Abstract
Objective:
To estimate the total energy and micronutrient intakes of children 9–24 months of age and evaluate the probability of adequacy (PA) of the diet in seven MAL-ED sites.
Design:
...Cohort study. Food intake was registered monthly using 24-h recalls beginning at 9 months. We estimated PA for thirteen nutrients and overall mean PA (MPA) by site and 3-month periods considering estimated breast milk intake.
Setting:
Seven sites in Asia, Africa and Latin America.
Participants:
1669 children followed from birth to 24 months of age.
Results:
Median estimated %energy from breast milk ranged from 4 to 70 % at 9–12 months, and declined to 0–39 % at 21–24 months. Iron bioavailability was low for all sites, but many diets were of moderate bioavailability for zinc. PA was optimal for most nutrients in Brazil and South Africa, except for iron and vitamin E (both), calcium and zinc (South Africa). PA for zinc increased only for children consuming a diet with moderate bioavailability. MPA increased 12–24 months as the quantity of complementary foods increased; however, PA for vitamin A remained low in Bangladesh and Tanzania. PA for vitamins D and E and iron was low for most sites and age groups.
Conclusions:
MPA increased from 12 to 24 months as children consumed higher quantities of food, while nutrient density remained constant for most nutrients. Ways to increase the consumption of foods containing vitamins D, E and A, and calcium are needed, as are ways to increase the bioavailability of iron and zinc.
Sphingosine kinase 1 (SphK1) has emerged as an attractive drug target for different diseases. Recently, discovered SphK1 inhibitors have been recommended in cancer therapeutics; however, selectivity ...and potency are great challenges. In this study, a novel series of benzimidazoles was synthesized and evaluated as SphK1 inhibitors. Our design strategy is twofold: It aimed first to study the effect of replacing the 5‐position of the benzimidazole ring with a polar carboxylic acid group on the SphK1‐inhibitory activity and cytotoxicity. Our second aim was to optimize the structures of the benzimidazoles through the elongation of the chain. The enzyme inhibition potentials against all the synthesized compounds toward SphK1 were evaluated, and the results revealed that most of the studied compounds inhibited SphK1 effectively. The binding affinity of the benzimidazole derivatives toward SphK1 was measured by fluorescence binding and molecular docking. Compounds 33, 37, 39, 41, 42, 43, and 45 showed an appreciable binding affinity. Therefore, the SphK1‐inhibitory potentials of compounds 33, 37, 39, 41, 42, 43, and 45 were studied and IC50 values were determined, to reveal high potency. The study showed that these compounds inhibited SphK1 with effective IC50 values. Among the studied compounds, compound 41 was the most effective one with the lowest IC50 value and a high cytotoxicity on a wide spectrum of cell lines. Molecular docking revealed that most of these compounds fit well into the ATP‐binding site of SphK1 and form hydrogen bond interactions with catalytically important residues. Overall, the findings suggest the therapeutic potential of benzimidazoles in the clinical management of SphK1‐associated diseases.
A novel series of benzimidazoles was synthesized and evaluated as sphingosine kinase 1 (SphK1) inhibitors. Compounds 33, 37, 39, 41, 42, 43, and 45, which showed an appreciable binding affinity toward SphK1, also inhibited SphK1 with effective IC50 values. Molecular docking revealed that most of these compounds fit well into the ATP‐binding site of SphK1 and form hydrogen bond interactions with catalytically important residues.
Interest and effort in re-introducing civil supersonic transport (SST) airplanes as a means of travel have surged in the past decade. Current major endeavours are underway for both commercial and ...business supersonic vehicles. The value proposition for these aircraft exists for high-net-worth individuals and business-class travellers who value time savings more than the potential cost associated with supersonic travel. One important driver for the higher travel cost is the increase in fuel consumption for an SST due to higher cruise speeds. Even though the new SSTs in development should be more fuel-efficient than SSTs of the past, comparing to a subsonic aircraft flying the same routes, an SST that burns more fuel while having fewer passengers (pax) on board per trip yields significantly higher fuel burn per passenger for these operations. However, due to the higher ticket costs and other limitations such as noise and emissions, supersonic commercial operation is not expected to capture a large portion of the aviation market. This means that in the broader scope of global aviation, the effect of increased fuel burn per pax on fleet-level carbon dioxide (CO
2
) emissions is unknown. Also, due to uncertainties in the effectiveness of sonic boom reduction technologies, it remains unclear whether supersonic over-land flight will be permitted in the future. This study formulates a methodology that employs a bottom-up approach for estimating the demand for supersonic commercial operations in the coming decades, using only publicly available subsonic baseline-fleet data. The scope of this work focuses specifically on the supersonic commercial aviation market and does not consider the supersonic business jet market. The constraints and limitations identified while using publicly available data is key to understanding the data requirements for executing market assessment studies of this type. The bottom-up methodology for demand estimation is implemented, and the environmental impact of the estimated market is determined. The results identify a supersonic commercial flight demand of 34–776 daily, global flights in 2035, growing to 52–1164 in 2050, corresponding to low and high demand scenarios, respectively. These fleets will contribute approximately 1.43–28.25 megatonnes (MT) of CO
2
to global aviation emissions in 2035, growing to 2.20–42.50 MT of CO
2
in 2050. These emissions in 2035 and 2050 represent a 0.16–3.08% and 0.24–4.63% increase in CO
2
emissions with respect to the 2018 global subsonic commercial aviation fleet.
Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of ...diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.
The restrictions associated with the 2020 COVID-19 pandemic has resulted in changes to young children's daily routines and habits. The impact on their participation in movement behaviours (physical ...activity, sedentary screen time and sleep) is unknown. This international longitudinal study compared young children's movement behaviours before and during the COVID-19 pandemic.
Parents of children aged 3-5 years, from 14 countries (8 low- and middle-income countries, LMICs) completed surveys to assess changes in movement behaviours and how these changes were associated with the COVID-19 pandemic. Surveys were completed in the 12 months up to March 2020 and again between May and June 2020 (at the height of restrictions). Physical activity (PA), sedentary screen time (SST) and sleep were assessed via parent survey. At Time 2, COVID-19 factors including level of restriction, environmental conditions, and parental stress were measured. Compliance with the World Health Organizations (WHO) Global guidelines for PA (180 min/day ≥60 min moderate- vigorous PA), SST (≤1 h/day) and sleep (10-13 h/day) for children under 5 years of age, was determined.
Nine hundred- forty-eight parents completed the survey at both time points. Children from LMICs were more likely to meet the PA (Adjusted Odds Ratio AdjOR = 2.0, 95%Confidence Interval CI 1.0,3.8) and SST (AdjOR = 2.2, 95%CI 1.2,3.9) guidelines than their high-income country (HIC) counterparts. Children who could go outside during COVID-19 were more likely to meet all WHO Global guidelines (AdjOR = 3.3, 95%CI 1.1,9.8) than those who were not. Children of parents with higher compared to lower stress were less likely to meet all three guidelines (AdjOR = 0.5, 95%CI 0.3,0.9).
PA and SST levels of children from LMICs have been less impacted by COVID-19 than in HICs. Ensuring children can access an outdoor space, and supporting parents' mental health are important prerequisites for enabling pre-schoolers to practice healthy movement behaviours and meet the Global guidelines.
The overall goal of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study is to evaluate the ...roles of repeated enteric infection and poor dietary intakes on the development of malnutrition, poor cognitive development, and diminished immune response. The use of 8 distinct sites for data collection from Latin America, sub-Saharan Africa, and South Asia allow for an examination of these relationships across different environmental contexts. Key to testing study hypotheses is the collection of appropriate data to characterize the dietary intakes and nutritional status of study children from birth through 24 months of age. The focus of the current article is on the collection of data to describe the nature and adequacy of infant feeding, energy and nutrient intakes, and the chosen indicators to capture micronutrient status in children over time.
Profunda femoris artery pseudo aneurysm is a rare occurrence following fractures of the proximal femur or their surgical fixation. They usually present late because of the deep position of the ...artery. Patients present with a painful expansile mass in the thigh with or without progressive anaemia. Modalities such as ultrasound scanning may aid in diagnosis but CT arteriography is used mostly for accurate diagnosis and intervention. We report a case of delayed presentation of profunda femoris pseudo aneurysm following dynamic hip screw fixation for intertrochanteric femur fracture.
The Pakistan study site of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study is located in ...Molhan union council of Naushahro Feroze district in the Sindh province. The study site is located in a rural district, where the majority of the population has an agrarian livelihood. Most families are nuclear families and the average household has 7 persons. More than half the women in the region have no formal education, and the median parity is 6. Only 48%–61% of the households across the district, province, and country have access to an improved toilet facility. Similar to the provincial and national estimates, the district has a low rate of exclusive breastfeeding at 6 months, and the prevalence of prelacteal feeding is high. There is also a high proportion of malnourished children. In addition, the acute respiratory infection and diarrheal illness burden and the mortality rates in children <5 years old in the district are high but comparable with the provincial and national estimates. Overall, the district is representative of rural populations at the regional and national level in terms of demographics, socioeconomic status, and general health and mortality indicators.
Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The ...regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer's disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.
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