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A monoclonal antibody (NDOG2) against placental alkaline phosphatase (PLAP) in ovarian cancer has been used in three ways by the Bristol University Department of Obstetrics & Gynaecology. First, in an indirect immunoperoxidase technique, NDOG2 demonstrated positive standing in 64% of 56 ovarian carcinomas as well as in 25% of 44 benign tumours. The majority of these positive tumours were serous cystadenocarcinomas or serous cystadenomas and there was considerable variation in the expression of this antigen from tumour to tumour. NDOG2 was also used as the basis of two serum assays and, when labelled with 123-iodine (123I), in radioimmunoscintigraphy (RIS) to monitor patients' response to therapy. The first serum assay measures the enzymic activity of PLAP and the second recognizes the antigenicity of the molecules. Assay 2 proved more useful in that it predicted the course of the disease in 45% of patients followed up, whereas Assay 1 was only of use in 25% of cases. RIS proved to be a useful imaging technique and was at least as sensitive as conventional imaging techniques. The common causes of false-positive and false-negative results are described. [ABSTRACT FROM AUTHOR]

John-Michael Gamble,1,* Jill J Hall,2,* Thomas J Marrie,3 Cheryl A Sadowski,2 Sumit R Majumdar,4 Dean T Eurich5 1School of Pharmacy, Memorial University of Newfoundland, St John's, NL, 2Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, 3Faculty of Medicine, Dalhousie University, Halifax, NS, 4Faculty of Medicine and Dentistry, 5School of Public Health, University of Alberta, Edmonton, AB, Canada *These authors contributed equally to this work Background/objective: Medication changes at transitions of care and polypharmacy are growing concerns that adversely impact optimal drug use. We aimed to describe transitions and patterns of medication use before and 1 year after older patients were hospitalized for community-acquired pneumonia, the second-most common reason for admission in North America. Materials and methods: This was an analysis of a population-based clinical registry of patients treated in any of the six hospitals or seven emergency departments in Edmonton, Alberta, Canada, comprising 2,105 patients 65 years and older with community-acquired pneumonia who had survived at least 1 year. The prevalence of polypharmacy (five or more unique prescription drugs), as well as new use and persistence of common drug classes were assessed. Results: The mean age was 78 years (standard deviation 8 years), 50% were female, 62% were hospitalized, and 58% had severe pneumonia. Among the 2,105 patients, 949 (45%) were using five or more medications prior to hospitalization, increasing to 1,559 (74%) within 90 days postdischarge and remaining over 70% at 1 year. Overall, 1,690 (80%) patients newly started and 1,553 (74%) patients stopped at least one medication in the first 90 days of follow-up. The prevalence of the most common drug classes (ie, cardiovascular, alimentary/metabolism) remained stable, with the exception of anti-infective agents, whereby 25% of patients were dispensed an anti-infective agent 3 months to 1 year after hospitalization. Conclusion: Most older patients with pneumonia are subject to polypharmacy, and almost every patient had a medication started or stopped during 1-year follow-up, with 25% using antibiotics again. The period following an episode of pneumonia represents an opportunity potentially to optimize pharmacotherapy. Keywords: polypharmacy, drug utilization, elderly, community-acquired pneumonia, pharmacoepidemiology

Total rotational energy transfer (RET) rate constants, state-to-state RET rate constants, and radiative lifetimes have been measured for CN(B [sup 2]Σ[sup +], v=0, N[sub i]=0, 4, 6, 7, 8, 11 and 13). All experiments were conducted under single collision conditions in a static cell filled with previously prepared C[sub 2]N[sub 2]/He mixtures at various total pressures up to a maximum of 800 mTorr. The above initial states were prepared by pumping CN(X) with a pulsed dye laser tuned to appropriate frequencies in the P-branch of the CN-violet (0,0) band following the production of CN(X) by the excimer laser photolysis of C[sub 2]N[sub 2] at 157 nm. Total RET rate constants and radiative lifetimes were determined from decay constants obtained with a transient digitizer over the above range of cell pressures. State-to-state RET rate constants were obtained from time-averaged fluorescence spectra in the R branch of the (0,0) band of the CN violet system at various cell pressures within the above range. A weak propensity for odd jumps in N was discernable in state-to-state RET rate constants in CN(B)/He collisions for N>4. Total RET rate constants varied only slightly with N[sub i] for 0<=N i<=19 with He as collision partner, but decreased monotonically with increasing N[sub i] when C[sub 2]N[sub 2] served as collision partner. No firm evidence for collisionally induced CN(B)↔CN(A) was apparent from our data. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Objective: Study objectives were to develop a questionnaire to assess factors influencing pharmacists’ adoption of prescribing (i.e., continuing, adapting or initiating therapy), describe use of pre-incentive and mixed mode survey, and establish survey psychometric properties. Methods: Questions were developed based on prior qualitative research and Diffusion of Innovation theory. Expert review, cognitive testing, survey pilot, and main survey were used to test the questionnaire. Six content experts reviewed the questionnaire to establish face and content validity. Ten pharmacists from diverse practice settings were purposefully recruited for a cognitive interview to verify question readability. Content analysis was used to analyze the results. A pre-survey introduction letter with a monetary incentive was mailed via post to 100 (i.e. pilot) and 700 (i.e., main survey) randomly selected pharmacists. This was followed by an e-mail with a personalized link to the online questionnaire, e-mail reminders, and a telephone reminder if required. The psychometric properties of scales were evaluated with an exploratory factor analysis and Cronbach’s alpha. Scale responses were described. Results: Engagement of six experts and ten pharmacists clarified definitions (e.g., prescribing), terminology, recall periods, and response options for the 34-item response scale. Fifty-six pharmacists completed the online pilot survey. Based on this data, ambiguous questions and routing issues were addressed. Three hundred and seventy-eight pharmacists completed the online main survey for a response rate of 54.6%. The factors analysis resulted in 27 questions in eight scales: (1) self-efficacy, (2) support from practice environment, (3) support from interprofessional relationship, (4) impact on professionalism, (5) impact on patient care), (6) prescribing beliefs, (7) technical use of electronic health record (EHR) and (8) patient care use of the EHR. Prescribing beliefs and technical use of the EHR scales had low reliability while the remaining six scales had strong evidence for reliability and validity. Conclusion: Through a multi-stage process, a survey instrument was developed to capture pharmacists’ perceptions of prescribing influences. This questionnaire may support future research to develop interventions to enhance adoption of prescribing and enhance direct patient care by pharmacists.

The cell cycle is a fundamental process involved in bacterial reproduction and cellular differentiation. For Sinorhizobium meliloti , cell cycle outcomes depend on its growth environment. This bacterium shows a tight coupling of DNA replication initiation with cell division during free-living growth. In contrast, it undergoes a novel program of endoreduplication and terminal differentiation during symbiosis within its host. While several DivK regulators at the top of its CtrA pathway have been shown to play an important role in this differentiation process, there is a lack of resolution regarding the downstream molecular activities required and whether they could be unique to the symbiosis cell cycle. The DivK kinase CbrA is a negative regulator of CtrA activity and is required for successful symbiosis. In this work, spontaneous symbiosis suppressors of Δ cbrA were identified as alleles of divL and cckA . In addition to rescuing symbiotic development, they restore wild-type cell cycle progression to free-living Δ cbrA cells. Biochemical characterization of the S. meliloti hybrid histidine kinase CckA in vitro demonstrates that it has both kinase and phosphatase activities. Specifically, CckA on its own has autophosphorylation activity, and phosphatase activity is induced by the second messenger c-di-GMP. Importantly, the CckA A373S suppressor protein of Δ cbrA has a significant loss in kinase activity, and this is predicted to cause decreased CtrA activity in vivo . These findings deepen our understanding of the CbrA regulatory pathway and open new avenues for further molecular characterization of a network pivotal to the free-living cell cycle and symbiotic differentiation of S. meliloti .IMPORTANCE Sinorhizobium meliloti is a soil bacterium able to form a nitrogen-fixing symbiosis with certain legumes, including the agriculturally important Medicago sativa . It provides ammonia to plants growing in nitrogen-poor soils and is therefore of agricultural and environmental significance as this symbiosis negates the need for industrial fertilizers. Understanding mechanisms governing symbiotic development is essential to either engineer a more effective symbiosis or extend its potential to non-leguminous crops. Here, we identify mutations within cell cycle regulators and find that they control cell cycle outcomes during both symbiosis and free-living growth. As regulators within the CtrA two-component signal transduction pathway, this study deepens our understanding of a regulatory network shaping host colonization, cell cycle differentiation, and symbiosis in an important model organism., Competing Interests: The authors declare no conflict of interest.

Purpose: To investigate the safety and efficacy of direct oral anticoagulants (DOACs) in the treatment of the acute phase of heparin-induced thrombocytopenia (HIT)., Summary: A systematic review of the literature was conducted on PubMed, MEDLINE, Embase, and Web of Science Core Collection through July 2023. Search terms included "heparin-induced thrombocytopenia AND direct-oral-anticoagulants" in addition to a list of oral anticoagulants. Adult patients who used direct oral anticoagulants as the initial treatment for the acute phase of HIT were included. A total of 1,188 articles were initially identified, with 770 articles reviewed following removal of duplicates. Following the application of inclusion and exclusion criteria, 12 articles were ultimately included. Rivaroxaban was the most-utilized DOAC (28 patients), followed by apixaban (7 patients) and dabigatran (1 patient). All patients with thrombocytopenia demonstrated successful platelet recovery, with two patients presenting with normal platelet counts. One patient developed a deep venous thrombosis with no other new or recurrent thromboses. There were no reported clinically significant adverse events in any patient. Obstacles and deterrents to the use of the standards of care in the acute phase of HIT exist. Argatroban and bivalirudin require intravenous infusion and require close aPTT monitoring and dose adjustment. Fondaparinux requires injection and is contraindicated with body weight <50kg. DOACs would offer the novel ability for an oral treatment in the treatment of the acute phase HIT and allow for minimal monitoring and consistent dosing strategies. Therefore, DOACs are an intriguing choice for the treatment of the acute phase of HIT., Conclusion: Data from 12 publications and across 36 patients suggests that the use of DOACs in the acute phase of HIT may be a safe and efficacious treatment option with favorable ease of monitoring and management., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Older patients with diabetic kidney disease (DKD) often do not receive optimal pharmacological treatment. Current clinical practice guidelines (CPGs) do not incorporate the concept of personalised care. Clinical decision support (CDS) algorithms that consider both evidence and personalised care to improve patient outcomes can improve the care of older adults. The aim of this research is to design and validate a CDS algorithm for prescribing renin-angiotensin-aldosterone system inhibitors (RAASi) for older patients with diabetes., Methods: The design of the CDS tool included the following phases: (1) gathering evidence from systematic reviews and meta-analyses of randomised clinical trials to determine the number needed to treat (NNT) and time-to-benefit (TTB) values applicable to our target population for use in the algorithm. (2) Building a list of potential cases that addressed different prescribing scenarios (starting, adding or switching to RAASi). (3) Reviewing relevant guidelines and extracting all recommendations related to prescribing RAASi for DKD. (4) Matching NNT and TTB with specific clinical cases. (5) Validating the CDS algorithm using Delphi technique., Results: We created a CDS algorithm that covered 15 possible scenarios and we generated 36 personalised and nine general recommendations based on the calculated and matched NNT and TTB values and considering the patient's life expectancy and functional capacity. The algorithm was validated by experts in three rounds of Delphi study., Conclusion: We designed an evidence-informed CDS algorithm that integrates considerations often overlooked in CPGs. The next steps include testing the CDS algorithm in a clinical trial., Competing Interests: Competing interests: J-PL reported honoraria from Amgen Canada, AstraZeneca Canada and Otsuka Canada for work not related to this study. SH reported honoraria from AstraZeneca Canada, and research support from GSK and Merck unrelated to this study. CS reports funding from Pfizer Canada ULC for research unrelated to this study. The remaining authors have declared no conflict of interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical decision-support (CDS) tools are systems that provide healthcare providers (HCPs) with recommendations based on knowledge and patient-specific factors to facilitate informed decisions., Objectives: To identify the key components of a CDS tool that are most important to HCPs in caring for older adults with kidney disease, and to understand the facilitators and barriers toward using CDS tools in daily clinical practice., Methods: Design: A cross-sectional survey of Canadian HCPs was undertaken., Data Collection: Participants affiliated with a provincial college, nephrology organization, or advocacy body were contacted. The survey was conducted between August and October 2021., Instrument: A 59-item questionnaire was developed and divided into five main domains/themes. Analysis was done descriptively., Results: Sixty-three participants completed the questionnaire. Physicians (60%) and pharmacists (22%) comprised the majority of the participants. Most of the participants were specialized in nephrology (65%). The most important components in a CDS tool for prescribing to older patients with kidney disease were the safety and efficacy of the medication (89%), the goal of therapy (89%), and patient's quality of life (87%). 90% were willing to use CDS tools and 57% were already using some CDS tools for prescribing. The majority of the participants selected the validation of CDS tools (95%), accompanying the recommendations by the supporting evidence (84%), and the affiliation of the tools with known organizations (84%), as factors that facilitate the use of CDS tools., Conclusion: CDS tools are being used and are accepted by HCPs and have value in their assistance in engaging patients in making well-informed decisions., (© 2024. The Author(s).)

Background: Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP., Methods: We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated., Results: Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19-3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19-3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15-4.42)., Conclusions: Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve. Clinical Trials Registration. NCT01582711., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Treatment completion is essential for the effectiveness of any latent tuberculosis infection (LTBI) regimen. The Tuberculosis Trials Consortium (TBTC) Study 33 (iAdhere) combined self-report and pill counts - standard of care (SOC) with a medication event monitoring system (MEMS) to determine treatment completion for 12-dose once-weekly isoniazid and rifapentine (3HP). Understanding the performance of SOC relative to MEMS can inform providers and suggest when interventions may be applied to optimize LTBI treatment completion., Method: iAdhere randomized participants to directly observed therapy (DOT), SAT, or SAT with text reminders in Hong Kong, South Africa, Spain and the United States (U.S.). This post-hoc secondary analysis evaluated treatment completion in both SAT arms, and compared completion based on SOC with MEMS to completion based on SOC only. Treatment completion proportions were compared. Characteristics associated with discordance between SOC and SOC with MEMS were identified., Results: Overall 80.8% of 665 participants completed treatment per SOC, compared to 74.7% per SOC with MEMS, a difference of 6.1% (95%CI: 4.2%, 7.8%). Among U.S. participants only, this difference was 3.3% (95% CI: 1.8%, 4.9%). Differences in completion was 3.1% (95% CI: -1.1%, 7.3%) in Spain, and 36.8% (95% CI: 24.3%, 49.4%) in South Africa. There was no difference in Hong Kong., Conclusion: When used for monitoring 3HP, SOC significantly overestimated treatment completion in U.S. and South Africa. However, SOC still provides a reasonable estimate of treatment completion of the 3HP regimen, in U.S., Spain, and Hong Kong., Competing Interests: Declaration of Competing Interest The authorship team members have declared (below or attached) any potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Published by Elsevier Inc.)

Aim: To assess the effect of surgical root coverage (RC) on dentin hypersensitivity (DH) associated with gingival recession., Materials and Methods: Two independent reviewers conducted electronic literature searches in MEDLINE (PubMed), EMBASE, Cochrane Library, Web Of Science, Dentistry & Oral Sciences Source, ScienceDirect, and ClinicalTrials.gov databases as well as a manual search to identify eligible clinical studies from January 2000 to March 2022. Randomized controlled trials (RCTs) comparing two surgical RC techniques or a surgical RC technique with or without adjuvant were included. Meta-analyses were performed on data provided by RCTs., Results: Thirteen RCTs with a total of 701 patients (1086 recessions) were included. The percentage of DH suppression was 70.8% (95% confidence interval [CI] [64.4-76.6]; I 2  = 39.2% [3.5-61.8], Q-test = 0.02) after surgical RC. Recession reduction and percentage of RC were both statistically significantly associated with DH suppression (estimate = 0.66 [0.10-1.23], p = .022, R 2  = 14.45% and estimate = 0.04 [0.01-0.08], p = .012, R 2  = 29.54%, respectively). Coronally advanced flap (CAF) + connective tissue graft showed results statistically more effective than CAF + xenogeneic collagen matrix in DH suppression (73.3% [65.6-79.8] and 61.4% [51.7-70.3], respectively; p = .048)., Conclusions: Success of surgical RC is associated with DH suppression., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Efficient management of study drug inventory shipments is critical to keep research sites enrolling into multisite clinical treatment trials. A standard manual drug-management process used by the Tuberculosis Trials Consortium (TBTC), did not accommodate import permit approval timelines, shipment transit-times and time-zone differences. We compared a new web-based solution with the manual process, during an international 34-site clinical trial conducted by the TBTC and the AIDS Clinical Trials Group (ACTG); TBTC Study 31/ACTG A5349., Material and Methods: We developed and implemented a technological solution by integrating logistical and regulatory requirements for drug importation with statistical simulations that estimated stock-out times in an online Drug Management Module (DMM). We measured the average shipment-related drug stock-outs and time to drug availability, to assess the efficiency of the DMM compared to the manual approach., Results: An Interrupted Time-Series (ITS) analysis showed a 15.4% [p-value = 0.03; 95% C.I. (-28.8%, -2.0%)] reduction in average shipment-related study drug stock-out after DMM implementation. The DMM streamlined the restocking process at study sites, reducing median transit-time for sites associated with a depot by 2 days [95% C.I. (-3.0, -1.0)]. Under the DMM, study drugs were available for treatment assignment on the day received, compared to one day after receipt under the manual process., Discussion: The DMM provided TBTC's Data and Coordinating Center and site staff with more efficient procedures to manage and consistently maintain study drug inventory at enrolling sites. This DMM framework can improve efficiency in future multicenter clinical trials., Trial Registration: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015., (Published by Elsevier Inc.)

The muskrat ( Ondatra zibethicus ) is an iconic species in Canada, valued for both its fur and its integral role in wetland ecosystems, and widely regarded for its perseverance. However, the resilience of this semiaquatic mammal seems to be in question now as increasing evidence points to widespread population declines. Recent analyses of harvest data across North America suggest a reduction in their numbers, but this has not been widely corroborated by population surveys. In this study we replicated historic muskrat house count surveys at two large Great Lakes coastal wetlands and present confirmation that declines in muskrat harvest correspond to actual declines in muskrat abundance. At the Point Pelee National Park marsh and the Matchedash Bay-Gray Marsh wetland we found that mean muskrat house counts declined by 93% and 91% respectively between historic surveys 40-50 yrs ago and contemporary surveys over the past 7 yrs. The factors responsible for these dramatic declines remain unclear but there may be a relationship with changes in the habitat quality of these wetlands that have occurred over the same time frame. Not only is the loss of muskrats an issue for the resulting loss of the wetland ecosystem services they provide, but it may be an indication of broader marsh ecosystem degradation. As such, a scarcity of muskrats should be considered a red flag for the state of biodiversity in our wetlands. Continued surveys and ongoing research are needed to shed more light on the current status of muskrat populations and their marsh habitats across their native range., Competing Interests: The authors declare there are no competing interests or conflicts of interest., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: This article aims to identify best practices, improve risk controls, and aid regulatory agencies in developing guidance for environmental and biosafety risk assessment for commercial-scale cell and gene therapy manufacturing., Methods: A cross-functional team should start with hazard classification and testing requirements for materials used or generated by the process and process hazard characterization., Results: The team develops a safety profile of the process to mitigate risks, including: product biological contamination risk and process controls, including raw materials, facilities, operator and environmental controls, and method of detection;a technical review of the process to evaluate the operational and engineering controls;monitoring systems to mitigate the risk of failure and/or breach of the system, preventing the release of material to the facility or operator exposure;site sanitization strategy and facility containment measures, including engineering designs, air handling systems, spill containment measures, surface cleanability, waste flows, and decontamination practices;a review of site practices, including process, employee, material and waste flows, staff training, controlled access, operator gowning, and emergency response plans/measures., Discussion: The cross-functional team should regularly reconvene to provide solutions for enhanced process control, process life-cycle management, monitor assumptions, and track performance. The plan must be revised following any relevant failure event or process change., Conclusion: A risk assessment template is shared to bring to the reader's attention the complexity of commercial-scale manufacturing, areas to assess, potential questions to ask, and other pertinent parties who may input to the risk assessment., (© ABSA International 2020.)

Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22 † -July 3, 2020 were analyzed. The analysis was limited to 23 states § with >70% complete race/ethnicity information and five or more laboratory-confirmed COVID-19 cases among both AI/AN persons (alone or in combination with other races and ethnicities) and non-Hispanic white (white) persons. Among 424,899 COVID-19 cases reported by these states, 340,059 (80%) had complete race/ethnicity information; among these 340,059 cases, 9,072 (2.7%) occurred among AI/AN persons, and 138,960 (40.9%) among white persons. Among 340,059 cases with complete patient race/ethnicity data, the cumulative incidence among AI/AN persons in these 23 states was 594 per 100,000 AI/AN population (95% confidence interval [CI] = 203-1,740), compared with 169 per 100,000 white population (95% CI = 137-209) (rate ratio [RR] = 3.5; 95% CI = 1.2-10.1). AI/AN persons with COVID-19 were younger (median age = 40 years; interquartile range [IQR] = 26-56 years) than were white persons (median age = 51 years; IQR = 32-67 years). More complete case report data and timely, culturally responsive, and evidence-based public health efforts that leverage the strengths of AI/AN communities are needed to decrease COVID-19 transmission and improve patient outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The Bruyère Evidence-Based Deprescribing Guideline Symposium included a forum on health professional education that brought together health professionals, researchers, professional organization representatives and public members. The goal was to facilitate partnerships among educators and to build knowledge, skills and support for behaviour change to integrate the use of evidence-based deprescribing guidelines into health care professional education. Participant discussions were analyzed under the thematic headings of teaching, learning, and assessment, impact of heuristics in learning, the importance of patient/public understanding and the role of leadership in enabling curricular change to include deprescribing. Deprescribing is considered to be on a continuum with prescribing, and it was recognized that related skills are not consistently taught or assessed, which may be interpreted by learners and health professionals as being less important than diagnostic or other skills. Strategies used currently to teach prescribing may also imply that it is a technical skill, not enabling learners to understand that prescribing and deprescribing involve complex tasks requiring patient consultation. Social barriers to deprescribing were also discussed and the importance of patient perspective in teaching prescribing/deprescribing was recognized. Based on the symposium discussions, the authors make several recommendations that include better teaching of optimal prescribing and deprescribing within an interprofessional context, that education be supported from the pre-licensure, post-graduate levels through to continuing professional development, and that assessment, demonstrating competence in prescribing and deprescribing, be embedded within programs., (Copyright © 2018. Published by Elsevier Inc.)

MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies.

Fusarium head blight (FHB), caused by the fungal plant pathogen Fusarium, is a fungal disease that occurs in wheat and can cause significant yield and grain quality losses. The present paper examines variation in the resistance of spring wheat lines derived from a cross between Zebra and Saar cultivars. Experiments covering 198 lines and parental cultivars were conducted in three years, in which inoculation with Fusarium culmorum was applied. Resistance levels were estimated by scoring disease symptoms on kernels. In spite of a similar reaction of parents to F. culmorum infection, significant differentiation between lines was found in all the analyzed traits. Seven molecular markers selected as linked to FHB resistance QTLs gave polymorphic products for Zebra and Saar: Xgwm566, Xgwm46, Xgwm389, Xgwm533, Xgwm156, Xwmc238, and Xgwm341. Markers Xgwm389 and Xgwm533 were associated with the rate of Fusarium-damaged kernels (FDK) as well as with kernel weight per spike and thousand kernel weight in control plants. Zebra allele of marker Xwmc238 increased kernel weight per spike and thousand kernel weight both in control and infected plants, whereas Zebra allele of marker Xgwm566 reduced the percentage of FDK and simultaneously reduced the thousand kernel weight in control and infected plants.

Unlabelled: CbrA is a DivJ/PleC-like histidine kinase of DivK that is required for cell cycle progression and symbiosis in the alphaproteobacterium Sinorhizobium meliloti. Loss of cbrA results in increased levels of CtrA as well as its phosphorylation. While many of the known Caulobacter crescentus regulators of CtrA phosphorylation and proteolysis are phylogenetically conserved within S. meliloti, the latter lacks the PopA regulator that is required for CtrA degradation in C. crescentus. In order to investigate whether CtrA proteolysis occurs in S. meliloti, CtrA stability was assessed. During exponential growth, CtrA is unstable and therefore likely to be degraded in a cell cycle-regulated manner. Loss of cbrA significantly increases CtrA stability, but this phenotype is restored to that of the wild type by constitutive ectopic expression of a CpdR1 variant that cannot be phosphorylated (CpdR1(D53A)). Addition of CpdR1(D53A) fully suppresses cbrA mutant cell cycle defects, consistent with regulation of CtrA stability playing a key role in mediating proper cell cycle progression in S. meliloti. Importantly, the cbrA mutant symbiosis defect is also suppressed in the presence of CpdR1(D53A). Thus, regulation of CtrA stability by CbrA and CpdR1 is associated with free-living cell cycle outcomes and symbiosis., Importance: The cell cycle is a fundamental process required for bacterial growth, reproduction, and developmental differentiation. Our objective is to understand how a two-component signal transduction network directs cell cycle events during free-living growth and host colonization. The Sinorhizobium meliloti nitrogen-fixing symbiosis with plants is associated with novel cell cycle events. This study identifies a link between the regulated stability of an essential response regulator, free-living cell cycle progression, and symbiosis., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes and their processed products being the most abundant sources. A high number of conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant properties are considered to be primarily involved in many beneficial health effects. The present study was designed to assess the protective effect of lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into six groups. Four groups were treated with tomato paste, per os, for 28 days in doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled water. Pretreatment with tomato paste protected the antioxidant enzymes: superoxide dismutase, catalase and glutathione reductase. Their activity was recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with a lower dose of tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with tomato paste caused a decrease in plasma concentration of protein carbonyls, even below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA damage in leucocytes caused by NDEA was observed. The tomato paste tested was able to suppress NDEA-induced oxidative stress in rats.

Aleutian mink disease virus (AMDV) occurs in the American mink (Neovison vison) in wild populations and on mink farms and can cause illness and death. The North American river otter (Lontra canadensis) may be exposed to AMDV because of shared space and habitat with mink. Using serology and real-time PCR, we tested river otters across Ontario for AMDV infection. We found no evidence of infection in otters, a surprising finding given the sympatric distribution, niche overlap, and close phylogenetic relationship of the river otter and the American mink. Our results are consistent with the hypothesis that the major point of spillover of AMDV between mink farms and wildlife is manure and composting carcasses on mink farms. Mink farms in Ontario are generally in agricultural landscapes; it is unlikely that river otter use these habitats and thus are likely not exposed to AMDV. We found no evidence that AMD is an important disease for the river otters in Ontario.

Introduction and Aims: Dependence on ethanol increases the risk of depression in patients and leads to a damage and deficiencies of brain function, which manifest in cognitive functions impairment. Aripiprazole (ARI) is an atypical antipsychotic drug, which has also been shown to have a beneficial effect on cognitive function. Results of many studies show that, for ARI's antidepressant effect to manifest itself, it is necessary to use a combined therapy with a drug from the group of selective serotonin reuptake inhibitors (SSRIs). The aim of this paper was to assess the antidepressant and impact of ARI on spatial memory in alcohol-preferring rats (EtNPRs)., Design and Methods: In our study, we used Porsolt's forced swimming test (antidepressant effect) and Morris water maze test. The tests have been conducted upon administration of ARI (6 mg/kg i.p.), fluoxetine (FLX; 5 mg/kg p.o.) and combined administration of both drugs in alcohol-dependent rats., Results: The results of behavioural tests carried out have shown a lack of antidepressant and procognitive effects of either ARI or FLX in EtPRs after acute and chronic treatment. Combined administration of both drugs would lead to spatial memory deterioration in the study animals., Discussion and Conclusions: Our results suggest that ARI applied in the experiment had no antidepressant effect and failed to improve spatial memory in study rats. Potential antidepressant and procognitive properties of this drug resulting from its mechanism of action encourage attempts (design) of further research aimed at developing a dose, which will show such effects in alcohol-preferring animals.

Wintertime physiology of captive striped skunks (Mephitis mephitis) in response to cold ambient temperature (Ta) and fasting was investigated with body temperature (Tb) and activity recordings and analyses of hematology, plasma biochemistry and tissue fatty acids (FA). After 105 days of food deprivation, the skunks were in phase II of fasting indicated by the elevated plasma nonesterified FA and glycerol but no accumulation of nitrogen end products. Shorter-chain saturated and monounsaturated FA together with C18-20 n-3 polyunsaturated FA were preferentially mobilized. Individual amino acids responded to fasting in a complex manner, while essential and nonessential amino acid sums remained stable. Increases in hemoglobin and hematocrit suggested dehydration. The activity levels were lower in mid-January-early March, and the activity bouts were mostly displayed between 17:00-23:00 h. Daily torpor was observed in two females with 29 and 46 bouts. The deepest torpor (Tb<31 °C) occurred between dawn and early afternoon and lasted for 3.3 ± 0.18 h. The average minimum Tb was 29.2 ± 0.15 °C and the lowest recorded Tb was 25.8 °C. There was significant relation between the average 24-h Tb and Ta. Increases in wintertime Ta, as predicted by climate change scenarios, could influence torpor patterns in the species., (© 2013.)

Lyme disease (also called borreliosis) is a prevalent chronic disease transmitted by ticks and caused by Borrelia burgdorferi s. l. spirochete. At least one tick protein, namely TROSPA from I. scapularis, commonly occurring in the USA, was shown to be required for colonization of the vector by bacteria. Located in the tick gut, TROSPA interacts with the spirochete outer surface protein A (OspA) and initiates the tick colonization. Ixodes ricinus is a primary vector involved in B. burgdorferi s. l. transmission in most European countries. In this study, we characterized the capacities of recombinant TROSPA protein from I. ricinus to interact with OspA from different Borrelia species and to induce an immune response in animals. We also showed that the N-terminal part of TROSPA (a putative transmembrane domain) is not involved in the interaction with OspA and that reduction of the total negative charge on the TROSPA protein impaired TROSPA-OspA binding. In general, the data presented in this paper indicate that recombinant TROSPA protein retains the capacity to form a complex with OspA and induces a significant level of IgG in orally immunized rats. Thus, I. ricinus TROSPA may be considered a good candidate component for an animal vaccine against Borrelia.

Kura clover (Trifolium ambiguum M. Bieb.), a rhizomatous, persistent legume native to the Caucasus region, has received recent attention in North America and New Zealand as a pasture and silage crop. It is reported to be resistant to most pathogens affecting other clovers, including Sclerotinia trifoliorum Eriks. (3,4), one of the most destructive pathogens of clovers in northern Europe. Kura clover (cv. KTA202) was established in May 2009 near Mochełek, Poland (53° 13' N, 17° 51' E) on a Luvisol soil. By May 2011, 70% of plants grown in an experimental field (350 m 2 ) had died, and 20% of the remaining plants were yellow and wilted. At crowns and the lower stem regions, wet, brown lesions with delicate white mycelium were observed. Lesion development was followed by death of the entire plant in a few days. By early June, only a few asymptomatic plants per square meter remained in the field. Tissue fragments of 20 symptomatic plants were surface-sterilized with 1% NaOCl for 1 min and plated on potato dextrose agar (PDA). A fungus with morphological characteristics of S. trifoliorum was consistently isolated. DNA isolation from sclerotia was performed with the DNeasy Plant Mini Kit (Qiagen, USA). Amplification and sequencing of the ITS region of rDNA was performed with primers ITS1/ITS4. NCBI Blast analysis of the 542-bp segment showed a 99% homology with most of S. trifoliorum and S. sclerotiorum strains in GenBank (e.g., AY547267.1 and EU082466.1). Sequence of isolate St0211TA was deposited in GenBank (Accession No. JQ743329). To determine growth rate of hyphae, morphology, and dimensions of sclerotia, colonies were grown in three replications on PDA at 20 ± 1°C in the dark. S. trifoliorum (CBS 122377) and S. sclerotiorum from our local collection were used as controls. Mean growth rate of S. trifoliorum isolates (20.5 mm/day) was slower compared to S. sclerotiorum (32.3 mm/day). Sclerotia began to form on delicate and smooth mycelium of S. trifoliorum on the entire surface of the plate in 7 to 8 days. Sclerotial size on day 28 was 2.0 to 9.0 × 2.0 to 7.0 mm (average 4.2 × 3.6 mm). Ultimately, the identification of S. trifoliorum was confirmed on the basis of ascospore morphology. Apothecia grew from sclerotia in wet sand at 12°C after 12 weeks. Asci contained dimorphic ascospores: four larger 13.0 to 16.0 × 6.0 to 9.0 mm (average 14.1 × 7.4 μm) and four smaller 10.0 to 12.0 × 5.4 to 6.0 mm (average 10.6 × 6.0 μm), typical for this species (1). Isolate St0511TA, which most intensively produced apothecia, was deposited in CBS (No. 133234). Koch's postulates were fulfilled by pathogenicity tests carried out on 2-week-old T. ambiguum seedlings grown in pots (6 × 30 plants), sprayed with a mycelial fragment suspension, and incubated at 15°C (2). Brown, wet spots with delicate white mycelium were observed on cotyledons after 3 days. After 5 days, approximately 10% of cotyledons were killed and mycelium appeared on stems and leaves, and after 10 days, 73% of seedlings were dead. S. trifoliorum was reisolated from all symptomatic tissues. To our knowledge, this is the first report of S. trifoliorum stem blight on T. ambiguum in the field. References: (1) E. N. Njambere et al. Plant Dis. 92:917, 2008. (2) L. H. Rhodes, Sclerotinia Crown and Stem Rot Resistance, http://www.naaic.org/stdtests/scleroti.htm , 1991. (3) A. K. Slesaravichyus et al., Selektsiya i Semenovodstvo Moskva 6:21, 1988. (4) N. L. Taylor and R. R. Smith, Adv. Agron. 63:153, 1998.

Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD) and emphysema. Although cigarette smoke represses cellular proliferation, the molecular mechanisms underlying this phenomenon are unknown. CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of cell cycle progression, differentiation and pro-inflammatory gene expression, are regulated predominantly at the translational level and may be involved in the pathogenesis of COPD. The aim of this study was to assess the effect of cigarette smoke on proliferation and the expression and translational regulation of C/EBPα and C/EBPβ in nondiseased primary human lung fibroblasts. Fibroblasts were exposed to cigarette smoke-conditioned medium (10% and 20% for 24 h). Proliferation was determined by [(3)H]thymidine incorporation. Protein expression levels were determined by immunoblotting and translation was monitored using a translation control reporter system. Cigarette smoke significantly reduced fibroblast proliferation and significantly upregulated full-length C/EBPα and C/EBPβ proteins due to a shift in the translational control of CEBPA and CEBPB mRNAs. This shift involved the re-initiation of mRNA translation via the regulatory upstream open reading frame, which coincided with increased interleukin-8 release and a decrease in functional elastin level. These findings provide a novel mechanism to understanding the tissue remodelling observed in the lungs of COPD patients.

Background: The aim of this study was to evaluate antidepressant-like effect (Porsolt test), locomotor activity and motor coordination of joint administration of tramadol (TRM) and venlafaxine (VEN) in rats., Methods: The tests were performed on male Wistar rats after single and chronic treatment (7 and 14 days) with TRM intraperitoneally (ip) and VEN orally (po) administered once a day. The controls were given 0.5% carboxymethylcellulose (CMC) solution (0.5 ml per rat, ip and po)., Results: It was found that combination of TRM (5 mg/kg ip) with VEN (20 mg/kg po) caused an increased antidepressant effect compared to TRM and VEN administered alone, with no effect on locomotor activity or motor coordination in rats, which may be of clinical significance. It was also observed that reduced time of active swimming of animals in Porsolt test with an increased dose (10 and 20 mg/kg) and time of administration (7 and 14 days) of TRM were correlated with a decreased locomotor activity in rats. It may indicate the development of tolerance to TRM's antidepressant effect in rats during chronic treatment with doses higher than 5 mg/kg., Conclusion: It can be expected that combination of low doses of TRM and VEN could potentially be feasible and relatively safe in cases with acute pain with co-existing depression, however, further investigations are needed.

Objective: To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand., Methods: This investigator-initiated, single-center, randomized, double-blind, placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0-100-mm visual analog scale (VAS) and functional impairment of at least 6 (0-30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent-to-treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy., Results: There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores -8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores -2.14; P = 0.008). There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups., Conclusion: This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile., (Copyright © 2011 by the American College of Rheumatology.)

A newly developed person-portable gas chromatography-mass spectrometry (GC-MS) system was used to analyze several solvent standards, contact cement, paint thinner, and polychlorinated biphenyl samples. Passive solid phase microextraction sampling and fast chromatography with a resistively heated low thermal mass GC column were used. Results (combined sampling and analysis) were obtained in <2 min for solvent, contact cement, and paint thinner samples, and in <13 min for the polychlorinated biphenyl sample. Mass spectra produced by the small toroidal ion trap detector used were similar to those produced with heavily used transmission quadrupole mass spectrometers for polychlorinated biphenyl compounds, simple alkanes, and cycloalknes, while mass spectra for benzene and the ketone compounds analyzed showed evidence for ion/molecule reactions in the ion trap. For one of the contact cement samples analyzed, no evidence was found to indicate the presence of n-hexane, although the relevant material safety data sheet listed this ingredient. Specific chemical constituents corresponding to a potentially wide range of petroleum distillate compounds were identifiable from GC-MS analyses. The possibility for an improved basic characterization step in the exposure assessment process exists with the availability of fast, person-portable GC-MS, although work is needed to further refine this tool and understand the best ways it may be used.

As shown in clinical studies, combinations of first generation normothymics (carbamazepine - CBZ) with atypical neuroleptics (olanzapine - OLA) lead to improvements in approximately half of patients treated for relapses of bipolar affective disease. Our previous studies have shown OLA to have an antidepressant effect when administered at a dose of 0.5 mg/kg only upon single administration; the effect did not last throughout chronic administration, whereas CBZ administered at a dose of 30 mg/kg showed an antidepressant effect only after 7 days of administration. As shown in our previous studies, both OLA and CBZ improve memory in rats but only after chronic administration. The improved antidepressant effect of many drugs, including OLA and CBZ used in combined therapy - as observed in our clinic - as well as confirmed evidence of OLA's and CBZ's positive effects on cognitive functions in humans and animals substantiated commencement of research on defining the effect of combined administration of OLA and CBZ on sedation (tested in a locomotor activity test), antidepressant effect (Porsolt test) and spatial memory (Morris test) in animals. The tests were performed on male Wistar rats. It was found that in combined administration of CBZ and OLA for 7 and 14 days, OLA would completely prevent the CBZ's sedative effect. With combined administration of CBZ and OLA, both as a single dose and after prolonged treatment for 7 days, a significant reduction in immobility time was observed. Combined administration of CBZ and OLA did not improve memory in rats that received these drugs in a single dose, whereas statistically significant differences were observed in the chronic experiments. It can be assumed that the observed effects of combined administration of CBZ and OLA may be due to the pharmacokinetic interactions, but further studies are necessary to confirm these assumptions.

Vitamin D was initially thought only to function in calcium homeostasis. However, it has multiple roles in human health, including neuromuscular and immune modulation. Recently, its deficiency is increasingly implicated in many diseases. This discovery has led both popular culture and research to find ways that vitamin D can either treat or prevent many diseases. Since vitamin D not only affects the expression of many genes, but also has intra-individual pharmacokinetic variation, a simplistic cause and effect between vitamin D deficiency and illnesses should not be expected. Older adults pose a challenge not only because diseases become more prevalent with ageing, but they also are often complicated with other comorbidities. This article reviews the link of vitamin D deficiency and the associated medical conditions in middle aged and older adults. It also examines the variability in testing vitamin D values and evaluates dosing recommendations based on current evidence.

Background: Numerous studies have reported on the immunophenotype of plasma cells (PCs) in monoclonal gammopathy of undetermined significance (MGUS) and in plasma cell myeloma (PCM), but very few have examined the immunophenotype of normal PCs. In this study, an objective definition of normal range of expression for each antigen was found on normal control PCs. Using these new ranges of normal expression (new method) is different from using a static 20% of PCs cut-off for all antigens as described in the literature (traditional method). These newly calculated normal ranges for each antigen were applied to our data, and compared to histologic and immunohistochemical findings., Methods: Bone marrow samples from 46 patients with PC neoplasms and 15 normal controls were studied. A minimum of 100 PC were analyzed for each patient and control sample. An 8-color staining method was applied to study the immunophenotype of PCs, using a BD FACSCanto II., Results: By the new ranges of normality calculated in this study it was determined that different antigens have different level of expression on polyclonal PCs. CD19 correlated with histology by both the traditional and new methods, but had superior correlation by the new method., Conclusions: This report is the first 8-color immunophenotypic study of PCM in which a "range of normal expression" for each antigen is defined. This is a critical step to help distinguish between a normal and neoplastic PC immunophenotype and discern which antigens are of diagnostic importance., ((c) 2010 Clinical Cytometry Society.)

Objective: To review the evidence for the efficacy of products used for environmental or hand cleaning on the rates of Clostridium difficile-associated diarrhea (CDAD)., Quality of Evidence: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for articles pertinent to the efficacy of cleaning products against C. difficile or studies with outcomes related to rates of CDAD. Evidence was level II., Main Message: Minimizing the incidence of CDAD in geriatric rehabilitation units is essential to achieving the goals of increasing patient function and independence for discharge into the community. Attention to environmental control of C. difficile and its spores by health care workers and patient visitors is an important secondary prevention strategy., Conclusion: Chlorine-releasing agents are more effective than detergents for killing spores produced by C. difficile. No level I evidence is available to determine if the use of chlorine-releasing agents has an effect on rates of CDAD. Hand-washing is currently the recommended strategy for reducing transmission of C. difficile. Alcohol gels do not inactivate C. difficile spores; however, increased use of alcohol hand gel has not been associated with higher rates of CDAD.

Phytophthora cambivora was isolated from rooted bases and roots of Castanea sativa, Chamaecyparis lawsoniana and Cotoneaster spp. as well as from water ponds Located in HNS. In the laboratory trials the species colonised leaf blades and stem parts of 3 tested plant species. Differentiated reaction of tested plant species on P. cambivora was observed.

Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient's follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.