The evolutionarily conserved RNA Polymerase II Rpb4/7 sub-complex has been thoroughly studied in yeast and impacts gene expression at multiple levels including transcription, mRNA processing and decay. In addition Rpb4/7 exerts differential effects on gene expression in yeast and Rpb4 is not obligatory for yeast (S. cerevisiae) survival. Specialised roles for human (hs) Rpb4/7 have not been extensively described and we have probed this question by depleting hsRpb4/7 in established human cell lines using RNA interference. We find that Rpb4/7 protein levels are inter-dependent and accordingly, the functional effects of depleting either protein are co-incident. hsRpb4/7 exhibits gene-specific effects and cells initially remain viable upon hsRpb4/7 depletion. However prolonged hsRpb4/7 depletion is cytotoxic in the range of cell lines tested. Protracted cell death occurs by an unknown mechanism and in some cases is accompanied by a pronounced elongated cell morphology. In conclusion we provide evidence for a gene-specific role of hsRpb4/7 in human cell viability.
Cell Line ; Cell Nucleus ; metabolism ; Cell Survival ; drug effects ; Gene Expression Profiling ; HeLa Cells ; Humans ; RNA Interference ; RNA Polymerase II ; antagonists & inhibitors ; genetics ; metabolism ; RNA, Small Interfering ; pharmacology

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.
Animals ; Apoptosis ; drug effects ; Brain Chemistry ; Cell Line ; Cell Proliferation ; drug effects ; Erythropoietin ; pharmacology ; Humans ; Mice ; Neoplasm Proteins ; analysis ; Neurons ; drug effects ; Oncogene Proteins ; analysis ; Proto-Oncogene Proteins ; analysis ; Receptors, Cytokine ; analysis ; Receptors, Thrombopoietin ; Thrombopoietin ; pharmacology

PURPOSE: Because the shock wave passes through various body tissues before reaching the stone, stone composition may affect the treatment efficacy of shock wave lithotripsy (SWL). We investigated the effect of various tissue components along the shock wave path on the success of SWL. MATERIALS AND METHODS: From October 2008 to August 2010, a total of 206 patients with kidney stones sized 5 to 20 mm were prospectively recruited for a study of the factors that affect the outcome of treatment with a Sonolith Vision lithotripter. Successful SWL was defined as either stone-free status or residual fragments <4 mm at 12 weeks. Logistic regression analysis was performed to assess the factors that predicted treatment outcomes. Potential predictors included the patient's age, shock wave delivery rate, stone volume (SV), mean stone density (MSD), skin-to-stone distance (SSD), and the mean thickness of the three main components along the shock wave path: renal cortical thickness (KT), muscle thickness (MT), and soft-tissue thickness (ST). RESULTS: The mean age of the patients was 53.8 years (range, 25-82 years). The overall treatment success rate after one session of SWL was 43.2%. The mean KT, MT, and ST were 26.9, 16.6, and 40.8 mm, respectively. The logistic regression results showed that a slower shock wave delivery rate, smaller SV, a lower MSD, and a thicker KT were found to be significant predictors for successful SWL. SSD, MT, and ST were not predictors of successful treatment. CONCLUSIONS: Among the main tissue components along the shock wave path, a thicker KT was a favorable factor for successful SWL after adjustment for SV, MSD, and the shock wave delivery rate.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney Calculi/*therapy ; Kidney Cortex/*radiography ; *Lithotripsy ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

PURPOSE: The aims of this study were to investigate the prevalence of upper tract involvement in ketamine-associated uropathy, and to determine the predictors of hydronephrosis in patients with a history of ketamine abuse. METHODS: This was a cross-sectional study of a prospective cohort of patients with ketamine-associated uropathy. Data including demographics, pattern of ketamine abuse, pelvic pain and urgency or frequency (PUF) symptom score, uroflowmetry (UFM) parameters, serum renal function, and liver function tests were collected. Upon consultation, ultrasonography was performed to assess the function of the urinary system. RESULTS: From December 2011 to October 2015, we treated 572 patients with ketamine-associated uropathy. Of these patients, 207 (36.2%) had managed to achieve abstinence at the time of their first consultation. Ninety-six patients (16.8%) in the cohort were found to have hydronephrosis on ultrasonography. Univariate analysis identified age, duration of ketamine abuse, PUF symptom score, voided volume on UFM, serum creatinine levels >100 μmol/L, and an abnormal serum liver enzyme profile as factors associated with hydronephrosis. Logistic regression revealed the following parameters to be statistically related to hydronephrosis: age (adjusted odds ratio [OR], 1.090; 95% confidence interval [CI], 1.020–1.166; P=0.012), functional bladder capacity (adjusted OR, 0.997; 95% CI, 0.995–0.999; P=0.029), serum creatinine >100 μmol/L (adjusted OR, 3.107; 95% CI, 1.238–7.794; P=0.016, and an abnormal serum liver enzyme profile (adjusted OR, 1.967; 95% CI, 1.213–3.187; P=0.006). CONCLUSIONS: Ketamine-associated uropathy can involve the upper urinary tract. Patient demographics as well as investigations of UFM, renal function tests, and liver function tests may allow us to identify at-risk patients.
Cohort Studies ; Creatinine ; Cross-Sectional Studies ; Cystitis ; Demography ; Humans ; Hydronephrosis ; Ketamine ; Liver ; Liver Function Tests ; Logistic Models ; Lower Urinary Tract Symptoms ; Odds Ratio ; Pelvic Pain ; Prevalence ; Prospective Studies ; Ultrasonography ; Urinary Bladder ; Urinary Tract* ; Urination Disorders

BACKGROUNDProactive infection control management is crucial in preventing the introduction of multiple drug resistant organisms in the healthcare setting. In Hong Kong, where vancomycin-resistant enterococci (VRE) endemicity is not yet established, contact tracing and screening, together with other infection control measures are essential in limiting intra- and inter-hospital transmission. The objective of this study was to illustrate the control measures used to eradicate a VRE outbreak in a hospital network in Hong Kong.

METHODSWe described an outbreak of VRE in a healthcare region in Hong Kong, involving a University affiliated hospital and a convalescent hospital of 1600 and 550 beds respectively. Computer-assisted analysis was utilized to facilitate contact tracing, followed by VRE screening using chromogenic agar. Multi-locus sequence typing (MLST) was performed to assess the clonality of the VRE strains isolated. A case-control study was conducted to identify the risk factors for nosocomial acquisition of VRE.

RESULTSBetween November 26 and December 17, 2011, 11 patients (1 exogenous case and 10 secondary cases) in two hospitals with VRE colonization were detected during our outbreak investigation and screening for 361 contact patients, resulting in a clinical attack rate of 2.8% (10/361). There were 8 males and 3 females with a median age of 78 years (range, 40 - 87 years). MLST confirmed sequence type ST414 in all isolates. Case-control analysis demonstrated that VRE positive cases had a significantly longer cumulative length of stay (P < 0.001), a higher proportion with chronic cerebral and cardiopulmonary conditions (P = 0.001), underlying malignancies (P < 0.001), and presence of urinary catheter (P < 0.001), wound or ulcer (P < 0.001), and a greater proportion of these patients were receiving β-lactam/β-lactamase inhibitors (P = 0.009), carbapenem group (P < 0.001), fluoroquinolones (P = 0.003), or vancomycin (P = 0.001) when compared with the controls.

CONCLUSIONExtensive contact tracing and screening with a "search-and-confine" strategy was a successful tool for outbreak control in our healthcare region.

Aged ; Aged, 80 and over ; Enterococcus faecium ; growth & development ; pathogenicity ; Female ; Gram-Positive Bacterial Infections ; epidemiology ; prevention & control ; Hong Kong ; epidemiology ; Humans ; Male ; Middle Aged ; Vancomycin Resistance

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.
Age Factors ; Aged ; Aged, 80 and over ; Databases, Factual ; Humans ; Kaplan-Meier Estimate ; Lower Urinary Tract Symptoms ; Male ; Middle Aged ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Transurethral Resection of Prostate/methods* ; Urinary Retention/surgery*