Bioinspired 5-caffeoylquinic acid capped silver nanoparticles using Coffee arabica leaf extract for high-sensitive cysteine detection.

Selection of plant extracts as bioactive phytochemical source to synthesize nanoparticles is highly demanding due to the biocompatibility, nontoxicity, and cost-effectiveness over other available physical and chemical methods. Here, for the first time, Coffee arabica leaf extracts (CAE) were used to produce highly stable silver nanoparticles (AgNPs) and the corresponding bio reduction, capping and stabilization mechanism mediated by dominant isomer 5-caffeoylquinic acid (5-CQA) is discussed. UV-Vis, FTIR, µRaman spectroscopy, TEM, DLS and Zeta potential analyzer measurements were employed to characterize these green synthesized NPs. The affinity of 5-CQA capped CAE-AgNPs to thiol moiety of amino acid is utilized for the selective as well as sensitive detection of L-cysteine (L-Cys) to a low detection limit of 0.1 nM, as obtained from its µRaman spectra. Hence, the proposed novel, simple, eco-friendly, and economically sustainable method can provide a promising nanoplatform in the field of biosensors compliant with large-scale industrial production of AgNPs without aid of further instrumentation.

Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

Dataset for the reporting of urinary tract carcinoma-biopsy and transurethral resection specimen: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.

Analysis of benzene air quality standards, monitoring methods and concentrations in indoor and outdoor environment.

Benzene is a proven carcinogen. Its synergistic action with other pollutants can damage different components of the biosphere. Literature comparing the air quality standards of benzene, its monitoring methods and global concentrations are sparse. This study compiles the worldwide available air quality standards for benzene and highlights the importance of strict and uniform standards all over the world. It was found that out of the 193 United Nation member states, only 53 countries, including the European Union member states, have ambient air quality standard for benzene. Even where standards were available, in most cases, they were not protective of public health. An extensive literature review was conducted to compile the available monitoring and analysis methods for benzene, and found that the most preferred method, i.e, analyzing by Gas Chromatography and Mass spectroscopy is not cost effective and not suitable for real-time continuous monitoring. The study compared the concentrations of benzene in the indoor and outdoor air reported from different countries. Though the higher concentrations of benzene noticed in the survey were mostly from Asian countries, both in the case of indoor and outdoor air, the concentrations were not statistically different across the various continents. Based on the analyzed data, the average benzene level in the ambient air of Asian countries (371 µg/m3) was approximately 3.5 times higher than the indoor benzene levels (111 µg/m3). Similarly, the outdoor to the indoor ratio of benzene level in European and North American Countries were found to be 1.2 and 7.7, respectively. This compilation will help the policymakers to include/revise the standards for benzene in future air quality guideline amendments.

Transporter-Mediated Hepatic Uptake Plays an Important Role in the Pharmacokinetics and Drug-Drug Interactions of Montelukast.

Montelukast, a leukotriene receptor antagonist commonly prescribed for treatment of asthma, is primarily metabolized by cytochrome P450 (CYP)2C8, and has been suggested as a probe substrate for investigating CYP2C8 activity in vivo. We evaluated the quantitative role of hepatic uptake transport in its pharmacokinetics and drug-drug interactions (DDIs). Montelukast was characterized with significant active uptake in human hepatocytes, and showed affinity towards organic anion transporting polypeptides (OATPs) in transfected cell systems. Single-dose rifampicin, an OATP inhibitor, decreased montelukast clearance in rats and monkeys. Clinical DDIs of montelukast were evaluated using physiologically based pharmacokinetic modeling; and simulation of the interactions with gemfibrozil-CYP2C8 and OATP1B1/1B3 inhibitor, clarithromycin-CYP3A and OATP1B1/1B3 inhibitor, and itraconazole-CYP3A inhibitor, implicated OATPs-CYP2C8-CYP2C8 interplay as the primary determinant of montelukast pharmacokinetics. In conclusion, hepatic uptake plays a key role in the pharmacokinetics of montelukast, which should be taken into account when interpreting clinical interactions.

An anatomical evaluation of the serratus anterior plane block.

The serratus anterior plane block has been described for analgesia of the hemithorax. This study was conducted to determine the spread of injectate and investigate the anatomical basis of the block. Ultrasound-guided serratus anterior plane block was performed on six soft-fix embalmed cadavers. All cadavers received bilateral injections, on one side performed with 20 ml latex and on the other with 20 ml methylene blue. Subsequent dissection explored the extent of spread and nerve involvement. Photographs were taken throughout dissection. The intercostal nerves were involved on three occasions with dye, but not with latex. The lateral cutaneous branches of the intercostal nerve contained dye and latex on all occasions. The serratus plane block appears to be mediated through blockade of the lateral cutaneous branches of the intercostal nerves. Anatomically, serratus plane block does not appear to be equivalent to paravertebral block for rib fracture analgesia.

[Intraductal carcinoma of the prostate]. / Intraduktales Karzinom der Prostata.

For many tumor entities, especially in breast cancer, an intraductal carcinoma is generally perceived as a precursor lesion, which precedes the emergence of invasive carcinoma. Therefore, in addition to parameters of the invasive carcinoma, histological parameters of the intraductal component have always played an important role in therapy planning of breast cancer. This is different in prostate cancer and although the term "intraductal carcinoma" has long been propagated by some authors, its routine use remains rare and inconsistent. This is certainly not only due to the far simpler therapy options of prostate cancer, in which focal and organ-preserving therapies still play a subordinate role, but also due to substantial interobserver variation and our inconsistent perception of intraductal carcinomas. This article gives a brief overview of currently available literature on this topic and explains why intraductal carcinoma of the prostate deserves our attention. In contrast to breast cancer, intraductal carcinoma of the prostate usually represents a post-invasive lesion, in which an aggressive tumor exhibits spread into pre-existing ducts; however, in rare cases, intraductal carcinoma may represent a true precursor lesion.

Variation in reporting of cancer extent and benign histology in prostate biopsies among European pathologists.

It is not known how uropathologists currently report histopathological features of prostate biopsies such as core length, tumor extent, perineural invasion, and non-tumor-associated features such as inflammation and hyperplasia in needle biopsies. A web-based survey was distributed among 661 members of the European Network of Uropathology. Complete replies were received from 266 pathologists in 22 European countries. Total core lengths were reported by 64 %. The numbers of cores positive for cancer was given by 79 %. Linear cancer extent was reported by 81 %, most often given in millimeters for each core (53 %) followed by the estimation of percentage of cancer in each core (40 %). A gap of benign tissue between separate cancer foci in a single core would always be subtracted by 48 % and by 63 % if cancer foci were minute and widely separated. Perineural invasion was reported by 97 %. Fat invasion by tumor was interpreted as extraprostatic extension by 81 %. Chronic and active/acute inflammation was always reported by 32 and 56 % but only if pronounced by 54 and 39 %, respectively. While most (79 %) would never diagnose benign prostatic hyperplasia on needle biopsy, 21 % would attempt to make this diagnosis. Reporting practices for prostate biopsies are variable among European pathologists. The great variation in some methodologies used suggests a need for further international consensus, in order for retrospective data to be comparable between different institutions.

Suitability of PSA-detected localised prostate cancers for focal therapy: experience from the ProtecT study.

BACKGROUND: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. METHODS: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. RESULTS: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38-66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. CONCLUSION: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.

Early onset adenovirus infection after simultaneous kidney-pancreas transplant.

Adenoviruses (AdV) are increasingly recognized as important viral pathogens in immunocompromised hosts. The clinical spectrum ranges from asymptomatic viremia to allograft dysfunction, and death. Most of the medical literature is on AdV infection in children and bone marrow transplant recipients. We report a case of AdV in an adult recipient in the first month after simultaneous kidney-pancreas transplant with thymoglobulin induction. This is a rare report of adenovirus infection after multiorgan transplant, and is unique in that it exhibited tissue invasive disease without any localizing signs or allograft dysfunction, while other cases in medical literature had invasive disease of the allograft with allograft dysfunction, failure, or death. In addition, this is the first report of a radiologic presentation of AdV nephritis.

Antioxidant status and smoking habits: relationship with diet.

INTRODUCTION: The present study was conducted to assess the association between smoking, dietary intake of antioxidants and plasma indices of oxidative stress and antioxidant defences in male smokers (cigarette and bidi smokers). METHODS: The study sample consisted of 100 healthy men, including 50 non-smokers and 50 smokers, who were subclassified into 25 cigarette smokers and 25 bidi smokers, aged 18-55 years. Erythrocyte superoxide dismutase and plasma ascorbic acid were measured as antioxidants and erythrocyte malondialdehyde as an oxidative stress index, by colorimetric methods. RESULTS: Smokers ate less fruits and vegetables than non-smokers, leading to them having a lower antioxidant level. Erythrocyte superoxide dismutase was significantly lower in cigarette smokers (0.193 U/mgP, p-value is less than 0.05) and bidi smokers (0.169 U/mgP, p-value is less than 0.001) as compared to non-smokers (0.231 U/mgP). Plasma ascorbic acid was also significantly lower in cigarette smokers (1.45 mg/100 ml, p-value is less than 0.05) as well as in bidi smokers (1.38 mg/100 ml, p-value is less than 0.001) as compared to non-smokers (1.73 mg/100 ml). There was a significant increase in erythrocyte malondialdehyde concentration levels in cigarette smokers (171.47 micromol/gHb, p-value is less than 0.05) as well as in bidi smokers (231.04 micromol/gHb, p-value is less than 0.001) as compared to non-smokers (127.30 micromol/gHb). CONCLUSION: These results provide enough evidence of increased oxidative stress and a compromised antioxidant defence system in smokers, and they are more profound in bidi smokers than in those smoking cigarettes. This study also revealed that the diet and nutrient intake of smokers are different from that of non-smokers.

Handling and reporting of radical prostatectomy specimens in Europe: a web-based survey by the European Network of Uropathology (ENUP).

AIMS: To survey current European practices in handling and reporting of radical prostatectomy (RP) specimens. METHODS AND RESULTS: A European Network of Uropathology (ENUP) was organized for the dissemination of information, survey studies and research collaborations. Contact data of uropathologists were collected from 321 pathology laboratories in 15 West European countries. In the first ENUP survey, 67.6% (217/321) of the members replied to a web-based questionnaire. Some practices were adopted by a large majority, e.g. inking of the specimen (96.6%), Gleason grading (99.5%), stratifying extraprostatic extension (EPE) according to extent (88.2%), reporting TNM stage (88.6%) and reporting location of positive margins (98%). As many as 71.6% of respondents always embedded the entire prostate and only 10.8% always practised partial embedding. Whole mounts were routinely used by 37.5% and standard blocks by 55.5%. Among areas with variable routines were methods to define focal versus extensive EPE and methods to quantify margin positivity, probably reflecting that the optimal method has yet to be determined. CONCLUSIONS: Some practices are almost universally adopted in Europe, whereas others still need to be standardized. The results of the study may be helpful when judging what recommendations are reasonable to issue.

Management of patients with breast cancer: are we ready in India for sentinel lymph node biopsy?

Breast cancer is the commonest cancer among women worldwide. Surgery plays an important role in its management. Axillary lymph node dissection has been the standard of care for staging, prognostication and control of axillary disease for almost a century. However, this time-tested paradigm is shifting gradually in the western world, because of the increasing use of screening mammography resulting in the detection of a large proportion of node-negative early breast cancers and a significant incidence of axillary lymph node dissection-related arm morbidity. Minimally invasive and less morbid procedures such as sentinel lymph node biopsy are being used more commonly in the West. However, the western experience cannot be directly extrapolated to the Indian scenario because of the differences in patient profile, treatment standards and expertise available. There is a need to critically analyse these issues before the Indian medical community advocates sentinel lymph node biopsy as a routine procedure for managing patients with breast cancer.

Radiotherapy after radical prostatectomy for adenocarcinoma of the prostate: a UK institutional experience and review of published studies.

AIMS: The role of radiotherapy to the prostate bed after radical prostatectomy is the subject of much debate. We carried out a retrospective analysis of all patients treated with either adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) in a single UK cancer centre and compared outcomes with published studies. MATERIALS AND METHODS: All patients receiving radiotherapy at any time after a radical prostatectomy were identified and data collected. Patients were referred for ART because of positive surgical margins. SRT was carried out in patients with a detectable or rising prostate-specific antigen (PSA) postoperatively. Patients received either 55 Gy in 20 fractions or 60-64 Gy in 30-32 fractions. All but eight patients were treated using three-dimensional conformal radiotherapy. Both groups were combined for statistical analysis. Biochemical progression-free survival (BPFS) was calculated and displayed using Kaplan-Meier curves. Cox regression was used for univariate and multivariate analysis. RESULTS: In total, 40 patients received postoperative radiotherapy and had a 3-year overall BPFS of 64%. There was no significant difference in 3-year BPFS between ART and SRT (73% vs 61%, P=0.33). Univariate analysis showed that 3-year BPFS was significantly longer if the highest postoperative PSA was<0.5 ng/ml compared with> or =0.5 ng/ml (83% vs 47%, P=0.019), and if the Gleason grade was <7 compared with > or =7 (92% vs 49%, P=0.007). A PSA at diagnosis<10 ng/ml, positive surgical margins, absence of seminal vesicle involvement and neoadjuvant hormones were all associated with a trend towards improved BPFS. Patients with all of these factors had a 3-year BPFS of 91%. Multivariate analysis of the same parameters showed that only Gleason grade remained statistically significant (P=0.019). CONCLUSIONS: The results from this series are in line with published studies, and support the evidence that prostate bed radiotherapy may affect biochemical control in a proportion of patients at risk of relapse. It is not clear whether ART in patients at high risk of relapse or SRT on relapse is most effective.

Infection by Panton-Valentine leukocidin-producing Staphylococcus aureus clinically mimicking Lemierre's syndrome.

Lemierre's syndrome is an oropharyngeal infection which leads to severe septic thrombophlebitis of the internal jugular vein and metastatic abscesses of the lungs and other organs. It is usually caused by Fusobacterium necrophorum, a Gram-negative obligate anaerobe. An unusual case of Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus infection masquerading as Lemierre's syndrome is reported here. A 32-year-old fit and otherwise healthy male presented on Christmas morning with a boil on his left cheek for 2 days and generalized rash for 3 h. His general condition began to worsen, he developed facial swelling and loss of vision in the left eye and was transferred to the intensive care unit. His treatment was taken over by team of specialists and further investigations revealed thrombophlebitis of the left internal jugular vein and cavernous sinus thrombosis with multiple brain infarcts and lung abscesses. His condition remained critical with multiple cranial nerve involvement despite being on broad-spectrum antibiotics. Blood cultures grew S. aureus which was producing PVL toxin. He improved gradually over several weeks. He underwent intensive physiotherapy and made a good recovery. Although a rare entity, it is important to consider Lemierre's syndrome in septic patients who present with rapidly worsening symptoms.

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure.

BACKGROUND: Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were affected by the type of surgical procedure used for adipose tissue harvesting, i.e. resection, tumescent liposuction and ultrasound-assisted liposuction. METHODS: Frequencies of ASC in the stromal vascular fraction were assessed in limiting dilution assays. The phenotypical marker profile of ASC was determined, using flow cytometry, and growth kinetics were investigated in culture. ASC were cultured under chondrogenic and osteogenic conditions to confirm their differentiation potential. RESULTS: The number of viable cells in the stromal vascular fraction was affected by neither the type of surgical procedure nor the anatomical site of the body from where the adipose tissue was harvested. After all three surgical procedures, cultured ASC did express a CD34+ CD31- CD105+ CD166+ CD45- CD90+ ASC phenotype. However, ultrasound-assisted liposuction resulted in a lower frequency of proliferating ASC, as well as a longer population doubling time of ASC, compared with resection. ASC demonstrated chondrogenic and osteogenic differentiation potential. DISCUSSION: We conclude that yield and growth characteristics of ASC are affected by the type of surgical procedure used for adipose tissue harvesting. Resection and tumescent liposuction seem to be preferable above ultrasound-assisted liposuction for tissue-engineering purposes.

Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature.

Varma M & Jasani B (2005) Histopathology47, 1-16 Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literatureImmunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. We critically review the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. We also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.