The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

INTRODUCTION: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. METHODS: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. RESULTS: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). DISCUSSION: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. CONCLUSIONS: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium.

Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption.

This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.

Empowering Hospitalized Patients With Diabetes: Implementation of a Hospital-wide CGM Policy With EHR-Integrated Validation for Dosing Insulin.

OBJECTIVE: We aimed to assess the feasibility, clinical accuracy, and acceptance of a hospital-wide continuous glucose monitoring (CGM) policy with electronic health record (EHR)-integrated validation for insulin dosing. RESEARCH DESIGN AND METHODS: A hospital policy was developed and implemented at Stanford Health Care for using personal CGMs in lieu of fingerstick blood glucose (FSBG) monitoring. It included requirements specific to each CGM, accuracy monitoring protocols, and EHR integration. User experience surveys were conducted among a subset of patients and nurses. RESULTS: From November 2022 to August 2023, 135 patients used the CGM protocol in 185 inpatient encounters. This included 27% with type 1 diabetes and 24% with automated insulin delivery systems. The most-used CGMs were Dexcom G6 (44%) and FreeStyle Libre 2 (43%). Of 1,506 CGM validation attempts, 87.8% met the %20/20 criterion for CGM-based insulin dosing and 99.3% fell within Clarke zones A or B. User experience surveys were completed by 27 nurses and 46 patients. Most nurses found glucose management under the protocol effective (74%), easy to use (67%), and efficient (63%); 80% of nurses preferred inpatient CGM to FSBG. Most patients liked the CGM protocol (63%), reported positive CGM interactions with nursing staff (63%), and felt no significant interruptions to their diabetes management (63%). CONCLUSIONS: Implementation of a hospital-wide inpatient CGM policy supporting multiple CGM types with real-time accuracy monitoring and integration into the EHR is feasible. Initial feedback from nurses and patients was favorable, and further investigation toward broader use and sustainability is needed.

Protective effect of N-acetylcysteine against hepatocellular carcinoma in hepatitis B virus carriers.

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC), contributing to cancer development through direct genomic integration and chronic inflammation. N-acetylcysteine (NAC), known for its antioxidant properties, is widely utilized in cancer prevention. However, clinical evidence regarding its protective effect against HCC in HBV carriers remains sparse. In this retrospective cohort study spanning 2008 to 2018, we utilized Taiwan's National Health Insurance Research Database (NHIRD) to include 1,061,174 chronic HBV carriers. Participants were stratified into NAC users and non-users using Propensity Score Matching. We assessed the incidence of HCC in both cohorts, examining the relationship between NAC usage duration and HCC incidence, and evaluating the dose-response effect. NAC users exhibited a significantly lower risk of developing HCC (adjusted hazard ratio [aHR]: 0.38; 95% confidence interval [CI]: 0.36-0.40; P < 0.0001). A dose-response relationship was evident, with higher cumulative defined daily doses (cDDDs) of NAC correlating with reduced HCC risk, revealing a significant trend (P < 0.0001). Notably, a daily NAC intensity of > 1.4 DDDs was associated with a decreased risk of HCC in HBV patients. Our results demonstrate that the use of NAC, in a dose-dependent manner, is intricately linked with a diminished incidence of HCC in individuals chronically infected with the HBV.

Survival impact of pre-transplant local treatments in liver transplant recipients with BCLC stage A hepatocellular carcinoma.

This study aimed to evaluate the impact of different pre-transplant local treatments on the survival of liver transplantation (LTx) recipients with BCLC Stage A Hepatocellular Carcinoma (HCC). We analyzed data from the Taiwan Cancer Registry and National Health Insurance Research Databases spanning 2012 to 2018. Employing propensity score matching, patients were categorized into three groups: those receiving local treatments (180 patients), hepatectomy (179 patients), and combined treatments (180 patients). The primary outcomes were overall mortality and HCC-specific death, assessed using time-varying Cox regression models and Kaplan-Meier survival analysis. During a median follow-up period of 3.92 years, all-cause mortality rates were observed as 74.44% for local treatments, 42.46% for hepatectomy, and 65.00% for combined treatments. HCC-specific mortality rates followed a similar pattern at 65.00%, 39.11%, and 59.44%, respectively. Adjusted hazard ratios demonstrated significantly elevated mortality risks associated with local and combined treatments compared to hepatectomy. Notably, the 2-year overall and HCC-specific survival rates were highest in the hepatectomy group, surpassing those observed in both the combined treatment and local treatment groups. The findings of our study highlight that for patients with BCLC Stage A HCC, undergoing hepatectomy prior to LTx is associated with superior survival outcomes compared to solely local treatments. This underscores the importance of considering hepatectomy as a vital component of the treatment strategy in this patient population.

Effects of N-acetylcysteine on hepatocellular carcinoma in chronic hepatitis C.

Hepatitis C virus (HCV) infection significantly contributes to global hepatocellular carcinoma (HCC) incidence. N-Acetylcysteine (NAC), known for its antioxidant properties, is a potential therapeutic agent. However, evidence on its efficacy in reducing HCC risk among HCV patients is limited. A retrospective cohort analysis using Taiwan's National Health Insurance Research Database (2008-2018) included ≥18-year-old HCV patients. NAC usage (≥28 cumulative defined daily doses [cDDDs]) was assessed for its association with HCC risk using Cox regression models and propensity score matching. The study comprised 269,647 HCV patients, with detailed NAC dosage characterization and hazard ratios (HRs) for HCC risk. Post-matching, NAC usage emerged as the significant predictor of reduced HCC risk (adjusted HR: 0.39, 95% CI: 0.37-0.41, P<0.0001). Dose-response analysis showed reduced HCC risk with increasing cDDDs of NAC (P<0.0001). Higher daily NAC dosage (≥1 DDD) was associated with significantly lower HCC risk (adjusted HR: 0.33, 95% CI: 0.31-0.36, P<0.0001). The study provides compelling evidence for NAC's potential in reducing HCC risk among HCV patients. Insights into dose-dependent effects and optimal daily intensity thresholds offer valuable directions for future therapeutic strategies and clinical trials targeting HCC burden in HCV-infected individuals.

Ameliorative effect of α-tocopherol and tocotrienol-rich palm oil extract on menopause-associated mood disorder in ovariectomized mice.

Menopause-associated mood disorder is characterized by emotional depression, anxiety, and stress, which accompany hypogonadism in women in the menopausal phase. The current treatment for menopause-associated mood disorder provides only symptomatic relief and is associated with many side effects. Supplementation with vitamin E has been shown to be effective in ameliorating anxiety and depression. However, the effects of vitamin E and its underlying mechanism in ameliorating menopause-associated mood disorders remain uncertain. This work evaluated the effects of α-tocopherol and tocotrienol-rich palm oil extract on depressive and anxiety-related phenotypes induced by estrogen deficiency through ovariectomy in mice. Our study revealed that ovariectomized mice exhibited alterations in behavior indicative of depressive- and anxiety-like behaviors. The serum corticosterone level, a glucocorticoid hormone associated with stress, was found to be elevated in ovariectomized mice as compared to the sham group. Oral administration of α-tocopherol (50 and 100 mg/kg) and tocotrienol-rich palm oil extract (100 and 200 mg/kg) for 14 days alleviated these behavioral changes, as observed in open field, social interaction, and tail suspension tests. However, treatment with tocotrienol-rich palm oil extract, but not α-tocopherol, modulated the depressive- and anxiety-like responses in ovariectomized mice subjected to chronic restraint stress. Both treatments suppressed the elevated serum corticosterone level. Our findings suggested that α-tocopherol and tocotrienol-rich palm oil extract alleviated menopause-associated mood disorder, at least in part, by modulating the hypothalamic-pituitary-adrenal (HPA) axis. The findings of this study can provide a new foundation for the treatment of menopause-associated depressive- and anxiety-like phenotypes, for the betterment of psychological wellbeing.

Resurgence of Clinical Malaria in Ethiopia in the Era of Anopheles stephensi Invasion.

Background: The invasion of Anopheles stephensi into Africa poses a potential threat to malaria control and elimination on the continent. However, it is not clear if the recent malaria resurgence in Ethiopia has linked to the expansion of An. stephensi. We aimed to summarize the major achievements and lesson learnt in malaria control in Ethiopia from 2001 to 2022, to assess the new challenges and prospects for the control of An. stephensi. Methods and findings: We obtained the clinical malaria case reports, antimalarial drug treatment records, insecticide-treated and long-lasting insecticidal net (ITN/LLIN) distribution and utilization records, and indoor residual spraying (IRS) coverage data from the Ethiopian Ministry of Health (MoH) for the period 2001-2022. We analyzed clinical malaria hotspots using spatially optimized hotspot analysis. We investigated malaria outbreaks in 2022 and examined the potential role of An. stephensi in the outbreaks.Clinical malaria cases in Ethiopia decreased by 80%, from 5.2 million cases (11% confirmed) in 2004 to 1.0 million cases (92% confirmed) in 2018; however, cases increased steadily to 2.6 million confirmed cases (98% confirmed) in 2022. Plasmodium vivax cases and proportion have increased significantly in the past 5 years. Clinical malaria hotspots are concentrated along the western Ethiopian border areas and have grown significantly from 2017 to 2022. Major malaria outbreaks in 2022/23 were detected in multiple sites across Ethiopia, and An. stephensi was the predominant vector in some of these sites, however, it was absence from many of the outbreak sites. Conclusions: The malaria burden has been significantly reduced in Ethiopia in the past two decades, but in recent years it has increased substantially, and the cause of such increase is a subject of further investigation. Major gaps exist in An. stephensi research, including vector ecology, surveillance, and control tools, especially for adult mosquito control.

Directed Self-Assembly of Polystyrene-Block-Polyhedral Oligomeric Silsesquioxane Monolayer by Nano-Trench for Nanopatterning.

This work pioneers to combine fast self-assembly of polyhedral oligomeric silsesquioxanes (POSS) nanocage-based giant surfactants with high etching contrast and directed self-assembly for reliable long-range lateral order to create well-aligned sub-10 nm line nanopatterns via reactive ion etching (RIE). Polystyrene-block-oligo(dimethylsiloxane) substituted POSS (PS-b-oDMS7POSS) with seven oligo(dimethylsiloxane) at the corners of the POSS nanocage and one polystyrene (PS) tail is designed and synthesized as a giant surfactant with self-assembly behaviors like block copolymer (BCP). In contrast to BCP, oDMS7POSS gives a volume-persistent "nanoatom" particle with higher mobility for fast self-assembly and higher segregation strength with PS for smaller feature size. By taking advantage of directed self-assembly using nano-trench fabricated by electron beam lithography, well-ordered nanostructured monolayer with well-aligned parallel oDMS7POSS cylinders can be formed by confined self-assembly within the nano-trench. With the optimization of the RIE treatment using O2 as an etchant, the high etching contrast from the oDMS7POSS and PS gives the formation of well-defined line nanopatterns with sub-10 nm critical dimension that can serve as a mask for pattern transfer in lithography. These results demonstrate a cost-effective approach for nanopatterning by utilizing a creatively designed giant surfactant with sub-10 nm feature size and excellent etching contrast for modern lithographic applications.

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on haemoglobin levels in Ethiopia: a longitudinal cohort study.

BACKGROUND: To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. METHODS: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. RESULTS: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28-15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to - 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (- 0.60 g/dL) than in the G6PDd ACT alone group (- 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = - 0.00 to 0.20) and 0.05 g/dl (95% CI = - 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). CONCLUSIONS: This study's findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes.

Large-area and few-layered 1T'-MoTe2thin films grown by cold-wall chemical vapor deposition.

This study employs cold-wall chemical vapor deposition to achieve the growth of MoTe2thin films on 4-inch sapphire substrates. A two-step growth process is utilized, incorporating MoO3and Te powder sources under low-pressure conditions to synthesize MoTe2. The resultant MoTe2thin films exhibit a dominant 1T' phase, as evidenced by a prominent Raman peak at 161 cm-1. This preferential 1T' phase formation is attributed to controlled manipulation of the second-step growth temperature, essentially the reaction stage between Te vapor and the pre-deposited MoOxlayer. Under these optimized growth conditions, the thickness of the continuous 1T'-MoTe2films can be precisely tailored within the range of 3.5-5.7 nm (equivalent to 5-8 layers), as determined by atomic force microscopy depth profiling. Hall-effect measurements unveil a typical hole concentration and mobility of 0.2 cm2Vs-1and 7.9 × 1021cm-3, respectively, for the synthesized few-layered 1T'-MoTe2films. Furthermore, Ti/Al bilayer metal contacts deposited on the few-layered 1T'-MoTe2films exhibit low specific contact resistances of approximately 1.0 × 10-4Ω cm2estimated by the transfer length model. This finding suggests a viable approach for achieving low ohmic contact resistance using the 1T'-MoTe2intermediate layer between metallic electrodes and two-dimensional semiconductors.

Lipopolysaccharide-Induced Lysosomal Cell Death Through Reactive Oxygen Species in Rat Liver Cell Clone 9.

In sepsis, bacterial components, particularly lipopolysaccharide (LPS), trigger organ injuries such as liver dysfunction. Although sepsis induces hepatocyte damage, the mechanisms underlying sepsis-related hepatic failure remain unclear. In this study, we demonstrated that the LPS-treated rat hepatocyte cell line Clone 9 not only induced reactive oxygen species (ROS) generation and apoptosis but also increased the expression of the autophagy marker proteins LC3-II and p62, and decreased the expression of intact Lamp2A, a lysosomal membrane protein. Additionally, LPS increased lysosomal membrane permeability and galectin-3 puncta formation, and promoted lysosomal alkalization in Clone 9 cells. Pharmacological inhibition of caspase-8 and cathepsin D (CTSD) suppressed the activation of caspase-3 and rescued the viability of LPS-treated Clone 9 cells. Furthermore, LPS induced CTSD release associated with lysosomal leakage and contributed to caspase-8 activation. Pretreatment with the antioxidant N-acetylcysteine (NAC) not only diminished ROS generation and increased the cell survival rate, but also decreased the expression of activated caspase-8 and caspase-3 and increased the protein level of Lamp2A in LPS-treated Clone 9 cells. These results demonstrate that LPS-induced ROS causes lysosomal membrane permeabilization and lysosomal cell death, which may play a crucial role in hepatic failure in sepsis. Our results may facilitate the development of new strategies for sepsis management.

Oral and topical administration of a geranyl acetophenone attenuates DNCB-induced atopic dermatitis-like skin lesions in BALB/c mice.

Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.

Investigation of Degradation and Biocompatibility of Indirect 3D-Printed Bile Duct Stents.

This study proposes a bile duct stent based on indirect 3D printing technology. Four ratio materials were synthesized from lactic acid (LA) and glycolide (GA) monomers by melt polymerization: PLA, PLGA (70:30), PLGA (50:50), and PLGA (30:70). The four kinds of material powders were preliminarily degraded, and the appearance was observed with an optical microscope (OM) and a camera. The weight and appearance of the four materials changed significantly after four weeks of degradation, which met the conditions for materials to be degraded within 4-6 weeks. Among them, PLGA (50:50) lost the most-the weight dropped to 13.4%. A stent with an outer diameter of 10 mm and an inner diameter of 8 mm was successfully manufactured by indirect 3D printing technology, demonstrating the potential of our research. Then, the degradation experiment was carried out on a cylindrical stent with a diameter of 6 mm and a height of 3 mm. The weight loss of the sample was less than that of the powder degradation, and the weight loss of PLGA (50:50) was the largest-the weight dropped to 79.6%. The nano-indenter system measured the mechanical properties of materials. Finally, human liver cancer cells Hep-3B were used to conduct in vitro cytotoxicity tests on the scaffolds to test the biocompatibility of the materials. A bile duct stent meeting commercial size requirements has been developed, instilling confidence in the potential of our research for future medical applications.

Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).

Aromatherapy for the prevention of postoperative nausea and vomiting: A systematic review and meta-analysis.

Objectives: Postoperative nausea and vomiting (PONV) are common complications following surgical procedures. While drug-based treatments are standard, there is increasing interest in nonpharmacological alternatives, such as aromatherapy, due to potential benefits and minimal side effects. This study aimed to assess the effectiveness of aromatherapy in preventing PONV. Materials and Methods: A comprehensive systematic review and meta-analysis were conducted using PubMed, Cochrane Library, EMBASE, and CINAHL databases for studies published up to May 2023. The included studies were randomized controlled trials (RCTs) and nonrandomized studies of interventions that examined the impact of aromatherapy on PONV. The risk of bias was assessed, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was employed to evaluate the certainty of the evidence. Results: Eleven studies were selected for review, with eight RCTs included in the meta-analysis. Aromatherapy effectively reduced postoperative nausea severity (standardized mean difference [SMD]: -0.93, 95% confidence interval [CI]: -1.64 to -0.22; P = 0.010), but the reduction in vomiting episodes was not statistically significant (SMD: -0.81, 95% CI: -1.98-0.37; P = 0.180). Subgroup analysis indicated that ginger essence, lavender, and peppermint oils were particularly effective in managing postoperative nausea. However, due to significant statistical heterogeneity and potential biases in the studies, the results should be interpreted with caution. The certainty of the evidence, as evaluated by the GRADE approach, was low. Conclusion: Preliminary evidence supports the potential benefit of aromatherapy in reducing the severity of postoperative nausea. However, given the low certainty of current evidence, more rigorous and standardized research is needed. The safety, affordability, and potential benefits to patient comfort make aromatherapy a promising area for further research in postoperative care.

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

BACKGROUND: Chronic inflammation may increase susceptibility to pneumonia. RESEARCH QUESTION: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. METHODS: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. RESULTS: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). CONCLUSIONS: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

What is the best predictor of mortality in patients with type 2 diabetes and chronic kidney disease: mean, variability of HbA1c or HbA1c-Hemoglobin ratio?

AIM: Limitations in the measurement of glycated hemoglobin (HbA1c) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) result in uncertainty about the best predictor of mortality among these patients. Our study aimed to determine the association between the mean and average real variability (ARV) of HbA1c, as well as HbA1c-hemoglobin (HH) ratio with mortality among patients with T2D and CKD. MATERIALS AND METHODS: We identified 16,868 T2D patients with stage 3 or above CKD from outpatient visits during 2003-2018. We ascertained all-cause and cardiovascular mortality through linkage to Taiwan's National Death Registry. Mortality rates were estimated using the Poisson distribution, and we conducted Cox proportional hazards regressions to assess relative risks of mortality corresponding to the mean HbA1c, ARV of HbA1c and HH ratio. RESULTS: Compared to patients with a mean HbA1c of 7.0-7.9%, a mean HbA1c < 7.0% was persistently associated with highest risk of all-cause but not cardiovascular mortality after adjusting for confounders. On the contrary, patients with HbA1c-ARV in the second to fourth quartiles and HH ratios in the higher quartiles showed increased risk of all-cause and cardiovascular mortality compared to those in the first quartiles. CONCLUSIONS: HbA1c-ARV was more effective than mean HbA1c or HH ratio in predicting mortality in T2D patients with CKD. Apart from optimal glucose control, multidisciplinary care focusing on glycemic variability is essential for reducing mortality in these patients.