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This article discusses a case of a 64-year-old man who presented with back pain and cough. Imaging revealed masses in the chest and abdomen, as well as pleural effusions. Pathological examination of the tissue revealed a poorly differentiated malignant neoplasm that initially appeared to be anaplastic large-cell lymphoma (ALCL) based on immunohistochemical staining. However, further molecular testing confirmed a diagnosis of ALK-rearranged lung adenocarcinoma. The patient has responded to ALK-inhibitor therapy. The article emphasizes the importance of careful interpretation of immunohistochemical stains in cases of poorly differentiated ALK+/CD30+ neoplasms. [Extracted from the article]

Background and Aims: Neurodegeneration underpins the pathological processes of younger‐onset dementia (YOD) and has been implicated in primary psychiatric disorders (PSYs). Cerebrospinal fluid (CSF) neurofilament light (NfL) has been used to investigate neurodegeneration severity through correlation with structural brain changes in various conditions, but has seldom been evaluated in YOD and PSYs. Methods: This retrospective study included patients with YOD or PSYs with magnetic resonance imaging (MRI) of the brain and CSF NfL analysis. Findings from brain MRI were analysed using automated volumetry (volBrain) to measure white matter (WM), grey matter (GM) and whole brain (WB) volumes expressed as percentages of total intracranial volume. Correlations between NfL and brain volume measurements were computed whilst adjusting for age. Results: Seventy patients (47 with YOD and 23 with PSY) were identified. YOD types included Alzheimer disease and behavioural variant frontotemporal dementia. PSY included schizophrenia and major depressive disorder. MRI brain sequences were either fast spoiler gradient‐echo (FSPGR) or magnetization‐prepared rapid acquisition gradient‐echo (MPRAGE). In the total cohort, higher NfL was associated with reduced WB in the FSPGR and MPRAGE sequences (r = −0.402 [95% confidence interval (CI), −0.593 to −0.147], P = 0.008 and r = −0.625 [95% CI, −0.828 to −0.395], P < 0.001, respectively). Higher NfL was related to reduced GM in FSPGR (r = 0.385 [95% CI, −0.649 to −0.014], P = 0.017) and reduced WM in MPRAGE (r = −0.650 [95% CI, −0.777 to −0.307], P < 0.001). Similar relationships were seen in YOD, but not in PSY. Conclusion: Higher CSF NfL is related to brain atrophy in YOD, further supporting its use as a nonspecific marker of neurodegeneration severity. [ABSTRACT FROM AUTHOR]

Questions: Livestock grazing is an expanding land management tool for habitat and fuel management in California grassland ecosystems, despite mixed conclusions about its effects. Our study investigated the following questions: Does a targeted grazing regime promote grassland functioning by clearing bare ground and reducing dead litter cover?Does targeted grazing reduce grassland fuels?Does targeted grazing promote native species cover and diversity?Does targeted grazing reduce non‐native, invasive species cover and diversity? Location: The Santa Lucia Preserve, Carmel, California, USA. Methods: Monitoring grazed and ungrazed treatment plots within 17 study sites, we surveyed the effects of a targeted grazing regime on bare ground cover, litter cover and depth, herb height, and diversity and cover of different native and non‐native species groups over an eight‐year period. Results: On average, grazing successfully increased bare ground (by 2.8% cover), decreased litter depth (by 3.5 cm) and cover (by 12%), and decreased herb height (by 3.9 cm). Grazed plots had greater cover of native annual forbs (+1.2% cover), while decreasing invasive Bromus diandrus (by 6.0% cover). There was no difference in either native or non‐native species diversity. Conclusions: Targeted grazing can be an appropriate tool to accomplish conservation goals, including biomass management and canopy clearing, while improving native annual forbs without risk to native species as a whole. Further steps in adaptive management must examine how the application of grazing may be altered to further promote native species and to inhibit invasive species. [ABSTRACT FROM AUTHOR]

Objectives: To compare survival and risk factors associated with mortality in common young‐onset dementias (YOD) including Huntington's disease. Methods: This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. Results: There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5–8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD‐subtypes related to dementia and mental/behavioural disorders. Discussion: This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision. Key points: Dementia is a leading cause of death in Australia and the leading cause of death in females. There is limited mortality information pertaining to younger people with dementia.We investigated mortality and risk factors in young‐onset dementia, including Huntington's disease. Huntington's disease had the longest survival ‐ 18.8 years, with Alzheimer's disease, frontotemporal and vascular dementias having 11 and 13 years median survival. Young‐onset dementia conferred between 5 and 8 times increased risk of death compared to the general population.Young‐onset dementia is a fatal disease with shortened lifespan. Early identification and timely age‐appropriate services are necessary for these individuals. [ABSTRACT FROM AUTHOR]

Background: Using Personal‐Disclosure Mutual‐Sharing (PDMS) with students transitioning to Higher Education (HE) has yet to be researched in education. Aims: In two studies, we aimed to explore the immediate effects of a Coping Oriented Personal‐Disclosure Mutual‐Sharing (COPDMS) intervention on first‐year undergraduate students' relational and organizational identification, perceived social support availability, and self‐efficacy for learning and performance. In our second study, we also aimed to examine student‐perceptions of participating in a COPDMS intervention. Sample and Methods: At the beginning of induction week in both studies, first‐year undergraduate students on the same degree programme at a HE provider in England received an education session where COPDMS was introduced. Students participated in a COPDMS session a few days later. During COPDMS sessions, students mutually‐shared and disclosed personal information and/or stories relating to transitional experiences. Results: Across both studies, students' relational identification with staff and perceived emotional, esteemed, and informational support availability from others on the degree programme significantly increased from pre‐ to post‐COPDMS phases. Findings relating to relational identification with other Year 1 students and perceived availability of tangible support were mixed. No significant changes occurred for organizational identification with the university and self‐efficacy for learning and performance. In Study 2, five higher‐order themes relating to students' perceptions of COPDMS were found: (1) emotionality; (2) personal development; (3) storytelling; (4) enhanced group processes; and (5) task appropriateness and value. Conclusions: Study findings provide evidence that COPDMS is a useful psychological intervention to deliver to students transitioning to HE. Practical considerations, limitations, and future research suggestions are provided. [ABSTRACT FROM AUTHOR]

Objectives: Carer burden in dementia is associated with poor outcomes, including early nursing home placement for people with dementia and psychological distress for their carers. Carers of people with young-onset dementia (YOD) are particularly vulnerable to carer burden. Yet they are often overlooked by clinicians as dementia services are generally designed for older people. We sought to estimate the rate of burden and psychological distress in carers of YOD at a state-wide tertiary service based in Australia.Methods: We conducted a cross-sectional study examining 71 dyads from a Neuropsychiatry service. We collected patient demographic and clinical data including the Neuropsychiatry Unit Cognitive Assessment tool (NUCOG) and Mini-Mental State Examination (MMSE). Carer data, such as demographics and psychological distress, were obtained using Depression Anxiety Stress Scale 21 (DASS-21). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI).Results: Higher carer burden, measured using ZBI, was associated with longer duration of dementia and greater severity of overall cognitive impairment. Carers who felt burdened reported higher levels of stress, depression, and anxiety measured using DASS-21. Multiple linear regression analysis found carer burden was independently predicted by duration of dementia, total cognition score and carers experiencing psychological stress.Discussion: We found that patient variables of dementia duration and cognitive impairment and carer variable of carer stress to be associated with carer burden. Poor executive function was associated with carer stress. Early identification and management of carer burden and psychological distress is important for outcomes. Ideally, this should be provided by a specialist YOD service. [ABSTRACT FROM AUTHOR]

Prostate cancer, Gleason pattern 3, Gleason score 3 + 3 = 6, ISUP Grade Group 1, tumour grading, tumour classification Keywords: prostate cancer; Gleason pattern 3; Gleason score 3 + 3 = 6; ISUP Grade Group 1; tumour grading; tumour classification EN prostate cancer Gleason pattern 3 Gleason score 3 + 3 = 6 ISUP Grade Group 1 tumour grading tumour classification 741 743 3 11/14/22 20221201 NES 221201 Abbreviations ASAP atypical small acinar proliferation GS Gleason score ISUP International Society of Urological Pathology PIN prostatic intraepithelial neoplasia In a pair of recent articles [1,2], Eggener et al. revived the decade-old argument, which we refuted previously [3], that Gleason score 3 + 3 = 6 (GS6; International Society of Urological Pathology [ISUP] Grade Group 1) prostatic adenocarcinoma should no longer be labelled cancer. Low-grade prostate cancer should still be labelled cancer. [Extracted from the article]

Chronic graft-versus-host disease (cGVHD) complicating allogeneic haemopoietic stem cell transplantation rarely involves the nervous system; oromandibular parafunction has not been previously reported. We describe five patients with cGVHD, presenting with bruxism, limitation of mouth opening, jaw locking, pain and masseter hypertrophy. Pathophysiological mechanisms are discussed. Targeted botulinum toxin injections were an effective treatment with minimal side-effects. [ABSTRACT FROM AUTHOR]

A patient with a 6‐year‐old left upper arm brachial cephalic AVF presented with symptoms of hemodialysis access‐induced distal ischemia (HAIDI). Physical exam findings showed a well‐developed AVF, but compression of the AVF aggravated arm pain and induced diffuse erythema of the left upper extremity. Angiographic evaluation disclosed the presence of a large axillary artery vascular malformation (AVM) as well as distal forearm hypo‐perfusion. We elected to publish this case report to describe the interesting physical exam findings related to the AVM, and discuss HAIDI treatment options that are peculiar to this case. We also highlight the importance of thorough vascular evaluation prior to AV access creation as well as during the investigation of the cause of HAIDI. [ABSTRACT FROM AUTHOR]

Anion exchange between ubiquitous low‐molecular‐weight organic acids (LMWOA), such as oxalate, and surface‐retained inorganic anions, such as F−, SO42− and OH−, can play a critical role in Al bioavailability and transport in acidic alpine tundra soil. A series of batch equilibration and composite soil column leaching studies were conducted to examine anion exchange reactions between F−, oxalate and OH−, and the impact of increased soil solution F− concentration on Al transport. The addition of either F− or oxalate to soil suspensions resulted in significantly higher solution pH, suggesting F− and oxalate exchange with surface –OH groups. Distinct stages of OH− release were observed for all soil horizons leached with 1.32 × 10−3 mol l−1 F−, with OH− release decreasing in the order O/A1 ~ A2> > Bw. A similar OH− release pattern was observed in the O/A1 horizon for the 7.81 × 10−4 mol l−1 oxalate treatment, suggesting that both F− and oxalate may be competing for common exchange sites in the O/A1 horizon. Fluoride displacement by oxalate, in batch equilibration experiments, was observed for both the 2.84 × 10−4 mol l−1 and 7.81 × 10−4 mol l−1 oxalate treatment. Individual soil horizons leached with 7.81 × 10−4 mol l−1 oxalate exhibited increased F− leaching in the order O/A1 > A2 ~ Bw, with pulsed F− movement being observed in the O/A1 horizon. Soil columns eluted with 1.32 × 10−3 mol l−1 F− exhibited increased Al solubilization and transport, with Al leaching increasing in the order Bw > A2 > O/A1. Sequential leaching of soil columns in the order D. I. H2O → 1.32 × 10−3 mol l−1 F− → D.I. H2O → 7.81 × 10−4 mol l−1 oxalate indicated that previously adsorbed F− was displaced by oxalate. Displacement of F− by oxalate increased in the order O/A1 > A2 > Bw. Hydroxyl displacement by both F− and oxalate may be an important source of acid neutralization in a soil wetting front, affecting Al speciation and transport. Highlights: Oxalate and F− compete for similar OH− exchange sites, increasing soil pH.Adsorbed F− can be displaced by oxalate anions.Al solubilization increases with F− adsorption in alpine tundra soil.Aluminium fluoride speciation changes rapidly within the soil wetting front.Anion exchange reactions should be considered in assessing soil ANC. [ABSTRACT FROM AUTHOR]

Surgical infection is one of the most pressing problems in the field of orthopedic surgery; however, current detection methods are plagued by high costs and long wait times. This study seeks to demonstrate the ability of a novel assay using fluorescently conjugated antibodies and confocal laser scanning microscopy (CLSM) to accurately detect bacterial presence on orthopedic surgical explants, tissue, and synovial fluid in 30 min. Explanted hardware, tissue, and synovial fluid samples suspected to be infected were collected from human subjects with institutional review board consent. Samples were prepared using a 30‐min protocol, consisting of rinsing, nonspecific blocking and staining steps, and imaged using CLSM. Images were analyzed using ImageJ (National Institute of Health) to determine the percent area of Gram positive and Gram negative bacteria. Results of the assay were compared to the hospital's microbiological laboratory and Gram staining results. Ninety three samples were collected and tested using the 30‐min testing protocol; 75 samples were synovial fluid and 18 were tissue and explants. Seventy four of 75 (98.6%) synovial fluid samples correlated with the hospital laboratory's microbiological findings. Of the 18 explant and tissue samples, our assay found bacterial presence in 14 of 18 samples, while the hospital microbiology laboratory found bacterial presence in 13 of 18 samples. This assay reliably stained and rapidly identified the presence of Gram negative and Gram positive bacteria on surgical explants, tissue and synovial fluid in 30 min. This methodology may serve as a point of service tool for the determination of bacterial presence during surgical procedures. [ABSTRACT FROM AUTHOR]

Objectives: Younger‐onset dementia (YOD) refers to a dementia where symptom onset occurs when the patient is less than 65 years of age. YOD is far less common than late‐onset dementia (occurring when patients are over 65 years old) and more challenging to diagnose due to its heterogeneous presentation. There have been relatively few studies describing demographic and diagnostic characteristics of patients with YOD in the community, particularly with follow‐up information. Methods: A retrospective cohort study was performed of inpatients admitted to a tertiary neuropsychiatry service, located in metropolitan Victoria, Australia, from 2009 to 2019. Inpatients with a YOD diagnosis were identified and data regarding diagnosis, demographics and investigations were obtained. Results: There were 849 individual inpatients who were admitted to the service in the 10‐year period and received comprehensive assessment. There were 306 individuals who received a YOD diagnosis, using contemporaneous diagnostic criteria (frequency 36%). The most common diagnoses were Alzheimer's disease (24.2%), frontotemporal dementia (23.1%), Huntington's disease (16.7%) and vascular dementia (7.8%). More than half of these inpatients were followed up and 6.5% had a diagnostic change when reviewed. Conclusions: This study reports on the largest cohort of YOD to date, with diagnostic breakdown similar to previous retrospective file reviews. The neuropsychiatry service is funded to follow‐up its patients, thus allowing re‐assessment and continuity of care. While there are limitations in this study such as the lack of neuropathological outcomes, the findings emphasise the strengths of follow‐up and appropriate service provision for these patients. [ABSTRACT FROM AUTHOR]

Abbreviation ISUP International Society of Urological Pathology In November 2014, the International Society of Urological Pathology (ISUP) convened a consensus meeting in Chicago, Illinois, USA to consider grading criteria for prostatic adenocarcinoma [1]. While cribriform cancer used to be included in either Gleason pattern 3 or 4, depending on the size and shape of the glands, the ISUP 2014 revision considers all cribriform cancer to be Gleason pattern 4, or even 5 if comedonecrosis is present [19]. An explanation for this increasing interest may be that the Gleason inflation that was fueled by the ISUP 2005 consensus recommendations has pushed a considerable number of cancers from Gleason score 6 to 7 [21]. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and proposal for a new grading system. [Extracted from the article]

Background: Although the COVID‐19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID‐19. Objective: To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future. Conclusion: Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD. [ABSTRACT FROM AUTHOR]

Historical outcomes remain poor for patients with relapsed/refractory diffuse large B-cell (DLBCL) and high-grade B-cell lymphoma (HGBCL) (Crump I et al i ., [3]). We included patients treated from 2011 to 2018, including those with transformed disease, patients with I MYC i , I BCL2 i and I BCL6 i translocations (including HGBCL), and patients treated with concurrent rituximab. Though more patients with transformed FL were treated with concurrent rituximab compared to patients with I de novo i GCB disease, there was no difference in efficacy between patients treated with or without concurrent rituximab. One patient with "triple HIT" disease had a complete response, which allowed the patient to receive chimeric antigen receptor T-cell therapy. [Extracted from the article]

Aims: Little has been written on the frequency and nature of incidental splenic lesions diagnosed on histopathological examination of pancreatosplenectomy specimens. Methods and results: For 191 such specimens, incidental histological findings after haematopathologist re‐review were tabulated. Cases suspicious for lymphoid malignancy underwent molecular analysis for immunoglobulin heavy and kappa light chain rearrangement. Follow‐up was obtained on selected cases. In five cases (3%), the spleen was sampled but not mentioned in the original microscopic report; all were normal on re‐review. Otherwise, most (171 of 186, 92%) were initially diagnosed as normal, with 160 (94%) remaining so on re‐review. Findings on re‐review not initially described (n = 11, 6%) included four cases with splenic morphology suspicious for possible leukaemia/lymphoma involvement. Additional findings included abscess formation, foamy macrophages, necrotising granulomas and simple cysts. Fifteen spleens were initially diagnosed as abnormal; the histopathological process was confirmed in all, including non‐necrotising granulomas, cysts, Gamna–Gandy bodies, foamy macrophages, involvement by pancreatic neoplasm and involvement by known chronic lymphocytic leukaemia (CLL). Molecular analysis was performed on the five cases of known/suspected lymphoma and two were positive for monoclonal gene rearrangement, including the known CLL and a previously undiagnosed case with similar immunophenotype. Conclusions: Incidental splenic findings are not uncommon in pancreatosplenectomy specimens. While most are of limited clinical significance, low‐grade lymphoproliferative disorders may go undetected if the spleen is overlooked. We recommend careful observation of splenic findings in these specimens, with a low threshold for haematopathological consultation when in doubt. [ABSTRACT FROM AUTHOR]

Background: Management of acute ischaemic stroke is time critical. Reducing time to treatment with thrombolysis is strongly associated with improved outcomes in properly selected patients. However, there are barriers to ensuring timely treatment in the hospital setting. Aim: To determine if simple, no‐cost protocol changes could improve time to treatment for acute ischaemic stroke at a busy tertiary hospital. Methods: Prospectively collected routine clinical data were compared retrospectively before and after a protocol change designed to mirror the successful model from Helsinki University Central Hospital. Consecutive patients who activated a 'code stroke' (presentation consistent with acute stroke, eligible for acute stroke therapy) during working hours were included. Results: Prior to the protocol change, 143 patients activated a code stroke, and 30 patients received thrombolysis. Following the protocol change, 134 patients activated a code stroke, and 14 patients received thrombolysis. The median time to administer thrombolysis was reduced from 76 min (interquartile range 54–91) to 33 min (27–44), P < 0.01. The median time to perform diagnostic computed tomography was unchanged between the two groups, 23 (14–54) min versus 22 (9–49) min, P = 0.12. However, this was reduced on subgroup analysis of patients whose arrival was pre‐notified by the ambulance service, 16 (9–22) min versus 8 (4–14) min, P < 0.01. Conclusion: Time to treatment in acute stroke was dramatically improved with a simple intervention. This was achieved without a large stroke team or additional funding, making it highly accessible to other health services also seeking to improve their stroke service. [ABSTRACT FROM AUTHOR]

Objectives: To present long‐term oncological outcomes of patients with paratesticular sarcoma treated by a multidisciplinary team. Patients and methods: Patients managed at the Princess Margaret Cancer Centre, between 1990 and 2012, were analysed. A sarcoma expert performed central pathology review. Kaplan–Meier graphs compared local recurrence (LR), metastasis, and overall survival (OS) of patients treated with hemiscrotectomy vs those who did not. Univariable Cox proportional hazards analysis was performed to delineate predictors of LR, metastasis, and OS. Results: Overall, 51 patients with a median (interquartile range) follow‐up of 132 (51.6–226.8) months were analysed. At presentation, 92.2% (47 patients) had localised disease. Only five patients (9.8%) had undergone initially planned hemiscrotectomy. Completion and salvage hemiscrotectomy was performed in 25 (54.3%) and seven (15.2%) patients, respectively. Recurrence and metastasis occurred in 12 (25.5%) and 10 patients (19.6%), respectively. At the last follow‐up, 21.6% (11 patients) had died, with eight dying from their disease. Kaplan–Meyer graphs demonstrated that hemiscrotectomy improved LR (median not reached vs 62.4 months, log‐rank P = 0.008) and OS (median not reached vs 168 months, log‐rank P = 0.081). Univariable analysis found hemiscrotectomy to be associated with a lower LR rate (hazard ratio [HR] 0.21, P = 0.02), whilst positive margins at initial surgery were associated with increased LR (HR 4.81, P = 0.047). No metastasis predictors were found, but age (HR 1.04, 95% confidence interval [CI] 1.0–1.08; P = 0.02) and non‐localised disease at presentation (HR5.17, 95% CI 1.33–20.06; P = 0.017) were associated with worse OS. Conclusion: Paratesticular sarcoma is a rare tumour, predominantly manifesting as localised disease. Most patients receive an initial suboptimal oncological surgery. Improved long‐term outcomes are demonstrated following early hemiscrotectomy. [ABSTRACT FROM AUTHOR]

Three biflavonoids [cupressuflavone (1), amentoflavone (2), and sumaflavone (3)], four diterpenoids [13-epi-cupressic acid (4), imbricatholic acid (5), 3-hydroxy-sandaracopimaric acid (6), and dehydroabietic acid (7)], and one lignan [β-peltatin methyl ether (8)] were isolated from the cytotoxic fractions of the extracts of the leaves of the Libyan Juniperus phoenicea L. The structures of these compounds were elucidated by spectroscopic means. Cytotoxicity of compounds 1-6 were assessed against the human lung cancer cell line A549 using the MTT assay. Compounds 1 and 3 showed cytotoxicity against the A549 cells (IC50  = 65 and 77 μM, respectively), whereas compound 2 did not show any activity. Diterpenes 4-6 exhibited weak cytotoxicity against the A549 cells with the IC50 values of 159, 263, and 223 μM, respectively. The cytotoxicity of each compound was compared with the anticancer drug, etoposide (IC50  = 61 μM). Cupressuflavone (1) was evaluated also for cytotoxicity against both the human PC3 cancer cell line and the normal prostate cell line (PNT2), and this compound revealed a high degree of cytotoxic selectivity towards the prostate cancer cells (PC3), with IC50 value of 19.9 μM, without any evidence of cytotoxicity towards the normal prostate cell line (PNT2). [ABSTRACT FROM AUTHOR]

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The article offers a study that aims to report the rate of nodal metastases in patients undergoing salvage laryngectomy and neck dissection. It discussed to identify predictors of occult neck metastases and to investigate the relationship between surgical complications and extent of surgery. It mentions the rate of pharyngocutaneous fistula during neck dissection in salvage laryngectomy cohort.

Aims: Intraductal and cribriform carcinoma of the prostate are increasingly recognised as independent prognosticators of poor outcome, both in prostate biopsies and surgical specimens. We studied the concordance of biopsy and prostatectomy diagnosis for these two subpathologies in relationship with pathological stage. Methods and results: Mandatory synoptic reporting of intraductal and cribriform carcinoma in prostate biopsies and prostatectomy specimens was adopted by two academic institutions in November 2015. Synoptic reports of 245 biopsy and corresponding prostatectomy specimens were interrogated to determine the prevalence of intraductal and cribriform carcinoma. Sensitivity and specificity were determined, with prostatectomy diagnosis as the gold standard. Associations with pathological stage as primary outcome parameter were determined using univariable and multivariable logistic regression analysis. Prevalence of the combination of intraductal and cribriform carcinoma was 26.9% in biopsies and 51.8% in prostatectomy specimens. Sensitivity and specificity at biopsy were 47.2% and 94.9%, respectively. Intraductal and cribriform carcinoma at biopsy were associated with advanced pathological stage independent of grade (P = 0.013). Among patients with grade group 2 prostate cancer at biopsy, the more advanced pathological stage distribution was similar for those with a false negative and a true positive biopsy diagnosis of intraductal and cribriform carcinoma (P = 0.29). Conclusion: In spite of low sensitivity, intraductal and cribriform carcinoma at biopsy was associated strongly with advanced stage at radical prostatectomy. As a false negative biopsy diagnosis was equally associated with advanced pathological stage, efforts should be undertaken to improve the sensitivity of biopsy diagnosis for intraductal and cribriform carcinoma. [ABSTRACT FROM AUTHOR]

Aims: The International Collaboration on Cancer Reporting (ICCR) has provided detailed data sets based upon the published reporting protocols of the Royal College of Pathologists, the Royal College of Pathologists of Australasia and the College of American Pathologists. Methods and results: The data set for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use, and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the fourth edition of the World Health Organisation Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are required and recommended components of the report. Required elements are: specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are: preoperative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). Conclusions: It is anticipated that the implementation of this data set in routine clinical practice will inform patient treatment as well as provide standardised information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. [ABSTRACT FROM AUTHOR]

Commiphora africana (A. Rich.) Endl. (Burseraceae) is a medicinal plant widely used in Nigerian ethnomedicine. The in vitro cytotoxicity of the stem bark extract of C. africana and isolated cytotoxic compounds was investigated. Three resveratrol derivatives: (E)-resveratrol 3-O-rutinoside (1), 5-methoxy-(E)-resveratrol 3-O-rutinoside (2), and pinostilbene (3), together with 3-hydroxy-5-methoxybenzoic acid (4) were isolated from the methanol fraction of C. africana. Their structures were determined by extensive analysis of their HREIMS and NMR spectra. The cytotoxicity of the isolated compounds against four human carcinoma cells was determined using the MTT assay. Compound 1 displayed the highest antiproliferative effect on the cell lines, with IC50 values of 16.80, 21.74, 17.89, and 17.44 μM, against MCF7, A549, PC3, and HepG2 human cancer cell lines, respectively. In addition, compounds 1-3 showed low toxicity against normal human prostate cell line, with selectivity indices greater than five across the carcinoma cells, indicating that the compounds possess potential in the development of low-toxicity chemotherapeutic agents. These results support the traditional use of this plant in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present the case of a 30‐year‐old woman with a history of perinatal complications as well as bladder and urinary disease through her childhood and adult life. Microarray comparative genomic hybridization (aCGH) analysis revealed a 1.3 megabase duplication at chromosome 8q21.11 encompassing the CASC9 and HNF4G genes. We present the case of a 30‐year‐old woman with a history of perinatal complications as well as bladder and urinary disease through her childhood and adult life. Microarray comparative genomic hybridization (aCGH) analysis revealed a 1.3 megabase duplication at chromosome 8q21.11 encompassing the CASC9 and HNF4G genes. [ABSTRACT FROM AUTHOR]

Aims: Despite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading. Methods and results: The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62–0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two‐thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non‐members are able to access a limited number of cases. Conclusions: It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified. [ABSTRACT FROM AUTHOR]

Aims The current World Health Organization classification categorises high-grade neuroendocrine ( NE) carcinomas of the prostate into small-cell and large-cell types. A distinct form of carcinoma showing synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. The aim of this study was to investigate the clinicopathological features of a series of metastatic prostate carcinoma ( PCa) cases with amphicrine features. Methods and results Five cases of high-grade PCa showing an amphicrine immunohistochemical phenotype were prospectively collected. The serum prostate-specific antigen ( PSA) level at diagnosis ranged from 38 ng/ml to 992 ng/ml (median 200 ng/ml). All five patients had metastatic disease, four at initial presentation. Microscopically, the tumours showed a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei, and macronucleoli. Morphological features of small-cell or large-cell NE carcinoma were absent. As compared with conventional high-grade PCa, the tumour cells showed a higher level of nuclear pleomorphism, brisk mitotic activity, and a high Ki67 proliferation index (median 50%). All cases showed immunohistochemical positivity for PSA, androgen receptor, and prostate-specific acid phosphatase, combined with diffuse or confluent/non-focal positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a clinical response to androgen deprivation therapy. Conclusion This series highlights a previously undefined, clinically aggressive variant of PCa showing dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology, and ultimately improve their clinical management. [ABSTRACT FROM AUTHOR]

Aims Despite efforts to standardize histopathology practice through the development of guidelines, the interpretation of morphology is still hampered by subjectivity. We here describe Pathology Imagebase, a novel mechanism for establishing an international standard for the interpretation of pathology specimens. Methods and results The International Society of Urological Pathology ( ISUP) established a reference image database through the input of experts in the field. Three panels were formed, one each for prostate, urinary bladder and renal pathology, consisting of 24 international experts. Each of the panel members uploaded microphotographs of cases into a non-public database. The remaining 23 experts were asked to vote from a multiple-choice menu. Prior to and while voting, panel members were unable to access the results of voting by the other experts. When a consensus level of at least two-thirds or 16 votes was reached, cases were automatically transferred to the main database. Consensus was reached in a total of 287 cases across five projects on the grading of prostate, bladder and renal cancer and the classification of renal tumours and flat lesions of the bladder. The full database is available to all ISUP members at . Non-members may access a selected number of cases. Conclusions It is anticipated that the database will assist pathologists in calibrating their grading, and will also promote consistency in the diagnosis of difficult cases. [ABSTRACT FROM AUTHOR]

In Australia 1% of individuals aged over 50 years have Parkinson disease ( PD). Guidance for commencing device-assisted therapies ( DAT) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important aspects when considering which DAT to use are the preferences of the patient and their carers, patient comorbidities, age, cognitive function and neuropsychiatric status. Patients and their families need to be provided with treatment options that are suitable to them, with adequate explanations regarding the recommendations and comparison of potential device-related complications. DAT are best managed, where possible, in a specialist centre with experience in all three types of therapy. Proactive and early management of symptoms during disease progression is essential to maintain optimally motor responses and quality of life in patients with PD. [ABSTRACT FROM AUTHOR]

The bioassay-guided fractionation of the n-hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), β-amyrin (4), stigmasterol (5), β-sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI-MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1-6 were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n-hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC50 s of 45.6 and 54.7 μg/mL, respectively. Moreover, the 70% ethyl acetate in n-hexane chromatographic fraction showed significant activity displaying IC50 values of 53.0, 52.4 and 49.1 μg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC50 of 510.0 μg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n-hexane fraction in the range of 9.6-10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC50 values in the range of 18.2-96.3, 9.2-34.1 and 7.5-97.2 μg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Sleep benefit ( SB) in Parkinson's disease refers to improved motor symptoms upon waking despite an entire night without medications. Although it was first proposed 30 years ago, this phenomenon proved difficult to investigate, and its true prevalence and underlying mechanisms remain unclear. Objective This study aimed to identify and quantify SB through measurement of motor function using a validated smartphone application and to identify disease characteristics that predicted SB. Methods Ninety-two patients recruited from 2 Movement Disorder Services were clinically assessed at home using a validated smartphone application. Each patient was tested in the on-state, at the end of dose, and on waking (before medications) 3 times. Differences between the 3 states were used to determine the impact of sleep and levodopa on motor function. SB was considered to be a 'measurable improvement in parkinsonism from the end of dose.' Results The morning waking motor function of 20 patients (22%) improved compared with the end-of-dose function, with 9 patients demonstrating superior function compared with their on-state. No clinical features predicted SB. Although all participants subjectively reported motor fluctuations, only 35 patients (38%) demonstrated an objective improvement with levodopa. Patients who had SB more often demonstrated objective motor fluctuations compared with those who did not (65% vs. 31%; P = 0.008). Conclusions SB is a genuine motor phenomenon: 1 in 5 patients have a measurable improvement in motor function on waking. It remains questionable whether this improvement is a direct effect of sleep. Until its underlying mechanism is better understood, it is more appropriate to refer to this phenomenon as simply morning improvement or diurnal fluctuation of motor symptoms. [ABSTRACT FROM AUTHOR]

Objectives To develop and externally validate a nomogram that predicts risk of side-specific extraprostatic extension ( EPE) at time of surgery, using commonly available preoperative markers. Materials and Methods A consecutive sample of 753 men treated by radical prostatectomy ( RP) at the University Health Network, Toronto, between 2009 and 2015, was used to develop the nomogram. The validation cohort consisted of 311 men treated by RP at Ottawa Hospital Research Institute, between 1992 and 2014. The study outcome was presence of ipsilateral EPE. The association between predictors considered and EPE was tested using univariate and multivariate logistic regression analyses. The predictive accuracy of the nomogram was determined using the area under the receiver-operating characteristic curve. Results The overall rate of EPE was 19.8% of all lobes in the developmental cohort and 28.9% in the validation cohort. Significant variables in the models were age, prostate-specific antigen and ipsilateral Gleason score, percentage of positive cores and highest core involvement (all P < 0.05). The nomogram predicting risk of EPE had a predictive accuracy of 0.74 in the external validation cohort. Conclusion We developed and externally validated a nomogram that predicts the risk of ipsilateral EPE based on commonly used preoperative markers. This nomogram may be used to assist surgical decision-making prior to RP. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease ( AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca2+ levels in human SK-N- SH neuroblastoma cells. The Sig2R ligands SAS-0132 and JVW-1009 are neuroprotective in a C. elegans model of amyloid precursor protein-mediated neurodegeneration. Since this neuroprotective effect is replicated by genetic knockdown and knockout of vem-1, the ortholog of progesterone receptor membrane component-1 ( PGRMC1), these results suggest that Sig2R ligands modulate a PGRMC1-related pathway. Last, we demonstrate that SAS-0132 improves cognitive performance both in the Thy-1 hAPPLond/Swe+ transgenic mouse model of AD and in healthy wild-type mice. These results demonstrate that Sig2R is a promising therapeutic target for neurocognitive disorders including AD. [ABSTRACT FROM AUTHOR]

Trillium govanianum Wall. (Melanthiaceae alt. Trilliaceae), commonly known as 'nag chhatri' or 'teen patra', is a native species of the Himalayas. It is used in various traditional medicines containing both steroids and sex hormones. In folk medicine, the rhizomes of T. govanianum are used to treat boils, dysentery, inflammation, menstrual and sexual disorders, as an antiseptic and in wound healing. With the only exception of the recent report on the isolation of a new steroidal saponin, govanoside A, together with three known steroidal compounds with antifungal property from this plant, there has been no systematic pharmacological and phytochemical work performed on T. govanianum. This paper reports, for the first time, on the cytotoxicity of the methanol extract of the roots of T. govanianum and its solid-phase extraction (SPE) fractions against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549) and urinary bladder (EJ138), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide cytotoxicity assay and liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry analysis of the SPE fractions. The methanol extract and all SPE fractions exhibited considerable levels of cytotoxicity against all cell lines, with the IC50 values ranging between 5 and 16 µg/mL. Like other Trillium species, presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography mass spectrometry data. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. Methods and results Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. 'Consensus' was defined as at least 80% agreement, and 'favoured' as 60-80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern ('complex fused'). Conclusions Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (cc RCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in cc RCC. In a cohort of 234 patients with primary cc RCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary cc RCC ( P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival ( P = 0.041) and overall survival ( P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in cc RCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses ( P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. cc RCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in cc RCC. [ABSTRACT FROM AUTHOR]

A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor ( CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen-directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time. [ABSTRACT FROM AUTHOR]

Pro-glacial landscapes are some of the most active on Earth. Previous studies of pro-glacial landscape change have often been restricted to considering either sedimentological, geomorphological or topographic parameters in isolation and are often mono-dimensional. This study utilized field surveys and digital elevation model (DEM) analyses to quantify planform, elevation and volumetric pro-glacial landscape change at Sólheimajökull in southern Iceland for multiple time periods spanning from 1960 to 2010. As expected, the most intense geomorphological changes persistently occurred in the ice-proximal area. During 1960 to 1996 the pro-glacial river was relatively stable. However, after 2001 braiding intensity was higher, channel slope shallower and there was a shift from overall incision to aggradation. Attributing these pro-glacial river channel changes to the 1999 jökulhlaup is ambiguous because it coincided with a switch from a period of glacier advance to that of glacier retreat. Furthermore, glacier retreat (of ~40 m yr−1) coincided with ice-marginal lake development and these two factors have both altered the pro-glacial river channel head elevation. From 2001 to 2010 progressive increase in channel braiding and progressive downstream incision occurred; these together probably reflecting stream power due to increased glacier ablation and reduced sediment supply due to trapping of sediment by the developing ice-marginal lake. Overall, this study highlights rapid spatiotemporal pro-glacial landscape reactions to changes in glacial meltwater runoff regimes, glacier terminus position, sediment supply and episodic events such as jökuhlaups. Recognizing the interplay of these controlling factors on pro-glacial landscapes will be important for understanding the geological record and for landscape stability assessments. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized psychiatric complication in Parkinson's disease (PD). Other impulsive-compulsive behaviors (ICBs) have been described in PD, including punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Possible risk factors for ICDs include male sex, younger age and younger age at PD onset, a pre-PD history of ICDs, and a personal or family history of substance abuse, bipolar disorder, or gambling problems. Given the paucity of treatment options and potentially serious consequences, it is critical for PD patients to be monitored closely for development of ICDs as part of routine clinical care. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Fueled by the growing interest in stem cell biology and the promise of regenerative medicine, study of the hematopoietic stem cell (HSC) microenvironment has provided critical insights into normal and malignant hematopoiesis. Notch receptor signaling in this microenvironment is a critical regulator of HSC fate and differentiation. Notch signaling also has the potential to modulate the growth of various malignant cell types, as evidenced by the growing list of hematologic cancers and other malignancies associated with either mutations in Notch genes or alterations in Notch signaling. In both health and disease, activation of Notch signaling predominantly exerts influence through stromal cell interactions with the tumor or stem cell microenvironments. Definitive evidence from transgenic mouse models has shown that alterations in stromal cell signaling from the bone marrow niche can induce malignant outgrowth of preleukemic clones and leukemia. Understanding how Notch receptor signals in the bone marrow microenvironment govern stem cell behavior will advance our understanding of cancer pathogenesis in hematologic malignancies and may have implications for treating metastatic solid tumors involving bone. These microenvironmental interactions are potential therapeutic targets for treating and preventing a variety of diseases, including bone marrow failure disorders, myelodysplastic syndromes, leukemia, and lymphoma. [ABSTRACT FROM AUTHOR]

The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed. [ABSTRACT FROM AUTHOR]

Aims Ductal adenocarcinoma of the prostate ( DAC) is clinically important, because its behaviour may differ from that of acinar adenocarcinoma. Our aims were to investigate the interobserver variability of this diagnosis among experts in uropathology and to define diagnostic criteria. Methods and results Photomicrographs of 21 carcinomas with ductal features were distributed among 20 genitourinary pathologists from eight countries. DAC was diagnosed by 18 observers (mean 13.2 cases, range 6-19). In 11 (52%) cases, a 2/3 consensus was reached for a diagnosis of DAC, and in five (24%) there was consensus against. In DAC, the respondents reported papillary architecture (86%), stratification of nuclei (82%), high-grade nuclear features (54%), tall columnar epithelium (53%), elongated nuclei (52%), cribriform architecture (40%), and necrosis (7%). The most important diagnostic feature reported for DAC was papillary architecture (59%), whereas nuclear and cellular features were considered to be most important in only 2-11% of cases. The most common differential diagnoses were intraductal prostate cancer (52%), high-grade PIN (37%), and acinar adenocarcinoma (17%). The most common reason for not diagnosing DAC was lack of typical architecture (33%). Conclusions Papillary architecture was the most useful diagnostic feature of DAC, and nuclear and cellular features were considered to be less important. [ABSTRACT FROM AUTHOR]