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Objectives: Migraine affects more than 80 million people in Western Europe. The present study evaluated disability and health‐related quality of life (HRQoL) among patients with episodic migraine (EM) and chronic migraine (CM) who had failed multiple preventive treatments. Materials and Methods: This study was an analysis of cross‐sectional, web‐based survey data from adult patients with migraine (EM and CM) from the United Kingdom, France, and Spain who had self‐reported failure of two or more preventive treatments. Patient characteristics and patient‐reported HRQoL, migraine‐related disability, healthcare resource use (HCRU), and burden of migraine were evaluated by classification (CM and EM) and country (EM only). Results: In this sample of 316 patients (United Kingdom, n = 106; Spain, n = 105; France, n = 105), 76 (24.1%) patients had CM, the mean (standard deviation [SD]) age was 39.5 (12.3) years, and 164 (51.9%) patients were female. Those patients with CM reported greater migraine‐related disability based on Migraine Disability Assessment (MIDAS) scores versus those with EM (mean [SD]: 43.8 [44.7] vs. 23.2 [28.3]), as well as greater pain‐related impact on daily activities and higher HCRU. Among patients with EM, MIDAS scores indicated disability was severe in Spain (mean [SD]: 31.6 [31.1]) and France (24.3 [31.1]) and moderate in the United Kingdom (13.8 [17.9]), while HRQoL was similar across countries. Regarding the burden of EM, higher levels of pain and symptom‐related interference with many aspects of life, including occupational functioning, were reported in the United Kingdom and Spain versus France. Conclusions: Migraine is associated with substantial disability and decreased HRQoL among patients who have failed previous preventive therapies. Although migraine burden varied by country, the results suggest high unmet needs in all countries. Appropriate treatment could reduce migraine‐related burden and HCRU among patients with difficult‐to‐treat migraine. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model. Methods: The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2–4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted. Results: Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses. Conclusion: In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population. [ABSTRACT FROM AUTHOR]

Introduction: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Methods: Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. Results: In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex. Conclusions: Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population (N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased by 3.60 days (95% confidence interval [CI]: −5.26, −1.94, p < 0.001) and PI was reduced by 0.43 (95% CI: −0.77, −0.09, p = 0.012) at the final visit. Statistically significant reductions were seen in both MHD (−4.61, 95% CI: −6.84, −2.39; p < 0.001) and PI (−0.52, 95% CI: −0.84. −0.09; p = 0.017) among patients naïve to mAbs against CGRP or its receptor. No unexpected adverse events were observed. Conclusion: Concomitant fremanezumab and onabotA for CM prevention were effective at reducing the number of MHD and lessening PI, particularly in patients with difficult-to-treat CM who are naïve to mAbs against CGRP or its receptor. [ABSTRACT FROM AUTHOR]

Background: Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. Methods: This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]). Results: Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. Conclusions: In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb). [ABSTRACT FROM AUTHOR]

Background: Following approval of fremanezumab for the prevention of migraine in adults, health care decision makers are interested in understanding real-world clinical characteristics and treatment patterns among patients initiating fremanezumab therapy. Methods: Data were obtained for this retrospective (pre-post) study from the Veradigm Health Insights database. The study period was January 1, 2014, to June 30, 2019. Patients were included if they were aged ≥ 18 years; had ≥ 1 migraine diagnosis during the study period; and had a medication record for fremanezumab on or after diagnosis during the identification period (September 1, 2018–December 31, 2018). Treatment patterns, including adherence, persistence, and utilization of acute and preventive migraine medication prescriptions, were evaluated. Results: Of 987 patients initiating fremanezumab during the study period, 738 (74.8%) were adherent to fremanezumab by proportion of days covered (PDC; ≥ 80%) and 780 (79.0%) were adherent by medication possession ratio (MPR; ≥ 80%). A total of 746 (75.6%) patients were persistent for ≥ 6 months. Quarterly fremanezumab (n = 186) was associated with higher rates of adherence versus monthly fremanezumab (n = 801) by PDC (quarterly, 91.3%; monthly, 84.9%; P < 0.001) and MPR (quarterly, 92.2%; monthly, 87.9%; P = 0.006) and higher persistence at ≥ 6 months (quarterly, 82.8%; monthly, 73.9%; P = 0.011). After fremanezumab initiation, patients who were persistent for ≥ 6 months experienced significant reductions from baseline in the mean monthly number of acute and preventive migraine medication prescriptions (P < 0.001). Subgroup analyses in patients with comorbid depression and anxiety showed meaningful real-world benefits based on significant reductions in the number of patients who were prescribed antidepressants (baseline, 68.6%; follow-up, 56.4%; P = 0.0025) and anxiolytic medications (baseline, 55.0%; follow-up, 47.2%; P = 0.037), respectively. In a subgroup of patients with comorbid hypertension at baseline, fremanezumab treatment resulted in nonsignificant reductions in blood pressure. Conclusions: Overall, adherence and persistence to fremanezumab in this real-world study was high in patients with migraine, with higher rates observed for quarterly fremanezumab. Patients who were persistent for ≥ 6 months experienced significant reductions in acute and preventive migraine medication use, while a subgroup of migraine patients with comorbid depression and anxiety at baseline showed significant reductions in antidepressant and anxiolytic medication use. [ABSTRACT FROM AUTHOR]

Background: The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. Methods: This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. Results: This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. Conclusions: This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

This study sought to determine how different dehydration methods affect the quality of Ghanaian ginger. Slices of ginger rhizomes were subjected to freeze drying (FD), relative humidity convective drying (RHCD), infrared drying (IR), microwave drying (MC), and pulsed vacuum drying (PVD). The quality characteristics of the dried slices were assessed and compared based on their levels of selected gingerols or gingerol derivatives and their chromatic properties, antioxidant activities, and flavonoid content. Analysis of the chromatic properties of the dried samples revealed that the chroma value and hue angle values were highest for the samples subjected to FD (32.99, 88.13°) compared with those subjected to RHCD (28.90, 85.69°), IR (26.66, 83.79°), MC (24.36, 79.78°), and PVD (21.73, 78.96°). FD best preserved and retained the total flavonoid content (69.01 mg GAE/g db) and antioxidant activities evidenced by results of DPPH (124.53 mgTE/g db) and CUPRAC (90.71 mgTE/g db) determinations than the samples subjected to RHCD, IR, MC, and PVD. Finally, the cytotoxic and anti‐inflammatory effects of extracts of the various dried ginger samples were evaluated using RAW 264.7 cells. Holistically, the samples from FD and RHCD gave the best outcomes for all the parameters compared. These two techniques are therefore recommended for large‐scale application because they enhance the quality of ginger by maintaining its chemical integrity. These findings provide a deeper understanding of the different dehydration techniques as well as serve as a guide on the selection of the right drying technique for fresh ginger. Novelty impact statement: Ginger is one of the most extensively used spices in the world, but because of its high moisture content, it is usually dried to extend its shelf‐life. For commercial purposes, an effective, safe, and efficient dryer is necessary to produce high‐quality dried ginger. This dryer must be able to maintain the product quality while reducing processing time and energy usage. The findings of this study provide a deeper understanding of the different dehydration techniques as well as serve as a guide on the selection of the right drying technique for fresh ginger. [ABSTRACT FROM AUTHOR]

Recently, Gao et al. published an article titled "Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials" which concluded that monthly administration of fremanezumab led to significant reduction in monthly migraine days (MMD) when compared to quarterly fremanezumab. We have noted a critical flaw in Gao et al. meta-analysis wherein the authors have mistakenly utilized standard error values in place of standard deviation values in performing their pooled analyses. This error directly impacts the study results and conclusions. In this brief communication, we present revised analysis using correct methods. Using the correct SD values, our pooled analysis showed no significant difference in mean change from baseline in MMD between the two fremanezumab dosing regimens (P = 0.17). Furthermore, in the corrected subgroup analyses by type of migraine, there were no significant differences in mean change from baseline in MMD between monthly fremanezumab and quarterly fremanezumab (chronic migraine, P = 0.50; episodic migraine, P = 0.69). Overall, results from our corrected meta-analyses show that there is no significant difference in migraine prevention efficacy between monthly and quarterly fremanezumab dosing. [ABSTRACT FROM AUTHOR]

Background: Reslizumab, an anti-IL-5 monoclonal antibody, is indicated as add-on maintenance treatment for adults with severe eosinophilic asthma.Research Question: What are the real-world outcomes associated with reslizumab use in patients with severe eosinophilic asthma in a US clinical practice?Study Design and Methods: In this retrospective study, patient-level data from adults treated with reslizumab were obtained from center- and panel-based medical chart reviews. Eligible patients had available medical records and treatment history for ≥ 6 months before initiation of reslizumab treatment (index date) to ≥ 7 months after reslizumab initiation. The primary outcome was response to reslizumab treatment, based on clinical expert predefined definitions of response. Other outcomes included clinical asthma exacerbations (CAEs), use of maintenance oral corticosteroids (OCS), FEV1 percent predicted, Asthma Control Test (ACT) score, and health-care resource use (HRU).Results: Medical charts were obtained for 215 patients. Most patients (58.6%) showed an excellent response, 16.3% showed a clinically meaningful response, 21.9% showed a partial response, and 3.3% were nonresponders or treatment failures. A significant reduction was observed in the proportion of patients experiencing a CAE in a 6-month period (from 86.0% to 40.5%; P < .001) and in the mean number of CAEs per patient (2.84 [SD, 2.41] vs 0.94 [SD, 1.86]) after reslizumab initiation. Improvements were observed in FEV1 percent predicted (65.1% [SD, 20.5%] vs 73.1% [SD, 23.1%]; P < .001) and in ACT scores (13.8 [SD, 4.2] vs 18.6 [SD, 4.0]; P < .001) before to after reslizumab initiation. Among patients using maintenance OCS at baseline, more than half discontinued use of these by approximately 10 months after reslizumab initiation. Significant reductions in asthma-related HRU were observed after reslizumab initiation.Interpretation: In clinical practice, reslizumab may have been initiated in response to heavy symptom burden and CAEs. Reslizumab was associated with improved clinical and patient-reported outcomes and significant reductions in asthma-related HRU. [ABSTRACT FROM AUTHOR]

In this paper we study the effect of the order and dose of H and He sequential implantation on H interaction with Si lattice defects. We use systematic infrared absorption measurements to investigate the evolution of hydrogenated point defects complexes during isothermal annealing. This analysis combined with the electron microscopy data led to the identification of the infrared absorption modes corresponding to the formation of the partially amorphized layer. The obtained results provide an important input for the optimization of the implantation conditions in order to achieve fracture in Si in the wide temperature range. [ABSTRACT FROM AUTHOR]

The occurrence of ochratoxin A (OTA) has been reported in cereals, feeds and food. Biological control of OTA has been considered as a promising strategy. Our previous study has shown that Yarrowia lipolytica Y‐2 could degrade OTA. In this study, proteome and transcriptome analysis were performed to investigate the possible mechanisms involved in OTA degradation by Y. lipolytica Y‐2 and the responses of this antagonistic yeast to OTA. The results showed that many proteins and genes involved in removal of reactive O2 species were up‐regulated in Y. lipolytica Y‐2 to respond to the oxidative stress caused by OTA. Also, some proteins and genes involved in the removal of generated toxicants under stress condition were up‐regulated to improve tolerance of this antagonistic yeast to OTA stress. Furthermore, some genes encoding transport proteins and multidrug resistance proteins were up‐regulated significantly to transport and expel OTA from cells and alleviate the toxicity to Y. lipolytica Y‐2. Notably, the gene ECM14 (encoding putative metallocarboxypeptidase ECM14) directly involved in OTA degradation was up‐regulated in Y. lipolytica Y‐2 treated with this mycotoxin. To defend against OTA stress, some genes related to tricarboxylic acid cycle were induced by OTA to generate abundant energy for Y. lipolytica Y‐2. Besides, the down‐regulation of some genes involved in DNA replication and repair decreased the ability of Y. lipolytica Y‐2 to repair DNA damage caused by OTA. These results may imply that OTA degradation by this antagonistic yeast was the synergetic effect of multifarious defence responses to OTA stress. [ABSTRACT FROM AUTHOR]

Inhaled medications are the cornerstone of treatment and management of asthma and COPD. However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation. These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes. To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes. Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations. Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD. Patients who had a reduction in errors over time had improved outcomes. These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a mycotoxin produced by some Penicillium, Aspergillus , and Byssochlamys species. Rhodotorula mucilaginosa is able to degrade PAT in vivo as well as in vitro , up till date, the process and molecular mechanism(s) involved patulin degradation still remains unknown. Protein lysine crotonylation (Kcr) plays an important role in regulating chromatin dynamics, gene expression, and metabolic pathways in mammals and eukaryotes. Investigation of the Kcr changes accompanying degradation of patulin in R. mucilaginosa were observed to investigate the mechanisms of patulin inhibition. Tandem mass tag (TMT) labeling and Kcro affinity enrichment, followed by high-resolution LC-MS/MS analysis, were used to perform quantitative lysine crotonylome analysis on R. mucilaginosa. Consequently, 1691 lysine crotonylation sites in 629 protein groups were identified, among which we quantified 1457 sites in 562 proteins. Among the quantified proteins, 79 and 46 crotonylated proteins were up-regulated and down-regulated, respectively. The differentially up expressed modified proteins were mainly involved in tricarboxylic acid cycle and gluconeogenic pathway. The differentially down expressed Kcr proteins were mainly classified to ribosome and carbohydrate transport and metabolism. Bioinformatic analyses were performed to annotate the quantifiable lysine crotonylated targets. Moreover, interaction networks and high confidence domain architectures of crotonylated proteins were investigated with the aid of bioinformatic tools, and these results showed that there was an increase in the number of yeasts with crotonylated proteins. The results also provided information on the various roles of crotonylation, which are involved in PAT degradation. [ABSTRACT FROM AUTHOR]

In this study, seven strains of Fusarium graminearum were isolated from wheat, of which six were identified to produce deoxynivalenol and the production of deoxynivalenol was assessed. F. graminearum strain Fg1 was noted to produce 1.0 μg/g deoxynivalenol during the incubation period in the Czapek yeast broth, while none was detected in F. graminearum strain Fg2. Hence, the differences in proteomes and transcriptomes of Fg1 and Fg2 were compared to analyze the mechanism underlying deoxynivalenol production. Among the 66 significantly differentially expressed proteins in Fg1, 39 and 27 were more or less abundant expressed. Functional analysis suggested that the enzymes involved in the methylerythritol 4-phosphate and mevalonate pathways, which provide a substrate for biosynthesis of farnesyl pyrophosphate, a precursor of DON, were activated in Fg1. The transcriptomics data demonstrated that the expression level of a majority of genes, including trichothecene biosynthetic genes, protein kinases, and transcription factors, involved in trichothecene biosynthesis was higher in Fg1 than in Fg2. The results also revealed differential expression profiles of deoxynivalenol biosynthesis genes in strains Fg1 and Fg2, which emphasized their deoxynivalenol producing ability and the underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested a greater benefit for various outcomes in men diagnosed with benign prostatic hyperplasia (BPH) who are treated with dutasteride than for men treated with finasteride. This study investigates whether the rates of BPH-related prostate surgery and acute urinary retention (AUR) differ between dutasteride and finasteride users in the Netherlands.Methods: From the PHARMO Database Network, men aged ≥50 years with a dispensing of dutasteride or finasteride with or without concomitant alpha-blocker treatment between March 1, 2003 and December 31, 2011 were selected. The incidence of BPH-related prostate surgery and AUR was determined during dutasteride or finasteride treatment and stratified by type of initial BPH-treatment (5-ARI monotherapy or combination with alpha-blocker) and prescriber (general practitioner (GP) or urologist). Comparison of the incidence of BPH-related prostate surgery and AUR between the treatment groups was done by Cox proportional hazard regression.Results: 11,822 dutasteride users and 5,781 finasteride users were identified. Most users started treatment in combination with an alpha-blocker. Overall, dutasteride users had a lower risk of BPH-related prostate surgery was lower among dutasteride users than finasteride users (HR: 0.75; 95 % CI: 0.56-0.99). This lower risk among dutasteride users was also seen when stratifying by monotherapy or combination therapy (HR: 0.73; 95 % CI: 0.54-0.98 for monotherapy and HR: 0.85; 95 % CI: 0.74-0.97 for combination therapy). However, the association was only present among men treated by urologists. For AUR the rates were low and no statistical significant difference was observed between dutasteride and finasteride users.Conclusions: The risk of undergoing BPH-related prostate surgery was lower among men using dutasteride compared to men using finasteride. The association was observed for monotherapy as well as combination therapy, however, only among men who received their prescription from a urologist. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor ( BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal ( HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (si RNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown ( KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice ( KD mice). Delivery of si RNA in the rat brain decreased BDNF levels in the hippocampus (−31%) and hypothalamus (−35%) but not in the amygdala, frontal cortex and pituitary. In addition, si RNA induced no change of the basal HPA axis activity. BDNF si RNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone ( ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. [ABSTRACT FROM AUTHOR]

It is clear that lupus autoimmunity is marked by a variety of abnormalities, including those found at a macroscopic scale, cells and tissues, as well as more microenvironmental influences, originating at the individual cell surface through to the nucleus. The convergence of genetic, epigenetic, and perhaps environmental influences all lead to the overt clinical expression of disease, reflected by the presences of autoantibodies and tissue pathology. This review will address several specific areas that fall among the non-genetic factors that contribute to lupus autoimmunity and related syndromes. In particular, we will discuss the importance of understanding various protein post-translational modifications (PTMs), mechanisms that mediate the ability of 'modified self' to trigger autoimmunity, and how these PTMs influence lupus diagnosis. Finally, we will discuss altered pathways of autoantigen presentation that may contribute to the perpetuation of chronic autoimmune disease. [ABSTRACT FROM AUTHOR]

Invasive Trichosporon infection is a rare, life-threatening infection in immunocompromised patients. It has been reported as an emerging opportunistic infection in those with acquired immune deficiency syndrome (AIDS). Only 12 cases of invasive trichosporonosis in patients with HIV have been documented, none in Southeast Asia. We report a case of fatal, disseminated trichosporonosis in a Filipino AIDS patient with severe cutaneous and pulmonary involvement. Invasive trichosporonosis should be considered in HIV-positive patients with disseminated fungal infection since this may be refractory to conventional antifungal treatment. [ABSTRACT FROM PUBLISHER]

Receptor-interacting protein 140 (RIP140) is a negative transcriptional coregulator of nuclear receptors such as estrogen, retinoic acid or glucocorticoid receptors. Recruitment of RIP140 results in an inhibition of target gene expression through different repressive domains interacting with histone deacetylases or C-terminal binding proteins. In this study, we analyzed the role of RIP140 activity in memory processes using RIP140-deficient transgenic mice. Although the RIP140 protein was clearly expressed in the brain (cortical and hippocampus areas), the morphological examination of RIP140−/− mouse brain failed to show grossly observable alterations. Using male 2-month-old RIP140−/−, RIP140+/− or RIP140+/+ mice, we did not observe any significant differences in the open-field test, rotarod test and in terms of spontaneous alternation in the Y-maze. By contrast, RIP140−/− mice showed long-term memory deficits, with an absence of decrease in escape latencies when animals were tested using a fixed platform position procedure in the water maze and in the passive avoidance test. Noteworthy, RIP140−/− mice showed decreased swimming speed, suggesting swimming alterations that may in part account for the marked alterations measured in the water maze. Moreover, RIP140+/− and RIP140−/− mice showed a significant increase in immobility time in the forced swimming test as compared with wild-type animals. These observations showed that RIP140 gene depletion results in learning and memory deficits as well as stress response, bringing to light a major role for this transcriptional coregulator in the neurophysiological developmental mechanisms underlying cognitive functions. [ABSTRACT FROM AUTHOR]

Music research in Africa has tended to focus on the analysis of lyrics in search of overt political content. This has yielded enormous and sometimes incisive academic work. However, research in music is yet to explore the political economy of the infrastructure of music production from composition, recording, marketing and paying of royalties. One aspect of music research that has also received little scholarly attention is the role of songs not simply in carrying the messages from composer to audience, but in helping in the creation of new words that are then popularised in cultural communities where these words are absorbed into the community's cultural and linguistic grammars. In Zimbabwe, two momentous historical periods, which are the liberation struggle (1970s) and the era of the Third Chimurenga (from 2000), reveal how the medium of song was used to generate a new vocabulary that has become part of the country's orthography. While some of the vocabulary so created during these periods is yet to enter dictionaries, most of these vocabularies have become the lingua franca in most African communities. This paper illustrates how the three domains of culture, politics and economics have benefitted from the capacity of song in creating, assimilating, appropriating and naming new realities in contexts marked by the inexorable processes of the violent uncoupling between the old political order and the new nationalist political dispensation ushered in by the various and legitimate phases of Zimbabwe's liberation struggles. [ABSTRACT FROM PUBLISHER]

Objectives This study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers9 exposure to psychosocial and physical risk factors. Methods 37 departments (n=3047 workers) from four Dutch companies participated in this cluster randomised controlled trial; 19 (n=1472 workers) were randomised to an intervention group (participatory ergonomics) and 18 (n=1575 workers) to a control group (no participatory ergonomics). During a 6 h meeting guided by an ergonomist, working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3 months in their departments. Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months. Psychosocial risk factors were measured using the Job Content Questionnaire and physical risk factors using the Dutch Musculoskeletal Questionnaire. Intervention effects were studied using multilevel analysis. Results Intervention group workers significantly increased on decision latitude (0.29 points; 95% CI 0.07 to 0.52) and decision authority (0.16 points; 95% CI 0.04 to 0.28) compared to control workers. However, exposure to awkward trunk working postures significantly increased in the intervention group (OR 1.86; 95% CI 1.15 to 3.01) compared to the control group. No significant differences between the intervention and control group were found for the remaining risk factors. After 6 months, loss to follow-up was 35% in the intervention group and 29% in the control group. Conclusion Participatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers. [ABSTRACT FROM AUTHOR]

Objective: The aim this randomized controlled trial (RCT) was to investigate the effectiveness of the Stay@Work participatory ergonomics (PE) program to prevent low-back and neck pain. Methods: A total o137 departments were randomly allocated to either the mervemion (PR) or control group (no PU). During a six-hour meeting, working groups followed the PU steps and composed and prioritized ergonomic measures aimed at preventing low-hack and neck pain. Subsequently, working groups were requested to implement the ergonomic measures in the departments. The primary outcomes were low-hack and neck pain prevalence and secondary outcomes were pain intensity and duration. Data were collected by questionnaires at baseline, and after 3-. 6-, 9-, and 12-months follow-up. Additionally the course of low-back and neck pain (transitions from no symptoms to symptoms and from symptoms to no symptoms) as modeled. Results: Tue randomizationprocedure resulted in 19 intervention departments(N=l472 workers) and 18 control departments (N= 1575 workers). Ailer 12 months. the intervention was not more effective than the control group in reducing the prevalence of low-back and neck pain or reducing pain intensity and duration. PR did not increase the probability ofpreventing low-hack pain [odds ratio (OR) 1.23. 15% conFidence interval (95% Cl) 0.97-1 .571 or neck pain (OR 1.01,95% CI 0.74-1.40). However, PU increased the probability ufrecosering from low-hack pain (OR 1.41, 95% CI 1.01-1.96), but not from neek pain (OR O.')5, 95° CI 0.72-1.261. Conclusion PE neither reduced low-back and neck pain prevalence nor pain intensity and duration nor was it effective in the prevention of low-hack and neck pain or the recovery from neck paul. However. PE was more effective in the recovery from low-back pain. [ABSTRACT FROM AUTHOR]

One of the major challenges of writing the Rwandan genocide is how to move away from figuring it as a spectacle, without minimising the significance of the genocide in the cultural history of Rwanda. Although nearly a million Tutsis and some moderate Hutus perished in the Rwandan genocide, some Tutsis and moderate Hutus survived. Yet very little creative art has devoted itself to exploring in metaphors and images how these people survived. Celebrated films such as Hotel Rwanda provide gory scenes of the killing of the Tutsis as background to the creation of their heroes. In sharp contrast Andrew Brown's novel, Inyenzi: a story of love and genocide, is not oblivious to this dimension, but it deliberately foregrounds the positive contribution of individuals and the much reviled Christian Church showing that some Hutus and Tutsis joined forces to redefine themselves through identities that transcended ethnicity. The aim of this article is to briefly highlight the figurative contours of what Julia Kristeva (1982) has described as the abject depicted in the novel Inyenzi: a story of love and genocide. The article argues that the presence of the abject in literature underlines or invokes the desire to work for the creation of a just Rwandan society. The article demonstrates that the depiction of the abject in Inyenzi: a story of love and genocide gives way to the re-establishment, retrieval and re-interpretation of romantic narratives whose social vision reveals an aspiration for a peaceful life and social reconciliation amongst the ethnic groups of Rwanda. [ABSTRACT FROM AUTHOR]

Creative literary cultures, unlike the visible political institutions such as education, law and the security forces, are less amenable to total destruction even in the face of the most brutal and dictatorial regimes. The possibilities that creative cultures can be manipulated by tyrants can never be doubted and in post-independence Zimbabwe, the scars of abuse of creativity by the ruling elites abound. However, creative literary cultures work with their own logic; the fact of a social, political and economic meltdown can be the suitable condition of possibility of rebirth of creative art that interrogates this slide. This means that creative cultures can authorize their own narrative patterns in ways that both confirm and interrogate the conditions of the country and of the arts' terms of imaging the Zimbabwe crisis. The subversive element in literature and other creative cultures is that even creative work by official griots is destabilized from within its symbolisms so that when read, listened to and watched on television using different protocols, these forms of art can contradict the collective national memories that a regime such as the one in Zimbabwe seeks to claim as its own. This article demonstrates that Zimbabwean literature in English and the Shona languages and the popular musical creative cultures are born out of, confront, and have been at the forefront of documenting the different kinds of crises that have defined Zimbabwe since 1890. The literature and popular music also depict the crises that any narrative has to endure and suffer; literary narratives can never command sufficient vocabulary that can enable them at any imagined secure vantage perspective to capture all the nuances of the Zimbabwe crises in their political, economic and legal dimensions. This inability to settle on an absolute representation of the Zimbabwe crises can be viewed as a welcome development if it should be expected that literature's images and metaphors are flexible enough to anticipate the shifting nature of the crises and allow varied interpretations. [ABSTRACT FROM AUTHOR]

Background: Both low back pain (LBP) and neck pain (NP) are major occupational health problems. In the workplace, participatory ergonomics (PE) is frequently used on musculoskeletal disorders. However, evidence on the effectiveness of PE to prevent LBP and NP obtained from randomised controlled trials (RCTs) is scarce. This study evaluates the process of the Stay@Work participatory ergonomics programme, including the perceived implementation of the prioritised ergonomic measures.Methods: This cluster-RCT was conducted at the departments of four Dutch companies (a railway transportation company, an airline company, a steel company, and a university including its university medical hospital). Directly after the randomisation outcome, intervention departments formed a working group that followed the steps of PE during a six-hour working group meeting. Guided by an ergonomist, working groups identified and prioritised risk factors for LBP and NP, and composed and prioritised ergonomic measures. Within three months after the meeting, working groups had to implement the prioritised ergonomic measures at their department. Data on various process components (recruitment, reach, fidelity, satisfaction, and implementation components, i.e., dose delivered and dose received) were collected and analysed on two levels: department (i.e., working group members from intervention departments) and participant (i.e., workers from intervention departments).Results: A total of 19 intervention departments (n = 10 with mental workloads, n = 1 with a light physical workload, n = 4 departments with physical and mental workloads, and n = 4 with heavy physical workloads) were recruited for participation, and the reach among working group members who participated was high (87%). Fidelity and satisfaction towards the PE programme rated by the working group members was good (7.3 or higher). The same was found for the Stay@Work ergocoach training (7.5 or higher). In total, 66 ergonomic measures were prioritised by the working groups. Altogether, 34% of all prioritised ergonomic measures were perceived as implemented (dose delivered), while the workers at the intervention departments perceived 26% as implemented (dose received).Conclusions: PE can be a successful method to develop and to prioritise ergonomic measures to prevent LBP and NP. Despite the positive rating of the PE programme the implementation of the prioritised ergonomic measures was lower than expected.Trial Registration: Current Controlled Trials ISRCTN27472278. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) and neck pain (NP) are common among workers. Participatory Ergonomics (PE) is used as an implementation strategy to prevent these symptoms. By following the steps of PE, working groups composed and prioritised ergonomic measures, and developed an implementation plan. Working group members were responsible to implement the ergonomic measures in their departments. Little is known about factors that hamper (barriers) or enhance (facilitators) the implementation of ergonomic measures. This study aimed to identify and understand the possible barriers and facilitators that were perceived during implementation.Methods: This study is embedded in a cluster randomised controlled trial that investigated the effectiveness of PE to prevent LBP and NP among workers. For the purpose of the current study, questionnaires were sent to 81 working group members. Their answers were used to make a first inventory of possible barriers and facilitators to implementation. Based on the questionnaire information, 15 semi-structured interviews were held to explore the barriers and facilitators in more detail. All interviews were audio taped, transcribed verbatim, and analysed according to a systematic approach.Results: All possible barriers and facilitators were obtained from questionnaire data, indicating that the semi-structured interviews did not yield information about new factors. Various barriers and facilitators were experienced. The presence of implementation plans for ergonomic measures that were already approved by the management facilitated implementation before the working group meeting. In these cases, PE served as a strategy to improve the implementation of the approved measures. Furthermore, the findings showed that the composition of a working group (i.e., including decision makers and a worker who led the implementation process) was important. Moreover, stakeholder involvement and collaboration were reported to considerably improve implementation.Conclusions: This study showed that the working group as well as stakeholder involvement and collaboration were important facilitating factors. Moreover, PE was used as a strategy to improve the implementation of existing ergonomic measures. The results can be used to improve PE programmes, and thereby may contribute to the prevention of LBP and NP.Trial Registration Number: ISRCTN27472278. [ABSTRACT FROM AUTHOR]

This article aims to discuss the contradictory principle that informs various functions of songs in the ritual-myth of Kurova Guva among the Shona of Zimbabwe. The discussion of this ritualmyth will focus on selected songs that are sung during the ritual-myth of Kurova Guva. While the Shona are not perceived as a group with homogeneous cultural values, there is general agreement that Kurova Guva is a distinct Shona cultural rite of passage. It will be argued that the ritual-myth of Kurova Guva rests on the acceptance that someone physically dies. However, the physical death of the flesh is not the ultimate terminus of 'human' life. The Kurova Guva ritual-myth ceremony reasserts the continued spiritual existence of the dead person by seeking to bring that person back into the community of ancestral spirits that are recognised by the dead person's surviving family members. During Kurova Guva, which usually takes place on Friday and Saturday, popular songs and drumming constitute the medium through with the ritual-myth of bringing home the spirit of the 'dead' is carried out. [ABSTRACT FROM AUTHOR]

The article discusses various papers published within the issue including Zodwa Motsa's analysis of the book "Long Walk to Freedom," by Nelson Mandela, and an article on the national anthem of Zimbabwe.

The aim of this article is to render thinkable the idea of reading the Zimbabwean national anthem, Simudzai Mureza weZimbabwe, as a political biography. Biographies are people's lives narrated by others. However, the act of writing the lives of the nation in the form of an anthem, and then projecting these experiences as epitomising the lives of the individuals within the nation, is in fact marked by a disjuncture. This happens because by their very nature, acts of narrating individual or collective identities should always be viewed as approximations of that lived reality. Furthermore, national anthems as wish lists are based on some selected themes deemed of national importance by others and not everybody. This problem is at the heart of reading the Zimbabwean national anthem as a political biography. This article argues that if it is remembered that the lyrics of Simudzai Mureza weZimbabwe were composed by a literary figure, and selected and adopted by the Government of Zimbabwe, amongst other compositions, then there is reason to believe that there are, from that competition, some versions of the national anthem that were turned down, whose lyrical content Zimbabweans may never come to know of. Read from this “subversive” perspective, the Zimbabwean national anthem is a political biography “complete in its incompleteness” or incomplete in it completeness.2 [ABSTRACT FROM AUTHOR]

In the absence of the international coverage of the Rwandan genocide, most international audiences came to know the Rwandan tragedy through the film, Hotel Rwanda, which was directed by Terry George, and which came out in 2004 - ten years after the genocide of 1994. The film is a chilling visual account of how nearly one million Tutsis were massacred by Hutu extremists in the span of nearly 100 days. However, following on the “heels” of the production of Hotel Rwanda, Paul Rusesabagina and Tom Zoellner published An ordinary man: the true story behind “Hotel Rwanda” (2006) a book that claims to tell the “truth” behind the film. The question then is: How much of what happened in the Rwandan genocide in 1994 was Hotel Rwanda authorized to tell and not to tell? This article does not seek to confirm whether or not what the film depicts corresponds point for point with what is in the book. Rather, using Derrida's concept of “iteration”, this article explores the dynamics that exist when a subject or theme narrativized in one form is repeated in another. The article then links iteration, which produces differance in textual meanings to Bakhtin's idea of the “chronotope” as a place of encounter in genres of popular culture. The article argues that films construct meanings during moments of enunciation and that these meanings can significantly alter the narratives contained in a novel on the same theme. A novel can elaborate what film time may not achieve in a limited time-span, while a film can also offer transgressive meanings through its visual language that words on the page of a novel may not be able to animate. [ABSTRACT FROM AUTHOR]

This article explores the notion of a diaspora and identity in the context of Southern Africa musical cultures. Musical diaspora studies have tended to analyse songs re-recorded in contexts separated from the settings of the initial recordings and production. While this has generated a wealth of critical works and encouraged an awareness of how lyrics migrate from one setting to another, this has not encouraged explorations of musical lyrics by singers who are themselves in experiences of willed and sometimes enforced diasporas. This article takes Zimbabwe as a point of analysis for musical migrations in and outside the country. Zimbabweans and non-Zimbabweans alike have participated in creating a diasporic identity in response to the flux from the traditional to the modern, from the colonial to independence, from independence to betrayal, and then towards embracing transnational forms of resistances realised through cross-border migrations of singers and their musical cultures. [ABSTRACT FROM AUTHOR]

In the wake of the current quicksilver advances in technology, generally speaking, intellectual property has had its share of the benefits, and losses, of the exploitation of online works. In copyright law, as in other aspects of intellectual property (Matheson and Bonny 2007, 20), the landscape in sound recording has changed. This article investigates four issues arising from these changes: first, the ease with which ringtones can be created using user-generated content (UGC) devices in contrast with analogue recording of ringtones; second, when copyright arises in ringtones; third, the composition of right holders in ringtones; and fourth, if there are any rights in ringtones, whether the Copyright Act of South Africa (hereafter the Act) adequately protects those rights from infringement, particularly in view of the economic benefits that can be derived from the exploitation of such rights in favour of ordinary users and historically disadvantaged individuals in South Africa. [ABSTRACT FROM AUTHOR]

The article studies the electoral challenge the Massachusetts Republican Party mounted in 2004 to the Democratic Party dominance of the state legislature. It discusses the district level independent variables which include the percent of independent voters in the district, the percent candidate Mitt Romney received in the district in 2002, and whether or not the district had an open seat. It also discourses candidate level variables.

The aim of this article is to explore the changing perceptions on the discourses of death and purity as articulated in African popular music. In African traditional cultures, the death of a human being is considered a sacred event. It is viewed with fear, confusion and as dislocator of assumed human connectivity and it is then considered inhuman to celebrate the death of tyrant, dictator and even common thieves. African poetry abound in imagery that depicts death as the nemesis and the antithesis of life. These commonplace views on death and purity have been given philosophical justification in Afrocentric writings. The problem is that these views (of death) fail to explain and morally justify when, if ever, the death of a human being should be celebrated. In recent writings and popular culture in Zimbabwe, popular musicians have “crossed the line” and have, in fact, begun to sing of death as sometimes a desirable necessity that can end serious social ills. Epistemological discourses that equate death with purity have also failed to distinguish death as metonym and death as metaphor. In this article, Wafawanaka, a song made popular by the Zimbabwean singer Extra Large in post-independence Zimbabwe is explored in order to reveal and problematise the shifts that have taken place in the discourses of death as purity (i.e. against the emergence of those discourses that argue that death is desirable in some contexts because it ameliorates human suffering). [ABSTRACT FROM AUTHOR]

This exploratory study attempts to explain how journalistic routines for covering violent conflict lead to the construction of ethnocentric news. A distinction is made between two sets of routines. One set is permanent and ensures ethnocentric control over the flow of information, while a second set varies as journalists construct coherent narratives for particular events. This latter set of routines is further broken down into what are labeled the 'Victims Mode' and 'Defensive Mode' of reporting. The Victims Mode is used when one's own citizens have suffered an especially tragic loss of life, while the Defensive Mode is employed when one's forces have carried out an attack that has inflicted a similar loss on the enemy. It is argued that each of these modes of reporting parallels psychological reactions that have been found in individuals. The ideas raised in the theoretical discussion are investigated by comparing coverage of two events by Israeli and Palestinian television. Two events were chosen for analysis: a Palestinian suicide bombing that killed 19 Israelis, and the killing of Hamas leader Sheik Salach Shehadeh in which 16 Palestinians were killed. An in-depth reading of the six news broadcasts provides important insights into how journalists' routines ensure a steady flow of culturally acceptable news stories that reinforce hatred between enemies. [ABSTRACT FROM AUTHOR]

The most serious health concern in Zimbabwe today is the alarming spread of HIV/AIDS. Since 1987, the state radio stations, television channels, public and private print media have been at the forefront, giving information about the AIDS pandemic to the people. But as Danlabi Musa observes, 'diversity' and bigger audience are not the function of channel multiplicity' but have also to do with “...access and programming” (Musa, in Gecau et al. 1996:23). This chapter looks at how the prevalence of AIDS in Zimbabwe is influencing the construction of the identity of black women in Zimbabwe, as is revealed in the popular songs and some oral poems. Unlike television, which only the rich have, access to newspapers, messages which depend on the taught skill of reading, songs, oral poems can be more open and democratic forms. Both are oral and aural and can break the boundaries imposed by writing or reading. Anybody can appropriate them for different purposes. Although male or female singers in Zimbabwe have been singing about the plight of women as minors in private and public circles, negative images of black women continue to be produced, circulated and consumed through song and some oral poetry. This chapter argues that the prevalence of HIV/AIDS in Zimbabwe has produced a new moral discourse in which women are objectified as “dangerous” and “loose” on the one hand, and are expected to become “respectable” and “disciplined” to attain the newly projected status of a “proper” women on the other. [ABSTRACT FROM AUTHOR]

Background and purpose:Tetrahydro-N, N-dimethyl-5, 5-diphenyl-3-furanmethanamine hydrochloride (ANAVEX1-41) is a potent muscarinic and sigma1 (σ1) receptor ligand. The σ1 receptor modulates glutamatergic and cholinergic responses in the forebrain and selective agonists are potent anti-amnesic and antidepressant drugs. We have here analysed the σ1 component in the behavioural effects of ANAVEX1-41.Experimental approach:Binding of ANAVEX1-41 to muscarinic and σ1 receptors were measured using cell membranes. Behavioural effects of ANAVEX1-41 were tested in mice using memory (spontaneous alternation, passive avoidance, water-maze) and antidepressant-like activity (forced swimming) procedures.Key results:In vitro, ANAVEX1-41 was a potent muscarinic (M1>M3, M4>M2 with Ki ranging from 18 to 114 nM) and selective σ1 ligand (σ1, Ki=44 nM; σ2, Ki=4 μM). In mice, ANAVEX1-41 failed to affect learning when injected alone (0.03–1 mg kg−1), but attenuated scopolamine-induced amnesia with a bell-shaped dose response (maximum at 0.1 mg kg−1). The σ1 antagonist BD1047 blocked the anti-amnesic effect of ANAVEX1-41 on both short- and long-term memories. Pretreatment with a σ1 receptor-directed antisense oligodeoxynucleotide prevented effects of ANAVEX1-41 only in the passive avoidance procedure, measuring long-term memory. ANAVEX1-41 reduced behavioural despair at 30 and 60 mg kg−1, without involving the σ1 receptor, as it was not blocked by BD1047 or the antisense oligodeoxynucleotide.Conclusions and implications:ANAVEX1-41 is a potent anti-amnesic drug, acting through muscarinic and σ1 receptors. The latter component may be involved in the enhancing effects of the drug on long-term memory processes.British Journal of Pharmacology (2007) 152, 267–279; doi:10.1038/sj.bjp.0707386; published online 6 August 2007 [ABSTRACT FROM AUTHOR]

One of the most effective cultural tools used by the colonial governments in Africa to make their rule acceptable to African indigenous populations was film. In Rhodesia (now known as Zimbabwe) the colonial government created the Central Film Unit whose major aim was to teach Africans new agricultural methods. The response by Africans to this colonial initiative was mixed. Some welcomed and enjoyed the films and made use of the skills that the films popularised, but others were cynical and viewed these films as a tool to consolidate British white settler rule in Rhodesia. This article analyses six colonial films produced in the 1940s and 1950s. The article argues that through the use of colonial films, the Rhodesia government was able to persuade African communal farmers to adopt modern methods of farming. The irony of this is that the use of modern farming methods made it possible for the same colonial authorities to later blame Africans for the ecological disaster in the communal areas. [ABSTRACT FROM AUTHOR]

Whenever Zimbabwean music is debated in the country or outside, the reflections tend to centre on established male singers such as Thomas Mapfumo, Oliver Mtukudzi, Simon Chimbetu and others. Female singers are on the margin of theoretical works despite the fact that Susan Mapfumo, Dorothy Masuku and Stella Chiweshe have been singing from the 1950s, through the 1970s and certainly up to the present day (in the case of Stella Chiwese). In Zimbabwe today, the performances and creativity of new female singers such as Mbuya Madhuve, Chiwoniso Maraire and Fungisai Zvakavapano2 steal the musical charts. And yet very little research has been done on their work in order to explore the phenomenon of a female singing culture and to explain how they contribute and give shape to the contours of Zimbabwe's national culture. The main aim of this article is to consider the musical contributions of Mbuya Madhuve and Chiwoniso Maraire to the debates on democracy in Zimbabwe. These singers have been neglected even in those studies that have analysed the songs of women such as Stella Chiweshe, Dorothy Masuku and Susan Mapfumo (Kwaramba 1997, Vambe 2004, Makwenda 2005). In analysing the lyrics of Mbuya, Madhuve and Chiwoniso we do not try to link the lives of the singers to their creativity.3 We argue, instead, that what female singers intend their songs to mean, and how these very songs are received by the listening audience, constitute the arena of national culture formation. [ABSTRACT FROM AUTHOR]

Background and purpose:The acetylcholinesterase inhibitor, donepezil, is also a high affinity σ1 receptor agonist. We examined the involvement of σ1 receptors in its anti-amnesic and neuroprotective properties against amyloid β25-35 peptide-induced toxicity in mice.Experimental approach:Mice were given an intracerebroventricular (i.c.v.) injection of Aβ25-35 peptide (9 nmol) 7-9 days before being tested for spontaneous alternation and passive avoidance. Hippocampal lipid peroxidation was measured 7 days after Aβ25-35 injection to evaluate oxidative stress. Donepezil, the σ1 agonist PRE-084 or the cholinesterase (ChE) inhibitors tacrine, rivastigmine and galantamine were administered either 20 min before behavioural sessions to check their anti-amnesic effects, or 20 min before Aβ25-35 injection, or 24 h after Aβ25-35 injection and then once daily before behavioural sessions, to check their pre- and post-i.c.v. neuroprotective activity, respectively.Key results:All the drugs tested were anti-amnesic, but only the effects of PRE-084 and donepezil were prevented by the σ1 antagonist BD1047. Only PRE-084 and donepezil showed neuroprotection when administered pre i.c.v.; they blocked lipid peroxidation and learning deficits, effects inhibited by BD1047. Post i.c.v., PRE-084 and donepezil showed complete neuroprotection whereas the other ChE inhibitors showed partial effects. BD1047 blocked these effects of PRE-084, attenuated those of donepezil, but did not affect the partial effects of the other ChE inhibitors.Conclusions and implications.The potent anti-amnesic and neuroprotective effects of donepezil against Aβ25-35-induced toxicity involve both its cholinergic and σ1 agonistic properties. This dual action may explain its sustained activity compared to other ChE inhibitors.British Journal of Pharmacology (2006) 149, 998–1012. doi:10.1038/sj.bjp.0706927; published online 23 October 2006 [ABSTRACT FROM AUTHOR]

Cultural critics of the Zimbabwean government argue that the passing into law of the 75 percent requirement of local content on television and radio is the most visible expression of musical censorship. The critics argue that control of television and radio helps the government to censor the content of music of those singers whose visions of Zimbabwe do not agree with that of the ruling Zanu-PF. While the idea of 100 per cent local content on the air waves might seem noble and positive at first sight, in that it seems to represent the movement of local music from the periphery to the mainstream, in reality this has implications for the character of Zimbabwean music, as it increasingly strives to imitate American music. Thus, local content quotas may kill the music industry as Zimbabwe does not possess enough material to meet the local content criteria. Censorship also manifests itself in the form of a campaign of intimidation against artists, and in the suggestion that what people watch on Zimbabwe television and listen to on state radio is not local Zimbabwean content but Zanu-PF propaganda. These views are not shared by all musicians and listeners. In fact, the identification of local content with lyrics gives birth to the perception that people are what they listen to. However, a reconsideration of music in terms of lyrics, rhetoric and voice creates a different framework of understanding music in which people can generate their own meanings and be what they do not listen to. Using the music of Tambaoga, Zhakata and Chipanga, this article argues that the politics of listening as performance forces us to take notice that other than lyrics, singers use musical rhetoric and voice to evade official censorship as well as expand the conceptual understanding of the question of what is ‘local’ in the debate on localising musical content in Zimbabwe. [ABSTRACT FROM PUBLISHER]

Offers a look at the position of the Catholic Church on the Supreme Court case Goodridge v. the Department of Public Health in Massachusetts in November 2003, in which the court recognized the right of same sex couples to marry. Specifics of the case; Arguments raised by the Catholic Action League of Massachusetts against the decision; Brief history on the political influence exhibited by the Catholic Church in Massachusetts; Information on the Massachusetts Catholic Conference.

The high selectivity of the phencyclidine derivative PRE-084 for sigma (σ) sites is demonstrated. We previously reported that this compound is able to markedly attenuate the impairment of learning induced in mice by the non-competitive NMDA antagonist MK-801, and the cholinergic nicotinic antagonist mecamylamine. In this study, we examined the effect of PRE-084 on the impairment of learning induced by acute administration of the calcium channel antagonist nimodipine. Nimodipine (0.3mg/kg i.p.) impaired the spontaneous alternation behaviour in a Y-maze, decreased the step-down latency (SDL) in a passive avoidance task, and altered place learning and retention in a water-maze paradigm, with no marked effect on the motility observed using an open-field test. Preadministration of PRE-084 resulted in an attenuation of the impairment of alternation, in the 0.3-1 mg/kg s.c. range, in a marked increase in SDL, at 1-3 mg/kg, and improved place learning and retention in the water-maze, at 1 mg/kg. The effects on alternation behaviour and passive avoidance were completely prevented by co-administration of the purported σ antagonist BMY-14802 (10 mg/kg i.p.), implicating the σ sites. These results confirm the beneficial effect of the σ ligand PRE-084 on pharmacological models of learning impairments, and indicate that σ sites may modulate Ca fluxes through VDCC, which may in turn bear some as yet unknown relationship to the previously described interaction with neurotransmitter systems. [ABSTRACT FROM AUTHOR]