Effect of sarcopenia and frailty on outcomes among patients with brain metastases.

PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.

Atrophy of the cholinergic regions advances from early to late mild cognitive impairment.

PURPOSE: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. METHODS: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. RESULTS: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. CONCLUSIONS: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.

Desmopressin nasal spray inhibiting parasympathetic function on isolated tracheal smooth muscle.

Objectives: Nocturia with or without asthma is one of the aging diseases. Desmopressin has been used as a nasal spray for patients who are suffering from nocturia. This study determined the effects of desmopressin on isolated tracheal smooth muscle in vitro. Methods: We evaluated desmopressin's efficiency on isolated rat tracheal smooth muscle. Desmopressin was evaluated for the following effects on tracheal smooth muscle: (1) effect on resting tension; (2) effect on contraction brought on by parasympathetic mimetic 10-6 M methacholine; and (3) effect on electrically produced tracheal smooth muscle contractions. Results: As the concentration grew, desmopressin by itself had no impact on the trachea's baseline tension. Addition of desmopressin at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Desmopressin could also inhibit spike contraction of the trachea induced by electrical field. Conclusion: According to this study, desmopressin at high quantities may prevent the trachea's parasympathetic activity. Due to its ability to block parasympathetic activity and lessen the contraction of the tracheal smooth muscle brought on by methacholine, Desmopressin nasal spray might help nocturia sufferers experience fewer asthma attacks.

Integrative ATAC-seq and RNA-seq analysis associated with diabetic nephropathy and identification of novel targets for treatment by dapagliflozin.

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.

Hypoxia-Inducible Factor 2α Attenuates Renal Ischemia-Reperfusion Injury by Suppressing CD36-Mediated Lipid Accumulation in Dendritic Cells in a Mouse Model.

BACKGROUND: Hypoxia and hypoxia-inducible factors (HIFs) play essential and multiple roles in renal ischemia-reperfusion injury (IRI). Dendritic cells (DCs) comprise a major subpopulation of the immunocytes in the kidney and are key initiators and effectors of the innate immune responses after IRI. The role of HIF-2α in DCs remains unclear in the context of renal IRI. METHODS: To investigate the importance of HIF-2α in DCs upon renal IRI, we examined the effects of DC-specific HIF-2α ablation in a murine model. Bone marrow-derived DCs (BMDCs) from DC-specific HIF-2α-ablated mice and wild-type mice were used for functional studies and transcriptional profiling. RESULTS: DC-specific ablation of HIF-2α led to hyperactivation of natural killer T (NKT) cells, ultimately exacerbating murine renal IRI. HIF-2α deficiency in DCs triggered IFN-γ and IL-4 production in NKT cells, along with upregulation of type I IFN and chemokine responses that were critical for NKT cell activation. Mechanistically, loss of HIF-2α in DCs promoted their expression of CD36, a scavenger receptor for lipid uptake, increasing cellular lipid accumulation. Furthermore, HIF-2α bound directly to a reverse hypoxia-responsive element (rHRE) in the CD36 promoter. Importantly, CD36 blockade by sulfo-N-succinimidyl oleate (SSO) reduced NKT cell activation and abolished the exacerbation of renal IRI elicited by HIF-2α knockout. CONCLUSIONS: Our study reveals a previously unrecognized role of the HIF-2α/CD36 regulatory axis in rewiring DC lipid metabolism under IRI-associated hypoxia. These findings suggest a potential therapeutic target to resolve long-standing obstacles in treatment of this severe complication.

Development of modified MgO/biochar composite for chemical adsorption enhancement to cleanup fluoride-contaminated groundwater.

Fluoride contamination in groundwater has become a global environmental issue. Magnesium oxide (MgO) has demonstrated effectiveness as an adsorbent in treating fluoride pollution in groundwater. However, its use in powder and fine granular form often results in losses during the adsorption process, posing challenges for post-treatment recovery and potentially causing secondary environmental pollution. In this study, two novel fluoride adsorbents [rice husk (RH) and spent coffee grounds (SCG)-based magnesium oxide (MgO) biochar composites (MgO/RH and MgO/SCG)] were developed to cleanup fluoride-polluted groundwater. During the adsorbent synthesis process, RH and SCG biochar were pyrolyzed at 500 °C and modified by calcination using MgO. Both MgO/RH and MgO/SCG surfaces exhibited abundant pore structures and formed MgO crystal phases. Batch experiments results show that when the MgO/RH and MgO/SCG material dosages were 1 g/L, fluoride removal rates reached 80% and 86% respectively. The isotherms and kinetics of fluoride adsorption with MgO/RH and MgO/SCG followed the Langmuir isotherm equation and pseudo-second-order kinetic model. The maximum fluoride adsorption capacities of MgO/RH and MgO/SCG were 63.47 mg/g and 141.98 mg/g, respectively, indicating these materials used mono-layer adsorption mechanism for fluoride adsorption. The addition of MgO into the pores of porous adsorbent materials effectively increased their reactive sites and enhanced the adsorption performance of carbon materials. Particularly, SCG biochar had a richer pore structure than RH biochar, providing a larger contact surface area, facilitating the effective dispersion and doping of MgO into the pores. Therefore, MgO/SCG composite exhibited excellent fluoride adsorption properties in water, indicating the potential for developing a new type of MgO-modified SCG adsorbent material with green prospects. This composite effectively mitigated fluoride contamination, reducing the fluoride concentration in groundwater. Both RH and SCG are agricultural and food waste by-products, thus offering the opportunity to significantly reduce production, operation, and maintenance costs.

The minimum weight and age of kidney donors: en bloc kidney transplantation from preterm neonatal donors weighing less than 1.2 kg to adult recipients.

En bloc kidney transplantation (EBKT) to adults from preterm neonates following donation after circulatory death has not been described in the literature. We report 2 successful cases of EBKT from preterm neonatal donation after circulatory death donors weighing <1.2 kg to adult recipients. The first case was a preterm female infant born at 29 weeks' gestational age, weighing 1.07 kg. The recipient was a 34-year-old woman weighing 75 kg. At the 9-month follow-up, the patient demonstrated excellent graft function with a creatinine concentration of 1.48 mg/dL. The second donor was a preterm female infant born at 29 weeks and 5 days' gestation, weighing 1.17 kg. The recipient was a 25-year-old woman weighing 46 kg. By 5 months post surgery, the serum creatinine level had gradually decreased to 1.47 mg/dL. In our experience, EBKT from preterm neonates <30 weeks' gestation and weighing <1.2 kg has demonstrated acceptable short- to medium-term results.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F. tularensis can cause pneumonia and respiratory failure and is associated with high mortality rates without early treatment. Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action. Gepotidacin selectively inhibits bacterial DNA replication via a unique binding mode, has activity against multidrug-resistant target pathogens, and has demonstrated in vitro activity against diverse collections of F. tularensis isolates (MIC90 of 0.5 to 1 µg/mL). Gepotidacin was evaluated in the cynomolgus macaque model of inhalational tularemia, using the SCHU S4 strain, with treatment initiated after exposure and sustained fever. Macaques were dosed via intravenous (i.v.) infusion with saline or gepotidacin at 72 mg/kg/day to support a human i.v. infusion dosing regimen of 1,000 mg three times daily. The primary study endpoint was survival, with survival duration and bacterial clearance as secondary endpoints. Gepotidacin treatment resulted in 100% survival compared to 12.5% in the saline-treated control group (P < 0.0001) at Day 43 postinhalational challenge. All gepotidacin-treated animals were blood and organ culture negative for F. tularensis at the end of the study. In contrast, none of the saline control animals were blood and organ culture negative. Gepotoidacin's novel mechanism of action and the efficacy data reported here (aligned with the Food and Drug Administration Animal Rule) support gepotidacin as a potential treatment for pneumonic tularemia in an emergency biothreat situation.

Value of conventional ultrasound and contrast-enhanced ultrasound for the assessment of renal allograft dysfunction and prognosis.

BACKGROUND: Ultrasound (US) is the primary imaging modality for the assessment of transplanted kidneys. This study aims to investigate the ability of conventional US and contrast-enhanced US (CEUS) in assessing renal allograft function and prognosis. METHODS: A total of 78 consecutive renal allograft recipients were enrolled. Patients were classified as normal allograft function (n = 41) and allograft dysfunction (n = 37) groups. All patients underwent US and parameters were measured. The independent-samples t-test or Mann-Whitney U test, logistic regression analysis, Kaplan-Meier survival plots, and Cox regression analysis were used. RESULTS: In multivariable analysis, cortical echo intensity (EI) and cortical peak intensity (PI) were determinant US parameters for renal allograft dysfunction (p = .024 and p = .003, respectively). The combination of cortical EI and PI showed an area under the receiver operating characteristic curve (AUROC) of .785 (p < .001). Of 78 patients (median follow-up: 20mo), 16 (20.5%) exhibited composite end points. Cortical PI had a general prediction accuracy with an AUROC of .691, sensitivity of 87.5%, and specificity of 46.8% at the threshold of 22.08 dB in predicting prognosis (p = .019). The combination of estimated-glomerular filtration rate (e-GFR) and PI in predicting prognosis showed an AUROC of .845 with a cut-off value of .836, sensitivity of 84.0%, and specificity of 67.3% (p < .001). CONCLUSION: This study indicates that cortical EI and PI are useful US parameters for evaluating renal allograft function and e-GFR combined with PI may provide a more accurate predictor of survival.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

Shear wave elastography parameters adds prognostic value to adverse outcome in kidney transplantation recipients.

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Cleanup of Cr(VI)-polluted groundwater using immobilized bacterial consortia via bioreduction mechanisms.

Cr(VI) bioreduction has become a remedial alternative for Cr(VI)-polluted site cleanup. However, lack of appropriate Cr(VI)-bioreducing bacteria limit the field application of the in situ bioremediation process. In this study, two different immobilized Cr(VI)-bioreducing bacterial consortia using novel immobilization agents have been developed for Cr(VI)-polluted groundwater remediation: (1) granular activated carbon (GAC) + silica gel + Cr(VI)-bioreducing bacterial consortia (GSIB), and (2) GAC + sodium alginate (SA) + polyvinyl alcohol (PVA) + Cr(VI)-bioreducing bacterial consortia (GSPB). Moreover, two unique substrates [carbon-based agent (CBA) and emulsified polycolloid substrate (EPS)] were developed and used as the carbon sources for Cr(VI) bioreduction enhancement. The microbial diversity, dominant Cr-bioreducing bacteria, and changes of Cr(VI)-reducing genes (nsfA, yieF, and chrR) were analyzed to assess the effectiveness of Cr(VI) bioreduction. Approximately 99% of Cr(VI) could be bioreduced in microcosms with GSIB and CBA addition after 70 days of operation, which caused increased populations of total bacteria, nsfA, yieF, and chrR from 2.9 × 108 to 2.1 × 1012, 4.2 × 104 to 6.3 × 1011, 4.8 × 104 to 2 × 1011, and 6.9 × 104 to 3.7 × 107 gene copies/L. In microcosms with CBA and suspended bacteria addition (without bacterial immobilization), the Cr(VI) reduction efficiency dropped to 60.3%, indicating that immobilized Cr-bioreducing bacteria supplement could enhance Cr(VI) bioreduction. Supplement of GSPB led to a declined bacterial growth due to the cracking of the materials. The addition of GSIB and CBA could establish a reduced condition, which favored the growth of Cr(VI)-reducing bacteria. The Cr(VI) bioreduction efficiency could be significantly improved through adsorption and bioreduction mechanisms, and production of Cr(OH)3 precipitates confirmed the occurrence of Cr(VI) reduction. The main Cr-bioreducing bacteria included Trichococcus, Escherichia-Shigella, and Lactobacillus. Results suggest that the developed GSIB bioremedial system could be applied to cleanup Cr(VI)-polluted groundwater effectively.

Magnetic Resonance Imaging Quantification of Accumulation of Epicardial Adipose Tissue Adds Independent Risks for Diastolic Dysfunction among Dialysis Patients.

BACKGROUND: Diastolic dysfunction (DD) frequently occurs in dialysis patients; however, the risk factors of DD remain to be further explored in such a population. Epicardial adipose tissue (EAT) volume has proven to be an independent clinical risk factor for multiple cardiac disorders. PURPOSE: To assess whether EAT volume is an independent risk factor for DD in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 113 patients (mean age: 54.5 ± 14.4 years; 41 women) who had underwent dialysis for at least 3 months due to uremia. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence for cine imaging, modified Look-Locker imaging (MOLLI) for T1 mapping and gradient-recalled-echo for T2*. ASSESSMENT: All participants were performed cardiac magnetic resonance imaging (MRI) and echocardiogram. For MRI images analysis, borders of the EAT were manually delineated, as well as, pericardial adipose tissue (PeAT) and paracardial adipose tissue (PaAT), T1 mapping, T2* mapping, global longitudinal strain (GLS), and left atrial strain. For echocardiogram assessments, the thickness of PaAT, e' velocity, E velocity, E/e ratio, A velocity, and deceleration time were measured. STATISTICAL TESTS: Univariate and multivariate logistic regressions were performed to explore the independent risk factors for DD. P value less than 0.05 was considered as significant. RESULTS: Compared with the DD(-) group, the DD(+) group had significantly more epicardial tissue fat (18.5 ± 1.3 vs. 30.9 ± 2.3) In addition, EAT volumes increased significantly with the grades of DD (grade 1 vs. grade 2 and 3: 27.9 ± 15.9 vs. 35.4 ± 13.1). Moreover, EAT had significant correlations with T1 mapping, T2* mapping, GLS, left atrial strain, e' velocity, and E/e ratio. EAT accumulation added an independent risk for DD (Odds Ratio = 1.03) over conventional clinical risk factors including age, diabetes mellitus, and hemodialysis. DATA CONCLUSION: EAT was associated with diastolic function, and its accumulation may be an independent risk factor for DD among dialysis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Attention to renal involvement: report of 17 Joubert syndrome cases in children of a single center in China.

BACKGROUND: Joubert Syndrome (JS) is a rare genetic developmental disorder. We are aiming for increasing awareness of this disease especially kidney involvement in children with JS. METHODS: Clinical and genetic data of 17 cases of JS in Beijing children's hospital in the past 21 years were collected retrospectively. RESULTS: Twelve males and 5 females, aged from 12d to 15y8m. The most common involvement was neurological system involvement. The second most common involvement was renal involvement: end stage kidney disease in 6 cases (35%), hematuria in 5 cases (29%), proteinuria in 5 cases (29%), renal diffuse lesions in 4 cases (24%), renal cystic lesions in 2 cases (12%), and echogenic enhancement of parenchyma in 2 cases (12%). 10 cases did genetic tests. 3 cases with renal deficiency all had RPGRIP1L gene mutation. CONCLUSIONS: The most common involvement of JS is neurological involvement, and the second is renal involvement. Pediatricians should improve awareness of JS and conduct systemic evaluation of children. More attention should be paid to renal involvement which may be onset hidden but fatal. Early recognition and diagnosis are the goals to delay the start to dialysis and improve quality of patients' life. The RPGRIP1L gene mutation maybe the most common gene mutation in JS and may have correlations with renal involvement.

Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

BACKGROUND: Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. METHODS: Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). CONCLUSION: This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.

A single-cell survey of the human glomerulonephritis.

Glomerulonephritis is the one of the major causes of the end-stage kidney disease, whereas the pathological process of glomerulonephritis is still not completely understood. Single-cell RNA sequencing (scRNA-seq) emerges to be a powerful tool to evaluate the full heterogeneity of kidney diseases. To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension (MH) sample and 1 human chronic interstitial nephritis (CIN) sample, all tissues were taken from the biopsy. After filtering the cells with < 200 genes and > 10% mitochondria (MT) genes, the resulting 14 932 cells can be divided into 20 cell clusters, consistently with the previous report, in disease samples dramatic immune cells infiltration was found, among which a proximal tubule (PT) subset characterized by wnt-ß catenin activation and a natural killer T (NKT) subset high expressing LTB were found. Furthermore, in the cluster of the podocyte, three glomerulonephritis related genes named FXYD5, CD74 and B2M were found. Compared with the mesangial of donor, the gene CLIC1 and RPS26 were up-regulated in mesangial of IgA nephropathy(IgAN), whereas the gene JUNB was up-regulated in podocyte of IgAN in comparison with that of donor. Meanwhile, some membranous nephropathy (MN) high expressed genes such as HLA-DRB5, HLA-DQA2, IFNG, CCL2 and NR4A2, which involve in highest enrichment pathway, display the cellular-specific expression style, whereas monocyte marker of lupus nephritis (LN) named TNFSF13B was also found and interferon alpha/beta signalling pathway was enriched in B and NKT of LN comparing with donor. By scRNA-seq, we first defined the podocyte markers of glomerulonephritis and specific markers in IgA, MN and LN were found at cellular level. Furthermore, the critical role of interferon alpha/beta signalling pathway was enriched in B and NKT of LN was declared.

Texture Analysis of Native T1 Images as a Novel Method for Noninvasive Assessment of Uremic Cardiomyopathy.

BACKGROUND: Noncontrast cardiac T1 times are increased in dialysis patients which might indicate fibrotic alterations in uremic cardiomyopathy. PURPOSE: To explore the application of the texture analysis (TA) of T1 images in the assessment of myocardial alterations in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 117 subjects, including 22 on hemodialysis, 44 on peritoneal dialysis, and 51 healthy controls. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence, modified Look-Locker imaging (MOLLI). ASSESSMENT: Two independent, blinded researchers manually delineated endocardial and epicardial borders of the left ventricle (LV) on midventricular T1 maps for TA. STATISTICAL TESTS: Texture feature selection was performed, incorporating reproducibility verification, machine learning, and collinearity analysis. Multivariate linear regressions were performed to examine the independent associations between the selected texture features and left ventricular function in dialysis patients. Texture features' performance in discrimination was evaluated by sensitivity and specificity. Reproducibility was estimated by the intraclass correlation coefficient (ICC). RESULTS: Dialysis patients had greater T1 values than normal (P < 0.05). Five texture features were filtered out through feature selection, and four showed a statistically significant difference between dialysis patients and healthy controls. Among the four features, vertical run-length nonuniformity (VRLN) had the most remarkable difference among the control and dialysis groups (144 ± 40 vs. 257 ± 74, P < 0.05), which overlap was much smaller than Global T1 times (1268 ± 38 vs. 1308 ± 46 msec, P < 0.05). The VRLN values were notably elevated (cutoff = 170) in dialysis patients, with a specificity of 97% and a sensitivity of 88%, compared with T1 times (specificity = 76%, sensitivity = 60%). In dialysis patients, VRLN was significantly and independently associated with left ventricular ejection fraction (P < 0.05), global longitudinal strain (P < 0.05), radial strain (P < 0.05), and circumferential strain (P < 0.05); however, T1 was not. DATA CONCLUSION: The texture features obtained by TA of T1 images and VRLN may be a better parameter for assessing myocardial alterations than T1 times. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Cost-Effective Analysis of Dual-Energy Computed Tomography for the Diagnosis of Occult Hip Fractures Among Older Adults.

OBJECTIVE: Early and accurate diagnosis of hip fractures minimizes morbidity and mortality. Although current guidelines favor magnetic resonance imaging (MRI) for the diagnosis of occult hip fractures, a new technology called dual-energy computed tomography (DECT) seems an effective alternative. This article investigates a potentially cost-effective strategy for the diagnosis of occult hip fractures in older adults in Singapore. METHODS: A decision tree model was developed to compare costs from a payer's perspective and outcomes in terms of quality-adjusted life-years (QALYs) of different imaging strategies for diagnosing occult hip fracture, comparing MRI with DECT supplementing single-energy computed tomography (SECT) and SECT alone. Model inputs were obtained from local sources where available. Sensitivity analyses are performed to test the robustness of the results. RESULTS: The MRI strategy was dominated by the DECT strategy, whereas DECT supplementing SECT provided 0.30 more QALYs at an incremental cost of SGD106.41 with an incremental cost-effectiveness ratio of SGD352.52 per QALY relative to SECT alone. DECT seemed a cost-effective strategy at a willingness-to-pay threshold of SGD50 000 per QALY. CONCLUSION: DECT supplementing SECT is a cost-effective imaging strategy to diagnose occult hip fractures among older adults in Singapore and should be included in clinical pathways to expedite timely treatment and considered for reimbursement schemes.

Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss.

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

A case-control study on the risk factors for hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an endemic communicable disease in China, accounting for 90% of total reported cases worldwide. In this study, the authors want to investigate the risk factors for HFRS in recent years to provide the prevention and control advices. METHODS: A community-based, 1:2 matched case-control study was carried out to investigate the risk factors for HFRS. Cases were defined as laboratory-confirmed cases that tested positive for hantavirus-specific IgM antibodies. Two neighbourhood controls of each case were selected by sex, age and occupation. Standardized questionnaires were used to collect information and identify the risk factors for HFRS. RESULTS: Eighty-six matched pairs were investigated in the study. The median age of the cases was 55.0 years, 72.09% were male, and 73.26% were farmers. In the multivariate logistic regression analysis, cleaning spare room at home (OR = 3.310, 95%CI 1.335-8.210) was found to be risk factor for infection; storing food and crops properly (OR = 0.279 95%CI 0.097-0.804) provided protection from infection. CONCLUSION: Storing food and crops properly seemed to be protective factor, which was important for HFRS prevention and control. More attention should be paid to promote comprehensive health education and behaviour change among high-risk populations in the HFRS endemic area.