Inactivation of AMPKα1 induces asthenozoospermia and alters spermatozoa morphology

AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit α1 gene [α1AMPK knockout (KO)]. In the testis, the α1AMPK subunit is expressed in germ cells and also in somatic cells (Sertoli and Leydig cells). α1AMPK KO male mice show a decrease in fertility, despite no clear alteration in the testis morphology or sperm production. However, in α1AMPK(-/-) mice, we demonstrate that spermatozoa have structural abnormalities and are less motile than in control mice. These spermatozoa alterations are associated with a 50% decrease in mitochondrial activity, a 60% decrease in basal oxygen consumption, and morphological defects. The α1AMPK KO male mice had high androgen levels associated with a 5- and 3-fold increase in intratesticular cholesterol and testosterone concentrations, respectively. High concentrations of proteins involved in steroid production (3β-hydroxysteroid dehydrogenase, cytochrome steroid 17 alpha-hydroxylase/17,20 lysate, and steroidogenic acute regulatory protein) were also detected in α1AMPK(-/-) testes. In the pituitary, the LH and FSH concentrations tended to be lower in α1AMPK(-/-) male mice, probably due to the negative feedback of the high testosterone levels. These results suggest that total α1AMPK deficiency in male mice affects androgen production and quality of spermatozoa, leading to a decrease in fertility.     

DROP-OUT FROM CHRONIC PAIN TREATMENT PROGRAMMES: IS RANDOMIZATION JUSTIFIED IN BIOPSYCHOSOCIAL APPROACHES?

ObjectiveTo identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management.PatientsA total of 575 patients were included in the study. Of these, 203 were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; and psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and therefore were termed a “self-hypnosis/self-care demanders” group.MethodsSocio-demographics and behavioural data were included in the analyses. Univariates analyses, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers were conducted in order to select variables to include in a multivariate logistic regression.ResultsUnivariate analyses yielded 8 variables, out of 18 potential predictors for drop-out, which were eligible for inclusion in the multivariate logistic regression. The model showed that having an intermediate or high educational level protects against dropping out early or late in the pain management process. Having to wait for more than 4 months before starting the treatment increases the risk of never starting it. Being randomized increases the risk of never starting the treatment.ConclusionIn a context in which randomization is considered a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.LAY ABSTRACTThe aim of this study was to identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management. A total of 575 patients were included in the study. Of these, 203 patients were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and hence formed a “self-hypnosis/self-care demanders” group. Analyses of socio-demographics and behavioural data were conducted, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers. Results showed that having an intermediate or high educational level protects against dropping out early or late in the management process. Having to wait for more than 4 months before starting the treatment, and being randomized, increases the risk of never starting it. Thus, in a context in which randomization is considered as a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.Key words: chronic pain, non-pharmacological treatment, randomization, drop-out, loss to follow-up, attrition

Chronic pain is a complex disorder in which pain appears persistent and prolonged (> 3 months) and includes biological, psychological and socio-professional factors that undermine patients’ everyday life. Patients and healthcare providers are increasingly turning to non-pharmacological treatments, such as hypnosis and music therapy, combined with cognitive behavioural therapy (CBT) (1). The efficacy of these treatment in managing chronic pain has been demonstrated (2–4).A major problem in clinical research is drop-out, which ranges from 5% to 46%, in chronic pain management, depending on the study (5). The first issue concerns the definition of drop-out, since this varies between authors: some regard drop-out as patients ending therapy before the agreed-end-of-treatment (6), others consider it as not attending therapy sessions even though patients have agreed to attend (7). The second issue is that few clinical studies in the field of chronic pain take drop-out into account, thus generating a bias in the overall results of clinical trials investigating the efficacy of such treatments (8). The lack of studies and the disagreement regarding definitions lead to a range of results in the study of drop-out predictors in chronic pain. Some authors have highlighted that a low educational level increases the risk of dropping out from therapy (cohort study (9)), while others have shown the contrary (randomized trial (10)). The same controversy can be seen when considering age, sex and personality (systematic review (5); randomized trial (10); retrospective study (11); non-randomized trial (12)). Predictors outside of patient-related factors have mostly been studied in the mental health literature. As the management of chronic pain and mental health is relatively similar, consideration of these factors seems relevant. A meta-analysis showed that, in psychotherapy settings, the therapist expertise had an influence on drop-out. The results demonstrated that when trainees (pre-degree attainment) lead the group therapy, patients tended to be more likely to drop-out (13). Another meta-analysis showed that patients’ motivational level predicted drop-out from psychotherapy (14). A further barrier to completing treatments is the waiting period between initial contact and the effective start of the treatment (retrospective study (15)). Another retrospective study highlighted that the longer the patients in a substance abuse treatment programme had to wait until the onset of treatment (≥8 days), the more likely they were not to attend the first session of the programme (16).Given the lack of consensus, a better understanding of the profile of drop-outs and contextual risk factors, is essential in order to prevent this phenomenon, enhance treatment adherence and, consequently, ameliorate the study of treatment efficacy in chronic pain.The aim of this study was to retrospectively identify patient- and context-related factors to explain drop-out from randomized biopsychosocial-based treatment programmes.     

Epidemiology of pertussis in a West African community before and after introduction of a widespread vaccination program

The control of pertussis remains a worldwide concern. Little has been documented about its epidemiology in Africa. The authors have studied pertussis in a prospective cohort of children in a rural West African community over a 13-year period comprising time before and after introduction of a vaccination program. Children under age 15 years who were residents of the Niakhar study area in Senegal were followed prospectively between January 1984 and December 1996 for the occurrence of pertussis. Morbidity and mortality rates were extremely high before the launch of immunization. Crude incidence was 183 per 1,000 child-years at risk under age 5 years, with a 2.8% case-fatality rate. After the introduction of the vaccination program, overall incidence dropped rapidly and dramatically-by 27% after 3 years and 46% after 6 years. The decline in incidence involved all age groups but was most substantial in the group under age 5 years and was particularly pronounced in unvaccinated infants. The median age of acquisition of the disease rose steadily with population vaccine coverage. This study shows the tremendous magnitude of the disease burden in children and the rapid decline after vaccination, and it suggests a strong herd-immunity effect.     

Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparum Isolates from Dakar,Senegal, in 2013-2014

The kelch 13 (K13) propeller gene is associated with artemisinin resistance. In a previous work, there were no mutations found in 138 Plasmodium falciparum isolates collected in 2012 and 2013 from patients residing in Dakar, Senegal (M. Torrentino-Madamet et al., Malar J 13:472, 2014, http://dx.doi.org/10.1186/1475-2875-13-472). However, the N554H, Q613H, and V637I mutations were identified in the propeller region of K13 in 92 (5.5%) isolates in 2013 and 2014. There were five polymorphisms identified in the Plasmodium/Apicomplexa-specific domain (K123R, N137S, N142NN/NNN, T149S, and K189T/N).     

Intrauterine fallopian tube incarceration: an uncommon complication of termination of pregnancy by vacuum aspiration

A 34-year-old woman presented with an intermittent abdominal pain 5 years after voluntary vacuum aspiration for interruption of a first-trimester pregnancy. Magnetic resonance imaging demonstrated complete septate uterus and a cystic mass that infiltrated the posterior myometrial wall of the right side of the uterus. Laparoscopy and hysteroscopy revealed an intra uterine fallopian tube incarceration.     

A Randomized Trial of Artesunate Mefloquine versus Artemether Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Senegalese Children

An open randomized clinical trial study was carried out to compare efficacy and tolerability of artesunate mefloquine 25 mg/kg body weight (Artequin paediatric) versus artemether lumefantrine (Coartem) in the treatment of uncomplicated Plasmodium falciparum malaria in children. In each arm, 160 patients were assigned to receive either AS + MQ or AL with 28 days follow-up. The adequate clinical and parasitological response at Day 28 for per protocol analysis was after polymerase chain reaction correction, 100% for AS + MQ and 96.8% for AL. In the intention-to-treat analysis, the respective cure rates were 96.2% for AS + MQ and 93.7% for AL. No serious adverse events (AEs) were reported. The most frequent AE was vomiting, 30% in AS + MQ arm and 36% in AL arm. No biological significant abnormal values related to the study drug have been reported. The new pediatric artesunate mefloquine formulated in granule fixed dose combination is well adapted to children in Africa.