Biopsy, Fine-Needle ; methods ; Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; genetics ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes ; metabolism ; pathology ; Lymphoma ; diagnosis ; genetics ; pathology ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; diagnosis ; genetics ; pathology

Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.
Transforming Growth Factor beta ; Cell Line ; Cathepsin D ; seconds ; public service announcement

In June 2015, invitations were sent by email to 151 APAME journals to participate in an online survey with an objective of gaining insight into the common publication misconduct encountered by APAME editors. The survey, conducted through SurveyMonkey over a 20-day-period, comprised 10 questions with expansions to allow anecdotes limited to 400 characters, estimated to take less than 10 minutes to complete. Only one invitation was issued per journal, targeting (in order of priority) editors, editorial board members and editorial staff, and limited by email availability. 54 (36%) journals responded. 98% of respondents held Editor or Editorial Board positions. All respondent journals have editorial policies on publication ethics and 96% provide instructions related to ethics. 45% use anti-plagiarism software to screen manuscripts, the most popular being iThenticate, CrossCheck and Turnitin. Up to 50% of journals had encountered studies without IRB approval. Author misconduct encountered were (in rank order): plagiarism (75%), duplicate publication (58%), unjustified authorship (39%), authorship disputes (33%), data falsification (29%), data/image manipulation (27%), conflict of interest (25%), copyright violation (17%) and breach of confidentiality (10%). Reviewer misconduct encountered were: conflict of interest (19%), plagiarism (17%), obstructive behavior (17%), abusive language (13%) and breach of confidentiality (13%). Notwithstanding the limitations of the survey and the response rate, a few insights have been gained: (1) the need for strengthening the ethical culture of researchers/authors and reviewers, (2) anti-plagiarism software can improve plagiarism detection by about 15%, and (3) the need for technical support to detect plagiarism, duplicate publication and image manipulation.

This editorial aims to refine the severe polytrauma management principles. While keeping ABCDE priorities, the termination of futile resuscitation and the early use of tourniquet to stop exsanguinating limb bleeding are crucial. Difficult-airway-management (DAM) is by a structured 5-level approach. The computerised tomography (CT) scanner is the tunnel to death for hemodynamically unstable patients. Focused Abdominal Sonography for Trauma–Ultrasonography (FAST USG) has replaced diagnostic peritoneal lavage (DPL) and is expanding to USG life support. Direct whole-body multidetector-row computed tomography (MDCT) expedites diagnosis & treatment. Non-operative management is a viable option in rapid responders in shock. Damage control resuscitation comprising of permissive hypotension, hemostatic resuscitation & damage control surgery (DCS) help prevent the lethal triad of trauma. Massive transfusion protocol reduces mortality and decreases the blood requirement. DCS attains rapid correction of the deranged physiology. Mortality reduction in major pelvic disruption requires a multi-disciplinary protocol, the novel pre-peritoneal pelvic packing and the angio-embolization. When operation is the definitive treatment for injury, prevention is best therapy.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

OBJECTIVETo determine the differential diagnostic value of high molecular cytokeratin 34betaE12 as a benign marker in mammary lesions.

METHODS90 cases (30 benign non-proliferative diseases, 20 benign proliferative diseases, 10 intraductal carcinomas and 30 invasive carcinomas) were collected, all of which had undergone fine needle aspiration cytology (FNAC) examination and a follow-up operation. Immunohistochemical staining was performed using monoclonal antibodies against 34betaE12 on FNAC smears and the follow-up paraffin sections. SPSS 10.0 software was applied to analyze the differential diagnostic value of 34betaE12 in benign and malignant mammary lesions.

RESULTS(1) No significant difference was found in the expression of 34betaE12 between benign non-proliferative and proliferative disease. (2) A significant difference was found between the expression of 34betaE12 in mammary benign disease and mammary carcinoma. 66.7% and 66.3% of the carcinoma cases showed either lack of 34betaE12 expression or had only a few isolated 1+ cells which were cytoplasmic positive for 34betaE12 immunoreaction on FNAC smear and paraffin section respectively. The remaining 33% of cases having 2+ to 3+ cells mainly displayed cytoplasmic granular positive reaction rather than strong membranous and cytoplasmic positive reaction as benign lesions. In contrast with carcinoma, most benign lesions showed strong immunoreaction of 2+ to 3+ and especially exhibited complete strong membranous and cytoplasmic positive reaction on paraffin section, their positive expressive character differed from those of carcinoma. The positive rates on FNAC smear and paraffin section were 100% and 78% respectively. (3) Certain types of intraductal carcinoma, including low grade cribriform, papillary and solid type either lacked 34betaE12 expression or revealed a few isolated 1+ cells with cytoplasmic positivity for 34betaE12 immunoreaction. Pronounced immunoreaction of 3+ was only seen in high grade comedotype intraductal carcinoma.

CONCLUSIONS34betaE12 may serve as a marker of benign mammary disease for differential diagnosis. When there is a total or predominant lack of 34betaE12 expression, the possibility of carcinoma should be strongly considered. If 34betaE12 is expressed diffusely in the suspicious area with a strong membranous staining in particular, a benign proliferative process rather than carcinoma must be considered.

Biopsy, Needle ; Breast Neoplasms ; chemistry ; diagnosis ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; diagnosis ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Logistic Models

OBJECTIVETo summarize the diagnostic features of fine needle aspiration cytology (FNAC) of myxoid lesions in soft tissue, and to define the cytological criteria for differentiating benign lesions from sarcomas and between various myxoid lesions.

METHODSFNAC data of 24 soft tissue myxoid lesions (14 benign lesions, 10 malignant lesions) from 1993 to 2006 from Kiang Wu Hospital, Macau were reviewed in correlation with the clinical course or the results of biopsy.

RESULTSGanglion, myxoma, and myxoid nodular fasciitis were the most common benign myxoid lesions of the soft tissues, all of which had low cellularity and lack of marked cellular atypia in smears in common. Ganglion was characterized by the disappearance of or the gradual minimization of the nodule after aspiration and the lack of blood vessel in smears. Myxoid nodular fasciitis was characterized by a pleomorphic pattern of proliferative cells and the presence of ganglion cell-like cells. Myxoid liposarcoma, extraskeletal myxoid chondrosarcoma and myxofibrosarcoma were the most common myxoid sarcomas. Cytologically, they had high cellularity and various degrees of cellular atypia. Myxoid liposarcoma exhibited branching chicken-wire like capillary vessels and/or lipoblasts; myxofibrosarcoma were prominent in both pleomorphic and atypia of the cells. The data revealed that the diagnostic accuracy of FNAC was nearly 100% in differentiating benign and malignant myxoid lesions of the soft tissues. The coordinate rate to the histopathology diagnosis of the common myxoid lesions of the soft tissues was above 75% (benign 71.4% and malignancy 80% respectively).

CONCLUSIONSFNAC is an effective method in diagnosing myxoid lesions of soft tissue, in correlation with the clinical data and the accessory examinations. FNAC can provide an objective basis for the treatment of myxoid lesions and prevention of unnecessary surgical operations.

Adolescent ; Adult ; Aged ; Biopsy, Fine-Needle ; methods ; Bone Neoplasms ; pathology ; surgery ; Chondrosarcoma ; pathology ; surgery ; Diagnosis, Differential ; Fasciitis ; pathology ; surgery ; Female ; Fibrosarcoma ; pathology ; surgery ; Ganglion Cysts ; pathology ; surgery ; Humans ; Liposarcoma, Myxoid ; pathology ; surgery ; Male ; Middle Aged ; Myxoma ; pathology ; surgery ; Prognosis ; Sarcoma ; pathology ; surgery ; Soft Tissue Neoplasms ; pathology ; surgery ; Young Adult

INTRODUCTIONHIV-associated neurocognitive disorders (HAND) comprise a wide spectrum of cognitive, motor, and mood abnormalities prevalent in people living with HIV and AIDS (PLWHAs). This field of HIV medicine has gained renewed prominence in recent years with evidence contending that anti-retroviral agents with increased central nervous system (CNS) penetration may improve neurocognitive outcomes in those affected. This review aims at evaluating the available evidence and postulating further study direction in Singapore.

MATERIALS AND METHODSA PubMed search was carried out for original articles and systematic reviews on the subject of HIV-associated neurocognitive disorders, and the results reviewed by the authors.

RESULTSThere is a growing body of evidence that HAND is not uncommon, and the advent of highly active anti-retroviral therapy has increased its prevalence by improving the prognosis of HIV infection, and hence increasing the likelihood of diagnosing of this neurocognitive condition. Screening and diagnosing HAND is important, and requires clinical suspicion as well as validated test batteries for optimal accuracy. The authors recommend strategies for detection in the local context involving stepwise targeted screening. Anti-retroviral agents with good CNS penetration and activity, as well as adjunctive neuro-rehabilitative interventions, may improve the impairments experienced by affected individuals.

CONCLUSIONIncreased awareness of HAND, with earlier diagnosis and targeted, multi-disciplinary management of this challenging condition, may lead to better all-round outcomes for people living with HIV and AIDS in Singapore.

AIDS Dementia Complex ; Anti-HIV Agents ; therapeutic use ; Anti-Retroviral Agents ; therapeutic use ; Antiretroviral Therapy, Highly Active ; HIV Infections ; drug therapy ; Humans ; Neurocognitive Disorders ; Prevalence

OBJECTIVETo study the value of immunocytochemical study for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 in fine needle aspiration cytology (FNAC) diagnosis of mammary lesions.

METHODSOne hundred and thirty-five cases of breast diseases, all with FNAC performed and follow-up histologic correlation available, were enrolled into the study. These included 43 cases of benign non-proliferative diseases, 45 cases of benign proliferative diseases and 47 cases of mammary carcinoma. Immunostaining for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 was carried out on FNAC smears and paraffin sections of the corresponding biopsy specimens. The statistical significance was analyzed using SPSS11.5 software.

RESULTSNo statistically significant difference was observed in the expression of cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 within the groups of benign non-proliferative and benign proliferative breast diseases. On the other hand, a significant difference in immunostaining results was found between benign breast lesions and mammary carcinoma (P < 0.001). A panel of cyclin D1, 34betaE12 and c-erbB-2 immunostaining is highly sensitive and specific in confirming the diagnosis of mammary carcinoma in FNAC samples. A positive reaction for cyclin D1 and c-erbB-2, when coupled with a negative reaction for 34betaE12, showed to be the most reliable supportive evidence for the malignant cytologic diagnosis. When taking the results of either cyclin D1 or 34betaE12 immunostaining into consideration, the sensitivity and specificity for diagnosing carcinoma was 95.7% and 94.3% respectively. On the other hand, when any of the three immunostains suggested carcinoma, the diagnostic sensitivity and specificity became 97.9% and 92.0% respectively. If the immunostaining results of any two of the three markers suggested carcinoma, the diagnostic sensitivity and specificity became 72.3% and 100% respectively. Within the carcinoma group, the degree of expression of cyclin D1, p21(CIP1/WAF1) and 34betaE12 showed little difference amongst different cytologic grades (according to Robinson cytologic grading system). There were however differences in expression of c-erbB-2 and Ki-67. Highest expression rate was observed in grade 3 carcinoma, while lowest expression rate was observed in grade 1 carcinoma (only in 40.0% and 33.3% of cases respectively). Whenever either cyclin D1 positivity or 34betaE12 negativity was demonstrated, the diagnostic accuracy for grade 1 and grade 2 carcinoma was 93.3% and 96.2 % respectively.

CONCLUSIONSImmunocytochemical study using a panel of antibodies for cyclin D1, c-erbB-2, and 34betaE12 has significant diagnostic value in distinguishing between benign breast diseases and mammary carcinoma in FNAC samples. Cyclin D1 and 34betaE12 are especially useful in confirming the cytologic diagnosis of low-grade cancer.

Biopsy, Fine-Needle ; Breast ; chemistry ; pathology ; Breast Diseases ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma ; metabolism ; pathology ; Cyclin D1 ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratins ; metabolism ; Receptor, ErbB-2 ; metabolism