A Non-Inferiority,Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy

Background

The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach.

Methods and Findings

An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups.

Conclusions

Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated.

Trial Registration

ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122     

Mitochondrial respiration in human viable platelets—Methodology and influence of gender,age and storage

Studying whole cell preparations with intact mitochondria and respiratory complexes has a clear benefit compared to isolated or disrupted mitochondria due to the dynamic interplay between mitochondria and other cellular compartments. Platelet mitochondria have a potential to serve as a source of human viable mitochondria when studying mitochondrial physiology and pathogenic mechanisms, as well as for the diagnostics of mitochondrial diseases. The objective of the present study was to perform a detailed evaluation of platelet mitochondrial respiration using high-resolution respirometry. Further, we aimed to explore the limits of sample size and the impact of storage as well as to establish a wide range of reference data from different pediatric and adult cohorts. Our results indicate that platelet mitochondria are well suited for ex-vivo analysis with the need for minute sample amounts and excellent reproducibility and stability.     

Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study

Objective To examine the effect of cardiovascular risk factors before pregnancy on risk of pre-eclampsia.Design Population based prospective study.Setting Linkage between a Norwegian population based study (Nord-Trøndelag health study, HUNT-2) and Norway''s medical birth registry.Participants 3494 women who gave birth after participating in the Nord-Trøndelag health study at baseline; of whom 133 (3.8%) delivered after a pre-eclamptic pregnancy.Main outcome measure Odds ratio of developing pre-eclampsia.Results After adjustment for smoking; previous pre-eclampsia; parity; maternal age, education, and socioeconomic position; and duration between baseline measurements and delivery, positive associations were found between prepregnancy serum levels of triglycerides, cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and blood pressure and risk of pre-eclampsia. The odds ratio of developing pre-eclampsia for women with baseline systolic blood pressures greater than 130 mm Hg (highest fifth) was 7.3 (95% confidence interval 3.1 to 17.2) compared with women with systolic blood pressures less than 111 mm Hg (lowest fifth). Similar results were found for nulliparous and parous women. Women who used oral contraceptives at baseline had half the risk of pre-eclampsia compared with never or former users (0.5, 0.3 to 0.9).Conclusion Women with cardiovascular risk factors may be predisposed to pre-eclampsia.     

Sclerosperma fossils from the late Oligocene of Chilga,north-western Ethiopia

The palm family, Arecaceae, is notoriously depauperate in Africa today, and its evolutionary, paleobiogeographic, and extinction history there are not well documented by fossils. In this article we report the pollen of two new extinct species of the small genus, Sclerosperma (Arecoideae), from a late Oligocene (27–28 Ma) stratum exposed along the Guang River in Chilga Wereda of north-western Ethiopia. The pollen are triporate, and the two taxa can be distinguished from each other and from modern species using a combination of light and scanning electron microscopy, which reveals variations in the finer details of their reticulate to perforate exine sculpture. We also report a palm leaf fragment from a stratum higher in the same section that is in the Arecoideae subfamily, and most likely belongs to Sclerosperma. The implications of these discoveries for the evolutionary history of this clade of African arecoid palms is that their diversification was well underway by the middle to late Oligocene, and they were much more widespread in Africa at that time than they are now, limited to West and Central Africa. Sclerosperma exhibits ecological conservatism, as today it occurs primarily in swamps and flooded forests, and the sedimentology of the Guang River deposits at Chilga indicate a heterogeneous landscape with a high water table. The matrix containing the fossil pollen is lignite, which itself indicates standing water, and a variety of plant macrofossils from higher in the section have been interpreted as representing moist tropical forest or seasonally inundated forest communities.     

Invasion of the Atlantic rock crab (Cancer irroratus) at high latitudes

With the increase in global oceanic trade the establishment of non-indigenous marine organisms has become a major environmental and economic problem worldwide. Recently, the Atlantic rock crab (Cancer irroratus) was reported in Icelandic waters, Eastern North Atlantic. This is the first record of this relatively large crab species outside its natural range, i.e. the east coast of North America. The crab was most likely transferred to Iceland as larvae in ballast water and has successfully established a reproducing population in Icelandic waters. The species is distributed along the southwestern- and western-coast of Iceland. Adult specimens are now common in Faxaflói Bay, Southwest Iceland, but with sporadic occurrences in western and northwestern Icelandic waters. The green crab (Carcinus maenas) and the spider crab (Hyas araneus) are the only native brachyuran decapod species commonly found in its new habitat, but despite its recent colonization the rock crab was the most abundant brachyuran in the areas studied in southwest Iceland. Egg bearing rock crab and green crab females were found from June to October, while egg bearing spider crab females were seen from July to December. In Southwest Iceland both rock crab and green crab larvae were abundant in mid-summer but rare in both spring and autumn, which is opposite of what was observed for the spider crab. The size and abundance of adult crabs, their reproductive conditions, and occurrence of all larval stages, indicate that the Atlantic rock crab has successfully colonized Iceland.     

Urokinase Plasminogen Activator Receptor (uPAR) and Plasminogen Activator Inhibitor-1 (PAI-1) Are Potential Predictive Biomarkers in Early Stage Oral Squamous Cell Carcinomas (OSCC)

Oral squamous cell carcinoma (OSCC) is often associated with metastatic disease and a poor 5 year survival rate. Patients diagnosed with small tumours generally have a more favourable outcome, but some of these small tumours are aggressive and lead to early death. To avoid harmful overtreatment of patients with favourable prognosis, there is a need for predictive biomarkers that can be used for treatment stratification. In this study we assessed the possibility to use components of the plasminogen activator (PA) system as prognostic markers for OSCC outcome and compared this to the commonly used biomarker Ki-67. A tissue-micro-array (TMA) based immunohistochemical analysis of primary tumour tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC was conducted. The expression of the biomarkers was compared with clinicopathological variables and disease specific death. The statistical analyses revealed that low expression of uPAR (p = 0.031) and PAI-1 (p = 0.021) in the tumour cells was significantly associated with low disease specific death in patients with small tumours and no lymph node metastasis (T1N0). The commonly used biomarker, Ki-67, was not associated with disease specific death in any of the groups of patients analysed. The conclusion is that uPAR and PAI-1 are potential predictive biomarkers in early stage tumours and that this warrants further studies on a larger cohort of patients.     

Fine-scale parallel patterns in diversity of small benthic Arctic charr (Salvelinus alpinus) in relation to the ecology of lava/groundwater habitats

It is critical to study factors that are important for origin and maintenance of biological diversity. A comparative approach involving a large number of populations is particularly useful. We use this approach to study the relationship between ecological factors and phenotypic diversity in Icelandic Arctic charr (Salvelinus alpinus). Numerous populations of small benthic charr have evolved in lava springs in Iceland. These charr appear morphologically similar, but differ in important morphological features related to feeding. We found a clear relationship between diversity in morphology, diet, and ecological factors among populations. In particular, there were clear differences in morphology and diet between fish coming from habitats where the lava spring flowed on as a stream compared to habitats where the lava spring flowed into a pond. Our study shows that ecological factors are important for the origin and maintenance of biological diversity. The relationship between phenotype and ecological factors are observed on a fine scale, when comparing numerous populations that are phenotypically similar. This strongly suggests that for understanding, managing, and conserving biological diversity important ecological variables have to be taken into the account.     

Adult male mice emit context-specific ultrasonic vocalizations that are modulated by prior isolation or group rearing environment

Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals.