Preterm birth increases cerebral palsy hazards in children of mothers with chronic hypertension in pregnancy.

BACKGROUND: Children of mothers with chronic-hypertension in pregnancy have high rates of preterm-birth (<37 weeks of gestation) and small-for-gestational-age (SGA), both of which are risk factors of cerebral palsy (CP). This study investigated the cumulative risks of CP in children exposed to maternal chronic-hypertension vs. other types of hypertensive-disorders-of-pregnancy (HDP), and whether preterm-birth and SGA potentiate the antenatal impact of chronic-hypertension to increase CP hazards. METHODS: This population-based cohort study enrolled 1,417,373 mother-child pairs with singleton live births between 2004 and 2011 from the Taiwan Maternal and Child Health Database. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for CP outcome until age 6-13 years. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between chronic-hypertension and CP hazard were assessed with adjusted hazard ratios (HR) and 95% confidence intervals (CI) in Cox proportional hazards regression models, and the effects of preterm-birth and SGA on the associations were examined. RESULTS: The HDP group had higher rates of CP (0.8%) than the normotensive group (0.5%), particularly the subgroup of preeclampsia-with-chronic-hypertension (1.0%), followed by preeclampsia (0.9%), chronic-hypertension (0.7%) and gestational-hypertension (0.6%). Preterm-birth, but not SGA, exerted moderating effects to increase CP risks in children exposed to maternal chronic-hypertension. Before adjustments, chronic-hypertension alone had no substantial contribution to CP hazard (HR 1.35, 95% CI 1.00-1.83), while preeclampsia alone (1.64, 1.28-2.11) or with superimposed-chronic-hypertension (1.83, 1.16-2.89) had significant effects. After including preterm-birth in the multivariable model, the CP hazard for chronic-hypertension alone rather than other types of HDP was raised and became significant (1.56, 1.15-2.12), and the significance remained after stepwise adjustments in the final model (1.74, 1.16-2.60). CONCLUSIONS: Preterm-birth might potentiate CP hazards in children of mothers with chronic-hypertension in pregnancy.

Urine cadmium and urolithiasis: A systematic review and meta-analysis.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 µg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 µg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure.

Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome.

The epidermal growth factor receptor (EGFR) plays important roles in multiple cellular events, including growth, differentiation, and motility. A major mechanism of downregulating EGFR function involves its endocytic transport to the lysosome. Sorting of proteins into intracellular pathways involves cargo adaptors recognizing sorting signals on cargo proteins. A dileucine-based sorting signal has been identified previously for the sorting of endosomal EGFR to the lysosome, but a cargo adaptor that recognizes this signal remains unknown. Here, we find that phosphoglycerate kinase 1 (PGK1) is recruited to endosomal membrane upon its phosphorylation, where it binds to the dileucine sorting signal in EGFR to promote the lysosomal transport of this receptor. We also elucidate two mechanisms that act in concert to promote PGK1 recruitment to endosomal membrane, a lipid-based mechanism that involves phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and a protein-based mechanism that involves hepatocyte growth factor receptor substrate (Hrs). These findings reveal an unexpected function for a metabolic enzyme and advance the mechanistic understanding of how EGFR is transported to the lysosome.

Estimation of lifetime productivity loss from patients with chronic diseases: methods and empirical evidence of end-stage kidney disease from Taiwan.

OBJECTIVE: Studies that examine the broad allocation of resources, regardless of who bears the costs, should ideally estimate costs from a societal perspective. We have successfully integrated survival rates, employment ratios, and earnings to address the significant challenge of evaluating societal value through productivity assessments of patients with end-stage kidney disease (ESKD) in Taiwan. METHODS: Using a theoretical framework, we interconnected two nationwide databases: the Taiwan National Health Insurance (NHI) and the Taiwan Mortality Registry from 2000 to 2017. Due to the statutory retirement age of 65, we collected data on all patients (83,358) aged 25-64 years diagnosed with ESKD and undergoing maintenance dialysis. We estimated the lifetime survival function through a rolling extrapolation algorithm, which was then combined with the monthly employment ratio and wages to calculate the lifetime employment duration and productivity up to the legal retirement age of ESKD patients. These were compared with sex-, age-, and calendar year-matched referents to determine the loss of employment duration and productivity of ESKD patients. RESULTS: ESKD patients experienced a loss of approximately 25-56% in lifetime employment duration and a larger loss of about 32-66% in lifetime productivity after adjustments for different age, sex, and calendar year. The annual productivity loss per male (female) ESKD patient relative to that of the age-and calendar year-matched referent ranges from 75.5% to 82.1% (82.3% to 90.3%). During the periods when they are able to work (over the on-the-job duration) male ESKD patients lose between 34 and 56% of their income, and female ESKD patients lose between 39 and 68% of their income, compared to the age-and calendar year-matched referents. The loss of lifetime productivity is a combination of reduced lifetime employment duration, functional disability, absenteeism, and presenteeism at the workplace. The loss related to presenteeism is implied by the reduced wages. CONCLUSIONS: In addition to the loss of employment duration, we have empirically demonstrated the lifetime loss of productivity in patients with ESKD, also indicating the "presenteeism" resulted from inability to perform their job with full capacity over long-term periods.

Epidermal Growth Factor Receptor Inhibitor Mobocertinib Resensitizes Multidrug-Resistant Cancer Cells by Attenuating the Human ATP-Binding Cassette Subfamily B Member 1 and Subfamily G Member 2.

ATP-binding cassette (ABC) transporters, notably ABCB1 (P-glycoprotein) and ABCG2, play a crucial role in the development of multidrug resistance (MDR) during the administration of chemotherapy for cancer patients. With a lack of approved treatments for addressing multidrug-resistant cancers, MDR remains a substantial challenge to the effective management of cancer. Rather than focusing on developing novel synthetic inhibitors, a promising approach to combat MDR involves repurposing approved therapeutic agents to enhance the sensitivity to cytotoxic antiproliferative drugs of multidrug-resistant cancer cells with high expression of ABCB1 or ABCG2. In this investigation, we observed a substantial reversal of MDR conferred by ABCB1 and ABCG2 in multidrug-resistant cancer cells through the use of mobocertinib, an approved third-generation inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Mobocertinib demonstrated the ability to hinder drug transport function without causing changes in protein expression. The interactions between mobocertinib and ABCB1, as well as ABCG2, were validated through ATPase assays. Furthermore, in silico docking simulations were utilized to substantiate the binding of mobocertinib within the drug-binding pockets of both ABCB1 and ABCG2. We conclude that further testing of mobocertinib in combination therapy is warranted for patients with tumors expressing elevated levels of the ABC drug transporters ABCB1 and ABCG2.

A Gate-Tunable Ambipolar Quantum Phase Transition in a Topological Excitonic Insulator.

Coulomb interactions among electrons and holes in 2D semimetals with overlapping valence and conduction bands can give rise to a correlated insulating ground state via exciton formation and condensation. One candidate material in which such excitonic state uniquely combines with non-trivial band topology are atomic monolayers of tungsten ditelluride (WTe2 ), in which a 2D topological excitonic insulator (2D TEI) forms. However, the detailed mechanism of the 2D bulk gap formation in WTe2 , in particular with regard to the role of Coulomb interactions, has remained a subject of ongoing debate. Here, it shows that WTe2 is susceptible to a gate-tunable quantum phase transition, evident from an abrupt collapse of its 2D bulk energy gap upon ambipolar field-effect doping. Such gate tunability of a 2D TEI, into either n- and p-type semimetals, promises novel handles of control over non-trivial 2D superconductivity with excitonic pairing.

Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport.

The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2.

Furmonertinib, a Third-Generation EGFR Tyrosine Kinase Inhibitor, Overcomes Multidrug Resistance through Inhibiting ABCB1 and ABCG2 in Cancer Cells.

ATP-binding cassette transporters, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in cancer patients undergoing conventional chemotherapy. The absence of approved therapeutic agents for multidrug-resistant cancers presents a significant challenge in effectively treating cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether furmonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters. Furmonertinib stands out due to its ability to inhibit drug transport without affecting protein expression. The discovery of this characteristic was validated through ATPase assays, which revealed interactions between furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of furmonertinib offered insights into potential interaction sites within the drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed drug. Given the encouraging results, we propose that furmonertinib should be explored as a potential candidate for combination therapy in patients with tumors that have high levels of ABCB1 and/or ABCG2. This combination therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in cancer treatment.

Maternal hypertensive pregnancy disorders increase childhood intellectual disability hazards independently from preterm birth and small for gestational age.

BACKGROUND: Children of mothers with hypertensive-disorders-of-pregnancy (HDP) have high rates of preterm-birth (<37 weeks' gestation) and small-for-gestational-age (SGA), both of which are risk factors of intellectual disability (ID). AIMS: To test the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ID hazards, and HDP might not have independent effects. METHODS: This population-based cohort study enrolled 1,417,373 mother-child pairs between 2004 and 2011. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for ID outcome until 6-13 years of age. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and ID hazards were assessed with adjusted hazard ratios (aHR) and 95 % confidence intervals (CI), and the effects of preterm-birth and SGA on the associations were examined. RESULTS: The HDP group had higher cumulative rates of ID (1.6 %) than the normotensive group (0.9 %), particularly the subgroup of preeclampsia-with-chronic-hypertension (2.4 %), followed by preeclampsia (1.7 %), chronic-hypertension (1.5 %) and gestational hypertension (1.0 %). Preterm-birth and SGA exerted aggravating effects on ID hazards in children exposed to any HDP. After adjustments, maternal chronic-hypertension (aHR 1.59, 95 % CI 1.28-1.97), preeclampsia (1.52, 1.26-1.83), and preeclampsia-with-chronic-hypertension (1.86, 1.38-2.51) independently contributed to ID outcome. CONCLUSIONS: Maternal HDP other than gestational hypertension increased offspring's ID hazards independently from the potentiating hits of preterm-birth and SGA, implicating long-lasting influence of in-utero HDP exposure on children's cognitive development.

Preterm birth and small for gestational age potentiate the association between maternal hypertensive pregnancy and childhood autism spectrum disorder.

Children of mothers with hypertensive disorders of pregnancy (HDP) have high rates of preterm-birth (gestational age < 37 weeks) and small-for-gestational-age (SGA), both of which are risk factors of autism spectrum disorder (ASD). This study tested the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ASD hazards, and HDP might not be a major contributor. The propensity-score-matched cohort enrolled 18,131 mother-child pairs with HDP and 90,655 normotensive controls between 2004 and 2011. Children with siblings born to the same mothers were excluded for analysis to reduce the potential familial-genetic influence. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and the cumulative ASD risks were assessed with hazard ratios, and the effects of preterm-birth and SGA on the associations were examined. The HDP group had a higher cumulative rate of ASD (1.5%) than the normotensive group (1.2%). Preterm-birth and SGA exerted moderating effects to aggravate ASD hazards in children exposed to chronic-hypertension or gestational-hypertension. None of HDP types significantly contributed to ASD after adjustments. In conclusion, antenatal HDP exposure might predispose to ASD outcome through susceptibility to the impact of preterm-birth and SGA.

Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics.

Advances in disease-related gene discovery have led to tremendous innovations in the field of epilepsy genetics. Identification of genetic mutations that cause epileptic encephalopathies has opened new avenues for the development of targeted therapies. Clinical testing using extensive gene panels, exomes, and genomes is currently accessible and has resulted in higher rates of diagnosis and better comprehension of the disease mechanisms underlying the condition. Children with developmental disabilities have a higher risk of developing epilepsy. As our understanding of the mechanisms underlying encephalopathies and epilepsies improves, there may be greater potential to develop innovative therapies tailored to an individual's genotype. This article provides an overview of the significant progress in epilepsy genomics in recent years, with a focus on developmental and epileptic encephalopathies in children. The aim of this review is to enhance comprehension of the clinical utilization of genetic testing in this particular patient population. The development of effective and precise therapeutic strategies for epileptic encephalopathies may be facilitated by a comprehensive understanding of their molecular pathogenesis.

Neuropsychiatric Symptoms and Caregiver Stress in Parkinson's Disease with Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

BACKGROUND: A better understanding of factors associated with caregiver burden might facilitate the construction of coping strategies to improve their clinical outcomes and the comprehensive care model for dementia. OBJECTIVE: To investigate the cognitive and neuropsychiatric domains that contribute to caregiver burden in three types of neurodegenerative disorders: Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal disease (FTD). METHODS: Eight hundred and fourteen patients and their caregivers were invited to participate; among them, 235 had PD with cognitive impairment; 429 had AD, and 150 had FTD. The evaluation protocol included the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, the Chinese Version Verbal Learning Test, the modified Trail Making Test B, semantic fluency, and a geriatric depression score. Statistical comparisons of the cognitive tests, NPI total scores, and caregiver burden among the three diagnosed types of dementia, matched for a Clinical Dementia Rating (CDR) of 0.5 or 1, were performed, and multivariate linear regression models were used to evaluate the parameter significance. RESULTS: Caregivers for patients with PD and FTD showed significant burden increments when the CDR scores changes from 0.5 to 1. For CDR = 0.5, the PD group had significantly lower caregiver burdens than the AD group, but the NPI total scores were significantly higher. Factors related to caregiver burden were the presence of delusion among all diagnosis groups, while the impact of NPI total scores related to caregiver burden was the highest in FTD, followed by AD and PD. CONCLUSIONS: At the mild to moderate stages, our results suggested different degrees of significance in terms of the cognitive test scores or NPI subdomains for predicting caregiver stress among the three types of dementia.

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

Prenatal and postnatal exposure to PM2 .5 and the risk of tic disorders.

BACKGROUND: Tic disorders are common neurodevelopmental disorders during childhood. Whether prenatal and postnatal exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5 ) plays a role in the development of tic disorders remains unexplored. OBJECTIVES: To investigate the association of exposure between PM2.5 during the pregnancy and infancy periods and the risk of tic disorders. METHODS: This birth cohort study recruited singleton live births at term gestations in central Taiwan from the Taiwan Maternal and Child Health Database between 2004 and 2012 and followed up to the end of 2017. New cases of tic disorders were defined using the ICD-9-CM (307.2) and ICD-10-CM (F95), which include all tic spectrum disorders. We assigned daily PM2.5 concentrations derived from a satellite-based model to individuals based on maternal residential addresses at delivery. We fit Cox proportional hazard model and distributed lag non-linear model to estimate the associations between PM2.5 and tic disorders, with hazard ratio (HR) with 95% confidence interval (CI) as the effect measure. RESULTS: Of the 309,376 singleton live births at term gestations, we identified 5902 (1.9%) tic disorder cases. The HR of tic disorders was positively associated with a 10 µg/m3 increase in PM2.5 : during pregnancy HR 1.09, 95% CI 1.04, 1.15 and during infancy HR 1.12, 95% CI 1.06, 1.18. The vulnerable time window for infants with increased risk of tic disorders was 6-52 weeks after birth. We observed a nonlinear relationship between PM2.5 and the risk of tic disorders, with exposure to PM2.5 between 16 and 64 µg/m3 being associated with the risk of tic disorders. The association was restricted to Tourette's disorder group. Infant sex did not modify these associations. CONCLUSIONS: Infants delivered at term and exposed to PM2.5 are associated with an increased risk of tic disorders (6-52 weeks). Further studies are needed to confirm these associations.

The effectiveness of child-centered play therapy for executive functions in children with attention-deficit/hyperactivity disorder.

INTRODUCTION: Child-centered play therapy (CCPT) is a practical and recommended non-medication intervention for children with Attention-deficit/hyperactivity disorder (ADHD) but the mechanism in between is unclear. AIM: This study proposed to examine the effectiveness of CCPT on neuropsychological deficits and behavioral symptoms in ADHD. METHODS: Participants with ADHD diagnosis were referred from senior child and adolescent psychiatrists, and typical developmental children (TD) were recruited from community as a control group. All participants' executive functions were evaluated using Cambridge Neuropsychological Test Automated Battery. First of all, the participants were evaluated using Child Behavior Checklist (CBCL) by their parents. The ADHD participants were assigned into CCPT (ADHDc) and waitlist (ADHDw) group; and the ADHDc group then received CCPT weekly for 12 sessions, while the ADHDw continuously received their regular treatment (i.e., medication treatment or other alternative treatments) as usual. RESULTS: Total 52 participants were recruited (17 with ADHD and 35 typically developed children, TD). The results showed that overall the ADHD groups had worse neuropsychological performance and more behavioural disturbance than did the TD (ps < .05). After receiving the CCPT, the results showed that the ADHDc group had significant improvement in the cognitive flexibility (p < .05); while the ADHDw group had no changes.

Structural and Functional Neural Correlates in Individuals with Excessive Smartphone Use: A Systematic Review and Meta-Analysis.

Background: Despite known association of internet addiction with a reduced brain volume and abnormal connectivity, the impact of excessive smartphone use remains unclear. Methods: PubMed, Embase, ClinicalTrial.gov, and Web of Science databases were systematically searched from inception to July 2022 using appropriate keywords for observational studies comparing differences in brain volumes and activations between excessive smartphone users and individuals with regular use by magnetic resonance imaging. Results: Of the 11 eligible studies retrieved from 6993 articles initially screened, seven and six evaluated brain volumes and activations, respectively. The former enrolled 421 participants (165 excessive smartphone users vs. 256 controls), while the latter recruited 276 subjects with 139 excessive smartphone users. The results demonstrated a smaller brain volume in excessive smartphone users compared to the controls (g = −0.55, p < 0.001), especially in subcortical regions (p < 0.001). Besides, the impact was more pronounced in adolescents than in adults (p < 0.001). Regression analysis revealed a significant positive association between impulsivity and volume reduction. Regarding altered activations, the convergences of foci in the declive of the posterior lobe of cerebellum, the lingual gyrus, and the middle frontal gyrus were noted. Conclusions: Our findings demonstrated a potential association of excessive smartphone use with a reduced brain volume and altered activations.

Hyperosmolar Hyperglycemic Crisis After Burn Injury in a Patient With Advanced Amyotrophic Lateral Sclerosis: A Case Report.

ABSTRACT: Metabolic disturbance in patients of amyotrophic lateral sclerosis is a rare presentation that might be related to disease progression and outcomes. Hypermetabolic status after major burn injury remains a critical issue in the modern medical care. Here, we present a rare case of a patient sporadic amyotrophic lateral sclerosis who suffered from minor burn injury (8% total body surface area), developing critical hyperosmolar hyperglycemic state during early hospitalization. Newly diagnosed diabetes is established and found related to the underlying disease of this patient. The accumulative metabolic alteration among vulnerable patients of amyotrophic lateral sclerosis and burn injury is noteworthy. Judicious monitoring of fluid and metabolic status helps to prevent the occurrence of acute hyperosmolar hyperglycemic state.

How a winding-down oil refinery park impacts air quality nearby?

It is always difficult to compare, let alone estimate, the difference of air pollutant concentrations before and after closure of a major source because the pollutants cannot be traced or predicted after entering the ambient. Indeed, we are not aware of any studies specifically related to the air pollutants impacted by a winding-down source. In this work, we applied nine years (2010-2018) online measurement of air pollutants (including PM10, PM2.5, NO2, SO2, O3 and VOCs) to investigate (i) the temporal behavior of air pollutants before and after closure of an oil refinery park by using pair-wise statistics and correlations between wind speed and direction, and (ii) the source impacts on O3 concentrations using PMF coupled with multiple linear regression (MLR) analysis (PMF-MLR). Example applications are presented at two monitoring sites (A and B) close to the Kaohsiung Oil Refinery (KOR), located in the southern industrial city of Taiwan. The results show that the KOR shutdown changed air pollutant concentrations to a certain extent in these study areas. We also conclude that, instead of using propylene-equivalent and ozone formation potential (OFP) concentrations, it is better to estimate the formation of O3 based on PMF-MLR analysis as developed in this study. The PMF analysis has identified various VOCs sources at both sites including solvent usage, petrochemical industrial sources, industrial emissions, vehicle-related sources, vegetation emissions and aged air-masses. Also, the MLR model shows that both the background sources and petrochemical industrial sources may significantly change O3 concentrations.

Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy.

Deficiency in DNA damage response (DDR) genes leads to impaired DNA repair functions that will induce genomic instability and facilitate cancer development. However, alterations of DDR genes can serve as biomarkers for the selection of suitable patients to receive specific therapeutics, such as immune checkpoint blockade (ICB) therapy. In addition, certain altered DDR genes can be ideal therapeutic targets through adapting the mechanism of synthetic lethality. Recent studies indicate that targeting DDR can improve cancer immunotherapy by modulating the immune response mediated by cGAS-STING-interferon signaling. Investigations of the interplay of DDR-targeting and ICB therapies provide more effective treatment options for cancer patients. This review introduces the mechanisms of DDR and discusses their crucial roles in cancer therapy based on the concepts of synthetic lethality and ICB. The contemporary clinical trials of DDR-targeting and ICB therapies in breast, colorectal, and pancreatic cancers are included.