Experiences of Kurdish war-wounded refugees in communication with Swedish authorities through interpreter

Objective

To study experiences of war-wounded Kurdish refugees with respect to cross-cultural communication through interpreters.

Method

Semi-structured interviews were conducted with ten men, aged 31–42. Content analysis was used for analysis and interpretation of data.

Result

War-wounded Kurdish refugees experienced a number of difficulties regarding communication through interpreters, mainly related to the insufficient language link to the Swedish authorities, particularly health care personnel. In many instances, interpreters were selected based on the immigrant's citizenship rather than mother tongue, leading to a more complex, tri-lingual interpretation situation. Differences in cultural background, fear, suspicion and lack of confidence in interpreters were addressed as other problems by the participants.

Conclusion

Interpreter competence and patient confidence in the interpreter are essential for an adequate cross-cultural health communication. Assignment of interpreters should be based on knowledge of the patient's/client's mother tongue, rather than citizenship, and the outcome is improved by a common ethnic and cultural background of interpreter and patient/client. Our study should be considered as a pilot study, and the results should be validated in larger cohorts as well as in other ethnic and language groups.

Practice implications

In order to minimize communication misunderstandings, complicated tri-lingual interpretation situations should be avoided. Interpreters should ideally be assigned according to patient's/client's mother tongue rather than citizenship. Interpreters’ competence and patient's/client's confidence in interpreter may have significant impact on communication outcome.     

Flywheel resistance training calls for greater eccentric muscle activation than weight training

Changes in muscle activation and performance were studied in healthy men in response to 5 weeks of resistance training with or without “eccentric overload”. Subjects, assigned to either weight stack (grp WS; n = 8) or iso-inertial “eccentric overload” flywheel (grp FW; n = 9) knee extensor resistance training, completed 12 sessions of four sets of seven concentric–eccentric actions. Pre- and post-measurements comprised maximal voluntary contraction (MVC), rate of force development (RFD) and training mode-specific force. Root mean square electromyographic (EMG_RMS) activity of mm. vastus lateralis and medialis was assessed during MVC and used to normalize EMG_RMS for training mode-specific concentric (EMG_CON) and eccentric (EMG_ECC) actions at 90°, 120° and 150° knee joint angles. Grp FW showed greater (p < 0.05) overall normalized angle-specific EMG_ECC of vastii muscles compared with grp WS. Grp FW showed near maximal normalized EMG_CON both pre- and post-training. EMG_CON for Grp WS was near maximal only post-training. While RFD was unchanged following training (p > 0.05), MVC and training-specific strength increased (p < 0.05) in both groups. We believe the higher EMG_ECC activity noted with FW exercise compared to standard weight lifting could be attributed to its unique iso-inertial loading features. Hence, the resulting greater mechanical stress may explain the robust muscle hypertrophy reported earlier in response to flywheel resistance training.     

Vaccination of Rhesus Macaques with the Anthrax Vaccine Adsorbed Vaccine Produces a Serum Antibody Response That Effectively Neutralizes Receptor-Bound Protective Antigen In Vitro

Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (Macaca mulatta) that survived an aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines.Anthrax is caused by infection with Bacillus anthracis, and its pathogenesis is associated with an antiphagocytic poly-d-glutamic acid capsule and a binary anthrax toxin (ATx). The ATx comprises two protein exotoxins: lethal toxin (LTx) and edema toxin (ETx). The two toxins both have a binding protein called protective antigen (PA) but have separate effector proteins, edema factor (EF) and lethal factor (LF) (3, 20, 56). LTx is composed of PA and LF, and ETx is composed of PA and EF. In the initial stages of infection by B. anthracis, full-length 83-kDa PA (PA83) secreted by the bacterium binds to either one or both of at least two host cell ATx receptors (ATRs): tumor endothelial marker 8 (TEM8) (7, 27, 57) or capillary morphogenesis protein 2 (CMG2) (51).Vaccines containing PA as the major component confer protective efficacy in various animal models of multiple routes of infection (5, 14-16, 29, 42-44, 59). PA has four domains: an amino-terminal domain (domain 1, which is composed of subregions 1a and 1b) that contains two calcium ions and the S₁₆₃RKKRS₁₆₈ cleavage site for activating proteases, a heptamerization domain (domain 2) that contains a large flexible loop implicated in membrane insertion, a small domain (domain 3) hypothesized to aid in oligomerization, and a carboxy-terminal receptor-binding domain (domain 4) (26, 41). Upon binding to an ATR, PA is proteolytically cleaved by the cell surface protease furin to a 63-kDa polypeptide (PA63), releasing a 20-kDa amino-terminal fragment (domain 1a). Cleavage and release of domain 1a facilitate assembly of the PA prepore; a heptameric ring-shaped structure with a negatively charged lumen. Assembly of the prepore exposes a large hydrophobic surface for binding of LF and/or EF molecules to form ATx (9, 17, 19, 26, 33, 35, 37, 41). One PA63 heptamer is able to bind up to three LF and/or EF molecules. The ATx is then endocytosed by a lipid raft-mediated clathrin-dependent process (1, 34). The low-pH conditions (pH 5.5) in the endosome induce the prepore to undergo a conformational switch that translocates ATx to the target cell cytosol (6, 17, 18, 24, 32, 37, 41, 55).The current licensed vaccine for use in humans is anthrax vaccine adsorbed (AVA [BioThrax]; Emergent BioSolutions, Lansing, MI). AVA is a cell-free filtrate from a toxigenic, nonencapsulated B. anthracis strain, V770-NP1-R (2, 10, 45). The primary immunogen is PA (59) adsorbed to aluminum hydroxide adjuvant (10, 29). The current AVA vaccination schedule consists of five 0.5-ml intramuscular (i.m.) injections at 0 and 4 weeks and 6, 12, and 18 months, with annual boosters (10, 30).There are various potential molecular targets in which the host humoral antibody response to vaccination with AVA or PA can interfere with ATx-mediated cytotoxicity. These targets include, but are not limited to, (i) blocking of free PA83 binding to the host cell ATx receptor (TEM8 or CMG2); (ii) inhibition of PA83 proteolytic cleavage by the host cell surface furin-like enzyme or serum proteases, leaving the PA unprocessed and thus unable to form toxin complexes; (iii) interruption of PA63 heptamerization to form the prepore on the host cell surface; (iv) blocking the binding of LF and EF monomers to the PA heptamer prepore; and (v) disruption of internalization and translocation of the ATx. Consequently, PA has become a focal point in developing immunotherapies and next-generation vaccines for the prevention and treatment of anthrax (4, 13, 21, 22, 31, 36, 39, 40, 53, 58, 60).Most of the anti-PA therapies under development specifically target PA domains 2 and 4, with domain 4 being the most frequent target (21, 53, 60). The therapeutic effects of antibodies targeted against domain 4 are considered to be based primarily on blocking the interaction of PA with its host cell receptor (26, 49). However, in active immunization, there will be multiple epitopes presented to the host immune system that are critical to mounting a protective immune response and, likewise, others that may make little or no contribution. Although PA20 is cleaved from PA83 and has no described role in the intoxication process, recent reports have proposed that in AVA-vaccinated humans, the PA20 fragment (domain 1a) contains immunodominant epitopes (48, 61). Therefore, it was postulated that vaccines containing full-length PA (PA83) may be suboptimal due to the dominance of PA20 and that perhaps PA63-based vaccines may be more advantageous (47, 48).To address the question of suboptimal immune responses in PA83-based vaccine and therapeutic design, we developed two low-temperature anthrax lethal toxin (LTx) neutralization activity (TNA) assays, the noncomplexed TNA (NC-TNA) and receptor-bound TNA (RB-TNA) assays. These assays allow comparison of antibody-mediated neutralization of LTx both before and after receptor binding by PA. The goal of this work was to evaluate the ability of anti-PA antibody responses in AVA-vaccinated and inhalation anthrax-challenged rhesus macaques (Macaca mulatta) to neutralize anthrax LTx in vitro both before and after PA has bound to, and been processed at, the cell surface receptor.     

Decrease of pregnant women's pelvic pain after acupuncture: a randomized controlled single-blind study

BACKGROUND: The efficacy of acupuncture on low-back and/or pelvic pain in late pregnancy is reviewed in few reports. Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition. METHODS: In a prospective randomized controlled single-blind study, pregnant women with pelvic pain, median gestational age 26 weeks (range 18-35), were given 10 acupuncture treatments. Needles were inserted subcutaneously over acupuncture points without further stimulation (superficial, n=22), or intramuscular and stimulated repeatedly until a perceived sensation of numbness, de qi, (deep, n=25). Self-reported pain intensity at rest and during daily activities was assessed on a visual analog scale. The variables pain, emotional reactions, and loss of energy were assessed according to the Nottingham Health Profile questionnaire. Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes. RESULTS: After acupuncture stimulation, significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen. The results also showed additional individual changes in most variables. In this study, no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed. CONCLUSION: Acupuncture stimulation that is individually designed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy.     

Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy

BACKGROUND: The accuracy of maternal self-reported smoking information, especially exposure to environmental tobacco smoke, has been questioned. This study aimed to validate self-reported smoking, smoking cessation, and environmental tobacco smoke exposure in early and late pregnancy, using the biomarker cotinine as the gold standard. METHODS: Prospective cohort study of 953 pregnant Swedish women between 1996 and 1998. In-person interviews and cotinine measurements were performed at 6-12 and 31-34 completed weeks of gestation. All women were asked about nicotine exposures throughout pregnancy, including cigarette smoking, oral snuff, nicotine replacement therapy, and environmental tobacco smoke exposure. RESULTS: The validity of self-reported daily smoking was high in early and late pregnancy. However, among women reporting smoking cessation before the first interview and between the first and second interviews, 13% and 25% misreported active smoking, respectively. According to cotinine measurements, 22% of non-smoking women were exposed to environmental tobacco smoke in early pregnancy, and 8% were exposed in late pregnancy. Self-reported information on environmental tobacco smoke exposure in early and late pregnancy misclassified most exposed women as unexposed. CONCLUSION: The results of this study indicate that self-reported smoking information among pregnant women can be trusted. However, among women reporting smoking cessation during pregnancy, the misclassification rate increased with recency of quitting. Environmental tobacco smoke exposure was common among non-smokers, and the low validity of self-reported environmental tobacco smoke exposure suggests that future studies on environmental tobacco smoke exposure and risks of pregnancy outcomes may have to rely on biomarker assessments.     

The major subunit, CfaB, of colonization factor antigen i from enterotoxigenic Escherichia coli is a glycosphingolipid binding protein

Bacterial adherence to mucosal surfaces is an important virulence trait of pathogenic bacteria. Adhesion of enterotoxigenic Escherichia coli (ETEC) to the intestine is mediated by a number of antigenically distinct colonization factors (CFs). One of the most common CFs is CFA/I. This has a fimbrial structure composed of a major repeating subunit, CfaB, and a single tip subunit, CfaE. The potential carbohydrate recognition by CFA/I was investigated by binding CFA/I-fimbriated bacteria and purified CFA/I fimbriae to a large number of variant glycosphingolipids separated on thin-layer chromatograms. For both fimbriated bacteria and purified fimbriae, specific interactions could be identified with a number of nonacid glycosphingolipids. These included glucosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, neolactotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, the H5 type 2 pentaglycosylceramide, the Lea-5 glycosphingolipid, the Lex-5 glycosphingolipid, and the Ley-6 glycosphingolipid. These glycosphingolipids were also recognized by recombinant E. coli expressing CFA/I in the absence of tip protein CfaE, as well as by purified fimbriae from the same strain. This demonstrates that the glycosphingolipid-binding capacity of CFA/I resides in the major CfaB subunit.     

Muscle synergy organization is robust across a variety of postural perturbations

We recently showed that four muscle synergies can reproduce multiple muscle activation patterns in cats during postural responses to support surface translations. We now test the robustness of functional muscle synergies, which specify muscle groupings and the active force vectors produced during postural responses under several biomechanically distinct conditions. We aimed to determine whether such synergies represent a generalized control strategy for postural control or if they are merely specific to each postural task. Postural responses to multidirectional translations at different fore-hind paw distances and to multidirectional rotations at the preferred stance distance were analyzed. Five synergies were required to adequately reconstruct responses to translation at the preferred stance distance—four were similar to our previous analysis of translation, whereas the fifth accounted for the newly added background activity during quiet stance. These five control synergies could account for >80% total variability or r² > 0.6 of the electromyographic and force tuning curves for all other experimental conditions. Forces were successfully reconstructed but only when they were referenced to a coordinate system that rotated with the limb axis as stance distance changed. Finally, most of the functional muscle synergies were similar across all of the six cats in terms of muscle synergy number, synergy activation patterns, and synergy force vectors. The robustness of synergy organization across perturbation types, postures, and animals suggests that muscle synergies controlling task-variables are a general construct used by the CNS for balance control.     

Bioassay-guided fractionation of a thymol-deprived hydrophilic thyme extract and its antispasmodic effect

Ethnopharmacological relevance

Extracts from Thymus vulgaris L. and Thymus zygis L. are traditionally used for bronchitis, catarrhs of the respiratory tract and supportive treatment of pertussis. A potential spasmolytic effect is thought to be due to the presence of the monoterpenoid phenols thymol and carvacrol in the extract. Based on previous data the present investigation aimed to clarify if thymol-deprived thyme extracts (as been in use within German drug market) have antispasmodic activity. Additionally compounds responsible for this effect had to be identified.

Materials and methods

Thyme fluid extract was subsequently fractionated by FCPC, LPLC, and HPLC and compounds isolated were identified by spectroscopic methods. Bioassay testing was done by quantification of antispasmodic activity in the preconstricted rat smooth muscle trachea model against papaverin as positive control.

Results

Thymol-deprived spissum extract (SE) had good antispasmodic activity (−37%, related to the maximum contraction). Bioassay-guided fractionation indicated that rosmarinic acid and apigenin do not contribute to this effect. Luteolin contributed significantly to the antispasmodic activity (−9%).

Conclusions

Thyme extracts have antispasmodic activity, which is at least due to synergistic effects of phenolic volatile oil compounds and the flavone luteolin. Specifications of thyme-containing preparations should refer to this flavone in addition to focusing on the volatile phenols.     

A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression-free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression-free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.     

Population pharmacokinetics of cytarabine,etoposide, and daunorubicin in the treatment for acute myeloid leukemia

Purpose  

Interpatient variability in the pharmacokinetics (PK) of cytarabine, etoposide, and daunorubicin following body surface area–adjusted doses calls for studies that point to other covariates to explain this variability. The purpose of this study was to investigate such relationships and give insights into the PK of this combination treatment.