (SUCRA) was utilized to rank the treatments in different outcomes. Results. Finally, 157 RCTs with 15570 patients were included. A total of eight types DSCIs were identified. Based on the results, Sodium Tanshinone IIA Sulfonate injection (STS) plus western medicine (WM) had better effect on the clinical effectiveness rate, neurological impairment, and activities of daily living function than others. Meanwhile, Danhong injection (DS) and Danshen Salvianolic Acids injection (DSSA) had excellent performance in perfecting hemorheological indexes. Conclusions. In conclusion, STS plus WM may be the optimum treatment for ACI. The following therapies were DS plus WM and DSSA plus WM. Nevertheless, in terms of the limitations of the study, more large samples, multicenter, and double-blind RCTs are still needed for validating our findings.

http://bit.ly/2UActv2

Metabolite Markers for Characterizing Sasang Constitution Type through GC-MS and 1H NMR-Based Metabolomics Study

Sasang constitutional medicine classifies human beings into four types based on their physical and psychological characteristics. Despite its potential value in achieving personalized medicine, the diagnosis of sasang constitution (SC) type is complex and subjective. In this study, gas chromatography–mass spectrometry and 1H nuclear magnetic resonance–based metabolic analyses were conducted to find maker metabolites in serum and urine according to different SC types. Although some samples were overlapped on orthogonal projection to latent structure discriminant analysis score plots, serum samples showed separation between different SC types. Levels of lactate, glutamate, triglyceride, and fatty acids in serum and glycolic acid in urine of Tae-Eum type were higher than those of So-Eum and So-Yang type. Fatty acids, triglyceride, and lactate levels were found to be metabolites related to body mass index, indicating that marker metabolites for the diagnosis of SC type could be associated with obese. However, Tae-Eum type showed higher lactate levels in serum than So-Yang type for both normal weight and overweight groups, suggesting that the contents of serum lactate might be dependent on the SC type regardless of body weight. These results suggest that metabolomics analysis could be used to determine SC type.

http://bit.ly/2G7IqYf

Study on the Differences between Traditional Chinese Medicine Syndromes in NYHA I–IV Classification of Chronic Heart Failure

Objectives. This study investigated the distribution of characteristics of traditional Chinese medicine syndromes and their association with symptoms in 1027 patients with chronic heart failure (CHF). Methods. An observational study was performed by researchers, collecting data from 1036 patients with CHF from 24 Chinese medicine hospitals from May 2009 to December 2014. Due to incomplete information from nine patients, 1027 patients with CHF were analysed. The distribution of syndromes in CHF and association between high-frequency syndromes and symptoms were investigated. Results. The primary syndromes were qi deficiency, blood stasis, fluid retention, yin deficiency, phlegm turbidity, and yang deficiency. The primary sites of disease were the heart, kidney, lung, and spleen. In patients with CHF of differing cardiac function, there was no significant difference in the frequency of yin deficiency (P>0.05). The distribution of yang deficiency was significantly different between New York Heat Association (NYHA) classes II, III, and IV and between classes I+II and III+IV (P

http://bit.ly/2UD6AgF

Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.

http://bit.ly/2G7IbMR

High Carbohydrate High Fat Diet Induced Hepatic Steatosis and Dyslipidemia Were Ameliorated by Psidium guajava Leaf Powder Supplementation in Rats

Psidium guajava leaf is reported to contain many bioactive polyphenols which play an important role in the prevention and treatment of various diseases. Our investigation aimed to study the effect of Psidium guajava leaf powder supplementation on obesity and liver status by using experimental rats. To study the effects of guava leaf supplementation in high fat diet induced obesity, rats were randomly divided into four experimental groups (n=7), control (group I), control + guava leaf (group II), HCHF (group III), and HCHF + guava leaf (group IV). At the end of the experimental period (56 days), glucose intolerance, liver enzymes activities, antioxidant enzymes activities, and lipid and cholesterol profiles were evaluated. Our results revealed that guava leaf powder supplementation showed a significant reduction in fat deposition in obese rats. Moreover, liver enzyme functions were increased in high fat diet fed rats compared to the control rats significantly which were further ameliorated by guava leaf powder supplementation in high fat diet fed rats. High fat diet feeding also decreased the antioxidant enzyme functions and increased the lipid peroxidation products compared to the control rats. Guava leaf powder supplementation in high fat diet fed rats reduced the oxidative stress markers and reestablished antioxidant enzyme system in experimental animals. Guava leaf powder supplementation in high fat diet fed rats also showed a relative decrease in inflammatory cells infiltration and collagen deposition in the liver compared to the high fat diet fed rats. The present study suggests that the supplementation of guava leaf powder prevents obesity, improves glucose intolerance, and decreases inflammation and oxidative stress in liver of high carbohydrate high fat diet fed rats.

http://bit.ly/2UBDtKq

Chinese Herbal Medicine (Chaihu-Huaji Decoction) Alleviates Postembolization Syndrome following Transcatheter Arterial Chemoembolization and Improves Survival in Unresectable Hepatocellular Cancer: A Retrospective Study

Objective. To examine the efficacy of Chaihu-huaji decoction combined with transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) patients. Methods. We retrospectively reviewed the data of 125 HCC patients treated in Chongqing Cancer Hospital between January 2012 and December 2014, including 64 patients who received Chaihu-huaji decoction and TACE (Chaihu-huaji group) and 61 patients who received only TACE (control group). The patients were examined until the last follow-up or death. Complications, hepatotoxicity, and nephrotoxicity were compared between the two groups. Results. Fever, nausea, vomiting, poor appetite, and leukocytopenia were alleviated in patients who received Chaihu-huaji decoction, and no cases of significant hepatic and renal toxicities related to the herbal medicine were observed in the Chaihu-huaji group. The 3-year overall survival probability was significantly higher in the Chaihu-huaji group (26.47%) than in the control group (13.06%). Conclusion. Chaihu-huaji decoction may prevent adverse events after TACE and prolong overall survival of unresectable HCC patients when combined with TACE.

http://bit.ly/2G7fbF9

Phytopharmacovigilance in the Elderly: Highlights from the Brazilian Amazon

Practices described as traditional medicine may coexist with formalized, science-based medicine. In this context, the present study aimed to verify the profile of the elderly who consumed herbal medicines concomitantly with medications and to identify suspected adverse drug reactions (ADRs) in the Brazilian Amazon (Macapá, Amapá). The study was carried out in two steps: a cross-sectional study (structured questionnaire) and a clinical study (pharmacotherapeutic follow-up). Out of 208 participants, 78.8% were female with age between 60 and 69 years (58.7%), 59.1% used herbal medicines concurrently with medications, and 40.9% did not report use of herbal medicine. Losartan was the most used medication, and Lippia alba (Mill.) N.E. Br was the most common herbal medicine used. The total prevalence of suspected ADRs, among the elderly who answered the structured questionnaire, was 41.3%, with 27.4% being in the elderly who used herbal medicines and medications, and 13.9% being in the elderly who used only medications. Meanwhile, the total prevalence of suspected ADRs was 71.0% among the elderly patients who underwent pharmacotherapeutic follow-up, 60.5% in elderly who used herbal medicines and medications, and 10.5% in elderly who used only medications. The most reported ADR symptoms were related to disorders that affect the nervous system (38.4%) in the structured questionnaire and related to digestive disorders (36.4%) in the pharmacotherapeutic follow-up. The probability associated with the occurrence of a given ADR in the face of a set of demographic, socioeconomic, and clinical variables was estimated; the results showed that, in the studied population, only sex (p = 0.030) had an influence on the occurrence of ADR. The prevalence of ADRs with probable causality was high in this study population, but it was only sex-related, although more prevalent in the elderly who consume herbal medicines.

http://bit.ly/2UBQqnI

The Contribution of Complementary and Alternative Medicine to Reduce Antibiotic Use: A Narrative Review of Health Concepts, Prevention, and Treatment Strategies

Aim. The aim of this narrative review was to explore the potential contributions of CAM to reduce antibiotic use. Methods. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews with a specific, limited set of search terms and collected input from a group of expert CAM researchers to answer the question: What is known about the contribution of CAM health and health promotion concepts, infection prevention, and infection treatment strategies to reduce antibiotic use? Results. The worldview-related CAM health concepts enable health promotion oriented infection prevention and treatment aimed at strengthening or supporting the self-regulating ability of the human organism to cope with diseases. There is some evidence that the CAM concepts of health (promotion) are in agreement with current conceptualization of health and that doctors who practice both CAM and conventional medicine prescribe less antibiotics, although selection bias of the presented studies cannot be ruled out. There is some evidence that prevention and some treatment strategies are effective and safe. Many CAM treatment strategies are promising but overall lack high quality evidence. Conclusions. CAM prevention and treatment strategies may contribute to reducing antibiotic use, but more rigorous research is necessary to provide high quality evidence of (cost-)effectiveness.

http://bit.ly/2G5r8uZ

Mechanisms of Acupuncture Therapy for Simple Obesity: An Evidence-Based Review of Clinical and Animal Studies on Simple Obesity

Simple obesity is a worldwide epidemic associated with rapidly growing morbidity and mortality which imposes an enormous burden on individual and public health. As a part of Traditional Chinese Medicine (TCM), acupuncture has shown the positive efficacy in the management of simple obesity. In this article, we comprehensively review the clinical and animal studies that demonstrated the potential mechanisms of acupuncture treatment for simple obesity. Clinical studies suggested that acupuncture regulates endocrine system, promotes digestion, attenuates oxidative stress, and modulates relevant molecules of metabolism in patients of simple obesity. Evidence from laboratory indicated that acupuncture regulates lipid metabolism, modulates inflammatory responses, and promotes white adipose tissue browning. Acupuncture also suppresses appetite through regulating appetite regulatory hormones and the downstream signaling pathway. The evidence from clinical and animal studies indicates that acupuncture induces multifaceted regulation through complex mechanisms and moreover a single factor may not be enough to explain the beneficial effects against simple obesity.

http://bit.ly/2UBDrCi

Local Knowledge and Conservation Priorities of Medicinal Plants near a Protected Area in Brazil

We investigated the influence of socioeconomic factors (age, gender, and occupation) on the local knowledge of medicinal plants in the Araripe National Forest, Brazil, and the priority of conservation of the species as perceived by people. Additionally, priority species for in situ conservation were identified by calculating conservation priority (CP). Initially, free lists were developed with 152 informants in order to identify the plants known and used by them. Based on the most cited plants in these lists, a salience analysis was performed to identify the ten most prominent tree species. In a second moment, through a participatory workshop, these ten species were classified by the perception of local experts as to their environmental availability and intensity of exploitation. Then, the population size of the forest plant species was quantified through a phytosociological sampling and the conservation priority index (CP) of the species was calculated. A total of 214 ethnospecies were cited by the informants, which were identified in 167 species. Local knowledge was influenced by socioeconomic factors, with positive correlation between age and local knowledge and difference in knowledge among professions. Among the ten most prominent tree species in terms of their medicinal importance, Hancornia speciosa was highlighted as a priority for conservation in the experts' perception because it has low environmental availability and a high exploitation rate. The ten species were ordered by the CP differently from the ordering made by the local experts' perception, indicating that people's perception of species conservation status may not correspond to the actual situation in which they are found in the forests. Conservationist measures based on the perception of informants need complementary ecological studies on the species accessed.

http://bit.ly/2G7f8cr

A Data Mining-Based Analysis of Medication Rules in Treating Bone Marrow Suppression by Kidney-Tonifying Method

Objective. To investigate the rule of kidney-tonifying method in Chinese medicine for the treatment of bone marrow suppression (BMS), in order to provide evidence and references for the clinical application of herbs and formulae. Design. Collecting and sorting the information about the treatment of BMS related to kidney-tonifying (Bushen) method in Chinese medicine literatures on databases including Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), establishing a database of BMS treating formulae after radiotherapy and chemotherapy with traditional Chinese medicine (TCM) kidney-tonifying method, and finally applying the relevant theories and techniques of data mining to analyze the medication rules of it. Results. A total of 239 formulae and 202 herbs were included in this database, in which the herbs occurred 2,602 times in general. The high frequency herbs included Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), and Ligustri Lucidi Fructus (Nvzhenzi). The main herb categories were deficiency-tonifying herbs, blood-activating herbs, dampness-draining diuretic herbs, heat-clearing herbs, and digestant herbs. Deficiency-tonifying herbs accounted for 64.60% of the total number. A total of 8 clustering formulae are summarized according to cluster analysis and 26 herb suits association rules are identified by Apriori algorithm. Conclusion. The treatment of BMS is mainly based on the method of invigorating the spleen and tonifying the kidney and liver to strengthen healthy qi, supplementing with blood-activating herbs, and dampness-draining diuretic herbs to eliminate pathogenic factors.

http://bit.ly/2UD6BkJ

Evidence on Integrating Pharmacokinetics to Find Truly Therapeutic Agent for Alzheimer’s Disease: Comparative Pharmacokinetics and Disposition Kinetics Profiles of Stereoisomers Isorhynchophylline and Rhynchophylline in Rats

Isorhynchophylline (IRN) and rhynchophylline (RN), a pair of stereoisomers, are tetracyclic oxindole alkaloids isolated from Uncaria rhynchophylla, a commonly used Chinese medicinal herb. These two compounds have drawn extensive attention due to their potent neuroprotective effects with promising therapeutic potential for the treatment of Alzheimer's disease (AD). However, IRN and RN can interconvert into each other in vivo after oral administration. The present study aimed to elucidate the pharmacokinetic profiles and disposition kinetics of the administered and generated stereoisomers in the brain and cerebrospinal fluid (CSF) after oral administration of equal dose of IRN or RN to rats. Our study demonstrated that after oral administration, RN showed significantly higher systemic exposure (6.5 folds of IRN, p

http://bit.ly/2G6TftW

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action of the Wei Pi Xiao Decoction for the Treatment of Gastric Precancerous Lesions

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

http://bit.ly/2UHA0KL

Persistent sciatic artery resembles a soft-tissue sarcoma in presentation

Hana Kamal Almadani<br />Jan 29, 2019; 12:e227250-e227250<br />

http://bit.ly/2G7ImHZ

The Impact of an Augmented Reality Application on Learning Motivation of Students

The research on augmented reality applications in education is still in an early stage, and there is a lack of research on the effects and implications of augmented reality in the field of education. The purpose of this research was to measure and understand the impact of an augmented reality mobile application on the learning motivation of undergraduate health science students at the University of Cape Town. We extend previous research that looked specifically at the impact of augmented reality technology on student learning motivation. The intrinsic motivation theory was used to explain motivation in the context of learning. The attention, relevance, confidence, and satisfaction (ARCS) model guided the understanding of the impact of augmented reality on student motivation, and the Instructional Materials Motivation Survey was used to design the research instrument. The research examined the differences in student learning motivation before and after using the augmented reality mobile application. A total of 78 participants used the augmented reality mobile application and completed the preusage and postusage questionnaires. The results showed that using an augmented reality mobile application increased the learning motivation of students. The attention, satisfaction, and confidence factors of motivation were increased, and these results were found to be significant. Although the relevance factor showed a decrease it proved to be insignificant.

http://bit.ly/2UFeZ3h

Outcomes of a Dose-Escalated Stereotactic Body Radiation Phase I/II trial for Patients with Low and Intermediate-Risk Prostate Cancer

This study presents a prospective phase I, IRB-approved dose-escalated stereotactic body radiotherapy (SBRT) trial for prostate cancer (CaP) to assess the impact of dose level on quality of life, toxicity, and clinical outcomes.

http://bit.ly/2WL9HoK

Ten-year outcomes of moderately hypofractionated (70 Gy in 28 fractions) intensity modulated radiotherapy for localized prostate cancer

We present a large institutional series with over 11 years of follow up in 854 patients with localized prostate cancer treated with moderately hypofractionated (70 Gy in 28 fractions) intensity modulated radiation therapy (IMRT) with daily image guidance (IGRT). NCCN high risk patients composed 29% of the cohort. Outcomes beyond 10 years remained excellent, with low rates of late grade ≥ 3 GU and GI toxicities at 2 and 1%, respectively.

http://bit.ly/2RzDIUD

Cover Picture: Eur. J. Lipid Sci. Technol. 2∕2019

http://bit.ly/2SoEBUr

Development of a 450 nm laser irradiation desorption method for fast headspace solid‐phase microextraction of volatiles from krill oil (Euphausia superba)

Abstract

A laser irradiation desorption (LID) method was developed using a 450 nm blue semiconductor laser and gas chromatography mass spectrometry (GC/MS) for analyzing the flavor of Antarctic krill oil (Euphausia superba). The experimental parameters of LID were optimized by response surface methodology (RSM), and the optima were obtained as following, laser power (10 w), irradiation time (5 min), and sample volume (3 g). The results showed that a total of 41 volatile molecular species were detected, including 6 alcohols, 10 aldehydes, 5 ketones, 14 hydrocarbons, and 6 other compounds. Compared with the conventional heating assisted desorption technique, the LID could release volatile molecular species with higher abundance in a considerably reduced extraction time from 30 to 5 min. Finally, the proposed method was validated in terms of sensitivity, precision, linearity and recovery, which demonstrated its advantages with high efficient and simplified procedure.

Practical applications: A laser irradiation desorption (LID) method was developed using a 450 nm blue semiconductor laser for analyzing the flavor of Antarctic krill oil (Euphausia superba). Compared with the conventional heating assisted desorption technique, the LID could release more volatile molecular species with higher abundance in a considerably shorter extraction time, and the intensive laser power would not induce the autoxidation of polyunsaturated fatty acids. It showed the advantages of high efficient, and simplified procedure.

http://bit.ly/2SoEKXZ

Assessment of the suitability of pitanga leaf extracts as a natural antioxidant for enhancing canola oil stability: Monitoring lipid oxidation parameters

Abstract

The efficiency of pitanga leaf extracts (PLE) to protect vegetable oils against lipid oxidation was evaluated and compared with the synthetic antioxidant butylated hydroxytoluene (BHT). For this purpose, the main phenolic compounds and antioxidant properties of PLE were determined by UPLC‐DAD‐MS/MS and spectrophotometric methods. Moreover, the fatty acid composition and lipid oxidation of canola oil containing five different concentrations of PLE (200‐1000 ppm), BHT or without any antioxidant added were evaluated after being subjected to accelerated oxidation conditions (60 °C during 16 days). The results showed a considerable amount of phenols (229.4 mg gallic acid/g extract) with two major phenolic compounds (miricitrin and quercetin 3‐α‐fucopiranoside) in the PLE intermediate fraction. The fatty acid composition of canola oils with additives did not change significantly after 16‐day accelerated oxidation (7.3% SFA, 64.5% MUFA and 27.8% PUFA). The incorporation of PLE, even at the minimum concentration assayed (200 ppm), offers important decreases of primary and secondary oxidation products with respect to the control sample, obtaining reduction percentages of 74%, 58%, 62% and 61% for peroxides, conjugated dienes, p‐anisidine, and TBARS values, respectively. Similar stability for canola oil was observed with BHT at equivalent concentrations, enhancing the inhibitory effects against lipid oxidation in different oxidations steps.

Practical applications: The incorporation of pitanga leaf extracts to canola oils is a promising strategy to preserve their polyunsaturated fatty acids, avoiding their lipid oxidation during storage. This procedure is of great interest due to the natural origin of the additive under study versus synthetic antioxidants like butylated hydroxytoluene.

http://bit.ly/2GjImnI

Sinapic acid and its derivatives increase oxidative stability in different model lipid systems

Abstract

Sinapic acid and its derivatives syringic acid, syringaldehyde, three sinapoyl esters (ethyl, propyl, butyl sinapates), 4‐vinylsyringol and sinapine were investigated for anti‐radical activity in relation to different free radical species, reaction environments and model systems, and with special emphasis on lipid peroxidation in different lipid systems: as an emulsion, bulk oil, oleogel and liposome suspension. Syringic acid and sinapic acid showed the highest DPPH and O₂^‐ scavenging activities, whereas for the OH‐scavenging the highest activities were for ethyl sinapate, propyl sinapate and sinapine. While sinapic acid esters had the highest activities in the emulsion and liposome suspension, in bulk oil, the more polar sinapic acid, syringic acid and syringaldehyde showed the greatest inhibition of lipid peroxidation. In oleogel‐based system a noted increase in the activity of less polar compounds, especially 4‐vinylsyringol and butyl sinapate was recorded, while the level of inhibition for the more polar sinapic acid, syringic acid and syringaldehyde remained unchanged, compared to the bulk oil. In oleogel the potential interactions of these less polar compounds with the oil structuring agent might be an additional factor that influences their inhibitory actions.

Practical Applications: This study examines the potential for the application of sinapic acid and its derivatives for inhibition of lipid peroxidation, using different lipid systems as models for real food matrices. The study shows how modifications to the naturally occurring compound sinapic acid can affect its activity, and which of these modifications would be appropriate for each lipid system. It is also shown that contrary to the polar paradox, the influence of lipophilic antioxidants on the oxidative stability of oleogel‐based products might be due to their interactions with the oleogelation agents, which will thus further stabilise the oleogels. In addition to their antioxidant actions, this would open new possibilities for the application of lipophilic antioxidants to oil‐based products.

http://bit.ly/2SfIr2j

Antioxidant Activity of Spent Coffee Ground Extracts towards Soybean Oil and Fish Oil

Abstract

Although studies have shown that spent coffee ground (SCG) extracts have antioxidant activity, no systematic study has been reported under actual storage conditions. The purpose of this study was to estimate the feasibility of practical application of SCG extracts as natural antioxidants for soybean oil and fish oil. An ethanol extract (EE), an acetone extract (AE), and polar compounds isolated from oil (PCO) were prepared and their activity was compared to a synthetic antioxidant, butylated hydroxytoluene (BHT). EE showed the strongest radical scavenging activity for 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radicals and the highest total phenolic content (TPC) followed by AE and then PCO. However, during storage of soybean oil and fish oil at 35 and 50 °C, AE had the strongest antioxidant activity as determined by peroxide value, conjugated diene value, p‐anisidine value, and headspace volatile analyses. In soybean oil, 0.25% AE had antioxidant activity that was equal to or better than 0.02% BHT. In fish oil, the antioxidant activity of 0.25% AE was inferior to that of 0.02% BHT. However, increased concentrations of AE showed improved antioxidant activity. This study showed that SCG extracts can be practically used as natural antioxidants for vegetable oils and omega‐3 oils.

Practical application: Due to lack of information about the antioxidant activity of spent coffee ground (SCG) extracts, this study was specifically aimed and designed to provide information on their activity towards soybean oil and fish oil during actual storage. This study showed that 0.25% acetone extract had equal or better protective effects than butylated hydroxytoluene (BHT) in soybean oil at 35 and 50 °C. The activity was further improved with increasing concentration. The activity of the acetone extract in fish oil was not as strong as in soybean oil, but higher concentrations further improved the antioxidant activity. In this study, it was clearly demonstrated that the SCG extracts could have practical use as natural antioxidants for vegetable oils and oils with high concentration of omega‐3 fatty acids.

http://bit.ly/2GjNV5r

Stabilization of fish oil‐loaded electrosprayed capsules with seaweed and commercial natural antioxidants: effect on the oxidative stability of capsule‐enriched mayonnaise

Abstract

This study investigated the stabilization of fish oil‐loaded electrosprayed capsules with different natural antioxidants: i) an ethanol extract from the brown alga Fucus vesiculosus, or ii) a combination of δ‐tocopherol and rosemary extract. The seaweed extract enhanced the oxidative stability of fish oil‐loaded capsules with dextran as the main biopolymer wall material, but showed a prooxidant effect in fish oil‐loaded capsules having glucose syrup as the main biopolymer. These results can mainly be explained by the higher encapsulation efficiency of dextran capsules when compared to glucose capsules (90 vs. 83‐85%), which prevented interaction of metal ions present in the extract with non‐encapsulated oil. On the contrary, the addition of a lipophilic radical scavenger such as δ‐tocopherol in combination with synergistic antioxidants such as carnosic acid and carnosol present in rosemary extract improved the oxidative stability of glucose syrup capsules during 21 day storage, but not when the capsules were added to mayonnaise. Moreover, the capsule‐containing mayonnaise presented a larger droplet size and higher apparent viscosity than mayonnaise enriched with neat fish oil. Both findings indicate that the structure of capsules may have been lost when added to a water‐based food matrix (e.g. mayonnaise) and this requires further investigation.

Practical applications: Novel omega‐3 delivery systems that are more easily dispersed and still maintain their oxidative stability are needed by the food industry. Electrosprayed capsules with a reduced size when compared to spray‐dried capsules, and which are produced without the need of heat for drying emulsions are promising omega‐3 powdered encapsulates. Moreover, the addition of natural antioxidants, commonly used by the industry to further stabilize omega‐3 encapsulates, deserves scientific attention. This study reveals the effect of seaweed antioxidants (e.g. phlorotannins) and commercial natural antioxidants (e.g. δ‐tocopherol and rosemary extract) on the oxidative stability of electrosprayed capsules loaded with fish oil. In addition, the effect of adding the capsules to a food matrix such as mayonnaise has been investigated. Although further development is necessary, these results will open up new strategies to enrich food products with omega‐3 polyunsaturated fatty acids.

http://bit.ly/2SfIo6D

Omega‐3 polyunsaturated fatty acids as an adjunct to non‐surgical treatment of periodontitis

Abstract

Recently, a growing interest in products containing omega‐3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is observed. It turned out that omega‐3 PUFAs have therapeutic, anti‐inflammatory and protective properties in the patients with rheumatoid arthritis, ulcerative colitis, asthma, cardiovascular and periodontal diseases. Omega‐3 PUFAs inhibit the synthesis of pro‐inflammatory factors such as cytokines and eicosanoids. Moreover, omega‐3 PUFAs are enzymatically transformed into lipid mediators, i.a. resolvins and protectins possessing the properties to soothe the ongoing inflammatory process and minimize tissue damage as well as to increase tissue protection in acute inflammation.

The use of omega‐3 PUFAs in the treatment of periodontitis may be beneficial due to controlling an inflammatory response against subgingival biofilm, reducing the level of pro‐inflammatory cytokines and inhibiting osteoclast function. This, in turn, improved clinical parameters of periodontitis, such as bleeding on probing (BOP), periodontal probing depth (PD) and connective tissue attachment level (CAL). In this paper, we discussed the most important information about the mechanisms of omega‐3 PUFAs EPA and DHA action, and their sources in the daily diet. We also reviewed the recent literature regarding the effects of using omega‐3 PUFAs as a complementary and supportive element in the non‐surgical treatment of periodontitis.

Practical Applications: Studies in humans and animals have suggested a beneficial therapeutic effect of omega‐3 fatty acids in the control of inflammation and periodontal tissue protection in periodontitis.

http://bit.ly/2GjNRmd

Analytical Determination of Phylloquinone (Vitamin K1) in Olive Oils. Comparison with Other Vegetable Oils

http://bit.ly/2Gjrrld

Editorial Board: Eur. J. Lipid Sci. Technol. 2∕2019

http://bit.ly/2So3AHx

Contents: Eur. J. Lipid Sci. Technol. 2∕2019

http://bit.ly/2GjBois

Central nervous system effects of the histamine‐3 receptor antagonist CEP‐26401, in comparison with modafinil and donepezil, after a single dose in a cross‐over study in healthy volunteers

Abstract

Aims

In previous studies, the H₃R antagonist CEP‐26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20μg), and a dose‐dependent disruption of sleep. In the current study, three low dose levels of CEP‐26401 were compared with modafinil and donepezil.

Methods

In this double‐blind, placebo‐ and positive‐controlled, randomized, partial six‐way cross‐over study, 40 healthy subjects received single doses of placebo, CEP‐26401 (5, 25, or 125 μg) or modafinil 200mg or donepezil 10mg. Pharmacokinetic and pharmacodynamic measurements were performed pre‐dose and at designated time points post‐dose.

Results

The main endpoint between‐errors of the SWM‐10‐boxes task only improved for the 125 μg dose of CEP‐26401 with a difference of 2.92 (CI ‐1.21 – 7.05), 3.24 (CI ‐1.57 – 8.04) and 7.45 (CI 2.72 – 12.19) for respectively the 5, 25 and 125 μg dose of CEP‐2640, ‐1.65 (CI ‐.572 – 1.96) for modafinil and ‐3.55 (CI ‐7.13 – 0.03) for donepezil. CEP‐26401 induced an improvement of adaptive tracking, saccadic peak velocity and reaction time during N‐back, but a dose‐related inhibition of sleep and slight worsening of several cognitive parameters at the highest dose. CEP‐26401 significantly changed several subjective VAS scales, which was strongest at 25 μg, causing the same energizing and happy feeling as modafinil, but with a more relaxed undertone.

Discussion

Of the doses tested, the 25 μg dose of CEP‐26401 had the most optimal balance between favourable subjective effects and sleep inhibition. Whether CEP‐26401 can have beneficial effects in clinical practice remains to be studied.

http://bit.ly/2t1SAkE

PHARMACOKINETICS OF TICARCILLIN‐CLAVULANATE IN PREMATURE INFANTS

Abstract

Ticarcillin‐clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin‐clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin‐clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6‐44) and gestational age of 25 weeks (23‐28). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043‐0.075]) compared with a PNA ≥14‐45 days (0.078 L/kg/h [0.047‐0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14d) or q8h (PNA ≥14‐45d) achieved the target exposure for organisms with an MIC ≤16 μ/mL in >90% of simulated infants. For highly resistant organisms (MIC 32 μg/mL), increased dosing frequency or extended infusion are necessary.

http://bit.ly/2HPP1Z9

Testing umbilical cord tissue for drugs: Lower analytical limits, better concordance with meconium results

Colby et al discussed the equivalency of umbilical cord and meconium testing to evaluate in utero exposure to drugs.1 The authors applied "commercial" umbilical cord tissue and gold standard meconium toxicology tests for detection of several drugs in paired umbilical cord and meconium samples from 501 neonates. The results in both specimens were often discordant. However, the overall prevalence of drugs in umbilical cord and meconium was similar for several groups, and the agreement between both specimens ranged from 80% to 100%.

http://bit.ly/2UAFA1q

Prenatal Maternal Psychological Distress and Offspring Risk for Recurrent Respiratory Infections

To assess the relation between maternal prenatal psychological distress, comprising depression and anxiety symptoms and relationship quality, and the risk of recurrent respiratory infections (RRIs) in children up to 2 years of age. Children with RRIs frequently use health care services and antibiotics. Prenatal maternal psychological distress can be one, previously unidentified risk factor for RRIs.

http://bit.ly/2UwJWq0

Steroid Free Treatment of Autoimmune Hepatitis in Selected Children

Current guidelines recommend steroids for induction of remission in all children diagnosed with autoimmune hepatitis regardless of the clinical presentation. In this report, we describe our experience in treating selected asymptomatic children with autoimmune hepatitis using a steroid-free regimen; this treatment strategy was safe and effective in inducing remission.

http://bit.ly/2S70Sqm

Re-conceptualizing Associations between Race and Morbidities of Extreme Prematurity

In this volume of The Journal, Ryan et al report a secondary analysis from the 11 centers included in the Prematurity and Respiratory Outcome Program (PROP).1 The purpose of PROP was to identify biomarkers and other factors associated with long-term respiratory morbidity among preterm infants, and the goal of this secondary analysis was to determine whether black infants were at lower risk of bronchopulmonary dysplasia (BPD). In PROP, enrolled extremely low gestational age black infants had a lower incidence of BPD (38%) compared with white infants (45%).

http://bit.ly/2S3nUP4

Caterpillar Sign in an Infant with Hypertrophic Pyloric Stenosis

A 7-week-old boy presented to the emergency department with a 2-week history of emesis. He was born at 39 weeks of gestation with a birth weight of 3495 g via normal spontaneous vaginal delivery. He had no history of taking macrolide antibiotics. He presented with postprandial, projectile, nonbilious vomitus after vigorously feeding on breast or formula milk. His weight decreased by 220 g, suggesting more than 5% dehydration over the previous 2 weeks. Physical examination revealed dry mucous membranes, but no abdominal mass, abdominal distension, or high-pitched bowel sounds.

http://bit.ly/2UzDlv2

Individual Participant Data Meta-Analysis Explained

In a study published in The Journal, Shaffer et al1 report the results of a PRISMA-compliant individual participant data (IPD) meta-analysis2 on the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone in very preterm infants. The primary conclusion from this IPD meta-analysis, which included the pooling of data from 4 randomized controlled trials representing 982 participants, was that early low-dose hydrocortisone therapy is beneficial for survival without bronchopulmonary dysplasia (BPD) in very preterm infants.

http://bit.ly/2S4YOzq

GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice

Abstract

The transcription factor GATA2 regulates normal hematopoiesis, particularly in stem cell maintenance and myeloid differentiation. Various heteroallelic GATA2 gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired GATA2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans. GATA2 hypomorphic mutant (G2 ^fGN/fGN) mice that were generated by the germline insertion of a neo‐cassette into the Gata2 gene locus avoided the early embryonic lethality observed in Gata2‐null mice. However, adult G2 ^fGN/fGN mice suffered from exacerbated leukocytosis concomitant with progressive anemia and thrombocytopenia and eventually developed massive granulo‐monocytosis accompanied by tri‐lineage dysplasia. The reconstitution activity of G2 ^fGN/fGN mouse stem cells was impaired. Furthermore, G2 ^fGN/fGN progenitors showed myeloid lineage‐biased proliferation and differentiation. Myeloid progenitor accumulation started at a younger age in G2 ^fGN/fGN mice and appeared to worsen with aging. G2 ^fGN/fGN mice exhibited increased expression of transcripts encoding cytokine receptors, such as M‐CSFR and IL6R, in granulocyte‐monocyte progenitors. This increased expression may be correlated with the hypersensitive granulo‐monocytic proliferation reaction when the mice were exposed to lipopolysaccharide. Taken together, these observations demonstrate that GATA2 hypomorphism leads to a hyperreactive defense response to infections, and this reaction is attributed to a unique intrinsic cell defect in the regulation of myeloid expansion that increases the risk for hematological neoplasm transformation.

This article is protected by copyright. All rights reserved.

http://bit.ly/2MMdZYh

Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice

Short session (≤10 min) high intensity interval training (HIIT) is emerging as an alternative to longer exercise modalities, yet the shorter variants are rarely modeled in animal studies. Here, we describe a 10 min, 3 day a week, uphill treadmill HIIT protocol that enhances physical performance in male and female aged mice.

http://bit.ly/2S36eTR

Modified Blood Collection from Tail Veins of Non-anesthetized Mice with a Vacuum Blood Collection System and Eyeglass Magnifier

This study reports blood sampling from tail vein in mice using a vacuum extraction tube system with eyeglass magnifier. Our method is easy to practice and could be used for repeat blood sampling in mice.

http://bit.ly/2UCCj1y

Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

Abstract

Late-onset Alzheimer's disease (AD) is a complex age-related neurodegenerative disorder that likely involves epigenetic factors. To better understand the epigenetic state associated with AD, we surveyed 420,852 DNA methylation (DNAm) sites from neurotypical controls (N = 49) and late-onset AD patients (N = 24) across four brain regions (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex and cerebellum). We identified 858 sites with robust differential methylation collectively annotated to 772 possible genes (FDR < 5%, within 10 kb). These sites were overrepresented in AD genetic risk loci (p = 0.00655) and were enriched for changes during normal aging (p < 2.2 × 10⁻¹⁶), and nearby genes were enriched for processes related to cell-adhesion, immunity, and calcium homeostasis (FDR < 5%). To functionally validate these associations, we generated and analyzed corresponding transcriptome data to prioritize 130 genes within 10 kb of the differentially methylated sites. These 130 genes were differentially expressed between AD cases and controls and their expression was associated with nearby DNAm (p < 0.05). This integrated analysis implicates novel genes in Alzheimer's disease, such as ANKRD30B. These results highlight DNAm differences in Alzheimer's disease that have gene expression correlates, further implicating DNAm as an epigenetic mechanism underlying pathological molecular changes associated with AD. Furthermore, our framework illustrates the value of integrating epigenetic and transcriptomic data for understanding complex disease.

http://bit.ly/2D1vTSo

Bioinformatics Analysis Makes Revelation to Potential Properties on Regulation and Functions of Human Sox2

Abstract

Sex determining region Y-box 2 (Sox2) is a transcription factor that is essential for maintaining self-renewal or pluripotency of undifferentiated embryonic stem cells. The expression and distribution of Sox2 in tumor tissues have been extensively recorded, which are related to the progression and metastasis of tumor. However, a complete mechanistic understanding of Sox2 regulation and function remains to be studied. Herein, we show new potential properties of Sox2 regulation and functions from bioinformatics analysis. We use numerous algorithms to characterize the Sox2 gene promoter elements and the Sox2 protein structure, physio-chemical, localization properties and its evolutionary relationships. The expression of Sox2 is regulated by a diverse set of transcription factors and associated with the levels of methylation of CpG Islands in promoters. The structural properties of Sox2 indicate that Sox2 expresses as a stem cell marker in a variety of stem cells. Sox2 together with other transcription factors or proteins regulate the expression of downstream target genes, which makes a great difference to the biological function of stem cells. Not only stem cells, Sox2 also play an important role in tumor cells. In conclusion, this information from bioinformatics analysis will help to understand Sox2 regulation and functions better in future attempts.

http://bit.ly/2WCi9Xm

A Simple Migration/Invasion Workflow Using an Automated Live-cell Imager

The current protocol describes an integrated method investigating cancer cell migration and invasion on a single platform in real-time, providing an easily reproducible and time-efficient option to study cell mobility and morphology.

http://bit.ly/2Ry2ILV

Efficacy of self-administered complex decongestive therapy on breast cancer-related lymphedema: a single-blind randomized controlled trial

Abstract

Purpose

After surgery, breast cancer-related lymphedema (BCRL) is a frequent chronic condition. The complex decongestive therapy (CDT) delivered by physiotherapists at hospitals is the state-of-the-art treatment choice. As lymphedema requires continuous management, we designed a 1-month-long course to train women to professionally carry out a self-administered CDT (saCDT) and tested its efficacy while keeping the benefits of CDT.

Methods

Consecutive patients treated with CDT over a 1-year period at an Italian facility were randomly assigned to either experimental (EXP, saCDT course) or control (CTRL, usual care) group. Women were assessed before, at 1, and 6 months from enrolment. Pain assessed by the numerical pain rating scale (NPRS) was the primary outcome. Arm asymmetry assessed by the excess limb volume (ELV) was the secondary outcome. Outcome variations were compared to their MCID to classify women as improved, stable, or worsened.

Results

Forty-one women were included. The proportion of stable or improved women was significantly different between EXP and CTRL groups at 6 months after enrolment for both arm pain (p = 0.01) and asymmetry (p < 0.01). Noteworthy, only one EXP woman had worsened after 6 months. NPRS significantly decreased in the EXP group only, with a median variation of 2 points. Arm ELV significantly decreased with respect to the baseline value in the EXP group only, with a median reduction of 8%.

Conclusions

Teaching saCDT to women with BCRL is effective in maintaining or improving the benefits of CDT and can be used as a self-care tool in the management of BCRL.

http://bit.ly/2t2Vtlh

Production of Extracellular Matrix Fibers via Sacrificial Hollow Fiber Membrane Cell Culture

The goal of this protocol is production of whole extracellular matrix fibers targeted for wound repair which are suitable for preclinical evaluation as part of a regenerative scaffold implant. These fibers are produced by the culture of fibroblasts on hollow fiber membranes and extracted by dissolution of the membranes.

http://bit.ly/2D3Qg1b

Cereal Crop Ear Counting in Field Conditions Using Zenithal RGB Images

We present a protocol for counting durum wheat and barley ears, using natural color (RGB) digital photographs taken in natural sunlight under field conditions. With minimal adjustments for camera parameters and some environmental condition limitations, the technique provides precise and consistent results across a range of growth stages.

http://bit.ly/2G4Y4nn

RSPO2 gene rearrangement: a powerful driver of {beta}-catenin activation in liver tumours

Objective

We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC).

Design

Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed.

Results

A roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of β-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of β-catenin and transcriptional activation of β-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three β-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter—known to drive malignant transformation of CTNNB1-mutated HCA—seem to be dispensable for RSPO2 rearranged HCA and HCC.

Conclusion

The RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.

http://bit.ly/2TsUt5I

What is a pituitary adenoma? A pituitary adenoma is a fairly common benign growth that occurs in the...

What is a pituitary adenoma? A pituitary adenoma is a fairly common benign growth that occurs in the pituitary gland....

http://bit.ly/2t0T0aX

Model-informed Drug Development Approach Supporting Approval of the 4-week (Q4W) Dosing Schedule for Nivolumab (Opdivo) across Multiple Indications: A Regulatory Perspective

Abstract

Background

A nivolumab dosage regimen of 480 mg intravenously (IV) every 4 weeks (Q4W) was approved by FDA for the majority of the approved indications for nivolumab.

Methods

The proposed new dosage regimen was supported by pharmacokinetic modeling and simulation, dose/exposure response relationships for efficacy and safety in the indicated patient populations, and the clinical safety data with the 480 mg Q4W dosage regimen. Pharmacokinetic exposures achieved with 480 mg Q4W were predicted for 4,166 patients in 21 clinical studies with various types of solid and hematological tumors. Exposure-response analyses were conducted to predict 480 mg Q4W safety and efficacy across all FDA-approved indications for nivolumab.

Results

For the overall population, the geometric mean exposure achieved with 480 mg IV Q4W was 5.2% higher for steady state C_avg and 15.6% lower for C_trough than those with 3 mg/kg IV Q2W, the approved dosage regimen. The simulated concentration-time course achieved with 480 mg Q4W regimen was below the median concentration achieved with 10 mg/kg IV Q2W that was also studied in clinical trials. The predicted probability of adverse events was similar between 480 mg Q4W and that observed with the 3 mg/kg Q2W regimen. Efficacy results were found to be similar between Q2W and Q3W dosage regimens in patients with RCC. The predicted efficacy for each indication suggested that the efficacy with 480 mg Q4W is unlikely to be compromised compared to that observed with 3 mg/kg Q2W.

Conclusions

The model-informed analyses of predicted exposure, efficacy and safety based on data from extensive clinical experience with nivolumab suggest that the benefit-risk profile of 480 mg Q4W regimen is comparable to the approved 3 mg/kg Q2W regimen, thus providing the regulatory basis for the approval of 480 mg Q4W regimen in the absence of clinical efficacy data with this new dosage regimen.

http://bit.ly/2G75bLX

Editorial Annals of Oncology

http://bit.ly/2Gj9pPT

Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Ann Oncol 2018; 29: iv238–iv255 (doi:10.1093/annonc/mdy308)

http://bit.ly/2G6v1Qk

Crimean Congo hemorrhagic fever serosurvey in humans for identifying high-risk populations and high-risk areas in the endemic state of Gujarat, India

Crimean Congo Hemorrhagic Fever (CCHF) is a highly infectious zoonotic disease of humans transmitted by Hyalomma ticks. Earlier studies have shown CCHF seroprevalence in livestock throughout India, yet sporadic o...

http://bit.ly/2HLhT4Y

Two variants of the IIR spline adaptive filter for combating impulsive noise

It has been pointed out that the nonlinear spline adaptive filter (SAF) is appealing for modeling nonlinear systems with good performance and low computational burden. This paper proposes a normalized least M-...

http://bit.ly/2HLC6HN

Effect of bladder distension on arginine vasopressin secretion in rats

Urine production is regulated throughout the night to ensure that it remains within functional bladder capacity. Increasing bladder capacity may thus play an important role in urine production. We investigated...

http://bit.ly/2HWzxT4

Measles case, immunization coverage and its determinant factors among 12–23 month children, in Bassona Worena Woreda, Amhara Region, Ethiopia, 2018

The aims of this study were: (1) to calculate measles vaccination coverage and characterize its determinants, and (2) to qualitatively explore factors associated with reasons associated with not immunization a...

http://bit.ly/2t2luRS

Mixed alcoholic fermentation of Schizosaccharomyces pombe and Lachancea thermotolerans and its influence on mannose-containing polysaccharides wine Composition

This study researched the winemaking performance of new biotechnology involving the cooperation of Lachancea and Schizosaccharomyces genera in the production of wine. In all fermentations where Lachancea thermoto...

http://bit.ly/2TqPPVO

Coupled changes of bacterial community and function in the gut of mud crab (Scylla Paramamosain) in response to Baimang disease

Increasing evidence has revealed a close association between intestinal bacterial community and hosts health. However, it is unclear whether and what extend Baimang disease alters the intestinal microbiota in ...

http://bit.ly/2BfaFAc

Pneumonia in hospitalized neurologic patients: trends in pathogen distribution and antibiotic susceptibility

Bed-ridden state, dysphagia, altered mental state, or respiratory muscle weakness are common in neurologic patients and increase the risk of pneumonia. The major causes of pneumonia in neurologic patients may ...

http://bit.ly/2G5E6J5

Pathological diagnosis of thyroid nodules based on core needle biopsies: comparative study between core needle biopsies and resected specimens in 578 cases

Pathological diagnosis based on core needle biopsy (CNB) should be different from a resected specimen because it is difficult to apply the histological criteria established for resected specimens to CNB due to...

http://bit.ly/2D1YpDx

Elevated expression of ciRS-7 in peripheral blood mononuclear cells from rheumatoid arthritis patients

Circular RNAs (circRNAs) represent a class of widespread and variety endogenous RNAs that may regulate gene expression. Thousands of mammalian circRNAs harbor miRNA response elements (MREs), suggesting a poten...

http://bit.ly/2G640wA

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary

Pagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is diffic...

http://bit.ly/2D4iJnL

Midwives’ views of traditional birth attendants within formal healthcare in Nigeria

Publication date: Available online 2 February 2019

Source: Women and Birth

Author(s): Magdalena Ohaja, Jo Murphy-Lawless, Margaret Dunlea

Abstract

Background

Discourses around the journey to motherhood in many poorly-resourced countries, particularly in the sub-Saharan African region, with no link to death and danger are limited. The custodians of traditional practices – the traditional birth attendants – are often blamed for the high maternal deaths in this region. Conventional institutional and international thinking about traditional birth attendants is that they are dangerous and therefore should no longer be allowed to practice.

Aim

To explore midwives' views of traditional birth attendants' place within formal healthcare settings in Nigeria.

Methods

Hermeneutic phenomenological and poststructural feminist approaches were used. Seven midwives volunteered for semi-structured individual face to face interviews.

Findings

The responses of the midwives were diverse and conflicting. Some midwives believe that the traditional birth attendants should be banned, arguing that they are responsible for low uptake of hospital-based maternity care by women which in turn leads to an increase in maternal deaths. Contrastingly, other midwives expressed a view that the traditional birth attendants 'cannot be phased out' due to their valid contributions, particularly in the rural areas where access to formal maternity care is limited by intractable structural problems.

Conclusion

Policy makers need to reconsider the role of traditional birth attendants. This should involve not only their integration into formal healthcare to work alongside formally trained maternity care providers, but also fostering a healthcare atmosphere where respect and recognition of each practitioner's skill is paramount.

http://bit.ly/2S61D2U

Predictors of postpartum depression service use: A theory-informed, integrative systematic review

Publication date: Available online 2 February 2019

Source: Women and Birth

Author(s): Rena Bina

Abstract

Problem

Postpartum depression affects many women globally, yet rates of treatment use are low. A comprehensive view of factors associated with treatment use, from women's and providers' perspectives, based on a theoretical model is lacking.

Background

Several studies examined various factors associated with postpartum depression service use; however, each study focused on a small number of factors.

Aim

This study describes a systematic literature review based on the Behavioral Model of Health Service Use. The purpose of this article is to review and synthesize the available literature regarding factors associated with women's mental health service use for postpartum depression from women's and healthcare providers' perspectives, and provide a comprehensive integrative view of the subject.

Methods

Three electronic databases were searched, and 35 studies published up to 2018 in English language journals met inclusion criteria for review. Factors associated with postpartum depression service use were classified according to the Behavioral Model of Health Service Use's constructs.

Findings

Service use for postpartum depression is a function of a woman's predisposition to use mental health services; individual, familial, and communal factors which enable or pose barriers to use of mental health services; and the woman's perceived or evaluated need for treatment. In addition, societal determinants impact the woman's decision to seek help directly or through impacting the health and mental health care service system's resources and organization.

Conclusion

This review illustrates key factors for researchers and practitioners to consider when treating postpartum women and developing interventions to enhance postpartum depression treatment use.

http://bit.ly/2UzmrNe

Comparison of Capecitabine (Xeloda) vs. Combination of Capecitabine and Oxaliplatin (XELOX) as Neoadjuvant CRT for Locally Advanced Rectal Cancer

Abstract

We decided to compare pathologic complete response (pCR) and disease-free survival (DFS) in rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy (CRT) with capecitabine plus oxaliplatin (XELOX) or capecitabine (Xeloda). In this study, patients with non-metastatic locally advanced rectal cancer (tumor stages of T2, T3, or T4) with or without lymph node involvement were retrospectively included. Patients received concomitant radiation (50.4–54 Gy external beam radiation in 28 to 30 fractions) and neoadjuvant therapy as either Xeloda (capecitabine, 2500 mg/m² concomitantly with radiation therapy) (42patients) or XELOX [(oxaliplatin (50 mg/m² intravenously once a week for five weeks) and capecitabine)] (72 patients). Surgery was done eight weeks after CRT. The endpoints were pCR (defined as no evidence of viable tumoral cells) and DFS (the interval from the initial treatment to the first tumor recurrence). Rectal sphincter preservation via low-anterior resection (LAR) was achieved in 73.8% of Xeloda group which was similar to XELOX group (70.8%), P = 0.61. pCR was documented in 11 (26.9%) of Xeloda group and 26 patients (36.1%) of XELOX group (P = 0.27). Tumor recurrence was recorded in 97 patients (85.1%). Mean (±SD) DFS was 52.13 (±31.92) months (median = 48 months). Mean (95% CI) DFS was 129.42 (110.19 to 148.64) in Xeloda group vs. 122.77 (110.72 to 134.83) in XELOX group (P = 0.74). Addition of oxaliplatin to capecitabine as neoadjuvant CRT for locally advanced rectal cancer did not result in improved pCR or better DFS.

http://bit.ly/2S8hePT

Quality of life in elderly breast cancer patients with localized disease receiving endocrine treatment: a prospective study

Abstract

Purpose

In this paper we study the quality of life (QoL) of elderly breast cancer patients receiving endocrine treatment (ET). More QoL data on elderly patients treated with ET are needed. Our aims are to study QoL in early-stage breast cancer patients throughout the treatment period and compare the QoL of ET groups.

Methods

148 patients > 65 years who began ET with either tamoxifen or aromatase inhibitor (AI) completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) questionnaires three times over 3 years of ET. Linear mixed-effect models were used to evaluate longitudinal QoL changes. ET group comparisons were conducted after 3 years of treatment via ANCOVA adjusted by basal QoL.

Results

QoL scores were high (> 80/100 points) in most QoL areas, with moderate limitations (> 30) in sexual functioning and enjoyment and in future perspective. After 3 years of ET, four QoL areas improved (< 6 points) compared to baseline and 3-month assessments. Hot flushes worsened (8 points) at the 3-month assessment but by 3 years had recovered. AI patients showed more hot flushes, pain and diarrhea and less sexual enjoyment than tamoxifen patients after 3 years of ET (differences 3–12 points).

Conclusions

Results indicate that elderly early-stage breast cancer patients adapted well to their disease and ET treatment over the 3 years. Few QoL differences were observed between ET groups.

http://bit.ly/2UBYCV3

Incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer: data from NEOcoping study

Abstract

Background

Our study analyzes the incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer.

Methods

A multi-institutional, prospective, observational study was conducted with 750 participants of 14 hospitals in Spain. Participants' socio-demographic and clinical characteristics were collected using a standardized self-report form and using EORTC QoL-QLQ-C30, BSI, Mini-MAC questionnaires.

Results

In women, sleep problems, depression and anxious preoccupation were observed in 65, 41 and 21%, respectively. In men, sleep problems, depression and anxious preoccupation were reported in 51, 29 and 61%, respectively. More sleep problems, depression and anxious preoccupation were found among women than males. Depression was a significant predictor of anxious preoccupation. In males, sleep problems partially mediated this association. This was not confirmed in women.

Conclusion

Our findings point toward the importance of developing interventions that decrease depression and sleep problems in cancer.

http://bit.ly/2S3yHIR

Letrozole improves the sensitivity of breast cancer cells overexpressing aromatase to cisplatin via down-regulation of FEN1

Abstract

Purpose

Flap endonuclease 1 (FEN1) is up-regulated by estrogen (17β-estradiol, E2) and related to cisplatin resistance of human breast cancer cells. Letrozole, an aromatase inhibitor, suppresses the change of testosterone into estrogen and is frequently used to treat breast cancer. However, the effects of letrozole on FEN1 expression and cisplatin sensitivity in breast cancer cells overexpressing aromatase have not been revealed.

Methods

The expression of FEN1 and the proteins in ERK/Elk-1 signaling were evaluated by RT-PCR and Western blot. Cisplatin sensitivity was explored through CCK-8 and flow cytometry analysis, respectively. FEN1 siRNAs and FEN1 expression plasmid were transfected into cells to down-regulate or up-regulate FEN1 expression. The promotor activity of FEN1 was detected using luciferase reporter assay.

Results

FEN1 down-regulation improved cisplatin sensitivity of breast cancer cells overexpressing aromatase. Letrozole down-regulated FEN1 expression and increased cisplatin sensitivity. The sensitizing effect of letrozole to cisplatin was dependent on FEN1 down-regulation. FEN1 overexpression could block the sensitizing effect of letrozole to cisplatin. Testosterone up-regulated the promotor activity, protein expression of FEN1, and phosphorylation of ERK/Elk-1, which could be eliminated by both letrozole and MEK1/2 inhibitor U0126. Letrozole down-regulated FEN1 expression in an ERK/Elk-1-dependent manner.

Conclusions

Our findings clearly demonstrate that letrozole improves cisplatin sensitivity of breast cancer cells overexpressing aromatase via down-regulation of FEN1 and suggest that a combined use of letrozole and cisplatin may be a potential treatment protocol for relieving cisplatin resistance in human breast cancer.

http://bit.ly/2UBZg4H

Incidence and survival of central nervous system tumors in childhood and adolescence in Girona (Spain) 1990–2013: national and international comparisons

Abstract

Introduction

Pediatric central nervous system tumors are one of the most frequent types of neoplasms in children but epidemiological data on these tumors have been sparsely reported in the medical literature.

Materials and methods

We analyze the epidemiology of this type of tumors performing a retrospective population-based study in pediatrics and adolescent age in the population of Girona and compare them with series from Spain, Europe and worldwide. Cases were registered using the International Classification of Disease for Oncology, third edition and grouping according the International Classification of Childhood Cancer, third edition (ICCC-3).

Results

For all the histologies and the whole population between 0 and 19 years old, ASRw was 41.8 cases per million person-years. In children population, meaning under 14 years old, we found 104 cases with ASRw of 45.6. Males were the most affected by CNS tumors with a 1.2 sex ratio between 0 and 14 years old, and 1.1 between 0 and 19 years old. The analysis of trends in incidence did not find any statistically significant increase or decrease. Five-year observed survival was 68%, both for patients under 19 and 14 years of age.

Conclusions

The incidence in our area was among the highest in Spain and worldwide, while survival was comparable to others reported.

http://bit.ly/2S3yBkt

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells

Signal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays...

http://bit.ly/2MNUCxP

Antilisterial efficacy of Lactobacillus brevis MF179529 from cow: an in vivo evidence

Listeria monocytogenes is an opportunistic foodborne pathogen that causes human Listeriosis and high mortality particularly in immunocompromised individuals. Pregnant women are more prone to L. monocytogenes infe...

http://bit.ly/2DPpY4i

Impact of levosimendan on weaning from peripheral venoarterial extracorporeal membrane oxygenation in intensive care unit

Few data are available on the impact of levosimendan in refractory cardiogenic shock patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The aim of this study was to eval...

http://bit.ly/2GiykTW

Severe toxicity from checkpoint protein inhibitors: What intensive care physicians need to know?

Checkpoint protein inhibitor antibodies (CPI), including cytotoxic T-lymphocyte-associated antigen 4 inhibitors (ipilimumab, tremelimumab) and the programmed cell death protein 1 pathway/programmed cell death ...

http://bit.ly/2SpMNDK

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases

Abstract

Objectives

Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation.

Methods

We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing.

Results

Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines.

Conclusions

The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

http://bit.ly/2G5Crn4

Cancers, Vol. 11, Pages 175: Connexin43 Suppresses Lung Cancer Stem Cells

Cancers, Vol. 11, Pages 175: Connexin43 Suppresses Lung Cancer Stem Cells

Cancers doi: 10.3390/cancers11020175

Authors: Randall J. Ruch

Alterations in gap junctions and their protein components, connexins, have been associated with neoplastic transformation and drug resistance, and more recently have been shown to play important roles in cancer stem cells (CSCs). However, there is less knowledge of connexins and gap junctions in lung CSCs. To address this, Connexin43 (Cx43), the major human lung epithelial gap junction protein, was expressed ectopically in poorly expressing National Cancer Institute-125 (NCI-H125) metastatic human lung adenocarcinoma cells, and phenotypic characteristics of malignant cells and abundance of CSCs were evaluated. The ectopic expression of Cx43 resulted in the formation of functional gap junctions; a more epithelial morphology; reduced proliferation, invasion, colony formation, tumorsphere formation, pluripotency marker expression, and percentage of aldehyde dehydrogenase (ALDH)-positive cells; and increased cisplatin sensitivity. Similarly, in NCI-H522 (human lung adenocarcinoma) and NCI-H661 (human lung large cell carcinoma) cell lines, which express Cx43 and functional gap junctions endogenously, the Cx43 content was lower in tumorspheres and ALDH-positive cells than in bulk cells. These results demonstrate that Cx43 can reverse several neoplastic characteristics and reduce the abundance of human lung CSCs.

http://bit.ly/2MNS4Qh

Saliva as a Diagnostic Tool in Oral Squamous Cell Carcinoma – a Systematic Review with Meta Analysis

Abstract

Whole saliva is mainly composed of fluid produced by major and minor salivary glands. Major salivary glands including parotid, submandibular, and sublingual glands, are known to secrete fluid transported from serum as well as surrounding glandular tissues [1]. Beside the secretions from salivary glands, oral mucosa, periodontium, as well as oral microflora also contribute to the final content of whole saliva [1]. Whole saliva therefore represents a complex balance among local and systemic sources [2]. This allows for the application of saliva in the diagnosis not only for salivary gland disorders but also for oral diseases and systemic conditions [2]. The role of saliva as a diagnostic tool in detecting Oral Squamous Cell Carcinoma. Articles published in PUBMED, EMBASE, COCHRANE, GOOGLE, manual search and back references of the articles for last 5 years extracted 77 articles. Studies which considered saliva as a diagnostic tool were included. Statistical analysis with Receivers Operating Curve to establish sensitivity and specificity of the salivary biomarkers as a diagnostic tool to detect Oral Squamous Cell Carcinoma were included for meta analysis. The measure of effect with 95% confidence interval were meta analysed for 9 articles in which 308 healthy individuals compared with 340 patients with Oral Squamous Cell Carcinoma. Highly sensitive salivary biomarkers for detecting Oral Squamous Cell Carcinoma were MMP-9, Chemerin, Choline + Betaine + Pipecolinic Acid + I – Carnitine(confidence interval ranges from 0.83–1.0). The narrow confidence interval of 0.95 + (0.88–1.00) was seen for MMP-9 followed by 1.00 + (0.78–1.00) for chemerin. Highly specific biomarkers for Oral Squamous Cell Carcinoma were MMP-9 (specificity −100%,), Chemerin(specificity-100%), over expressed mi RNA 136 with specificity of 0.88(0.69–0.97), under expressed mi RNA 27B with specificity of 1.0(0.66–1.00). Saliva can be used as a diagnostic tool with highly sensitive and specific markers namely MMP-9, Chemerin for early detection of Oral Squamous Cell Carcinoma.

http://bit.ly/2WDhNiV

S -adenosylmethionine biosynthesis is a targetable metabolic vulnerability of cancer stem cells

Abstract

Purpose

Many transformed cells and embryonic stem cells are dependent on the biosynthesis of the universal methyl-donor S-adenosylmethionine (SAM) from methionine by the enzyme MAT2A to maintain their epigenome. We hypothesized that cancer stem cells (CSCs) rely on SAM biosynthesis and that the combination of methionine depletion and MAT2A inhibition would eradicate CSCs.

Methods

Human triple (ER/PR/HER2)-negative breast carcinoma (TNBC) cell lines were cultured as CSC-enriched mammospheres in control or methionine-free media. MAT2A was inhibited with siRNAs or cycloleucine. The effects of methionine restriction and/or MAT2A inhibition on the formation of mammospheres, the expression of CSC markers (CD44^hi/C24^low), MAT2A and CSC transcriptional regulators, apoptosis induction and histone modifications were determined. A murine model of metastatic TNBC was utilized to evaluate the effects of dietary methionine restriction, MAT2A inhibition and the combination.

Results

Methionine restriction inhibited mammosphere formation and reduced the CD44^hi/C24^low CSC population; these effects were partly rescued by SAM. Methionine depletion induced MAT2A expression (mRNA and protein) and sensitized CSCs to inhibition of MAT2A (siRNAs or cycloleucine). Cycloleucine enhanced the effects of methionine depletion on H3K4me3 demethylation and suppression of Sox9 expression. Dietary methionine restriction induced MAT2A expression in mammary tumors, and the combination of methionine restriction and cycloleucine was more effective than either alone at suppressing primary and lung metastatic tumor burden in a murine TNBC model.

Conclusions

Our findings point to SAM biosynthesis as a unique metabolic vulnerability of CSCs that can be targeted by combining methionine depletion with MAT2A inhibition to eradicate drug-resistant CSCs.

http://bit.ly/2t4176R

Sustainable cytopathology in the precision medicine era: Exploring new sources for molecular testing in thyroid cytology specimens

http://bit.ly/2GjKo7w

Cancers, Vol. 11, Pages 174: Treatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review

Cancers, Vol. 11, Pages 174: Treatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review

Cancers doi: 10.3390/cancers11020174

Authors: Denise Fabian Maria del Pilar Guillermo Prieto Eibl Iyad Alnahhas Nikhil Sebastian Pierre Giglio Vinay Puduvalli Javier Gonzalez Joshua D. Palmer

Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment, GBM almost always recurs. The current standard-of-care for treatment of newly diagnosed GBM has remained relatively unchanged since 2005: maximal safe resection followed by concomitant chemoradiation (CRT) with temozolomide (TMZ), and subsequent adjuvant TMZ. In 2011, the first-generation tumor treating fields (TTF) device, known at the time as the NovoTTF-100A System (renamed Optune), was approved by the Food and Drug Administration (FDA) for treatment of recurrent GBM. The TTF device was subsequently approved as an adjuvant therapy for newly-diagnosed GBM in 2015. The following is a review of the TTF device, including evidence supporting its use and limitations.

http://bit.ly/2DP105g

Atypical diaphyseal femoral fractures: considerations on surgical technique

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Maria Silvia Spinelli, Eleonora Marini, Primo Andrea Daolio, Andrea Piccioli

Abstract

In the last two decades bisphosphonates (BP) has become the mainstream therapy for osteoporosis and the benefit in reducing the incidence of fractures has been well demonstrated in several studies, together with the drug long term (5–10 years) efficacy and safety.

A complication of the long-term use of bisphosphonates is a low-energy stress fractures located in the sub-trochanteric region and the femoral shaft called atypical femur fracture (AFF).

These stress fractures can be seen on plain radiographs as simple transverse patterns, with unicortical beaking and hypertrophy of the diaphyseal lateral cortex. Usually a localized thigh pain in the prodromal phase may precede the fracture by months. The current surgical treatment of choice for AFFs is intramedullary nailing (IMN). However, the treatment of AFFs is associated with a higher rate of intra-operative and post-surgical complications. This is related to anatomical e biomechanical reasons. Iatrogenic fractures, deformities, medial gap opening, eccentric position of the distal nail tip with anterior cortex perforation, delayed or non-union are frequent complications of this procedure and healing rate of AFFs. The average healing time of almost 8 months for AFFs appeared to be longer than that for typical femoral fractures, which heal at an average of 3 to 6 months.

The purpose of this study is to analyze the different surgical devices and techniques and to advance some considerations that can be useful to diminish the rate of failure and/or complications in the treatment of AFFs in both oncologic and osteoporotic patients.

http://bit.ly/2MKOAhA

BALLOON KYPHOPLASTY COMBINED WITH POSTERIOR SCREW-ROD SYSTEM IN TYPE A POST-TRAUMATIC VERTEBRAL FRACTURES: ARE BONE SUBSTITUTES REALLY USEFUL IN THIS ASSOCIATION?

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Andrea Piazzolla, Giuseppe Solarino, Davide Bizzoca, Claudia Parato, Biagio Moretti

Abstract

Introduction

Recent studies have shown the efficacy and feasibility of the association between balloon kyphoplasty (BK) and minimally invasive posterior pedicle screw fixation, in post-traumatic type A vertebral fractures. None of them, however, has investigated the usefulness of PMMA or bone substitutes in this technique.

Materials and methods

55 patients (32 males, 23 females; mean age: 29.2), with post-traumatic thoracolumbar spine fractures, were treated with cementless BK combined with the posterior screw-rod system. Inclusion criteria: type A thoracolumbar vertebral fractures; absence of neurological deficit; one or more of these features (signs of vertebral instability; an anterior body wall compression >50° or a vertebral kyphosis (VK) >15°). Exclusion criteria: absence of a traumatic event; lumbar or hip T-score<-2.5; history of spinal infections; pre-existent disease that could compromise surgical procedure (i.e. previous vertebroplasty of the involved vertebrae); pregnancy; history of malignant neoplasm; BMI > 30; scoliosis>40°; metal allergies; any contraindication to CT.

At recruitment, the patients underwent a CT and a MRI of the spine to classify the fracture. Clinical evaluation was performed, using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI), at baseline, 48 hours after surgery, at 3-months follow-up (fu), 6-months fu, 48 hours after the instrumentation removal and at 15-months fu. At each fu, VK, regional kyphosis (RK), central wall (MH/PH) and anterior wall (AH/PH) heights were assessed on lateral spine x-rays. At 6-months fu, a CT scan of the spine was performed to investigate the fracture healing. The posterior instrumentation was removed 7 months after surgery (range: 6-10 months).

Results

A significant reduction of mean VAS (p < 0.05) and ODI (p < 0.05) was observed after surgery; no impairment of these scores were observed after the instrumentation removal. A significant correction of VK, RK, AH/PH and MH/PH was recorded after surgery; no significant changes of these values were noticed at subsequent fu. After the instrumentation removal, only a RK impairment was recorded, but it was not significant.

Conclusions

PMMA or bone substitutes are not necessary, to keep the reduction of the endplate obtained with the balloon tamp, when BK is performed in the association with posterior percutaneous pedicle screws instrumentation.

http://bit.ly/2DPXHLi

Aetiology of trauma-related acute compartment syndrome of the leg: A systematic review

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Marco Stella, Emmanuele Santolini, Francesca Sanguineti, Lamberto Felli, Giovanni Vicenti, Davide Bizzoca, Federico Santolini

Abstract

Background

Acute compartment syndrome (ACS) is characterised by abnormal pressure inside a compartment, resulting in ischemia of muscles and nerves. Most orthopaedic surgeons, especially those who work in major trauma centres, have been or will be facing a case of ACS in their clinical activity.

Fortunately, complications related to untreated compartment syndrome have become less frequent thanks to a better understanding of pathogenesis and to early recognition and prompt surgical treatment. The aim of this study is to identify the existing evidence regarding aetiology of trauma-related ACS of the leg.

Methods

A systematic review of the literature was undertaken using PubMed Medline, Ovid Medline and the Cochrane library, extended by a manual search of bibliographies. Retrieved articles were eligible for inclusion if they reported data about aetiology of trauma-related compartment syndrome of the tibia.

Results

Ninety-five studies that fulfilled the inclusion criteria were identified. By dividing the studies into three groups according to the traumatic aetiology, we were able to classify traumatic ACS as fracture related, soft tissue injury related and vascular injury related. Fracture related was the most represented group, comprising 58 papers, followed by the soft tissue injury related group which includes 44 articles and vascular injury related group with 24 papers.

Conclusions

Although traditionally ACS has been associated mainly with fractures of tibial diaphysis, literature demonstrates that other localisations, in particular in the proximal tibia, are associated with an increased incidence of this serious condition.

The forms of ACS secondary to soft tissues injuries represent an extremely variable spectrum of lesions with an insidious tendency for late diagnosis and consequently negative outcomes. In the case of vascular injury, ACS should always be carefully considered as a priority, given the high incidence reported in the literature, as a result of primitive vascular damage or as a result of revascularisation of the limb.

Knowledge of aetiology of this serious condition allows us to stratify the risk by identifying a population of patients most at risk, together with the most frequently associated traumatic injuries.

http://bit.ly/2MKOyGu

Diagnosis and management of periprosthetic femoral fractures after hip arthroplasty

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Stefano Giaretta, Alberto Momoli, Giovanna Porcelli, Gian Mario Micheloni

ABSTRACT

Introduction

Periprosthetic femoral fracture represent a severe complication, at present the third cause of revision surgery, with an estimated incidence from 0,1 to 2,1%. The number of these fracture can be expect to increase in line with the aging of population and amount of THA implants also in younger high demanding patients.

Materials and Methods

The aim of this study is analyze the diagnostic and therapeutic decision making processes performed in 64 patients with periprosthetic fractures treated surgically from January 2012 and October 2016 in our center. We analysed instrumental exams and surgical reports focusing on type of procedure, surgical access, operative time and type of fixation.

Results

Average age was 80,9 years and a mean follow-up 23,1 months.

According to Vancouver system and after X-rays, CT scan and intraoperative evaluation, 26 fractures were classified as type B1, 31 as type B2, 3 type B3 and 4 type C.

Follow up results were divided on the basis of the surgical treatment: in ORIF group (23 type B1 fractures and 4 type C fracture) fracture union was obtained in 16 cases (59,3%) and the final HHS mean value was 61,61; in Revision group (3 type B1, 31 type B2 and 3 type B3) bone healing was reported in 26 cases (70,3%) with mean HHS score of 71,94.

Conclusions

In this surgery the objectives are provide an adequate bone healing and return to previous functional status as soon as possible. Many reasons make these goals challenging, in particular advanced age, osteoporosis, co-morbidity and weakness that lead to low energy trauma, the most frequent cause of these injuries. In our opinion a crucial aspect is the evaluation of stem stability, considering an implant mobilized until the opposite is clearly evident. Reduction of surgical time and early mobilization are goals of this surgery, often associated with several complications and high mortality rate.

http://bit.ly/2DS5WpZ