Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni- and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients.     

Isolation and molecular characterization of Staphylococcus sciuri in the hospital environment

Staphylococcus sciuri is a principally animal-associated bacterial species, but its clinical relevance for humans is increasing. Our study aimed to provide the first insight into the prevalence of this bacterium in a hospital environment. A 3-month surveillance was conducted in a hospital located in Belgrade, Serbia, and 1,028 samples taken from hands of medical personnel, medical devices, and various hospital surfaces were screened for S. sciuri presence. In total, 108 isolates were obtained, which resulted in a relatively high rate of colonization (10.5%). These isolates, along with 7 S. sciuri strains previously isolated in the same hospital (n = 115), were phenotypically and genotypically characterized. Antimicrobial susceptibility testing revealed that 73% of the strains were resistant to one or more antibiotics, with 4.3% strains displaying multiresistance. Examination of 16S-23S ribosomal DNA intergenic spacer length polymorphism identified the strains at the subspecies level, and 74 (64.3%) strains of S. sciuri subsp. sciuri, 37 (32.2%) strains of S. sciuri subsp. rodentium, and 4 (3.5%) strains of S. sciuri subsp. carnaticus were established. Pulsed-field gel electrophoresis (PFGE) analysis showed 21 distinct pulsotypes, including 17 main types and 4 subtypes. One dominant cluster with 62 strains was found, while 19 (90.5%) of the PFGE types and subtypes identified had 5 or fewer strains. The predominance of small PFGE clusters suggests that the ubiquitous presence of S. sciuri in the outside environment presents the continuous source for colonization of the hospital environment. The presence of one dominant PFGE cluster of strains indicates that some S. sciuri strains may be capable for adaptation to hospital environment conditions and continuous existence in this environment.     

Increased incidence of prostate cancer in Nigerians

An increased incidence of prostate cancer among African-American men (now the second most common cause of cancer death) has been attributed mainly to the introduction of screening techniques, which have enabled earlier diagnosis of patients. This study reviewed male cancer patients recorded in a Nigerian cancer registry to assess the current trends in prostate cancer in Nigeria. For comparison, data were broken into two groups: 1980-1988 and 1989-1996. Only the top 10 cancers occurring in both periods were considered initially in this report. For emphasis, an analysis of adult male cancers was done per decade since 1960. Results show that prostate cancer has become the number one cancer in Nigerian men and constitutes 11% of all male cancers. The median age of patients was 67.5 years (variance 5.6), and the mean age was 71.4 years (variance 14.3). These results indicate that despite the absence of screening programs in Nigeria, the number of prostate cancer cases has increased. The known risk factors probably contribute to a varying degree among Nigerians, who are generally of average build or in the low-normal range for body mass index. Moreover, the role of genetics cannot be underplayed. Given its biological characteristics, more cases of prostate cancer probably would be recorded among this population if screening were undertaken.     

Synergistic Antimicrobial Activities of Phytoestrogens in Crude Extracts of Two Sesame Species Against Some Common Pathogenic Microorganisms

Intensive studies on extracts and biologically active compounds isolated from medicinal plants have doubled in the last decade worldwide. However, as a result of paucity of knowledge and folkloric claim on the effectiveness of sesame leaves in infectious disease treatments, we aimed to determine the synergistic antimicrobial activity of essential oils and lignans present in the crude leaves extracts of Sesame radiatum and Sesame indicum. Ethanolic, methanolic and aqueous extracts of both leaves were studied for their in-vitro synergistic antimicrobial activity against both Gram positive and Gram negative micro-organisms, and Yeast using Agar diffusion method. The GC-MS phytochemical screening of methanolic extract showed that the major compounds in essential oils are of carboxylic acids and phenolic groups especially, the most potent antioxidants known to man like sesamol, sesamolin and sesamin among others. Methanolic and ethanolic extracts have broad spectrum antimicrobial effect against all the tested pathogenic micro-organisms except Streptococcus pneumoniae and Staphylococcus aureus respectively, while the aqueous extract exhibited inhibitory activity on Staphylococcus aureus, Streptococcus pneumoniae and Candida albicans. The result confirmed the folkloric claims of the antimicrobial effectiveness of locally consumed sesame leaves extracts especially against bacterial and common skin infection in many areas of Nigeria.     

Once-Daily Triple Therapy in Patients with Advanced COPD: Healthcare Resource Utilization Data and Associated Costs from the FULFIL Trial

Introduction

Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.

Methods

FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study. Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.

Results

Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%). Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs. 32.7%). Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs. £763.32 and £749.22 vs. £988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs. £1,267.45).

Conclusions

This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.

Trial Registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK

     

Molecular identification and characterization of mannitol-negative methicillin-resistant Staphylococcus aureus

We report on the isolation, molecular identification, and characterization of 5 mannitol-negative methicillin-resistant Staphylococcus aureus (MRSA) from clinical samples in KwaZulu-Natal (KZN) province, South Africa. Identification based on phenotypic testing and polymerase chain reaction detection of the S. aureus species-specific nuc gene and the coagulase gene indicated that the mannitol-negative isolates were S. aureus. Furthermore, they were mecA positive, and SCCmec typing demonstrated that all the isolates harbored type IV SCCmec. API STAPH (Biomerieux, Marcy-l'Etoile, France) misidentified 2 mannitol-negative MRSA that belonged to the major clone in KZN province, as Staphylococcus lugdunensis. Although the prevalence and mechanism of mannitol-negative MRSA is unknown, laboratories are encouraged to investigate S. aureus with atypical characteristics.     

p16INK4a expression and clinicopathologic parameters in renal cell carcinoma

OBJECTIVES: The tumour suppressor gene p16INK4a is a cyclin-dependent kinase inhibitor, for which inactivation attributable to promoter hypermethylation or homozygous deletion has been described in malignancies. Little is known about p16INK4a protein levels in renal cell carcinoma (RCC) and its association with clinicopathologic parameters or disease progression. METHODS: The expression of the p16INK4a gene was analysed with the use of immunohistochemistry and tissue microarrays (TMA). Tissue cores were obtained from the primary tumour itself, the tumoural invasion front, and histologically benign peritumoural tissue of 397 nephrectomies. For statistical analysis, sections were classified into four groups according to the relative amount of positively stained cells: negative (0%), low (1-10%), intermediate (11-50%), and high positivity (>50%). Follow-up data were analyzed for 198 patients (follow-up period: 2-240 mo; median: 138 mo). RESULTS: Absent or low expression of p16INK4a was observed in 82% of tumour samples. No statistically significant association was found between protein levels detected in tumour, invasion front, or normal renal tissues and any of the clinicopathologic variables. Survival analysis by Kaplan-Meier revealed a significant association between high expression (>50%) of p16INK4a in tumours and better disease-specific survival (p=0.03, log-rank test). Cox regression analysis showed that p16INK4a expression is an independent covariate in disease-specific survival (p<0.01). CONCLUSIONS: The absence of p16INK4a expression in most tumour cells indicates that p16INK4a could be involved in the tumourigenesis of RCC. Immunohistochemically detected positivity for p16INK4a is a positive prognosticator for specific survival in both uni- and multivariate analyses.     

Rapid antigen detection in the diagnosis of highly pathogenic avian influenza (H5N1) virus in Nigeria

Highly pathogenic avian influenza (AI) is an infectious disease of agroeconomic and public health importance. The outbreak that occurred in Nigeria (2006–2008) was devastating to the poultry industry and raised public health concerns. In the course of its control, rapid laboratory confirmation of suspected cases in poultry was essential for prompt mobilization of control logistics for depopulation and decontamination of affected premises. Commercial rapid test kit was evaluated in the diagnosis of highly pathogenic AI (HPAI) as a preliminary to virus isolation. Between 2006 and 2007, 382 cases were tested out of which 149 were positive by rapid antigen detection. Virus isolation yielded 171 positive cases. The relative diagnostic sensitivity of Anigen Rapid AIV Ag test was 84.3% (95% confidence interval [CI], 78.1–88.9%), whereas the relative diagnostic specificity was 97.7% (95% CI, 94.2–99.1%). Rapid antigen detection is a useful technique for prompt diagnosis of HPAI for early detection and containment.