Taste and pheromonal inputs govern the regulation of time investment for mating by sexual experience in male Drosophila melanogaster.

Males have finite resources to spend on reproduction. Thus, males rely on a 'time investment strategy' to maximize their reproductive success. For example, male Drosophila melanogaster extends their mating duration when surrounded by conditions enriched with rivals. Here we report a different form of behavioral plasticity whereby male fruit flies exhibit a shortened duration of mating when they are sexually experienced; we refer to this plasticity as 'shorter-mating-duration (SMD)'. SMD is a plastic behavior and requires sexually dimorphic taste neurons. We identified several neurons in the male foreleg and midleg that express specific sugar and pheromone receptors. Using a cost-benefit model and behavioral experiments, we further show that SMD behavior exhibits adaptive behavioral plasticity in male flies. Thus, our study delineates the molecular and cellular basis of the sensory inputs required for SMD; this represents a plastic interval timing behavior that could serve as a model system to study how multisensory inputs converge to modify interval timing behavior for improved adaptation.

Pharmacological Modulation of the Crosstalk between Aberrant Janus Kinase Signaling and Epigenetic Modifiers of the Histone Deacetylase Family to Treat Cancer.

Hyperactivated Janus kinase (JAK) signaling is an appreciated drug target in human cancers. Numerous mutant JAK molecules as well as inherent and acquired drug resistance mechanisms limit the efficacy of JAK inhibitors (JAKi). There is accumulating evidence that epigenetic mechanisms control JAK-dependent signaling cascades. Like JAKs, epigenetic modifiers of the histone deacetylase (HDAC) family regulate the growth and development of cells and are often dysregulated in cancer cells. The notion that inhibitors of histone deacetylases (HDACi) abrogate oncogenic JAK-dependent signaling cascades illustrates an intricate crosstalk between JAKs and HDACs. Here, we summarize how structurally divergent, broad-acting as well as isoenzyme-specific HDACi, hybrid fusion pharmacophores containing JAKi and HDACi, and proteolysis targeting chimeras for JAKs inactivate the four JAK proteins JAK1, JAK2, JAK3, and tyrosine kinase-2. These agents suppress aberrant JAK activity through specific transcription-dependent processes and mechanisms that alter the phosphorylation and stability of JAKs. Pharmacological inhibition of HDACs abrogates allosteric activation of JAKs, overcomes limitations of ATP-competitive type 1 and type 2 JAKi, and interacts favorably with JAKi. Since such findings were collected in cultured cells, experimental animals, and cancer patients, we condense preclinical and translational relevance. We also discuss how future research on acetylation-dependent mechanisms that regulate JAKs might allow the rational design of improved treatments for cancer patients. SIGNIFICANCE STATEMENT: Reversible lysine-ɛ-N acetylation and deacetylation cycles control phosphorylation-dependent Janus kinase-signal transducer and activator of transcription signaling. The intricate crosstalk between these fundamental molecular mechanisms provides opportunities for pharmacological intervention strategies with modern small molecule inhibitors. This could help patients suffering from cancer.

Identification of mitogen-activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies.

Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure-based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan-assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug-like properties. All-atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7-ZINC12296700 and MAPK7-ZINC02123081 docked complexes. According to the molecular mechanics Poisson-Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.

The protein phosphatase-2A subunit PR130 is involved in the formation of cytotoxic protein aggregates in pancreatic ductal adenocarcinoma cells.

As a major source of cellular serine and threonine phosphatase activity, protein phosphatase-2A (PP2A) modulates signaling pathways in health and disease. PP2A complexes consist of catalytic, scaffolding, and B-type subunits. Seventeen PP2A B-type subunits direct PP2A complexes to selected substrates. It is ill-defined how PP2A B-type subunits determine the growth and drug responsiveness of tumor cells. Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis. We analyzed the responses of murine and human mesenchymal and epithelial PDAC cells to the specific PP2A inhibitor phendione. We assessed protein levels by immunoblot and proteomics and cell fate by flow cytometry, confocal microscopy, and genetic manipulation. We show that murine mesenchymal PDAC cells express significantly higher levels of the PP2A B-type subunit PR130 than epithelial PDAC cells. This overexpression of PR130 is associated with a dependency of such metastasis-prone cells on the catalytic activity of PP2A. Phendione induces apoptosis and an accumulation of cytotoxic protein aggregates in murine mesenchymal and human PDAC cells. These processes occur independently of the frequently mutated tumor suppressor p53. Proteomic analyses reveal that phendione upregulates the chaperone HSP70 in mesenchymal PDAC cells. Inhibition of HSP70 promotes phendione-induced apoptosis and phendione promotes a proteasomal degradation of PR130. Genetic elimination of PR130 sensitizes murine and human PDAC cells to phendione-induced apoptosis and protein aggregate formation. These data suggest that the PP2A-PR130 complex dephosphorylates and thereby prevents the aggregation of proteins in tumor cells.

Loss-of-Resistance Versus Dynamic Pressure-Sensing Technology for Successful Placement of Thoracic Epidural Catheters: A Randomized Clinical Trial.

BACKGROUND: The traditional loss-of-resistance (LOR) technique for thoracic epidural catheter placement can be associated with a high primary failure rate. In this study, we compared the traditional LOR technique and dynamic pressure-sensing (DPS) technology for primary success rate and secondary outcomes pertinent to identifying the thoracic epidural space. METHODS: This pragmatic, randomized, patient- and assessor-blinded superiority trial enrolled patients ages 18 to 75 years, scheduled for major thoracic or abdominal surgeries at a tertiary care teaching hospital. Anesthesiology trainees (residents and fellows) placed thoracic epidural catheters under faculty supervision and rescue. The primary outcome was the success rate of thoracic epidural catheter placement, evaluated by the loss of cold sensation in the thoracic dermatomes 20 minutes after injecting the epidural test dose. Secondary outcomes included procedural time, ease of catheter placement, the presence of a positive falling meniscus sign, early hemodynamic changes, and unintended dural punctures. Additionally, we explored outcomes that included number of attempts, needle depth to epidural space, need for faculty to rescue the procedure from the trainee, patient-rated procedural discomfort, pain at the epidural insertion site, postoperative pain scores, and opioid consumption over 48 hours. RESULTS: Between March 2019 and June 2020, 133 patients were enrolled; 117 were included in the final analysis (n = 57 for the LOR group; n = 60 for the DPS group). The primary success rate of epidural catheter placement was 91.2% (52 of 57) in the LOR group and 96.7% (58 of 60) in the DPS group (95% confidence interval [CI] of difference in proportions: -0.054 [-0.14 to 0.03]; P = .264). No difference was observed in procedural time between the 2 groups (median interquartile range [IQR] in minutes: LOR 5.0 [7.0], DPS 5.5 [7.0]; P = .982). The number of patients with epidural analgesia onset at 10 minutes was 49.1% (28 of 57) in the LOR group compared to 31.7% (19 of 60) in the DPS group ( P = .062). There were 2 cases of unintended dural punctures in each group. Other secondary or exploratory outcomes were not significantly different between the groups. CONCLUSIONS: Our trial did not establish the superiority of the DPS technique over the traditional LOR method for identifying the thoracic epidural space ( Clinicaltrials.gov identifier: NCT03826186).

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.

Attachment security, environmental adversity, and fast life history behavioral profiles in human adolescents.

One species-general life history (LH) principle posits that challenging childhood environments are coupled with a fast or faster LH strategy and associated behaviors, while secure and stable childhood environments foster behaviors conducive to a slow or slower LH strategy. This coupling between environments and LH strategies is based on the assumption that individuals' internal traits and states are independent of their external surroundings. In reality, individuals respond to external environmental conditions in alignment with their intrinsic vitality, encompassing both physical and mental states. The present study investigated attachment as an internal mental state, examining its role in mediating and moderating the association between external environmental adversity and fast LH strategies. A sample of 1169 adolescents (51% girls) from 9 countries was tracked over 10 years, starting from age 8. The results confirm both mediation and moderation and, for moderation, secure attachment nullified and insecure attachment maintained the environment-LH coupling. These findings suggest that attachment could act as an internal regulator, disrupting the contingent coupling between environmental adversity and a faster pace of life, consequently decelerating human LH.

Promoting responsive care and early learning practices in Northern Ghana: results from a counselling intervention within nutrition and health services.

OBJECTIVE: This study assesses change in caregiver practices after integrating responsive care and early learning (RCEL) in nutrition and health services and community platforms in northern Ghana. DESIGN: We trained health facility workers and community health volunteers to deliver RCEL counselling to caregivers of children under 2 years of age through existing health facilities and community groups. We assessed changes in caregivers' RCEL practices before and after the intervention with a household questionnaire and caregiver-child observations. SETTING: The study took place in Sagnarigu, Gushegu, Wa East and Mamprugu-Moagduri districts from April 2022 to March 2023. Study sites included seventy-nine child welfare clinics (CWC) at Ghana Health Service facilities and eighty village savings and loan association (VSLA) groups. PARTICIPANTS: We enrolled 211 adult caregivers in the study sites who had children 0-23 months at baseline and were enrolled in a CWC or a VSLA. RESULTS: We observed improvements in RCEL and infant and young child feeding practices, opportunities for early learning (e.g. access to books and playthings) in the home environment and reductions in parental stress. CONCLUSIONS: This study demonstrates the effectiveness of integrating RCEL content into existing nutrition and health services. The findings can be used to develop, enhance and advocate for policies integrating RCEL into existing services and platforms in Ghana. Future research may explore the relationship between positive changes in caregiver behaviour and improvements in child development outcomes as well as strategies for enhancing paternal engagement in care practices, improving child supervision and ensuring an enabling environment.

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.

Safety, timing, and outcomes of early post-operative cardiac catheterisation following congenital heart surgery.

OBJECTIVE: The safety of early post-operative cardiac catheterisation has been described following congenital heart surgery. Optimal timing of early post-operative cardiac catheterisation remains uncertain. The aim of this study was to describe the safety of early post-operative cardiac catheterisation and its impact on cardiac ICU and hospital length of stay, duration of mechanical ventilation, and extracorporeal support. METHODS: This single-centre retrospective cohort study compared clinical and outcome variables between "early" early post-operative cardiac catheterisation (less than 72 hours after surgery) and "late" early post-operative cardiac catheterisation (greater than 72 hours after surgery) groups using Chi-squared, Student's t, and log-rank test (or appropriate nonparametric test). RESULTS: In total, 132 patients were included, 22 (16.7%) "early" early post-operative cardiac catheterisation, and 110 (83.3%) "late" early post-operative cardiac catheterisation. Interventions were performed in 63 patients (51.5%), 7 (11.1%) early and 56 (88.9%) late. Complications of catheterisation occurred in seven (5.3%) patients, two early and five late. There were no major complications. Patients in the late group trended towards a longer stay in the cardiac ICU (19 days [7, 62] versus 11.5 days [7.2, 31.5], p = 0.6) and in the hospital (26 days [9.2, 68] versus 19 days [13.2, 41.8], p = 0.8) compared to the earlier group. CONCLUSION: "Early" early post-operative cardiac catheterisation was associated with an overall low rate of complications. Earlier catheterisations trended towards shorter cardiac ICU and hospital length of stays. Earlier catheterisations may lead to earlier recovery for patients not following an expected post-operative course.

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.

Cultural values, parenting and child adjustment in Jordan.

This study examined associations between maternal and paternal cultural values (individualism, collectivism and conformity) and parenting dimensions (warmth, psychological control, autonomy granting, rule setting, knowledge solicitation and family obligations) and children's adjustment (internalising and externalising behaviours) in 113 families with children (Mage = 10.8 years) recruited from Zarqa, Jordan. Bivariate correlations and multiple regression analyses were used to examine study question. Results revealed that mothers' individualism was positively correlated with more maternal warmth, more rules/limit-setting and fathers' and children's perceptions regarding children's greater family obligations. Fathers' individualism was not significantly correlated with any parenting or child adjustment variables. Mothers' and fathers' higher collectivism was correlated with more maternal and paternal warmth, respectively; however, mothers' and fathers' higher conformity values were not significantly correlated with any parenting or child adjustment variables. Mothers' collectivism was not associated with any parenting or child adjustment variables after taking into account the other cultural values, child gender and mothers' education; however, fathers' higher collectivism was associated with more paternal warmth, fathers' higher expectations for children's family obligations and less child internalising behaviour. The findings have implications for understanding how cultural values are related to parenting and children's adjustment in Jordan.

Individualism, collectivism and conformity in nine countries: Relations with parenting and child adjustment.

This study investigated how individualism, collectivism and conformity are associated with parenting and child adjustment in 1297 families with 10-year-old children from 13 cultural groups in nine countries. With multilevel models disaggregating between- and within-culture effects, we examined between- and within-culture associations between maternal and paternal cultural values, parenting dimensions and children's adjustment. Mothers from cultures endorsing higher collectivism and fathers from cultures endorsing lower individualism engage more frequently in warm parenting behaviours. Mothers and fathers with higher-than-average collectivism in their culture reported higher parent warmth and expectations for children's family obligations. Mothers with higher-than-average collectivism in their cultures more frequently reported warm parenting and fewer externalising problems in children, whereas mothers with higher-than-average individualism in their culture reported more child adjustment problems. Mothers with higher-than-average conformity values in their culture reported more father-displays of warmth and greater mother-reported expectations for children's family obligations. Fathers with higher-than-average individualism in their culture reported setting more rules and soliciting more knowledge about their children's whereabouts. Fathers who endorsed higher-than-average conformity in their culture displayed more warmth and expectations for children's family obligations and granted them more autonomy. Being connected to an interdependent, cohesive group appears to relate to parenting and children's adjustment.

Hot fomentation of newborn fontanelles as an indigenous practice in Ghana: implications for policy and integrated community-based health care in Covid-19 pandemic and beyond.

OBJECTIVE: African newborns undergo numerous traditional and religious practices ranging from fontanelle fomentation to total head shaving, scalp molding, skin scarification and ano-genital irrigation which can negatively impact the health of neonates. Hot fomentation of fontanelles has been a predominant indigenous home-based postnatal practice in Ghana and among Africans in the diaspora. Mobility restrictions during the Covid-19 pandemic has impacted direct access to facility-based care as well as home care. The flourishing of newborn traditional practices among African populations during this Covid-19 pandemic offers opportunities to rethink the provision of family healthcare support for newborns during the ongoing pandemic and beyond. Hence, the aim of this critical review was to examine and describe a common indigenous practice-hot fontanelle fomentation to inform home birth support, discharge planning, and the delivery of optimal home-based care support. STUDY DESIGN: This study is a review of literature on hot fomentation of newborn fontanelles. METHODS: Literature search in CINAHL, PubMed, African Index Medicus and Scopus, was conducted and evidence synthesised from articles ranging from 1983-2022. Sixty articles were reviewed; however, 10 manuscripts were excluded prior to screening. The other 19 were exempted because they were either below 1983 or were not the best fit for the study purpose. In all, 31 studies were included in the study. The study was guided by Madeleine Leininger's Culture Care Diversity and Universality care theory. RESULTS: The current study identifies hot fomentation of newborn fontanelles practices in Ghana, the description of hot fomentation practices and the dangers associated with it. The findings and suggested ways to help overcome this challenge. CONCLUSION: There are several neonatal indigenous practices including fontanelle fomentation which pose threat to the health of the neonate as discussed in this study. Future research needs to investigate innovative ways of fontanelle fomentation where necessary instead of the use of hot water by mothers, especially in this Covid-19 pandemic where health and mobility restrictions impact physical access to timely health care. This research will help educate mothers about the dangers of fontanel fomentation and reduce the practice, especially in rural areas of developing countries. This could help reduce neonatal mortality and unnecessary healthcare costs.

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 Muscle-Conditioned Medium Containing Protocatechuic Acid Improves Insulin Resistance by Modulating Muscle Communication with Liver and Adipose Tissue.

Diabetes mellitus is a public health concern, affecting 10.5% of the population. Protocatechuic acid (PCA), a polyphenol, exerts beneficial effects on insulin resistance and diabetes. This study investigated the role of PCA in improving insulin resistance and the crosstalk between muscle with liver and adipose tissue. C2C12 myotubes received four treatments: Control, PCA, insulin resistance (IR), and IR-PCA. Conditioned media from C2C12 was used to incubate HepG2 and 3T3-L1 adipocytes. The impact of PCA was analyzed on glucose uptake and signaling pathways. PCA (80 µM) significantly enhanced glucose uptake in C2C12, HepG2, and 3T3-L1 adipocytes (p < 0.05). In C2C12, PCA significantly elevated GLUT-4, IRS-1, IRS-2, PPAR-γ, P-AMPK, and P-Akt vs. Control (p ≤ 0.05), and modulated pathways in IR-PCA. In HepG2, PPAR-γ and P-Akt increased significantly in Control (CM) vs. No CM, and PCA dose upregulated PPAR-γ, P-AMPK, and P-AKT (p < 0.05). In the 3T3-L1 adipocytes, PI3K and GLUT-4 expression was elevated in PCA (CM) vs. No CM. A significant elevation of IRS-1, GLUT-4, and P-AMPK was observed in IR-PCA vs. IR (p ≤ 0.001). Herein, PCA strengthens insulin signaling by activating key proteins of that pathway and regulating glucose uptake. Further, conditioned media modulated crosstalk between muscle with liver and adipose tissue, thus regulating glucose metabolism.

APOE ε4-Allele in Middle-Aged and Older Autistic Adults: Associations with Verbal Learning and Memory.

Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer's disease (Alz) and other dementias compared to neurotypical (NT) adults. The ε4-allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alz and negatively impacts cognition in middle-aged and older (MA+) adults. This study aimed to determine the impact of the APOE ε4-allele on verbal learning and memory in MA+ autistic adults (ages 40-71 years) compared to matched NT adults. Using the Auditory Verbal Learning Test (AVLT), we found that ε4 carriers performed worse on short-term memory and verbal learning across diagnosis groups, but there was no interaction with diagnosis. In exploratory analyses within sex and diagnosis groups, only autistic men carrying APOE ε4 showed worse verbal learning (p = 0.02), compared to autistic men who were not carriers. Finally, the APOE ε4-allele did not significantly affect long-term memory in this sample. These findings replicate previous work indicating that the APOE ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults and presents new preliminary findings that MA+ autistic men may be vulnerable to the effects of APOE ε4 on verbal learning. Future work with a larger sample is needed to determine if autistic women may also be vulnerable.

Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies).

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.

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.