Effects of Parental Predictors on Postpartum Depression.

BACKGROUND: Postpartum depression (PPD) is highly prevalent and plagues a significant proportion of parents. Postpartum depression also exerts various negative consequences on infant development and parent-infant relationships. Social support is identified as an important factor influencing many parental predictors, and may affect the development of PPD. OBJECTIVE: This study aimed to investigate how perceived social support can indirectly influence PPD symptoms in parents at 6 months postpartum by influencing postpartum anxiety, parental satisfaction, and parental self-efficacy (PSE). METHODS: A secondary analysis of data from a randomized controlled trial was used with a cross-sectional exploratory design. A total of 400 Singaporean parents (200 couples) were included, and structural equation modeling was used to analyze the relationships between PPD and potential predictors. RESULTS: Findings revealed a less adequate fit between the hypothesized model and the data collected. Social support was found to be a significant predictor of postpartum anxiety, PSE, and parental satisfaction. Postpartum anxiety was a significant predictor of PPD, but PSE and parental satisfaction were not. CONCLUSION: This study provides an overview of how different parental predictors may be associated with PPD among Asian parents. Postpartum anxiety significantly predicted PPD, but social support had negative effects on postpartum anxiety, parenting satisfaction, and PSE. The findings provide further insight into how parents at risk of PPD can be identified and demonstrated how social support might negatively impact parental outcomes. More qualitative research with Asian parents is needed to further explain these findings and inform the development of future interventions.

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.

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation.

Macrophages and microglia are professional phagocytes that sense and migrate toward "eat-me" signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out "find-me" signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between "eat-me" and "don't-eat-me" signals at different stages in their lifespan, while the "don't-eat-me" signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the "don't-eat-me" CD47/SIRPα and "eat-me" CALR/STC1 ligand-receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).

Development and validation of the Dermatology Social Comparison (DSC) Scale.

BACKGROUND: Social comparison, the process of evaluating one's characteristics in relation to others, influences individuals' self-perception and behavior. However, instruments are scarce for assessing social comparison in the medical setting. OBJECTIVES: Our aim was to develop and validate a new scale for assessing social comparison. MATERIALS AND METHODS: Seven statements were developed, encompassing the perceived normality of having rashes, the tendency to compare their situation with others, and the emotional response when seeing someone better or worse off than themselves. The instrument was piloted in 15 patients for readability and face validity, then prospectively validated using modern psychometric methods in 1,053 adult patients with eczema or psoriasis from three tertiary dermatological centers in Singapore. RESULTS: Of 1,053 adult patients, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Exploratory factor analysis (using a 70% sample split) showed a single factor model comprising three questions (Eigenvalue: 1.4). Confirmatory factor analysis with the remaining 30% of the sample confirmed an excellent model fit. Cronbach's alpha was 0.7, and inter-item correlations ranged from 0.42 to 0.46. In the Rasch analysis, item fit statistics and item characteristic curves showed appropriate discrimination between response options, although reliability was suboptimal with a person separation reliability of 0.63. CONCLUSIONS: Comprising 3 questions, the newly derived social comparison scale showed acceptable psychometrics as a measure of social comparison for clinical and research purposes in dermatology. Its brief nature likely results from its brevity and applicability to conditions beyond eczema and psoriasis, which warrants further investigation.

Activin receptors in human cancer: Functions, mechanisms, and potential clinical applications.

Activins are members of the transforming growth factor-ß (TGF-ß) superfamily and act as key regulators in various physiological processes, such as follicle and embryonic development, as well as in multiple human diseases, including cancer. They have been established to signal through three type I and two type II serine/threonine kinase receptors, which, upon ligand binding, form a final signal-transducing receptor complex that activates downstream signaling and governs gene expression. Recent research highlighted the dysregulation of the expression or activity of activin receptors in multiple human cancers and their critical involvement in cancer progression. Furthermore, expression levels of activin receptors have been associated with clinicopathological features and patient outcomes across different cancers. However, there is currently a paucity of comprehensive systematic reviews of activin receptors in cancer. Thus, this review aimed to consolidate existing knowledge concerning activin receptors, with a primary emphasis on their signaling cascade and emerging biological functions, regulatory mechanisms, and potential clinical applications in human cancers in order to provide novel perspectives on cancer prognosis and targeted therapy.

Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility.

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.

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.

Macrophage polarization in spinal cord injury repair and the possible role of microRNAs: A review.

The prevention, treatment, and rehabilitation of spinal cord injury (SCI) have always posed significant medical challenges. After mechanical injury, disturbances in microcirculation, edema formation, and the generation of free radicals lead to additional damage, impeding effective repair processes and potentially exacerbating further dysfunction. In this context, inflammatory responses, especially the activation of macrophages, play a pivotal role. Different phenotypes of macrophages have distinct effects on inflammation. Activation of classical macrophage cells (M1) promotes inflammation, while activation of alternative macrophage cells (M2) inhibits inflammation. The polarization of macrophages is crucial for disease healing. A non-coding RNA, known as microRNA (miRNA), governs the polarization of macrophages, thereby reducing inflammation following SCI and facilitating functional recovery. This study elucidates the inflammatory response to SCI, focusing on the infiltration of immune cells, specifically macrophages. It examines their phenotype and provides an explanation of their polarization mechanisms. Finally, this paper introduces several well-known miRNAs that contribute to macrophage polarization following SCI, including miR-155, miR-130a, and miR-27 for M1 polarization, as well as miR-22, miR-146a, miR-21, miR-124, miR-223, miR-93, miR-132, and miR-34a for M2 polarization. The emphasis is placed on their potential therapeutic role in SCI by modulating macrophage polarization, as well as the present developments and obstacles of miRNA clinical therapy.

Manganese-Based Nanotheranostics for Magnetic Resonance Imaging-Mediated Precise Cancer Management.

Manganese (Mn)-based magnetic resonance imaging (MRI) has become a competitive imaging modality for cancer diagnosis due to its advantages of non-invasiveness, high resolution and excellent biocompatibility. In recent years, a variety of Mn contrast agents based on different material systems have been synthesized, and a series of multi-purpose Mn nanocomposites have also emerged, showing satisfactory relaxation efficiency and MRI performance thus possess the transformation and application value in MRI-synergized cancer diagnosis and treatment. This tutorial review starts from the classification and properties of Mn-based nanomaterials, and then summarizes various preparation and functionalization strategies of nanosized Mn contrast agents, especially focuses on the latest progress of Mn contrast agents in MRI-synergized precise cancer theranostics. In addition, present review also discusses the current clinical transformation obstacles such as unclear molecular mechanisms, potential nanotoxicity, and scale production constraints. This paper provides evidence-based recommendations about the future prospects of multifunctional nanoplatforms, as well as technical guidance and panoramic expectations for the design of clinically meaningful cancer management programs.

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.

Understanding Discordant Perceptions of Disease Severity Between Physicians and Patients With Eczema and Psoriasis Using Structural Equation Modeling.

Importance: Patients and physicians often have differing opinions on the patient's disease severity. This phenomenon, termed discordant severity grading (DSG), hinders the patient-physician relationship and is a source of frustration. Objective: To test and validate a model explaining the cognitive, behavioral, and disease factors associated with DSG. Design, Setting, and Participants: A qualitative study was first performed to derive a theoretical model. In this subsequent prospective cross-sectional quantitative study, the qualitatively derived theoretical model was validated using structural equation modeling (SEM). Recruitment was conducted between October 2021 and September 2022. This was a multicenter study in 3 Singapore outpatient tertiary dermatological centers. Dermatology patients and their attending physicians were recruited by convenience sampling. Patients were aged 18 to 99 years with psoriasis or eczema of at least 3 months' duration and recruited only once. The data were analyzed between October 2022 to May 2023. Main Outcomes and Measures: The outcome was the difference between global disease severity (0-10 numerical rating scale with a higher score indicating greater severity) as independently scored by the patient and the dermatologist. Positive discordance was defined as patient-graded severity more than 2 points higher (graded more severely) than physicians, and negative discordance if more than 2 points lower than physicians. Confirmatory factor analysis followed by SEM was used to assess the associations between preidentified patient, physician, and disease factors with the difference in severity grading. Results: Of the 1053 patients (mean [SD] age, 43.5 [17.5] years), a total of 579 (55.0%) patients were male, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Of 44 physicians recruited, 20 (45.5%) were male, 24 (54.5%) were aged between 31 and 40 years, 20 were senior residents or fellows, and 14 were consultants or attending physicians. The median (IQR) number of patients recruited per physician was 5 (2-18) patients. Of 1053 patient-physician pairs, 487 pairs (46.3%) demonstrated discordance (positive, 447 [42.4%]; negative, 40 [3.8%]). Agreement between patient and physician rating was poor (intraclass correlation, 0.27). The SEM analyses showed that positive discordance was associated with higher symptom expression (standardized coefficient B = 0.12; P = .02) and greater quality-of-life impairment (B = 0.31; P < .001), but not patient or physician demographics. A higher quality-of-life impairment was in turn associated with lower resilience and stability (B = -0.23; P < .001), increased negative social comparisons (B = 0.45; P < .001), lower self-efficacy (B = -0.11; P = .02), increased disease cyclicity (B = 0.47; P < .001), and greater expectation of chronicity (B = 0.18; P < .001). The model was well-fitted (Tucker-Lewis: 0.94; Root Mean Square Error of Approximation: 0.034). Conclusions and Relevance: This cross-sectional study identified various modifiable contributory factors to DSG, increased understanding of the phenomenon, and set a framework for targeted interventions to bridge this discordance.

miR-31 ameliorates type 2 diabetic vascular damage through up-regulation of hypoxia-inducible factor-1α/vascular endothelial growth factor-A.

AIMS: microRNA may be a new therapeutic direction for diabetes. As a typical tumor marker, miR-31 is involved in a variety of metabolic diseases, but the specific role is still unclear. This study aimed to investigate the effect of miR-31 on type 2 diabetes mellitus and its accompanying vascular injury, as well as on the effects of hypoxia-inducible factor-1α inhibitor (HIF1AN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF)-A expression in vitro and in vivo. MATERIALS AND METHODS: In vitro, a model of high-fat and high-glucose-induced human aortic endothelial cell (HAEC) injury was established to simulate diabetes mellitus (DM). Cell functions were compared between the control group, the DM damage group, and the group transfected with miR-31 after DM damage. In vivo, overexpressing miR-31 FVB mice and FVB mice were divided into the control and induced type 2 diabetes mellitus groups. Type 2 diabetes mellitus models were induced by a high-fat diet combined with streptozotocin. The lipid metabolism levels, viscera, and vascular damage were compared between the control and type 2 diabetes mellitus groups. RESULTS: In vitro, miR-31 improved the proliferation ability of damaged cells by targeting HIF1AN and up-regulating the expression of HIF-1α and VEGF-A. In vivo, miR-31 ameliorated the development of type 2 diabetes mellitus, disturbance of glucose and lipid metabolism, and damage to some organs. Meanwhile, miR-31 had a protective effect on vascular damage complicated by type 2 diabetes mellitus by increasing the levels of HIF-1α and VEGF-A. CONCLUSION: Our experiments show that miR-31 can delay the progression of type 2 diabetes mellitus and ameliorate diabetic vascular injury.

Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) has relatively ineffective first/second-line therapy for advanced disease and only 18% five-year survival for early disease. Drug-induced mitochondrial priming measured by dynamic BH3 profiling identifies efficacious drugs in multiple disease settings. We use high throughput dynamic BH3 profiling (HTDBP) to identify drug combinations that prime primary MPM cells derived from patient tumors, which also prime patient derived xenograft (PDX) models. A navitoclax (BCL-xL/BCL-2/BCL-w antagonist) and AZD8055 (mTORC1/2 inhibitor) combination demonstrates efficacy in vivo in an MPM PDX model, validating HTDBP as an approach to identify efficacious drug combinations. Mechanistic investigation reveals AZD8055 treatment decreases MCL-1 protein levels, increases BIM protein levels, and increases MPM mitochondrial dependence on BCL-xL, which is exploited by navitoclax. Navitoclax treatment increases dependency on MCL-1 and increases BIM protein levels. These findings demonstrate that HTDBP can be used as a functional precision medicine tool to rationally construct combination drug regimens in MPM and other cancers.

Evaluating the Effects of the Supportive Parenting App on Infant Developmental Outcomes: Longitudinal Study.

BACKGROUND: Previous studies have investigated the various effects of parenting on infant developmental outcomes. In particular, parental stress and social support have been found to significantly affect the growth of the newborn. Although many parents today use mobile apps to obtain more support in parenting and perinatal care, few studies have examined how these apps could affect infant development. OBJECTIVE: This study aimed to examine the effectiveness of the Supportive Parenting App (SPA) in improving infant developmental outcomes during the perinatal period. METHODS: This study adopted a 2-group parallel prospective longitudinal design and recruited 200 infants and their parents (N=400 mothers and fathers). The parents were recruited at 24 weeks of gestation for a randomized controlled trial conducted from February 2020 to July 2022. They were randomly allocated to either the intervention or control group. The infant outcome measures included cognition, language, motor skills, and social-emotional development. Data were collected from the infants when they were aged 2, 4, 6, 9, and 12 months. Linear and modified Poisson regressions were used to analyze the data to examine between- and within-group changes. RESULTS: At 9 and 12 months post partum, the infants in the intervention group were found to have better communication and language skills than those in the control group. An analysis of motor development revealed that a larger proportion of the infants in the control group fell under the at-risk category, where they scored approximately 2 SDs below the normative scores. The control group infants scored higher on the problem solving domain at 6 months post partum. However, at 12 months postpartum, the infants in the intervention group performed better on cognitive tasks than those in the control group. Despite not being statistically significant, the intervention group infants were found to have consistently scored better on the social components of the questionnaires than the control group infants. CONCLUSIONS: Overall, the infants whose parents had received the SPA intervention tended to fare better in most developmental outcome measures than those whose parents had received standard care only. The findings of this study suggest that the SPA intervention exerted positive effects on the communication, cognition, motor, and socioemotional development of the infants. Further research is needed to improve the content and support provided by the intervention to maximize the benefits gained by infants and their parents. TRIAL REGISTRATION: ClinicalTrials.gov NCT04706442; https://clinicaltrials.gov/ct2/show/NCT04706442.

Evaluating the Effectiveness of the Supportive Parenting App on Parental Outcomes: Randomized Controlled Trial.

BACKGROUND: Adjusting to new or additional parenting responsibilities increases stress and affects parental well-being. Existing research has highlighted both parents' desire to receive more support. It has also been found that receiving sufficient social support enhances parenting outcomes. With the increasing popularity of mobile health apps, a Supportive Parenting App (SPA) intervention was developed to fulfill the support needs of parents during the perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of the SPA on parental outcomes during the perinatal period. METHODS: A 2-group pretest and repeated posttest randomized controlled trial was conducted wherein 200 couples (N=400 mothers and fathers) were recruited from 2 public health care institutions in Singapore. Parents were randomly assigned to intervention (100/200, 50%) or control (100/200, 50%) groups. The SPA intervention consisted of a mobile app-based psychoeducation and peer support program to support parents from pregnancy to 6 months post partum. The outcome measures included postnatal depression, anxiety, parental bonding, parental self-efficacy, perceived social support, and parenting satisfaction. Data were collected at baseline (at >24 weeks of gestation-age of viability in Singapore) and at the first, second, fourth, sixth, ninth, and 12th month post partum. Linear mixed models were used to compare parental outcomes between the groups, and a linear mixed model for repeated measures was used to examine within-group changes. RESULTS: Parents in the intervention group mostly showed better outcomes compared with those in the control group. Parents in the intervention group had higher perceived social support than those in the control group at the first (effect size=1.59, 95% CI 0.38-2.80; Cohen standardized effect size=1.31; P=.01), second (effect size=1.98, 95% CI 1.09-2.88; Cohen standardized effect size=2.21; P=.003), and fourth (effect size=2.57, 95% CI 1.62-3.51; Cohen standardized effect size=2.72; P=.048) months post partum. However, parents in the intervention group showed significantly poorer parental bonding (effect size=1.67, 95% CI 0.24-3.11; Cohen standardized effect size=1.16; P=.02). The other parental outcomes did not differ significantly between groups. The scores of mothers and fathers also differed significantly for all outcomes except parental self-efficacy. CONCLUSIONS: Parents in the intervention group generally fared better, especially regarding perceived social support. However, the lack of statistical significance in most outcomes showed the limited effectiveness of the SPA intervention, which may be because of the COVID-19 pandemic. Parental differences in outcome scores suggest that mothers and fathers have different support needs; therefore, interventions should be tailored accordingly. Further improvements and evaluations are needed to examine the effectiveness of the SPA intervention in enhancing parental outcomes. Despite statistically insignificant results, limitations should be considered to further improve mobile health app-based interventions such as SPA, as they could serve as reliable and convenient sources of support for parents. TRIAL REGISTRATION: Clinicaltrails.gov NCT4706442; https://clinicaltrials.gov/ct2/show/NCT04706442.

MiR-31 improves spinal cord injury in mice by promoting the migration of bone marrow mesenchymal stem cells.

BACKGROUND: Stem cell transplantation therapy is a potential approach for the repair of spinal cord injuries and other neurodegenerative diseases, but its effectiveness is hampered by the low rate of targeted migration of cells to the area of injury. The aim of this study was to investigate the effects of miR-31 on the migration of bone marrow mesenchymal stem cells (BMSCs) and the regulation of MMP-2 and CXCR4 expression in vitro and in vivo. METHODS: eGFP-expressing BMSCs were isolated and cultured for subsequent experiments. The experiments were divided into three groups: control group, miR-31agomir group, and miR-31antagomir group. Proliferation was analyzed using CCK-8 and flow cytometry; cell migration in vitro was analyzed using wound-healing and transwell assays. The mouse SCI model was prepared by the impact method, and cells were transplanted (3 groups, 12 per group). Relevant inflammatory factors were detected by ELISA. The BMS score was used to evaluate the functional recovery of the mouse spinal cord and the frozen section was used to analyze the cell migration ability in vivo. The in vitro and in vivo expression levels of MMP-2 and CXCR4 were evaluated by Western blot and immunohistochemical staining. RESULTS: In vitro experiments showed that cells in the miR-31agomir group exhibited enhanced cell proliferation (P<0.05, P<0.001) and migration (P<0.001) and upregulated protein expression levels of CXCR4 (P<0.01) and MMP-2 (P<0.001) compared with cells in the control group. The results of in vivo experiments showed that the expression of pro-inflammatory factors was reduced after cell transplantation treatment. Cells in the miR-31agomir group showed enhanced cell-targeted migration ability (P<0.001), improved the function of damaged tissues (P<0.001), and upregulated CXCR4 and MMP-2 expression compared to the control group (P<0.001). CONCLUSION: Our experiment demonstrated that miR-31 could promote the migration of BMSCs and miR-31 could repair and improve the function of damaged tissues in SCI.

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.

Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer.

Conventional chemotherapy is still of great utility in oncology and rationally constructing combinations with it remains a top priority. Drug-induced mitochondrial apoptotic priming, measured by dynamic BH3 profiling (DBP), has been shown in multiple cancers to identify drugs that promote apoptosis in vivo. We therefore hypothesized that we could use DBP to identify drugs that would render cancers more sensitive to conventional chemotherapy. We found that targeted agents that increased priming of non-small cell lung cancer (NSCLC) tumor cells resulted in increased sensitivity to chemotherapy in vitro. To assess whether targeted agents that increase priming might enhance the efficacy of cytotoxic agents in vivo as well, we carried out an efficacy study in a PC9 xenograft mouse model. The BH3 mimetic navitoclax, which antagonizes BCL-xL, BCL-w, and BCL-2, consistently primed NSCLC tumors in vitro and in vivo. The BH3 mimetic venetoclax, which electively antagonizes BCL-2, did not. Combining navitoclax with etoposide significantly reduced tumor burden compared to either single agent, while adding venetoclax to etoposide had no effect on tumor burden. Next, we assessed priming of primary patient NSCLC tumor cells on drugs from a clinically relevant oncology combination screen (CROCS). Results confirmed for the first time the utility of BCL-xL inhibition by navitoclax in priming primary NSCLC tumor cells and identified combinations that primed further. This is a demonstration of the principle that DBP can be used as a functional precision medicine tool to rationally construct combination drug regimens that include BH3 mimetics in solid tumors like NSCLC.