bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Alangium lamarckii Bark for Antiplasmodial and Cytotoxic Constituents and Isolation of a Novel Tubulosine Analogue
Authors: Kantamreddi Venkata Siva Satyanarayana , Marston Gemma , Shnyder Steven D. , Wright Colin W.
Published: March 2019

Alangium lamarkii is traditionally used in India for the treatment of malaria. Partial activity guided-fractionation of the basic chloroform fraction of the methanolic extract of the bark led to the isolation of a novel tubulosine analogue, 10-demethyl-9'- N-methyltubulosine (1), for which the trivial name tubulosatine is suggested. In addition, the known A. lamarkii constituents, tubulosine (2), cephaeline and emetine were isolated as potent antiplasmodial and cytotoxic constituents, but 1 was up to 1000-fold less potent than the former alkaloids against both malaria parasites and human cancer cell lines. The compounds were active against both chloroquine-sensitive and chloroquine-resistant malaria parasites, but no selective toxicity was observed towards malaria parasites compared with cancer cells with any of the alkaloids. Further work to explore the basis for the relatively weak biological activities of 1 would be worthwhile. Betulinic acid, stigmasterol and its 3- O-glucoside were isolated from the neutral chloroform fraction of the methanolic extract.
Isolation and Structure Elucidation of Secondary Metabolites from a Microcystis sp. Bloom Material Collected in Southern Israel
Authors: Hasin Ohad , Carmeli Shmuel
Published: March 2019

The hydrophilic extract of Microcystis sp. bloom material collected from Bror Hayil Reservoir in southern Israel afforded four new metabolites, (2 S,3 S)-3-hydeoxy-1,4-diphenylbutan-2-yl-acetate, aeruginosins BH604, BH462A and BH462B, and two known metabolites cyanopeptolins S and SS. The planar structure of 1–4 was established by analyses of their 1D and 2D NMR data and mass spectrometric data. The absolute configurations of the chiral centers of 1 were established by Mosher method and analysis of the coupling constants between H-2 and H-3, and those of 2–4 by Merfay's method and advanced Merfay's method and chiral HPLC. The compounds do not inhibit the serine proteases trypsin and thrombin.
The Use of Trimethyl Orthoacetate for the Conversion of Natural Mono- and Dihydroxynaphthazarins and Related Compounds to Their Methyl Ethers
Authors: Balaneva Nadezhda N. , Shestak Olga P. , Novikov Vyacheslav L.
Published: March 2019

Trimethyl orthoacetate can be used as an alternative to CH2N2 on the methylation of β-OH groups of (poly)hydroxynaphthazarins. In contrast to CH2N2 it can be applied both to complete and to selective methylation of these groups.
New Verrucosidin Derivatives from the Marine-Derived Fungus Penicillium sp. XL-01
Authors: Xu Yan , Zhang Miao , Liu Qing-Ai , Hu Lian-Dong , Li Wan , Zhu Hua-Jie , Liu Li , Cao Fei
Published: March 2019

Two new verrucosidin derivatives, named nordeoxyverrucosidin (1) and norverrucosidinol acetate (2), along with three known analogues (3–5) were isolated from the marine-derived fungus Penicillium sp. XL-01 collected from the Bohai Sea. Their structures and relative configurations were elucidated by comparing with literature data and a combination of spectroscopic techniques. The absolute configuration of 1 was assigned by quantum chemical calculation of the electronic circular dichroism (ECD) spectrum. Compounds 1 and 3 displayed promising cytotoxic activity against the MGC-803 cell line, with IC50 values of 0.96 and 1.14 μM, respectively, more effective than the positive control (cisplatin).
Vasorelaxation Caused by Eugenol, Curcumin and Nanocurcumin is Partially Mediated by Activation of Aminoguanidine-sensitive iNOS in the Middle Uterine Artery of Non-pregnant and Pregnant Capra hircus
Authors: Jandhyam Harithalakshmi , Parija Subas Chandra
Published: March 2019

Natural products like eugenol and curcumin have been reported to control hypertension. The purpose of our study was to examine the role of iNOS in eugenol/curcumin/nanocurcumin–induced vasorelaxation in the middle uterine artery (MUA) obtained from non-pregnant (NP) and pregnant (P) Capra hircus ( Ch). The MUA rings were mounted in an automatic organ bath attached to a powerlab data acquisition system. Vasorelaxation was induced by eugenol/curcumin/nanocurcumin in either the absence or presence of aminoguanidine in phenylephrine precontracted MUA rings. The vasorelaxation response was recorded isometrically by a highly sensitive isometric force transducer automatic organ bath connected to powerlab and analysed using Labchart 7.1.3 software. The maximal vasorelaxation (Rmax) obtained from eugenol, curcumin and nanocurcumin -induced concentration related contractile response elicited in PE- precontracted ED+ MUA rings was 49.5%, 42.6%, and 40.4% in NP, and 79.5%, 55.5%, and 44.1% in P Ch. Aminoguanidine attenuated the Rmax of eugenol, curcumin and nanocurcumin to 28.2%, 28.5%, and 16.4% in MUA of NP, and 57.2%, 57.4%, and 38.0% in MUA of P Ch, respectively. The results demonstrated that vasorelaxation to (i) Eugenol is partly mediated by partial activation of aminoguanidine-sensitive iNOS in the uterine artery and this pathway is augmented in pregnancy, (ii) Nanocurcumin is mediated by activation of aminoguanidine-sensitive iNOS in the uterine artery of NP, but not in P Ch and (iii) Curcumin is mediated by minimal activation of aminoguanidine sensitive iNOS only in the uterine artery of NP, but not in P Ch. In conclusion, eugenol and nanocurcumin possess a greater potential than curcumin in the control of hypertension due to partial activation of iNOS. These nutraceuticals could be useful to improve blood flow to the uterus to maintain oestrus cycle, maternal and fetal health.
Floral Scents in Pachira aquatica (Malvaceae): A Species with Diverse Floral Visitors in a Mexican Lowland Forests
Authors: Pale-Ezquivel Iván , Aguirre-Jaimes Armando , Hernández Javier , Coates Rosamond , Domínguez Zaira
Published: March 2019

The chemical composition of the floral scent released by Pachira aquatica was analyzed in situ using standard dynamic headspace and Gas Chromatography-Mass Spectroscopy. A total of 34 compounds were found in the scent, 31 of which were identified and classified as terpenoids, benzenoids, fatty acid derivatives or nitrogen containing compounds. The predominant compounds emitted are trans-β-ocimene (51.74 %), ( Z)-3-hexenyl acetate (7.96 %), one of the unknown compounds (7.44 %), pentyl butanoate (7.02 %), trans-caryophyllene (4.49 %), methyl salicylate (3.49 %) and methyl benzoate (2.26 %).
Two New Oleanane-type Saponins from Hydrocotyle multifida
Authors: Carrillo Mayra Rengifo , Mitaine-Offer Anne-Claire , Paululat Thomas , Pouységu Laurent , Quideau Stéphane , Rojas Luis , Porcar Carmelo Rosquete , Lacaille-Dubois Marie-Aleth
Published: March 2019

A phytochemical study of a Venezuelan species Hydrocotyle multifida led to the isolation of five oleanane-type glycosides: two previously undescribed and three known ones. Their structures were established by 2D NMR spectroscopic techniques and mass spectrometry as 3- O-β-D-galactopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucuronopyranosyloleanolic acid and 3- O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyrano-syloleanolic acid. These results represent a significative contribution to the chemotaxonomy of the Hydrocotyle genus.
Application of Racemization Process to Dynamic Resolution of (RS)-Phenylephrine to (R)-Phenylephrine β-D-Glucoside by Nicotiana tabacum Glucosyltransferase
Authors: Fujitaka Yuya , Uesugi Daisuke , Hamada Hatsuyuki , Hamada Hiroki , Shimoda Kei , Yanagi Masayoshi , Inoue Manami , Ozaki Shin-ichi
Published: March 2019

Enzymatic glucosylation of racemic phenylephrine by glucosyltransferase from Nicotiana tabacum gave ( R)-phenylephrine glucoside and recovered ( S)-phenylephrine. [RuCl2( p-cymene)]2 complex associated with simple hemisalen ligands or zeolite were able to racemize ( S)-phenylephrine. The [RuCl2( p-cymene)]2/Ligand/TEMPO or zeolite racemization was associated with the enantioselective glycosylation of racemic phenylephrine with glucosyltransferase. The ( R)-stereoselective glucosylation of ( RS)-phenylephrine occurred to produce a high yield of ( R)-phenylephrine glucoside in high yield.
Polyphenol Compounds Melanin Prevented Hepatic Inflammation in Rats with Experimental Obesity
Authors: Belemets Natalia , Kobyliak Nazarii , Falalyeyeva Tetyana , Kuryk Olena , Sulaieva Oksana , Vovk Tetyana , Beregova Tetyana , Ostapchenko Liudmila
Published: March 2019

Melanin produced by yeast Nadsoniella nigra strain X-1 lead to significant reduction of steatosis, lobular inflammation and ballooning degeneration, according to NAFLD activity score (NAS), in liver of rats with monosodium glutamate (MSG) induced obesity. These histological changes were associated with substantial decrease of TNF-α expression in sinusoid cells that prevented NF-kB activation in hepatocytes.
Phenolic Constituents from Xyloselinum leonidii
Authors: Hanh Nguyen Phuong , Khang Nguyen Sinh , Ha Chu Thi Thu , Binh Nguyen Quoc , Dat Nguyen Tien
Published: March 2019

One new and seven known phenolic compounds were isolated from the twigs of Xyloselinum leonidii, and identified by means of spectroscopic methods. They were identified to be a new hydroxyaetophenone, xyloselin (1) together with four coumarins decursinol (2), decursinol glucoside (3), pteryxin (4), and praeroside I (5), two chromones angelicain (6), and cimifugin (7), and a flavonoid hesperidin (8). Among the isolated compounds, pteryxin showed the strongest inhibitory effect on the nitric oxide production (IC50 = 17.4 μM) while xyloselin showed weak inhibition. The present paper is the first report on the phenolic contents and the anti-inflammatory activity of the genus Xyloselinum.
A New Noriridoid and Six Phenolic Compounds from Rhopalocnemis phalloides
Authors: Hung Nguyen Quang , Luyen Nguyen Thi , Cuong Nguyen The , Thai Tran Huy , Tung Nguyen Thanh , Dat Nguyen Tien
Published: March 2019

A rare noriridoid and six known phenolic compounds were isolated from the parasite plant Rhopalocnemis phalloides. Using spectroscopic methods, these compounds were identified as 10-acetoxy- cis-2-oxabicyclo[4.3.0]nonan-7-en-3-one (1), p-hydroxybenzoic acid (2), protocatechuic acid (3), gallic acid (4), coniferyl aldehyde (5), l- O-trans-cinnamoyl-β-D-glucoside (6), and coniferin (7). The noriridoid compound is the first reported from the family Balanophoraceae. Of the isolated compounds, coniferyl aldehyde had the strongest inhibitory effect on nitric oxide production (IC50 = 8.24 μM).
Characterization and Biological Properties of Zederone and Zedoarondiol from Rhizomes of En-Lueang (Curcuma cf. amada)
Authors: Anuchapreeda Songyot , Khumpirapang Nattakanwadee , Chiampanichayakul Sawitree , Nirachonkul Wariya , Saiai Aroonchai , Usuki Toyonobu , Okonogi Siriporn
Published: March 2019

Curcuma cf. amada Roxb., also known as En-Lueang in Thailand, belongs to the Zingiberaceae family and grows from rhizomes. These rhizomes have been used in the Thai and Ayurveda systems of medicine. However, to our knowledge, no biologically active compounds isolated from En-Lueang have been reported. In this study, natural compounds were isolated from En-Lueang and their structures were determined by spectroscopic methods. The two isolated compounds were identified as zederone (1) and zedoarondiol (2) and their cytotoxicities against KG1a cells were investigated. The EtOH extract and EtOAc fraction showed stronger cytotoxic activity than n-hexane fraction against KG1a cells. In contrast, compound 1 showed strong cytotoxicity against KG1a cells, but low cytotoxicity toward normal peripheral blood mononuclear cells (PBMCs). Moreover, all the extracts and 1 had no effect on red blood cell hemolysis. The antioxidant properties of 1 were almost 2-fold higher than that of 2, in accordance with its total phenolic content of 8.8 mg/g, which is 2-fold higher than that of 2 (4.1 mg/g). In summary, two sesquiterpene compounds with leukemic cytotoxicity activity against the KG1a cell line were identified in En-Lueang extracts.
A New Pentacyclic Ergosteroid from Fungus Aspergillus sp. SCSIO41211 Derived of Mangrove Sediment Sample
Authors: Tao Huaming , Li Yunqiu , Lin Xiuping , Zhou Xuefeng , Dong Junde , Liu Yonghong , Yang Bin
Published: March 2019

Chemical investigation of the fungus Aspergillus sp. SCSIO41211 derived of mangrove sediment sample afforded a ergostane-type pentacyclic steroid, (22 S, 23 R)-12α,14α,23α-trihydroxy-16,22-epoxy-ergosta-4,8-dien-3,11-dione (1), together with seven known compounds, flavacol (2), aspergilliamide (3), ochratoxin A methyl ester (4), ochratoxin A ethyl ester (5), dihydroaspyrone (6), aspilactonol E (7) and aspilactonol F (8). The structures were determined on the basis of NMR and MS analysis. The isolated compounds were tested for their antiviral activity against H3N2 and EV71 viruses, cytotoxic, and antituberculosis effects. Among them, compounds 2 and 5 showed significant cytotoxicity against ten human cancer cell lines. None of the compounds displayed a significant antiviral activity against H3N2 and EV71 viruses nor antimycobacterial activities.
A Comparison of the Bioactivity of Usnic Acid versus Methylphloroacetophenone
Authors: Sarkar Ratul , Mittal Navriti , Sorensen John , Sen Tuhinadri
Published: March 2019

The identification of natural products that disrupt biofilm formation has become an area of recently expanded interest in combating antibiotic resistance. The formation of biofilms has been correlated with increased pathogenesis in many strains of Gram-negative bacteria. Molecules that disrupt the formation of biofilms therefore represent a potentially novel way to combat pathogenesis. Lichen natural products are an underexplored source of biofilm disrupting natural products. We have investigated the biofilm disrupting activity of the lichen natural product usnic acid (UA) in comparison to the biosynthetic precursor methylphloroacetophenone (MPA). We have observed in our assays that UA is more bioactive than MPA, suggesting a rationale for the biosynthesis of UA in a wide variety of lichen species. These results suggest that lichen natural products may prove to be a rich source of biofilm inhibitors.
Synthesis of New Simplified and Racemic Hemiasterlin Derivatives with Extremely High Cytotoxicity
Authors: Chinh Pham The , Anh Đang Thi Tuyet , Quynh Duong Huong , Giang Le Nhat Thuy , Thanh Nguyen Ha , Thanh Hoang Thi , Tam Khieu Thi , Tham Pham Thi , Anh Le Thị Tu , Phuong Hoang Thi , Van Tuyen Nguyen , Van Kiem Phan
Published: March 2019

Hemiasterlin is a potent antimitotic agent acting through inhibition of microtubule depolymerization. For this reason, the synthesis of new hemiasterlin derivatives has attracted a lot of interest in the organic chemistry community recently. In this paper, the synthesis and evaluation of the cytotoxicity of new simplified and racemic hemiasterlin derivatives were reported. All of the synthesized analogues were evaluated in vitro for cytotoxic activity against four human cell lines (KB, Hep-G2, LU and MCF7). Most of these analogues possess a strong cytotoxic activity on two human cancer cell lines (KB and Hep-G2) and very weak activity on LU and MCF7 cell lines.
Investigation of Origanum libanoticum Essential Oils Chemical Polymorphism by Independent Components Analysis (ICA)
Authors: Zgheib Raviella , Chaillou Sylvain , Ouaini Naim , Rutledge Douglas N. , Stien Didier , Kassouf Amine , Beyrouthy Marc El
Published: March 2019

The essential oils obtained from Origanum libanoticum Boiss., a plant endemic to Lebanon, were analyzed by GC/MS. Seventy compounds were identified, covering till 99.8% of the total oil composition. All samples were p-cymene and/or β-caryophyllene chemotype, with variable percentage of other compounds such as α-pinene, myrcene, α-phellandrene, limonene, etc. Compared to traditional drying method, lyophilized samples provided the highest essential oil (EO) yields and yields were higher at flowering stage (Chouwen: 0.33% in 2013 and 0.32% in 2014; Qartaba: 0.27% in 2013 and 0.37% in 2014). According to independent components analysis (ICA), date and site of harvest, altitude and drying technique had no effect on the variation of O. libanoticum EO chemical composition. An annual variation of EOs composition was observed since a particular variation in some major components concentration was revealed monthly and annually between 2013 and 2014.
Eremophilane-type Glycosides: A Mini-Review
Authors: Ponomarenko Ludmila P. , Stonik Valentin A.
Published: March 2019

The occurrence, special aspects of structural determination, biological activities, and potential taxonomic application of eremophilane-type glycosides, a rare group of metabolites from higher plants, are reviewed. This mini review covers the literature published for period 2006 to 2018.
Seasonal variation in the prevalence of profound hyponatremia (<125 mmol/l) in patients on admission to an acute hospital in Japan
Authors: Sasaki Nobukazu , Aoki Yuji
Published: March 2019

Hyponatremia is a common but important electrolyte disorder mostly complicated with other diseases. Recently, we experienced a case of a hypertensive patient in her seventies taking a thiazide diuretic, who presented with disorientation due to severe hyponatremia (serum sodium level, 104 mmol/l) on admission. Taking this opportunity, patients with profound hyponatremia (<125 mmol/l) on admission were investigated. Patients newly admitted to Matsumoto Medical Center (an acute hospital) were surveyed retrospectively for one year from May 1, 2016 to April 30, 2017. Patients with profound hyponatremia on admission were selected, and their clinical characteristics were evaluated. A total of 108 out of 4223 patients (2.6%; 67 men, 41 women) showed profound hyponatremia, and 101 out of 108 patients were 65 years old and over. The prevalence of profound hyponatremia in the warm season of April to October (3.1%, 76 in 2444 patients) was significantly ( p = 0.002, χ2 test) higher than that in the cold season of November to March (1.8%, 32 in 1779 patients). The monthly prevalence tended to correlate with the monthly average temperature of the local area ( r = 0.517, p = 0.085). There were six patients treated with thiazide diuretics in the warm season, while there were no such patients in the cold season, not reaching a significant difference ( p = 0.240). The present study demonstrated an increased risk of hyponatremia in elderly patients during the warm season. Considering also the relevant literature, health professionals should pay enough attention to thiazide- or drug-induced hyponatremia and the impact of water/salt intake for heat exposure.
Rescue treatment in patients with poorly responsive Guillain–Barre syndrome
Authors: Alboudi Ayman Mahmoud , Sarathchandran Pournamy , Geblawi Samar Sameer , Kayed Deeb Maxwell , Inshasi Jihad , Purayil Sadhik Puthan , Almadani Abu Baker , Katirji Bashar
Published: March 2019

Objectives:

To evaluate the effectiveness of rescue treatment (intravenous immunoglobulin or plasma exchange) in patients with Guillain–Barre syndrome who did not respond or deteriorated after the initial management with intravenous immunoglobulin.

Methods:

We performed a retrospective review of the medical records of patients who responded poorly or did not respond to intravenous immunoglobulin treatment. The disability parameters of those who received second-line treatment with intravenous immunoglobulin or plasma exchange (20 patients) were compared with those who did not receive second-line treatment (19 patients).

Results:

There was a statistically significant improvement in disability scores at 1 month in the patients who received the rescue treatment (p = 0.033). However, there was no significant difference in the disability scores at 3 and 6 months, or in length of intensive care unit stay.

Conclusion:

Our study showed that a second course of treatment to carefully selected patients may be beneficial
Predictive risk factors towards liver fluke infection among the people in Kamalasai District, Kalasin Province, Thailand
Authors: Wichaiyo Woragon , Parnsila Wirat , Chaveepojnkamjorn Wisit , Sripa Banchob
Published: March 2019

Background:

Liver fluke disease caused by Opisthorchis viverrini remains a major public health problem with its crucial risk factors caused by some individual habits or false beliefs among the people in northeastern Thailand concerning the consumption of raw fish meat dishes.

Objectives:

This study explores the predictive risk factors for the infection of liver fluke disease.

Methods:

The sample consisted of 400 people aged 30 years and above in Thanya sub-district, Kamalasai district, Kalasin province. A cross-sectional analytic study, using the χ2 test, odds ratio and 95% confidence interval, was used to find the influence of each variable, along with the use of multiple logistic regression (p = 0.05). A questionnaire form was used as the research instrument.

Results:

Factors found in the results are as follows: households with a cat were 7.00 times more at risk than households without a cat; eating raw fish dishes prepared by themselves increases the risk of infection by 2.58 times; eating raw fish dishes prepared by family members increases the risk by 4.74 times; and raw fish dishes bought from a community market increases the risk by 2.33 times.

Conclusion:

A campaign should be launched to educate people not to eat raw or undercooked fish dishes, but to fully cook fish dishes before eating, as the food is still delicious, but also safe, healthy, and free from liver fluke infection.
Impact of first‐line infliximab on the pharmacokinetics of second‐line vedolizumab in inflammatory bowel diseases
Authors: Liefferinckx Claire , Verstockt Bram , Gils Ann , Tops Sophie , Van Moerkercke Wouter , Vermeire Severine , Franchimont Denis
Published: March 2019

Background

Very little is known about the impact of the wash‐out period on the pharmacokinetics of a second‐line biologic.

Objective

The objective of this article is to explore the impact of two different wash‐out periods on the pharmacokinetics of vedolizumab and infliximab.

Methods

Patients switching from infliximab to vedolizumab were retrospectively identified. The population was divided into two groups according to wash‐out period: <6 weeks or >6 weeks. Vedolizumab and infliximab trough levels (TLs) were determined and correlated with clinical and biological outcomes.

Results

A total of 71 inflammatory bowel disease patients were included. At week 6, in patients previously treated with infliximab, median vedolizumab TLs were 21.9 µg/ml and 24.9 µg/ml for the <6 weeks and >6 weeks wash‐out period, respectively (p = 0.31), whereas median residual infliximab TLs were 0.5 µg/ml and 0 µg/ml (p = 0.034). The rate of treatment discontinuation was similar (p = 0.64), and the infectious events were six and two for the <6 weeks and >6 weeks wash‐out period, respectively (p = 0.12) by week 30.

Conclusions

This study suggests clinicians may not need to be concerned about the impact of wash‐out period on the pharmacokinetics of the second‐line biologic when switching infliximab to vedolizumab. More data are required on the impact of wash‐out period on safety.
Enforcing public data archiving policies in academic publishing: A study of ecology journals
Authors: Sholler Dan , Ram Karthik , Boettiger Carl , Katz Daniel S
Published: March 2019

To improve the quality and efficiency of research, groups within the scientific community seek to exploit the value of data sharing. Funders, institutions, and specialist organizations are developing and implementing strategies to encourage or mandate data sharing within and across disciplines, with varying degrees of success. Academic journals in ecology and evolution have adopted several types of public data archiving policies requiring authors to make data underlying scholarly manuscripts freely available. The effort to increase data sharing in the sciences is one part of a broader “data revolution” that has prompted discussion about a paradigm shift in scientific research. Yet anecdotes from the community and studies evaluating data availability suggest that these policies have not obtained the desired effects, both in terms of quantity and quality of available datasets. We conducted a qualitative, interview-based study with journal editorial staff and other stakeholders in the academic publishing process to examine how journals enforce data archiving policies. We specifically sought to establish who editors and other stakeholders perceive as responsible for ensuring data completeness and quality in the peer review process. Our analysis revealed little consensus with regard to how data archiving policies should be enforced and who should hold authors accountable for dataset submissions. Themes in interviewee responses included hopefulness that reviewers would take the initiative to review datasets and trust in authors to ensure the completeness and quality of their datasets. We highlight problematic aspects of these thematic responses and offer potential starting points for improvement of the public data archiving process.
Prolonged QTc in HIV-Infected Patients: A Need for Routine ECG Screening
Authors: Myerson Merle , Kaplan-Lewis Emma , Poltavskiy Eduard , Ferris David , Bang Heejung
Published: March 2019

Background:

With HIV-infected patients living longer, there is an increased burden of comorbidities related to aging, HIV itself, and polypharmacy. Cardiac morbidity is of particular importance.

Methods:

This 2-group comparison study (156 HIV-positive and 105 HIV-negative patients) investigated the prevalence of abnormalities in and factors associated with an electrocardiogram (ECG) measure, corrected QT interval (QTc), where prolongation can lead to arrhythmia and sudden death. Medications prescribed (antiretroviral therapy, psychiatric medications, methadone, and antibiotics) at the time of ECG were noted. Patient characteristics, medications, QTc, and ECG characteristics were compared between the 2 groups.

Results:

Prolongation (29% versus 19%) and extreme prolongation (6% versus 1%) in QTc were more frequent in those with HIV. Antiretroviral therapy was associated with lower odds of prolonged QTc (odds ratio [OR] = 0.35; P = .04), while methadone with higher odds (OR = 4.6; P = .01) in HIV-positive patients. With methadone and medication groups adjusted, HIV status was still associated with 17-millisecond longer QTc ( P = .04).

Conclusion:

This study provides evidence that patients with HIV may have clinically relevant longer QTc interval on ECG. Baseline and routine ECG monitoring may be warranted among patients living with HIV in clinical practice based on cumulative evidence.
Defining Learning Communities in Undergraduate Medical Education: A National Study
Authors: Shochet Robert , Fleming Amy , Wagner James , Colbert-Getz Jorie , Bhutiani Monica , Moynahan Kevin , Keeley Meg
Published: March 2019

Background:

Learning communities (LCs) are intentionally designed groups that are actively engaged in learning with and from each other. While gaining prominence in US medical schools, LCs show significant variability in their characteristics across institutions, creating uncertainty about how best to measure their effects.

Objective:

The aim of this study is to describe the characteristics of medical school LCs by primary purpose, structures, and processes and lay the groundwork for future outcome studies and benchmarking for best practices.

Methods:

Medical school LC directors from programs affiliated with the Learning Communities Institute (LCI) were sent an online survey of program demographics and activities, and asked to upload a program description or summary of the LC’s purpose, goals, and how it functions. Descriptive statistics were computed for survey responses and a qualitative content analysis was performed on program descriptions by 3 authors to identify and categorize emergent themes.

Results:

Of 28 medical school LCs surveyed, 96% (27) responded, and 25 (89%) provided program descriptions for qualitative content analysis. All programs reported longitudinal relationships between students and faculty. Most frequently cited objectives were advising or mentoring (100%), professional development (96%), courses (96%), social activities (85%), and wellness (82%). Primary purpose themes were supporting students’ professional development, fostering a sense of community, and creating a sense of wholeness. Structures included a community framework, subdivisions into smaller units, and governance by faculty and students. Process themes included longitudinal relationships, integrating faculty roles, and connecting students across class years.

Conclusions:

Medical school LCs represent a collection of high-impact educational practices characterized by community and small-group structures, relational continuity, and collaborative learning as a means to guide and holistically support students in their learning and development as physicians. In describing 27 medical school LCs, this study proposes a unifying framework to facilitate future educational outcomes studies across institutions.
A Practical Guide to Variable Selection in Structural Equation Modeling by Using Regularized Multiple-Indicators, Multiple-Causes Models
Authors: Jacobucci Ross , Brandmaier Andreas M. , Kievit Rogier A.
Published: March 2019

Methodological innovations have allowed researchers to consider increasingly sophisticated statistical models that are better in line with the complexities of real-world behavioral data. However, despite these powerful new analytic approaches, sample sizes may not always be sufficiently large to deal with the increase in model complexity. This difficult modeling scenario entails large models with a limited number of observations given the number of parameters. Here, we describe a particular strategy to overcome this challenge: regularization, a method of penalizing model complexity during estimation. Regularization has proven to be a viable option for estimating parameters in this small-sample, many-predictors setting, but so far it has been used mostly in linear regression models. We show how to integrate regularization within structural equation models, a popular analytic approach in psychology. We first describe the rationale behind regularization in regression contexts and how it can be extended to regularized structural equation modeling. We then evaluate our approach using a simulation study, showing that regularized structural equation modeling outperforms traditional structural equation modeling in situations with a large number of predictors and a small sample size. Next, we illustrate the power of this approach in two empirical examples: modeling the neural determinants of visual short-term memory and identifying demographic correlates of stress, anxiety, and depression.
Quality Improvement Initiative to Improve Tobacco Cessation Efforts in Radiation Oncology
Authors: Singer Lisa , Sharee Keith , Boreta Lauren , Silveira William R. , Braunstein Steve , Fogh Shannon
Published: March 2019

PURPOSE:

Although continued tobacco use in patients who are treated with radiation therapy is associated with inferior outcomes and increased treatment-related toxicity, multiple studies have shown that current tobacco cessation efforts in oncology are insufficient. A quality improvement (QI) initiative was developed with the goal of improving tobacco cessation efforts in radiation oncology.

METHODS:

Using iterative plan-do-study-act cycles, barriers to tobacco cessation were identified and then addressed with a single-institutional QI initiative designed to improve physician assessment of patient readiness to quit tobacco by 50% or more. Residents assessed readiness to quit tobacco during new patient consultations and recorded this assessment in prespecified fields within the electronic health record. Feedback on assessment efforts was provided to our department via an automated search of the electronic health record.

RESULTS:

From December 2014 to February 2015, before the initiation of the QI initiative, 4% of patients were assessed for their readiness to quit tobacco. After implementing the initiative, 67% of patients were assessed for their readiness to quit.

CONCLUSION:

After instituting a QI initiative at our institution, significantly more patients were assessed for readiness to quit tobacco before treatment with radiation therapy. Ongoing efforts in our department are aimed at improving the efficacy of this intervention.
Models of Outpatient Palliative Care Clinics for Patients With Cancer
Authors: Finlay Esme , Newport Kristina , Sivendran Shanthi , Kilpatrick Laurel , Owens Michelle , Buss Mary K.
Published: March 2019

PURPOSE:

Early integration of outpatient palliative care (OPC) benefits patients with advanced cancer and also the health care systems in which these patients are seen. Successful development and implementation of models of OPC require attention to the needs and values of both the patients being served and the institution providing service.

In the 2016 clinical guideline, ASCO recommended integrating palliative care early in the disease trajectory alongside cancer-directed treatment. Despite strong endorsement and robust evidence of benefit, many patients with cancer lack access to OPC. Here we define different models of care delivery in four successful palliative care clinics in four distinct health care settings: an academic medical center, a safety net hospital, a community health system, and a hospice-staffed clinic embedded in a community cancer center. The description of each clinic includes details on setting, staffing, volume, policies, and processes.

CONCLUSION:

The development of robust and capable OPC clinics is necessary to meet the growing demand for these services among patients with advanced cancer. This summary of key aspects of functional OPC clinics will enable health care institutions to evaluate their specific needs and develop programs that will be successful within the environment of an individual institution.
Ability of an Arterial Waveform Analysis–Derived Hypotension Prediction Index to Predict Future Hypotensive Events in Surgical Patients
Authors: Davies Simon James , Vistisen Simon Tilma , Jian Zhongping , Hatib Feras , Scheeren Thomas W. L.
Published: March 2019

BACKGROUND:

Intraoperative hypotension is associated with worse perioperative outcomes for patients undergoing major noncardiac surgery. The Hypotension Prediction Index is a unitless number that is derived from an arterial pressure waveform trace, and as the number increases, the risk of hypotension occurring in the near future increases. We investigated the diagnostic ability of the Hypotension Prediction Index in predicting impending intraoperative hypotension in comparison to other commonly collected perioperative hemodynamic variables.

METHODS:

This is a 2-center retrospective analysis of patients undergoing major surgery. Data were downloaded and analyzed from the Edwards Lifesciences EV1000 platform. Receiver operating characteristic curves were constructed for the Hypotension Prediction Index and other hemodynamic variables as well as event rates and time to event.

RESULTS:

Two hundred fifty-five patients undergoing major surgery were included in the analysis yielding 292,025 data points. The Hypotension Prediction Index predicted hypotension with a sensitivity and specificity of 85.8% (95% CI, 85.8%–85.9%) and 85.8% (95% CI, 85.8%–85.9%) 5 minutes before a hypotensive event (area under the curve, 0.926 [95% CI, 0.925–0.926]); 81.7% (95% CI, 81.6%–81.8%) and 81.7% (95% CI, 81.6%–81.8%) 10 minutes before a hypotensive event (area under the curve, 0.895 [95% CI, 0.894–0.895]); and 80.6% (95% CI, 80.5%–80.7%) and 80.6% (95% CI, 80.5%–80.7%) 15 minutes before a hypotensive event (area under the curve, 0.879 [95% CI, 0.879–0.880]). The Hypotension Prediction Index performed superior to all other measured hemodynamic variables including mean arterial pressure and change in mean arterial pressure over a 3-minute window.

CONCLUSIONS:

The Hypotension Prediction Index provides an accurate real time and continuous prediction of impending intraoperative hypotension before its occurrence and has superior predictive ability than the commonly measured perioperative hemodynamic variables.
fs(1)h controls metabolic and immune function and enhances survival via AKT and FOXO in Drosophila
Authors: Sharrock Jessica , Estacio-Gomez Alicia , Jacobson Jake , Kierdorf Katrin , Southall Tony D. , Dionne Marc S.
Published: March 2019

The Drosophila fat body is the primary organ of energy storage as well as being responsible for the humoral response to infection. Its physiological function is of critical importance to the survival of the organism; however, many molecular regulators of its function remain ill-defined. Here, we show that the Drosophila melanogaster bromodomain-containing protein FS(1)H is required in the fat body for normal lifespan as well as metabolic and immune homeostasis. Flies lacking fat body fs(1)h exhibit short lifespan, increased expression of immune target genes, an inability to metabolize triglyceride, and low basal AKT activity, mostly resulting from systemic defects in insulin signalling. Removal of a single copy of the AKT-responsive transcription factor foxo normalises lifespan, metabolic function, uninduced immune gene expression and AKT activity. We suggest that the promotion of systemic insulin signalling activity is a key in vivo function of fat body fs(1)h.

This article has an associated First Person interview with the first author of the paper.
New quantitative approach reveals heterogeneity in mitochondrial structure–function relations in tumor-initiating cells
Authors: Spurlock Brian , Gupta Priyanka , Basu Malay Kumar , Mukherjee Avik , Hjelmeland Anita B. , Darley-Usmar Victor , Parker Danitra , Foxall McKenzie E. , Mitra Kasturi
Published: March 2019

Steady-state mitochondrial structure or morphology is primarily maintained by a balance of opposing fission and fusion events between individual mitochondria, which is collectively referred to as mitochondrial dynamics. The details of the bidirectional relationship between the status of mitochondrial dynamics (structure) and energetics (function) require methods to integrate these mitochondrial aspects. To study the quantitative relationship between the status of mitochondrial dynamics (fission, fusion, matrix continuity and diameter) and energetics (ATP and redox), we have developed an analytical approach called mito-SinCe2. After validating and providing proof of principle, we applied mito-SinCe2 on ovarian tumor-initiating cells (ovTICs). Mito-SinCe2 analyses led to the hypothesis that mitochondria-dependent ovTICs interconvert between three states, that have distinct relationships between mitochondrial energetics and dynamics. Interestingly, fusion and ATP increase linearly with each other only once a certain level of fusion is attained. Moreover, mitochondrial dynamics status changes linearly with ATP or with redox, but not simultaneously with both. Furthermore, mito-SinCe2 analyses can potentially predict new quantitative features of the opposing fission versus fusion relationship and classify cells into functional classes based on their mito-SinCe2 states.

This article has an associated First Person interview with the first author of the paper.
Genetic and environmental effects on the scaling of metabolic rate with body size
Authors: Fossen Erlend I. F. , Pélabon Christophe , Einum Sigurd
Published: March 2019

Metabolic rate (MR) often scales with body mass (BM) following a power function of the form MR=aBMb, where b is the allometric exponent (i.e. slope on a log-log scale). The variational properties of b have been debated, but very few studies have tested for genetic variance in b, and none have tested for a genotype-by-environment (G×E) interaction in b. Consequently, the short-term evolutionary potentials of both b and its phenotypic plasticity remain unknown. Using 10 clones of a population of Daphnia magna, we estimated the genetic variance in b and assessed whether a G×E interaction affected b. We measured metabolic rate on juveniles of different sizes reared and measured at three temperatures (17, 22 and 28°C). Overall, b decreased with increasing temperature. We found no evidence of genetic variance in b at any temperature, and thus no G×E interaction in b. However, we found a significant G×E interaction in size-specific metabolic rate. Using simulations, we show how this G×E interaction can generate genetic variation in the ontogenetic allometric slope of animals experiencing directional changes in temperature during growth. This suggests that b can evolve despite having limited genetic variation at constant temperatures.
Are there synergistic or antagonistic effects of multiple maternally-derived egg components (antibodies and testosterone) on offspring phenotype?
Authors: Torres Roxana , Chin Eunice , Rampton Rowan , Williams Tony D
Published: March 2019

Eggs are ‘multivariate’ in that they contain multiple maternally-derived egg components (e.g. hormones, antibodies, mRNA, antioxidants) which are thought to influence offspring phenotype. However, most studies have focused on single egg components and on short-term effects. Here, we simultaneously manipulated two egg components, maternally-derived antibodies (MAb) and yolk testosterone (T) to assess potential synergistic or antagonistic effects on offspring phenotype from hatching to sexual maturity. We found no evidence for short-or long-term effects of either MAb or yolk T alone, or their interaction, on hatching mass, size at fledging (tarsus), body mass at sexual maturity (day 82), chick survival, humoral immune function, or any measured female reproductive trait at sexual maturity. There was a positive effect of yolk T, but not MAb, on offspring PHA response at 26 days of age but at 82 days of age MAb, but not yolk T, had a positive effect on PHA response. There was also a MAb*sex interaction on 30 day chick mass, and a positive effect of yolk T on male courtship behaviour at sexual maturity. However, we found no evidence for synergy, i.e. where offspring treated both with MAb and yolk T had higher trait values than offspring treated with either MAb or yolk T alone for any measured trait. Similarly, evidence for antagonistic (compensatory) effects, where offspring treated both with MAb and yolk T had intermediate trait values compared with offspring treated with either MAb or yolk T alone, was equivocal.
Distribution of Toxoplasma gondii IgM and IgG antibody seropositivity among age groups and gestational periods in pregnant women
Authors: Sadiqui Shahida , Shah Syed Rafiq Hussain , Almugadam Babiker Saad , Shakeela Qismat , Ahmad Shehzad
Published: March 2019

Background: Toxoplasmosis is a globally distributed parasitic disease. The present study aimed to estimate the prevalence and geographic distribution of toxoplasmosis as well as evaluate the role of animal contact in disease development and determine the percentage of toxoplasmosis-associated IgM and IgG seropositivity among different age groups. In addition, it aimed to estimate the proportion of toxoplasma IgM seropositivity among pregnancy trimesters.

Methods: A total of 500 pregnant women were included in this study. From each participant, a 5-ml venous blood sample was collected and centrifuged to obtain serum that was tested for Toxoplasma gondii IgM and IgG antibodies using immunochromatographic testing and ELISA.

Results: The overall seroprevalence of toxoplasmosis was 24.8%, with rates of acute infection of 8%. Among positive cases of every trimester, 54.34% of first trimester positive cases had a serologic marker for acute toxoplasmosis. Among the overall positive cases, out of the 35 pregnant women with previous history of cow/buffalo contact and toxoplasmosis, 45.7% were seropositive for toxoplasma IgM; and out of 15 women with prior history of dog contact, 33.3% had a serological marker of acute toxoplasmosis.

Conclusions: In this study, there is a high prevalence of toxoplasmosis and contact with domestic animals is a risk factor of this illness. Therefore, it is necessary to test every pregnant woman for toxoplasmosis and distinguish the type of infection, as well as the conduction of public health education programs to generate the awareness.
Investigating the basis of sexual dysfunction during late-onset hypogonadism
Authors: Tharakan Tharu , Miah Saiful , Jayasena Channa , Minhas Suks
Published: March 2019

Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction.
Anti-infective efficacy of Psidium guajava L. leaves against certain pathogenic bacteria
Authors: Patel Pooja , Joshi Chinmayi , Birdi Tannaz , Kothari Vijay
Published: March 2019

Water extracts of Psidium guajava leaves prepared by three different extraction methods were compared with respect to their anti-infective activity against Pseudomonas aeruginosa and Staphylococcus aureus in the nematode host Caenorhabditis elegans. The water extract prepared by Microwave Assisted Extraction method was found to have better anti-infective activity, and its activity was further compared with hydroalcoholic extract prepared using the same extraction method against five different pathogenic bacteria. Both these extracts could attenuate virulence of P. aeruginosa, S. aureus, Serratia marcescens, and Chromobacterium violaceum, towards C. elegans. Anti-infective efficacy of P. guajava leaf extract seems partly to stem from its quorum-modulatory property, as it could modulate production of quorum sensing-regulated pigments in all the susceptible bacteria.
Lifting the fog in intermediate-risk (submassive) PE: full dose, low dose, or no thrombolysis?
Authors: Bhamani Amyn , Pepke-Zaba Joanna , Sheares Karen
Published: March 2019

Acute pulmonary embolism (PE) is a disease frequently encountered in clinical practice. While the management of haemodynamically stable, low risk patients with acute PE is well established, managing intermediate disease often presents a therapeutic dilemma. In this review, we discuss the various therapeutic options available in this patient group. This includes thrombolysis, surgical embolectomy and catheter directed techniques. We have also explored the role of specialist PE response teams in the management of such patients. ​
Case Report: Takayasu arteritis in a male patient
Authors: Uddin Syed Mohammad Mazhar , Haq Aatera , Haq Zara , Yaqoob Uzair , Mohiuddin Osama , Khan Anosh Aslam
Published: March 2019

Takayasu arteritis (TA) is a type of primary systemic vasculitis mainly affecting the medium and large arteries. The signs and symptoms are due to systemic inflammation or ischemia of an organ or limb and include angiodynia, claudication, peripheral pulselessness, murmurs, ischemic stroke, myocardial infarction and severe systemic arterial hypertension. The disease tends to affect more women than men. Here we present a case of TA in a 22-year-old male patient. Our patient presented with complaints of aphasia and right-sided weakness, with on-and-off symptoms of malaise, generalized weakness, unilateral headache, fatigue and shortness of breath lasting two years. Color Doppler ultrasound was sufficient for a diagnosis of TA, after which we started the patient on medical treatment and also consulted the department of vascular surgery. Overall, this case report highlights the importance of screening for TA in male patients so that the diagnosis is not overlooked, and also adds more data to the limited literature on male patients.