Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a crucial enzyme involved in phospholipid metabolism and is essential for maintaining the structure and functionality of biofilms. However, a comprehensive examination of the role of LPCAT1 across various cancer types is lacking. Multiple public databases have been utilized to examine LPCAT1 expression, genetic alterations, methylation, prognosis, biological function, and its relationship with antitumor immunity in different cancer types. The function of LPCAT1 in glioma, breast cancer and liver cancer cells was further verified using in vitro experiments. Our research indicated that LPCAT1 is upregulated in various cancers and is accompanied by a wide range of amplification mutations. Higher LPCAT1 expression was associated with poorer prognosis across multiple cancers. Further in vitro experiments demonstrated that interfering with LPCAT1 expression increased apoptosis in glioma, breast cancer and liver cancer cells and concurrently suppressed their proliferation and migration. Functional enrichment analysis revealed that LPCAT1-associated genes were primarily enriched in immune and cancer progression pathways, such as the JAK/STAT, MYC, and EMT, etc. Moreover, LPCAT1 expression was closely associated with immune cell infiltration and immune checkpoint-related gene expression. Interestingly, LPCAT1 expression levels were generally higher in patients in the immunotherapy response group. The combination of LPCAT1 and PDL1 serves as an effective predictor of immunotherapy response. In conclusion, LPCAT1 is involved in immune regulation and tumor progression and holds promise as a biomarker for predicting patient outcomes and immunotherapy efficacy.

Transcriptomic and targeted metabolomic analyses provide insights into the flavonoids biosynthesis in the flowers of Lonicera macranthoides.

BACKGROUND: Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. RESULTS: In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3'H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6''-O-acetyl)-glucoside, cosmosiin and apigenin-4'-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. CONCLUSION: The findings are helpful for genetic improvement of varieties in L.macranthoides.

How adolescents' lives were disrupted over the course of the COVID-19 pandemic: A longitudinal investigation in 12 cultural groups in 9 nations from March 2020 to July 2022.

It is unclear how much adolescents' lives were disrupted throughout the COVID-19 pandemic or what risk factors predicted such disruption. To answer these questions, 1,080 adolescents in 9 nations were surveyed 5 times from March 2020 to July 2022. Rates of adolescent COVID-19 life disruption were stable and high. Adolescents who, compared to their peers, lived in nations with higher national COVID-19 death rates, lived in nations with less stringent COVID-19 mitigation strategies, had less confidence in their government's response to COVID-19, complied at higher rates with COVID-19 control measures, experienced the death of someone they knew due to COVID-19, or experienced more internalizing, externalizing, and smoking problems reported more life disruption due to COVID-19 during part or all of the pandemic. Additionally, when, compared to their typical levels of functioning, adolescents experienced spikes in national death rates, experienced less stringent COVID-19 mitigation measures, experienced less confidence in government response to the COVID-19 pandemic, complied at higher rates with COVID-19 control measures, experienced more internalizing problems, or smoked more at various periods during the pandemic, they also experienced more COVID-19 life disruption. Collectively, these findings provide new insights that policymakers can use to prevent the disruption of adolescents' lives in future pandemics.

Factors affecting long-term myopic regression after corneal refractive surgery for civilian pilots in southwest China.

BACKGROUND: The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. METHODS: We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. RESULTS: A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was - 2.92 ± 1.11 D (range from - 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P < 0.001). The OR for continuous near-work time was 0.635 with a P value of 0.038. CONCLUSIONS: This is the first report to analyze myopic regression after CRS in civilian pilots. Our study found that for each year increase in age, the risk of civilian pilots experiencing myopic regression was increased. Intrastromal ablations had a lower risk of long-term myopia regression than subepithelial ablations. There is a higher risk of myopic progression with continuous near-work time > 45 min and poor accommodative function may be related factors in this specific population.

Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells.

The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export. TPR expression is significantly increased in lung cancer tissues and correlated with poor prognosis. Consistently, knockdown of TPR inhibits tRNA nuclear export, protein synthesis and cell growth in lung cancer cell lines. We further show that NXF1, a well-known mRNA nuclear export factor, associates with tRNAs and mediates their transport through nuclear pores. Collectively, our findings uncover a conserved mechanism that regulates nuclear export of tRNAs, which is a limiting step in protein synthesis in eukaryotes.

Adolescents' relationships with parents and romantic partners in eight countries.

INTRODUCTION: Creating romantic relationships characterized by high-quality, satisfaction, few conflicts, and reasoning strategies to handle conflicts is an important developmental task for adolescents connected to the relational models they receive from their parents. This study examines how parent-adolescent conflicts, attachment, positive parenting, and communication are related to adolescents' romantic relationship quality, satisfaction, conflicts, and management. METHOD: We interviewed 311 adolescents at two time points (females = 52%, ages 15 and 17) in eight countries (China, Colombia, Italy, Kenya, the Philippines, Sweden, Thailand, and the United States). Generalized and linear mixed models were run considering the participants' nesting within countries. RESULTS: Adolescents with negative conflicts with their parents reported low romantic relationship quality and satisfaction and high conflicts with their romantic partners. Adolescents experiencing an anxious attachment to their parents reported low romantic relationship quality, while adolescents with positive parenting showed high romantic relationship satisfaction. However, no association between parent-adolescent relationships and conflict management skills involving reasoning with the partner was found. No associations of parent-adolescent communication with romantic relationship dimensions emerged, nor was there any effect of the country on romantic relationship quality or satisfaction. CONCLUSION: These results stress the relevance of parent-adolescent conflicts and attachment as factors connected to how adolescents experience romantic relationships.

Developmental Trajectories of Parental Self-Efficacy as Children Transition to Adolescence in Nine Countries: Latent Growth Curve Analyses.

Little is known about the developmental trajectories of parental self-efficacy as children transition into adolescence. This study examined parental self-efficacy among mothers and fathers over 3 1/2 years representing this transition, and whether the level and developmental trajectory of parental self-efficacy varied by cultural group. Data were drawn from three waves of the Parenting Across Cultures (PAC) project, a large-scale longitudinal, cross-cultural study, and included 1178 mothers and 1041 fathers of children who averaged 9.72 years of age at T1 (51.2% girls). Parents were from nine countries (12 ethnic/cultural groups), which were categorized into those with a predominant collectivistic (i.e., China, Kenya, Philippines, Thailand, Colombia, and Jordan) or individualistic (i.e., Italy, Sweden, and USA) cultural orientation based on Hofstede's Individualism Index (Hofstede Insights, 2021). Latent growth curve analyses supported the hypothesis that parental self-efficacy would decline as children transition into adolescence only for parents from more individualistic countries; parental self-efficacy increased over the same years among parents from more collectivistic countries. Secondary exploratory analyses showed that some demographic characteristics predicted the level and trajectory of parental self-efficacy differently for parents in more individualistic and more collectivistic countries. Results suggest that declines in parental self-efficacy documented in previous research are culturally influenced.

Factors affecting time to treatment initiation after diagnosis for multidrug-resistant/rifampicin-resistant tuberculosis patients: A mixed-methods study in Jakarta, Indonesia.

OBJECTIVE: To investigate the time to treatment initiation (TTI) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients after diagnosis in Indonesia and biological, psychological and social factors associated with the time interval. METHODS: This study was conducted in Persahabatan Hospital, Jakarta using a mixed-methods approach. Registry data and medical records of MDR/RR-TB patients were collected and matched (hospital dataset), and linked with psychosocial assessment results (linked dataset). Descriptive analysis was conducted to understand patient characteristics and the distribution of TTI after RR-TB diagnosis by GeneXpert. Generalised linear regression was used to analyse factors associated with delay duration, and logistic regression to explore factors associated with the delay longer than the median duration for both datasets (basic vs. extended model). In-depth interviews were conducted with patients and healthcare workers to understand the procedure of treatment initiation and how different factors led to delay. RESULTS: The hospital dataset included 275 patient-matched cases, and 188 were further linked with psychosocial assessment results. The median time interval was 24 days [interquartile range (IQR) 23.5] and 26 days (IQR 21.25), respectively. Regression analysis showed that in the extended model, comorbidities (exp [coefficient]= 1.93), unemployment (exp [coefficient] = 1.80) and poor knowledge of MDR/RR-TB (exp (coefficient) = 1.67) seemed to have the strongest effects on prolonging the time interval (p < 0.05). Unsuccessful TB treatment history was the only factor that significantly increased the risk of delay longer than the median duration (p < 0.05) in the basic model, while none of the factors were significant in the extended model. The qualitative study identified provider-side factors (centralised service provision and insufficient human resources) and patient-side factors (physical weakness, psychological stress and financial concern) associated with treatment delay. CONCLUSION: MDR/RR-TB patients in Persahabatan Hospital, Jakarta, Indonesia waited around 25 days for treatment initiation after RR-TB diagnosis. Health system solutions are needed to address challenges facing both MDR/RR-TB patients and healthcare providers to reduce delay in treatment initiation.

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.

Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3ß inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3ß inhibitor with an IC50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aß-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3ß by up-regulating the expression of phosphorylated GSK-3ß at Ser9 and down-regulating the expression of phosphorylated GSK-3ß at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl3-induced zebrafish AD model, 54 significantly ameliorated the AlCl3-induced dyskinesia, demonstrating its anti-AD activity in vivo.

Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia.

BACKGROUND: Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010. OBJECTIVES: To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment. DATA COLLECTION AND ANALYSIS: For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias. Treatment of women with eclampsia (four comparisons) One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence). One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence). One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence). One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. Prevention of eclampsia for women with pre-eclampsia (five comparisons) Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women). One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence). Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women). Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women). One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. AUTHORS' CONCLUSIONS: Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.

The impact of growth monitoring and promotion on health indicators in children under five years of age in low- and middle-income countries.

BACKGROUND: Undernutrition in the critical first 1000 days of life is the most common form of childhood malnutrition, and a significant problem in low- and middle-income countries (LMICs). The effects of undernutrition in children aged under five years are wide-ranging and include increased susceptibility to and severity of infections; impaired physical and cognitive development, which diminishes school and work performance later in life; and death. Growth monitoring and promotion (GMP) is a complex intervention that comprises regular measurement and charting of growth combined with promotion activities. Policymakers, particularly in international aid agencies, have differing and changeable interpretations and perceptions of the purpose of GMP. The effectiveness of GMP as an approach to preventing malnutrition remains a subject of debate, particularly regarding the added value of growth monitoring compared with promotion alone. OBJECTIVES: To evaluate the effectiveness of child growth monitoring and promotion for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children under five years of age in low- and middle-income countries. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 3 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cohort studies, and controlled before-after studies that compared GMP with standard care or nutrition education alone in non-hospitalised children aged under five years. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods to conduct a narrative synthesis. Our primary outcomes were anthropometric indicators, infant and child feeding practices, and health service usage. Secondary outcomes were frequency and severity of childhood illnesses, and mortality. We used GRADE to assess the certainty of evidence for each primary outcome. MAIN RESULTS: We included six studies reported in eight publications. We grouped the findings according to intervention. Community-based growth monitoring and promotion (without supplementary feeding) versus standard care We are unsure if GMP compared to standard care improves infant and child feeding practices, as measured at 24 months by the proportion of infants who have fluids other than breast milk introduced early (49.7% versus 70.5%; 1 study; 4296 observations; very low-certainty evidence). We are unsure if GMP improves health service usage, as measured at 24 months by the proportion of children who receive vitamin A (72.5% versus 62.9%; 1 study; 4296 observations; very low-certainty evidence) and the proportion of children who receive deworming (29.2% versus 14.6%; 1 study; 4296 observations; very low-certainty evidence). No studies reported selected anthropometric indicators (weight-for-age z-score or height-for-age z-score) at 12 or 24 months, infant and child feeding practices at 12 months, or health service usage at 12 months. Community-based growth monitoring and promotion (with supplementary feeding) versus standard care Two studies (with 569 participants) reported the mean weight-for-age z-score at 12 months, providing very low-certainty evidence: in one study, there was little or no difference between GMP and standard care (mean difference (MD) -0.07, 95% confidence interval (CI) -0.19 to 0.06); in the other study, mean weight-for-age z-score worsened in both groups, but we were unable to calculate a relative effect. GMP versus standard care may make little to no difference to the mean height-for-age z-score at 12 months (MD -0.15, 95% CI -0.34 to 0.04; 1 study, 337 participants; low-certainty evidence). Two studies (with 564 participants) reported a range of outcome measures related to infant and child feeding practices at 12 months, showing little or no difference between the groups (very low-certainty evidence). No studies reported health service usage at 12 or 24 months, feeding practices at 24 months, or selected anthropometric indicators at 24 months. AUTHORS' CONCLUSIONS: There is limited uncertain evidence on the effectiveness of GMP for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children aged under five years in LMICs. Future studies should explore the reasons for the apparent limited impact of GMP on key child health indicators. Reporting of GMP interventions and important outcomes must be transparent and consistent.

Pre-pandemic psychological and behavioral predictors of responses to the COVID-19 pandemic in nine countries.

Prior to the COVID-19 pandemic, adolescents (N = 1,330; Mages = 15 and 16; 50% female), mothers, and fathers from nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, United States) reported on adolescents' internalizing and externalizing problems, adolescents completed a lab-based task to assess tendency for risk-taking, and adolescents reported on their well-being. During the pandemic, participants (Mage = 20) reported on changes in their internalizing, externalizing, and substance use compared to before the pandemic. Across countries, adolescents' internalizing problems pre-pandemic predicted increased internalizing during the pandemic, and poorer well-being pre-pandemic predicted increased externalizing and substance use during the pandemic. Other relations varied across countries, and some were moderated by confidence in the government's handling of the pandemic, gender, and parents' education.

Predicting child aggression: The role of parent and child endorsement of reactive aggression across 13 cultural groups in 9 nations.

Parent and child endorsement of reactive aggression both predict the emergence of child aggression, but they are rarely studied together and in longitudinal contexts. The present study does so by examining the unique predictive effects of parent and child endorsement of reactive aggression at age 8 on child aggression at age 9 in 1456 children from 13 cultural groups in 9 nations. Multiple group structural equation models explored whether age 8 child and parent endorsement of reactive aggression predicted subsequent age 9 child endorsement of reactive aggression and child aggression, after accounting for prior child aggression and parent education. Results revealed that greater parent endorsement of reactive aggression at age 8 predicted greater child endorsement of aggression at age 9, that greater parent endorsement of reactive aggression at age 8 uniquely predicted greater aggression at age 9 in girls, and that greater child endorsement of reactive aggression at age 8 uniquely predicted greater aggression at age 9 in boys. All three of these associations emerged across cultures. Implications of, and explanations for, study findings are discussed.

The Intergenerational Transmission of Maladaptive Parenting and its Impact on Child Mental Health: Examining Cross-Cultural Mediating Pathways and Moderating Protective Factors.

Using a sample of 1338 families from 12 cultural groups in 9 nations, we examined whether retrospectively remembered Generation 1 (G1) parent rejecting behaviors were passed to Generation 2 (G2 parents), whether such intergenerational transmission led to higher Generation 3 (G3 child) externalizing and internalizing behavior at age 13, and whether such intergenerational transmission could be interrupted by parent participation in parenting programs or family income increases of > 5%. Utilizing structural equation modeling, we found that the intergenerational transmission of parent rejection that is linked with higher child externalizing and internalizing problems occurs across cultural contexts. However, the magnitude of transmission is greater in cultures with higher normative levels of parent rejection. Parenting program participation broke this intergenerational cycle in fathers from cultures high in normative parent rejection. Income increases appear to break this intergenerational cycle in mothers from most cultures, regardless of normative levels of parent rejection. These results tentatively suggest that bolstering protective factors such as parenting program participation, income supplementation, and (in cultures high in normative parent rejection) legislative changes and other population-wide positive parenting information campaigns aimed at changing cultural parenting norms may be effective in breaking intergenerational cycles of maladaptive parenting and improving child mental health across multiple generations.

Predicting Adolescent Mental Health Outcomes Across Cultures: A Machine Learning Approach.

Adolescent mental health problems are rising rapidly around the world. To combat this rise, clinicians and policymakers need to know which risk factors matter most in predicting poor adolescent mental health. Theory-driven research has identified numerous risk factors that predict adolescent mental health problems but has difficulty distilling and replicating these findings. Data-driven machine learning methods can distill risk factors and replicate findings but have difficulty interpreting findings because these methods are atheoretical. This study demonstrates how data- and theory-driven methods can be integrated to identify the most important preadolescent risk factors in predicting adolescent mental health. Machine learning models examined which of 79 variables assessed at age 10 were the most important predictors of adolescent mental health at ages 13 and 17. These models were examined in a sample of 1176 families with adolescents from nine nations. Machine learning models accurately classified 78% of adolescents who were above-median in age 13 internalizing behavior, 77.3% who were above-median in age 13 externalizing behavior, 73.2% who were above-median in age 17 externalizing behavior, and 60.6% who were above-median in age 17 internalizing behavior. Age 10 measures of youth externalizing and internalizing behavior were the most important predictors of age 13 and 17 externalizing/internalizing behavior, followed by family context variables, parenting behaviors, individual child characteristics, and finally neighborhood and cultural variables. The combination of theoretical and machine-learning models strengthens both approaches and accurately predicts which adolescents demonstrate above average mental health difficulties in approximately 7 of 10 adolescents 3-7 years after the data used in machine learning models were collected.

[Observational Comparison of the Safety and Effectiveness of Myopic Children Wearing Defocus Incorporated Soft Contact Lenses or Orthokeratology Lenses].

Objective: To observe and compare the effectiveness and safety of controlling myopia in children by wearing defocus incorporated soft contact (DISC) lenses or orthokeratology (OrthoK) lenses. Methods: A total of 75 children who came to our hospital between January 2018 and September 2020 were enrolled for this retrospective study. The DISC group consisted of 30 myopic children (60 eyes) wearing peripheral defocal soft incorporated contact lenses during daytime. There were 10 males and 20 females aged (9.9±1.00) years old in this group and their spherical equivalent refractions were (-2.78±0.70) D. The OrthoK group consisted of 45 myopic children (90 eyes) wearing OrthoK lenses. There were 30 female and 15 males aged (9.67±1.11) and their spherical equivalent refractions were (-2.67±0.71) D. All subjects had previously worn prescription glasses for 12 months or longer before they started wearing contact lenses. The subjects were followed up for 12 months once they started wearing contact lenses. The axial changes and corneal and conjunctival complications of the two groups of myopic children were compared and analyzed. Results: Myopic children in both groups experienced relatively rapid increase in ocular axial length while they were wearing prescription glasses, with the ocular axial length increase in the prescription-glass-wearing period being (0.34±0.09) mm in the OrthoK group and (0.37± 0.07) mm in the DISC group. In the 12 months of wearing contact lenses, the ocular axial length of children in the OrthoK group increased by (0.18±0.04) mm, while that of the DISC group increased by (0.19±0.05) mm. The increase in ocular axial length was reduced in both groups after the children were switched to the new myopia prevention methods, showing significant difference ( P<0. 05). The two groups using two different contact lenses had similar axial length increase, showing no significant difference ( P>0.05). During the 12-month period while the subjects wore the two types of contact lenses, the incidence of chronic follicular conjunctivitis was 11.20% in the OrthoK group and 20.00% in the DISC group, with that of the DISC group being slightly higher without showing significant difference ( P>0.05). The incidence of grade-1corneal staining was 66.70% in the OrthoK group and 56.70% in the DISC group, and the incidence of grade-2 corneal staining was 17.80% in the OrthoK group and 16.70% in the DISC group. In other words, the OrthoK group had slightly higher findings, but the difference was not significant ( P>0.05). The incidence of contact lens-associated papillary conjunctivitis was 2.20% in the OrthoK group and 10.00% in the DISC group, which was slightly higher than that in the orthokeratology lens group, but the difference was not significant( P>0.05). Conclusion: Both DISC lenses and OrthoK lenses can effectively control the increase in axial length in myopic children, and their have better effects than those of prescription glasses. The two tyes of contact lenses showed similar effects for controlling axial length increase. Both contact lenses have fewer corneal and conjunctival complications and better safety.

Investigation of retinal microvasculature and choriocapillaris in adolescent myopic patients with astigmatism undergoing orthokeratology.

BACKGROUND: To observe alterations of fundus microcirculation and retinal thickness in adolescent myopic patients with astigmatism after toric and spherical orthokeratology using optical coherence tomography angiography (OCTA), to explore the effects of orthokeratology on the retinal thickness and choroidal blood flow. METHODS: A total of 48 patients were enrolled and divided into two group (toric orthokeratology (T) group and spherical orthokeratology (S) group) according to the type of lens design. OCTA was used to measure the superficial and deep retinal vessel densities at the macular region, radial peripapillary capillary (RPC) density, foveal avascular zone (FAZ) area, and choriocapillaris (ChC) perfusion area before and after orthokeratology for 3 months. The data were statistically analyzed by SPSS 19.0 software. RESULTS: Compared with before orthokeratology, the superficial vessel density in the fovea and parafovea in the T group significantly increased, and the deep vessel density in the whole area and fovea were significantly elevated after 3 months (P < 0.05). The superficial vessel density was significantly higher only in the parafovea in the S group after 3 months than that before orthokeratology (P < 0.05), deep vessel density in the whole area and parafovea after 3 months was significantly higher than that before orthokeratology (P < 0.05). RPC density in the two groups increased after 3 months of orthokeratology in the whole area and inside the disc area (P < 0.05). Three months after toric orthokeratology, FAZ area in the T group was significantly reduced by 0.05 (- 0.41 to + 0.08) mm2, while ChC perfusion area was enlarged by 0.06 ± 0.12 mm2. FAZ area in the S group significantly decreased by 0.01 (- 0.19 to + 0.01) mm2, whereas ChC perfusion area increased by 0.06 (- 0.07 to + 0.50) mm2. Retinal thickness in the two groups increased after 3 months of orthokeratology in the whole area and parafoveal area (P < 0.05). CONCLUSION: Orthokeratology improved retinal blood flow in macular area and RPC while controlling myopia. The changes in FAZ and ChC perfusion areas did not significantly differ between toric and spherical orthokeratology.

The co-management of tuberculosis-diabetes co-morbidities in Indonesia under the National Tuberculosis Control Program: results from a cross-sectional study from 2017 to 2019.

BACKGROUND: Indonesia suffers from a high burden of tuberculosis (TB) and diabetes (DM). The government initiated national TB-DM co-management activities under the National TB Control Program in 2017. This study investigates the detection and treatment outcomes of TB-DM in Jakarta after implementing these activities, and identifies the main factors associated with these outcomes. METHODS: A cross-sectional study was conducted using TB registry data in two districts of Jakarta, East Jakarta (low-income) and South Jakarta (high-income). A 5-step cascade analysis was used: diagnosed TB patients; TB patients tested for DM; diagnosed TB-DM patients; and patients received and completed TB treatment/cured. We conducted descriptive analyses to understand the characteristics of TB and TB-DM patients, and used a two-level mixed-effect logistic regression to explore factors associated with having a DM test and completing TB treatment/being cured. RESULTS: Over the study period (2017-2019) 50.8% of the new pulmonary TB patients aged over 15 were tested for DM. The percentage increased from 41.7% in 2017-2018 to 60.1% in 2019. Of the TB patients tested for DM, 20.8% were diagnosed with DM. Over 90% of the detected TB-DM patients received standard TB treatment, 86.3% of whom completed treatment/were cured. Patients in East Jakarta were more likely to be tested for DM and to complete standard TB treatment/be cured than patients in South Jakarta (P <  0.001). Bacteriologically positive TB patients were more likely to be tested for DM (OR = 1.37, 95% CIs 1.17,1.60). Patients diagnosed in sub-district level healthcare centers had a higher likelihood of being tested for DM than those in government and private hospitals (P <  0.05). Receiving DM treatment was associated with a higher likelihood of completing TB treatment/being cured (OR = 1.82, 95% CIs 1.20, 2.77). CONCLUSIONS: TB-DM case detection significantly improved in 2019 after introducing TB-DM co-management activities in Jakarta, while gaps in TB-DM co-management existed between bacteriologically positive and clinically diagnosed TB patients, and across different types of health facilities. Collaboration between TB and DM departments should be strengthened, and more resources need to be mobilized to further improve the co-management of TB-DM in Indonesia.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) catalyses the hyperphosphorylation of tau protein in the Alzheimer's disease (AD) pathology. A series of novel thieno[3,2-c]pyrazol-3-amine derivatives were designed and synthesised and evaluated as potential GSK-3ß inhibitors by structure-guided drug rational design approach. The thieno[3,2-c]pyrazol-3-amine derivative 16b was identified as a potent GSK-3ß inhibitor with an IC50 of 3.1 nM in vitro and showed accepted kinase selectivity. In cell levels, 16b showed no toxicity on the viability of SH-SY5Y cells at the concentration up to 50 µM and targeted GSK-3ß with the increased phosphorylated GSK-3ß at Ser9. Western blot analysis indicated that 16b decreased the phosphorylated tau at Ser396 in a dose-dependent way. Moreover, 16b effectively increased expressions of ß-catenin as well as the GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth. Therefore, the thieno[3,2-c]pyrazol-3-amine derivative 16b could serve as a promising GSK-3ß inhibitor for the treatment of AD.