Risk factors for and outcomes of heatstroke-related intracerebral hemorrhage.

Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death.

Hepatic portal venous gas initially manifesting as severe shock: a case series.

Hepatic portal venous gas is often referred to as the "sign of death" because it signifies a very poor prognosis if appropriate treatments are not promptly administered. The etiologies of hepatic portal venous gas are diverse and include severe complex abdominal infections, mesenteric ischemia, diving, and complications of endoscopic surgery, and the clinical manifestations are inconsistent among individual patients. Thus, whether emergency surgery should be performed remains controversial. In this report, we present three cases of hepatic portal venous gas. The patients initially exhibited symptoms consistent with severe shock of unknown etiology and were treated in the intensive care unit upon admission. We rapidly identified the cause of each individual patient's condition and selected problem-directed intervention measures based on active organ support, antishock support, and anti-infection treatments. Two patients recovered and were discharged without sequelae, whereas one patient died of refractory infection and multiple organ failure. We hope that this report will serve as a valuable reference for decision-making when critical care physicians encounter similar patients.

Decompression sickness followed by diabetic ketoacidosis and sepsis shock: an unusual case report.

Decompression sickness (DCS) is caused by abrupt changes in extracorporeal pressure with varying severity. Symptoms range from mild musculoskeletal pain to severe organ dysfunction and death, especially among patients with chronic underlying disease. Here, we report an unusual case of a 49-year-old man who experienced DCS after a dive to a depth of 38 meters. The patient's symptoms progressed, starting with mild physical discomfort that progressed to disturbance of consciousness on the second morning. During hospitalization, we identified that in addition to DCS, he had also developed diabetic ketoacidosis, septic shock, and rhabdomyolysis. After carefully balancing the benefits and risks, we decided to provide supportive treatment to sustain vital signs, including ventilation support, sugar-reducing therapy, fluid replacement, and anti-infection medications. We then administered delayed hyperbaric oxygen (HBO2) when his condition was stable. Ultimately, the patient recovered without any sequelae. This is the first case report of a diver suffering from DCS followed by diabetic ketoacidosis and septic shock. We have learned that when DCS and other critical illnesses are highly suspected, it is essential to assess the condition comprehensively and focus on the principal contradiction.

Non-Invasive and Label-Free On-Chip Impedance Monitoring of Heatstroke.

Heatstroke (HS) is a life-threatening injury requiring neurocritical care which could lead to central nervous system dysfunction and severe multiple organ failure syndrome. The cell-cell adhesion and cell permeability are two key factors for characterizing HS. To investigate the process of HS, a biochip-based electrical model was proposed and applied to HS. During the process, the value of TEER is associated with cell permeability and CI which represents cell-cell adhesion decreases that are consistent with the reduction in cell-cell adhesion and cell permeability characterized by proteins (occludin, VE-Cadherin and ZO-1) and RNA level. The results imply that the model can be used to monitor the biological process and other biomedical applications.

Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells.

BACKGROUND: Kinesin family member 4A (KIF4A) is upregulated in a variety of cancers. However, its expression and potential downstream targets in urothelial bladder carcinoma (UBC) remain unclear. METHODS: Expression data of KIF4A in UBC and noncancerous tissues were downloaded from the GEPIA database. Cell proliferation, migration, invasion, and apoptosis of T24 and 5637 UBC cells were examined using wound healing, transwell, colony formation, CCK-8, and flow cytometry assays. KIF4A and potential downstream genes were analyzed using qRT-PCR, western blot analysis, and immunohistochemistry. RESULTS: In UBC samples, KIF4A expression was significantly higher than in corresponding noncancerous samples. UBC patients with high KIF4A expression had poor cancer-specific survival and overall survival. Knockdown of KIF4A significantly inhibited proliferation and promoted apoptosis of UBC cells, accompanied by dephosphorylation of AKT and increased the protein level of proapoptotic factors. Additionally, knockdown of KIF4A reduced migration and invasion of UBC cells whereas overexpression of KIF4A exhibited opposite effects, along with altered protein level in epithelial-mesenchymal transition-related genes. Furthermore, overexpression of YAP1 promoted KIF4A expression whereas knockdown of YAP1 suppressed KIF4A expression in UBC cells. Alternatively, KIF4A knockdown reduced YAP1 nuclear protein level whereas KIF4A overexpression suppressed YAP1 phosphorylation and facilitated YAP1 nuclear translocation. CONCLUSIONS: KIF4A upregulation correlates with poor prognosis of UBC. Knockdown of KIF4A inhibits proliferation, migration, and invasion of UBC cells while inducing apoptosis possibly through dephosphorylation of AKT, changes in EMT-related genes, and interaction with YAP1.

CCL25 Inhibition Alleviates Sepsis-Induced Acute Lung Injury and Inflammation.

Purpose: Acute lung injury (ALI) is a common clinical syndrome with high mortality. The chemokine ligand 25 (CCL25) is involved in inflammation, leukocyte trafficking and immunoregulation. However, the role and mechanism of CCL25 in ALI are not fully understood yet. The aim of this study was to explore the relationship between acute lung injury and CCL25. Patients and Methods: In this study, we first examined chemokine expression in sepsis patients and found that serum CCL25 expression levels were relatively high in sepsis patients compared to healthy individuals. Based on this, we designed in vitro and in vivo experiments to verify the validity of the theory. In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs). In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis. Results: In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs) and found significantly higher expression of CCL25 by enzyme-linked immunosorbent assay. Inhibition of CCL25 resulted in a significant decrease in the expression of inflammatory cytokines in HPMECs. In addition, we found that CCL25 promoted increased endothelial permeability by reducing the expression of tight junction proteins and was associated with activation of the P38 MAPK pathway by measuring the transepithelial electrical resistance and fluorescence intensity of fluorescein isothiocyanate. Results from luciferase assays and chromatin immunoprecipitation assays showed that inhibition of NF-κB activity in HPMECs decreased CCL25 expression, but addition of recombinant CCL25 increased cell permeability and inflammatory cytokine expression. In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis. We found that inhibition of CCL25 significantly reduced inflammatory cytokine expression in a CLP-induced sepsis model, thereby alleviating lung tissue damage in mice. Conclusion: Our study suggests that CCL25 contributed to the development of ALI by modulating the functions of microvascular endothelial cells.

Cuprous oxide nanoparticles trigger reactive oxygen species-induced apoptosis through activation of erk-dependent autophagy in bladder cancer.

Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer. However, as more than 50% of patients are ineligible for cisplatin-based chemotherapy, there is an urgent need to develop new drugs. Cuprous oxide nanoparticles (CONPs), as a new nano-therapeutic agent, have been proved to be effective in many kinds of tumors. In the present study, CONPs showed dose-dependent and time-dependent inhibitory effects on various bladder cancer cell lines (T24, J82, 5637, and UMUC3) and weak inhibitory effects on non-cancerous epithelial cells (SVHUCs). We found that CONPs induced cell cycle arrest and apoptosis in bladder cancer cells. We further demonstrated that the potential mechanisms of CONP-induced cytotoxicity were apoptosis, which was triggered by reactive oxygen species through activation of ERK signaling pathway, and autophagy. Moreover, the cytotoxic effect of CONPs on bladder cancer was confirmed both in orthotopic xenografts and subcutaneous nude mouse models, indicating that CONPs could significantly suppress the growth of bladder cancer in vivo. In further drug combination experiments, we showed that CONPs had a synergistic drug-drug interaction with cisplatin and gemcitabine in vitro, both of which are commonly used chemotherapy agents for bladder cancer. We further proved that CONPs potentiated the antitumor activity of gemcitabine in vivo without exacerbating the adverse effects, suggesting that CONPs and gemcitabine can be used for combination intravesical chemotherapy. In conclusion, our preclinical data demonstrate that CONPs are a promising nanomedicine against bladder cancer and provide good insights into the application of CONPs and gemcitabine in combination for intravesical bladder cancer treatment.

Prognostic value of the combined expression of tumor-associated trypsin inhibitor (TATI) and p53 in patients with bladder cancer undergoing radical cystectomy.

BACKGROUND: Urothelial carcinoma of the bladder is a heterogeneous disease for which reliable prognostic molecular biomarkers have not been established. OBJECTIVE: To investigate the prognostic value of tumor-associated trypsin inhibitor (TATI) expression combined with p53 expression in bladder cancer patients who have undergone radical cystectomy. METHODS: Tissue microarrays from 110 patients were analyzed immunohistochemically for TATI and p53 protein expression. Complete clinical-pathological information and follow-up data were collected. Univariable Kaplan-Meier analysis and log-rank test were performed to assess the association between TATI and p53 expression patterns with clinical outcomes. Cox's proportional hazard analysis was performed to identify potential independent risk factors for predicting disease progression and evaluate the prognostic value of combining the expression of TATI and p53 on progression-free survival (PFS) and overall survival (OS). RESULTS: TATI expression was positively correlated with favorable differentiation of bladder cancer, and lower tumor stage. p53 expression was positively related to tumor stage, tumor grade, and lymph-node invasion. Univariate Kaplan-Meier analysis revealed significant differences between TATI-positive vs. TATI-negative and p53-positive vs. p53-negative patients, regarding PFS. Multivariate analysis showed that both TATI and p53 expression were independent factors for predicting disease progression. CONCLUSION: TATI expression patterns could enhance the prognostic value of p53 overexpression on progression.

Dysbiosis signatures of the microbial profile in tissue from bladder cancer.

BACKGROUND: To examine the microbial profiles in parenchyma tissues in bladder cancer. METHODS: Tissue samples of cancerous bladder mucosa were collected from patients diagnosed with bladder cancer (22 carcinoma tissues and 12 adjacent normal tissues). The V3-V4 region of the bacterial 16S rRNA gene was PCR amplified, followed by sequencing on an Illumina MiSeq platform. Bioinformatics analysis for microbial classification and functional assessment was performed to assess bladder microbiome diversity and variations. RESULTS: The predominant phylum in both tissues was Proteobacteria. The cancerous tissues exhibited lower species richness and diversity. Beta diversity significantly differed between the cancerous and normal tissues. Lower relative abundances of the microbial genera Lactobacillus, Prevotella_9, as well as Ruminococcaceae were observed, whereas those of Cupriavidus spp., an unknown genus of family Brucellaceae, and Acinetobacter, Anoxybacillus, Escherichia-Shigella, Geobacillus, Pelomonas, Ralstonia, and Sphingomonas were higher in the cancerous tissues. These findings indicate that these genera may be potentially utilized as biomarkers for bladder cancer. PICRUSt analysis revealed that several pathways involved in the metabolism of harmful chemical compounds were enriched in the cancer tissues, thereby providing evidence that environmental factors are strongly associated with bladder cancer etiology. CONCLUSION: This is the first study that has described and analyzed the dysbiotic motifs of urinary microbiota in the parenchymatous tissues of bladder cancer via 16S rRNA gene sequencing. Our results suggest that changes in the bladder microbiome may serve as biomarkers for bladder cancer, possibly assisting in disease screening and monitoring.

Tumor­infiltrating M2 macrophages driven by specific genomic alterations are associated with prognosis in bladder cancer.

The present study aimed to explore the mechanism by which the immune landscape of the tumor microenvironment influences bladder cancer. CIBERSORT and ssGSEA analyses revealed that M2 macrophages accounted for the highest proportion from 22 subsets of tumor­infiltrating immune cells and were enriched in higher histologic grade and higher pathologic stage bladder cancer and 'basal' subtype of muscle invasive bladder cancer (MIBC). Kaplan­Meier survival curve analysis indicated that patients with high numbers of infiltrating M2 macrophages had worse overall and disease­specific survival rates. RNA sequencing and immunohistochemistry results indicated that M2 macrophages were enriched in MIBC and promoted angiogenesis. M2 macrophage infiltration was higher in bladder cancer tissues with mutant TP53, RB transcriptional corepressor 1, phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit α, lysine methyltransferase 2A, lysine demethylase 6A and apolipoprotein B mRNA editing enzyme catalytic­polypeptide­like, but lower in tissues with mutant fibroblast growth factor receptor 3 (FGFR3), E74­like ETS transcription factor 3, PC4 and SFRS1 interacting protein 1 and transmembrane and coiled­coil domains 4. In addition, M2 macrophage infiltration was lower in the tissues with amplified FGFR3, erb­b2 receptor tyrosine kinase 2, BCL2­like 1, telomerase reverse transcriptase and tyrosine­3­monooxygenase/tryptophan­5­monooxygenase activation protein ζ, as well as in the tissues with deleted cyclin­dependent kinase inhibitor 2A, CREB binding protein, AT­rich interaction domain 1A, fragile histidine triad diadenosine triphosphatase, phosphodiesterase 4D, RAD51 paralog B, nuclear receptor corepressor 1 and protein tyrosine phosphatase receptor type D. Finally, seven micro (mi) RNAs (miR­214­5p, miR­223­3p, miR­155­5p, miR­199a­3p, miR­199b­3P, miR­146b­5p, miR­142­5p) which were expressed differentially in at least three mutant genes and were positively correlated with M2 macrophage infiltration as well as expressed highly in high grade bladder cancer were identified. Overall, the present study concluded that M2 macrophages are the predominant tumor­infiltrating immune cell in bladder cancer and differentially expressed miRNAs due to cancer­specific genomic alterations may be important drivers of M2 macrophage infiltration. These findings suggested that M2 macrophage infiltration may serve as a potential immunotherapy target in bladder cancer.

Prognostic value of TOP2A in bladder urothelial carcinoma and potential molecular mechanisms.

BACKGROUND: The prognosis of bladder urothelial carcinoma (BLCA) varies greatly among patients, and conventional pathological predictors are generally inadequate and often inaccurate to predict the heterogeneous behavior of BLCA. This study aims to investigate the prognostic value and function of TOP2A in BLCA. METHODS: TOP2A expression level was examined by RNA-sequencing, quantitative real time polymerase chain reaction and immunohistochemistry from 10, 40 and 209 BLCA samples, respectively. Public databases were analyzed for validation. Cell proliferation, migration, invasion assays were performed to explore potential functions of TOP2A in BLCA. Flow cytometry was performed for cell cycle and apoptosis analysis. Univariable and multivariable Cox regression models were performed to identify independent risk factors for the prognosis of BLCA. RESULTS: We found TOP2A was significantly upregulated in BLCA samples, especially for high-grade and advanced stage tumors, compared with matched normal epithelial tissue. Univariable COX regression analysis revealed high TOP2A expression was significantly associated with poorer cancer-specific, progression-free and recurrence-free survival, but not independently of clinical characteristics in the multivariable models. Knockdown of TOP2A remarkably inhibited the proliferation of BLCA cells and non-cancerous urothelial cells. Furthermore, migration and invasion capacity of BLCA cells were strongly suppressed after TOP2A knockdown. Moreover, flow cytometry suggested TOP2A had anti-apoptotic function, and knockdown of TOP2A could induce resistance to doxorubicin in J82 cells. CONCLUSIONS: In our study, TOP2A was overexpressed in BLCA and could serve as a prognostic biomarker for BLCA. Moreover, TOP2A is functionally important for the proliferation, invasion and survival of BLCA cells.

Prognostic value of differentially methylated gene profiles in bladder cancer.

DNA methylation can regulate gene expression and is pivotal in the occurrence and development of bladder cancer. In this study, we analyzed whole-genome DNA methylation on the basis of data from The Cancer Genome Atlas to select epigenetic biomarkers predictive of survival and further understand the molecular mechanisms underlying methylation patterns in bladder cancer. We identified 540 differentially methylated genes between tumor and normal tissues, including a number of independent prognostic factors based on univariate analysis. Genes (MIR6732, SOWAHC, SERPINI1, OR10W1, OR7G3, AIM1, and ZFAND5) were integrated to establish a risk model for prognostic assessment based on multivariate Cox analysis. The methylation of SOWAHC was negatively correlated with its messenger RNA expression, and together these were significantly correlated with prognosis. This study took advantage of high-throughput data mining to provide new bioinformatics evidence and ideas for further study into the pathogenesis and prognosis of bladder cancer.

Total parenteral nutrition versus early enteral nutrition after cystectomy: a meta-analysis of postoperative outcomes.

BACKGROUND: This study aimed to systematically summarize and analyze the current evidence regarding the effect of total parenteral nutrition (TPN) versus early enteral nutrition (EEN) on postoperative outcomes of cystectomy. METHODS: A comprehensive search of online databases was conducted to identify comparative studies on the postoperative outcomes of patients receiving TPN and EEN after cystectomy. Our subsequent meta-analysis followed the PRISMA Protocol and the Cochrane Handbook. RESULTS: Five studies with 556 participants were included for meta-analysis. EEN was shown to have a significant effect on reducing the overall complications (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.37-0.75, P < 0.01) and infectious complications (OR 0.32, 95% CI 0.21-0.49, P < 0.01) compared with TPN. Additionally, EEN saved €614-€3120 in costs compared to TPN. There were no significant differences between TPN and EEN groups regarding mortality rate (OR 0.47, 95% CI 0.06-3.51, P = 0.46), the incidence of postoperative ileus (OR 0.90, 95% CI 0.55-1.47, P = 0.68), length of hospital stay (mean difference (MD) 2.12, 95% CI - 0.15 to 4.40, P = 0.07), or time to resume a full diet (MD 1.31, 95% CI - 1.15 to 3.77, P = 0.30). CONCLUSION: EEN was found to have a significant effect on reducing infectious complications and costs compared with TPN treatment after cystectomy. Remarkably, EEN had no significant impact on mortality incidence, postoperative ileus, length of hospital stay, or the time to resumption of full diet.

Overexpression of G2 and S phase-expressed-1 contributes to cell proliferation, migration, and invasion via regulating p53/FoxM1/CCNB1 pathway and predicts poor prognosis in bladder cancer.

Bladder cancer is one of the most common urogenital tumors worldwide. The specific function and molecular mechanism of GTSE1 in bladder cancer remain unknown. In the present study, real-time quantitative polymerase chain reaction and Western blotting were used to identify GTSE1 expression in bladder cancer tissues and cells, and immunohistochemical assays were conducted to investigate GTSE1 expression in tissue microarray. Regression analyses explored the relationship between GTSE1 expression and pathological characteristics. A series of functional tests were performed to observe the effects of GTSE1 knockdown or overexpression, and the related mechanism was also performed. GTSE1 expression was significantly higher in bladder cancer tissues; overexpression of GTSE1 was positively associated with disease recurrence history, lymph node invasion, and progression. Patients with higher GTSE1 expression were more likely to experience shorter survival time, and GTSE1 expression served as a prognostic factor for the disease progression. Knockdown of GTSE1 obviously suppressed the proliferation, migration, and invasion capacity whereas increasing GTSE1 led to the opposite trend, which suggested that GTSE1 could serve as a potential therapeutic target for bladder cancer. GTSE1 overexpression in bladder cancer might participate in the regulation of FoxM1/CCNB1 expression via the induction of the transfer of p53 to cytoplasm.

Overexpression of long non­coding RNA n346372 in bladder cancer tissues is associated with a poor prognosis.

Accumulating evidence has confirmed that dysregulated long non­coding RNAs (lncRNAs) participate in the initiation and progression of a number of solid tumors and have potential applications for early diagnosis, targeted therapy, and the prognosis of patients with bladder cancer. In the present study, via high­throughput sequencing technology and bioinformatics analysis, a total of 169 lncRNAs with significantly differential expression between bladder cancer tissues and paired adjacent normal tissues (n=10) were initially identified by screening. Reverse­transcription­quantitative polymerase chain reaction was carried out to validate the expression levels of lncRNA­n346372 in 60 pairs of tissue samples from bladder cancer patients. The results indicated that lncRNA­n346372 was upregulated in bladder cancer tissues compared with the matched adjacent normal tissues (P<0.05). In addition, the results of fluorescence in situ hybridization analysis of bladder cancer cells and tissues demonstrated that lncRNA­n346372 is located in the cytoplasm, and the expression of lncRNA­n346372 in bladder cancer tissues was significantly increased compared with the paired normal tissues. Following a χ2 test with common clinical variables among the patients, the expression level of lncRNA­n346372 was demonstrated to be positively associated with advanced tumor stage and poor histological differentiation of bladder cancer. Kaplan­Meier survival analysis revealed that patients with high expression of n346372 were more likely to have a poor prognosis compared with patients with low n346372 expression. Finally, univariate and multivariate analyses indicated that the relative level of n346372, apart from tumor stage and histological grade, may serve as an independent prognostic factor of bladder cancer. To the best of the authors' knowledge, this is the first study to verify the dysregulated expression of lncRNA­n346372 in bladder cancer; an association of this lncRNA with overall survival of bladder cancer patients was also uncovered in the present study, suggesting that lncRNA­n346372 may contribute to the initiation and/or progression of bladder cancer with potential applications in the clinic.

DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association. METHODS: Studies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software. RESULTS: A total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83-8.82, P<0.00001). The frequency of DAPK promoter methylation was equal in bladder cancer tissue and paired adjacent normal tissue (OR: 0.87; 95%CI = 0.31-2.48, P = 0.794). Furthermore, DAPK promoter methylation was associated with higher histological grade (OR: 1.52; 95%CI = 1.10-2.09, P = 0.011) but not associated with tumor stage (OR: 1.12; 95%CI = 0.67-1.87, P = 0.668). CONCLUSIONS: The result suggests that DAPK promoter methylation is significantly increased in bladder cancer patients compared to normal controls. DAPK promoter methylation could serve as a biomarker for bladder cancer detection and management.

Effect of halo substitution on the geometry of arenethiol films on Cu(111).

Incomplete coverages of p-fluorothiophenol, p-chlorothiophenol, and p-bromothiophenol form ordered islands on a Cu(111) surface even at low temperatures. The complexity of the molecular patterns increases from a simple (3 x 4) superlattice to a honeycomb (8 x 8)R19 degrees structure with increasing substituent electronegativity. We propose a model based on quadrupolar intermolecular interactions to account for this observation.