Midwifery students' perspectives of physical and virtual mobility activities including preferences for e-learning: A cross-sectional survey.

BACKGROUND: Contemporary higher education requires that all midwifery students have insight and understanding of global health practice and demonstrate intercultural sensitivity. However, the mobility models currently offered do not often fit the lives of large numbers of midwifery students. OBJECTIVES: To investigate midwifery students' international physical mobility activities and factors that affect mobility; to determine midwifery students' learning needs and preferences for related e-learning packages. DESIGN: Multi-centre, descriptive quantitative survey. SETTINGS: Four European Higher Education Institutions based in the United Kingdom, Estonia, Italy and the Netherlands offering an undergraduate midwifery programme. PARTICIPANTS: The sample included 205 midwifery students from Italy (n = 93), the Netherlands (n = 51); United Kingdom (n = 35) and Estonia (n = 26). METHODS: Data were collected in June-July 2020 through an online cross-sectional, bespoke questionnaire and analysed using summary statistical analysis. RESULTS: There is a high level of interest across a range of mobility opportunities, especially those of shorter duration. Barriers to mobility comprised finance, caring responsibilities, concerns about fitting mobility activities into the midwifery programme, negative impact on studies and language barriers. The most frequently identified facilitators of mobility included professional perspectives such as interest in other cultures and midwifery in other settings and an endorsement that mobility would add value to their development as a midwife. When engaging in virtual learning, the most preferred resources mentioned by the students were videos, video calls with peers, choice quiz and discussion forum. CONCLUSIONS: The barriers identified require new approaches to enable all midwifery students to benefit from transnational learning. The survey findings provide insights into midwifery students' perspectives from which a new mobility model can be developed.

Pharmacology and anti-addiction effects of the novel κ opioid receptor agonist Mesyl Sal B, a potent and long-acting analogue of salvinorin A.

BACKGROUND AND PURPOSE: Acute activation of κ opioid (KOP) receptors results in anticocaine-like effects, but adverse effects, such as dysphoria, aversion, sedation and depression, limit their clinical development. Salvinorin A, isolated from the plant Salvia divinorum, and its semi-synthetic analogues have been shown to have potent KOP receptor agonist activity and may induce a unique response with similar anticocaine addiction effects as the classic KOP receptor agonists, but with a different side effect profile. EXPERIMENTAL APPROACH: We evaluated the duration of effects of Mesyl Sal B in vivo utilizing antinociception assays and screened for cocaine-prime induced cocaine-seeking behaviour in self-administering rats to predict anti-addiction effects. Cellular transporter uptake assays and in vitro voltammetry were used to assess modulation of dopamine transporter (DAT) function and to investigate transporter trafficking and kinase signalling pathways modulated by KOP receptor agonists. KEY RESULTS: Mesyl Sal B had a longer duration of action than SalA, had anti-addiction properties and increased DAT function in vitro in a KOP receptor-dependent and Pertussis toxin-sensitive manner. These effects on DAT function required ERK1/2 activation. We identified differences between Mesyl Sal B and SalA, with Mesyl Sal B increasing the Vmax of dopamine uptake without altering cell-surface expression of DAT. CONCLUSIONS AND IMPLICATIONS: SalA analogues, such as Mesyl Sal B, have potential for development as anticocaine agents. Further tests are warranted to elucidate the mechanisms by which the novel salvinorin-based neoclerodane diterpene KOP receptor ligands produce both anti-addiction and adverse side effects. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Detecting cognitive fatigue in multiple sclerosis: method matters.

BACKGROUND: Fatigue is a frequently reported and debilitating symptom in multiple sclerosis (MS). Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The effectiveness of the Paced Auditory Serial Addition Task (PASAT) and the Computerized Test of Information Processing (CTIP) at detecting CF was examined, as was the impact of methodology. Subjective fatigue was measured using the Fatigue Impact Scale (FIS). The relationship between objective and subjective fatigue was examined. METHODS: 70 MS and 72 healthy controls (HC) completed the PASAT (3″ and 2″), CTIP, and FIS as part of a larger battery. RESULTS: The MS and HCs performed worse on cognitively demanding tasks. Depending on methodology, PASAT performance varied between groups at the 3″ inter-stimulus interval (ISI) and the MS group showed greater susceptibility to CF as their ability to meet task demands declined as the task progressed. CTIP performance for both groups varied differently over time depending on task. The relationship between subjective and objective measures of fatigue varied depending on methodology, with PASAT generally correlating well with the Cognitive Dimension of the FIS. CONCLUSIONS: The PASAT is a sensitive measure of CF in MS. Additional information is obtained with different scoring methods, with percent dyad scoring method being most sensitive to CF. The ability to detect a relationship between objective and subjective measures varied with methodology.

Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study.

BACKGROUND: Dietary supplement use is increasing, but there are few comparable data on supplement intakes and how they affect the nutrition and health of European consumers. The aim of this study was to describe the use of dietary supplements in subsamples of the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Specific questions on dietary supplement use were asked as a part of single 24-h recalls performed on 36,034 men and women aged 35-74 years from 1995 to 2000. RESULTS: Between countries, the mean percentage of dietary supplement use varied almost 10-fold among women and even more among men. There was a clear north-south gradient in use, with a higher consumption in northern countries. The lowest crude mean percentage of use was found in Greece (2.0% among men, 6.7% among women), and the highest was in Denmark (51.0% among men, 65.8% among women). Use was higher in women than in men. Vitamins, minerals or combinations of them were the predominant types of supplements reported, but there were striking differences between countries. CONCLUSIONS: This study indicates that there are wide variations in supplement use in Europe, which may affect individual and population nutrient intakes. The results underline the need to monitor consumption of dietary supplements in Europe, as well as to evaluate the risks and benefits.

Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF.

Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats.

Flax seed oil and flax seed meal are good sources of omega-3 fatty acids. The objective of this study was to explicate the effects of feeding flax seed oil and flax seed meal on AOM-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Following an acclimatization period, rats were divided into six groups and fed AIN 93G diet Control (C), C+7 and 14% soybean oil (SBO), C+7 and 14% flax seed oil (FSO) and C+10 and 20% flax seed meal (FSM). All rats received 16 mg/kg body weight of AOM at 7 and 8 weeks of age. The rats were euthanized with CO2 at 17 weeks of age. FSM and FSO reduced the incidence of ACF which are putative precursor lesions in the development of colon cancer in the distal colon by 88% and 77%, in the proximal colon by 86% and 87% with a total reduction of 87.5% and 84%, respectively. Glutathione-S-transferase (GST) activities were significantly (P<0.05) higher in rats fed C+7 and 14% FSO and C+10 and 20% FSM, as compared to rats fed C+SBO diets. Results of this study showed that FSO and FSM reduced the incidence of AOM-induced ACF formation and may therefore be effective chemopreventive agents.

Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Red palm oil (RPO) contains significant levels of carotenoids and Vitamin E. In this experiment we compared the inhibitory effects of RPO (7% and 14% levels) and soybean oil (7% and 14%) on azoxymethane (AOM) induced aberrant crypt foci (ACF). Thirty-two male Fisher 344 rats were randomly assigned to four groups. Two groups received AIN-93 G control (C) diet containing 7% and 14% soybean oil (SBO), respectively. Groups 3 and 4 received a treatment diet consisting of 7% and 14% RPO, respectively. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at 7 and 8 weeks of age. At 17 weeks of age rats were killed by CO(2) asphyxiation. Numbers of ACF (mean+/-SE) in the proximal and distal colon were: 39.9 +/- 0.9, 53.8 +/- 2.8, 26.0 +/- 3.0, 27.5 +/- 1.5 and 118.2 +/- 1.7, 125.6 +/- 3.2, 41 +/- 7, 52.3 +/- 1.8 in rats fed 7% SBO, 14% SBO, 7% RPO and 14% RPO, respectively. The results of this study showed that RPO reduced the incidence of AOM induced ACF and may therefore have a beneficial effect in reducing the incidence of colon cancer.

Biologically active quassinoids and their chemistry: potential leads for drug design.

Quassinoids are highly oxygenated triterpenes, which were isolated as bitter principles from the plants of Simaroubaceae family. Their synthesis has attracted much attention because of the wide spectrum of their biological properties. The most prevalent quassinoids have C-20 picrasane skeleton, some known as bruceolides as they were isolated from the genus Brucea, which showed marked antileukemic and antimalarial activities.

Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene.

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2.

Pharmacological activities of some Argyranthemum species growing in the Canary Islands.

Methanolic extracts of eight subspecies of genus Argyranthemum were evaluated against brine shrimps, human cancer cell lines, malarial parasites and microorganisms under in vitro conditions. In the shrimp assay, samples of A. adauctum ssp. adauctum, A. adauctum ssp. erythrocarpon and A. frutetescens ssp. succulentum were active with ED50 values in the range of around 300 to 360 microg/ml. In the Caco-2, HepG2 and MCF-7 cell lines, the samples A. adauctum ssp. jacobaeifolium and A. adauctum ssp. palmensis were active with LC50 values ranging between 80-90 microg/ml. The secondary assay results of antimalarial activity of samples, A. adauctum ssp. adauctum, A. adauctum ssp. dugourii, A. adauctum ssp. erythrocarpon and A. adauctum ssp. jacobaeifolium have IC50 values <50 microg/ml. The samples demonstrated broad specific antimicrobial activity against five different microorganisms.

Solution-phase parallel synthesis of an isoflavone library for the discovery of novel antigiardial agents.

Combinatorial chemistry has become a dramatically useful tool for the development of new medicinal agents. In the search to discover a novel and effective lead for the treatment of giardiasis, solution-phase synthesis of a library of isoflavone derivatives has been accomplished. Of the products screened, several compounds such as P(A1,B1) and P(A1,B11) exhibited potent antigiardial activity. The details of synthesis, in vitro antigiardial assay, and preliminary structure-activity relationships of these compounds are described.

UK: the current state of regulation of complementary and alternative medicine.

There is no legislation that restricts the practice of CAM in the UK apart from the practice of chiropractic and osteopathy and limits on advertising the treatments of certain conditions such as cancer and tuberculosis. The UK government has increasingly recognised the need for comprehensive regulation of CAM, though it abandoned its original plan for a single overarching regulatory body. Initiatives to examine and hasten the process of regulation have included setting up a central, well-recognised charitable body to facilitate progress for individual professions, and an authoritative survey of the existing professional organisations. One pathway open to individual professions is statutory self-regulation, which requires a single governing body, a systematic corpus of knowledge, recognised training courses and demonstrated efficacy. The other pathway is voluntary self-regulation. Chiropractic and osteopathy have adopted statutory self-regulation, though this has proved expensive for individual members of these professions. A recent House of Lords report on CAM has recommended that the herbal medicine and acupuncture professions should also develop a system of statutory regulation. Other professions, such as aromatherapy, are in the process of establishing single professional bodies as a first step towards self-regulation. Among the issues that remain to be resolved is the relationship between the CAM professions and statutory registered practitioners who also practise CAM.

Biologically active steroidal glycosides from Tribulus terrestris.

The steroidal saponin constituents obtained from Tribulus terrestris were tested for their antimicrobial and cytotoxic effects. The spirostanol-based steroidal saponins 1-3 exhibited remarkable activity against fungal organisms (Candida albicans and Cryptococcus neoformans) and cancer cell lines [human malignant melanoma (SK-MEL), human oral epidermoid carcinoma (KB), human breast ductal carcinoma (BT-549), and human ovary carcinoma (SK-OV-3)], while none of the compounds possessing the furostanol framework 4-7 showed activity. The most active spirostanol glycoside, compound 3 exhibited a broad range of anticancer activity against cell lines, SK-MEL, KB, BT-549 and SK-OV-3 at IC50s of 6.0, 7.0, 6.0 and 8.2 micrograms/ml, respectively, while compounds 1 and 2 showed selective cytotoxicity against SK-MEL at 6.7 and 9.1 micrograms/ml, respectively. The minimum inhibitory concentrations (MIC) in antifungal bioassay for compounds 1-3 varied from 1.5 to 6.2 micrograms/ml, which prompted to conclude certain structural features are required for these bioactivities.

Phenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia myriantha yielded two new compounds, mattucinol-7-O-[4' ',6' '-O-(S)-hexahydroxydiphenoyl]-beta-D-glucopyranoside (1) and mattucinol-7-O-[4' ',6' '-di-O-galloyl]-beta-D-glucopyranoside (2), along with mattucinol-7-O-beta-D-glucopyranoside (3), ellagic acid (4), 3,3'-di-O-methyl ellagic acid-4-O-beta-D-xylopyranoside, and gallic acid. Complete (1)H and (13)C NMR assignments of compound 1, which possesses a hexahydroxydiphenoyl unit, were achieved using the HMBC technique optimized for small couplings to enhance the four-bond and two-bond H/C correlations. Compounds 1 and 4 showed inhibitory effects against Candida albicans secreted aspartic proteases, with IC(50) of 8.4 and 10.5 microM, respectively.

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides.

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).

An improved method for the determination of betaine in Echinacea products.

A rapid and sensitive HPLC method for the separation and quantification of betaine in Echinacea products has been developed. Strong cation-exchange (SCX) material was used as stationary phase, and a mixture of methanol and 50 mM choline buffer (pH 3.5) as mobile phase. After formation of the bromophenacyl derivative, betaine was detected at 254 nm with a detection limit of 0.2 microgram/ml. The method was successfully used to analyze several Echinacea market products, and significant variations in their betaine content from 0.04 to 0.64% were observed.

New indole alkaloids from the bark of Nauclea orientalis.

Four new alkaloids, nauclealines A (1) and B (2) and naucleosides A (3) and B (4), together with six known compounds, strictosamide (5), vincosamide (6), pumiloside (7), kelampayoside A, sitosterol, and sitosteryl beta-D-glucoside, were isolated from the bark of Nauclea orientalis. The structures of 1-4 were elucidated using 1D and 2D NMR spectral methods, including COSY, DEPT, HMQC, (13)C-(1)H HMBC, and (15)N-(1)H HMBC.

Determination of heavy metals and pesticides in ginseng products.

Medicinal plants may carry residuals of environmentally persistent pesticides or assimilate heavy metals in varying degrees. Several factors may influence contaminant accumulation, including species, level and duration of contaminant exposure, and topography. As part of a program for assessment of the quality of herbal medicines, we have analyzed 21 over-the-counter ginseng (Panax ginseng) products in various dosage forms. Chromium, mercury, and arsenic were undetectable above their limits of detection in both liquid and solid samples; while cadmium, lead, and nickel were present in the majority of samples. The chlorinated pesticide levels varied widely. In most samples, the total concentration of pesticides was below 100 ppb; while in 5 samples the total concentration exceeded 100 ppb.

Antimalarial, cytotoxic, and antifungal alkaloids from Duguetia hadrantha.

Bioassay-guided isolation of Duguetia hadrantha yielded two new 4,5-dioxo-1-azaaporphinoids, hadranthine A (1) and hadranthine B (2), together with the known alkaloids imbiline-1 (3), sampangine (4), and 3-methoxysampangine (5), whose structures were determined primarily from 2D-NMR 1H-13C HMBC, and 1H-15N HMBC experiments. This is the first report of the co-occurrence of the copyrine alkaloids 4 and 5, as well as the first report of either copyrine or imbiline type alkaloids from a Duguetia species. Compounds 1, 4, and 5 demonstrated in vitro antimalarial activity against Plasmodium falciparum (W-2 clone), while 2 was inactive. Instead, 2 showed in vitro cytotoxicity to selected human cancer cell lines (IC50 = 3-6 microg/mL against SK-MEL, KB, BT-549, and SK-OV-3), and 4 was also cytotoxic to human malignant melanoma (IC50 = 0.37 microg/mL). Sampangine (4) also inhibited cell aggregation with a MIC value of <0.15 microg/mL, while 3-methoxysampangine (5) was only weakly active.

Dihydrochalcones from Piper longicaudatum.

Bioactivity-guided fractionation of an ethanolic extract of the leaves and twigs of Piper longicaudatum Trelease & Yunker (Piperaceae) resulted in the isolation of one new (1) and three known (2-4) dihydrochalcones. The known compounds are: 2',6'-dihydroxy-4'-methoxydihydrochalcone (2), 2',6',4-trihydroxy-4'-methoxydihydrochalcone (asebogenin) (3), and 2'-hydroxy-4'-methoxy-2'-[1-hydroxy-1-methylethyl]-2",3"-dihy- drofurano[4",5":5',6"]-3"-[2-hydroxy-5-methoxycarbonylphe- nyl]dihydrochalcone (piperaduncin B) (4). The new compound is 2'-hydroxy-4'-methoxy-2"-[2-hydroxy-5-methoxycarbonyl- phenyl]-furano[4",5":5',6']-dihydrochalcone (longicaudatin) (1). Compounds 1-4 were tested for antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA); only compound 3 showed inhibitory activity (IC50 of 10 and 4.5 micrograms/ml, respectively).