Chiral Brønsted Acid-Catalyzed Intramolecular Asymmetric Dearomatization Reaction of Indoles with Cyclobutanones via Cascade Friedel-Crafts/Semipinacol Rearrangement.

The highly efficient synthesis of chiral indolines fused with an azabicyclo[2.2.1]heptanone moiety is achieved by an asymmetric dearomatization reaction of indoles with cyclobutanones. A new chiral imidodiphosphorimidate (IDPi) catalyst is synthesized and exhibits extraordinary activity in promoting a cascade Friedel-Crafts/semipinacol rearrangement. Target molecules are prepared in good yields (up to 95%) with excellent enantioselectivity (up to 98% ee) with operational convenience. Combined experimental and computational studies provide detailed mechanistic insights into the energy landscape and origin of the stereochemical induction of the reaction.

Impact of professional identity on learner well-being of undergraduate nursing students of "double tops" universities: Mediating effect of self-regulated learning.

OBJECTIVES: The pressure of internal competition at the college level has increased in recent years in China with an impact on nursing students' learning and well-being. This study aimed to investigate the current situation and factors affecting professional identity, learner well-being and self-regulated learning of undergraduate nursing students in the Neijuan ecology of the "double tops" universities, and to explore the relationships between these three variables. METHODS: A cross-sectional design was adopted to conduct an online survey of 322 Chinese undergraduate nursing students from seven "double tops" universities. The survey included socio-demographics characteristics, students' professional identity, learner well-being, and self-regulated learning. RESULTS: Results of Pearson correlation analysis showed that professional identity was significantly and positively correlated with learner well-being (R = 0.795, p < 0.001); professional identity was significantly and positively correlated with self-regulated learning (R = 0.843, p < 0.001); and, self-regulated learning was significantly and positively correlated with learner well-being (R = 0.852, p < 0.001). After mediation effect testing, self-regulated learning had a mediating effect between professional identity and learner well-being (95 % CI 0.366-0.548, p < 0.001). Professional identity had a positive predictive effect on self-regulated learning (a = 0.570, p < 0.001), and self-regulated learning also had a positive predictive effect on learner well-being (b = 0.798, p < 0.001). The direct effect of professional identity on learner well-being (0.225) and its mediating effect (0.455) account for 33.1 % and 66.9 % of the total effect (0.680), respectively. CONCLUSIONS: The learner well-being of undergraduate Chinese nursing students is in the middle to upper range, and it is crucial to enhance professional identity and develop students' self-regulated learning to improve their learner well-being. This study provides empirical evidence to support the mediating effect of self-regulated learning on the relationship between professional identity and learner well-being among undergraduate nursing students in "double tops" universities. Universities are expected to strengthen career planning guidance and professional competence training for students as early as possible in order to develop quality nursing education programs that produce graduates who enter and remain in the workforce.

All-cause and suicide mortality after first psychiatric admission in adolescents and young adults: A longitudinal follow-up study.

BACKGROUND: This study investigated all-cause and suicide mortality rates in adolescents and young adults following an initial psychiatric admission to elucidate the long-term outcomes for this vulnerable group by focusing on the risks associated with various psychiatric diagnostic categories. METHODS: This study involved 9762 adolescents and young adults discharged from their first psychiatric admission and matched 1:1 with 9762 individuals discharged following a diagnosis of appendicitis on the basis of birth year and sex by using Taiwan's National Health Insurance Research Database. Both stratified (model 1) and standard (model 2) Cox regression analyses were conducted to assess variations in all-cause and suicide mortality between the groups. RESULTS: Over the 15-year follow-up period, the adolescents and young adults discharged from their first psychiatric admission exhibited an approximately 3-fold increased risk of death from any cause (hazard ratio [HR]: 2.97 in model 1, 2.83 in model 2) and an approximately ten times higher risk of suicide (11.13 in model 1, 9.23 in model 2) compared with those discharged with a diagnosis of appendicitis. Those discharged with alcohol use disorder or major depressive disorder exhibited higher hazard ratios for both all-cause and suicide compared with the reference group. CONCLUSIONS: The findings reveal a considerable risk of all-cause and suicide mortality in adolescents and young adults following discharge from their first psychiatric admission. These results highlight an urgent need for tailored interventions and continued support for this demographic.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Nutritional support clinical efficacy in tuberculosis: quasi-experimental study.

OBJECTIVE: This study aimed to investigate the impact of nutritional support on the clinical efficacy in hospitalised tuberculosis patients with nutritional risk. METHODS: We selected a total of 266 eligible patients with tuberculosis for the experimental and 190 patients for control groups. The patients in intervention group received adjusted dietary structure, enteral nutrition via oral intake or gastric tube, total parenteral nutrition and combined enteral and parenteral nutrition. We recorded various factors, including age, sex, underlying disease, tuberculosis type, nutritional risk at admission, serum albumin (ALB), body mass index, complications during hospitalisation, nutritional support status, serum ALB before discharge and length of hospital stay. RESULTS: The incidences of nutritional risk in the control and experimental groups were 64.41% and 64.72%, respectively, with no statistically significant differences in baseline characteristics. The occurrence rates of complications and secondary infections in the experimental group were 57.89% and 51.5%, respectively, which were significantly lower than the control group's rates of 70.00% and 56.31%. These differences were statistically significant. The experimental group had a significantly shorter hospital stay (16.5±7.54 days) compared with the control group (19.55±7.33 days). Furthermore, the serum ALB levels of patients in the experimental group were higher on discharge than at admission. CONCLUSION: Hospitalised patients with tuberculosis often face a high incidence of nutritional risk. However, the implementation of standardised nutritional support treatment has shown promising results in improving the nutritional status of tuberculosis patients with nutritional risk. This approach not only helps reduce the occurrence of complications but also enhances short-term prognosis and improves overall clinical efficacy.

RNA nanotherapeutics with fibrosis overexpression and retention for MASH treatment.

Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed "Fibrosis overexpression and retention (FORT)". In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

The association between diverse psychological protocols and the efficacy of psilocybin-assisted therapy for clinical depressive symptoms: a Bayesian meta-analysis.

Objective: Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method: Five major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale. Results: There were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support(k=3), (iii) non-manualized nondirective psychological support(k=5); and (iv) non-manualized supportive psychotherapy(k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70). Conclusion: Compared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy. Systemic review registration: Open Science Framework: identifier (osf.io/3YUDV).

Risk of Dementia in Different Types of Cancer Survivors: A Nationwide Cohort Study.

OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.

How does ferrocene correlate with ferroptosis? Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agents.

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a "one stone kills two birds" strategy. Ferroptosis selectivity assays, GPX4 inhibitory activity and CETSA experiments validated the inhibition of novel compounds on GPX4. In particular, the ROS-related bioactivity assays highlighted the ROS-inducing ability of 17 at the molecular level and their ferroptosis enhancement at the cellular level. These data confirmed the dual role of ferrocene as both the bioisostere motif maintaining the inhibition capacity of certain molecules with GPX4 and also as the ROS producer to enhance the vulnerability to ferroptosis of cancer cells, thereby attenuating tumor growth in vivo. This proof-of-concept study of ferrocenyl-appended ferroptosis inducers via rational design may not only advance the development of ferroptosis-based anticancer treatment, but also illuminate the multiple roles of the ferrocenyl component, thus opening the way to novel bioorganometallics for potential disease therapies.

Glucose metabolism disorder related to follicular fluid exosomal miR-122-5p in cumulus cells of endometriosis patients.

MiR-122-5p, high expression in follicular fluid exosomes of patients with endometriosis, impairs the glucose metabolism function of cumulus cells and may further impair oocyte quality. Endometriosis (EMs) affects fertility in women of childbearing age in many ways. However, the mechanisms are complex, including the decrease in oocyte quality, which still needs to be studied. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, such as follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aims to elucidate the mechanism of EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST) and the control group (Ctrl). Mouse cumulus oocyte complexes (COCs) were cocultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG cells (human ovarian granulosa cell line) transfected with miRNA mimic and inhibitor. Our date suggest that follicular fluid exosomes from patients with untreated EMs reduce the maturation rate and damage the quality of mouse oocytes. MiR-122-5p, overexpressed in untreated EMs, inhibits the translation of key aldolase enzymes related to glucose metabolism and partially impairs cumulus cells of endometriosis patients.

Single-cell RNA sequencing uncovers cellular heterogeneity and the progression of heterotopic ossification of the elbow.

Heterotopic ossification of the elbow (HOE) is a complicated pathologic process characterized by extra bone formation in the elbow. Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells into osteoblasts. The aim of this study was to explore the cellular origin and progression of HOE by single-cell RNA sequencing. We identified 13 clusters of cells in HOE and further analyzed the subclusters for 4 of the main cell types. Six subclusters of osteoblasts, nine subclusters of chondrocytes, six subclusters of fibroblasts, and five subclusters of mononuclear phagocytes (MPs) were identified and analyzed. The new findings on osterix (OSX) and SOX9 expression in osteoblast subclusters and chondrocyte subclusters indicate that HOE is mediated through endochondral ossification. Further identification of the corresponding signature gene sets of distinct subclusters indicated that subclusters of osteoblasts_3, osteoblasts_4, osteoblasts_5, and osteoblasts_6 are relatively more mature during the osteoblastic progression of HOE. The trajectory analysis of the osteoblasts demonstrated that some genes were gradually downregulated, such as CRYAB, CCL3, SFRP4, WIF1, and IGFBP3, while other critical genes were upregulated, such as VCAN, IGFBP4, FSTL1, POSTN, MDK, THBS2, and ALPL, suggesting that these factors may participate in HOE progression. Cell-cell communication networks revealed extensive molecular interactions among the 13 HOE clusters. Ligand-receptor pairs for IL6, COL24A1, COL22A1, VWF, FZD6, FGF2, and NOTCH1 were identified, suggesting that multiple signaling pathways may be involved in HOE. In conclusion, this study provided the cellular atlas for HOE. We have established a greater extent of the heterogeneity of HOE cells than previously known through transcriptomic analysis at the single-cell level. We have observed gradual patterns of signature gene expression during the differentiation and maturation progression of osteoblasts from stem cells in HOE with higher resolution. The cell heterogeneity of HOE deserves further investigation to pave the way for identification of potential targets for HOE early diagnosis and therapeutic treatment.

Omentum pregnancy resulting in severe hemoperitoneum: Lessons learned from a review of the literature along with a case report.

Abdominal pregnancies are a rare form of ectopic pregnancy with omentum pregnancies being even rarer. Ectopic pregnancy should be diagnosed and terminated early to prevent the risk of harm to the mother. This case report describes a rare case of omentum pregnancy with severe hemoperitoneum. The patient had not visited a doctor until she failed to menstruate for 3 months, by which point she had developed severe hypogastralgia. The patient was diagnosed with a ruptured ectopic pregnancy after ultrasonography. The omentum pregnancy was complicated by severe hemoperitoneum, which was confirmed by emergency laparotomy. The patient was treated successfully with fetal extraction and partial omentectomy. Ultrasound examination in early pregnancy is essential to detect and treat ectopic pregnancies as early as possible, as surgery is usually required for abdominal pregnancies. Prompt treatment of ectopic pregnancies is critical, as an omentum pregnancy is dangerous and may result in severe intraperitoneal bleeding.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

Electrophile-Arene Affinity: An Energy Scale for Evaluating the Thermodynamics of Electrophilic Dearomatization Reactions.

Rational design and development of organic reactions are lofty goals in synthetic chemistry. Quantitative description of the properties of molecules and reactions by physical organic parameters plays an important role in this regard. In this Article, we report an energy scale, namely, electrophile-arene affinity (EAA), for evaluating the thermodynamics of electrophilic dearomatization reactions, a class of important transformations that can rapidly build up molecular complexity and structural diversity by converting planar aromatic compounds into three-dimensional cyclic molecules. The acquisition of EAA data can be readily achieved by theoretically calculating the enthalpy changes (ΔH) of the hypothetical reactions of various (cationic) electrophiles with aromatic systems (taking the 1-methylnaphthalen-2-olate ion as an example in this study). Linear correlations are found between the calculated ΔH values and established physical organic parameters such as the percentage of buried volume %VBur (steric effect), Hammett's σ or Brown's σ+ (electronic effect), and Mayr's E (reaction kinetics). Careful analysis of the ΔH values leads to the rational design of a dearomative alkynylation reaction using alkynyl hypervalent iodonium reagents as the electrophiles.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Carbene-mediated gelatin and hyaluronic acid hydrogel paints with ultra adhesive ability for arthroscopic cartilage repair.

In articular cartilage defect, particularly in arthroscopy, regenerative hydrogels are urgently needed. It should be able to firmly adhere to the cartilage tissue and maintain sufficient mechanical strength to withstand approximately 10 kPa of arthroscopic hydraulic flushing. In this study, we report a carbene-mediated ultra adhesive hybrid hydrogel paints for arthroscopic cartilage repair, which combined the photo initiation of double crosslinking system with the addition of diatomite, as a further reinforcing agent and biological inorganic substances. The double network consisting of ultraviolet initiated polymerization of hyaluronic acid methacrylate (HAMA) and carbene insertion chemistry of diazirine-grafted gelatin (GelDA) formed an ultra-strong adhesive hydrogel paint (H2G5DE). Diatomite helped the H2G5DE hydrogel paint firmly adhere to the cartilage defect, withstanding nearly 100 kPa of hydraulic pressure, almost 10 times that in clinical arthroscopy. Furthermore, the H2G5DE hydrogel supported cell growth, proliferation, and migration, thus successfully repairing cartilage defects. Overall, this study demonstrates a proof-of-concept of ultra-adhesive polysaccharide hydrogel paints, which can firmly adhere to the articular cartilage defects, can resist continuous hydraulic pressure, can promote effective cartilage regeneration, and is very suitable for minimally invasive arthroscopy.

Rh(III)-catalyzed atroposelective C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents.

An efficient Rh(III)-catalyzed enantioselective C-H alkynylation of isoquinolines is disclosed. The C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents proceeded in DMA at room temperature in the presence of 2.5 mol% chiral SCpRh(III) complex along with 20 mol% AgSbF6, providing axially chiral alkynylated 1-aryl isoquinolines in excellent yields (up to 93%) and enantioselectivity (up to 95% ee). The diverse transformations of the product further enhance the potential utility of this reaction.

Exposures to particulate matters and childhood sleep disorders-A large study in three provinces in China.

OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

Maternal phthalate exposure and BMI trajectory in children-an 18-year birth cohort follow-up study.

BACKGROUND: Obesity is a major health concern worldwide. Previous studies have suggested that phthalate plasticizers are obesogens. However, the relationship between early-life phthalate exposure and long-term obesity development remains unknown. OBJECTIVE: We investigated the association between prenatal phthalate exposure and children's body mass index (BMI) patterns in an 18-year birth cohort follow-up study in Taiwan. METHODS: Our analytical lab quantified seven phthalate metabolites in maternal urine during pregnancy using quantitative liquid chromatography-tandem mass spectrometry. In addition, we calculated BMI z scores for participated children at each follow-up, utilized trajectory analysis to describe children's BMI z-score patterns at 2-18 years of age, and adopted generalized estimating equations (GEE) and multivariate logistic regression models to assess the association between prenatal phthalate exposure and BMI z scores in children. RESULTS: A total of 208 mother-child pairs were included in the analysis. Maternal urinary diethyl phthalate (DEP) metabolites were associated with the increase of BMI z scores in children aged 2-18 years in the GEE model. Doubled maternal urinary ∑mDEHP (3 mono hexyl-metabolites of di-ethyl-hexyl phthalate (DEHP) increased the risk of children being in the stable-high BMI trajectory group until the age of eighteen. IMPACT STATEMENT: We observed that BMI trajectories of children remained stable after the age of 5 years. During each follow-up, a higher frequency of overweight or obese was observed in children, ranging from 15.9% to 35.6% for girls and 15.2-32.0% for boys, respectively. Prenatal phthalate exposure was associated with increasing BMI z scores in children. Prenatal DEHP exposure was associated with a stable-high BMI trajectory in children up to the age of 18 years.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.