Developing shelf-stable Microbiota Directed Complementary Food (MDCF) prototypes for malnourished children: Study protocol for a randomized, single-blinded, clinical study

BACKGROUND: Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria. METHODS: A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF. DISCUSSION: This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021

Influence of Chain Length of Alcohols on Stokes' Shift Dynamics in Catanionic Vesicles

In this paper, we explore the

PloS one

Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFalpha secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC(50) = 1.4 nM) than the other subtypes (PDE4A, IC(50) = 44 nM; PDE4B, IC(50) = 48 nM; and PDE4D, IC(50) = 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (K(i) = 148 nM) in comparison to rolipram (K(i) = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFalpha secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease

STECF Fisheries Dependent Information – FDI (STECF-19-11)

Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4–10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. The STECF reviewed the report of the EWG on Fisheries-dependent Information during its winter 2019 plenary meeting

Preliminary test results of LGADs from Teledyne e2v for the LHC’s High-Luminosity upgrade

This paper presents initial testing of the first batch of LGAD sensors fabricated by Teledyne e2v in collaboration with the University of Birmingham, University of Oxford, Rutherford Appleton Laboratory and the Open University. Wafers with different energy and dose of the gain layer implant have been characterised with IV, CV and gain measurements. The same set of measurements were made using PiN diodes fabricated on the same wafer as a reference. Results are in-line with expectations and with LGADs produced at more established vendors. Preliminary results suggests Te2v LGADs have a moderate gain in the order of 10 to 50 before irradiation at operational voltages well below breakdown, as required for optimal timing resolution

Depletion depth studies with the MALTA2 sensor, a depleted monolithic active pixel sensor

MALTA2 is a depleted monolithic active pixel sensor (DMAPS) developed in the Tower 180 nm CMOS imaging process. Monolithic CMOS sensors offer advantages over current hybrid imaging sensors both in terms of increased tracking performance due to lower material budget but also in terms of ease of integration and construction costs due to the monolithic design. Current research and development efforts are aimed towards radiation-hard designs up to 100 Mrad in Total Ionizing Dose and 3 × 1015 1 MeV neq / cm2 in Non-Ionizing Energy Loss. One important property of a sensor’s radiation hardness is the depletion depth at which efficient charge collection is achieved via drift movement. Grazing angle test-beam data was taken during the 2023 SPS CERN test beam with the MALTA telescope and Edge Transient Current Technique studies were performed at DESY in order to develop a quantitative study of the depletion depth for un-irradiated, epitaxial MALTA2 samples. The study is planned to be extended for irradiated and Czochralski MALTA2 samples