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Background: The development of communication, speech and language follows three stages (development of the parent--child relationship, interactions and actual speech and language acquisition). Children born with cleft lip and/or palate are at increased risk of communicative problems while parents may be going through an emotionally difficult time. Early parent-implemented logopaedic intervention that supports both parents and child is important. Three systematic reviews have examined the effects of early speech and language interventions, but not their structure and content. Aims: To investigate which early parent-implemented logopaedic interventions already exist for children with cleft lip and/or palate, and to evaluate their structure, content and time of onset against the three stages of communicative development. Methods: Six databases (PubMed, Embase, Web of Science, APA PsycInfo, Cinahl and Scopus) were searched between inception and 31 March 2023 to identify published articles that reported early parent-implemented logopaedic interventions in children with cleft lip and/or palate, aged 0 to 3 years, clearly describing the strategies used to train parents. Two authors independently assessed the eligibility of the studies. Quality assessment was conducted using the Physiotherapy Evidence Database quality assessment tool, Single-Case Experimental Design tool and the National Institutes of Health pre-post-study tools. The structure and content of the interventions were analysed taking into account the needs and difficulties of both the parents and the child according to the three stages of communicative development. Main contribution: The systematic literature search identified four studies that met the inclusion criteria. Three of them had a Level of Evidence III and one study had a Level of Evidence IV. Strategies appropriate for Stage 1 of communicative development (parent--child relationship) are well represented in only one study, but the psychosocial needs of parents are currently not included in these programmes. However, research shows that parental emotional difficulties can adversely impact a child's communicative development. Strategies appropriate for Stage 2 (promoting social interactions) are better represented. However, strategies appropriate for Stage 3 (acquiring correct speech and language patterns) are most represented in all intervention programmes. Conclusions: Three out of four intervention programmes focus on Stage 3 (actual speech and language stimulation). Stage 1 is underrepresented and the psychosocial needs of parents are currently not included in existing intervention programmes. Further research is needed in close collaboration with psychologists to construct a comprehensive, longitudinal, developmentally appropriate intervention programme that equally represents the three stages of communicative development and considers the psychosocial needs of parents.

Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer's disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating β-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.

Given the importance of soil for the global carbon cycle, it is essential to understand not only how much carbon soil stores but also how long this carbon persists. Previous studies have shown that the amount and age of soil carbon are strongly affected by the interaction of climate, vegetation, and mineralogy. However, these findings are primarily based on studies from temperate regions and from fine-scale studies, leaving large knowledge gaps for soils from understudied regions such as sub-Saharan Africa. In addition, there is a lack of data to validate modeled soil C dynamics at broad scales. Here, we present insights into organic carbon cycling, based on a new broad-scale radiocarbon and mineral dataset for sub-Saharan Africa. We found that in moderately weathered soils in seasonal climate zones with poorly crystalline and reactive clay minerals, organic carbon persists longer on average (topsoil: 201 ± 130 years; subsoil: 645 ± 385 years) than in highly weathered soils in humid regions (topsoil: 140 ± 46 years; subsoil: 454 ± 247 years) with less reactive minerals. Soils in arid climate zones (topsoil: 396 ± 339 years; subsoil: 963 ± 669 years) store organic carbon for periods more similar to those in seasonal climate zones, likely reflecting climatic constraints on weathering, carbon inputs and microbial decomposition. These insights into the timescales of organic carbon persistence in soils of sub-Saharan Africa suggest that a process-oriented grouping of soils based on pedo-climatic conditions may be useful to improve predictions of soil responses to climate change at broader scales.

No-till (NT) cropping systems have been proposed as a strategy to combat soil degradation by storing soil organic carbon (SOC) and total nitrogen (TN). We quantified the impacts of NT cropping systems on the changes in SOC and TN stocks and in particulate and mineral-associated organic matter fractions (POM and MAOM), to 100 cm depth, from three 13-year-old experiments in a tropical red Oxisol in Cambodia using diachronic and equivalent soil mass approaches. Established in 2009 and arranged in a randomized complete-block design with triplicates, the experiments included maize (MaiEx)-, soybean (SoyEx)-, and cassava (CasEx)-based cropping systems. Each experiment comprised three treatments: (1) mono-cropping of main crops (maize, soybean, and cassava) under conventional tillage (CTM); (2) mono-cropping of main crops under NT systems with the use of cover crops (NTM); and (3) bi-annual rotation of main crops under NT systems with the use of cover crops (NTR), with both crops being presented every year and represented by NTR1 and NTR2. Soil samples were collected in 2021, 10 years after the last sampling. All the NT systems significantly (p<0.05) increased SOC stock in the topsoil in SoyEx and MaiEx and down to 40 cm in CasEx. Considering the whole profile (0–100 cm), the SOC accumulation rates ranged from 0.86 to 1.47 and from 0.70 to 1.07 Mg C ha−1 yr−1 in MaiEx and CasEx, respectively. Although SOC stock significantly increased in CTM at 0–20 cm in MaiEx and CasEx, it remained stable at 0–100 cm in all the experiments. At 0–5 cm, NTR systems significantly increased TN stock in all the experiments, while, in NTM systems, it was only significant in MaiEx and SoyEx. At 0–100 cm, TN stock in all the experiments remained stable under NTR systems, whereas a significant decrease was observed under NTM systems in SoyEx and CasEx. Although C-POM stock significantly increased under all NT systems limited to 0–10 cm in MaiEx and SoyEx, all the NT systems significantly increased C-MAOM stock in the 0–10 cm layer in MaiEx and SoyEx and down to 40 cm in CasEx. All the NT systems significantly increased N-POM stock at 0–10 cm in MaiEx and SoyEx, while a significant decreased in N-MAOM stock was observed below 5 cm in CasEx and below 40 cm in MaiEx and SoyEx. Our findings showed that long-term NT systems with crop species diversification accumulated SOC not only on the surface but also in the whole profile by increasing SOC in both the POM and MAOM, even in the cassava-based system. This study highlights the potential of NT systems for storing SOC over time but raises questions about soil N dynamics.

We present results of simulations performed with a physical–biogeochemical ocean model of the Mediterranean Sea for the Last Glacial Maximum (LGM) and analyse the differences in physical and biochemical states between the historical period and the LGM. Long-term simulations with an Earth system model based on ice sheet reconstructions provide the necessary atmospheric forcing data, oceanic boundary conditions at the entrance to the Mediterranean Sea, and river discharge to the entire basin. Our regional model accounts for changes in bathymetry due to ice sheet volume changes, reduction in atmospheric CO2 concentration, and an adjusted aeolian dust and iron deposition. The physical ocean state of the Mediterranean during the LGM shows a reduced baroclinic water exchange at the Strait of Gibraltar, a more sluggish zonal overturning circulation, and the relocation of intermediate and deep-water-formation areas – all in line with estimates from palaeo-sediment records or previous modelling efforts. Most striking features of the biogeochemical realm are a reduction in the net primary production, an accumulation of nutrients below the euphotic zone, and an increase in the organic matter deposition at the seafloor. This seeming contradiction of increased organic matter deposition and decreased net primary production challenges our view of possible changes in surface biological processes during the LGM. We attribute the origin of a reduced net primary production to the interplay of increased stability of the upper water column, changed zonal water transport at intermediate depths, and lower water temperatures, which slow down all biological processes during the LGM. Cold water temperatures also affect the remineralisation rates of organic material, which explains the simulated increase in the organic matter deposition, which is in good agreement with sediment proxy records. In addition, we discuss changes in an artificial tracer which captures the surface ocean temperature signal during organic matter production. A shifted seasonality of the biological production in the LGM leads to a difference in the recording of the climate signal by this artificial tracer of up to 1 K. This could be of relevance for the interpretation of proxy records like, e.g., alkenones. Our study not only provides the first consistent insights into the biogeochemistry of the glacial Mediterranean Sea but will also serve as the starting point for transient simulations of the last deglaciation.

Sustainable intensification schemes such as integrated soil fertility management (ISFM) are a proposed strategy to close yield gaps, increase soil fertility, and achieve food security in sub-Saharan Africa. Biogeochemical models such as DayCent can assess their potential at larger scales, but these models need to be calibrated to new environments and rigorously tested for accuracy. Here, we present a Bayesian calibration of DayCent, using data from four long-term field experiments in Kenya in a leave-one-site-out cross-validation approach. The experimental treatments consisted of the addition of low- to high-quality organic resources, with and without mineral nitrogen fertilizer. We assessed the potential of DayCent to accurately simulate the key elements of sustainable intensification, including (1) yield, (2) the changes in soil organic carbon (SOC), and (3) the greenhouse gas (GHG) balance of CO2 and N2O combined. Compared to the initial parameters, the cross-validation showed improved DayCent simulations of maize grain yield (with the Nash–Sutcliffe model efficiency (EF) increasing from 0.36 to 0.50) and of SOC stock changes (with EF increasing from 0.36 to 0.55). The simulations of maize yield and those of SOC stock changes also improved by site (with site-specific EF ranging between 0.15 and 0.38 for maize yield and between −0.9 and 0.58 for SOC stock changes). The four cross-validation-derived posterior parameter distributions (leaving out one site each) were similar in all but one parameter. Together with the model performance for the different sites in cross-validation, this indicated the robustness of the DayCent model parameterization and its reliability for the conditions in Kenya. While DayCent poorly reproduced daily N2O emissions (with EF ranging between −0.44 and −0.03 by site), cumulative seasonal N2O emissions were simulated more accurately (EF ranging between 0.06 and 0.69 by site). The simulated yield-scaled GHG balance was highest in control treatments without N addition (between 0.8 and 1.8 kg CO2 equivalent per kg grain yield across sites) and was about 30 % to 40 % lower in the treatment that combined the application of mineral N and of manure at a rate of 1.2 t C ha−1 yr−1. In conclusion, our results indicate that DayCent is well suited for estimating the impact of ISFM on maize yield and SOC changes. They also indicate that the trade-off between maize yield and GHG balance is stronger in low-fertility sites and that preventing SOC losses, while difficult to achieve through the addition of external organic resources, is a priority for the sustainable intensification of maize production in Kenya.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study.

ABSTRACT Taniborbactam (formerly VNRX-5133) is a novel, investigational boronic acid β-lactamase inhibitor. The combination of cefepime (FEP) with taniborbactam is active against Enterobacterales carrying class A, B, C, and/or D enzymes. We assessed the activity of FEP-taniborbactam against Enterobacterales clinical strains carrying blaOXA-48 (N = 50, 100%), of which 78% harbored at least one extended-spectrum β-lactamase (ESBL). CLSI-based agar dilution susceptibility testing was conducted using FEP-taniborbactam and comparators FEP, meropenem-vaborbactam (MVB), and ceftazidime-avibactam (CZA). The addition of taniborbactam lowered FEP MICs to the provisionally susceptible range of ≤16 µg/mL; the MIC90 value decreased from ≥64 µg/mL for FEP to 4 µg/mL for FEP-taniborbactam. Notably, FEP-taniborbactam MIC50/MIC90 values (0.5/4 µg/mL) were lower than those for MVB (1/16 µg/mL) and comparable to those for CZA (0.5/1 µg/mL). Time-kill assays with E. coli clinical strains DOV (blaOXA-48, blaCTX-M-15, blaTEM-1, and blaOXA-1) and MLI (blaOXA-48, blaVEB, blaTEM-1, and blaCMY-2) revealed that FEP-taniborbactam at concentrations 1×, 2×, and 4× MIC displayed time-dependent reductions in the number of CFU/mL from 0 to 6 h, and at 4× MIC demonstrated bactericidal activity (3 log10 reduction in CFU/mL at 24 h). Therefore, taniborbactam in combination with FEP was highly active against this diverse panel of Enterobacterales with blaOXA-48 and represents a potential addition to our antibiotic arsenal.IMPORTANCEOXA-48-like β-lactamases are class D carbapenemases widespread in Klebsiella pneumoniae and other Enterobacterales and are associated with carbapenem treatment failures. As up to 80% of OXA-48-like positive isolates coproduce extended-spectrum β-lactamases, a combination of β-lactams with broad-spectrum β-lactamase inhibitors is required to counteract all OXA-48-producing strains effectively. Herein, we evaluated the activity of cefepime-taniborbactam against 50 clinical strains producing OXA-48. We report that adding taniborbactam shifted the minimum inhibitory concentration (MIC) toward cefepime’s susceptible range, restoring its antimicrobial activity. Notably, cefepime-taniborbactam MIC50/MIC90 values (0.5/4 µg/mL) were comparable to ceftazidime-avibactam (0.5/1 µg/mL). Finally, time-kill assays revealed sustained bactericidal activity of cefepime-taniborbactam for up to 24 h. In conclusion, cefepime-taniborbactam will be a welcome addition to the antibiotic arsenal to combat Enterobacterales producing OXA-48.

Predicting the quantity of soil organic carbon (SOC) requires understanding how different factors control the amount of SOC. Land use has a major influence on the function of the soil as a carbon sink, as shown by substantial organic carbon (OC) losses from the soil upon deforestation. However, predicting the degree to which land use change affects the OC content in soils and the depth down to which this occurs requires context-specific information related to, for example, climate, geochemistry, and land use history. In this study, 266 samples from forests and agricultural fields were collected from 94 soil profiles down to 300 cm depth in a subtropical region (Arvorezinha, southern Brazil) to study the impact of land use on the amount of stabilized OC along the soil profile. We found that the stabilized OC content was not affected by land use below a depth of 90 cm. Along the soil profile, the amount of stabilized OC was predominantly controlled by land use and depth in addition to the silt and clay content and aluminium ion concentrations. Below 100 cm, none of the soil profiles reached a concentration of stabilized OC above 50 % of the stabilized OC saturation point (i.e. the maximum OC concentration that can physically be stabilized in these soils). Based on these results, we argue that it is unlikely that deeper soil layers can serve as an OC sink over a timescale relevant to global climate change due to the limited OC input in these deeper layers. Furthermore, we found that the soil weathering degree was not a relevant control on the amount of stabilized OC in our profiles because of the high weathering degree of the studied soils. It is therefore suggested that, while the soil weathering degree might be an effective controlling factor of OC stabilization over a large spatial scale, it is not an informative measure for this process at regional and local scales (with similar climate, bedrock, and weathering history) in highly weathered soils.

Soil acidification and low nutrient availability are two major challenges facing agriculture in most regions of East Africa, resulting in aluminum toxicity and poor crop yields. The amendment of local sediments to cropland can potentially alleviate these challenges, but responses are variable. In this study, we investigated the potential of two different local sediments influenced by volcanic deposits to increase soil pH, Si and P availability and reduce Al toxicity, thereby improve barley yield. Hence, a field experiment was established in Eldoret, Western Kenya, using 1% and 3% addition by weight of two sediments in barley cultivated plots. The Baringo 3% amendment significantly increased soil pH (from 4.7 to 7.0), the available P content (from 0.01 mg g−1 to 0.02 mg g−1) and decreased the Al availability (from 3.03 mg g−1–2.17 mg g−1). This resulted in a barley yield of 4.7 t/ha (+1061%). The Nakuru 3% and Baringo 1% amendments increased yield to 2–3 t/ha, while the Nakuru 1% did not significantly increase yield. These results highlight that, from a biophysical perspective, there are natural and local opportunities to reduce soil acidification and to partly replace mineral fertilizer, but its magnitude depends on the sediment and the amendment rate.

Extracellular vesicles (EVs) contain microRNAs (miRNAs), which are important regulators of embryonic development. Nevertheless, little is known about the precise molecular processes controlling blastocyst development and quality. In a previous study, we identified bta-miR-665 as one of the miRNAs more abundantly present in extracellular vesicles of embryo-conditioned culture media of blastocysts compared to degenerate ones. Here, we investigated the effect and regulatory roles of bta-miR-665 in blastocyst development by supplementation of bta-miR-665 mimics or inhibitors to the culture media. Supplementation of bta-miR-665 mimics improved cleavage and blastocyst rate (P < 0.01), and blastocyst quality as indicated by increased inner cell mass rates and reduced apoptotic cell ratios (P < 0.01). Furthermore, supplementation of bta-miR-665 inhibitors had the opposite effect on these phenotypes. Low input transcriptome analysis and RT-qPCR revealed that bta-miR-665 acts on genes linked to microtubule formation and apoptosis/cell proliferation. These insights not only elucidate the important role of bta-miR-665 in embryo development, but also underscore its potential in improving reproductive efficiency in bovine embryo culture.

The concept of soil organic carbon (SOC) saturation emerged a bit more than 2 decades ago as our mechanistic understanding of SOC stabilization increased. Recently, the further testing of the concept across a wide range of soil types and environments has led some people to challenge the fundamentals of soil C saturation. Here, we argue that, to test this concept, one should pay attention to six fundamental principles or “rights” (R's): the right measures, the right units, the right dispersive energy and application, the right soil type, the right clay type, and the right saturation level. Once we take care of those six rights across studies, we find a maximum of C stabilized by minerals and estimate based on current data available that this maximum stabilization is around 82 ± 4 g C kg−1 silt + clay for 2 : 1-clay-dominated soils while most likely being only around 46 ± 4 g C kg−1 silt + clay for 1 : 1-clay-dominated soils. These estimates can be further improved using more data, especially for different clay types across varying environmental conditions. However, the bigger challenge is a matter of which C sequestration strategies to implement and how to implement them in order to effectively reach this 82/46 g C kg−1 silt + clay in soils across the globe.

Maintaining soil organic matter (SOM) is crucial for healthy and productive agricultural soils and requires understanding at the process level, including the role of SOM protection by soil aggregates and the connection between microbial growth and aggregate formation. We developed the Soil Aggregation through Microbial Mediation (SAMM) model, to represent this important connection. The pools of SAMM are fully measurable, and we calibrated and evaluated it against data from a long-term bare fallow experiment in a tropical sandy soil. This experiment received additions of plant litter of different compositions, which resulted in twice the soil carbon stocks in the best treatment compared to the control (about 8 vs. 4 t C ha−1 in 0–15 cm soil depth) after 25 years. As hypothesized, the SAMM model effectively represented the microbial growth response after the addition of litter and the subsequent formation and later destabilization of aggregates. The low correlations between different calibrated model parameters (r for all parameters; r>0.4 for only 4 of 22) showed that SAMM is parsimonious. SAMM was able to capture differences between treatments in soil organic carbon (Nash–Sutcliffe modeling efficiency (EF) of 0.68), microbial nitrogen (EF of 0.24), and litter carbon (EF of 0.80). The amount of carbon within the aggregates (EF of 0.60) and in the free silt and clay fraction (EF of 0.24) was also simulated very well to satisfactorily. Our model results suggested that in spite of the sandy soil, up to 50 % of carbon stocks were stabilized through aggregate protection mechanisms; and that microbial and physical aggregate formation coexists. A version of the SAMM model without aggregate protection (SAMMnoAgg) initially failed to stabilize soil organic carbon (EF decreased to −3.68) and the simulation of microbial nitrogen worsened (EF of 0.13). By recalibrating SAMMnoAgg, it was possible to partially correct for the lack of aggregate protection by reducing the rate of mineral-attached carbon decomposition by about 85 % (EF of 0.68, 0.75, and 0.18 for SOC, litter carbon, and microbial nitrogen, respectively). However, the slightly better evaluation statistics of SAMM (e.g., Akaike information criterion of 5351 vs. 5554) suggest that representing aggregate dynamics in SOM models can be beneficial and necessary to understand the mechanism behind SOM dynamics. Our results indicate that current models without aggregate formation partly compensate for the absence of aggregate protection by lowering the turnover rates of other pools. Thus, they remain suitable options where data on aggregate associated carbon are not available.

Conservation agriculture (CA), combining reduced or no tillage, permanent soil cover, and improved rotations, is often promoted as a climate-smart practice. However, our understanding of the impact of CA and its respective three principles on top- and subsoil organic carbon stocks in the low-input cropping systems of sub-Saharan Africa is rather limited. This study was conducted at two long-term experimental sites established in Zimbabwe in 2013. The soil types were abruptic Lixisols at Domboshava Training Centre (DTC) and xanthic Ferralsol at the University of Zimbabwe farm (UZF). The following six treatments, which were replicated four times, were investigated: conventional tillage (CT), conventional tillage with rotation (CTR), no tillage (NT), no tillage with mulch (NTM), no tillage with rotation (NTR), and no tillage with mulch and rotation (NTMR). Maize (Zea mays L.) was the main crop, and treatments with rotation included cowpea (Vigna unguiculata L. Walp.). The soil organic carbon (SOC) concentration and soil bulk density were determined for samples taken from depths of 0–5, 5–10, 10–15, 15–20, 20–30, 30–40, 40–50, 50–75 and 75–100 cm. Cumulative organic inputs to the soil were also estimated for all treatments. SOC stocks at equivalent soil mass were significantly (p) higher in the NTM, NTR and NTMR treatments compared with the NT and CT treatments in the top 5 cm and top 10 cm layers at UZF, while SOC stocks were only significantly higher in the NTM and NTMR treatments compared with the NT and CT treatments in the top 5 cm at DTC. NT alone had a slightly negative impact on the top SOC stocks. Cumulative SOC stocks were not significantly different between treatments when considering the whole 100 cm soil profile. Our results show the overarching role of crop residue mulching in CA cropping systems with respect to enhancing SOC stocks but also that this effect is limited to the topsoil. The highest cumulative organic carbon inputs to the soil were observed in NTM treatments at the two sites, and this could probably explain the positive effect on SOC stocks. Moreover, our results show that the combination of at least two CA principles including mulch is required to increase SOC stocks in these low-nitrogen-input cropping systems.