Factors Associated with Catch‐Up Growth in Early Infancy in Rural Pakistan: A Longitudinal Analysis of the Women's Work and Nutrition Study

The adverse health impacts of early infant stunting can be partially ameliorated by early catch‐up growth. Few studies have examined predictors of and barriers to catch‐up growth to identify intervention points for improving linear growth during infancy. This study aimed to estimate the prevalence of, and factors associated with, catch‐up growth among infants in Pakistan. A longitudinal study of mother–infant dyads (n = 1,161) was conducted in rural Sindh province, with enrolment between December 2015 and February 2016 (infants aged 0.5–3 months), and follow‐up (n = 1035) between November 2016 and January 2017 (infants aged 9–15 months). The outcome was catch‐up growth (change in conditional length‐for‐age z‐scores >0.67 between baseline and endline). Associated factors were examined using multivariable logistic regression analyses. The prevalence of stunting was 45.3% at baseline and 60.7% at follow‐up. 22.8% of infants exhibited catch‐up growth over this period. Factors positively associated with catch‐up growth included maternal height (odds ratio (OR) = 1.08 [1.05–1.11]), household wealth (OR = 3.61 [1.90–6.84]), maternal (OR = 2.43 [1.30–4.56]) or paternal (OR = 1.46 [1.05–2.03]) education, and households with two or more adult females (OR = 1.91 [1.26–2.88]). Factors negatively associated with catch‐up growth were two (OR = 0.64 [0.45–0.89]) or three or more (OR = 0.44 [0.29–0.66]) preschool children in the household and the infant being currently breastfed (OR = 0.59 [0.41–0.88]). Catch‐up growth was exhibited among approximately a quarter of infants despite living in challenging environments associated with extremely high rates of early infant stunting. Several modifiable factors were identified that might represent suitable programme intervention points to off‐set early infant stunting in rural Pakistan

Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood–brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents

Maternal BMI mediates the impact of crop-related agricultural work during pregnancy on infant length in rural Pakistan: a mediation analysis of cross-sectional data

Background: Stunted growth in early infancy is a public health problem in low-and-middle income countries. Evidence suggests heavy agricultural work during pregnancy is inversely associated with maternal body mass index (BMI) and infant birth weight in low- and middle-income countries; but pathways linking agricultural work to length-for-age Z-scores (LAZ) in early infancy have not been examined. This study aimed to investigate the relationship between agricultural work during pregnancy, post-natal maternal BMI and LAZ among young infants in rural Pakistan; and explored whether maternal BMI mediated the relationship between agricultural work and infant LAZ.Methods: A cross-sectional survey was conducted from December 2015 to January 2016 in rural Sindh, Pakistan. Mother-infant dyads were recruited via systematic random cluster sampling at 2–12 weeks’ post-partum (n = 1161). Anthropometric measurements (maternal and infant height/length and weight) and questionnaire data were collected. Multivariable linear regression and structural-equation based mediation analyses were used to examineassociations of agricultural work during pregnancy with maternal BMI and infant LAZ.Results: During pregnancy, women reported engaging in livestock-related work (57.0%), crop-related work (42.7%), and cotton harvesting (28.4%). All three forms of agricultural work were negatively associated with maternal BMI (β = − 0.67 [− 1.06; − 0.28], β = − 0.97 [− 1.51; − 0.48]; and β = − 0.87 [− 1.33; − 0.45], respectively). Maternal engagement in cotton harvesting alone was negatively associated with infant LAZ after controlling for confounding factors. The total negative effect of cotton harvesting on infant LAZ was − 0.35 [− 0.53; − 0.16]. The indirect effect ofmaternal BMI on infant LAZ was − 0.06 [− 0.08; − 0.03], revealing that 16% (− 0.06/− 0.35) of the relationship between cotton harvesting and infant LAZ, after adjustment, was mediated via maternal BMI.Conclusion: These results underscore a need to reduce labour-intensive agricultural workload demands during pregnancy, especially in cotton harvesting, to reduce risks of negative maternal energy balance and poor growth outcomes in early infancy.</div

Maternal BMI mediates the impact of crop-related agricultural work during pregnancy on infant length in rural Pakistan: a mediation analysis of cross-sectional data.

BACKGROUND: Stunted growth in early infancy is a public health problem in low-and-middle income countries. Evidence suggests heavy agricultural work during pregnancy is inversely associated with maternal body mass index (BMI) and infant birth weight in low- and middle-income countries; but pathways linking agricultural work to length-for-age Z-scores (LAZ) in early infancy have not been examined. This study aimed to investigate the relationship between agricultural work during pregnancy, post-natal maternal BMI and LAZ among young infants in rural Pakistan; and explored whether maternal BMI mediated the relationship between agricultural work and infant LAZ. METHODS: A cross-sectional survey was conducted from December 2015 to January 2016 in rural Sindh, Pakistan. Mother-infant dyads were recruited via systematic random cluster sampling at 2-12 weeks' post-partum (n = 1161). Anthropometric measurements (maternal and infant height/length and weight) and questionnaire data were collected. Multivariable linear regression and structural-equation based mediation analyses were used to examine associations of agricultural work during pregnancy with maternal BMI and infant LAZ. RESULTS: During pregnancy, women reported engaging in livestock-related work (57.0%), crop-related work (42.7%), and cotton harvesting (28.4%). All three forms of agricultural work were negatively associated with maternal BMI (β = - 0.67 [- 1.06; - 0.28], β = - 0.97 [- 1.51; - 0.48]; and β = - 0.87 [- 1.33; - 0.45], respectively). Maternal engagement in cotton harvesting alone was negatively associated with infant LAZ after controlling for confounding factors. The total negative effect of cotton harvesting on infant LAZ was - 0.35 [- 0.53; - 0.16]. The indirect effect of maternal BMI on infant LAZ was - 0.06 [- 0.08; - 0.03], revealing that 16% (- 0.06/- 0.35) of the relationship between cotton harvesting and infant LAZ, after adjustment, was mediated via maternal BMI. CONCLUSION: These results underscore a need to reduce labour-intensive agricultural workload demands during pregnancy, especially in cotton harvesting, to reduce risks of negative maternal energy balance and poor growth outcomes in early infancy

Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome

The five-year survival rate of lung cancer patients is very low, mainly because most newly diagnosed patients present with locally advanced or metastatic disease. Therefore, early diagnosis is key to the successful treatment and management of lung cancer. Unfortunately, early detection methods of lung cancer are not ideal. In this brief review, we described early detection methods such as chest X-rays followed by bronchoscopy, sputum analysis followed by cytological analysis, and low-dose computed tomography (LDCT). In addition, we discussed the potential of metabolomic fingerprinting, compared to that of other biomarkers, including molecular targets, as a low-cost, high-throughput blood-based test that is both feasible and affordable for early-stage lung cancer screening of at-risk populations. Accordingly, we proposed a paradigm shift to metabolomics as an alternative to molecular and proteomic-based markers in lung cancer screening, which will enable blood-based routine testing and be accessible to those patients at the highest risk for lung cancer.Medicine, Faculty ofNon UBCInfectious Diseases, Division ofMedicine, Department ofReviewedFacultyResearche

Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)&mdash;A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood&ndash;brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents

Comparison of Stapler, Single Layer and Double Layer Techniques for Colon Closure in Dogs

The present study was performed on 18 healthy dogs (aged 16.80±1.22 months) and body weight (17.07± 2.21 kg) to determine the best suturing technique among single layer, double layer and stapler technique for the closure of colon in dogs. All dog were divided into three groups, placing 6 animals in each group, i.e. group A was closed with single layer suture technique, group B was closed with double layer suture technique and group C was closed with stapler technique. The number of stitches required for colon closure were 8.83, 16.33 and 9.16 in groups –A, B and C respectively. The mean number of stitches and time taken for the completion of double layer technique was significantly higher (

Liquid Biopsy in Lung Cancer Screening: The Contribution of Metabolomics. Results of A Pilot Study

Background: Lung cancer is the most common cause of cancer-related deaths worldwide. Early diagnosis is crucial to increase the curability chance of the patients. Low dose CT screening can reduce lung cancer mortality, but it is associated with several limitations. Metabolomics is a promising technique for cancer diagnosis due to its ability to provide chemical phenotyping data. The intent of our study was to explore metabolomic effects and profiles of lung cancer patients to determine if metabolic perturbations in the SSAT-1/polyamine pathway can distinguish between healthy participants and lung cancer patients as a diagnostic and treatment monitoring tool. Patients and Methods: Plasma samples were collected as part of the SSAT1 Amantadine Cancer Study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and quantify metabolite concentrations in lung cancer patient and control samples. Standard statistical analyses were performed to determine whether metabolite concentrations could differentiate between healthy subjects and lung cancer patients, as well as risk prediction modeling applied to determine whether metabolic profiles could provide an indication of cancer progression in later stage patients. Results: A panel consisting of 14 metabolites, which included 6 metabolites in the polyamine pathway, was identified that correctly discriminated lung cancer patients from controls with an area under the curve of 0.97 (95% CI: 0.875-1.0). Conclusion: When used in conjunction with the SSAT-1/polyamine pathway, these metabolites may provide the specificity required for diagnosing lung cancer from other cancer types and could be used as a diagnostic and treatment monitoring tool

Supplementary Appendices for 'Maternal BMI mediates the impact of crop-related agricultural work during pregnancy on infant length in rural Pakistan: a mediation analysis of cross-sectional data'

Contents:Appendix 1. Sampling.Appendix 2. Baseline survey questionnaire.Appendix 3. Hypothesized models of pathways related to maternal BMI represented on a directed acyclic graph (DAG).Appendix 4. Sample flow chart.Abstract:BackgroundStunted growth in early infancy is a public health problem in low-and-middle income countries. Evidence suggests heavy agricultural work during pregnancy is inversely associated with maternal body mass index (BMI) and infant birth weight in low- and middle-income countries; but pathways linking agricultural work to length-for-age Z-scores (LAZ) in early infancy have not been examined. This study aimed to investigate the relationship between agricultural work during pregnancy, post-natal maternal BMI and LAZ among young infants in rural Pakistan; and explored whether maternal BMI mediated the relationship between agricultural work and infant LAZ.MethodsA cross-sectional survey was conducted from December 2015 to January 2016 in rural Sindh, Pakistan. Mother-infant dyads were recruited via systematic random cluster sampling at 2–12 weeks’ post-partum (n = 1161). Anthropometric measurements (maternal and infant height/length and weight) and questionnaire data were collected. Multivariable linear regression and structural-equation based mediation analyses were used to examine associations of agricultural work during pregnancy with maternal BMI and infant LAZ.ResultsDuring pregnancy, women reported engaging in livestock-related work (57.0%), crop-related work (42.7%), and cotton harvesting (28.4%). All three forms of agricultural work were negatively associated with maternal BMI (β = − 0.67 [− 1.06; − 0.28], β = − 0.97 [− 1.51; − 0.48]; and β = − 0.87 [− 1.33; − 0.45], respectively). Maternal engagement in cotton harvesting alone was negatively associated with infant LAZ after controlling for confounding factors. The total negative effect of cotton harvesting on infant LAZ was − 0.35 [− 0.53; − 0.16]. The indirect effect of maternal BMI on infant LAZ was − 0.06 [− 0.08; − 0.03], revealing that 16% (− 0.06/− 0.35) of the relationship between cotton harvesting and infant LAZ, after adjustment, was mediated via maternal BMI.ConclusionThese results underscore a need to reduce labour-intensive agricultural workload demands during pregnancy, especially in cotton harvesting, to reduce risks of negative maternal energy balance and poor growth outcomes in early infancy.</div