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We investigated the combined effects of ataxia telangiectasia and Rad3-related (ATR) inhibition, ablative radiotherapy, and immune checkpoint inhibitor (ICI) therapy against lung cancer. ATR inhibitor was administered combined with ablative radiotherapy to assess its radiosensitizing effect on lung cancer cells. Treatment response and survival were evaluated in vivo using A549 xenograft flank tumor and synchronous LLC lung and flank tumor mouse models. Mice received ablative radiotherapy (12 Gy/d for 2 d), ATR inhibitor, and ICI. The tumor microenvironment was assessed in irradiated flank and non-irradiated lung tumors. Programmed death-ligand 1 expression was upregulated after irradiation. ATR inhibition attenuated this upregulation. ATR inhibitor pretreatment decreased cell survival after irradiation by inhibiting DNA double-strand break repair, inducing mitotic cell death, and altering cell cycle progression. ATR inhibition enhanced radiation-induced damage-associated molecular patterns determined by high mobility group box 1 quantification and activated the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Combined ATR inhibition and ablative radiotherapy inhibited tumor growth and improved survival in mice. Adding ICI therapy further enhanced local antitumor effects, reducing the metastatic lung tumor burden and remodeling the tumor microenvironment through immunogenic cell death induction and enhanced immune cell infiltration. Triple therapy increased immune cell infiltration in distant non-irradiated lung tumors and stimulated the generation of protective T-cell immunity in splenocytes. Safety analysis showed minimal toxicity. ATR inhibition enhanced the efficacy of ablative radiotherapy and immunotherapy in lung cancer. These findings underscore the importance of combination therapies for enhancing systemic antitumor immune responses and outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is common in patients with diabetes mellitus (DM). Volatile organic compounds (VOCs) are widespread pollutants that may impact DM development. Objective: This study aims to explore the association between urinary VOC metabolites and CKD in patients with DM. Methods: Adult National Health and Nutrition Examination Survey (NHANES) 2011 to 2018 participants with DM were included in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Multivariable regression models were used to analyze the associations between urinary VOC metabolites and CKD. Results: A total of 1,295 participants with DM and a mean age of 59 years were included. After adjustment for demographic and clinical characteristics, elevated levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (tertile 2: adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI): 1.15–2.85, p = 0.012), N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) (tertile 2: aOR = 1.84, 95% CI: 1.10–3.08, p = 0.021), DHBMA (tertile 3: aOR = 1.93, 95% CI: 1.12–3.35, p = 0.020), and phenylglyoxylic acid (PGA) (tertile 3: aOR = 1.71, 95% CI: 1.11–2.63, p = 0.017) were significantly associated with increased likelihood of CKD. Conclusion: Specific urinary VOC metabolite levels are positively associated with an increased risk of CKD in patients with DM. These findings suggest that monitoring urinary VOC metabolites could be important for the prevention and management of CKD in this population. Future longitudinal studies should focus on establishing causality and elucidating the underlying mechanisms of these associations. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship of four chronic kidney disease–mineral and bone disorder (CKD–MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD–MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127–1790] vs. 1237 [251–3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06–1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: − 0.24–0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients. [ABSTRACT FROM AUTHOR]

Purpose: Development of a safe and effective systemic chemotherapeutic agent for concurrent administration with definitive thoracic radiotherapy remains a major goal of lung cancer management. The synergistic effect of PEGylated liposomal doxorubicin and irradiation was evaluated in lung cancer cell lines both in vitro and in vivo. Methods: In vitro radiosensitization of A549 and LLC cell lines was evaluated by colony formation assay, γH2AX fluorescent staining and western blot assay, and annexin V staining. A radiosensitization study with healthy human lung-derived cell line BEAS-2B was performed for comparative purposes. In vivo radiosensitization was evaluated by tumor ectopic growth, cell survival, pharmacokinetics, and biodistribution analyses. Cleaved caspase‑3, the marker for apoptosis, was assessed immunohistochemically in A549 xenograft tumors. Results: Treatment with PEGylated liposomal doxorubicin decreased A549 and LLC cell proliferation in a dose-dependent manner. In vitro studies revealed comparable radiosensitizer advantages of PEGylated liposomal doxorubicin and free doxorubicin, showing equivalent DNA double-strand breaks according to γH2AX fluorescent staining and western blot assays, similar numbers of apoptotic cells in the annexin‑V staining assay, and moderately decreased clonogenic survival. In vivo studies demonstrated markedly slow ectopic tumor growth with prolonged survival following treatment with PEGylated liposomal doxorubicin plus irradiation in both A549 and LLC mouse models, suggesting that PEGylated liposomal doxorubicin is more effective as a radiosensitizer than free doxorubicin in vivo. Pharmacokinetics evaluation showed a longer half-life of approximately 40 h for PEGylated liposomal doxorubicin, confirming that the liposomal carrier achieved controlled release. Biodistribution evaluation of PEGylated liposomal doxorubicin confirmed high accumulation of doxorubicin in tumors, indicating the promising drug delivery attributes of PEGylated liposomal doxorubicin. Although free doxorubicin caused histopathologic myocarditis with the cardiac muscle fibers showing varying degrees of damage, PEGylated liposomal doxorubicin caused no such effects. The immunohistochemical expression of cleaved caspase-3-positive cells was greatest expressed in the irradiation and PEGylated liposomal doxorubicin combined treatment group, indicating prolonged tumoricidal effects. Conclusions: Our study provides preclinical in vitro and in vivo evidence of the effectiveness of PEGylated liposomal doxorubicin as a radiosensitizer, supporting its potential clinical development as a component of chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Serum indices based on creatinine and cystatin C, including creatinine/cystatin C ratio (Cr/CysC), ratio and difference of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcys/eGFRcre and eGFRDiff), and serum creatinine × eGFRcys, are recently identified serum markers for sarcopenia. We aimed to evaluate the association between these serum indices and mortality in patients with chronic kidney disease (CKD). A single-center retrospective cohort study included 1141 adult patients with stage 1–5 CKD between 2016 and 2018. Basic characteristics, comorbidities, laboratory parameters, and serum creatinine and cystatin C values were obtained. Patients were followed up until death, dialysis, transfer to another hospital, or end of the study. The median age (interquartile range) of our participants was 71 (62–81) years. During a median follow-up of 39 months, 116 (10.2%) patients died. Compared to the survivor group, Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys were all lower in the non-survivors (p < 0.001 for all). The receiver operating characteristic curves of serum indices for predicting mortality showed that all four indices had significant discriminative power. Based on the Cox proportional hazard models, lower values of four serum indices, both as continuous and categorical variables, independently predicted mortality. Our findings suggest that low serum indices of Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys are independent indicators of mortality in patients with non-dialysis CKD. [ABSTRACT FROM AUTHOR]

Background: Despite growing national attention, there is limited understanding of the patient- and treatment-level characteristics related to treatment cost-associated distress ("financial toxicity") in breast cancer patients. Our aim is to identify risk factors for financial toxicity amongst breast cancer patients undergoing surgical treatment. Methods: This is a single-institution cross-sectional survey of adult female breast cancer patients who underwent lumpectomy or mastectomy between January 2018 and June 2019. Financial toxicity was measured via the 11-item comprehensive score for financial toxicity (COST) instrument. Responses were linked with data on patient demographics and clinical history abstracted from the corresponding medical record. Multivariate regression was used to identify patient- and treatment-level factors associated with worsening financial toxicity. Secondary outcome measures included self-reported coping strategies for high treatment costs. Results: A total of 571 patients were included; overall, these individuals were mostly white (76.0%), in-state residents (72.3%), and married (73.0%). Following multivariate analysis, lower financial distress was associated with the use of supplemental insurance, increasing annual household income, and a higher credit score (score > 740). Conversely, work reduction or cessation, increased out-of-pocket spending, advanced tumor stage, and being employed at the time of diagnosis were associated with increased financial distress. Patients with higher reported financial distress were more likely to decrease their spending on food, clothing, and leisure activities. Conclusions: Financial toxicity was associated with baseline demographic, disease, and treatment characteristics in our cohort of insured patients. These characteristics may be critical opportunities for interventions related to financial navigation along the treatment continuum. [ABSTRACT FROM AUTHOR]

C57BL/6 mice implanted in the flank with murine Lewis lung carcinoma cells were randomized into control, anti-angiogenic, anti-PD-L1, radiotherapy (RT), RT + anti-angiogenic, RT + anti-PD-L1, and RT + anti-PD-L1 + anti-angiogenic therapy groups. Immune response and immunophenotyping were determined by flow cytometry. Vasculature analysis after RT and anti-angiogenic therapy was assessed by quantified power Doppler sonography. Antitumor response, survival, and rechallenged tumor growth were evaluated. RT increased PD-L1 expression on CD8+ T, CD4+ T, dendritic, myeloid-derived suppressor cells (MDSCs), and tumor cells and increased PD-1 expression on CD8+ and CD4+ T cells. Anti-angiogenic therapy insignificantly decreased the RT-induced PD-1 expression on CD8+ and CD4+ T cells, implying a weak reversal of the immune-suppressive environment. Transient vessel collapse was observed within days after RT, and blood flow recovered at 1 week after RT. RT + anti-PD-L1 suppressed the tumor growth, improved survival, and prolonged immune memory capable of protecting against tumor recurrence, evidenced by local accumulation of CD8+ T cells and reduction in MDSCs in microenvironment. Similar and more prominent effects were observed when anti-VEGF was added to RT + anti-PDL1 therapies, implying an additive, rather than synergistic, antitumor immunity. Phenotypic analyses revealed that anti-cancer treatments increased the proportion of effector memory T cells in TILs and splenocytes, and RT, alone or in combination with other treatments, further increased the proportion of central memory T cells in splenocytes. These results provide evidence on operating the immunosuppressive tumor environment and offer insights into the design of the new combination treatment. [ABSTRACT FROM AUTHOR]

Purpose: Contralateral prophylactic mastectomy (CPM) is increasingly performed in average-risk patients despite the lack of survival benefit. In an era of heightened awareness of healthcare costs, we sought to determine the impact of CPM on financial toxicity in breast cancer. Methods: A single-institution propensity-matched analysis of female patients who underwent unilateral mastectomy (UM) with or without CPM for breast cancer over an 18-month period. Patients with a history of genetic predisposition or bilateral cancer were excluded. The validated Comprehensive Score for financial Toxicity (COST) evaluated financial toxicity among participants. Multivariable regression analysis evaluated the relationship between CPM and financial toxicity. Relevant domains of the Breast Q and SF12 instruments were examined as secondary outcomes. Sensitivity analysis was performed using propensity-weighting to examine robustness of results and increase our sample size. Results: Overall, 104 patients were identified, equally distributed across UM and CPM. CPM was not associated with financial toxicity, as evidenced by comparable COST scores (adjusted difference, 1.53 [− 3.24 to 6.29]). Minor complications were significantly lower in UM patients (UM, 8%; CPM, 31%). CPM was associated with significantly higher Breast Q psychosocial well-being score (adjusted difference, 10.58 [1.34 to 19.83]). BREAST Q surgeon satisfaction, SF12 mental and physical component scores were comparable. Similar results were noted on sensitivity analysis involving 194 patients. Conclusions: Choice for CPM was associated with higher minor complications, but led to improved psychosocial well-being without a higher degree of patient-reported financial toxicity. Prospective studies are needed to discern the influence of CPM on the incidence and trajectory of financial toxicity. [ABSTRACT FROM AUTHOR]

Sarcopenia is highly prevalent in patients undergoing chronic hemodialysis (HD). This study investigated the relationship among serum indoxyl sulfate (IS) levels, muscle mass, and strength in HD patients. A total of 108 HD patients were enrolled. Skeletal muscle mass and handgrip strength (HGS) were assessed, using bioimpedance analysis and a hand-held dynamometer, respectively. Skeletal muscle index (SMI) was defined as skeletal muscle mass/height2 (kg/m2). Serum IS, p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO) levels were determined using liquid chromatography–mass spectrometry. Patients were classified into two groups based on median serum IS values. HGS measurement was repeated after 2 years. Patients in the high IS group had longer HD duration and higher serum TMAO levels than those in the low IS group. Log-normalized IS level was negatively correlated with SMI (r = − 0.227; p = 0.018), but PCS and TMAO levels were not. Among 78 patients who completed 2-year follow-up, those in the high IS group (n = 41) showed greater absolute (− 2.48 kg versus − 0.25 kg, p = 0.035) and relative HGS loss (− 9.1% versus 1.4%, p = 0.036) than those in the low IS group, after adjustment for potential confounders. Indoxyl sulfate (IS) may play a significant role in uremic sarcopenia. Further large-scale studies are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

This paper extends one of the most extensively used multiple criteria decision analysis (MCDA) methods, the technique for order preference by similarity to ideal solutions (TOPSIS), to adapt to highly complicated uncertain environments based on interval-valued Pythagorean fuzzy (IVPF) sets. In contrast to classical TOPSIS methods, this paper develops a novel concept of Pearson-like IVPF correlation coefficients instead of distance measures to not only construct a useful and effective association measure between two IVPF characteristics but also depict the outranking relationship of IVPF information. Moreover, this paper proposes the (weighted) IVPF correlation-based closeness coefficients to establish a Pearson-like correlation-based TOPSIS model to manage MCDA problems within the IVPF environment. In particular, there is a definite improvement in determining the closeness coefficient required in the TOPSIS procedure. This paper considers anchored judgments with respect to the positive- and negative-ideal IVPF solutions and provides new approach- and avoidance-oriented definitions for the IVPF correlation-based closeness coefficient, which is entirely different from the traditional definition of relative closeness in TOPSIS. Furthermore, this paper proposes a comprehensive IVPF correlation-based closeness index to balance the consequences between ultra-approach orientation and ultra-avoidance orientation and acquire the ultimate compromise solution for decision support and aid. The feasibility and practicability of the developed methodology are illustrated by a practical MCDA problem of rehabilitation treatment for hospitalized patients with acute stroke. The application results, along with experimentations and comparative analyses, demonstrate that the developed methods are rational and effective. [ABSTRACT FROM AUTHOR]

Background: The Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014 stipulates that standardized functional status (self-care and mobility) and cognitive function data will be used for quality reporting in post-acute care settings. Thirty-day post-discharge unplanned rehospitalization is an established quality metric that has recently been extended to post-acute settings. The relationships between the functional domains in the IMPACT Act and 30-day unplanned rehospitalization are poorly understood.Objective: To determine the degree to which discharge mobility, self-care, and cognitive function are associated with 30-day unplanned rehospitalization following discharge from post-acute care.Design: This was a retrospective cohort study.Setting: Inpatient rehabilitation facilities submitting claims and assessment data to the Centers for Medicare and Medicaid Services in 2012-2013.Participants: Medicare fee-for-service enrollees discharged from post-acute rehabilitation in 2012-2013. The sample included community-dwelling adults admitted for rehabilitation following an acute care stay who survived for 32 days following discharge (N = 252,406).Interventions: Not applicable.Main Measures: Thirty-day unplanned rehospitalization following post-acute rehabilitation.Key Results: The unadjusted 30-day unplanned rehospitalization rate was 12.0 % (n = 30,179). Overall, patients dependent at discharge for mobility had a 50 % increased odds of rehospitalization (OR = 1.50, 95 % CI: 1.42-1.59), patients dependent for self-care a 36 % increased odds (OR = 1.36, 95 % CI: 1.27-1.47), and patients dependent for cognition a 19 % increased odds (OR = 1.19, 95 % CI: 1.09-1.29). Patients dependent for both self-care and mobility at discharge (n = 8312, 3.3 %) had a 16.1 % (95 % CI: 15.3-17.0 %) adjusted rehospitalization rate versus 8.5 % (95 % CI: 8.3-8.8 %) for those independent for both (n = 74,641; 29.6 %).Conclusions: The functional domains identified in the IMPACT Act were associated with 30-day unplanned rehospitalization following post-acute care in this large national sample. Further research is needed to better understand and improve the functional measures, and to determine if their association with rehospitalizations varies across post-acute settings, patient populations, or episodes of care. [ABSTRACT FROM AUTHOR]

BACKGROUND: The risk of readmission varies among hospitals. This variation has led the Centers of Medicare and Medicaid services to reduce payments to hospitals with excess readmissions. The contribution of patient characteristics, hospital characteristics and provider type to the variation in risk of readmission among hospitals has not been determined. OBJECTIVE: To describe the variation in risk of readmission among hospitals and partition it by patient characteristics, hospital characteristics and provider type. DESIGN: Retrospective research design of 100 % Texas Medicare data using multilevel, multivariable models. SUBJECTS: A total of 514,064 admissions of Medicare beneficiaries to 272 hospitals in Texas for medical diagnoses during the years 2008 and 2009. MAIN MEASURES: Using hierarchical generalized linear models, we describe the hospital-specific variation in risk of readmission that is attributable to patients characteristics, hospital characteristics and provider type by measuring the variance and intraclass correlation coefficients. KEY RESULTS: Of the total variation in risk of readmission, only a small amount (0.84 %) is attributed to hospitals. In further analyses modeling the components of this variation among hospitals, differences in patient characteristics in the hospitals explained 56.2 % of the variation. Hospital characteristics and the type of provider explained 9.3 % of the variation among hospitals and 0.08 % of the total variation in risk of readmission. CONCLUSIONS: Patient characteristics are the largest contributor to variation in risk of readmission among hospitals. Measurable hospital characteristics and the type of inpatient provider contribute little to variation in risk of readmission among hospitals. [ABSTRACT FROM AUTHOR]

The characteristic strength properties of structural glulam connections assembled with self-tapping screws were examined following the ASTM testing procedure in the study. Four screw types with various numbers were designated at each connection of the beam-girder structure with different nailing schedules. The results indicated that the maximum load capacity and dissipated energy of a connection fastened with 10-mm self-tapping screws were higher than those with 8-mm screws. And, the screws with both double-threaded sections and fully threaded shanks were higher than those of single-threaded screws. An improvement on the initial stiffness of a connection was found when the number of self-tapping screws increased. The connections assembled with the toe-nailing approach from the beam's bottom surface provided higher maximum loading capacity, medium initial stiffness, and a larger ductility factor, resulting in higher dissipated energy with less fragile failure. The derived allowable loading values for a beam-girder connection fastened with self-tapping screws using the face-nailing approach were close to the code values for bolted and pinned connections. And, a toe-nailing approach provided higher allowable loads for connections than using a face-nail approach. [ABSTRACT FROM AUTHOR]

BACKGROUND: There have been no prior population-based studies of variation in performance of hospitalists. OBJECTIVE: To measure the variation in performance of hospitalists. DESIGN: Retrospective research design of 100 % Texas Medicare data using multilevel, multivariable models. SUBJECTS: 131,710 hospitalized patients cared for by 1,099 hospitalists in 268 hospitals from 2006-2009. MAIN MEASURES: We calculated, for each hospitalist, adjusted for patient and disease factors (case mix), their patients' average length of stay, rate of discharge home or to skilled nursing facility (SNF) and rate of 30-day mortality, readmissions and emergency room (ER) visits. KEY RESULTS: In two-level models (admission and hospitalist), there was significant variation in average length of stay and discharge location among hospitalists, but very little variation in 30-day mortality, readmission or emergency room visit rates. There was stability over time (2008-2009 vs. 2006-2007) in hospitalist performance. In three-level models including admissions, hospitalists and hospitals, the variation among hospitalists was substantially reduced. For example, hospitals, hospitalists and case mix contributed 1.02 %, 0.75 % and 42.15 % of the total variance in 30-day mortality rates, respectively. CONCLUSIONS: There is significant variation among hospitalists in length of stay and discharge destination of their patients, but much of the variation is attributable to the hospitals where they practice. The very low variation among hospitalists in 30-day readmission rates suggests that hospitalists are not important contributors to variations in those rates among hospitals. [ABSTRACT FROM AUTHOR]

Background: There are no clear recommendations to guide posttreatment surveillance in patients with pancreatic cancer. Our goal was to describe the posttreatment surveillance patterns in patients undergoing curative-intent resection for pancreatic cancer. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data (1992-2005) to identify CT scans and physician visits in patients with pancreatic cancer who underwent curative resection ( n = 2393). Surveillance began 90 days after surgery, and patients were followed for 2 years at 6-month intervals. Patients were censored if they died, experienced recurrence of disease, or entered hospice. Results: A total of 2045 patients survived uncensored to the beginning of the surveillance period. CT scan use decreased from 20.9% of patients in month 4 to 6.4% in month 27. There was no temporal pattern in CT use to suggest regular surveillance. Twenty-three percent of patients did not receive a CT scan in the year after surgery, increasing to 42% the second year. Patients who underwent adjuvant therapy and patients diagnosed in later years had higher CT scan use over the surveillance periods. Most patients visited both a primary care physician and a cancer specialist in each 6-month surveillance period. Patients who visited cancer specialists were more likely to have any CT scan and to be scanned more frequently. Conclusions: Current surveillance patterns after resection for pancreatic cancer reflect the lack of established guidelines, implying a need for evaluation and standardization of surveillance protocols. The lack of a temporal pattern in CT testing suggests that most were obtained to evaluate symptoms rather than for routine surveillance. [ABSTRACT FROM AUTHOR]

The structural performance of finger-jointed laminated bamboo was investigated for two bamboo species by considering the finger length, profile orientation, lamination direction, culm growth height, and mechanical properties of bamboo materials. Based on the growth height variation and bamboo species, the best finger-jointed laminated bamboo was found for the lamina processed from the middle growth height of a moso bamboo culm with the finger profile shown on the width face of the beam. It was 38.7% higher in bending strength than the lowest group, with the lamina from the lower ma bamboo culm showing the finger profile on the thickness face of the beam. When considering the finger length and lamination orientation, the strongest finger-jointed laminated bamboo joined with an 18-mm finger, showing the finger profile on the width face of a vertically laminated beam was 50.1% higher in bending strength than the lowest group having a 12-mm finger showing the finger profile on the thickness face of a vertically laminated beam. The laminated ma bamboo showed higher finger-joint efficiency, 11.6%, than moso bamboo, and the members showing the finger profile on the width surface was 12.3% better in joint efficiency than that showing on the thickness surface of the beam. [ABSTRACT FROM AUTHOR]

Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours, but the mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs. [ABSTRACT FROM AUTHOR]

5-year-old boy suffering from abdominal pain accompanied by a fever of up to 39.5°C for 2 days was admitted to the hospital. Although Flomoxef was administered following admission, the boy's fever persisted and abdominal distension gradually worsened. On the 4th day, dry lips, red eyes and a strawberry tongue were noted. An echocardiogram revealed pericoronary enhancement with mild mitral valve regurgitation and a small degree of pericardial effusion, characteristics compatible with Kawasaki disease. Although intravenous immunoglobulin was administered, the fever and abdominal distension persisted. On the 8th day, a pediatric surgeon was consulted and an exploratory laparotomy was arranged. During the operation, intestinal pseudo-obstruction and fibrin coatings around the intestine near the splenic flexure were found. A colostomy was performed for decompression of the dilated bowel and a biopsy of the lymph node surrounding the splenic flexure was taken. The fever subsided dramatically after decompression of the bowel and the recovery course was uneventful. The pathologic report revealed necrotic lymphadenitis. We report this rare case and review the literature. [ABSTRACT FROM AUTHOR]