Structure-based design of non-hypertrophic apelin receptor modulator.

Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the ß-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-Gi1 complexes bound to three agonists with divergent signaling profiles. Combined with functional assays, we have identified "twin hotspots" in APLNR as key determinants for signaling bias, guiding the rational design of two exclusive G-protein-biased agonists WN353 and WN561. Cryo-EM structures of WN353- and WN561-stimulated APLNR-G protein complexes further confirm that the designed ligands adopt the desired poses. Pathophysiological experiments have provided evidence that WN561 demonstrates superior therapeutic effects against cardiac hypertrophy and reduced adverse effects compared with the established APLNR agonists. In summary, our designed APLNR modulator may facilitate the development of next-generation cardiovascular medications.

Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism.

Cannabis activates the cannabinoid receptor 1 (CB1), which elicits analgesic and emotion regulation benefits, along with adverse effects, via Gi and ß-arrestin signaling pathways. However, the lack of understanding of the mechanism of ß-arrestin-1 (ßarr1) coupling and signaling bias has hindered drug development targeting CB1. Here, we present the high-resolution cryo-electron microscopy structure of CB1-ßarr1 complex bound to the synthetic cannabinoid MDMB-Fubinaca (FUB), revealing notable differences in the transducer pocket and ligand-binding site compared with the Gi protein complex. ßarr1 occupies a wider transducer pocket promoting substantial outward movement of the TM6 and distinctive twin toggle switch rearrangements, whereas FUB adopts a different pose, inserting more deeply than the Gi-coupled state, suggesting the allosteric correlation between the orthosteric binding pocket and the partner protein site. Taken together, our findings unravel the molecular mechanism of signaling bias toward CB1, facilitating the development of CB1 agonists.

Mutagenesis of Odorant Receptor Coreceptor Orco Reveals the Odorant-Detected Behavior of the Predator Eupeodes corollae.

The successful mating of the hoverfly and the search for prey aphids are of great significance for biological control and are usually mediated by chemical cues. The odorant receptor co-receptor (Orco) genes play a crucial role in the process of insect odor perception. However, the function of Orco in the mating and prey-seeking behaviors of the hoverfly remains relatively unexplored. In this study, we characterized the Orco gene from the hoverfly, Eupeodes corollae, a natural enemy insect. We used the CRISPR/Cas9 technique to knock out the Orco gene of E. corollae, and the EcorOrco-/- homozygous mutant was verified by the genotype analysis. Fluorescence in situ hybridization showed that the antennal ORN of EcorOrco-/- mutant lack Orco staining. Electroantennogram (EAG) results showed that the adult mutant almost lost the electrophysiological response to 15 odorants from three types. The two-way choice assay and the glass Y-tube olfactometer indicated that both the larvae and adults of hoverflies lost their behavioral preference to the aphid alarm pheromone (E)-ß-farnesene (EBF). In addition, the mating assay results showed a significant decrease in the mating rate of males following the knock out of the EcorOrco gene. Although the mating of females was not affected, the amount of eggs being laid and the hatching rate of the eggs were significantly reduced. These results indicated that the EcorOrco gene was not only involved in the detection of semiochemicals in hoverflies but also plays a pivotal role in the development of eggs. In conclusion, our results expand the comprehension of the chemoreceptive mechanisms in the hoverflies and offers valuable insights for the advancement of more sophisticated pest management strategies.

Prognostic value and immune landscapes of immunogenic cell death-associated lncRNAs in lung adenocarcinoma.

Immunogenic cell death (ICD) has been demonstrated to activate T cells to kill tumor cells, which is closely related to tumor development, and long noncoding RNAs (lncRNAs) are also involved. However, it is not known whether ICD-related lncRNAs are associated with the development of lung adenocarcinoma (LUAD). We downloaded ICD-related genes from GeneCards and the transcriptome statistics of LUAD patients from The Cancer Genome Atlas (TCGA) and subsequently developed and verified a predictive model. A successful model was used together with other clinical features to construct a nomogram for predicting patient survival. To further study the mechanism of tumor action and to guide therapy, we performed enrichment analysis, tumor microenvironment analysis, somatic mutation analysis, drug sensitivity analysis and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Nine ICD-related lncRNAs with significant prognostic relevance were selected for model construction. Survival analysis demonstrated that overall survival was substantially shorter in the high-risk group than in the low-risk group (P < 0.001). This model was predictive of prognosis across all clinical subgroups. Cox regression analysis further supported the independent prediction ability of the model. Ultimately, a nomogram depending on stage and risk score was created and showed a better predictive performance than the nomogram without the risk score. Through enrichment analysis, the enriched pathways in the high-risk group were found to be primarily associated with metabolism and DNA replication. Tumor microenvironment analysis suggested that the immune cell concentration was lower in the high-risk group. Somatic mutation analysis revealed that the high-risk group contained more tumor mutations (P = 0.00018). Tumor immune dysfunction and exclusion scores exhibited greater sensitivity to immunotherapy in the high-risk group (P < 0.001). Drug sensitivity analysis suggested that the predictive model can also be applied to the choice of chemotherapy drugs. RT-qPCR analysis also validated the accuracy of the constructed model based on nine ICD-related lncRNAs. The prognostic model constructed based on the nine ICD-related lncRNAs showed good application value in assessing prognosis and guiding clinical therapy.

Prognostic value and immune landscapes of immunogenic cell death-related lncRNAs in hepatocellular carcinoma.

BACKGROUND: Both immunogenic cell death (ICD) and long noncoding RNAs (lncRNAs) are strongly associated with tumor development, but the mechanism of action of ICD-associated lncRNAs in hepatocellular carcinoma (HCC) remains unclear. METHODS: We collected data from 365 HCC patients from The Cancer Genome Atlas (TCGA) database. We formulated a prognostic signature of ICD-associated lncRNAs and a nomogram to predict prognosis. To explore the potential mechanisms and provide clinical guidance, survival analysis, enrichment analysis, tumor microenvironment analysis, tumor mutation burden (TMB), and drug sensitivity prediction were conducted based on the subgroups obtained from the risk score. RESULTS: A prognostic signature of seven ICD-associated lncRNAs was constructed. Kaplan-Meier (K-M) survival curves showed a more unfavorable outcome in high-risk patients. The nomogram had a higher predictive value than the nomogram constructed without the risk model. Enrichment analysis confirmed that risk lncRNAs were closely associated with cell proliferation and mitosis. Most of the immune checkpoints currently used in therapy (e.g., PDCD1 and CTLA4) appeared to be elevated in high-risk patients. Tumor microenvironment analysis showed differential expression of lymphocytes (including natural killer cells, regulatory T cells, etc.) in the high-risk group. TMB had a higher incidence of mutations in the high-risk group (P=0.004). Chemotherapy drug sensitivity prediction provides effective guidelines for individual therapy. RT-qPCR of human HCC tissues verified the accuracy of the model. CONCLUSION: We constructed an effective prognostic signature for patients with HCC using seven ICD-lncRNAs, which provides guidance for the prognostic assessment and personalized treatment of patients.

Membrane metalloendopeptidase (MME) is positively correlated with systemic lupus erythematosus and may inhibit the occurrence of breast cancer.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer (BRCA) than the general population. In this study, we explored the underlying molecular mechanism that is dysregulated in both diseases. METHODS: Weighted gene coexpression network analysis (WGCNA) was executed with the SLE and BRCA datasets from the Gene Expression Omnibus (GEO) website and identified the potential role of membrane metalloendopeptidase (MME) in both diseases. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of related proteins and miRNAs were performed to investigate the potential molecular pathways. RESULTS: WGCNA revealed that MME was positively related to SLE but negatively related to BRCA. In BRCA, MME expression was significantly decreased in tumor tissues, especially in luminal B and infiltrating ductal carcinoma subtypes. Receiver operating characteristic (ROC) analysis identified MME as a valuable diagnostic biomarker of BRCA, with an area under the curve (AUC) value equal to 0.984 (95% confidence interval = 0.976-0.992). KEGG enrichment analysis suggested that MME-related proteins and targeted miRNAs may reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway. Low MME expression was associated with favorable relapse-free survival (RFS) but no other clinical outcomes and may contribute to resistance to chemotherapy in BRCA, with an AUC equal to 0.527 (P value < 0.05). CONCLUSIONS: In summary, MME expression was significantly decreased in BRCA but positively correlated with SLE, and it might reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway.

Near-ultraviolet irradiation to stimulate unmodified polyether ether ketone to achieve stable and sustainable antibacterial activity.

OBJECTIVES: This study aims to investigate the cytotoxicity and sustainable antibacterial activity of unmodified PEEK under specific wavelength light treatment (365 nm), and its antibacterial mechanism was also preliminarily discussed. METHODS: A near-ultraviolet source with a wavelength of 365 nm and a power of 5 W were selected. The irradiation time was 30 min, and the distance was 100 mm. A water contact angle tester was used to characterize the surface of the PEEK after 1-15 light treatments. MC3TC-E1 cells were used to evaluate the cytotoxicity of the materials under light treatment. Five kinds of common oral bacteria were detected in vitro, and antibacterial efficiency was determined by colony-forming unit (CFU) and scanning electron microscope (SEM). The antibacterial mechanism of PEEK under light was preliminarily discussed by spectrophotometry. The membrane rupture of Staphylococcus aureus and Escherichia coli was detected by lactate dehydrogenase. Staphylococcus aureus and Staphylococcus mutans were selected for the cyclic antibacterial test. Statistical analysis was performed by one-way analysis of variance and Tukey multiple range test. A significance level of 0.05 was considered (α = 0.05). RESULTS: The results of the cell experiment showed that PEEK had no cytotoxicity (P > 0.05). CFU results showed that PEEK had an obvious antibacterial effect on Staphylococcus aureus, Staphylococcus mutans, Staphylococcus gordonii and Staphylococcus sanguis, but had no antibacterial effect on Escherichia coli (P < 0.05). The SEM results also verified the above antibacterial effect. The existence of singlet oxygen was confirmed by spectrophotometry. Meanwhile, the rupture of Staphylococcus aureus membrane was verified by lactate dehydrogenase assay. The water contact angle of the PEEK surface did not change significantly after 15 cycles of light treatment. Cyclic antibacterial experiments showed that the antibacterial effect was sustainable. CONCLUSIONS: This study showed that PEEK has good cytocompatibility with stable and sustainable antibacterial properties under near-ultraviolet. It provides a new idea to solve the non-antibacterial property of PEEK, and also provides a theoretical basis for its further application in dentistry.

Construction and validation of a model based on immunogenic cell death-associated lncRNAs to predict prognosis and direct therapy for kidney renal clear cell carcinoma.

BACKGROUND: Immunogenic cell death (ICD) is an important part of the antitumor effect, yet the role played by long noncoding RNAs (lncRNAs) remains unclear. We explored the value of ICD-related lncRNAs in tumor prognosis assessment in kidney renal clear cell carcinoma (KIRC) patients to provide a basis for answering the above questions. METHODS: Data on KIRC patients were obtained from The Cancer Genome Atlas (TCGA) database, prognostic markers were identified, and their accuracy was verified. An application-validated nomogram was developed based on this information. Furthermore, we performed enrichment analysis, tumor mutational burden (TMB) analysis, tumor microenvironment (TME) analysis, and drug sensitivity prediction to explore the mechanism of action and clinical application value of the model. RT-qPCR was performed to detect the expression of lncRNAs. RESULTS: The risk assessment model constructed using eight ICD-related lncRNAs provided insight into patient prognoses. Kaplan-Meier (K-M) survival curves showed a more unfavorable outcome in high-risk patients (p<0.001). The model had good predictive value for different clinical subgroups, and the nomogram constructed based on this model worked well (risk score AUC=0.765). Enrichment analysis revealed that mitochondrial function-related pathways were enriched in the low-risk group. The adverse prognosis of the higher-risk cohort might correspond to a higher TMB. The TME analysis revealed a higher resistance to immunotherapy in the increased-risk subgroup. Drug sensitivity analysis can guide the selection and application of antitumor drugs in different risk groups. CONCLUSIONS: This prognostic signature based on eight ICD-associated lncRNAs has significant implications for prognostic assessment and treatment selection in KIRC.

Vortex vein engorgement and different shapes of venous drainage systems in polypoid choroidal vasculopathy vs. age­related macular degeneration on indocyanine green angiography.

There are differences in vortex vein engorgement and appearance in polypoid choroidal vasculopathy (PCV), age-related macular degeneration (AMD), and healthy eyes. The present study aimed to use indocyanine green angiography (ICGA) to find a simple, clinically meaningful method for evaluating the filling degree of vortex veins in various eye diseases. Participant clinical characteristics were recorded. The number of vortex veins (NVV), central vortex vein diameter (CVVD), mean root area of the vortex vein (MRAVV), mean diameter of the thickest peripheral branch (MDPTB), subfoveal choroidal thickness and percentage of vortex vein anastomosis (PVVA) were obtained by marking the vortex veins on ICGA. The proportion of subretinal haemorrhage and the numbers and types of vortex veins in each quadrant were counted separately. The CVVD and MDPTB were significantly increased in the PCV compared with those in the AMD group (P<0.05). The CVVD, MRAV, and PVVA were significantly increased in the PCV compared with those in the healthy group (P<0.05). The type IV vortex vein (complete with ampulla) proportion was the lowest while the type I (vortex vein absent) proportion was the highest in the PCV group (P<0.001). NVV in the inferior-temporal region was increased in the PCV compared with that in the AMD group (P=0.034). Subretinal haemorrhage occurred in the inferior temporal choroid in 47.62% of examined eyes in PCV group, and in the superior temporal choroid in 23.81% of the PCV group, with significant differences between the quadrants (P<0.001). Vortex vein engorgement and shape differed significantly between PCV, AMD and healthy eyes. The vortex vein branches in PCV eyes were significantly dilated in the posterior pole; moreover, the peripheral choroid and the lower proportion of type IV vortex veins may be pathognomonic for PCV.

The orexinergic system mediates the excitatory effects of caffeine on the arousal and sympathetic activity.

Objective: Caffeine is a non-selective adenosine receptor antagonist with pro-arousal and pro-sympathetic nervous system excitatory effects, and these pharmacological effects fit well with the physiological functions of orexin. The purpose of this study was to investigate the role of the orexinergic nervous system in the pharmacological effects of caffeine. Methods: An animal model of sleepiness caused by adenosine accumulation was established by sleep deprivation, and caffeine's effects on the spontaneous activity and sympathetic nervous system of the model animals were evaluated by using the open-field experiment and gastrointestinal peristaltic observation, respectively, and the intervention of orexin receptor antagonists on the pharmacological effects of caffeine was also observed. Results: Mice with 8 h of sleep deprivation showed a significant decrease in spontaneous activity and a significant increase in gastrointestinal push distance. After caffeine intervention, the spontaneous activities of sleep-deprived mice significantly increased and gastrointestinal peristalsis significantly decreased dose-dependent, while orexin receptors antagonist blocked the pro-arousal and inhibitory gastrointestinal peristalsis effects of caffeine on sleep-deprived mice. Conclusions: Orexinergic nervous system mediated caffeine's excitatory effects on the pro-arousal and pro-sympathetic nervous systems. Orexin is likely to be an important performer in the pharmacological effects of caffeine.

Current Research Trends, Hotspots, and Frontiers of Physical Activity during Pregnancy: A Bibliometric Analysis.

PURPOSE: Physical activity (PA) during pregnancy has been proven beneficial to pregnant women, with a significant effect on ameliorating many severe gestational complications. This work aimed to reveal current research trends, hotspots, and future frontiers in PA during pregnancy. METHODS: Software CiteSpace was used to perform a bibliometric analysis with 1415 publications in the Web of Science Core Collection. RESULTS: the number of published papers on PA during pregnancy has increased gradually by year. The United States has made the most significant contribution to the research on this topic, ranking first in the world in both the number and centrality of research. A total of 54 articles (3.8%) were published in 2022. A majority of publications were research articles (n = 1176, 78.9%). The authors and institutions of the research published have more inter-country collaborations. Different patterns of PA, prevention, and amelioration of pregnancy complications are major research hotspots. Improvement of sedentary behaviour, lifestyle intervention through leisure-time PA, and preterm care are major research frontiers and have received extensive attention in recent years. CONCLUSIONS: The current scientometric study presents an overview of PA during pregnancy research conducted throughout the preceding decades. The conclusions of this work might serve as a reference for researchers who are interested in this field.

Auto-Segmentation Ultrasound-Based Radiomics Technology to Stratify Patient With Diabetic Kidney Disease: A Multi-Center Retrospective Study.

Background: An increasing proportion of patients with diabetic kidney disease (DKD) has been observed among incident hemodialysis patients in large cities, which is consistent with the continuous growth of diabetes in the past 20 years. Purpose: In this multicenter retrospective study, we developed a deep learning (DL)-based automatic segmentation and radiomics technology to stratify patients with DKD and evaluate the possibility of clinical application across centers. Materials and Methods: The research participants were enrolled retrospectively and separated into three parts: training, validation, and independent test datasets for further analysis. DeepLabV3+ network, PyRadiomics package, and least absolute shrinkage and selection operator were used for segmentation, extraction of radiomics variables, and regression, respectively. Results: A total of 499 patients from three centers were enrolled in this study including 246 patients with type II diabetes mellitus (T2DM) and 253 patients with DKD. The mean intersection-over-union (Miou) and mean pixel accuracy (mPA) of automatic segmentation of the data from the three medical centers were 0.812 ± 0.003, 0.781 ± 0.009, 0.805 ± 0.020 and 0.890 ± 0.004, 0.870 ± 0.002, 0.893 ± 0.007, respectively. The variables from the renal parenchyma and sinus provided different information for the diagnosis and follow-up of DKD. The area under the curve (AUC) of the radiomics model for differentiating between DKD and T2DM patients was 0.674 ± 0.074 and for differentiating between the high and low stages of DKD was 0.803 ± 0.037. Conclusion: In this study, we developed a DL-based automatic segmentation, radiomics technology to stratify patients with DKD. The DL technology was proposed to achieve fast and accurate anatomical-level segmentation in the kidney, and an ultrasound-based radiomics model can achieve high diagnostic performance in the diagnosis and follow-up of patients with DKD.

Physical activity before and during pregnancy and maternal mental health: A systematic review and meta-analysis of observational studies.

OBJECTIVE: To examine the influence of physical activity before and during pregnancy on maternal mental health outcomes. METHODS: Ten electronic databases were searched up to May 11, 2021. Studies of all observational designs (except case studies and reviews) were included, which contained information on the relevant population (women before and or during pregnancy), exposures (objective or subjective measures of physical activity), comparator (low or no physical activity), and outcomes (diagnosis and symptom severity of depression or anxiety, quality of life scores, stress and emotions). RESULTS: Forty-four observational studies (N = 132,399) were included. 'Low' to 'very low' certainty evidence revealed that compared with low levels of PA during pregnancy, high levels of PA were associated with a reduced odds of developing prenatal depression (odds ratio (OR): 0.68, 95% confidence interval (CI): 0.58 to 0.80) and anxiety (OR: 0.67, 95% CI: 0.54 to 0.83). We also found a reduction in the severity of prenatal depressive symptoms (standardized mean difference (SMD): -0.37, 95% CI -0.57 to -0.17), prenatal anxiety symptoms (SMD: -0.45, 95% CI -0.64 to -0.27), and prenatal stress (SMD: -0.33, 95% CI -0.55 to -0.11), concurrent with improved quality of life (SMD: 0.38, 95% CI 0.23 to 0.54). PA before pregnancy did not impact the outcomes of interest. CONCLUSION: Physical activity during pregnancy is associated with a reduction in the odds and severity of prenatal depression and anxiety, as well as reduced stress and improved quality of life. PROSPERO registration number: CRD42020208469.

Leisure-Time Physical Activity before and during Pregnancy Is Associated with Improved Insulin Resistance in Late Pregnancy.

A total of 83 third trimester pregnant women were recruited to examine the role of pre-pregnancy versus late-pregnancy physical activity on maternal insulin resistance. Principal component analysis plots demonstrated a distinction between the high and low Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) groups. The variation was driven primarily by exercise prior to and during pregnancy. Specifically, higher levels of physical activity prior to pregnancy was associated with a lower HOMA-IR and is not modified by other variables. Women who were active prior to pregnancy were more active during pregnancy. These results suggest that being active before pregnancy may be a good strategy for mitigating the risk of insulin resistance during late pregnancy.

Effects of prenatal artificial sweeteners consumption on birth outcomes: a systematic review and meta-analysis.

OBJECTIVE: To examine the influence of prenatal artificial sweetener (AS) consumption on birth outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Online databases (Medline, CINAHL, Embase, Cochrane Library, Scopus, Web of Science, FSTA - the food resource database, and ClinicalTrials.gov) were searched up to 9 April 2020. Studies of all designs (except case studies and reviews) were eligible, which contained information on the relevant population (pregnant women), intervention/exposure (any AS consumption), comparator (no AS consumption) and birth outcomes (preterm delivery, gestational age, birth weight). RESULTS: From 677 citations, ten cohort studies and one randomised controlled trial (n 138 007 women) were included. 'Low' to 'very low' certainty evidence revealed that daily consumption of AS was associated with an increased risk of preterm delivery (three studies, n 129 009; risk ratio = 1·18, 95 % CI 1·09, 1·28, I2 = 9 %), a 24 g increase in birth weight (three studies, n 64 417; mean difference (MD): 23·74 g, 95 % CI 0·89, 45·58, I2 = 0 %) and a 0·11 week decrease in gestational age (three studies, n 64 417; MD: -0·11 weeks, 95 % CI -0·19, -0·03, I2 = 0 %). CONCLUSIONS: 'Low' to 'very low' certainty evidence suggests daily AS consumption during pregnancy is associated with an increased risk of preterm delivery, increased birth weight and decreased gestational age. Additional 'high'-quality research is urgently needed to further assess these relationships.PROSPERO registration number: CRD42019136728.

A Diversified Dietary Pattern Is Associated With a Balanced Gut Microbial Composition of Faecalibacterium and Escherichia/Shigella in Patients With Crohn's Disease in Remission.

BACKGROUND AND AIMS: Crohn's disease [CD] is associated with alterations in gut microbial composition and function. The present controlled-intervention study investigated the relationship between patterns of dietary intake and baseline gut microbiota in CD patients in remission and examined the effects of a dietary intervention in patients consuming a non-diversified diet [NDD]. METHODS: Forty outpatients with quiescent CD were recruited in Calgary, Alberta, Canada. Based on 3-day food records, patients consuming a lower plant-based and higher red and processed meat-based diet were assigned to the NDD group [n = 15] and received a 12-week structured dietary intervention; all other patients were assigned to the diversified diet [DD] control group [n = 25] and received conventional management. Faecal microbiota composition, short chain fatty acids [SCFAs] and calprotectin were measured. RESULTS: At baseline the NDD and DD groups had a different faecal microbial beta-diversity [p = 0.003, permutational multivariate analysis of variance]. The NDD group had lower Faecalibacterium and higher Escherichia/Shigella relative abundances compared to the DD group [3.3 ±â€…5.4% vs. 8.5 ±â€…10.6%; 6.9 ±â€…12.2% vs. 1.6 ±â€…4.4%; p ≤ 0.03, analysis of covariance]. These two genera showed a strong negative correlation [rs = -0.60, q = 0.0002]. Faecal butyrate showed a positive correlation with Faecalibacterium [rs = 0.52, q = 0.002], and an inhibitory relationship with Escherichia/Shigella abundance [four-parameter sigmoidal model, R = -0.83; rs = -0.44, q = 0.01], respectively. After the 12 weeks of dietary intervention, no difference in microbial beta-diversity between the two groups was observed [p = 0.43]. The NDD group demonstrated an increase in Faecalibacterium [p < 0.05, generalized estimated equation model], and resembled the DD group at the end of the intervention [p = 0.84, t-test with permutation]. We did not find an association of diet with faecal SCFAs or calprotectin. CONCLUSIONS: Dietary patterns are associated with specific gut microbial compositions in CD patients in remission. A diet intervention in patients consuming a NDD modifies gut microbial composition to resemble that seen in patients consuming a DD. These results show that diet is important in shaping the microbial dysbiosis signature in CD towards a balanced community.

Prenatal Exercise and Cardiorespiratory Health and Fitness: A Meta-analysis.

PURPOSE: This study aimed to examine the influence of prenatal exercise on maternal cardiorespiratory health and fitness during pregnancy. METHODS: Online databases were searched up to February 25, 2019. Studies of randomized controlled trials (RCTs) were eligible, which contained information on the relevant population (pregnant women), intervention (subjective or objective measures of frequency, intensity, duration, volume, or type of exercise), comparator (no exercise intervention), and outcomes (maternal cardiorespiratory fitness, including V˙O2max, submaximal V˙O2, V˙O2 at anaerobic threshold, and cardiorespiratory health, including resting heart rate, and resting systolic and diastolic blood pressures during pregnancy). RESULTS: From 2699 unique citations, 26 RCTs (N = 2292 women) were included. Of these, one study reported measured V˙O2max, seven reported predicted V˙O2max, three reported submaximal V˙O2, and two studies reported VO2AT. "Low"- to "high"-certainty evidence revealed that exercise was associated with improved predicted/measured V˙O2max (5 RCTs, n = 430; mean difference [MD], 2.77 mL·kg·min; 95% confidence interval [CI], 0.32 to 5.21 mL·kg·min; I = 69%), reduced resting heart rate (9 RCTs, n = 637; MD, -1.71 bpm; 95% CI, -3.24 to -0.19 bpm; I = 13%), resting systolic blood pressure (16 RCTs, n = 1672; MD, -2.11 mm Hg; 95% CI, -3.71 to -0.51 mm Hg; I = 69%), and diastolic blood pressure (15 RCTs, n = 1624; MD, -1.77 mm Hg; 95% CI, -2.90 to -0.64 mm Hg; I = 60%). CONCLUSION: Prenatal exercise interventions improve maternal predicted/measured V˙O2max and reduce resting heart rate and blood pressure. This review highlights the need for additional high-quality studies of cardiorespiratory fitness (namely, V˙O2max and V˙O2 peak) in pregnancy.PROSPERO registration number: CRD42019131249.

The impact of occupational activities during pregnancy on pregnancy outcomes: a systematic review and metaanalysis.

OBJECTIVE: Data: An increasing number of studies suggest that exposure to physically demanding work during pregnancy could be associated with increased risks of adverse pregnancy outcomes, but the results remain conflicted and inconclusive. The purpose of this study was to examine the influence of occupational activities during pregnancy on maternal and fetal health outcomes. STUDY: Studies of all designs (except case studies and reviews) that contained information on the relevant population (women who engaged in paid work during pregnancy), occupational exposures (heavy lifting, prolonged standing, prolonged walking, prolonged bending, and heavy physical workload), comparator (no exposure to the listed physical work demands), and outcomes (preterm birth, low birthweight, small for gestational age, miscarriage, gestational hypertension, preeclampsia, gestational diabetes mellitus, stillbirth, and intrauterine growth restriction) were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Five electronic databases and 3 gray literature sources were searched up to March 15, 2019. RESULTS: Eighty observational studies (N=853,149) were included. Low-to-very low certainty evidence revealed that lifting objects ≥11 kg was associated with an increased odds ratio of miscarriage (odds ratio, 1.31; 95% confidence interval, 1.08-1.58; I2=79%), and preeclampsia (odds ratio, 1.35; 95% confidence interval, 1.07-1.71; I2=0%). Lifting objects for a combined weight of ≥100 kg per day was associated with an increased odds of preterm delivery (odds ratio, 1.31; 95% confidence interval, 1.11-1.56; I2=0%) and having a low birthweight neonate (odds ratio, 2.08; 95% confidence interval, 1.06-4.11; I2=73%). Prolonged standing was associated with increased odds of preterm delivery (odds ratio, 1.11; 95% confidence interval, 1.02-1.22; I2=30%) and having a small-for-gestational-age neonate (odds ratio, 1.17; 95% confidence interval, 1.01-1.35; I2=41%). A heavy physical workload was associated with increased odds of preterm delivery (odds ratio, 1.23; 95% confidence interval, 1.07-1.41; I2=32%) and having a low birthweight neonate (odds ratio, 1.79; 95% confidence interval, 1.11-2.87; I2=87%). All other associations were not statistically significant. Dose-response analysis showed women stand for >2.5 hours per day (vs no standing) had a 10% increase in the odds of having a preterm delivery. CONCLUSION: Physically demanding work during pregnancy is associated with an increased risk of adverse pregnancy outcomes.