Isoflavones in treating watchful waiting benign prostate hyperplasia: a double-blinded, randomized controlled trial

OBJECTIVES: This study aims to determine the efficacy and safety of soy isoflavones in controlling the symptoms and signs of lower urinary tract symptoms due to benign prostate hyperplasia (BPH). DESIGN: This was a prospective, randomized, double-blind, placebo-controlled pilot study. SETTING: This trial was conducted at two hospitals in Hong Kong between May 2006 and September 2007. PARTICIPANTS: One hundred and seventy-six (176) participants diagnosed with BPH were recruited from outpatient clinics. Participants with lower urinary tract symptoms were recruited through newspaper and radio interviews, posters placed at government outpatient clinics, and a public seminar offered by the investigators. INTERVENTIONS: Participants were randomly assigned to either intervention (40 mg of isoflavones daily from Soylife 40) or placebo groups in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome parameter of peak urine flow rate and the second outcome parameters of postresidual urine volume, lower urinary tract symptoms, testosterone, prostate-specific antigen, quality of life, diet, and safety profile (liver and renal function) were collected. All parameters were assessed at baseline, 6 months, and 12 months in a 12-month study period except testosterone, prostate-specific antigen, and safety profile, which were assessed at baseline and at 12 months. RESULTS: The peak urine flow rate (Qmax), postresidual urine volume, International Prostate Symptoms Scores (IPSS), and 36-Item Short Form Health Survey (SF-36) significantly improved from baseline to the 12th month within both groups. However, when compared between groups, Qmax (p=0.055) and incomplete emptying subscore in IPSS (p=0.05) were marginally/statistically different between the two groups from the 6th to the 12th months, in addition to the general health domain of SF-36 from the baseline to 12th month (p=0.02) and from the 6th month to the 12th month (p=0.055). Isoflavones were generally safe and well tolerated. CONCLUSIONS: This randomized control pilot study showed only slight superiority of isoflavones over placebo over 12 months with otherwise surprising beneficial effects in both groups. Tolerability of isoflavones was excellent; thus it has laid foundations for further studies of isoflavones in BPH with focus on dosage and possible specificity of the effect.published_or_final_versio

Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis

To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis

Prognostic factors in severe exacerbation of chronic hepatitis B

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n = 96) or no exacerbation (n = 96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of ≤35 g/L and bilirubin levels of >200 μM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P = .004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.published_or_final_versio

Temperature-dependent cross sections for meson-meson nonresonant reactions in hadronic matter

We present a potential of which the short-distance part is given by one gluon exchange plus perturbative one- and two-loop corrections and of which the large-distance part exhibits a temperature-dependent constant value. The Schrodinger equation with this temperature-dependent potential yields a temperature dependence of the mesonic quark-antiquark relative-motion wave function and of meson masses. The temperature dependence of the potential, the wave function and the meson masses brings about temperature dependence of cross sections for the nonresonant reactions pi pi -> rho rho for I=2, KK -> K* K* for I=1, KK* -> K* K* for I=1, pi K -> rho K* for I=3/2, pi K* -> rho K* for I=3/2, rho K -> rho K* for I=3/2 and pi K* -> rho K for I=3/2. As the temperature increases, the rise or fall of peak cross sections is determined by the increased radii of initial mesons, the loosened bound states of final mesons, and the total-mass difference of the initial and final mesons. The temperature-dependent cross sections and meson masses are parametrized.Comment: 42 pages with 10 figure

Towards a metagenomic understanding on enhanced biomethane production from waste activated sludge after pH 10 pretreatment

BACKGROUND: Understanding the effects of pretreatment on anaerobic digestion of sludge waste from wastewater treatment plants is becoming increasingly important, as impetus moves towards the utilization of sludge for renewable energy production. Although the field of sludge pretreatment has progressed significantly over the past decade, critical questions concerning the underlying microbial interactions remain unanswered. In this study, a metagenomic approach was adopted to investigate the microbial composition and gene content contributing to enhanced biogas production from sludge subjected to a novel pretreatment method (maintaining pH at 10 for 8 days) compared to other documented methods (ultrasonic, thermal and thermal-alkaline). RESULTS: Our results showed that pretreated sludge attained a maximum methane yield approximately 4-fold higher than that of the blank un-pretreated sludge set-up at day 17. Both the microbial and metabolic consortium shifted extensively towards enhanced biodegradation subsequent to pretreatment, providing insight for the enhanced methane yield. The prevalence of Methanosaeta thermophila and Methanothermobacter thermautotrophicus, together with the functional affiliation of enzymes-encoding genes suggested an acetoclastic and hydrogenotrophic methanogenesis pathway. Additionally, an alternative enzymology in Methanosaeta was observed. CONCLUSIONS: This study is the first to provide a microbiological understanding of improved biogas production subsequent to a novel waste sludge pretreatment method. The knowledge garnered will assist the design of more efficient pretreatment methods for biogas production in the future.published_or_final_versio

Transcriptomic dissection of tongue squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC.</p> <p>Results</p> <p>Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1), and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5). The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs.</p> <p>Conclusion</p> <p>In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.</p

Systematic review on the instruments used for measuring the association of the level of multimorbidity and clinically important outcomes

Objectives There are multiple instruments for measuring multimorbidity. The main objective of this systematic review was to provide a list of instruments that are suitable for use in studies aiming to measure the association of a specific outcome with different levels of multimorbidity as the main independent variable in community-dwelling individuals. The secondary objective was to provide details of the requirements, strengths and limitations of these instruments, and the chosen outcomes. Methods We conducted the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42018105297). We searched MEDLINE, Embase and CINAHL electronic databases published in English and manually searched the Journal of Comorbidity between 1 January 2010 and 23 October 2020 inclusive. Studies also had to select adult patients from primary care or general population and had at least one specified outcome variable. Two authors screened the titles, abstracts and full texts independently. Disagreements were resolved with a third author. The modified Newcastle-Ottawa Scale was used for quality assessment. Results Ninety-six studies were identified, with 69 of them rated to have a low risk of bias. In total, 33 unique instruments were described. Disease Count and weighted indices like Charlson Comorbidity Index were commonly used. Other approaches included pharmaceutical-based instruments. Disease Count was the common instrument used for measuring all three essential core outcomes of multimorbidity research: Mortality, mental health and quality of life. There was a rise in the development of novel weighted indices by using prognostic models. The data obtained for measuring multimorbidity were from sources including medical records, patient self-reports and large administrative databases. Conclusions We listed the details of 33 instruments for measuring the level of multimorbidity as a resource for investigators interested in the measurement of multimorbidity for its association with or prediction of a specific outcome. © 2021 Author(s). Published by BMJ

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12&nbsp;months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p &lt; 0.001 and r = - 0.518, p &lt; 0.001, respectively; T3: r = - 0.699; p &lt; 0.001 and r = - 0.523, p &lt; 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p &lt; 0.001; T3: r = 0.286, p &lt; 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score).ConclusionThe MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention