Gestational diabetes mellitus and development of intergenerational non-alcoholic fatty liver disease (NAFLD) after delivery: a systematic review and meta-analysis.

Background: It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing non-alcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring. Methods: Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random-effects meta-analysis to investigate the effect of GDM on NAFLD in mothers and offspring. Pooled odds ratio (OR) was calculated using hazards ratio (HR), relative risk (RR), or OR reported from each study, with corresponding 95% confidence intervals (CI), and statistical heterogeneity was assessed with the Cochran Q-test and I2 statistic, with two-sided p values. The study protocol was pre-registered on PROSPERO (CRD42023392428). Findings: Twenty studies pertaining to mothers and offspring met the inclusion criteria and 12 papers were included further for meta-analysis on intergenerational NAFLD development. Compared with mothers without a history of GDM, mothers with a history of GDM had a 50% increased risk of developing NAFLD (OR 1.50; 95% CI: 1.21-1.87, over a follow-up period of 16 months-25 years. Similarly, compared with offspring born to non-GDM-complicated pregnancies, offspring born to GDM-complicated pregnancies displayed an approximately two-fold elevated risk of NAFLD development (2.14; 1.57-2.92), over a follow-up period of 1-17.8 years. Interpretation: This systematic review and meta-analysis suggests that both mothers and offspring from GDM-complicated pregnancies exhibit a greater risk to develop NAFLD. These findings underline the importance of early monitoring of liver function and prompt intervention of NAFLD in both generations from GDM-complicated pregnancies. Funding: No funding was available for this research.

The effect of telemedicine interventions on patients with diabetic foot ulcers: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The meta-analysis was performed to evaluate the effectiveness of telemedicine interventions on patients with diabetic foot ulcers(DFU). APPROACH: The authors conducted a comprehensive search across eight databases. The aim was to identify randomized controlled trials examining the effectiveness of telemedicine for patients with DFU. Methodological qualities of included studies were assessed using Cochrane Handbook for Systematic Reviews of Intervention.. Subsequently, a meta-analysis was conducted using RevMan 5.3 to synthesize the findings. RESULTS: Ten studies involving 1678 patients with DFU were included in the meta-analysis. In comparison to the face-to-face intervention group, telemedicine interventions significantly reduced the amputation rate (risk ratio (RR) = 0.64, 95% confidence interval (CI) = 0.44－0.92, p = 0.02), decreased costs (mean difference (MD) = -4158.51, 95% CI = -7304.69－-1012.34, p = 0.01), better controlled fasting blood glucose( FPG)(MD = -0.89, 95% CI = -1.43－-0.36, p = 0.001), achieved superior glycated hemoglobin(HbA1c) control (MD = -0.71, 95% CI = -1.01－-0.41, p ˂ 0.00001). No significant differences were observed between the telemedicine group and the face-to-face group in terms of healing rate, mortality, and healing time.  Innovations: Our study suggests that telemedicine is a viable strategy for managing DFU. CONCLUSIONS: The meta-analysis indicates that telemedicine interventions have a positive effect on DFU. Nevertheless, more well-designed and high-quality studies are needed to reach a conclusion with greater confidence.

Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study.

BACKGROUND: Evidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function. OBJECTIVES: We investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy. METHODS: Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10-14 wk) and 5 thyroid biomarkers at 10-14, 15-26, 23-31, and 33-39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively. RESULTS: After sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: -0.31, -0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA-RR: 0.13; 0.06, 0.28; DTA-RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing. CONCLUSIONS: Certain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy. CLINICAL TRIAL REGISTRY: This trial was registered at https://beta. CLINICALTRIALS: gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.

Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study.

OBJECTIVE: To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. DESIGN, SETTING AND POPULATION: A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. METHODS: We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. MAIN OUTCOME MEASURES: We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. RESULTS: Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. CONCLUSIONS: Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.

Preconception maternal retinal venular widening and steeper resistance increments in the utero-fetoplacental circulation in pregnancy.

We investigated the relationship of preconception maternal retinal vasculature and utero-fetoplacental circulation in ensuing pregnancy. Embedded in a hospital-based, prospective preconception cohort, 396 women with a singleton live birth were included for analysis. We assessed retinal vascular caliber during preconception phase and retrieved ultrasonogram results documenting utero-fetoplacental circulatory indices using Doppler ultrasonography and documented them at 18-21 weeks, 24-28 weeks, and 32-34 weeks where available. We performed a modified Poisson regression to estimate the relative risk of utero-fetoplacental abnormalities, adjusting for major confounders including pre-pregnancy and blood pressure. Per 10 µm increment in maternal preconception retinal venules was associated with over two-fold risks in developing notching (Relative risk [RR]: 2.84; 95% confidence interval [CI]: 1.79, 4.81) and ≥95th percentile umbilical artery pulsatility index (2.36; 1.72, 3.23) during mid-to-late pregnancy, respectively. Women with preconception retinal venular widening tended to demonstrate steeper resistance increments in both maternal uterine arteries and fetal umbilical arteries during mid-to-late pregnancy.

Maternal glycemic status during pregnancy and mid-childhood plasma amino acid profiles: findings from a multi-ethnic Asian birth cohort.

BACKGROUND: Increasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers. METHODS: Data were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother-child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26-28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores. RESULTS: Approximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood. CONCLUSIONS: Increasing maternal fasting and post-OGTT glucose concentrations at 26-28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

Early Pregnancy Maternal Plasma Phospholipid Saturated Fatty Acids and Fetal Growth: Findings from a Multi-Racial/Ethnic Birth Cohort in US.

Saturated fatty acids (SFAs) during pregnancy are associated with disrupted metabolic programming among offspring at birth and later growth. We examined plasma phospholipid SFAs in early pregnancy and fetal growth throughout pregnancy. We enrolled 321 pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort at gestational weeks 8-13. Ultrasonogram schedules were randomly assigned to capture weekly fetal growth. We measured plasma phospholipid SFAs at early pregnancy using blood samples and modeled fetal growth trajectories across tertiles of SFAs with cubic splines using linear mixed models after full adjustment. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each SFA using the Wald test. We found that even-chain and very long even-chain SFAs were inversely associated, whereas odd-chain SFAs were positively associated with fetal weight and size. Compared with the lowest tertile, the highest tertile of pentadecanoic acid (15:0) had a greater fetal weight and size, starting from week 13 until late pregnancy (at week 39: 3429.89 vs. 3269.08 g for estimated fetal weight; 328.14 vs. 323.00 mm for head circumference). Our findings could inspire future interventions using an alternative high-fat diet rich in odd-chain SFAs for optimal fetal growth.

Mediterranean diet and female reproductive health over lifespan: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course. DATA SOURCES: We searched PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to identify eligible studies published till February 2022. Eligible references from identified studies and review articles were also considered. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, prospective cohort studies, or nested case-control studies examining Mediterranean diet and major female reproductive outcomes over the lifespan, including clinical outcomes from childhood to adulthood (menarche, polycystic ovary syndrome, endometriosis, and outcomes related to fertility, pregnancy, and menopause), were included for review. METHODS: Two independent reviewers screened and performed data extraction and risk-of-bias assessment. We performed random-effects meta-analysis to obtain summary relative risks and 95% confidence intervals for major female reproductive outcomes. Subgroup analyses were performed for several pregnancy outcomes according to timing of the interventions for randomized controlled trials and timing of the dietary assessment for observational studies. RESULTS: Thirty-two studies (9 randomized controlled trials, 22 prospective cohort studies, and 1 nested case-control study) involving 103,204 predominantly White women (>95%) were included. The pooled relative risk (95% confidence interval) comparing randomization to Mediterranean diet vs a control diet based on 7 randomized controlled trials was 0.74 (0.55-0.99) for gestational diabetes mellitus, 0.45 (0.26-0.76) for preterm birth, 0.71 (0.51-1.00) for gestational hypertension, and 0.82 (0.54-1.22) for preeclampsia; the effect sizes for preterm birth were greater in randomized controlled trials that initiated the interventions in first trimester vs after first trimester (P heterogeneity=.02). We observed inverse associations for all the above-mentioned pregnancy outcomes based on 9 cohort studies. There was suggestive evidence of favorable associations between Mediterranean diet adherence with fertility and gestational weight management. Limited studies suggested associations between higher Mediterranean diet adherence and later time to menarche and fewer vasomotor menopausal symptoms, null associations for polycystic ovary syndrome-like phenotype and pregnancy loss, and positive associations for luteal phase deficiency. CONCLUSION: Adherence to Mediterranean diet may lower risks of adverse pregnancy outcomes among predominantly White populations. For fertility-related outcomes, available evidence supporting potential beneficial effects is suggestive yet limited. For other reproductive outcomes across the lifespan, data remains sparse.

Exploring preconception signatures of metabolites in mothers with gestational diabetes mellitus using a non-targeted approach.

BACKGROUND: Metabolomic changes during pregnancy have been suggested to underlie the etiology of gestational diabetes mellitus (GDM). However, research on metabolites during preconception is lacking. Therefore, this study aimed to investigate distinctive metabolites during the preconception phase between GDM and non-GDM controls in a nested case-control study in Singapore. METHODS: Within a Singapore preconception cohort, we included 33 Chinese pregnant women diagnosed with GDM according to the IADPSG criteria between 24 and 28 weeks of gestation. We then matched them with 33 non-GDM Chinese women by age and pre-pregnancy body mass index (ppBMI) within the same cohort. We performed a non-targeted metabolomics approach using fasting serum samples collected within 12 months prior to conception. We used generalized linear mixed model to identify metabolites associated with GDM at preconception after adjusting for maternal age and ppBMI. After annotation and multiple testing, we explored the additional predictive value of novel signatures of preconception metabolites in terms of GDM diagnosis. RESULTS: A total of 57 metabolites were significantly associated with GDM, and eight phosphatidylethanolamines were annotated using HMDB. After multiple testing corrections and sensitivity analysis, phosphatidylethanolamines 36:4 (mean difference ß: 0.07; 95% CI: 0.02, 0.11) and 38:6 (ß: 0.06; 0.004, 0.11) remained significantly higher in GDM subjects, compared with non-GDM controls. With all preconception signals of phosphatidylethanolamines in addition to traditional risk factors (e.g., maternal age and ppBMI), the predictive value measured by area under the curve (AUC) increased from 0.620 to 0.843. CONCLUSIONS: Our data identified distinctive signatures of GDM-associated preconception phosphatidylethanolamines, which is of potential value to understand the etiology of GDM as early as in the preconception phase. Future studies with larger sample sizes among alternative populations are warranted to validate the associations of these signatures of metabolites and their predictive value in GDM.

Construction of polysubstituted pentafulvenes via palladium-catalyzed deacetylation of enones.

Herein, we report an efficient synthetic method for polysubstituted pentafulvenes via palladium-catalyzed deacetylative [2+2+1] annulation of enones with alkynes. Aryl-, alkenyl-, and alkyl-substituted α,ß-enones were suitable substrates, affording the pentafulvene products in moderate to good yields. This protocol shows excellent compatibility with sensitive halides, free hydroxyl groups, and heterocycles. One-pot gram-scale synthesis and further applications in the late-stage modification of natural products demonstrate the synthetic utility of this method.

Plasma Amino Acids in Early Pregnancy and Midpregnancy and Their Interplay With Phospholipid Fatty Acids in Association With the Risk of Gestational Diabetes Mellitus: Results From a Longitudinal Prospective Cohort.

OBJECTIVE: We prospectively evaluated plasma amino acids (AAs) in early pregnancy and midpregnancy and their interplay with phospholipid fatty acids (FAs) in association with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: From a longitudinal pregnancy cohort of 2,802 individuals, concentrations of 24 plasma AAs at 10-14 and 15-26 gestational weeks (GW) were assessed among 107 GDM case subjects and 214 non-GDM control subjects. We estimated adjusted odds ratios (OR) and 95% CI for the associations of plasma AAs and the joint associations of plasma AAs and phospholipid FAs with GDM risk, adjusting for risk factors including age, prepregnancy BMI, and family history of diabetes. RESULTS: Glycine at 10-14 GW was inversely associated with GDM (adjusted OR [95% CI] per SD increment: 0.55 [0.39-0.79]). Alanine, aspartic acid, and glutamic acid at 10-14 GW were positively associated with GDM (1.43 [1.08-1.88], 1.41 [1.11-1.80], and 1.39 [0.98-1.98]). At 15-26 GW, findings for glycine, alanine, aspartic acid, and the glutamine-to-glutamic acid ratio were consistent with the directions observed at 10-14 GW. Isoleucine, phenylalanine, and tyrosine were positively associated with GDM (1.64 [1.19-2.27], 1.15 [0.87-1.53], and 1.56 [1.16-2.09]). All P values for linear trend were <0.05. Several AAs and phospholipid FAs were significantly and jointly associated with GDM. For instance, the lowest risk was observed among women with higher glycine and lower even-chain saturated FAs at 10-14 GW (adjusted OR [95% CI] 0.15 [0.06, 0.37]). CONCLUSIONS: Plasma AAs may be implicated in GDM development starting in early pregnancy. Associations of AAs with GDM may be enhanced in the copresence of phospholipid FA profile.

Plasma Phospholipid Monounsaturated Fatty Acids and Gestational Diabetes Mellitus: A Longitudinal Study in the NICHD Fetal Growth Studies-Singletons Cohort.

Fatty acids (FAs) have been implicated in the development of gestational diabetes mellitus (GDM), but the role of monounsaturated FAs (MUFAs) remains understudied. We investigated the associations of plasma phospholipid MUFAs in early to mid-pregnancy with cardiometabolic biomarkers and GDM risk. From the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (2009-2013), we identified 107 women with GDM according to Carpenter and Coustan criteria and 214 control participants without GDM matched (2:1) on age, race/ethnicity, and gestational week (GW) of blood collection. MUFAs were measured at 10-14, 15-26, 23-31, and 33-39 GWs by gas chromatography mass spectrometry. We found that the concentration of total 18:1 MUFAs was significantly lower among women with GDM than those without GDM at 15-26 GWs. Each SD increment in the level of total 18:1 MUFAs was associated with a 40% lower risk of GDM at 15-26 GWs. Moreover, each SD increment in vaccenic acid (18:1n-7) levels at 10-14 and 15-26 GWs were associated with a 36% and 45% lower risk of GDM, respectively. Our extensive assessments of MUFAs advance our understanding of the unique associations of FA composition with GDM risk, suggesting the potentially beneficial role of MUFAs in GDM pathophysiology.

Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women.

OBJECTIVE: To better understand the underlying pathogenesis of spontaneous abortion that affects 10%-20% of recognized pregnancies. We used retinal imaging to study the role of systemic microvasculature and the risk of spontaneous abortion. DESIGN: A prospective multiethnic preconception cohort study conducted in Singapore. SETTING: Hospital-based. PATIENT(S): A total of 1,032 Southeast Asian women who intended to conceive naturally were screened at study entry, among which 480 women spontaneously conceived within the 12-month observation period. After excluding 24 women who were lost to follow-up, we calculated the spontaneous abortion rate among 456 women. Further, we included 379 women for the final association analysis because 63 women did not undergo preconception retinal imaging examination and 14 had other types of pregnancy loss instead of spontaneous abortion. INTERVENTION(S): Trained photographers performed retinal examination using a 45-degree nonmydriatic retinal camera at study entry during the preconception screening. Using a semiautomated, computer-based program, we assessed quantitative retinal microvascular measurements, including caliber, fractal dimension, curvature tortuosity, and branching angle. Clinical research coordinators collected information on sociodemographic status, menstrual characteristics, and lifestyle, and assessed blood pressure and anthropometry at study entry. MAIN OUTCOME MEASURE(S): We performed a modified Poisson regression model to estimate the relative risk (RR) and 95% confidence interval (CI) for each retinal microvascular feature and its association with spontaneous abortion after adjusting for major confounders such as maternal prepregnancy, body mass index, and previous pregnancy loss history. RESULT(S): We reported a spontaneous abortion rate of 13.4% (61 out of 456). Among all retinal microvascular features, retinal arteriolar caliber, retinal arteriolar, and venular curvature tortuosity were associated with a high risk of incident spontaneous abortion. In the regression model, per SD increase in retinal curvature tortuosity was associated with a 25%-34% increased risk of incident spontaneous abortion (arteriolar: unadjusted RR, 1.29 [95% CI, 1.06-1.56] and adjusted RR, 1.26 [1.04-1.53]; venule: unadjusted RR, 1.30 [1.08-1.55] and adjusted RR, 1.34 [1.09-1.64]). CONCLUSION(S): Our prospective cohort observed an increased risk of spontaneous abortion among Asian women with more tortuous retinal vessels assessed during the preconception phase. Our results indicate a role of vascular inflammatory and oxidative stress in the pathogenesis of spontaneous abortion. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03531658.

Gestational Diabetes Mellitus Among Asians - A Systematic Review From a Population Health Perspective.

Objective: Since Asians are particularly vulnerable to the risk of gestational diabetes mellitus (GDM), the lifecourse health implications of which are far beyond pregnancy, we aimed to summarize the literature to understand the research gaps on current GDM research among Asians. Methods: We systematically searched the articles in PubMed, Web of Science, Embase, and Scopus by 30 June 2021 with keywords applied on three topics, namely "GDM prevalence in Asians", "GDM and maternal health outcomes in Asians", and "GDM and offspring health outcomes in Asians". Results: We observed that Asian women (natives and immigrants) are at the highest risk of developing GDM and subsequent progression to type 2 diabetes among all populations. Children born to GDM-complicated pregnancies had a higher risk of macrosomia and congenital anomalies (i.e. heart, kidney and urinary tract) at birth and greater adiposity later in life. Conclusion: This review summarized various determinants underlying the conversion between GDM and long-term health outcomes in Asian women, and it might shed light on efforts to prevent GDM and improve the lifecourse health in Asians from a public health perspective. Systematic Review Registration: Prospero, CRD42021286075.

Plasma phospholipid polyunsaturated fatty acids composition in early pregnancy and fetal growth trajectories throughout pregnancy: Findings from the US fetal growth studies-singletons cohort.

BACKGROUND: We aimed to investigate plasma phospholipid PUFA levels in early pregnancy and fetal growth trajectories throughout pregnancy. METHODS: Within the NICHD Fetal Growth Studies-Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks 8-13 and randomly assigned them to four ultrasonogram schedules to capture weekly fetal growth throughout pregnancy. Eleven plasma phospholipid PUFAs were measured at early pregnancy using blood samples collected from a subsample of 321 pregnant women. We modeled fetal growth trajectories across tertiles of PUFAs with cubic splines using linear mixed models after adjusting for major confounders. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each PUFA using the Wald test. FINDINGS: Among plasma n-3 PUFAs in early pregnancy, docosahexaenoic acid (DHA, 22:6n3) and alpha-linolenic acid (ALA, 18:3n3) showed positive associations with all fetal growth measurements. For instance, compared with the lowest tertile, the highest tertile of DHA had greater estimated fetal growth (EFW) and abdominal circumference (AC), starting at 13 weeks of gestation and throughout pregnancy (at gestational week 38: 3235.3 vs. 3089.0 g for EFW; 344.6 vs. 339.2 mm for AC). As for plasma n-6 PUFAs, some showed positive associations (e.g., linoleic acid [LA], 18:2n6) while others (e.g., docosatetraenoic acid [DTA], 22:4n6) showed inverse associations with fetal growth measures. INTERPRETATION: Our data suggested that higher plasma levels of DHA and ALA in the first trimester were associated with increased fetal size and weight throughout subsequent pregnancy. FUNDING: National Institute of Child Health and Human Development intramural funding.

Homologation of aryl ketones to long-chain ketones and aldehydes via C-C bond cleavage.

Transition metal-catalyzed C-C bond cleavage is a powerful tool for the reconstruction of a molecular skeleton. We report herein the multi-carbon homologation of aryl ketones to long-chain ketones and aldehydes via ligand-promoted Ar-C(O) bond cleavage and subsequent cross coupling with alkenols. Various (hetero)aryl ketones are compatible in the reaction, affording the corresponding products wtih good to excellent yields with high regioselectivity. Further applications in the late-stage diversification of biologically important molecules demonstrate the synthetic utility of this protocol. Mechanistic studies indicate that the ligand plays an important role in both C-C bond cleavage and the asymmetric migration-insertion process.

Palladium-Catalyzed Alkynylation of Enones with Alkynylsilanes via C-C Bond Activation.

We report herein the synthesis of 1,3-enynes via palladium-catalyzed cross-coupling between enone derivatives and alkynylsilanes. The employment of an appropriate pyridine-oxazoline ligand is the key to the C-C cleavage and the high E/Z stereoselectivity. This protocol features broad substrate scope and wide functional-group tolerance, affording the desired products in moderate-to-good yields. Late-stage diversification of natural product ß-ionone further demonstrated the synthetic utility of this protocol.

Multidisciplinary non-surgical treatment of advanced periodontitis: A case report.

BACKGROUND: Patients with severe periodontitis often require multidisciplinary treatment to achieve healthy periodontal tissue, normal occlusion, and optimal aesthetics. In the present study, we aimed to evaluate the efficacy of multidisciplinary non-surgical treatment in a patient with stage IV/ grade C periodontitis, malocclusion, and dentition defects. CASE SUMMARY: A 47-year-old woman visited our periodontology department due to teeth mobility problems and difficulties chewing food. The patient had no history of drug allergies or systemic disease. Initial therapy involved scaling and root planning with a Gracey scaler and periodontal ultrasonic therapeutic apparatus using a periodontal endoscope (Perioscopy, Zest Dental Solutions, United States) to control the periodontal inflammation prior to treatment. Five months later, orthodontic treatment was then performed to treat occlusion and overall aesthetics. After completion, a Maryland bridge was used to restore Nos. 22, 31, and 41 teeth. Florida probing (Florida probe, United States) was performed every 2-3 mo to evaluate the periodontal condition throughout treatment. Overall, multidisciplinary non-surgical treatment resulted in satisfactory aesthetic results with healthy periodontal tissue and stable occlusion. CONCLUSION: In some patients with stage IV/grade C periodontitis, systematic and sequential non-surgical treatment can provide excellent therapeutic results.

Brief Report: Retinal Microvasculature and Immune Restoration Among South Eastern Asian Patients With HIV/AIDS Over a 9-Month Antiretroviral Therapy.

BACKGROUND: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy. METHODS: We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders. RESULTS: We found that narrower arteriolar caliber (per 10 µm decrease), wider venular caliber (per 10 µm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/µL (P = 0.006), 33.55 cells/µL (P = 0.01), and 39.09 cells/µL (P = 0.008), accordingly. CONCLUSION: Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy.