Search

BACKGROUND Due to interconnected structural determinants including low maternal health knowledge, economic marginalization, and remoteness from low-capacity health centers, ethnic minority women in remote areas of Vietnam face severe maternal, newborn, and child health (MNCH) inequities. As ethnic minorities represent 15% of the Vietnamese population, these disparities are significant. mMOM—a pilot mobile health (mHealth) intervention using SMS text messaging to improve MNCH outcomes among ethnic minority women in northern Vietnam—was implemented from 2013-2016 with promising results. Despite mMOM’s findings, exacerbated MNCH inequities, and digital health becoming more salient amid COVID-19, mHealth has not yet been scaled to address MNCH among ethnic minority women in Vietnam. OBJECTIVE We describe the protocol for adapting, expanding, and exponentially scaling the mMOM intervention qualitatively through adding COVID-19–related MNCH guidance and novel technological components (mobile app and artificial intelligence chatbots) and quantitatively through broadening the geographical area to reach exponentially more participants, within the evolving COVID-19 context. METHODS dMOM will be conducted in 4 phases. (1) Drawing on a review of international literature and government guidelines on MNCH amid COVID-19, mMOM project components will be updated to respond to COVID-19 and expanded to include a mobile app and artificial intelligence chatbots to more deeply engage participants. (2) Using an intersectionality lens and participatory action research approach, a scoping study and rapid ethnographic fieldwork will explore ethnic minority women’s unmet MNCH needs; acceptability and accessibility of digital health; technical capacity of commune health centers; gendered power dynamics and cultural, geographical, and social determinants impacting health outcomes; and multilevel impacts of COVID-19. Findings will be applied to further refine the intervention. (3) dMOM will be implemented and incrementally scaled across 71 project communes. (4) dMOM will be evaluated to assess whether SMS text messaging or mobile app delivery engenders better MNCH outcomes among ethnic minority women. The documentation of lessons learned and dMOM models will be shared with Vietnam’s Ministry of Health for adoption and further scaling up. RESULTS The dMOM study was funded by the International Development Research Centre (IDRC) in November 2021, cofacilitated by the Ministry of Health, and is being coimplemented by provincial health departments in 2 mountainous provinces. Phase 1 was initiated in May 2022, and phase 2 is planned to begin in December 2022. The study is expected to be complete in June 2025. CONCLUSIONS dMOM research outcomes will generate important empirical evidence on the effectiveness of leveraging digital health to address intractable MNCH inequities among ethnic minority women in low-resource settings in Vietnam and provide critical information on the processes of adapting mHealth interventions to respond to COVID-19 and future pandemics. Finally, dMOM activities, models, and findings will inform a national intervention led by the Ministry of Health. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/44720

The ciprofloxacin (CIP) removal ability of a Fe-Cu electrolytic material was examined with respect to pH (2–9), time (15–150 min), shaking speed (100–250 rpm), material mass (0.2–3 g/L), temperature (298, 308, 323) and initial CIP concentration (30–200 mg/L). The Fe-Cu electrolytic materials were fabricated by the chemical plating method, and Fe-C materials were mechanically mixed from iron powder and graphite. The results show that at a pH value of 3, shaking time 120 min, shaking speed 250 rpm, a mass of Fe-Cu, Fe-C material of 2 g/L and initial CIP concentration of 203.79 mg/L, the CIP removal efficiency of Fe-Cu material reached 90.25% and that of Fe-C material was 85.12%. The removal of CIP on Fe-Cu and Fe-C materials follows pseudo-first-order kinetics. The activation energy of CIP removal of Fe-Cu material is 14.93 KJ/mol and of Fe-C material is 16.87 KJ/mol. The positive ΔH proves that CIP removal is endothermic. A negative entropy of 0.239 kJ/mol and 0.235 kJ/mol (which is near zero and is also relatively positive) indicated the rapid removal of the CIP molecules into the removed products.

Mathematics enjoys a special status above all other sciences for one reason: The propositions of mathematics are absolutely certain and indisputable, while those of all other sciences are to some extent controversial and always in danger of being revised by newly discovered facts. This is how the German philosopher Carl Gustav Hempel (1905-1997) describes it.

In mathematical education – for example in so-called modeling cycles – the keyword mathematization is often mentioned as a matter of course as if it were a fixed and generally comprehensible term (Winter, 2016). Occasionally mathematization is described as a translation into mathematics, but it is not clear when the border to mathematics is crossed. Is mathematization merely algebraization (in the sense of formalization) or is looking at a problem with a mathematical way of thinking already a kind of mathematization? In its contribution “The laws of the free fall of Galilei – an exemplary case of mathematization”, Winter has shown, using the example of Galilei indicates not only how demanding but also how stimulating a “real” mathematization of a physical problem can be. (Winter, 2016).

In spite of the increasing demands for subject links within the subjects science, technology, engineering, and mathematics (STEM), there is no agreement on a definition of STEM itself (Baker and Galanti (2017); Fullan (2016)). In the opinion of some authors, STEM can already be spoken of if only two disciplines from this area are integrated (Riordain, Johnston, & Walshe, 2016). The curricular integration of subjects has been investigated by education research for several decades.

International audience; A set of 19 oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against two pathogenic slow-growing mycobacteria, Mycobacterium marinum and Mycobacterium bovis BCG, and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging minimal inhibitory concentrations (MIC) values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M.tb growth only with moderated MIC50, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. Of interest, all OX derivatives exhibited very low toxicity towards host macrophages. Among the six potential OXs identified, HPOX, a selective inhibitor of extracellular M. tb growth, was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP, in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.

International audience; Due to the high number of patients infected by tuberculosis (TB) and the sharp increase of drug resistant TB cases, developing new drugs to fight this disease has become increasingly urgent. In this context, a new class of compound, analogs of the naturally occurring enolphosphates Cyclipostins and Cyclophostin (CyC analogs), offer new therapeutic opportunities. The CyC analogs display potent activity both in vitro and in infected macrophages against several pathogenic mycobacteria including Mycobacterium tuberculosis and Mycobacterium abscessus. Interestingly, these CyC inhibitors target several enzymes with active site serine or cysteine residues that play key roles in mycobacterial lipid and cell wall metabolism. Among them, TesA, a putative thioesterase involved in the synthesis of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), has been identified. These two lipids (PDIMS and PPGLs) are non-covalently bound to the outer cell wall in several human pathogenic mycobacteria and are important virulence factors. Herein, we used biochemical and structural approaches to validate TesA as an effective pharmacological target of the CyC analogs. We have confirmed both thioesterase and esterase activities of TesA, and have shown that the most active inhibitor CyC17 binds covalently to the catalytic Ser104 residue leading to a total loss of enzyme activity. These data were supported by the X-ray structure, obtained at a 2.6 Å resolution, of a complex in which CyC17 is bound to TesA. Our study provides evidence that CyC17 inhibits the activity of TesA, thus paving the way to a new strategy for impairing the PDIM and PGL biosynthesis, potentially decreasing the virulence of associated mycobacterial species.

The progression of mycobacterial diseases requires the development of new therapeutics. This study evaluated the efficacy and selectivity of a panel of Cyclophostin and Cyclipostins analogues (CyCs) against various bacteria and mycobacteria. The activity 26 CyCs was first assayed by the agar plate method. Compounds exhibiting 50–100% growth inhibition were then selected to determine their minimum inhibitory concentrations (MICs) by the resazurin microtiter assay (REMA). The best drug candidate was further tested against clinical mycobacterial isolates and bacteria responsible for nosocomial infections, including 6 Gram-negative bacteria, 5 Gram-positive bacteria, 29 rapid-growing mycobacteria belonging to the Mycobacterium chelonae–abscessus clade and 3 slow-growing mycobacteria ( Mycobacterium marinum , Mycobacterium bovis BCG and Mycobacterium tuberculosis ). Among the 26 CyCs tested, 10 were active and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate ( CyC 17 ) was further tested against 26 clinical strains and showed high selectivity for mycobacteria, with MICs ( M. abscessus infections. Together, these results support the fact that such CyCs represent a new family of potent and selective inhibitors against mycobacteria. This is of particular interest for future chemotherapeutic developments against mycobacterial-associated infections, especially against M. abscessus , the most drug-resistant mycobacterial species.

International audience; An increasing prevalence of cases of drug-resistant tuberculosis requires the development of more efficacious chemotherapies. We previously reported the discovery of a new class of cyclipostins and cyclophostin (CyC) analogs exhibiting potent activity against Mycobacterium tuberculosis both in vitro and in infected macrophages. Competitive labeling/enrichment assays combined with MS have identified several serine or cysteine enzymes in lipid and cell wall metabolism as putative targets of these CyC compounds. These targets included members of the antigen 85 (Ag85) complex (i.e. Ag85A, Ag85B, and Ag85C), responsible for biosynthesis of trehalose dimycolate and mycolylation of arabinogalactan. Herein, we used biochemical and structural approaches to validate the Ag85 complex as a pharmacological target of the CyC analogs. We found that CyC7β, CyC8β, and CyC17 bind covalently to the catalytic Ser124 residue in Ag85C; inhibit mycolyltransferase activity (i.e. the transfer of a fatty acid molecule onto trehalose); and reduce triacylglycerol synthase activity, a property previously attributed to Ag85A. Supporting these results, an X-ray structure of Ag85C in complex with CyC8β disclosed that this inhibitor occupies Ag85C's substrate-binding pocket. Importantly, metabolic labeling of M. tuberculosis cultures revealed that the CyC compounds impair both trehalose dimycolate synthesis and mycolylation of arabinogalactan. Overall, our study provides compelling evidence that CyC analogs can inhibit the activity of the Ag85 complex in vitro and in mycobacteria, opening the door to a new strategy for inhibiting Ag85. The high-resolution crystal structure obtained will further guide the rational optimization of new CyC scaffolds with greater specificity and potency against M. tuberculosis.

Germinated rice seeds were inoculated with Azospirillum strains Mat 2–1b and DA 9–3a, then directly brought into the fields at several places of the Redriver Delta, North Vietnam.