Impact of urban form and street infrastructure on pedestrian-motorist collisions.

This study examines the impact of urban form and street infrastructure on pedestrian safety in Atlanta, Georgia, and Boston, Massachusetts. With a significant rise in pedestrian fatalities over the past decade, understanding how cities' built environments influence safety is critical. We conducted geospatial analyses and statistical tests, revealing unique patterns in each city. Atlanta's sprawling, motorist-oriented layout is associated with increased pedestrian accidents, particularly at crosswalks, due to limited land use diversity, arterial roads, and streets with high speed limits and multiple lanes. In contrast, Boston's compact, pedestrian-oriented design leads to improved safety, featuring safer pedestrian crossings, greater land use diversity, reduced arterial roads and lower speed limits on single-lane streets. This study also highlights the importance of diverse urban forms and pedestrian infrastructure in shaping pedestrian safety. While population density and land use diversity impact accident rates, the presence of crosswalks and street configurations play crucial roles. Our findings underscore the urgency for urban planners to prioritize pedestrian safety through targeted interventions, such as enhancing crosswalks, reducing speed limits and promoting mixed land use. Future research should explore additional variables, alternative modelling techniques and non-linear approaches to gain a more comprehensive understanding of these complex relationships.

Tryptanthrin inhibits tumor angiogenesis via Notch/Dll4 signaling pathway in zebrafish.

Background: Anti-angiogenic pathways are important for inhibiting tumor growth and migration. Tryptanthrin has anticancer properties in vivo but its anti-angiogenesis activities and associated mechanisms remain unclear. Methods: The effects of tryptanthrin were investigated in vivo using fluorescent labeling of blood vessels in zebrafish. Fluorescence quantitation was conducted to analyze the level of delta-like ligand 4 (Dll4) gene expression. Transcriptome sequencing and quantitative polymerase chain reaction (qPCR) analyses were performed to explore the molecular mechanisms of anti-tumor angiogenesis. Results: Significant anti-tumor effects were observed in all 48-hpf (hours post-fertilization) zebrafish treated with tryptanthrin (P<0.05). The 6-hpf zebrafish were cultured to 48 and 72 hpf following tryptanthrin treatment. It was found that compared with the control groups, the fluorescence area and the number of complete internode vessels reduced significantly following treatment with medium and high concentrations of tryptanthrin (P<0.05). The relative expression of Dll4 in the 48-hpf zebrafish was significantly inhibited only in the high concentration group (P<0.05). qPCR analysis revealed that the levels of Krt18b, desma, Tnnt2c, and Krt4 gene expression were significantly up-regulated in zebrafish following Dll4 overexpression. After Dll4 knockdown, the level of desma and Tnnt2c gene expression was significantly up-regulated. Conclusions: Tryptanthrin can inhibit tumor growth in vivo in a concentration-dependent manner by down-regulating Dll4 protein expression, and at the same time up-regulating the level of desma and Tnnt2c gene expression.

Development and Validation of a Clinical Risk Score to Predict Immune-mediated Liver Injury Caused by Sintilimab: Assessed for Causality Using Updated RUCAM.

Background and Aims: Immune-mediated liver injury is a fatal side effect of sintilimab. This study aimed to shed light on the associated risk factors and characteristics of this adverse event. Methods: The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity, as well as its incidence and outcome. The Roussel Uclaf Causality Assessment Method was used to identify cases of sintilimab-induced hepatotoxicity. Furthermore, logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors. Results: Of the 585 patients included in the study, 71 (12.1%) developed liver injury during sintilimab use. The median RUCAM score with interquartile range was 7 (6, 8). Hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity. A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors, which had a C-index value of 0.713 and a good calibration curve. When applied to patients with grade ≥3 and ≥4 sintilimab-induced immune-mediated liver injury, it achieved C-index values of 0.752 and 0.811, respectively. The nomogram model also showed a good prediction potential in patients ≥65 years and males. Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids. Conclusions: This study demonstrated that hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.

Hepatotoxicity of immune checkpoint inhibitors: What is Currently Known.

BACKGROUND: This systematic review and network meta-analysis aimed to provide a complete hepatotoxicity profile, hepatotoxicity spectrum, and safety ranking of immune checkpoint inhibitor drugs for cancer treatment. METHODS: PubMed, Embase, Scopus, CINAHL, Web of Science, psycINFO, Cochrane Library, and ClinicalTrials.gov. websites were searched, and a manual search of relevant reviews and trials up to January 1, 2022, was undertaken. Head-to-head III randomized controlled trials comparing any 2 or 3 of the following treatments or different doses of the same immune checkpoint inhibitor drug were included: programmed death 1 (PD-1), programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors and conventional therapy. We included 106 randomized trials (n=164,782) containing 17 treatment arms. RESULTS: The overall incidence of hepatotoxicity was 4.06%. The rate of fatal liver adverse events was 0.07%. The programmed death ligand 1 inhibitor+targeted therapy drug+chemotherapy group had the highest risk of treatment-related increases in all-grade alanine aminotransferase and aspartate aminotransferase levels, and the differences were significant. For immune-related hepatotoxicity, no significant difference was found between PD-1 and CTLA-4 inhibitors for all-grade hepatotoxicity; however, CTLA-4 inhibitors were associated with a higher risk of grade 3-5 hepatotoxicity than PD-1 inhibitors. CONCLUSIONS: The highest incidence of hepatotoxicity and fatality was observed with triple therapy. The overall incidence of hepatotoxicity was similar between different dual regimens. For immune checkpoint inhibitor monotherapy, the overall risk of immune-mediated hepatotoxicity related to CTLA-4 inhibitors did not differ significantly from that of PD-1 inhibitors. There was no direct relationship between the risk of liver injury and drug dose, whether monotherapy or combination therapy was used.

The efficacy and safety of Sacubitril/Valsartan in the treatment of chronic heart failure: a meta-analysis.

OBJECTIVE: A meta-analysis of the studies involving Sacubitril/Valsartan in chronic heart failure was performed to compare the efficacy and safety of Sacubitril/Valsartan with traditional drug therapy in chronic heart failure. METHODS: We searched databases from PubMed, EMBASE, the Cochrane Library, Web of Science, and clinicaltrials.gov for studies published between 2010 and 2020 that reported efficacy and safety following Sacubitril/Valsartan administration. RESULTS: Ten studies enrolling 1689 patients were included. Sacubitril/Valsartan outperformed traditional medicine (especially the Non-ARNI group) in terms of blood pressure, biomarkers and cardiac reverse remodeling indices, with striking changes in left ventricular ejection fraction, systolic blood pressure. Sacubitril/Valsartan showed significant benefit in renal function in patients with chronic heart failure. CONCLUSIONS: Compared with traditional drugs, Sacubitril/Valsartan significantly improved echocardiography, vital signs and biomarkers of patients with chronic heart failure, and reduced the incidence of hyperkalemia, renal dysfunction and other adverse reactions. Further large sample trials are needed in the future to determine the long-term effects of Sacubitril/Valsartan on efficacy and safety in patients with chronic heart failure.

Maternal, umbilical arterial metabolic levels and placental Nrf2/CBR1 expression in pregnancies with and without 25-hydroxyvitamin D deficiency.

BACKGROUND: The aim of this case-control study was to document maternal, umbilical arterial metabolic levels and correlations in pregnancies with and without 25-hydroxyvitamin D [25(OH)D] deficiency, while, also investigating the expression of nuclear factor erythroid 2 related factor 2 (Nrf2) and carbonyl reductase 1 (CBR1) in the placenta. METHODS: One hundred participants, 50 deficient for 25(OH)D and 50 normal, were recruited from among hospitalized single-term pregnant women who had elected for cesarean section. Umbilical arterial and placental samples were collected during cesarean section. Metabolic levels were assessed for the 25(OH)D deficiency and control groups' maternal, umbilical arterial samples. Nrf2 and CBR1 expression levels were investigated in the placentas of 12 pregnant women with 25(OH)D deficiency and 12 controls. RESULTS: Compared with the control participants, the 25(OH)D deficient women had significantly higher triglyceride (TG) levels (3.80 ± 2.11 vs. 2.93 ± 1.16 mmol/L, 3.64 ± 1.84 vs. 2.81 ± 1.16 mmol/L, p < .01, .001); lower high density lipoprotein cholesterol (HDL-C) levels (1.54 ± 0.32 vs. 1.82 ± 0.63 mmol/L, 1.41 ± 0.72 vs. 2.44 ± 1.68 mmol/L, p < .001, .01) in both material blood and the umbilical artery. In addition, Nrf2 and CBR1 expression levels were lower in the maternal 25(OH)D deficient placenta. CONCLUSION: 25(OH)D deficient pregnant women have higher TG levels and lower HDL-C levels in both material blood and the umbilical artery. TG level is negatively correlated with 25(OH)D in both the maternal serum and infant umbilical artery. 25(OH)D deficiency also lowers placental expression of Nrf2 and CBR1.Supplemental data for this article is available online at here.

Effects of sodium-glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Controlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) are beneficial for the survival of patients with heart failure (HF). However, it is unclear whether SGLT-2i can provide benefit in patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the outcomes of cardiovascular, renal, and safety outcomes of SGLT-2i administration in patients with cardiovascular diseases. METHODS: We searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2i in patients with cardiovascular disease with or without diabetes. Primary outcomes were cardiovascular outcomes and renal outcomes. Secondary outcomes were safety outcomes, including adverse endocrine outcomes and adverse infection outcomes. The effects of SGLT-2i were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality. RESULTS: We identified 10 randomised controlled trials (25,108 patients in the SGLT-2i group and 18,574 patients in the placebo group). Meta-analysis revealed that SGLT-2i treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI] 0.81-0.91; P < 0.00001; I2 = 0%; cardiovascular mortality RR: 0.85; 95% CI 0.79-0.92; P < 0.0001; I2 = 26%; HHF RR: 0.69; 95% CI 0.64-0.81; P < 0.00001; I2 = 0%). In patients with HF, mortality and HHF after SGLT-2i treatment for HF with reduced ejection fraction were significantly reduced, whereas HF with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2i induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher. CONCLUSIONS: SGLT-2i had significant clinical effects on cardiovascular outcomes and significantly influenced acute kidney injury. The effects of SGLT-2i on cardiovascular disease were independent of diabetic status. Sotagliflozin could have advantages over other SGLT-2i in lowering HHF.

Maternal 25-Hydroxyvitamin D Deficiency Promoted Metabolic Syndrome and Downregulated Nrf2/CBR1 Pathway in Offspring.

Metabolic syndrome is a disorder of energy use and storage, which is characterized by central obesity, dyslipidemia, and raised blood pressure and blood sugar levels. Maternal 25-hydroxyvitamin D deficiency is known to cause metabolic changes, chronic disease, and increased adiposity in adulthood. However, the underlying mechanism of induced metabolic syndrome (MetS) in the offspring in vitamin D deficient pregnant mothers remains unclear. We identified that maternal 25-hydroxyvitamin D deficiency enhances oxidative stress, which leads to the development of MetS in the mother and her offspring. Further, immunohistochemical, Western blotting, and qRT-PCR analyses revealed that maternal 25-hydroxyvitamin D deficiency inhibited the activation of the Nrf2/carbonyl reductase 1 (CBR1) pathway in maternal placenta, liver, and pancreas, as well as the offspring's liver and pancreas. Further analyses uncovered that application of 25-hydroxyvitamin D activated the Nrf2/CBR1 pathway, relieving the oxidative stress in BRL cells, suggesting that 25-hydroxyvitamin D regulates oxidative stress in offspring and induces the activation of the Nrf2/CBR1 pathway. Taken together, our study finds that maternal 25-hydroxyvitamin D deficiency is likely to result in offspring's MetS probably via abnormal nutrition transformation across placenta. Depression of the Nrf2/CBR1 pathway in both mothers and their offspring is one of the causes of oxidative stress leading to MetS. This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring's MetS.

Benefits of Mobile Apps for Cancer Pain Management: Systematic Review.

BACKGROUND: Pain ratings reported by patients with cancer continue to increase, and numerous computer and phone apps for managing cancer-related pain have been developed recently; however, whether these apps effectively alleviate patients' pain remains unknown. OBJECTIVE: This study aimed to comprehensively evaluate the role of mobile apps in the management of cancer pain. METHODS: Literature on the use of apps for cancer pain management and interventions, published before August 2019, was retrieved from the following databases: MEDLINE, Embase, Cochrane, CINAHL, Scopus, and PsycINFO. The effects of apps on cancer pain were evaluated using RevMan5.3 software, and the rates of adverse drug reactions were analyzed using the R Statistical Software Package 3.5.3. RESULTS: A total of 13 studies were selected for the analysis: 5 randomized controlled trials (RCTs), 4 before-after studies, 2 single-arm trials, 1 prospective cohort study, and 1 prospective descriptive study. The 5 RCTs reported data for 487 patients (240 patients in the intervention group and 247 patients in the control group), and the remaining studies reported data for 428 patients. We conducted a meta-analysis of the RCTs. According to the meta-analysis, apps can significantly reduce pain scores (mean difference [MD]=-0.50, 95% CI -0.94 to -0.07, I2=62%, P=.02). We then used apps that have an instant messaging module for subgroup analysis; these apps significantly reduced patients' pain scores (MD=-0.67, 95% CI -1.06 to -0.28, I2=57%, P<.01). Patients using apps without an instant messaging module did not see a reduction in the pain score (MD=0.30, 95% CI -1.31 to 1.92, I2=70%, P=.71). Overall, patients were highly satisfied with using apps. Other outcomes, such as pain catastrophizing or quality of life, demonstrated greater improvement in patients using apps with instant messaging modules compared with patients not using an app. CONCLUSIONS: The use of apps with instant messaging modules is associated with reduced pain scores in patients with cancer-related pain, and patient acceptance of these apps is high. Apps without instant messaging modules are associated with relatively higher pain scores. The presence of an instant messaging module may be a key factor affecting the effect of an app on cancer pain.

Improving estimates of built-up area from night time light across globally distributed cities through hierarchical modeling.

Built-up area has become an important indicator for studying urban environments, but mapping built-up area at the regional/global scale remains challenging due to the complexity of impervious surface features. Nighttime light data (NTL) is one of the major remote sensing data sources for regional/global built-up or impervious surface mapping. A single regression relationship between fractional built-up/impervious area and NTL or various indices derived based on NTL and vegetation index (e.g., NDVI) data had been established in many previous studies. However, due to the varying geographical, climatic, and socio-economic characteristics of cities, the same regression relationship may vary significantly across cities. In this study, we examined the regression relationship between percentage of built-up area (pBUA) and vegetation adjusted nighttime light urban index (VANUI) for 120 randomly selected cities around the world with a hierarchical hockey-stick regression model. We found that there is a substantial variability in the slope (0.658 ±â€¯0.318), the threshold VANUI (-1.92 ±â€¯0.769, log scale) after which the linear relationship holds, and the coefficient of determination R2 (0.71 ±â€¯0.14) among globally distributed cities. A small proportion of this substantial variability can be attributed to socio-economic status (e.g., total population, GDP per capita) and landscape structures (e.g., compactness and fragmentation). Due to these variations, our hierarchical model or no-pooling model (i.e., fit each city individually) can significantly improve model prediction accuracy (17% in terms of root mean squared error) over a complete-pooling model. We, however, recommend hierarchical models as they can provide meaningful priors for future modeling under a Bayesian framework, and achieve higher prediction accuracy than no-pooling models when sample size is small.

Curcumin protects against ischemic spinal cord injury: The pathway effect.

Inducible nitric oxide synthase and N-methyl-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin. Reverse transcription-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tarlov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyl-D-aspartate receptor expression.

Excessive wave reflections on admission predict post-discharge events in patients hospitalized due to acute heart failure.

AIMS: The role of wave reflections in the pathogenesis of acute heart failure syndrome (AHFS) remains unclear. The present study investigated the long-term prognostic values of the carotid augmentation index (cAI), carotid augmented pressure (cAP), amplitude of the reflected pressure wave from a decomposed carotid pressure wave (Pb), and carotid pulse pressure (PP) on admission in patients hospitalized due to AHFS. METHODS AND RESULTS: A total of 120 patients (72 ± 14 years, 83.3% men) hospitalized due to AHFS (55.8% with systolic heart failure) were enrolled. Measures of cAI, cAP, Pb, carotid PP, and carotid-femoral pulse wave velocity (cf-PWV) by tonometry and thoracic fluid content (TFC) by impedance cardiography were obtained within 24 h of admission. N-terminal pro brain natriuretic peptide (NT-proBNP) levels were determined before discharge. Patients were followed up for a median of 601 days, accruing 66 adverse events including re-hospitalization for heart failure, non-fatal myocardial infarction, non-fatal stroke, and death. In univariate Cox analysis, all measures significantly predicted post-discharge events (all P < 0.05). In multivariate analysis, cAP [hazard ratio per SD and 95% confidence interval: 1.32 (1.051-1.67), P = 0.017], Pb [1.44 (1.13-1.84), P = 0.004] and carotid PP [1.35 (1.05-1.73), P = 0.019], but not cAI, TFC, or cf-PWV, significantly independently predicted events with adjustments for age, estimated glomerular filtration rate, haemoglobin, and NT-proBNP. CONCLUSION: On-admission measures of wave reflection magnitude, including cAP, Pb, and carotid PP, may be useful for predicting long-term outcomes in AHFS patients. The results support a major role for wave reflection in the pathogenesis of AHFS.

Images in cardiovascular medicine: tuberculous aortitis.

Tuberculous aortitis is a rare disease entity indicative of disseminated tuberculosis. We report a case who presented with newly diagnosed hypertension one year after her last admission for pulmonary and pericardial tuberculosis. Chest CT and MRA, performed due to marked differences in pulse amplitude between upper and lower limbs, demonstrated long and severe segmental stenosis of the thoracic aorta. After the operation of bypass graft for the thoracic aorta, the patient recovered uneventfully. Tuberculous aortitis should be included in the list of differential diagnosis for secondary hypertension, especially if the patient has a recent disease history of pulmonary tuberculosis.

Estimation of central aortic systolic pressure from the second systolic peak of the peripheral upper limb pulse depends on central aortic pressure waveform morphology.

BACKGROUND: Direct identification of second systolic peaks of peripheral upper limb pulses (pSBP2) has been used to represent central systolic blood pressure (cSBP), but its accuracy at low SBP was questioned. OBJECTIVES: We investigated the relationship of pSBP2 with characteristics of central pressure waveforms. METHODS: High-fidelity central aortic and right brachial pressure waveforms were simultaneously recorded using a custom-made dual pressure sensor catheter in 78 patients (65.9 ± 12.9 years) during catheterization for 285 measurements. RESULTS: Overall agreement between cSBP and pSBP2 was good (mean difference -0.9 ±â€Š4.8, r = 0.98), with a systematic bias at low SBP. We examined agreements of different waveform types according to the relationship of the second systolic peak of aortic pressure waveforms (cSBP2) to cSBP. Of type A (positive late systolic augmentation) and type B (zero augmentation) aortic pressure waveforms, in which cSBP = cSBP2, agreement between pSBP2 and cSBP was excellent (mean difference -0.4 ±â€Š4.1, r = 0.99). There were 40 type C aortic pressure waveforms (negative augmentation; cSBP > cSBP2) with cSBP 107.2 ±â€Š13.9 mmHg. Their cSBP2, compared with cSBP, showed closer agreement (mean difference -0.6 ±â€Š3.2 vs. -4.0 ±â€Š7.2 mmHg) and better correlation (r = 0.97 vs. 0.85, P = 0.03) with pSBP2. CONCLUSION: pSBP2 can be used with type A and B aortic pressure waveforms for estimation of cSBP. However, it should not be used with type C aortic pressure waveforms, typically at low SBP, because pSBP2 is closer to cSBP2 than cSBP. This explains why pSBP2 underestimates cSBP at low SBP.