Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy.

Dormancy is a key feature of stem cell function in adult tissues as well as in embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state remains unclear. Here we show that microRNA activity, which is otherwise dispensable for preimplantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in the loss of pluripotent cells. Through the integration of high-sensitivity small RNA expression profiling of individual embryos and protein expression of miRNA targets with public data of protein-protein interactions, we constructed the miRNA-mediated regulatory network of mouse early embryos specific to diapause. We find that individual miRNAs contribute to the combinatorial regulation by the network, and the perturbation of the network compromises embryo survival in diapause. We further identified the nutrient-sensitive transcription factor TFE3 as an upstream regulator of diapause-specific miRNAs, linking cytoplasmic MTOR activity to nuclear miRNA biogenesis. Our results place miRNAs as a critical regulatory layer for the molecular rewiring of early embryos to establish dormancy.

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice.

Metabolic reprogramming is a potential treatment strategy for autosomal dominant polycystic kidney disease (ADPKD). Metformin has been shown to inhibit the early stages of cyst formation in animal models. However, metformin can lead to lactic acidosis in diabetic patients with advanced chronic kidney disease, and its efficacy in ADPKD is still not fully understood. Here, we investigated the effect of metformin in an established hypomorphic mouse model of PKD that presents stable and heritable knockdown of Pkd1. The Pkd1 miRNA transgenic mice of both genders were randomized to receive metformin or saline injections. Metformin was administrated through daily intraperitoneal injection from postnatal day 35 for 4 weeks. Unexpectedly, metformin treatment at a concentration of 150 mg/kg increased disease severity, including kidney-to-body weight ratio, cystic index and plasma BUN levels, and was associated with increased renal tubular cell proliferation and plasma lactate levels. Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including ß-catenin, hypoxia-inducible factor-1α, protein kinase Cα and Notch signaling pathways in the metformin-treated mutant mice. The plasma metformin concentrations were still within the recommended therapeutic range for type 2 diabetic patients. Short-term metformin treatment in a second Pkd1 hypomorphic model (Pkd1RC/RC) was however neutral. These results demonstrate that metformin may exacerbate late-stage cyst growth associated with the activation of lactate-related signaling pathways in Pkd1 deficiency. Our findings indicate that using metformin in the later stage of ADPKD might accelerate disease progression and call for the cautious use of metformin in these patients.

A newly evolved rice-specific gene JAUP1 regulates jasmonate biosynthesis and signalling to promote root development and multi-stress tolerance.

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources.

Comparison of Mini Nutritional Assessment Tool and Geriatric Nutrition Risk Index in Predicting 12-Y Mortality Among Community-Dwelling Older Persons.

BACKGROUND: Malnutrition is a common and dangerous condition in older adults, which has been associated with increased risk of mortality. OBJECTIVES: This study aimed to evaluate and compare the abilities of Mini Nutritional Assessment short form (MNA-SF), MNA full form (MNA-FF), and geriatric nutritional risk index (GNRI) to predict all-cause and expanded cardiovascular disease (CVD)-related mortality in community-dwelling older adults. METHODS: This research was an observational cohort study conducted in a community setting, with a 12-y follow-up involving 1001 community-living older adults aged 65 y or older who were enrolled in 2009 and followed up until 2021. Nutritional status assessment was carried out in 2009 using MNA-SF, MNA-FF, and GNRI. Multivariate Cox proportional hazards regression was applied to determine adjusted hazard ratios of mortality with 95% CIs. RESULTS: A total of 368 deaths (36.76%) and 122 expanded CVD-related deaths (12.19%) were observed after a median follow-up of 12 y. Compared with normal nutritional status, poor nutritional status assessed by the MNA-SF, MNA-FF, and GNRI was found to be associated with an increased all-cause mortality in older persons. MNA-SF and MNA-FF, but not GNRI, were associated with expanded CVD-related mortality. The MNA-FF showed better discriminatory accuracy for all-cause (C-statistics: 0.77; 95% CI: 0.63, 0.79) and expanded CVD-related mortality (C-statistics: 0.79; 95% CI: 0.70, 0.83) than MNA-SF (C-statistics: 0.76; 95% CI: 0.73-0.79; and C-statistics: 0.76; 95% CI: 0.72-0.81, respectively) and GNRI (C-statistics: 0.75; 95% CI: 0.73-0.79; and C-statistics: 0.76; 95% CI: 0.72-0.80, respectively). CONCLUSIONS: Our findings indicate that MNA-SF, MNA-FF, and GNRI were all independent predictors of all-cause mortality. In particular, the MNA-FF may be the best nutritional assessment tool for predicting all-cause and CVD-related mortality among older persons residing in community, compared with MNA-SF and GNRI.

Quartet of APOCs and the Different Roles They Play in Diabetes.

APOA1 and APOB are the structural proteins of high-density lipoprotein and APOB-containing lipoproteins, such as low-density lipoprotein and very low-density lipoprotein, respectively. The 4 smaller APOCs (APOC1, APOC2, APOC3, and APOC4) are exchangeable apolipoproteins; they are readily transferred among high-density lipoproteins and APOB-containing lipoproteins. The APOCs regulate plasma triglyceride and cholesterol levels by modulating substrate availability and activities of enzymes interacting with lipoproteins and by interfering with APOB-containing lipoprotein uptake through hepatic receptors. Of the 4 APOCs, APOC3 has been best studied in relation to diabetes. Elevated serum APOC3 levels predict incident cardiovascular disease and progression of kidney disease in people with type 1 diabetes. Insulin suppresses APOC3 levels, and accordingly, elevated APOC3 levels associate with insulin deficiency and insulin resistance. Mechanistic studies in a mouse model of type 1 diabetes have demonstrated that APOC3 acts in the causal pathway of diabetes-accelerated atherosclerosis. The mechanism is likely due to the ability of APOC3 to slow the clearance of triglyceride-rich lipoproteins and their remnants, thereby causing an increased accumulation of atherogenic lipoprotein remnants in lesions of atherosclerosis. Less is known about the roles of APOC1, APOC2, and APOC4 in diabetes.

Addressing causal relationship between drinking behavior and metabolic syndrome: one-sample Mendelian randomization analysis.

AIMS: Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis. METHODS: A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30-70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model. RESULTS: A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p < .001), 1.31 (1.23, 1.40, p < .001), and 1.87 (1.75, 2.00, p < .001), respectively, for the weighted genetic risk score. CONCLUSIONS: This study shows a modest relationship between drinking behavior and MetS by using MR analysis.

Sporadic pediatric vestibular schwannoma: a case report in a 4-year-old boy.

Sporadic vestibular schwannomas (VSs) are rare in children. When occurred in the pediatric population, they usually appear bilaterally and are related to neurofibromatosis type 2 (NF2). The current study reports a 4-year-old boy without family history of VS or NF2 who presented with a large (5.7-cm) VS involving the right cerebellopontine angle and internal auditory canal. Through seven-staged surgical interventions and two stereotactic γ­knife radiosurgery, the disease was stabilized. At 2-year follow-up, the child had right ear hearing loss, grade IV facial palsy, and normal motor function and gait. No definite evidence of gene mutation regarding NF2 can be identified after sequence analysis and deletion/duplication testing. This case highlights the significance of considering the possibility of sporadic VSs, even in very young children. It emphasizes the importance of not overlooking initial symptoms, as they may indicate the presence of a large tumor and could potentially result in delayed diagnosis.

A systematic scoping review and content analysis of organizational health literacy responsiveness assessment tools.

The characteristics of health literate organizations have been variously described in recognition that it is important for organizations to respond to the diversity of people's health literacy strengths and challenges. A systematic scoping review was conducted to identify, assess and classify international self-assessment tools aimed at measuring the capability of organizations to embody health literate characteristics. Following the JBI Scoping Manual, a search was conducted in six databases and identified 2693 articles. After screening, 16 studies published between 2007 and 2023 across eight countries were eligible for inclusion. Results were summarized and a finite list of items from existing tools was generated. Content analysis was performed to classify these items. Whilst most assessment tools in the included studies were healthcare-focused, other settings included schools and government departments. The 16 assessment tools included a total of 661 items, and 647 items were retained that met the definition of health literacy responsiveness. Items were classified into six domains (communication; navigation of resources; culture; policies and practice; involvement or engagement and workforce development), with high agreement between two researchers (91.5%). The 647 items were reviewed to exclude items that were too contextually specific, focused solely on service users, were too broad or had suitable alternatives; 210 items were finally retained. This research is two-fold: provides a synthesis of existing organizational health literacy responsiveness assessment tools across settings; and provides a list of items, which will be essential to developing context specific assessment tools through Delphi methods in the future.

Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury.

Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

Perinatal dietary patterns and symptomatic depression: A prospective cohort study.

To promote maternal and infant health, there is a need to optimise the dietary pattern of pregnant women to reduce perinatal depression. This prospective cohort study was conducted from June 2020 to February 2022, 300 women from a medical center were interviewed during late pregnancy and at 4-6 weeks postpartum. Dietary patterns were derived by factor analysis using a semiquantitative food frequency questionnaire. Symptomatic depression was defined using the Edinburgh Postpartum Depression Scale (EPDS, ranged 0-30). Their dairy, vegetable and fruit intakes were below the Taiwanese recommendations for pregnant women. Symptomatic depression (EPDS ≥10) affected 31.3% in the third trimester and 35.7% postpartum. Pre- and post-EPDS scores were positively correlated (r = 0.386, p < 0.001). Approximately 55% of those depressed before delivery were also depressed postpartum. For late pregnancy, four dietary patterns were identified ('Good oil', 'Vegetables and fruits', 'Omnivorous' and 'Refined-grain and organ meats'). Dietary patterns were classified according to quartiles (Q). Higher omnivorous pattern scores reduced the risk of depression. For prenatal depression, with Q1 as a reference, the risk was reduced by 38% for Q2, 43% for Q3 and 59% for Q4 (p for trend = 0.068). These findings became evident postpartum (reduced risk by 68% for Q2, 69% for Q3 and 70% for Q4 (p = 0.031; p for trend = 0.0032). The association between dietary patterns and depression encourages the routine nutritional management of pregnant women.

Leukocyte cell-derived chemotaxin 2 regulates epithelial-mesenchymal transition and cancer stemness in hepatocellular carcinoma.

Leukocyte cell-derived chemotaxin 2 (LECT2) acts as a tumor suppressor in hepatocellular carcinoma (HCC). However, the antineoplastic mechanism of LECT2, especially its influence on hepatic cancer stem cells (CSCs), remains largely unknown. In The Cancer Genome Atlas cohort, LECT2 mRNA expression was shown to be associated with stage, grade, recurrence, and overall survival in human HCC patients, and LECT2 expression was downregulated in hepatoma tissues compared with the adjacent nontumoral liver. Here, we show by immunofluorescence and immunoblot analyses that LECT2 was expressed at lower levels in tumors and in poorly differentiated HCC cell lines. Using functional assays, we also found LECT2 was capable of suppressing oncogenic behaviors such as cell proliferation, anchorage-independent growth, migration, invasiveness, and epithelial-mesenchymal transition in hepatoma cells. Moreover, we show exogenous LECT2 treatment inhibited CSC functions such as tumor sphere formation and drug efflux. Simultaneously, hepatic CSC marker expression was also downregulated, including expression of CD133 and CD44. This was supported by infection with adenovirus encoding LECT2 (Ad-LECT2) in HCC cells. Furthermore, in animal experiments, Ad-LECT2 gene therapy showed potent efficacy in treating HCC. We demonstrate LECT2 overexpression significantly promoted cell apoptosis and reduced neovascularization/CSC expansion in rat hepatoma tissues. Mechanistically, we showed using immunoblot and immunofluorescence analyses that LECT2 inhibited ß-catenin signaling via the suppression of the hepatocyte growth factor/c-MET axis to diminish CSC properties in HCC cells. In summary, we reveal novel functions of LECT2 in the suppression of hepatic CSCs, suggesting a potential alternative strategy for HCC therapy.

Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma.

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.

Contrast-enhanced CT and Acute Kidney Injury: Risk Stratification by Diabetic Status and Kidney Function.

Background Diabetes mellitus may be associated with an increased likelihood of CT contrast material-induced acute kidney injury (CI-AKI), but this has not been studied in a large sample with and without kidney dysfunction. Purpose To investigate whether diabetic status and estimated glomerular filtration rate (eGFR) are associated with the likelihood of acute kidney injury (AKI) following CT contrast material administration. Materials and Methods This retrospective multicenter study included patients from two academic medical centers and three regional hospitals who underwent contrast-enhanced CT (CECT) or noncontrast CT between January 2012 and December 2019. Patients were stratified according to eGFR and diabetic status, and subgroup-specific propensity score analyses were performed. The association between contrast material exposure and CI-AKI was estimated with use of overlap propensity score-weighted generalized regression models. Results Among the 75 328 patients (mean age, 66 years ± 17 [SD]; 44 389 men; 41 277 CECT scans; 34 051 noncontrast CT scans), CI-AKI was more likely in patients with an eGFR of 30-44 mL/min/1.73 m2 (odds ratio [OR], 1.34; P < .001) or less than 30 mL/min/1.73 m2 (OR, 1.78; P < .001). Subgroup analyses revealed higher odds of CI-AKI among patients with an eGFR less than 30 mL/min/1.73 m2, with or without diabetes (OR, 2.12 and 1.62; P = .001 and .003, respectively), when they underwent CECT compared with noncontrast CT. Among patients with an eGFR of 30-44 mL/min/1.73 m2, the odds of CI-AKI were higher only in those with diabetes (OR, 1.83; P = .003). Patients with an eGFR less than 30 mL/min/1.73 m2 and diabetes had higher odds of 30-day dialysis (OR, 1.92; P = .005). Conclusion Compared with noncontrast CT, CECT was associated with higher odds of AKI in patients with an eGFR of less than 30 mL/min/1.73 m2 and in patients with diabetes with an eGFR of 30-44 mL/min/1.73 m2; higher odds of 30-day dialysis were observed only in patients with diabetes with an eGFR less than 30 mL/min/1.73 m2. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Davenport in this issue.

MRI Quantification of Cortical Bone Porosity, Mineralization, and Morphologic Structure in Postmenopausal Osteoporosis.

Background Preclinical studies have suggested that solid-state MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are useful measures of bone health. Purpose To explore whether MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are affected in postmenopausal osteoporosis (OP) and to examine associations between MRI markers and bone mineral density (BMD) in postmenopausal women. Materials and Methods In this single-center study, postmenopausal women were prospectively recruited from January 2019 to October 2020 into two groups: participants with OP who had not undergone treatment, defined as having any dual-energy x-ray absorptiometry (DXA) T-score of -2.5 or less, and age-matched control participants without OP (hereafter, non-OP). Participants underwent MRI in the midtibia, along with DXA in the hip and spine, and peripheral quantitative CT in the midtibia. Specifically, MRI measures of cortical bone porosity (pore water and total water), osteoid density (bound water [BW]), morphologic structure (cortical bone thickness), and mineralization (phosphorous [P] density [31P] and 31P-to-BW concentration ratio) were quantified at 3.0 T. MRI measures were compared between OP and non-OP groups and correlations with BMD were assessed. Results Fifteen participants with OP (mean age, 63 years ± 5 [SD]) and 19 participants without OP (mean age, 65 years ± 6) were evaluated. The OP group had elevated pore water (11.6 mol/L vs 9.5 mol/L; P = .007) and total water densities (21.2 mol/L vs 19.7 mol/L; P = .03), and had lower cortical bone thickness (4.8 mm vs 5.6 mm; P < .001) and 31P density (6.4 mol/L vs 7.5 mol/L; P = .01) than the non-OP group, respectively, although there was no evidence of a difference in BW or 31P-to-BW concentration ratio. Pore and total water densities were inversely associated with DXA and peripheral quantitative CT BMD (P < .001), whereas cortical bone thickness and 31P density were positively associated with DXA and peripheral quantitative CT BMD (P = .01). BW, 31P density, and 31P-to-BW concentration ratio were positively associated with DXA (P < .05), but not with peripheral quantitative CT. Conclusion Solid-state MRI of cortical bone was able to help detect potential impairments in parameters reflecting porosity, morphologic structure, and mineralization in postmenopausal osteoporosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae in this issue.

Diagnostic accuracy of rotavirus antigen tests in children: A systematic review and meta-analysis.

OBJECTIVES: Rotavirus infection is the leading cause of acute gastroenteritis (AGE) in children. Children with rotavirus infection may have symptoms such as diarrhoea or vomiting. Diarrheal diseases caused by rotavirus and other enteric pathogens cannot be differentiated on the basis of clinical symptoms. Therefore, diagnostic testing is essential to confirm a diagnosis of rotavirus infection. The aim of the meta-analysis is to evaluate the diagnostic accuracy of immunochromatographic rotavirus antigen tests in children. METHODS: We searched the PubMed, Embase, Cochrane Library and Google Scholar databases for studies evaluating the diagnostic accuracy of antigen tests for rotavirus in children. We included studies that provided sufficient data to construct a 2 × 2 table on a per patient basis. The overall sensitivity and specificity of the antigen tests were determined using a bivariate random-effects model. RESULTS: In total, 12 studies with 4407 participants were included in the study. The meta-analysis yielded a pooled sensitivity of 89.2% (95% confidence interval [CI]: 77.4%-95.3%) and pooled specificity of 93.2% (95% CI: 83.8%-97.3%). A subgroup analysis of such tests in children aged ≤5 years yielded a pooled sensitivity of 87.1% and pooled specificity of 91.8%. Another subgroup analysis of high-quality studies involving 820 participants yielded a pooled sensitivity of 92.3% and pooled specificity of 95.2%. CONCLUSIONS: Rotavirus antigen tests have high sensitivity for the diagnosis of rotavirus infection in children with AGE. In addition, such tests may be effective for the identification and clinical management of rotavirus infection in children and the prevention of disease progression.

Accuracy of antigen tests for meningococcal meningitis in cerebrospinal fluid: A diagnostic meta-analysis.

OBJECTIVES: Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. RESULTS: Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). CONCLUSIONS: The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.