Infodemiology of Influenza-like Illness: Utilizing Google Trends' Big Data for Epidemic Surveillance.

Background: Influenza-like illness (ILI) encompasses symptoms similar to influenza, affecting population health. Surveillance, including Google Trends (GT), offers insights into epidemic patterns. Methods: This study used multiple regression models to analyze the correlation between ILI incidents, GT keyword searches, and climate variables during influenza outbreaks. It compared the predictive capabilities of time-series and deep learning models against ILI emergency incidents. Results: The GT searches for "fever" and "cough" were significantly associated with ILI cases (p < 0.05). Temperature had a more substantial impact on ILI incidence than humidity. Among the tested models, ARIMA provided the best predictive power. Conclusions: GT and climate data can forecast ILI trends, aiding governmental decision making. Temperature is a crucial predictor, and ARIMA models excel in forecasting ILI incidences.

Sustained acute kidney injury as an independent risk factor for neurodevelopmental and growth outcomes in a single NICU center.

PURPOSE: Acute kidney injury (AKI) is commonly seen in neonatal intensive care units (NICUs) and is potentially associated with adverse prognoses in later stages of life. Our study evaluated the impact of sustained AKI (SAKI) on both neurodevelopmental impairment (NDI) and early growth restriction (EGR) in neonates. METHODS: This case-control study retrospectively analyzed the medical records of neonates diagnosed with SAKI in the NICU of a tertiary medical center during the period from January 2007 to December 2020. Cases without subsequent follow-up and those resulting in death were excluded. We analyzed demographic, biochemical, and clinical outcome data. RESULTS: Of the 93 neonates with SAKI, 51 cases (54.8%) were included in this study, while 42 cases (45.2%) were excluded due to a lack of follow-up or death. An age-matched control group comprised 103 neonates, who had never experienced AKI or SAKI, were selected at random. In total, 59 (38.3%) cases were identified as NDI and 43 (27.9%) as EGR. Multivariate analysis revealed that patients with SAKI had significantly higher risks of developing NDI (odds ratio, [OR] = 4.013, p = 0.001) and EGR (OR = 4.894, p < 0.001). The AKI interval had an area under the receiver operating characteristic curve of 0.754 for NDI at 9.5 days and 0.772 for EGR at 12.5 days. CONCLUSIONS: SAKI is an independent risk factor for both NDI and EGR in neonates. Consequently, regular monitoring, neurological development assessments, and appropriate nutritional advice are crucial to these infants who have experienced renal injury.

ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. METHODS AND RESULTS: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. CONCLUSIONS: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

Correction: Huang et al. Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample. Cancers 2023, 15, 1985.

In the original publication [...].

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for one patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection prior to radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

Pulmonary Effects of Traumatic Brain Injury in Mice: A Gene Set Enrichment Analysis.

Acute lung injury occurs in 20-25% of cases following traumatic brain injury (TBI). We investigated changes in lung transcriptome expression post-TBI using animal models and bioinformatics. Employing unilateral controlled cortical impact for TBI, we conducted microarray analysis after lung acquisition, followed by gene set enrichment analysis of differentially expressed genes. Our findings indicate significant upregulation of inflammation-related genes and downregulation of nervous system genes. There was enhanced infiltration of adaptive immune cells, evidenced by positive enrichment in Lung-Th1, CD4, and CD8 T cells. Analysis using the Tabula Sapiens database revealed enrichment in lung-adventitial cells, pericytes, myofibroblasts, and fibroblasts, indicating potential effects on lung vasculature and fibrosis. Gene set enrichment analysis linked TBI to lung diseases, notably idiopathic pulmonary hypertension. A Venn diagram overlap analysis identified a common set of 20 genes, with FOSL2 showing the most significant fold change. Additionally, we observed a significant increase in ADRA1A→IL6 production post-TBI using the L1000 library. Our study highlights the impact of brain trauma on lung injury, revealing crucial gene expression changes related to immune cell infiltration, cytokine production, and potential alterations in lung vasculature and fibrosis, along with a specific spectrum of disease influence.

Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia.

Context: Although a monoallelic mutation in the calcium-sensing receptor (CASR) gene causes familial hypocalciuric hypercalcemia (FHH), the functional characterization of the identified CASR mutation linked to the clinical response to calcimimetics therapy is still limited. Objective: A 45-year-old male presenting with moderate hypercalcemia, hypocalciuria, and inappropriately high parathyroid hormone (PTH) had a good response to cinacalcet (total serum calcium (Ca2+) from 12.5 to 10.1 mg/dl). We identified the genetic mutation and characterized the functional and pathophysiological mechanisms, and then linked the mutation to calcimimetics treatment in vitro. Design: Sanger sequencing of the CASR, GNA11, and AP2S1 genes was performed in his family. The simulation model was used to predict the function of the identified mutant. In vitro studies, including immunoblotting, immunofluorescence, a cycloheximide chase study, Calbryte™ 520 Ca2+ detection, and half-maximal effective concentration (EC50), were examined. Results: This proband was found to carry a de novo heterozygous missense I554N in the cysteine-rich domain of CASR, which was pathogenic based on the different software prediction models and ACGME criteria. The simulation model showed that CASR I554N mutation decreased its binding energy with Ca2+. Human CASR I554N mutation attenuated the stability of CASR protein, reduced the expression of p-ERK 1/2, and blunted the intracellular Ca2+ response to gradient extracellular Ca2+ (eCa2+) concentration. The EC50 study also demonstrated the correctable effect of calcimimetics on the function of the CASR I554N mutation. Conclusion: This novel CASR I554N mutation causing FHH attenuates CASR stability, its binding affinity with Ca2+, and the response to eCa2+ corrected by therapeutic calcimimetics.

Comparative Analysis of Two Commercial Automated Systems with Agar Dilution for Oxacillin Susceptibility and Their Association with Genotypes of Invasive Staphylococcus aureus Isolates (2011-2021).

Background: Determining oxacillin susceptibility using reference methods and automated systems is crucial for treating invasive infections caused by Staphylococcus aureus. This study compares the oxacillin susceptibility results from the two automated systems with agar dilution and correlates them with genotypes of invasive S. aureus. Methods: Non-duplicate S. aureus invasive isolates were collected over an 11-year period. The oxacillin susceptibility was determined with Phoenix 100 (Jan 2011 to Aug 2018) or Vitek 2 (Sep 2018 to Dec 2021), and susceptibility for oxacillin and cefoxitin was determined with agar dilution. Methicillin-resistant S. aureus (MRSA) was confirmed with mecA existence, and the genotype was determined using SCCmec. The association between genotype and antibiotic susceptibility using two automated systems and agar dilution was evaluated. Results: A total of 842 invasive S. aureus, including 443 mecA+ MRSA and 399 mecA- MSSA, were collected. The susceptibility rates of oxacillin determined by two automated systems and agar dilution were 68.8% (76.8% for Phoenix 100 and 57.6% for Vitek 2) and 54.0%, respectively. When compared with the oxacillin susceptibility using agar dilution, the categorical agreement for Phoenix 100 and Vitek 2 were 0.46% and 0.88%, respectively (p < 0.001). One hundred and forty-three isolates were misinterpreted as oxacillin-susceptible S. aureus (OSSA) using automated systems while comparing with agar dilution, among which molecularly community-associated MRSA (CA-MRSA) outnumbered healthcare-associated MRSA (HA-MRSA) (99 vs 34, p < 0.001). There were 70 mecA+ OSSA (OS-MRSA) using agar dilution, among which 42 harbored SCCmec types were predominantly categorized as CA-MRSA (38, p < 0.001). Conclusion: The categorical agreement of Vitek 2 in determining oxacillin susceptibility and predicting mecA existence is comparable with agar dilution, whereas Phoenix 100 is not. Most of those ORSA determined by agar dilution but misinterpreted as OSSA by automated systems and OS-MRSA are categorized as CA-MRSA.

Dynamic expression of cathepsin L in the black soldier fly (Hermetia illucens) gut during Escherichia coli challenge.

The black soldier fly (BSF), Hermetia illucens, has the potential to serve as a valuable resource for waste bioconversion due to the ability of the larvae to thrive in a microbial-rich environment. Being an ecological decomposer, the survival of BSF larvae (BSFL) relies on developing an efficient defense system. Cathepsin L (CTSL) is a cysteine protease that plays roles in physiological and pathological processes. In this study, the full-length of CTSL was obtained from BSF. The 1,020-bp open reading frame encoded a preprotein of 339 amino acids with a predicted molecular weight of 32 kDa. The pro-domain contained the conserved ERFNIN, GNYD, and GCNGG motifs, which are all characteristic of CTSL. Homology revealed that the deduced amino acid sequence of BSF CTSL shared 74.22-72.99% identity with Diptera flies. Immunohistochemical (IHC) analysis showed the CTSL was predominantly localized in the gut, especially in the midgut. The mRNA expression of CTSL in different larval stages was analyzed by quantitative real-time PCR (RT-qPCR), which revealed that CTSL was expressed in the second to sixth instar, with the highest expression in the fifth instar. Following an immune challenge in vivo using Escherichia coli (E. coli), CTSL mRNA was significantly up-regulated at 6 h post-stimulation. The Z-Phe-Arg-AMC was gradually cleaved by the BSFL extract after 3 h post-stimulation. These results shed light on the potential role of CTSL in the defense mechanism that helps BSFL to survive against pathogens in a microbial-rich environment.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Anatomical Anal Stenosis after PPH: Insights from a Retrospective Study and Rat Model.

High-grade hemorrhoids are usually recommended to receive operational treatments. However, these traditional surgeries are associated with severe postoperative pain. A procedure for prolapse and hemorrhoids (PPH), a circular staple device, has been developed to improve short-term outcomes, including reducing the severity of postoperative pain. PPH, compared to conventional surgery, has been associated with the incidence of anatomical anal stenosis. The causes of stenosis after PPH are not yet clear. We first analyzed the complications of our patients with PPH, and then developed a rat model to verify the tension force of PPH using Hematoxylin-eosin, Masson's trichrome, immunohistochemistry, and immunofluorescence staining. Our clinical data showed that PPH significantly improved postoperative pain, but that it resulted in higher incidences of complications, including anal stenosis, than hemorrhoidectomy. We simulated the status of PPH and developed a rat model to verify PPH's tension force, including the scarring area and the deposition of proinflammatory factors, angiogenic factors, and fibrotic factors. The tension wound histological data showed more extensive granulation tissue and inflammatory cell infiltration and a thicker epidermis than the control group on day 12 post-operation and tension treatment. In addition to IL-1ß and IL-10 cytokines on day 3 and IL-1ß, IL-6, and IL-10 cytokines on day 12 post-operation in the tension group, two angiogenic factors, CD31 and VEGF-A, were found to have a more significant expression on day 7 post-operation in the tension group. The mean scar area was larger and the distribution of fibrotic proteins (collagen 1, α-SMA, CTGF, and MMP2) in the tension group was significantly broader than in the control on day 12 post-operation and tension treatment. Based on the findings of our animal model, the development of a lesser tensile force for PPH to decrease the deposition of proinflammatory factors, angiogenic factors, and fibrotic factors is urgently required.

Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in KEAP1 mutant lung cancer.

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases Tregs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.

Effect of early dexamethasone on outcomes of COVID-19: A quasi-experimental study using propensity score matching.

BACKGROUND: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. METHODS: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. RESULTS: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98). CONCLUSION: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Hybrid-Aligned Fibers of Electrospun Gelatin with Antibiotic and Polycaprolactone Composite Membranes as an In Vitro Drug Delivery System to Assess the Potential Repair Capacity of Damaged Cornea.

The cornea lacks the ability to repair itself and must rely on transplantation to repair damaged tissue. Therefore, creating alternative therapies using dressing membranes based on tissue engineering concepts to repair corneal damage before failure has become a major research goal. Themost outstanding features that are important in reconstructing a damaged cornea are the mechanical strength and transparency of the membrane, which are the most important standard considerations. In addition, preventing infection is an important issue, especially in corneal endothelial healing processes. The purpose of this study was to produce aligned fibers via electrospinning technology using gelatin (Gel) composite polycaprolactone (PCL) as an optimal transport and antibiotic release membrane. The aim of the composite membrane is to achieve good tenacity, transparency, antibacterial properties, and in vitro biocompatibility. Results showed that the Gel and PCL composite membranes with the same electrospinning flow rate had the best transparency. The Gel impregnated with gentamicin antibiotic in composite membranes subsequently exhibited transparency and enhanced mechanical properties provided by PCL and could sustainably release the antibiotic for 48 h, achieving good antibacterial effects without causing cytotoxicity. This newly developed membrane has the advantage of preventing epidermal tissue infection during clinical operations and is expected to be used in the reconstruction of damaged cornea in the future.

Imbalance of synaptic and extrasynaptic NMDA receptors induced by the deletion of CRMP1 accelerates age-related cognitive decline in mice.

Collapsin response mediator protein 1 (CRMP1) is involved in semaphorin 3A signaling pathway, promoting neurite extension and growth cone collapse. It is highly expressed in the nervous system, especially the hippocampus. The crmp1 knockout (KO) mice display impaired spatial learning and memory, and this phenomenon seemingly tends to deteriorate with age. Here we investigated whether CRMP1 is involved in age-related cognitive decline in WT and crmp1 KO mice at adult, middle-aged and older stages. The results revealed that cognitive dysfunction in the Morris water maze task became more severe and decreased glutamate and glutamine level in middle-aged crmp1 KO mice. Additionally, increasing levels of extrasynaptic NMDA receptors and phosphorylation of Tau were observed in middle-aged crmp1 KO mice, leading to synaptic and neuronal loss in the CA3 regions of hippocampus. These findings suggest that deletion of CRMP1 accelerates age-related cognitive decline by disrupting the balance between synaptic and extrasynaptic NMDA receptors, resulting in the loss of synapses and neurons.

The effects of incretin-based therapies on weight reduction and metabolic parameters in children with obesity: A systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that incretin-based therapies (IBTs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is) are effective and safe for treating pediatric obesity patients with or without type 2 diabetes. Therefore, we aimed to perform a systematic review and meta-analysis for updating current evidence. METHODS: We searched the PubMed, the Cochrane Library, and the EMBASE database for articles published until September 15, 2023, and limited to randomized control trials. The primary outcomes were changed from baseline in weight metrics and the cardiometabolic profile. A random effects model will be used, as high heterogeneity is expected. All analyses were performed using STATA 17.0. RESULTS: Fifteen trials with a total number of 1286 participants were included in our meta-analysis. Overall, the mean difference in weight change between the IBTs group and the control group was -2.89 kg (95% confidence interval, -5.12 to -0.65, p = 0.011). Additionally, IBTs significantly reduced the HbA1c level and fasting plasma glucose by 0.37% and 6.99 mg/dl, compared with control groups. IBTs showed a little increased risk of GI side effects and hypoglycemia events, but none of the severe hypoglycemia events were occurred in IBTs group. CONCLUSIONS: Our study results have proved that GLP-1 RAs are safe, acceptable, and effective in weight reduction and sugar control for children with obesity. In addition, DPP-4is seems to have no effect on glycemic control and weight loss in childhood obesity. Further research is needed to confirm these findings, especially in younger children.

Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Anti-Vascular Endothelial Growth Factor Injection.

OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into two groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS: A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR: 11.4, p=0.008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR: 13.8, p=0.003), patent ductus arteriosus ligation (OR: 10.7, p=0.032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR: 7.0, p=0.018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being higher with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.

Evaluation of the Feasibility of In Vitro Metabolic Interruption of Trimethylamine with Resveratrol Butyrate Esters and Its Purified Monomers.

Resveratrol (RSV), obtained from dietary sources, has been shown to reduce trimethylamine oxide (TMAO) levels in humans, and much research indicates that TMAO is recognized as a risk factor for cardiovascular disease. Therefore, this study investigated the effects of RSV and RSV-butyrate esters (RBE) on the proliferation of co-cultured bacteria and HepG2 cell lines, respectively, and also investigated the changes in trimethylamine (TMA) and TMOA content in the medium and flavin-containing monooxygenase-3 (FMO3) gene expression. This study revealed that 50 µg/mL of RBE could increase the population percentage of Bifidobacterium longum at a rate of 53%, while the rate was 48% for Clostridium asparagiforme. In contrast, co-cultivation of the two bacterial strains effectively reduced TMA levels from 561 ppm to 449 ppm. In addition, regarding TMA-induced HepG2 cell lines, treatment with 50 µM each of RBE, 3,4'-di-O-butanoylresveratrol (ED2), and 3-O-butanoylresveratrol (ED4) significantly reduced FMO3 gene expression from 2.13 to 0.40-1.40, which would also contribute to the reduction of TMAO content. This study demonstrated the potential of RBE, ED2, and ED4 for regulating TMA metabolism in microbial co-cultures and cell line cultures, which also suggests that the resveratrol derivative might be a daily dietary supplement that will be beneficial for health promotion in the future.