Improved Dosimetry with Daily Online Adaptive Radiotherapy for Cervical Cancer: Waltzing the Pear.

AIMS: Standard of care radiotherapy for locally advanced cervical cancer includes large margins to ensure the uterocervix remains within the treatment fields over the course of treatment. Daily online cone-beam adaptive radiotherapy corrects for interfractional changes by adjusting the plan to match the target position during each treatment session, thus allowing for significantly reduced clinical target volume (CTV) to planning target volume (PTV) margins. We hypothesise that reduced margins from daily online adaptive radiotherapy will reduce organ at risk dose without compromising target coverage. MATERIALS AND METHODS: Ten patients with cervical cancer (stage IIB-IIIC2) were treated with definitive chemoradiation using daily online cone-beam adaptive radiotherapy in 25-27 fractions. Initial and all adapted treatment plans were generated with CTV to PTV margins versus standard of care image-guided radiotherapy (IGRT) plans as follows: cervix/uterus/gross tumour volume (0.5 versus 1.5 cm), parametria/vagina (0.5 versus 1.0 cm) and nodal chains and gross nodes (0.5 versus 0.5 cm). IGRT plans were created and copied to synthetic computed tomography scans and contours generated from each daily adapted fraction. The dosimetry of each clinically treated online adapted fraction was compared with emulated IGRT plans. Statistical significance was defined as P < 0.05. RESULTS: Daily online cone-beam adaptive radiotherapy significantly improves bowel bag dosimetry compared with IGRT, with a reduction in V40 by an average of 91.3 cm3 [V40 (-6.2%) and V45 (-6.1%)]. The daily adapted plans showed significant improvements in bladder and rectum [V40 (-25.2% and -36.0%) and V30 (-9.7% and -17.1%), respectively]. Additionally, bone marrow had a significantly reduced dose [V10 (-2.7%) and V20 (-3.3%)]. Daily online cone-beam adaptive radiotherapy improved uterocervix CTV coverage and reduced hotspots compared with IGRT [D95% (+1.6%) and Dmax (-0.9%)]. CONCLUSIONS: Reduced CTV to PTV margins achievable with daily online adaptive radiotherapy improves organ at risk dosimetry and target coverage when compared with standard of care IGRT for locally advanced cervical cancer. The clinical impact of improved dosimetry is currently undergoing investigation.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

OBJECTIVES: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. DESIGN: A community-based longitudinal cohort study. SETTING: Yuanshan township in Yi-Lan County, Taiwan. PARTICIPANTS: A total of 889 community-dwelling residents aged 50 years or older. MEASUREMENTS: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. RESULTS: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. CONCLUSIONS: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Long-Term Mortality Risk in Older Adults with Sarcopenia: An 11-Year Prospective Cohort Study Comparing AWGS 2014 and AWGS 2019 Guidelines for Enhanced Clinical Utility and Accurate Risk Prediction.

OBJECTIVES: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. DESIGN: A prospective population-based cohort study. SETTING AND PARTICIPANTS: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. MEASUREMENTS: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. RESULTS: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. CONCLUSION: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.

Clinical Efficacy of Multidomain Interventions among Multimorbid Older People Stratified by the Status of Physio-Cognitive Declines: A Secondary Analysis from the Randomized Controlled Trial for Healthy Aging.

OBJECTIVES: To investigate the clinical efficacy of integrated multidomain intervention among community-living older adults with multimorbidity and physio-cognitive decline syndrome (PCDS). DESIGN, SETTING AND PARTICIPANTS: This is the secondary analysis from a randomized controlled trial that data of 340 participants with Montreal Cognitive Assessment (MoCA) scores≥18 were excerpted for analysis. INTERVENTION: Sixteen 2-hour sessions per year were provided for participants, including physical exercise, cognitive training, dietician education and individualized integrated care for multimorbidity. MEASUREMENTS: Handgrip strength, 6-m walking speed, MoCA (total score and sub-domains), Cardiovascular Health Study (CHS) frailty score, quality of life, and serum biochemistry biomarkers. RESULTS: Overall, 96/340 (28.2%) of all participants have PCDS, and the integrated multidomain intervention significantly improved global cognitive performance (overall difference 1.1, 95% CI 0.4 - 1.8, p=0.003), and domains of concentration (overall difference 0.3, 95%CI 0.1 - 0.5, p=0.011), language (overall difference 0.2, 95%CI 0.1 - 0.3, p=0.006), abstract thinking (overall difference 0.1, 95%CI 0.0 - 0.3, p=0.027), and orientation(overall difference 0.2, 95%CI 0.0 - 0.4, p=0.013) across all timepoints among those with PCDS. Besides, interventions also significantly reduced frailty score among those with cognitive impairment no dementia (overall difference -0.3, 95%CI -0.5 - -0.1, p=0.011) and mobility impairment no disability (overall difference -0.3, 95%CI -0.4 - -0.1, p=0.004). and improved quality of life at domain of physical role limitation among those with PCDS (overall difference 5.3, 95%CI 0.3 - 10.4, p=0.038). CONCLUSIONS: The integrated multidomain lifestyle intervention plus multimorbidity management significantly improved cognitive function, and enhanced quality of life among older adults with multimorbidity and PCDS in the communities.

Nutritional Status and Renal Function in Relation to Frailty among the Community-Dwelling Elderly Taiwanese Population.

OBJECTIVES: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese. DESIGN: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. MEASUREMENTS: We measured nutritional status (including serum albumin and total protein levels), renal function (including serum blood urea nitrogen, creatinine, urine protein, and urine creatinine levels), hand grip strength (GS) and calculated appendicular muscle mass (AMM). RESULTS: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs). For the men with normal and weak GS, serum albumin levels were 4.15 ± 0.2 and 4.10 ± 0.2 g/dL (p < 0.01), and UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2 (p < 0.001), respectively. GS was positively correlated with serum albumin and urine creatinine levels (r = 0.136 and 0.177, both p < 0.001). AMM was also positively correlated with serum albumin and urine creatinine levels (r = 0.078 and 0.091, both p < 0.001). In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p < 0.05 and p < 0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR (urine creatinine for women) which presented a variance of 22.1% and 13.8%, respectively. CONCLUSION: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among elder population in Taiwan.

[Energy metabolism characteristic with risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease].

Objective: To investigate and analyze the energy metabolism characteristics and the correlation between energy metabolism and the risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease (HBV-CLD). Methods: Data of 183 cases admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2020 were retrospectively analyzed. 79 cases of chronic hepatitis B, 51 cases of hepatitis B-related liver cirrhosis, and 53 cases of hepatitis B-related liver failure were collected. Among them patients with liver failure and decompensated liver cirrhosis were defined as severe liver disease group. The Quark RMR indirect calorimetry (COSMED Corporation, Italy) was used to exam the patients' energy metabolism condition, and the incidences of secondary bacterial infection of the patients during hospitalization were recorded. Shapiro-Wilk test and normal QQ plot were used to analyze the normal distribution of continuous variable data, which was consistent with the normal distribution and was described by mean ± standard deviation. In addition, if it did not conform to the normal distribution, the median and interquartile distance were used to describe it. Levene's test was used to test the homogeneity of variance of the data, which was consistent with the normal distribution. The t-test was used to compare the means of the two groups of samples. One-way analysis of variance was used to compare the mean values of the three groups of samples, and then the Tukey's test was used to compare the two groups. If the variance was uneven or did not conform to the normal distribution, the Wilcoxon rank sum test was used to compare the differences between the two groups. Kruskal-Wallis test (H test) was used to compare the differences between the three groups of samples, and then the Dunnett's test (Z test) was used for comparison between the two groups. Categorical variable data were analyzed using chi-square test. Logistic regression analysis was used to screen independent risk factors, and the criteria for variable inclusion (P < 0.05). Results: The respiratory entropy (RQ) and non-protein respiratory entropy (npRQ) of the three groups had statistically significant difference (P < 0.05). Among them, the RQ and npRQ of the chronic hepatitis B group were higher than hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group. There were statistically significant differences in fat oxidation rate (FAT%) and carbohydrate oxidation rate (CHO%) between the three groups (P < 0.05). Compared with hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group, chronic hepatitis B group (P < 0.05) had lower FAT% and higher CHO%. There were no statistically significant differences in the measured and predicted resting energy expenditure and protein oxidation rate (PRO%) between the three groups. The incidence of secondary bacterial infection in patients with severe liver disease was 48.39% (45/93). Compared with the non-infected group, the RQ and npRQ values ​​of the infected group were significantly decreased (P < 0.05), while FAT% was significantly increased (P < 0.05). Logistic regression analysis showed that glutamyltransferase, cholesterol, and npRQ were independent risk factors for secondary bacterial infections in patients with severe liver disease. Glutamyltransferase elevation, and cholesterol and npRQ depletion had suggested an increased risk of secondary bacterial infection. Subgroup analysis of patients with hepatitis B-related liver failure also showed that compared with non-infected group, RQ value and npRQ value of secondary bacterial infection group were significantly decreased (P < 0.05), while FAT% was significantly increased (P < 0.05). Conclusion: Patients with hepatitis B virus-related chronic liver disease generally have abnormal energy metabolism. Low RQ, npRQ, CHO% and high FAT% are related to the severity of the disease; while npRQ reduction is related to the risk of secondary bacterial infection in patients with severe liver disease, and thus can be used as a clinical prognostic indicator.

Oral Nutritional Supplement with ß-hydroxy-ß-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial.

OBJECTIVES: Supplementation of high protein oral nutrition shakes supplemented with ß-hydroxy-ß-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. METHODS: This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. RESULTS: Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (ß=0.71, 95% C.I.0.09-1.33, P=0.026). CONCLUSIONS: The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

[Effect of overexpression of apoptosis-stimulating protein 2 of p53 on activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 and its mechanism].

Objective: To study the effect of apoptosis-stimulating protein 2 of p53 (ASPP2) on the activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 (TGF - ß1), and to explore the role of autophagy in this process. Methods: Mouse hepatic stellate cells were primarily isolated and cultured with green fluorescent protein (GFP) expressing empty vector adenovirus (Ad-GFP) and ASPP2 expressing adenovirus (Ad-ASPP2) for 12 h by transfection kit, and then treated with TGF-ß1 (10ng/ml) for 24 h. The experiments were grouped as follows: control group: green fluorescent protein (GFP) expressing empty vector adeno (Ad-GFP); experimental group 1: transfected with Ad-GFP and added with TGF-ß1; experimental group 2: transfected with Ad-ASPP2 and induced by TGF-ß1. Western blot and quantitative fluorescence PCR were used to detect the expression of ASPP2, α-smooth muscle actin (SMA). At the same time, autophagy was determined by microtubule-associated protein 1 light chain 3-ß (LC3). Autophagy and apoptosis of MHSc were observed by immunocytochemistry and RNA interference (RNAi). Multiple pairwise-comparisons between the mean of groups was performed by one-way ANOVA. Results: The relative expression of α-SMA mRNA in mHSC of TGF-ß1 + Ad-GFP group (16.83 ± 2.41) was significantly higher than Ad-GFP group (3.62 ± 0.56) (P < 0.05), while the relative expression of α-SMA mRNA (4.22 ± 0.48) in TGF-ß1 + Ad-GFP group was significantly lower than TGF-ß1 + Ad-GFP group (P < 0.05). The expression of α-SMA protein in each group was consistent with mRNA expression. The proportion of mHSC autophagy in TGF-ß1 + Ad-GFP group (80%) was significantly higher than Ad-GFP group (35%); however, there was no statistically significant difference between the two groups. The proportion of mHSC autophagy in TGF-ß1 + Ad-ASPP2 group was 42%, which was significantly lower than TGF-ß1 + Ad-GFP group, but the apoptotic rate was significantly increased. Cells were simultaneously treated with autophagy inhibitors 3-MA and TGF-ß1. The level of autophagy was not statistically significantly different from that of TGF-ß1 + Ad-ASPP2 group, but the apoptotic rate was increased. In addition, the RNAi group added with ASPP2 had increased autophagy (LC3-II/LC3-I) than control RNAi group, and the rate of apoptosis was significantly decreased. Conclusion: Overexpression of ASPP2 can alleviate the activation of mHSC and promote the apoptosis of HSC by inhibiting autophagy, so as to alleviate liver fibrosis.

Jagged2 promotes cancer stem cell properties of triple negative breast cancer cells and paclitaxel resistance via regulating microRNA-200.

OBJECTIVE: To investigate the role of Jagged2 in triple negative breast cancer (TNBC) and its underlying mechanism. PATIENTS AND METHODS: Breast cancer tissues of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong Hospital from January 2015 to September 2017 were selected. TNBC patients were divided into the paclitaxel-resistant group (n=34) and non-resistance group (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group before and after treatment was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel-resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset was detected by flow cytometry. MicroRNA-200 expression was detected after Jagged2 knockdown in MDA-MB-231/TXR cells. RESULTS: Jagged2 was highly expressed in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance induced by Jagged2 knockdown were reversed by microRNA-200 knockdown. CONCLUSIONS: Jagged2 maintains CSC properties of TNBC cells and paclitaxel resistance via regulating microRNA-200.

Aeromonas shuberti as a cause of multi-organ necrosis in internal organs of Nile tilapia, Oreochromis niloticus.

A disease with white spots in internal organs of Nile tilapia occurred in Zhanjiang, southern China. Multiple, white nodules, 0.8-2.2 mm in diameter, were scattered throughout the liver, spleen and kidney of diseased fish. Signs of nodules reproduced after artificial infection with the isolated strain. Isolated bacteria were Gram-negative, facultative anaerobic, motile, short rod-shaped, with a length of 1.2-2.2 µm. Morphological and biochemical tests, as well as phylogenetic analysis, all strongly indicated that the isolate from tilapia is identical to Aeromonas schubertii (A. schubertii) which temporary named LF1708 strain. Antibiotic sensitivity assays showed the LF1708 is sensitive to 24 of 27 tested antibiotics. Pathogenicity test revealed that the isolate at the dose of 3.75 × 106 CFU/g killed 100% of experimental tilapia within 2 days and the dose of 1 × 107 CFU/g killed 100% of experimental zebrafish within 1 day. Histopathology of diseased tilapia infected with A. schubertii showed numerous necrotic lesions widely distributed in spleen, liver and kidney, and infiltration with a large number of bacteria. To our knowledge, this was the first report that associated A. schubertii with mortality in tilapia.

Optimization of PMA-qPCR for Staphylococcus aureus and determination of viable bacteria in indoor air.

Staphylococcus aureus may cause infections in humans from mild skin disorders to lethal pneumonia. Rapid and accurate monitoring of viable S. aureus is essential to characterize human exposure. This study evaluated quantitative PCR (qPCR) with propidium monoazide (PMA) to quantify S. aureus. The results showed comparable S. aureus counts between exclusively live cells and mixtures of live/dead cells by qPCR with 1.5 or 2.3 µg/mL PMA (P>.05), illustrating the ability of PMA-qPCR to detect DNA exclusively from viable cells. Moreover, qPCR with 1.5 or 2.3 µg/mL PMA performed optimally with linearity over 103 -108  CFU/mL (R2 ≥0.9), whereas qPCR with 10, 23 or 46 µg/mL PMA significantly underestimated viable counts. Staphylococcus aureus and total viable bacteria were further determined with PMA-qPCR (1.5 µg/mL) from 48 samples from a public library and two university dormitories and four from outside. Viable bacteria averaged 1.9×104 cells/m3 , and S. aureus were detected in 22 (42%) samples with a mean of 4.4×103 cells/m3 . The number of S. aureus and viable bacteria were positively correlated (r=.61, P<.005), and percentages of S. aureus relative to viable bacteria averaged 12-44%. The results of field samples suggest that PMA-qPCR can be used to quantify viable S. aureus cells.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Factors Determining Physical and Mental Quality of Life of Living Kidney Donors in Taiwan.

BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.