New protocol for contrast media reduction in atrial fibrillation ablation-planning CT with dual region of interest.

INTRODUCTION: Many patients with atrial fibrillation have impaired renal function, and therefore pre-operative CT for radiofrequency catheter ablation should minimize the use of contrast media. This study describes a dual-region-of-interest (D-ROI) protocol for the scanning of pulmonary veins and left atrium (PVs-LA) with less contrast media and optimized scan timing compared to the single-region-of-interest (S-ROI) protocol, without compromising image quality. METHODS: This study retrospectively included 100 patients who underwent PVs-LA CT between July 2019 and February 2022. The participants were divided into two groups: Those scanned using the S-ROI method (Group A, n = 50), and those scanned using the D-ROI method (Group B, n = 50). Descriptive statistical analysis of the contrast effect and scan timing was performed using quantitative and qualitative data collected from both groups of images. RESULTS: The contrast media dose was larger in group A than in group B (63.6 ± 10.1 mL vs. 45.6 ± 6.9 mL; p < 0.001). The CT values of the PVs-LA did not differ significantly between groups A and B [434.2 ± 77.0 Hounsfield units (HU) and 428.8 ± 77.2 HU, respectively; p = 0.73]. Two evaluators determined appropriate scan timing (when PVs-LA reached a relatively sufficient contrast effect for diagnosis) in 23 (46%) and 45 (90%) patients from groups A and B, respectively (p < 0.001). CONCLUSIONS: Although the radiation dose is slightly increased compared with the S-ROI method, the D-ROI method provides improved scan timing and images with similar contrast enhancement while reducing the amount of contrast medium administered. IMPLICATIONS FOR PRACTICE: The novel D-ROI bolus tracking technique can reduce the contrast medium dose while optimizing scan timing.

A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer.

BACKGROUND: miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. METHODS: RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). RESULTS: miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. CONCLUSIONS: A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.

IDENTIFICATION OF NOVEL BIOMARKERS FOR LUNG CANCER RISK IN HIGH LEVELS OF RADON BY PROTEOMICS: A PILOT STUDY.

Radon is the second most important risk factor for lung cancer after tobacco smoking. In Chiang Mai, Thailand, the values of indoor radon activity concentrations are considerably higher than global average values and it is a highest level among East Asian countries. The aim of our study is to identify novel biomarkers for lung cancer risk in high radon areas using a proteomic approach. In our transitional study, a total of 81 participants of non-smokers were examined, consist of 25 lung cancer patients (LC), 16 healthy controls from low levels of natural radiation areas (LLNRA) and 40 healthy controls from high levels of natural radiation areas (HLNRA). The results showed that a total of 799 differentially expressed proteins were identified. Among these, a total of 25 proteins were observed in both LC and HLNRA, but not in LINRA. Owing to the results obtained from this study, we also point out the research direction regarding the validation of some new candidate protein as a biomarker to screen population with high risk for lung cancer in the area with high levels of radon.

Page Kidney Following a Nonepisode Protocol Renal Allograft Biopsy: A Case Report.

Page kidney refers to a clinical condition that is characterized by the acute onset of hypertension and renal dysfunction owing to external compression of the kidney by a hematoma, tumor, lymphocele, or urinoma. We report a case in which Page kidney occurred after a nonepisode protocol renal allograft biopsy. A 31-year-old man with end-stage renal disease received a living related kidney transplant from his father. One year later, a nonepisode protocol renal allograft biopsy was performed. A day later, the patient's serum creatinine level increased to 4.23 mg/dL, and a subcapsular renal hematoma was detected using ultrasonography and computed tomography. Page kidney was diagnosed, and immediate surgical removal of the hematoma was performed. Nine days after the operation, the patient's serum creatinine level had improved to 1.89 mg/dL. Page kidney is a serious but treatable complication of renal allograft biopsies, and clinicians should pay attention to such complications, even in the setting of nonepisode protocol renal allograft biopsies.

A potential role for the silent information regulator 2 homologue 1 (SIRT1) in periapical periodontitis.

AIM: To investigate the role played by silent information regulator 2 homologue 1 (SIRT1) during angiogenesis of periapical periodontitis. METHODOLOGY: Periapical granulomas were subjected to dual-colour immunofluorescence imaging and real-time polymerase chain reactions assaying the expression levels of SIRT1, vascular endothelial growth factor (VEGF) and VE-cadherin. The association between Ki-67 and SIRT1 expression was also examined. Human umbilical vein endothelial cells (HUVECs) were treated with a combination of lipopolysaccharide and resveratrol (a SIRT1 activator) or sirtinol (a SIRT1 inhibitor); and the levels of mRNAs encoding SIRT1, VEGF and VE-cadherin were determined. HUVEC tube formation was assayed in the presence of resveratrol or sirtinol. The Mann-Whitney U-test or the Tukey-Kramer test was used for statistical analysis. RESULTS: Ki-67-expressing cells, including endothelial cells, lay adjacent to SIRT1-expressing cells in periapical granulomas. In addition, SIRT1-expressing cells were detected adjacent to VEGF-expressing cells and VEGF- or VE-cadherin-expressing endothelial cells. SIRT1, VEGF and VE-cadherin mRNA expression levels in periapical granulomas were significantly higher (P = 0.0054, 0.0090 and 0.0090, respectively) than those in healthy gingival tissues. HUVECs treated with resveratrol exhibited significantly higher expression of mRNAs encoding SIRT1, VEGF and VE-cadherin (P = 0.0019, 0.00005 and 0.0045, respectively) compared with controls, but sirtinol inhibited such expression. Resveratrol caused HUVECs to form tube-like structures, whilst sirtinol inhibited this process. CONCLUSIONS: These findings suggest that SIRT1 may stimulate angiogenesis in periapical granulomas by triggering the proliferation of endothelial cells and inducing VEGF and VE-cadherin expression.

Change in oral health status associated with menopause in Japanese dental hygienists.

OBJECTIVES: Oral symptoms such as xerostomia and burning mouth syndrome have been recognized to increase associated with menopause. The purpose of this study was to clarify the changes in oral health as well as systemic health due to menopause and their relations with hormonal change and mental status. METHODS: Ninety-seven female dental hygienists aged 40-59 years were assigned to premenopausal, menopausal and post-menopausal groups based on self-reported menstrual condition. Subjective health statuses were evaluated by questionnaire, and objective holistic and oral statuses were evaluated by measuring serum 17ß-estradiol (E2), salivary flow rate, α-amylase and secretory IgA (SIgA) and taste sensitivity. RESULTS: A significant difference among the three groups was observed in the self-rating questionnaire of depression (SRQ-D) score and serum E2 level as well as unstimulated salivary flow rate, whereas no significant difference was observed in Simplified menopausal index, Short-Form 36-Item Health Survey, General Oral Health Assessment Index, salivary α-amylase activity, salivary SIgA concentration and taste threshold. Serum E2 levels positively correlated with unstimulated salivary flow rates and negatively correlated with SRQ-D scores and α-amylase activities. CONCLUSIONS: The results demonstrated a negative correlation between E2 levels and SRQ-D scores as well as salivary α-amylase activities, suggesting an influence of E2 on mental condition. Furthermore, E2 decrease may result in reduction of salivary flow which in turn causes various problems of oral health. Since the participants were graduates from several dental hygienist schools and working at various places, these results can be generalized to Japanese dental hygienists to some extent.

Orthotopic Kidney Transplantation in an Elderly Patient With Various Severe Comorbid Conditions: A Case Report.

In recent years, the frequency of high-risk kidney transplantations has increased. We report a case in which a 72-year-old man with various severe comorbidities (prostate cancer, diabetes mellitus, complete atrioventricular block, coronary artery stenosis, severe stenosis of the popliteal arteries, and severe calcification of the iliac arteries) who received an orthotopic kidney transplantation. To prevent the occurrence of acute limb ischemia due to the steal phenomenon (caused by the kidney graft), we decided that a heterotopic kidney transplantation involving the iliac arteries was not an appropriate option. Therefore, as an alternative, left native nephrectomy was performed followed by an orthotopic kidney transplantation to the native renal artery and renal vein through a left subcostal incision. Postoperative ureteral stenosis occurred, and so stent exchange was required every 6 months. Despite the ureteral complication, the patient's serum creatinine level was 1.5 mg/dL at 2 years after the procedure.

Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection.

BACKGROUND: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated. METHODS: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group. RESULTS: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3-1570) ml (P = 0·048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0·043). CONCLUSION: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm).

Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report.

BACKGROUND: A significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx). CASE REPORT: A 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232 cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy. CONCLUSIONS: A case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.

The role of PSMB9 upregulated by interferon signature in the pathophysiology of cutaneous lesions of dermatomyositis and systemic lupus erythematosus.

BACKGROUND: Dermatomyositis (DM) and systemic lupus erythematosus (SLE) have common skin features, including dermal mucin deposition and interferon signature, although their roles are unknown. OBJECTIVES: To identify common or specific molecular changes in DM and SLE skin. METHODS: Proteomic analysis was performed using DM and healthy skin. Glycosaminoglycans were analysed by high-performance liquid chromatography. RESULTS: The expression of 60 proteins was upregulated or downregulated in DM skin compared with healthy skin in the proteomic analysis. Among those proteins, PSMB9, an immunoproteasome subunit, was upregulated in the epidermis of DM and SLE, but not in other skin diseases. Furthermore, versican V1, a core protein for glycosaminoglycans, was upregulated, while type I collagen was downregulated in the dermis of DM and SLE skin. Interferon stimulated PSMB9 expression in cultured keratinocytes and reduced collagen expression in dermal fibroblasts, but did not affect versican expression. The PSMB9 knock-down in keratinocytes led to significant suppression of transforming growth factor (TGF)-ß2 and TGF-ß3, inducers of versican synthesis. TGF-ß3 expression was upregulated in both DM and SLE, while TGF-ß2 expression was increased only in the DM epidermis. ΔDiHS-diS1, a component of heparan sulfate, was significantly increased only in DM. TGF-ß2 expression significantly increased the ΔDiHS-diS1 expression in dermal fibroblasts in vitro. CONCLUSIONS: The interferon signature in DM and SLE skin reduces collagen in dermal fibroblasts, whereas overexpression of PSMB9 induced by interferon stimulates versican inducers in epidermal keratinocytes. In addition, the TGF-ß2-ΔDiHS-diS1 pathway may be responsible for the specific molecular change in DM skin.

Comparative dosimetry for radon and thoron in high background radiation areas in China.

The present study focuses on internal exposure caused by the inhalation of radon and thoron progenies because the internal exposures have not yet been clarified. For their dose assessment, radon, thoron and thoron progeny concentrations were measured by passive monitors over a long period (for 6 months). Consequently, radon, thoron and equilibrium equivalent thoron concentrations were given as 124 ± 78, 1247 ± 1189 and 7.8 ± 9.1 Bq m(-3), respectively. Annual effective doses are estimated to be 3.1 ± 2.0 mSv for radon and 2.2 ± 2.5 mSv for thoron. Total dose are estimated to be 5.3 ± 3.5 mSv a(-1). The present study has revealed that the radon dose was comparable with the thoron dose, and the total dose was ∼2 times higher than the worldwide average.

Urinary tract reconstruction using uretero-ureteral end-to-side anastomosis in kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, the most widely used method for the reconstruction of the urinary pathway is ureteroneocystostomy, which may be difficult in cases with disused atrophic bladder. In this study, we evaluated kidney transplant recipients who underwent uretero-ureteral end-to-side anastomosis (UUA) in urinary reconstruction due to disused atrophic bladder. METHODS: To clarify the effectiveness of this method, we retrospectively reviewed the clinical records of kidney transplant recipients in our hospital. RESULTS: A total of 9 recipients with urinary reconstruction using UUA were evaluated. All of these patients had a history of long-term hemodialysis before transplantation, accompanied by complete anuria and small capacity of the bladder. In 4 patients, cranial native ureter was ligated, whereas it was not ligated in the remaining 5 patients. In 2 of 4 patients with cranial ligation, hydronephrosis developed in the native kidney with no further treatment being required. No patients experienced urinary tract complications including hydronephrosis in the graft, urine extravasation, or urinary tract infection in the follow-up period (757.6 ± 491.3 days). Allograft function was maintained well in all patients (serum creatinine level, 1.08 ± 0.23 mg/dL). CONCLUSIONS: Although UUA is not a routine method of urinary reconstruction in kidney transplantation, it can be safely performed and should be a surgical option, especially for recipients with disused atrophic bladder. The ligation of cranial native ureter may lead to hydronephrosis of the native kidney, and it is tentatively concluded that UUA without native ureteral ligation is clinically feasible.

Discrimination of lymph node metastases using desorption electrospray ionisation-mass spectrometry imaging.

Desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) has been used for the identification of cancer within lymph nodes with accurate spatial distribution in comparison to gold standard matched immuno-histopathological images. The metabolic profile of the cancerous lymph nodes was similar to that of the primary tumour site.

Note: Near-field imaging of thermal radiation at low temperatures by passive millimeter-wave microscopy.

Imaging of thermal radiation with a spatial resolution below the diffraction limit is demonstrated with a passive millimeter-wave microscope. This technique utilizes a sensitive radiometric receiver in combination with a scanning near-field microscope. Experiments were performed at 50 GHz (λ = 6 mm) with sample temperatures ranging from room temperature down to 160 K, and the performance was shown to be superior to that achieved with passive imaging systems in the infrared region. The images are affected by non-uniformities in the transmission of thermal radiation from the sample to the receiver via the near-field probe and the reflection of thermal radiation back to the receiver from the probe. The effects of these non-uniformities were successfully removed using a sample image acquired by active measurements using a vector network analyzer.

Pilocytic astrocytomas in elderly adults.

Pilocytic astrocytomas are classified as WHO grade I gliomas that occur predominantly in children and young adults. Reports of the tumors in elderly adults are extremely rare. We describe two cases of pilocytic astrocytoma in elderly adults, a 68-year-old man and a 71-year-old woman. Brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed well-circumscribed lesions associated with contrast enhancement and minimal surrounding edema. Pathological studies revealed findings consistent with pilocytic astrocytomas. Although these tumors are rarely found in elderly adults, pilocytic astrocytomas should be considered in the differential diagnosis if the radiographic features of the tumors are characteristic of pilocytic astrocytomas.

The role of the transcription factor AP-1 in colitis-associated and beta-catenin-dependent intestinal tumorigenesis in mice.

Chronic inflammation is an important cancer risk factor but the molecular pathways linking inflammation and cancer are incompletely understood. The transcription factor c-Jun/AP-1 (activator protein 1) is involved in inflammatory responses and tumorigenesis and has been proposed as an essential mediator of oncogenic beta-catenin signaling in the intestine. Here, we examined the functions of c-Jun in two distinct mouse models of conditional and intestine-specific activation of beta-catenin. c-Jun is strongly expressed in the small intestine of mutant mice. However, beta-catenin-dependent cell proliferation is surprisingly not affected in mice lacking c-jun in intestinal epithelium, suggesting that c-Jun is not an essential immediate target of beta-catenin signaling in the small intestine. To examine the functions of Jun and Fos proteins during inflammation and cancer in the colon, colitis-associated tumors were induced chemically in the respective knockout mice. Tumors were characterized by activated beta-catenin and strongly expressed c-Jun and JunB. However, tumorigenesis was not affected by inactivation of c-Jun in either intestinal epithelium or myeloid cells. Moreover, tumorigenesis was not altered in mice lacking junB, junD, c-fos, fra-1 or fra-2, suggesting that inhibition of c-Jun or other single AP-1 proteins is not a determining factor in colitis-associated cancer in mice.

Effects of colloidal iron overload on renal and hepatic siderosis and the femur in male rats.

Genetic hemochromatosis is an iron overload disorder, and osteopenic and osteoporotic. Femoral neck bone mineral density (BMD) appears to fall with rising hepatic iron concentrations. A critical role for iron in mediating tissue injury is played via hydroxyl radical formation in nephrotoxicity. We investigated the effects of a colloidal iron overload on renal function, organ siderosis, and femoral bone in male rats. Iron overload reduced body growth, and increased the weights of the liver and spleen. Marked deposition of iron was noted in liver and kidney. Activities of lactate dehydrogenase and alkaline phosphatase were decreased, and the concentrations of blood urea nitrogen and creatinine were increased with the reduction in plasma calcium and inorganic phosphorus levels, i.e. functions of the liver and kidney might be affected by reactive oxygen species such as the superoxide radical, H2O2, and the hydroxyl radical produced by overloaded iron. Damage to the proximal tubular epithelial cells of the kidney and a loss of connectivity of cancellous bone in the epiphysis and of trabecular bone in the metaphysis of the distal femur were observed in iron-overloaded rats with a reduction of femoral bone mineral density, i.e. reabsorption of calcium from the proximal tubular epithelial cells of the kidney might be affected and urinary discharge of calcium might be elevated. It was suggested that iron overload gave rise to osteoporosis combined with renal dysfunction and liver iron overload syndrome.

Kudo type-5 total elbow arthroplasty in mutilating rheumatoid arthritis: a 5- to 11-year follow-up.

We studied 11 patients (14 elbows) with gross rheumatoid deformity of the elbow, treated by total arthroplasty using the Kudo type-5 unlinked prosthesis, and who were evaluated between five and 11 years after operation. Massive bone defects were augmented by autogenous bone grafts. There were no major complications such as infection, subluxation or loosening. In most elbows relief from pain and stability were achieved. The results, according to the Mayo Elbow Performance Score, were excellent in eight, good in five and fair in one. In most elbows there was minimal or no resorption of the grafted bone. There were no radiolucent lines around the stems of the cementless components. This study shows that even highly unstable rheumatoid elbows can be replaced successfully using an unlinked prosthesis, with augmentation by grafting for major defects of bone.

Comparison of two types of ulnar component in type-5 Kudo total elbow arthroplasty in patients with rheumatoid arthritis: a long-term follow-up.

The purpose of this study was to assess the long-term results (more than ten years) of two types of cemented ulnar component with type-5 Kudo total elbow arthroplasty in a consecutive series of 56 patients (60 elbows) with rheumatoid arthritis, and to compare the results in elbows above and below a Larsen grade IV. There was no radiolucency around the humeral component. Patients in whom a metal-backed ulnar component and a porous-coated stem were used had better clinical results and significantly less progression of radiolucent line formation around the ulnar component. They also had a significantly better long-term survival than patients with an all-polyethylene ulnar component. The clinical results of arthroplasty using all-polyethylene ulnar components were inferior, regardless of the degree of joint destruction. We conclude that the type-5 Kudo total elbow arthroplasty with cementless fixation of the porous-coated humeral component and cemented fixation of a metal-backed ulnar component is acceptable and well-tolerated by rheumatoid patients.