Comparison of splenic embolization and splenectomy for traumatic splenic rupture: a meta-analysis.

INTRODUCTION: This study aims to assess the safety and clinical efficacy of percutaneous splenic embolization (PSE) and splenectomy as approaches to treating cases of traumatic splenic rupture (TSR). MATERIAL AND METHODS: Eligible articles published throughout August 2023 were identified. Endpoints compared between PSE and splenectomy patient groups included operative time, intraoperative hemorrhage, duration of hospitalization, postoperative complication rates, and measures of immune function. RESULTS: Thirteen studies, involving 474 and 520 patients in the PSE and splenectomy groups respectively, were incorporated into this meta-analysis. As compared to the splenectomy group, individuals treated via PSE exhibited a significant reduction in pooled operative time (p < 0.00001) and hospitalization duration (p < 0.00001), with corresponding reductions in rates of intraoperative hemorrhage (p < 0.00001), total complications (p < 0.0001), incisional infection (p < 0.0001), ileus (p = 0.0004), and abdominal infection (p = 0.02). The immune status of these PSE group patients was also improved, as evidenced by significantly higher pooled CD4+ (30 days), CD4+/CD8+ (30 days), and CD3+ (30 days) values (p < 0.0001, 0.0001, and 0.0001, respectively). CONCLUSIONS: Compared to splenectomy, PSE-based TSR treatment can significantly reduce operative time, rate of postoperative complications, and incidence of intraoperative hemorrhage, while improving post-procedural immune functionality.

Psychiatric Disorders Are Common Among Older US Veterans Prior to Traumatic Brain Injury.

OBJECTIVE: To estimate the impact of traumatic brain injury (TBI) on prevalence of posttraumatic stress disorder (PTSD), depression, and alcohol and substance use disorders. SETTING: A random sample of Veteran's Health Administration data. PARTICIPANTS: A total of 14 116 veterans aged ≥55 with incident late-life TBI between October 1, 1999, and September 31, 2021, were matched 1:3 on age and TBI date to 42 678 veterans without TBI. DESIGN: Retrospective cohort study. MAIN MEASURES: PTSD, depression, and alcohol and substance use disorders were identified using diagnostic codes. Participants were censored after the first diagnosis during the year before and the year after the TBI or matched date. Prevalence rates of PTSD, depression, alcohol, and substance use disorders were compared before and after incident TBI or matched date using Poisson regression. RESULTS: Pre-TBI prevalence rates of disorders were higher among those with TBI relative to those without TBI. Pre-TBI PTSD prevalence rates (per 1000 person-years) were 126.3 (95% CI, 120.2-132.4) compared to 21.5 (95% CI, 20.1-22.9) in the non-TBI cohort. In adjusted models, TBI was not associated with an increase in the prevalence of any of the studied disorders. CONCLUSIONS: Prevalence rates of depression, PTSD, and alcohol and substance use disorders were 5 to 10 times higher among older veterans before incident TBI. We did not observe an increase in the prevalence of these disorders after incident TBI. Older veterans with these disorders may be at increased risk for TBI.

Long-chain unsaturated fatty acids sensor controlling the type III/VI secretion system is essential for Edwardsiella piscicida infection.

Edwardsiella piscicida is an acute marine pathogen that causes severe damage to the aquaculture industry worldwide. The pathogenesis of E. piscicida is dependent mainly on the type III secretion system (T3SS) and type VI secretion system (T6SS), both of which are critically regulated by EsrB and EsrC. In this study, we revealed that fatty acids influence T3SS expression. Unsaturated fatty acids (UFAs), but not saturated fatty acids (SFAs), directly interact with EsrC, which abolishes the function of EsrC and results in the turn-off of T3/T6SS. Moreover, during the in vivo colonization of E. piscicida, host fatty acids were observed to be transported into E. piscicida through FadL and to modulate the expression of T3/T6SS. Furthermore, the esrCR38G mutant blocked the interaction between EsrC and UFAs, leading to dramatic growth defects in DMEM and impaired colonization in HeLa cells and zebrafish. In conclusion, this study revealed that the interaction between UFAs and EsrC to turn off T3/T6SS expression is essential for E. piscicida infection.

Deep-learning segmentation to select liver parenchyma for categorizing hepatic steatosis on multinational chest CT.

Unenhanced CT scans exhibit high specificity in detecting moderate-to-severe hepatic steatosis. Even though many CTs are scanned from health screening and various diagnostic contexts, their potential for hepatic steatosis detection has largely remained unexplored. The accuracy of previous methodologies has been limited by the inclusion of non-parenchymal liver regions. To overcome this limitation, we present a novel deep-learning (DL) based method tailored for the automatic selection of parenchymal portions in CT images. This innovative method automatically delineates circular regions for effectively detecting hepatic steatosis. We use 1,014 multinational CT images to develop a DL model for segmenting liver and selecting the parenchymal regions. The results demonstrate outstanding performance in both tasks. By excluding non-parenchymal portions, our DL-based method surpasses previous limitations, achieving radiologist-level accuracy in liver attenuation measurements and hepatic steatosis detection. To ensure the reproducibility, we have openly shared 1014 annotated CT images and the DL system codes. Our novel research contributes to the refinement the automated detection methodologies of hepatic steatosis on CT images, enhancing the accuracy and efficiency of healthcare screening processes.

Comparative physiology and transcriptome response patterns in cold-tolerant and cold-sensitive varieties of Solanum melongena.

BACKGROUND: Climate change has led to severe cold events, adversely impacting global crop production. Eggplant (Solanum melongena L.), a significant economic crop, is highly susceptible to cold damage, affecting both yield and quality. Unraveling the molecular mechanisms governing cold resistance, including the identification of key genes and comprehensive transcriptional regulatory pathways, is crucial for developing new varieties with enhanced tolerance. RESULTS: In this study, we conducted a comparative analysis of leaf physiological indices and transcriptome sequencing results. The orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted peroxidase (POD) activity and soluble protein as crucial physiological indicators for both varieties. RNA-seq data analysis revealed that a total of 7024 and 6209 differentially expressed genes (DEGs) were identified from variety "A" and variety "B", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs demonstrated that the significant roles of starch and sucrose metabolism, glutathione metabolism, terpenoid synthesis, and energy metabolism (sucrose and starch metabolism) were the key pathways in eggplant. Weighted gene co-expression network analysis (WGCNA) shown that the enrichment of numerous cold-responsive genes, pathways, and soluble proteins in the MEgrep60 modules. Core hub genes identified in the co-expression network included POD, membrane transporter-related gene MDR1, abscisic acid-related genes, growth factor enrichment gene DELLA, core components of the biological clock PRR7, and five transcription factors. Among these, the core transcription factor MYB demonstrated co-expression with signal transduction, plant hormone, biosynthesis, and metabolism-related genes, suggesting a pivotal role in the cold response network. CONCLUSION: This study integrates physiological indicators and transcriptomics to unveil the molecular mechanisms responsible for the differences in cold tolerance between the eggplant cold-tolerant variety "A" and the cold-sensitive variety "B". These mechanisms include modulation of reactive oxygen species (ROS), elevation in osmotic carbohydrate and free proline content, and the expression of terpenoid synthesis genes. This comprehensive understanding contributes valuable insights into the molecular underpinnings of cold stress tolerance, ultimately aiding in the improvement of crop cold tolerance.

Commonly used antiemetics for prophylaxis of postoperative nausea and vomiting after Caesarean delivery with neuraxial morphine: a network meta-analysis.

BACKGROUND: Dopamine antagonists, 5-HT3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. RESULTS: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT3 antagonists, dopamine antagonists, dexamethasone, and 5-HT3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. CONCLUSIONS: Combined 5-HT3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023454602.

Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.

Background: Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. Methods: The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Results: Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). Conclusions: This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.

Effects of different neuraxial analgesia modalities on the need for physician interventions in labour: A network meta-analysis.

BACKGROUND: Neuraxial labour analgesia can be initiated with epidural (EPL), combined spinal epidural (CSE) or dural puncture epidural (DPE) and maintained with continuous epidural infusion (CEI), patient-controlled epidural analgesia (PCEA) or programmed intermittent epidural bolus (PIEB), but the optimal analgesia modality is still controversial. OBJECTIVE: To compare the effects of commonly used neuraxial analgesia modalities on the proportion of women needing physician interventions, as defined by the need for physician-administered epidural top-ups for inadequate analgesia in labour. DESIGN: Bayesian network meta-analysis. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science and Wanfang Data were searched from January 1988 to August 2023 without language restriction. ELIGIBILITY CRITERIA: Randomised controlled trials comparing two or more modalities of the following six neuraxial analgesia modalities in healthy labouring women: EPL+CEI+PCEA, EPL+PIEB+PCEA, CSE+CEI+PCEA, CSE+PIEB+PCEA, DPE+CEI+PCEA and DPE+PIEB+PCEA. RESULTS: Thirty studies with 8188 women were included. Compared with EPL+CEI+PCEA, EPL+PIEB+PCEA [odds ratio (OR) = 0.44; 95% credible interval (CrI), 0.22 to 0.86], CSE+PIEB+PCEA (OR = 0.29; 95% CrI, 0.12 to 0.71) and DPE+PIEB+PCEA (OR = 0.19; 95% CrI, 0.08 to 0.42) significantly reduced the proportion of women needing physician interventions. DPE+PIEB+PCEA had fewer women needing physician interventions than all other modalities, except for CSE+PIEB+PCEA (OR = 0.63; 95% CrI, 0.25 to 1.62). There were no significant differences in local anaesthetic consumption, maximum pain score, and the incidence of instrumental delivery between the different neuraxial modalities. CONCLUSIONS: PIEB+PCEA is associated with a lower risk of physician interventions in labour than CEI+PCEA. DPE or CSE and PIEB+PCEA may be associated with a lower likelihood of physician interventions than other neuraxial modalities. Otherwise, the new neuraxial analgesia techniques do not appear to offer significant advantages over traditional techniques. However, these results should be interpreted with caution due to limited data and methodological limitations. TRIAL REGISTRATION: PROSPERO (CRD42023402540).

Highly sensitive ammonia sensor based on a PMMA/PANI microwire structure.

In this paper, a highly sensitive ammonia (N H 3) sensor based on a polymethyl methacrylate/polyaniline (PMMA/PANI) microwire structure is designed and implemented. First, a micron-sized PMMA microwire was fabricated and connected with two tapered single-mode fibers to form a coupling structure; thus, the Mach-Zehnder (MZ) interference was successfully excited due to the good light conductivity of the PMMA. It was demonstrated that the coupling structure behaved with a high refractive index detection sensitivity of 3044 nm/RIU. To make it sensitive to N H 3, the PANI was selected to mix with PMMA and then formed a micron-level PMMA/PANI fiber. The experimental results showed that the PMMA/PANI fiber can selectively sense N H 3 with a high sensitivity of 65.3 pm/ppm. This proposed N H 3 sensor not only solves the problem of sensitive film shedding, but also possesses the advantages of good integration, high sensitivity, good selectivity, and short response time.

Tandem Sulfonylative Annulation/Halogenation of 1,7-Enynes with Sodium Sulfinate and TBAX for the Assembly of 4-Methylenechromanes.

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

Translation of nonclinical to clinical safety findings for 27 biotherapeutics.

Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.3% for nonclinical adverse findings; sensitivity increased to 67.3% and PPV fell to 35.0% when including nonadverse findings. Nonclinical findings were associated with a greater likelihood of a human ADR in that organ category, especially for adverse findings [positive likelihood ratio (LR+) >10 (lower 95% confidence interval [CI] of >5)]. The specificity and negative predictive value (NPV) were very high (>85%). A lack of nonclinical findings in an organ category was associated with a lower likelihood of a human ADR in that organ category. About 40-50% of human ADRs and nonclinical adverse findings, and about 30% of nonclinical nonadverse findings, were attributed to pharmacology. Slightly more than half of the human ADRs with a translating nonclinical finding had findings in animals that could be considered very similar. Overall, 38% of nonclinical findings translated to a human ADR at the organ category level. When nonclinical findings did not translate to humans, the cause was usually higher exposures or longer dosing in animals. All programs with human ADRs attributed to immunogenicity also had nonclinical adverse or nonadverse findings related to immunogenicity. Overall, nonclinical adverse and nonadverse findings were useful in predicting human ADRs, especially at an organ category level, and the majority of human ADRs were predicted by nonclinical toxicity studies.

A pathologic scoring system for predicting postoperative prognosis in patients with ruptured hepatocellular carcinoma.

BACKGROUND: The accuracy of pathological factors to predict the prognosis of patients with ruptured hepatocellular carcinoma (rHCC) is unclear. We aimed to develop and validate a novel scoring system based on pathological factors to predict the postoperative survival of patients with rHCC. METHOD: Patients with rHCC who underwent hepatectomy were recruited from three hospitals and allocated to the training (n = 221) and validation (n = 194) cohorts. A new scoring system, namely the MSE (microvascular invasion-satellite foci-Edmondson Steiner) score, was established based on three pathological factors using univariate and multivariate Cox proportional hazards regression analyses, including microvascular invasion, satellite foci, and differentiation grade. Finally, patients were stratified into three groups based on their risk of prognosis (low, intermediate, or high) according to their MSE score. We also constructed MSE score-based nomograms. The performance of the nomograms was assessed by receiver operating characteristic and calibration curve analyses and validated using the validation cohort. RESULTS: Three pathological factors were significantly correlated with overall survival (OS) and recurrence-free survival (RFS), three of which were included in the MSE score. The score can clearly stratify rHCC patients after hepatectomy (P < 0.05). And we established nomograms based on the MSE score (MSE score, Barcelona Clinic Liver Cancer stage, and alpha-fetoprotein concentration) to predict postoperative OS and RFS in patients with rHCC. The nomograms showed good discrimination, with C-indices over 0.760 for OS and RFS at 1, 3, and 5 years, respectively. The calibration curve showed excellent nomogram calibration, which was also verified in the validation cohort. CONCLUSION: The clinical MSE score were accurate in predicting OS and RFS in patients with rHCC with resectable lesions after hepatectomy.

Identification and Molecular Characterization of the CAMTA Gene Family in Solanaceae with a Focus on the Expression Analysis of Eggplant Genes under Cold Stress.

Calmodulin-binding transcription activator (CAMTA) is an important calmodulin-binding protein with a conserved structure in eukaryotes which is widely involved in plant stress response, growth and development, hormone signal transduction, and other biological processes. Although CAMTA genes have been identified and characterized in many plant species, a systematic and comprehensive analysis of CAMTA genes in the Solanaceae genome is performed for the first time in this study. A total of 28 CAMTA genes were identified using bioinformatics tools, and the biochemical/physicochemical properties of these proteins were investigated. CAMTA genes were categorized into three major groups according to phylogenetic analysis. Tissue-expression profiles indicated divergent spatiotemporal expression patterns of SmCAMTAs. Furthermore, transcriptome analysis of SmCAMTA genes showed that exposure to cold induced differential expression of many eggplant CAMTA genes. Yeast two-hybrid and bimolecular fluorescent complementary assays suggested an interaction between SmCAMTA2 and SmERF1, promoting the transcription of the cold key factor SmCBF2, which may be an important mechanism for plant cold resistance. In summary, our results provide essential information for further functional research on Solanaceae family genes, and possibly other plant families, in the determination of the development of plants.

Radiomics based on T2-weighted and diffusion-weighted MR imaging for preoperative prediction of tumor deposits in rectal cancer.

AIM: Preoperative diagnosis of tumor deposits (TDs) in patients with rectal cancer remains a challenge. This study aims to develop and validate a radiomics nomogram based on the combination of T2-weighted (T2WI) and diffusion-weighted MR imaging (DWI) for the preoperative identification of TDs in rectal cancer. MATERIALS AND METHODS: A total of 199 patients with rectal cancer who underwent T2WI and DWI were retrospectively enrolled and divided into a training set (n â€‹= â€‹159) and a validation set (n â€‹= â€‹40). The total incidence of TDs was 37.2 â€‹% (74/199). Radiomics features were extracted from T2WI and apparent diffusion coefficient (ADC) images. A radiomics nomogram combining Rad-score (T2WI â€‹+ â€‹ADC) and clinical factors was subsequently constructed. The area under the receiver operating characteristic curve (AUC) was then calculated to evaluate the models. The nomogram is also compared to three machine learning model constructed based on no-Rad scores. RESULTS: The Rad-score (T2WI â€‹+ â€‹ADC) achieved an AUC of 0.831 in the training and 0.859 in the validation set. The radiomics nomogram (the combined model), incorporating the Rad-score (T2WI â€‹+ â€‹ADC), MRI-reported lymph node status (mLN-status), and CA19-9, showed good discrimination of TDs with an AUC of 0.854 for the training and 0.923 for the validation set, which was superior to Random Forests, Support Vector Machines, and Deep Learning models. The combined model for predicting TDs outperformed the other three machine learning models showed an accuracy of 82.5 â€‹% in the validation set, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 66.7 â€‹%, 92.0 â€‹%, 83.3 â€‹%, and 82.1 â€‹%, respectively. CONCLUSION: The radiomics nomogram based on Rad-score (T2WI â€‹+ â€‹ADC) and clinical factors provides a promising and effective method for the preoperative prediction of TDs in patients with rectal cancer.

A Novel Nomogram to Predict Resectable Gastric Cancer Based on Preoperative Circulating Tumor Cell.

INTRODUCTION: Circulating tumor cells (CTCs) have been suggested to have an important prognostic role in gastrointestinal tumors. We developed a preoperative CTC-based nomogram to predict the prognosis of patients with resectable gastric cancer after surgery and established a risk stratification system based on the nomogram. METHODS: From January 2012 to June 2017, we screened 258 patients with gastric cancer treated with surgery from one center as the training cohort and 133 patients with gastric cancer treated with surgery from another as the validation cohort, screened prognostic factors for the training cohort using univariate and multivariate Cox risk proportional models, created predictive overall survival (OS) and a recurrence-free survival (RFS) nomogram, and plotted the receiver operating characteristic curve and calibration curve for this nomogram in the training and validation cohorts. Risk score stratification was performed according to the nomogram, and OS curves were plotted for the low, medium, and high-risk groups using the Kaplan-Meier method. RESULTS: The CTC positivity rate was 78.5% in all patients. CTC, TNM stage, and Ki-67 were the prognostic factors affecting OS and RFS after gastric cancer surgery. The nomogram consisted of these 3 variables. In the training group, the area under the curve of the nomogram for OS at 1, 3, and 5 years was 0.918, 0.829, and 0.813, respectively, and the area under the curve for RFS was 0.900, 0884, and 0.839, respectively. There was a statistically significant difference in OS among the low, medium, and high-risk groups according to the risk stratification system constructed from nomogram scores ( P < 0.001). DISCUSSION: Two nomograms based on preoperative CTC were established to predict OS and RFS after resectable gastric cancer. The 2 nomograms had good discrimination and calibration and significant stratification ability of the risk stratification system established according to them.

Prognosis and safety of laparoscopic hepatectomy for BCLC stage 0/A hepatocellular carcinoma with clinically significant portal hypertension: a multicenter, propensity score-matched study.

BACKGROUND AND AIM: The latest Barcelona Clinic Liver Cancer (BCLC) staging system suggests considering surgery in patients with resectable BCLC stage 0/A hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH). This study aimed to evaluate the safety and short- and long-term outcomes of laparoscopic hepatectomy for BCLC stage 0/A HCC patients with CSPH. METHODS: We retrospectively reviewed the medical records of 647 HCC patients in BCLC stage 0/A who were treated at five centers between January 2010 and January 2019. Among these patients, 434 underwent laparoscopic hepatectomy, and 213 underwent open hepatectomy. We used Kaplan-Meier analysis to compare the overall survival (OS) rate and recurrence-free survival (RFS) rate between patients with and without CSPH before and after propensity score matching (PSM). Multivariate Cox regression analysis was performed to identify prognostic factors for BCLC stage 0/A patients, and subgroup analyses were also conducted. RESULTS: Among the 434 patients who underwent laparoscopic hepatectomy, 186 had CSPH and 248 did not. The Kaplan-Meier analysis showed that the OS and RFS rates were significantly worse in the CSPH group before and after PSM. Multivariate Cox regression analyses identified CSPH as a prognostic factor for poor OS and RFS after laparoscopic hepatectomy. However, CSPH patients treated laparoscopically had a better short- and long-term prognosis than those treated with open surgery. CONCLUSIONS: CSPH has a negative impact on the prognosis of BCLC stage 0/A HCC patients after laparoscopic hepatectomy. Laparoscopic hepatectomy is still recommended for treatment, but careful patient selection is essential.

Risk of dementia in older veterans with multiple sclerosis.

BACKGROUND: While it is widely accepted that multiple sclerosis (MS) often causes cognitive dysfunction, it is thought that these cognitive symptoms rarely progress to dementia. However, this has not been thoroughly investigated. The objectives of this cohort study are to determine whether people with MS have an increased risk of dementia compared to the general population and to identify factors, such as geographic latitude, which may modify this association. METHODS: We studied data from a random sample of US veterans aged ≥ 55 years followed at Veterans Affairs Health Care Systems nationwide from 1999 to 2019. We identified all patients diagnosed with MS using ICD codes over a two-year baseline period. We then identified a comparison cohort of patients without MS matched 1:1 on sex, age, race, and first encounter date. We constructed Cox proportional hazards regression models to determine the association between MS and dementia while controlling for demographic factors and comorbidities, with additional models to examine subgroup effects. We used Fine-Gray subdistribution hazard models accounting for competing risk of death to evaluate the sensitivity of the findings. RESULTS: The study included 4084 MS patients and a matched group of 4084 non-MS patients. Overall, patients had mean age 66, were 93.6% male, and 88.1% non-Hispanic White, with mean follow-up time 9.5 years (MS) and 10.8 years (non-MS). In unadjusted models, veterans with MS had greater risk of dementia compared to matched controls (cumulative incidence 16.7% vs 12.4%; Cox HR 1.58, 95% CI 1.41-1.78). The increased risk remained after adjustment for potential confounders (adjusted HR 1.56, 95% CI 1.39-1.76) and when considering death as a competing risk (Fine-Gray HR 1.36, 95% CI 1.21-1.53). The magnitude of the MS-dementia association increased with rising geographic latitude (North HR 1.86, 1.51-2.30; Central HR 1.61, 1.42-1.82; South HR 1.39, 1.18-1.64; interaction p = 0.04) and younger baseline age (interaction p<0.001). CONCLUSIONS: Among older veterans with MS, risk of dementia diagnosis was higher compared to matched controls even after controlling for comorbidities. The risk difference was highest in northern regions and in younger patients. Clinicians caring for older MS patients should be aware of this risk and offer screening and treatment accordingly.

Origin tracing and adulteration identification of bird's nest by high- and low-field NMR combined with pattern recognition.

Edible bird's nest (EBN) is a high-value health food with various nutrients and bioactive components. With increasing demand for EBN, they are often adulterated with cheaper ingredients or falsely labeled by the origin information, thus harming consumer interests. In this study, high- and low-field nuclear magnetic resonance (HF/LF-NMR) technology combined with multivariate statistical analysis was used to identify the geographical marker of EBN from different origins and authenticate the adulterated EBN with various adulterants at different adulteration rates. Authentic EBN samples from Malaysia were used to simulate adulteration using gelatin (GL), agar (AG) and starch (ST) at 10 %, 20 %, 40 %, 60 %, 80 %, and 100 % w/w, respectively. The results showed significant differences in composition among EBN from different origins, with isocaproate and citric acid serving as geographical markers for Malaysia and Vietnam, respectively. Leucine, glutamic acid, and N-acetylglycoprotein serving as geographical markers for Indonesia. In addition, PLS model further verified the accuracy of origin identification of EBN. The LF-NMR results of adulteration EBN showed a linear correlation between the transverse relaxation (T2, S2) and the adulterated ratio. The OPLS-DA based on T2 spectra could accurately identify authentic EBN from adulterated with GL, AG and ST at 40 %, 20 %, and 20 %, respectively. Fisher discrimination model was able to differentiate at 20 %, 20 %, and 40 %, respectively. These results show that the 1H NMR combined with multivariate statistical analysis method could be a potential tool for the detection of origin and adulteration of EBN.

Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy.

Chronic stress has a substantial influence on the tumor microenvironment (TME), leading to compromised effectiveness of anti-cancer therapies through diverse mechanisms. It disrupts vital functions of immune cells that play a critical role in anti-tumor immunity, such as the inhibition of dendritic cells (DCs) and lymphocytes, while simultaneously enhancing the activity of immune cells that support tumor growth, such as myeloid-derived suppressor cells and tumor-associated macrophages. Furthermore, chronic stress exerts a significant impact on crucial mechanisms within the TME, including angiogenesis, DNA repair, hypoxia, extracellular matrix deposition, and tumor metabolism. These alterations in the TME, induced by stress, result from the activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, in conjunction with epigenetic modifications. In conclusion, chronic stress significantly influences the TME and impedes the efficacy of anti-cancer treatments, underscoring the importance of targeting stress pathways to improve therapeutic results.

Corrigendum: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex improves attentional control in chronically stressed adults.

[This corrects the article DOI: 10.3389/fnins.2023.1182728.].