Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria

With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies

Scientific cruise report Elisabeth Mann-Borgese SUMMIX-MESO

Objectives: It was intended to investigate the meso-scale and sub-meso-scale dynamics of the upper layers (upper 80 m) in the central Baltic Sea, using towed instruments and acoustic profilers, to better understand the physical conditions for cyanobacteria blooms. Under optimal weather conditions, we intended to carry out 10 one-day quasi-synoptic surveys by cruising in large meandering patterns (see fig. 1) covering areas of 15 X 15 nautical miles or 8 X 8 nautical miles, depending on the survey mode, see below. This cruise was the meso-scale component of the two-ship SUMMIX experiment together with RV Meteor (Physical and biochemical exchange-, mixing- and transformation processes in the central Baltic Sea during summer stratification and their controls on the cyanobacterial summer bloom) which was intended to be located at a fixed position nearby RV Elisabeth Mann Borgese in order to survey the water column in high vertical, spatial and parameter resolution, including biogeochemical experiments on board. In addition to the physical parameters, also vertical and horizontal zooplankton net tows as well as water samples taken by CTD bottles were planned

Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso. Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03). MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention. ClinicalTrials.gov NCT00354380

Strong Gametocytocidal Effect of Methylene Blue-Based Combination Therapy against Falciparum Malaria: A Randomised Controlled Trial

With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso.An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days.The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline.MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies.(ClinicalTrials.gov) NCT00354380

S2k guideline: Diagnosis and treatment of chronic pruritus

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org

Comparison of two pore sizes of LAE442 scaffolds and their effect on degradation and osseointegration behavior in the rabbit model

The magnesium alloy LAE442 emerged as a possible bioresorbable bone substitute over a decade ago. In the present study, using the investment casting process, scaffolds of the Magnesium (Mg) alloy LAE442 with two different and defined pore sizes, which had on average a diameter of 400 μm (p400) and 500 μm (p500), were investigated to evaluate degradation and osseointegration in comparison to a ß‐TCP control group. Open‐pored scaffolds were implanted in both greater trochanter of rabbits. Ten scaffolds per time group (6, 12, 24, and 36 weeks) and type were analyzed by clinical, radiographic and μ‐CT examinations (2D and 3D). None of the scaffolds caused adverse reactions. LAE442 p400 and p500 developed moderate gas accumulation due to the Mg associated in vivo corrosion, which decreased from week 20 for both pore sizes. After 36 weeks, p400 and p500 showed volume decreases of 15.9 and 11.1%, respectively, with homogeneous degradation, whereas ß‐TCP lost 74.6% of its initial volume. Compared to p400, osseointegration for p500 was significantly better at week 2 postsurgery due to more frequent bone‐scaffold contacts, higher number of trabeculae and higher bone volume in the surrounding area. No further significant differences between the two pore sizes became apparent. However, p500 was close to the values of ß‐TCP in terms of bone volume and trabecular number in the scaffold environment, suggesting better osseointegration for the larger pore size

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells

Aberrant regulation of the Wnt/β-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in APC or β-catenin. However, it has remained a point of controversy whether these mutations are sufficient to activate the pathway or require additional upstream signals. Here we show that colorectal tumours express elevated levels of Wnt3 and Evi/Wls/GPR177. We found that in colon cancer cells, even in the presence of mutations in APC or β-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind β-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or β-catenin depend on Wnt ligands and their secretion for a sufficient level of β-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls