Self-monitoring of blood glucose levels among pregnant individuals with gestational diabetes: a systematic review and meta-analysis.

Introduction: The World Health Organization (WHO) recommends treatment and management of gestational diabetes (GD) through lifestyle changes, including diet and exercise, and self-monitoring blood glucose (SMBG) to inform timely treatment decisions. To expand the evidence base of WHO's guideline on self-care interventions, we conducted a systematic review of SMBG among pregnant individuals with GD. Setting: Following PRISMA guidelines, we searched PubMed, CINAHL, LILACS, and EMBASE for publications through November 2020 comparing SMBG with clinic-based monitoring during antenatal care (ANC) globally. Primary and secondary outcome measures: We extracted data using standardized forms and summarized maternal and newborn findings using random effects meta-analysis in GRADE evidence tables. We also reviewed studies on values, preferences, and costs of SMBG. Results: We identified 6 studies examining SMBG compared to routine ANC care, 5 studies on values and preferences, and 1 study on costs. Nearly all were conducted in Europe and North America. Moderate-certainty evidence from 3 randomized controlled trials (RCTs) showed that SMBG as part of a package of interventions for GD treatment was associated with lower rates of preeclampsia, lower mean birthweight, fewer infants born large for gestational age, fewer infants with macrosomia, and lower rates of shoulder dystocia. There was no difference between groups in self-efficacy, preterm birth, C-section, mental health, stillbirth, or respiratory distress. No studies measured placenta previa, long-term complications, device-related issues, or social harms. Most end-users supported SMBG, motivated by health benefits, convenience, ease of use, and increased confidence. Health workers acknowledged SMBG's convenience but were wary of technical problems. One study found SMBG by pregnant individuals with insulin-dependent diabetes was associated with decreased costs for hospital admission and length of stay. Conclusion: SMBG during pregnancy is feasible and acceptable, and when combined in a package of GD interventions, is generally associated with improved maternal and neonatal health outcomes. However, research from resource-limited settings is needed. Systematic Review Registration: PROSPERO CRD42021233862.

Self-monitoring of blood pressure among women with hypertensive disorders of pregnancy: a systematic review.

BACKGROUND: The World Health Organization (WHO) recommends self-monitoring of blood pressure (SMBP) for hypertension management. In addition, during the COVID-19 response, WHO guidance also recommends SMBP supported by health workers although more evidence is needed on whether SMBP of pregnant individuals with hypertension (gestational hypertension, chronic hypertension, or pre-eclampsia) may assist in early detection of pre-eclampsia, increase end-user autonomy and empowerment, and reduce health system burden. To expand the evidence base for WHO guideline on self-care interventions, we conducted a systematic review of SMBP during pregnancy on maternal and neonatal outcomes. METHODS: We searched for publications that compared SMBP with clinic-based monitoring during antenatal care. We included studies measuring any of the following outcomes: maternal mortality, pre-eclampsia, long-term risk and complications, autonomy, HELLP syndrome, C-section, antenatal hospital admission, adverse pregnancy outcomes, device-related issues, follow-up care with appropriate management, mental health and well-being, social harms, stillbirth or perinatal death, birthweight/size for gestational age, and Apgar score. After abstract screening and full-text review, we extracted data using standardized forms and summarized findings. We also reviewed studies assessing values and preferences as well as costs of SMBP. RESULTS: We identified 6 studies meeting inclusion criteria for the effectiveness of SMBP, 6 studies on values and preferences, and 1 study on costs. All were from high-income countries. Overall, when comparing SMBP with clinic-monitoring, there was no difference in the risks for most of the outcomes for which data were available, though there was some evidence of increased risk of C-section among pregnant women with chronic hypertension. Most end-users and providers supported SMBP, motivated by ease of use, convenience, self-empowerment and reduced anxiety. One study found SMBP would lower health sector costs. CONCLUSION: Limited evidence suggests that SMBP during pregnancy is feasible and acceptable, and generally associated with maternal and neonatal health outcomes similar to clinic-based monitoring. However, more research is needed in resource-limited settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021233839 .

Mediterranean-Style Diet and Risk of Preeclampsia by Race in the Boston Birth Cohort.

Background Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Given its large public health burden, there is a need to identify modifiable factors that can be targeted for preeclampsia prevention. In this study, we examined whether a Mediterranean-style diet is protective for preeclampsia in a large cohort of racially and ethnically diverse, urban, low-income women. Methods and Results We used data from the Boston Birth Cohort. Maternal sociodemographic and dietary data were obtained via interview and food frequency questionnaire within 24 to 72 hours postpartum, respectively. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records. We derived a Mediterranean-style diet score from the food frequency questionnaire and performed logistic regression to examine the association of the Mediterranean-style diet score with preeclampsia. Of 8507 women in the sample, 848 developed preeclampsia. 47% were Black, 28% were Hispanic, and the remaining were White/Other. After multivariable adjustment, greatest adherence with MSD was associated with lower preeclampsia odds (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% CI, 0.64-0.96). A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96). Conclusions Self-report of higher adherence to a Mediterranean-style diet is associated with lower preeclampsia odds, and benefit of this diet is present among Black women as well.

Self-management of iron and folic acid supplementation during pre-pregnancy, pregnancy and postnatal periods: a systematic review.

INTRODUCTION: While the use of folic acid pre-pregnancy and iron and folic acid (IFA) during pregnancy and postnatal have been demonstrated to be effective and are recommended interventions by WHO, ensuring individuals adhere to the supplementation regimen can be a challenge. Self-care interventions that support an individual's ability to promote their own health with or without the support of health workers could help promote the uptake and adherence to supplementation. This systematic review assessed the evidence around self-management of IFA or folic acid supplementation accessed over-the-counter during pre-pregnancy, pregnancy and postnatal periods. METHODS: Peer-reviewed studies were included if they compared self-management of IFA or folic acid supplementation with health worker-initiated supplement use on maternal and/or fetal and newborn health outcomes, end-users' or health workers' values and preferences, or cost and/or cost-effectiveness. We searched PubMed, CINAHL, LILACS and EMBASE for articles published through November 2020, hand-searched clinical trial registries, reviewed databases and contacted experts in the field. Abstract screening and full-text review were conducted independently by two reviewers. RESULTS: Overall, 2344 results were identified, and 28 studies were identified for full-text review. All studies were excluded, as they were not primary research, lacked the outcomes of interest, lacked specificity in supplement type, and/or lacked a comparison group. CONCLUSION: No evidence was identified that distinguishes self-management of folic acid supplements pre-pregnancy and of IFA supplements during pregnancy and postnatal, highlighting a gap in our current understanding of self-care related to dietary supplementation in pregnancy. The findings of this review identify an area for further research to support the current movement towards self-care interventions as an added choice to help individuals more fully attain their reproductive health and rights. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020205548.

Mediterranean-Style Diet and Birth Outcomes in an Urban, Multiethnic, and Low-Income US Population.

Findings on the role of Mediterranean-style diet (MSD) on duration of pregnancy and birth weight have been inconsistent and based largely on Non-Hispanic white populations, making it unclear as to whether they could extend to African Americans who are at a higher risk of unfavorable birth outcomes. Our study addresses this gap using a large urban, multiethnic, predominantly low-income cohort of mother-infant dyads from Boston, MA, USA. Dietary information was obtained via food frequency questionnaires; health information including birth outcomes were extracted from medical records. A Mediterranean-style diet score (MSDS) was formulated based on intake history, and linear and log-binomial regressions were performed to assess its association with birth outcomes. After adjustment, the lowest MSDS quintile from the overall sample was found to be associated with an increased relative risk (RR) of overall preterm birth (RR 1.18; 95% CI: 1.06-1.31), spontaneous preterm birth (1.28; 1.11-1.49), late preterm birth (1.21; 1.05-1.39), and low birth weight (1.11; 1.01-1.22), compared to the highest quintile. The findings were similar for the African American sample. Our study adds to the current understanding of the diet's influence on birth outcomes by demonstrating that adherence to MSD may improve birth outcomes for African American women.

Beyond taste and easy access: Physical, cognitive, interpersonal, and emotional reasons for sugary drink consumption among children and adolescents.

Consumption of sugary drinks is associated with the development of obesity and cardiometabolic diseases among children and adolescents. In addition to high added sugar content, many sugary drinks also contain caffeine. However, whether the combination of sugar and caffeine uniquely influences children's sugary drink intake is presently unknown. This study aimed to evaluate contextual factors surrounding children's sugary drink consumption and investigate reasons for sugary drink intake among children and adolescents, with a specific focus on caffeinated sodas and sweet tea. We also evaluated how sugary drink consumption makes children feel and how they anticipated that they would respond if sugary drinks were restricted. Focus group discussions (n = 9, 2-8 participants per group) were conducted with 37 predominantly AfricanAmerican children and adolescents, ages 8-14 years, who consumed ≥1 caffeine-containing sugary drink(s) daily, based on parental report. Focus groups were audio-recorded and transcribed verbatim. Transcripts were independently coded by two coders, after which emergent themes were identified. Reported reasons for sugary drink consumption encompassed five themes: 1) perceived need (e.g., satisfy cravings, quench thirst); 2) physical and cognitive benefits (e.g., provide energy, improve attention); 3) emotional and interpersonal benefits (e.g., relieve anger, facilitate socializing); 4) sensory properties (e.g., taste, carbonation); and, 5) external cues (e.g., family/peer modeling, availability). Negative consequences resulting from excess intake were also reported, including gastrointestinal symptoms, headaches, fatigue, hyperactivity, and chronic disease. Perceived physical, cognitive, emotional, and interpersonal benefits encourage sugary drink consumption and exacerbate well-described challenges of sugary drink reduction, including their palatability, accessibility, and affordability. Findings also suggest that incorporation of strategies to enhance physical, cognitive, and emotional health may hold promise in reducing sugary drink consumption among children and adolescents.

Differences in the sugar content of fast-food products across three countries.

OBJECTIVE: To compare the sugar content of items at four multinational fast-food chains, across three countries. DESIGN: Total sugar (g)/per serving was extracted from online nutrition information, and sugar/100 g serving was calculated. Foods were categorised as: breakfast sandwiches, burgers, sandwiches, desserts and condiments. Beverages were categorised as fountain, frozen or pre-packaged. Sugar (g) was compared across countries using linear mixed-effects models. Pairwise comparisons were performed with Tukey-Kramer adjustments. SETTING: USA, Germany and Australia. PARTICIPANTS: Burger King™ (Hungry Jack's™), Kentucky Fried Chicken™, McDonald's™ and Subway™. RESULTS: Differences in total sugar/100 g or ml were observed across countries for burgers (n 104), desserts (n 110), sandwiches (n 178), pre-packaged beverages (n 36) and frozen beverages (n 72). Comparing identical items across countries (e.g. BigMacTM from McDonalds in USA, Germany and Australia), burgers (n 10 available in all three countries) had lower sugar content in Australia (3·4 g/100 g) compared with the USA (4·7 g/100 g, P = 0·02) or Germany (4·6 g/100 g, P = 0·04), yet no differences were observed in other food categories. Comparing the same beverages across countries (e.g. chocolate shake from Burger King), frozen beverages (n 4 available in all three countries) had lower sugar content in Australia (14·2 g/100 ml), compared with the USA (20·3 g/100 ml, P = 0·0005) or Germany (17·8 g/100 ml, P = 0·0148), yet no differences were observed in other beverage categories. CONCLUSIONS: Heterogeneity in fast-food sugar content across countries suggests that reductions are possible and should be implemented to reduce health risks associated with excess added sugar intake.

SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A.

Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of PDE3A , and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A -TSSs using chromatin immunoprecipitation sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared to normal cervical tissue. Furthermore, over-expression of PDE3A induced sensitivity to anti-cancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity , offering a novel molecular target for the development of anticancer therapies.

Effects of heterologous expression of human cyclic nucleotide phosphodiesterase 3A (hPDE3A) on redox regulation in yeast.

Oxidative stress plays a pivotal role in pathogenesis of cardiovascular diseases and diabetes; however, the roles of protein kinase A (PKA) and human phosphodiesterase 3A (hPDE3A) remain unknown. Here, we show that yeast expressing wild-type (WT) hPDE3A or K13R hPDE3A (putative ubiquitinylation site mutant) exhibited resistance or sensitivity to exogenous hydrogen peroxide (H2O2), respectively. H2O2-stimulated ROS production was markedly increased in yeast expressing K13R hPDE3A (Oxidative stress Sensitive 1, OxiS1), compared with yeast expressing WT hPDE3A (Oxidative stress Resistant 1, OxiR1). In OxiR1, YAP1 and YAP1-dependent antioxidant genes were up-regulated, accompanied by a reduction in thioredoxin peroxidase. In OxiS1, expression of YAP1 and YAP1-dependent genes was impaired, and the thioredoxin system malfunctioned. H2O2 increased cyclic adenosine monophosphate (cAMP)-hydrolyzing activity of WT hPDE3A, but not K13R hPDE3A, through PKA-dependent phosphorylation of hPDE3A, which was correlated with its ubiquitinylation. The changes in antioxidant gene expression did not directly correlate with differences in cAMP-PKA signaling. Despite differences in their capacities to hydrolyze cAMP, total cAMP levels among OxiR1, OxiS1, and mock were similar; PKA activity, however, was lower in OxiS1 than in OxiR1 or mock. During exposure to H2O2, however, Sch9p activity, a target of Rapamycin complex 1-regulated Rps6 kinase and negative-regulator of PKA, was rapidly reduced in OxiR1, and Tpk1p, a PKA catalytic subunit, was diffusely spread throughout the cytosol, with PKA activation. In OxiS1, Sch9p activity was unchanged during exposure to H2O2, consistent with reduced activation of PKA. These results suggest that, during oxidative stress, TOR-Sch9 signaling might regulate PKA activity, and that post-translational modifications of hPDE3A are critical in its regulation of cellular recovery from oxidative stress.

Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury.

Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B(-/-) heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B(-/-) mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B(-/-) mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca(2+)-induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B(-/-) heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3-enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies.

Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model.

Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer.

Methylations of histone H3 lysine 9 and lysine 36 are functionally linked to DNA replication checkpoint control in fission yeast.

Recently, histone H4 lysine 20 and H3 lysine 79 methylations were functionally linked to DNA damage checkpoint. The crosstalk between histone methylation and the S-M checkpoint, however, has remained unclear. Here, we show that H3 lysine 9 (K9) and lysine 36 (K36) methylations catalyzed by two histone methyltransferases Clr4 and Set2 are involved in hydroxyurea (HU)-induced replication checkpoint. The clr4-set2 double mutants besides histone H3-K9 and K36 double mutants exhibited HU-sensitivity, a defective HU-induced S-M checkpoint, and a significant reduction of HU-induced phosphorylation of Cdc2. Intriguingly, the clr4-set2 double mutations impaired the HU-induced accumulation of a mitotic inhibitor Mik1. Double mutants in Alp13 and Swi6, which can specifically bind to H3-K36 and K9 methylations, exhibited phenotypes similar to those of the clr4-set2 mutants. Together, these findings suggest that methylations of histone H3-K9 and K36 by Clr4 and Set2 are functionally linked to DNA replication checkpoint via accumulation of Mik1.

ATP-binding motifs play key roles in Krp1p, kinesin-related protein 1, function for bi-polar growth control in fission yeast.

Kinesin is a microtubule-based motor protein with various functions related to the cell growth and division. It has been reported that Krp1p, kinesin-related protein 1, which belongs to the kinesin heavy chain superfamily, localizes on microtubules and may play an important role in cytokinesis. However, the function of Krp1p has not been fully elucidated. In this study, we overexpressed an intact form and three different mutant forms of Krp1p in fission yeast constructed by site-directed mutagenesis in two ATP-binding motifs or by truncation of the leucine zipper-like motif (LZiP). We observed hyper-extended microtubules and the aberrant nuclear shape in Krp1p-overexpressed fission yeast. As a functional consequence, a point mutation of ATP-binding domain 1 (G89E) in Krp1p reversed the effect of Krp1p overexpression in fission yeast, whereas the specific mutation in ATP-binding domain 2 (G238E) resulted in the altered cell polarity. Additionally, truncation of the leucine zipper-like domain (LZiP) at the C-terminal of Krp1p showed a normal nuclear division. Taken together, we suggest that krp1p is involved in regulation of cell-polarized growth through ATP-binding motifs in fission yeast.

Cloning and characterization of the kinesin-related protein, Krp1p, in Schizosaccharomyces pombe.

Kinesin have been cloned in many organisms. They played important roles in the transport of cell organelles, polarized growth, and secretion. We report here the identification of a kinesin-related protein in Schizosaccharomyces pombe, which was named kinesin-related protein (Krplp). The primer sequences were driven from the highly conserved area of the kinesin genes in other organisms. We cloned kinesin genes from S. pombe using the PCR technique. Sequence analysis revealed that krp1+ has a 1,665 bp open-reading frame (ORF) that encoded a protein that consisted of 554 amino acids with a molecular weight of 61,900. It is homologous to the proteins that belong to the kinesin heavy chain (KHC) superfamily [GenBank accession No. AF156966 (genomic DNA) and AF247188 (mRNA)]. To characterize Krplp, the gene was disrupted and overexpressed in S. pombe. Cells that contained a krp1+ null allele were viable. Overexpression of Krp1p resulted in the inhibition of mitotic growth; cells became elongated, branched, and formed aberrant septa. To identify proteins that interact with Krplp, the yeast two-hybrid system was used. As a result, the novel protein, designated kinesin associated protein (Kap1p), was identified and showed structural homology to the proteins of the myosin family (GenBank accession No. AF351206). The data from the overexpression and two-hybrid study of Krplp may provide information that Krplp can have roles in cytokinesis with myosin.