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Objectives: The prognostic value of preimplantation nutritional status is not yet known for older diabetic patients that received right ventricular pacing (RVP). The study aimed to investigate the clinical value of the four malnutrition screening tools for the prediction of heart failure hospitalization (HFH) in older diabetic patients that received RVP. Design: Retrospective observational cohort study. Setting and Participants: This study was conducted between January 2017 and January 2018 at the Fuwai Hospital, Beijing, China, and included older (age ≥ 65 years) diabetic patients that received RVP for the first time Measurements: The Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Naples Prognostic Score (NPS), and the Controlling Nutritional Status (CONUT) score were used to estimate the preimplantation nutritional status of the patients. Univariate and multivariate Cox proportional hazard regression analyses were performed to investigate the association between preimplantation malnutrition and HFH. Results: Overall, 231 older diabetic patients receiving RVP were included. The median follow-up period after RVP was 53 months. HFH was reported for 19.9% of the included patients. Our results showed preimplantation malnutrition for 18.2%, 15.2%, 86.6% and 66.2% of the included patients based on the PNI, GNRI, NPS, and CONUT score, respectively. The cumulative rate of HFH during follow-up period was significantly higher for patients in the preimplantation malnutrition group based on the PNI (log-rank = 13.0, P = 0.001), GNRI (log-rank = 8.5, P = 0.01), and NPS (log-rank = 15.7, P < 0.001) compared to the normal nutrition group, but was not statistically significant for those in the preimplantation malnutrition group based on the CONUT score (log-rank = 2.7, P = 0.3). As continuous variables, all the nutritional indices showed significant correlation with HFH (all P < 0.05). However, multivariate analysis showed that only GNRI was independently associated with HFH (HR = 0.97, 95% CI: 0.937–0.997, P = 0.032). As categorical variables, PNI, GNRI, and NPS showed significant correlation with HFH. After adjustment of confounding factors, moderate-to-severe degree of malnutrition was an independent predictor of HFH based on the PNI (HR = 4.66, 95% CI: 1.03-21.00, P = 0.045) and GNRI (HR = 3.02, 95% CI: 1.02-9.00, P = 0.047). Conclusion: Preimplantation malnutrition was highly prevalent in older diabetic patients that received RVP. The malnutrition prediction tools, PNI and GNRI, showed significant prognostic value in accurately predicting HFH in older diabetic patients with RVP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate risk factors for poor prognosis in vocal fold leukoplakia. Methods: Clinical data were collected for 344 patients with vocal fold leukoplakia who received surgical treatment in our otolaryngology department from October 2010 to June 2019. Univariate and multivariate logistic regression analyses of the relevant factors were conducted. Results: Among the 344 patients, 98 exhibited recurrence and 30 underwent a malignant change. Multivariate logistic regression analysis showed that size of the lesion (p = 0.03, odds ratio = 2.14), form of the lesion under white light (p < 0.001), surgical method (p < 0.001, odds ratio = 0.28) and pathological type (p < 0.001) were independent factors that affected the recurrence of vocal fold leukoplakia. In both univariate and multivariate analyses, the sole independent risk factor for malignant transformation of vocal fold leukoplakia was pathological type (p < 0.001). Conclusion: The outlook for vocal fold leukoplakia depends on several clinical factors, especially pathological type. The more severe the pathological type, the more likely it is to recur or become cancerous. [ABSTRACT FROM AUTHOR]

Objective: To assess whether vaginal secretions and breast milk of women with coronavirus disease 2019 (COVID-19) contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Design: Single centre cohort study.Setting: Renmin Hospital of Wuhan University, Wuhan, Hubei province, China.Population: We studied 13 SARS-CoV-2-infected pregnant women diagnosed between 31 January and 9 March 2020.Methods: We collected clinical data, vaginal secretions, stool specimens and breast milk from SARS-CoV-2-infected women during different stages of pregnancy and collected neonatal throat and anal swabs.Main Outcomes and Measures: We assessed viral presence in different biosamples.Results: Of the 13 women with COVID-19, five were in their first trimester, three in their second trimester and five in their third trimester. Of the five women in their third trimester who gave birth, all delivered live newborns. Among these five deliveries, the primary adverse perinatal outcomes included premature delivery (n = 2) and neonatal pneumonia (n = 2). One of nine stool samples was positive; all 13 vaginal secretion samples, and five throat swabs and four anal swabs collected from neonates, were negative for the novel coronavirus. However, one of three samples of breast milk was positive by viral nucleic acid testing.Conclusions: In this case series of 13 pregnant women with COVID-19, we observed negative viral test results in vaginal secretion specimens, suggesting that a vaginal delivery may be a safe delivery option. However, additional research is urgently needed to examine breast milk and the potential risk for viral contamination.Tweetable Abstract: New evidence for the safety of vaginal delivery and breastfeeding in pregnant women infected with SARS-CoV-2, positive viral result in a breast-milk sample. [ABSTRACT FROM AUTHOR]

Study Question: Can of Clinical Genetics, Maastricht University Medical Centre, Maastricht kisspeptin and its analogues regulate the motility of human decidual stromal cells and what intracellular signaling pathways are involved?Summary Answer: Kisspeptin analogue-mediated cell motility in human decidual stromal cells via the focal adhesion kinase (FAK)-steroid receptor coactivator (Src) pathway suggesting that kisspeptin may modulate embryo implantation and decidual programming in human pregnancy.What Is Known Already: The extravillous trophoblast invades the maternal decidua during embryo implantation and placentation. The motile behavior and invasive potential of decidual stromal cells regulate embryo implantation and programming of human pregnancy.Study Design, Size, Duration: Human decidual stromal cells were isolated from healthy women undergoing elective termination of a normal pregnancy at 6- to 12-week gestation, after informed consent.Participants/materials, Setting, Methods: Kisspeptin analogues were synthetic peptides. Cell motility was estimated by an invasion and migration assay. Immunoblot analysis was performed to investigate the expression of kisspeptin receptor and the effects of kisspeptin analogues on the phosphorylation of FAK and Src. Small interfering RNAs (siRNAs) were used to knock down the expression of kisspeptin receptor, FAK, Src, matrix metallo-proteinases (MMPs) 2 and 9, and extracellular signal-regulated protein kinase (ERK) 1/2.Main Results and the Role Of Chance: The kisspeptin receptor was expressed in human decidual stromal cells. Kisspeptin agonist decreased, but antagonist increased, cell motility. Kisspeptin agonist decreased the phosphorylation of FAK and Src tyrosine kinases, whereas antagonist increased it. These effects on phosphorylation were abolished by kisspeptin receptor siRNA. The activation of cell motility by kisspeptin analogues was suppressed by siRNA knockdown of endogenous FAK (decreased 66%), Src (decreased 60%), kisspeptin receptor (decreased 26%), MMP-2 (decreased 36%), MMP-9 (decreased 23%), and ERK 1/2 inhibitor (decreased 27%).Limitations, Reasons For Caution: Human decidual stromal cells were obtained from women having terminations after 6-12 weeks of pregnancy and differences in timing could affect their properties.Wider Implications Of the Findings: Kisspeptin acting within the endometrium has a potential modulatory role on embryo implantation and decidual programming of human pregnancy.Study Funding/competing Interest(s): This work was supported by grant NSC-104-2314-B-182A-146-MY2 (to H.-M.W.) from the Ministry of Science and Technology, Taiwan, and grants CMRPG3E0401 and CMRPG3E0402 (to H.-M.W.). This work was also supported by grants from the Canadian Institutes of Health Research to P.C.K.L. P.C.K.L. is the recipient of a Child & Family Research Institute Distinguished Investigator Award. The authors have no conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

The Wnt ligands display varied spatiotemporal expression in the epithelium and mesenchyme in the developing tooth. Thus far, the actions of these differentially expressed Wnt ligands on tooth development are not clear. Shh expression specifies the odontogenic epithelium during initiation and is consistently restricted to the dental epithelium during tooth development. In this study, we inactivate Wntless ( Wls), the key regulator for Wnt trafficking, by Shh-Cre to investigate how the Wnt ligands produced in the dental epithelium lineage act on tooth development. We find that conditional knockout of Wls by Shh-Cre leads to defective ameloblast and odontoblast differentiation. WlsShh-Cre teeth display reduced canonical Wnt signaling activity in the inner enamel epithelium and the underlying mesenchyme at the early bell stage, as exhibited by target gene expression and BAT-gal staining. The expression of Wnt5a and Wnt10b is not changed in WlsShh-Cre teeth. By contrast, Wnt10a expression is significantly increased in response to epithelial Wls deficiency. In addition, the expression of Hedgehog signaling pathway components Shh, Gli1, and Patched1 was greatly decreased in WlsShh-Cre teeth. Epithelial Wls loss of function in Shh lineage also leads to aberrant cell proliferation in dental epithelium and mesenchyme at embryonic day 16.5; however, the cell apoptosis is unaffected. Moreover, we find that Decorin and Col1a1, the key markers for odontoblast differentiation that are downregulated in WlsShh-Cre teeth, act as direct downstream targets of the canonical Wnt signaling pathway by chromatin immunoprecipitation analysis. Additionally, Decorin and Col1a1 expression can be increased by lithium chloride (LiCl) treatment in the in vitro tooth explants. Taken together, our results suggest that the spatial expression of Wnt ligands within the dental epithelial lineage regulates the differentiation of tooth structures in later stages. [ABSTRACT FROM AUTHOR]

Purpose: Kugel procedure is a classic preperitoneal herniorrhaphy via the posterior approach for inguinal hernias but it has a steep learning curve. The aim of the study is to evaluate the efficacy of the Kugel procedure via the internal ring approach.Methods: Kugel procedures via the internal ring approach were performed on 3673 patients with inguinal hernias between September, 2005 and August, 2017. Demographic data, peri-operative data and postoperative data were collected to evaluate of the efficacy of this technique.Results: None of the patients with inguinal hernias who underwent the Kugel procedure via the internal ring approach was converted to other procedures. The mean operation time for a unilateral hernia was 46.3 ± 15.2 min, with a mean blood loss of 28.9 ± 10.5 mL. The mean visual analogue scale score on postoperative day 1 was 3.1 ± 0.9. Drainage tubes were placed in 266 patients and were removed after a mean duration of 2.8 ± 0.5 days. The mean postoperative hospital stay was 1.2 ± 0.8 days. There were no serious intra-operative complications. Postoperative complications included seroma (n = 84), haematoma (n = 28), ecchymosis (n = 33), superficial incision infection (n = 1), recurrence (n = 1) and mild chronic pain (n = 11).Conclusions: The Kugel procedure via the internal ring approach is a safe, feasible and cost-effective technique for inguinal hernias that retains the benefits of the standard Kugel procedure and is easier to master. [ABSTRACT FROM AUTHOR]

Summary: In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. Introduction: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis. Methods: Here, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes. Results: Of the total of 3796 detected cytosolic proteins, we identified 16 significant ( P < 0.05) and an additional 22 suggestive ( P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration. Conclusions: The combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis. [ABSTRACT FROM AUTHOR]

Background Living donor liver transplantation may put the donor at risk of physical and psychological impacts. Recovery of physical and psychological function as well as quality of life (QOL) in living liver donors warrants investigation. Objectives This study aims to examine the recovery of liver function, emotional status, and QOL in living liver donors through a comparison with the general population and reference values. Methods This descriptive, comparative study included 97 living liver donors who underwent surgery from 2008 to 2012 and were divided into 4 groups according to their postoperative period (1 year [n = 31], 2 years [n = 31], 3 years [n = 21], and 4 years above [n = 14]). Data were collected retrospectively in a medical center in northern Taiwan. Results The mean aspartate aminotransferase level was 20.2–32.1 U/L, the mean alanine aminotransferase level was 14.7–33.5 U/L, and the mean total bilirubin level was 10.8–15.5 μmol/L among the 4 groups. Among donors of the 4 groups, 23.8%–51.6% and 0%–29% were defined as having a mild level of anxiety and depression, respectively. Donors in the 1- and 2-year groups had poorer QOL in the physical function, role physical, vitality, and mental health domains than did the general population of Taiwan ( P < .05). Conclusions Liver function was at normal levels in all 4 groups. The emotional and psychological function of living liver donors should be monitored and health-related QOL should be promoted during the first and second year after liver donation. [ABSTRACT FROM AUTHOR]

Modal analysis is carried out to test the natural frequencies of certain human teeth, including central incisors (CIs), canines (CAs), first premolars (FPs) and first molars (FMs). A total number of 1007 teeth are tested, taking into account tooth type, oral location, age and gender, to analyse the effects of the above-mentioned factors on the natural frequency of the sample teeth. The results reveal that no significant difference in the natural frequency is noted among teeth in the four different intra-oral quadrants. Nevertheless, tooth type and age elicit an effect upon the value of the natural frequency of teeth. On the other hand, the mean value for the natural frequency of CIs (1.27 +/- 0.15 kHz), CAs (1.30 +/- 0.15 kHz), FPs (1.27 +/- 0.15 kHz) and FMs (1.16 +/- 0.12 kHz) for males are significantly lower (p < 0.01) than the analogous figure for females (1.41 +/- 0.21 kHz for CIs, 1.40 +/- 0.18 kHz for CAs, 1.37 +/- 0.20 kHz for FPs, and 1.25 +/- 0.16 kHz for FMs). Moreover, the natural frequency of teeth in male subjects varies with age (p < 0.05). The highest mean frequency of CIs, CAs and FPs for the male subjects is found for the group aged between 40 and 49 years. On the other hand, the natural frequency for the similar set of teeth for the female subjects is shown to be in no way associated with age. [ABSTRACT FROM AUTHOR]

Cysteine phytase is the main phytate-degrading enzyme of ruminant animals. To explore the genetic diversity and dynamic expression profile of cysteine phytase in sheep rumen during a feeding cycle, four transcript (0, 4, 9 and 16 h after feeding) and one DNA (9 h after feeding) clone libraries were constructed, respectively. A total of 46 distinct gene fragments were identified, and most of these sequences had low identities (<60%) with known phytases. Great divergence was found in the constitution and abundance of genes at the genome and transcriptional levels, and the transcript data are more reliable to reflect the information of functional genes. Phylogenetic analysis indicated that the genes from uncultured bacteria instead of Firmicutes played the major phytate-degrading role. Further comparative analysis revealed the dynamic constitution of cysteine phytase genes in rumen at different time points. Significance and Impact of the Study Ruminal phytases, that are cysteine phytases, are novel in sequences and functions. Great divergence in the constitution and abundance of cysteine phytase genes at the genome and transcriptional levels suggested that transcript data are more reliable to reflect the information of functional genes. Phylogenetic and rarefaction analyses indicated that the cysteine phytase genes from uncultured bacteria instead of Firmicutes play the major phytate-degrading role in rumen, and their constitution is dynamic at different time points. This study provides a new insight into ruminal cysteine phytase genes and undermines their expression profiles over a whole feeding cycle. [ABSTRACT FROM AUTHOR]

Background Smoking tobacco is a global health problem, and this study highlights adolescent smoking in Taiwan. Smoking was completely banned on campuses under the Tobacco Hazards Prevention Act and School Health Regulations. Few have investigated the association between personnel smoking/school smoking policies and adolescent smoking in Taiwan. The smoking rate has gradually increased for senior high school students in Taiwan from 10.7% in 1994 to 14.7% in 2011. Aim This study examined the influence of family and friends' smoking on the association between the presence of teachers smoking and each stage of adolescents' smoking behaviour. Methods A cross-sectional survey was conducted in nine high schools ( n = 921). Logistic regression analysis was used to examine the association between smoking stage, father smoking, mother smoking, sibling smoking, friends smoking and the presence of smoking teachers. Results After adjusting for gender, school type and grade, fathers', siblings' and friends' smoking were significantly associated with adolescents' ever and current smoking behaviours, but mothers' smoking was only associated with adolescents' current smoking behaviours. Friends' smoking was strongly associated with being a smoker. While there was an interaction between friends' smoking and the presence of smoking teachers on current smoking behaviours indicating the effect of the presence of smoking teachers was increased when friends did not smoke. Discussion The results suggest that teachers smoking on school may increase the likelihood of being a current smoker as their friends do not smoke. Family and friends smoking are associated with adolescent smoking. Conclusion The Taiwanese government has regulated a comprehensive smoking ban in schools to prohibit both student and staff smoking on all school premises. To achieve this, schools should make tobacco control communication efforts. Nurses could address the combined influence of family and friends as well as the effect of school smoking restrictions to help prevent adolescents from smoking. [ABSTRACT FROM AUTHOR]

Abstract: Marbling is an important technical quality attribute of pork. Its assessment usually corresponds to a subjective score being given by trained panelists based on the marbling standards charts. The purpose of this study was to investigate objective determination of pork marbling using pattern analysis techniques. A line pattern recognition technique called the wide line detector (WLD) and a texture extraction technique based on an improved grey-level co-occurrence matrix (GLCM) were employed and compared. Fifty three fresh pork loin chops from the longissimus dorsi (LD) muscle were collected and their marbling scores were assessed in a plant. Red-Green-Blue (RGB) images of these chops were acquired using a digital camera. The loin eye area was selected as the region of interest (ROI) of the pork images. Marbling was extracted from the ROI by either GLCM or WLD. Proportion of marbling (PM) obtained from WLD or image texture measurement from GLCM (GI) was formulated as indices of the marbling score. Linear regressions based on the PM and GI were carried out at the red, green, and blue channels as well as the combined RGB channels. The results of WLD and GLCM based models showed the effectiveness of pattern analysis techniques for pork marbling assessment. The comparison indicated that the WLD based models had stronger predictive ability for pork marbling score determination than GLCM. The green channel was demonstrated to have the best explanatory for pork marbling assessment no matter which pattern analysis technique used. High correlation coefficients of calibration and validation (Rc = 0.94, Rv = 0.94) of the WLD based linear model at the green channel strongly indicated the great potential of pattern analysis techniques especially the line pattern recognition methods for the accurate and real-time evaluation of pork marbling. [Copyright &y& Elsevier]

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase ( ALT). Liver biopsy ( LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB-4 and aspartate aminotransferase ( AST)-to-platelet ratio index ( APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis ( Scheuer's score ≥ S2) were determined for the entire cohort and stratified by elevated (≥50 U/L) and normal ALT. Two-hundred and thirty-one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB-4 and 0.80 for APRI, compared with 0.71 for FIB-4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value ( PPV) and negative predictive value ( NPV) of FIB-4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB-4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV-infected patients with normal ALT and mildly elevated ALT. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis factor (TNF) is capable of activating the cell death pathway, and has been implicated in killing transformed cells. However, TNF also activates survival signals, including NF-kappaB activation and the subsequent expression of anti-apoptotic genes, leading to protection against TNF toxicity.Methods: In this study, we show that, although untransformed mouse embryonic fibroblasts (MEFs) were resistant to TNF killing, E1A/Ras-transformed MEFs were susceptible to extensive apoptosis induced by TNF. The key factors for determining TNF sensitivity were explored by comparing wild-type and E1A/Ras-transformed MEFs.Results: TNF signalling to NF-kappaB and to its target genes such as IkappaBalpha seemed to be mostly intact in E1A/Ras-transformed cells. Instead, the induction of A20 was completely abolished in E1A/Ras-transformed MEFs, although A20 is known to be NF-kappaB dependent. Reintroduction of A20 into E1A/Ras-transformed MEFs rescued these cells from TNF-induced death and reduced the formation of the FADD/caspase-8 complex. This impaired A20 induction in E1A/Ras MEFs was not because of the stabilisation of p53 or a defective TNF-induced p38 and Jun N-terminal kinase (JNK) signalling. Consistently, we found a reduced A20 promoter activity but normal NF-kappaB activity in TNF-treated E1A/Ras MEFs. However, Bcl-3 seemed to have a role in the transactivation of the A20 promoter in E1A/Ras cells.Conclusions: Our results suggest that specific inhibition of certain survival factors, such as A20, may determine the sensitivity to TNF-induced apoptosis in transformed cells such as E1A/Ras MEFs. [ABSTRACT FROM AUTHOR]

Background: Standard dosing regimens with lithium usually require significant time before the optimal serum concentration is achieved. Method: The present study compares a new method (Method 1) with two existing ones (Methods 2 and 3) for dosing of individual patients with lithium, to more rapidly achieve optimum concentrations. Thirty patients, who were on lithium therapy and who met the inclusion criteria, were evaluated. Results: The correlation coefficient between true and expected concentrations were 0·518 ( P < 0·01), 0·555 ( P < 0·01) and 0·424 ( P = 0·019) respectively. The mean ± standard deviation of the difference from the expected concentrations of three methods were 0·02 ± 0·20 mEq/L, 0·31 ± 0·22 and −0·27 ± 0·25 respectively. Conclusion: Method 1 was the least biased and most accurate among three methods for predicting the optimal therapeutic lithium dose in Taiwanese psychiatric patients. [ABSTRACT FROM AUTHOR]

Objective: To establish an ultrasonographic grading for semi-quantitative evaluation of the femoral condylar cartilage of knee osteoarthritis (OA), in vitro, and compare the ultrasonographic grading with the histologic grading.Design: Thirty-four patients going to receive total knee arthroplasty because of OA of the knee were recruited. Specimens of the distal medial and lateral femoral condyles were taken during the operation. The anterior and middle areas of the articular cartilage in each specimen were graded by in vitro ultrasonography (US) examination and histologic evaluation. The correlation between the US and histologic findings was analyzed.Results: Sixty-seven specimens were collected. Both US and histologic changes were graded from I to IV. The correlation between the grading of US and histology was good in both anterior and middle areas (Rho=0.78, 0.89, P<0.001). The correlation between US grading over anterior area and histology grading over middle area was moderate (Rho=0.70, P<0.001).Conclusions: The moderate correlation between in vitro US and histology might permit quantitative in vivo assessment of cartilage. [ABSTRACT FROM AUTHOR]

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35–134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.British Journal of Cancer (2005) 93, 699–708. doi:10.1038/sj.bjc.6602784 www.bjcancer.com Published online 13 September 2005 [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the potential for using natural frequency (NF) as an indicator for assessing the stability of a magnetic keeper device used in prosthodontic treatment. A three-dimensional finite element (FE) model of a root keeper-cement-dentine system was established for NF analysis. The model was first validated against a series of in vitro experiments. Then, NF values of the first vibrational mode of the FE model with various boundary conditions were calculated. The in vitro results showed that the measured NF values of the root keeper-incisor units decreased significantly (p<0.01) from 9.07 +/- 0.37 to 5.73 +/- 0.10 kHz when the units were embedded in simulated bony tissue. Results obtained from FE simulations demonstrated that the root keeper would fully loosen when the constant values of the spring elements were lower than 10(4) N-m(-1). Furthermore, a linear increase in the NF values of the model was observed from 6.16 to 15.52 kHz, when the constant was increased from 10(4) to 10(7) N-m(-1), and the values then reached a plateau. The results indicate that the NF value of a root keeper has the potential to be used for monitoring the stability of such a device. [ABSTRACT FROM AUTHOR]

The aim of the present work is to develop 3D finite element models of implant fixture with different wall thicknesses to predict maximum stress concentration sites and distribution contours after loading. A maximum lateral force of 150 N was applied to simulate horizontal occlusal forces. When the fixtures were constrained to simulate different boundary levels, the maximum equivalent stress (max EQV) was always located at the implant-bone interface. Max EQV increased when the wall thickness or boundary level was reduced to a certain extent. The fixture with a wall thickness of 0.97 mm demonstrated the smallest stress increase ratio when the boundary level was lowered. Our results indicated that both wall thickness and the boundary level played important roles in maintaining a well-distributed stress level within the fixture. The stress concentration decreased when the fixture wall became thicker, however, this effect was less significant when the surrounding bone level was reduced. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate prognostic factors in patients with recurrent cervical carcinoma who had undergone a primary radical hysterectomy and pelvic lymphadenectomy.Study Design: A retrospective analysis of 177 patients with recurrent cervical carcinoma after radical hysterectomy and pelvic lymphadenectomy for stage IB to II disease at a single institution was performed to evaluate clinicopathologic parameters, time to recurrence, pattern of failure, use of salvage therapy, and survival after recurrence.Results: The 5-year survival rate from diagnosis of recurrence in this series was 10.1%. Survival after recurrence was significantly decreased in patients with pelvic lymph node metastasis at primary surgery and adenocarcinoma-adenosquamous carcinoma histologic type. Patients with extravaginal recurrences receiving chemoradiation for recurrent cervical carcinoma had significantly better outcomes than those receiving radiation alone. Six patients who had a distant relapse at a sole site had prolonged survival after salvage therapy, which was accomplished by chemoradiation, surgery plus radiotherapy, or surgery alone.Conclusions: Our results demonstrate the benefit of adding chemotherapy to radiotherapy in the treatment of recurrent cervical carcinoma. Salvage multimodality treatment should be offered to selected patients who have isolated relapse at a single distant site. [ABSTRACT FROM AUTHOR]

Improper use of mitomycin-C in ocular medication may result in damage to corneal cells. In this study, the toxic effects of mitomycin-C on cultured porcine keratocytes and endothelial cells were estimated by MTT, 3H-thymidine uptake and cellular counting assay methods. It was found that mitomycin-C caused a dose-dependent toxic effect to keratocytes and endothelial cells. Both cells were treated with mitomycin-C at the concentration ranging from 100, 10, 1, 0.1 to 0.01 microg/ml for 3 min, 5 min or 100 min. The 50% inhibitory dose (ID50) of mitomycin-C to keratocytes and endothelial cells as measured by MTT assay was 0.40, 0.18, 0.16 mg/ml and 0.27, 0.15, 0.14 mg/ml, respectively, after 3, 5 and 100 minutes drug treatment. The ID50 for keratocytes and endothelial cells as measured by 3H-thymidine uptake immediately, 1 day and 7 days after 100 minutes mitomycin-C treatment was 0.3, 0.0002, 143.2 microg/ml and 45.1, 101.1, 450.2 microg/ml, respectively. The ID50 for keratocytes and endothelial cells as measured by cellular counting 1 day and 7 days after mitomycin-C treatment was 232.5, 109.7 microg/ml and 239.9, 367.5 microg/ml, respectively. It is concluded that mitomycin-C is more toxic to cellular proliferation in cultured corneal keratocytes than in endothelial cells. [ABSTRACT FROM AUTHOR]

Background: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer.Methods: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity).Conclusions: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To measure primary care physicians' familiarity with, attitudes toward, and confidence in preventive care practice guidelines for the elderly and to determine whether their attitudes are associated with implementation of guidelines into clinical practice.Design: A self-administered survey of physicians employed by a health maintenance organization (HMO) and of patients cared for by those physicians. Medical records were also reviewed to assess compliance with practice guidelines.Setting: An HMO in Southern California.Participants: Forty-eight primary care physicians completed the survey (100% response rate). The medical records of 3,249 randomly selected elderly patients (65 to 75 years old) were studied. Of these patients, 2,799 completed a preventive care survey (response rate 86.1%).Measurement and Results: Most HMO primary care physicians agreed or strongly agreed that guidelines will improve quality of medical care (88%) and that guidelines have caused them to change their care of patients (73%). Although the physicians' general attitudes about guidelines did not often correlate with their use of preventive care guidelines, the physicians who stated that practice guidelines had changed their practices were more likely to offer their patients clinical breast examinations (75.9% vs 67.2%, p = 0.04) and to counsel their patients to exercise (70% vs 58%, p = 0.01) than were the physicians who did not. There was a significant association between physicians' support for and adoption of specific practice guidelines regarding mammography (r = 0.34, p = 0.02) and immunizations against influenza (r = 0.42, p < 0.005), pneumococcal pneumonia (r = 0.47, p < 0.001), and tetanus (r = 0.31, p = 0.03).Conclusions: Physicians employed by an HMO were familiar with and hopeful about the role of guidelines for improving patient care. Physicians' attitudes toward specific preventive care guidelines and admission that guidelines had caused them to change their practice did at times, but not always, correlate with their implementation of guidelines into clinical practice. [ABSTRACT FROM AUTHOR]

In this study, we report a total of 292 mouse embryos cultured on Vero cell monolayers and 77 embryos cultured in medium alone at different preimplantation stages examined individually for embryonic mRNA of beta-actin, interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (icIL-1ra) and interleukin-1 receptor type I (IL-1RtI) using reverse transcription and two-step polymerase chain reaction (RT-PCR). The rates of blastocyst formation and blastocyst hatching were both significantly higher in embryos co-cultured with Vero cells in comparison with the embryos cultured in control medium (81.2 +/- 2.6 versus 42.2 +/- 3.7%, P < 0.001; 75.6 +/- 2.7 versus 19.2 +/- 6.2%, P < 0.001 respectively). We have identified a similar pattern of interleukin-1 family embryonic mRNA transcripts expressed from the compact morula stage through to hatching blastocyst in both control and Vero cell cultured embryos with significantly increased icIL-1ra transcript at hatching blastocyst stage (P < 0.05, P < 0.001 respectively). There was a significant increase in IL-1beta mRNA transcripts of embryos at hatching blastocyst stage compared to compact morula stage in Vero cell cultured embryos (P < 0.05). These findings support the hypothesis that the IL-1 system is an important factor in embryo-maternal molecular communication during the implantation process. [ABSTRACT FROM AUTHOR]

To determine the prevalence of cardiometabolic diseases (CMDs) among adults with abdominal obesity and to evaluate the necessity of differentiating severity of abdominal obesity. Cross-sectional study and prospective cohort study. National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2020 were included for cross-sectional analyses. Class I, II and III abdominal obesity were created by dividing waist circumference within sex-specific abdominal obesity range into tertiles. Age-standardized prevalence of CMDs was estimated and differences by severity of abdominal obesity were compared using Poisson regressions. Prospective analyses were performed using NHANES data between 1988 and 2018 with linked mortality data. Cox proportional hazards models were used to assess the association between severity of abdominal obesity and mortality. Among 23,168 adults included (mean age: 47.8 years, 49.3% men), 13,307 (57.4%) had abdominal obesity. Among adults with abdominal obesity, the estimated prevalence of diabetes was 17.3% (95% confidence interval: 16.3%, 18.2%), hypertension 39.3% (38.2%, 40.3%), dyslipidemia 59.5% (58.0%, 61.1%), cardiovascular disease 9.0% (8.3%, 9.8%), chronic kidney disease 16.8% (15.9%, 17.7%) and non-alcoholic fatty liver disease 39.9% (38.4%, 41.4%). The estimated prevalence was 55.5% (53.8%, 57.2%) for having ≥2 CMDs. Compared with class I abdominal obesity, class III abdominal obesity was related to a 43%–184% higher prevalence of CMDs and a 44% higher risk of all-cause mortality. The prevalence of CMDs was high and multimorbidity of CMDs was common among US adults with abdominal obesity. The prevalence of CMDs and risk of mortality differed significantly by severity of abdominal obesity. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.Results: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).Conclusions: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.Results: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer.Conclusions: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.). [ABSTRACT FROM AUTHOR]

Background: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab.Methods: We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival.Results: A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%).Conclusions: Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.). [ABSTRACT FROM AUTHOR]