A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (Catha Edulis (Vahl) Forssk. ex Endl.) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development

Khat (Catha edulis (Vahl) Forssk. ex Endl.) is habitually used as a natural stimulant by millions of people, but is associated with adverse effects on gastrointestinal, cardiovascular and central neural systems. At the cellular level khat toxicity involves p53 induction and cell cycle arrest, decreased mitochondrial function and activation of receptor- and mitochondria-mediated cell death pathways. In this study we have examined an extract of khat for induction of p53 post-translational modifications (PTMs) and the functional role of p53 in khat-mediated cell death. Khat was shown to induce phosphorylation and acetylation of p53 in both the khat-sensitive MOLM-13 and the khat-resistant MV-4-11 cell line, but accumulation of the full-length p53 isoform was only observed in the khat sensitive cell line. Small molecule inhibitors of p38 MAP kinase sensitized MV-4-11 cells for khat-treatment without concomitant stabilization of p53. Experiments using a p53 knock-down cell line and murine p53 knock-out bone marrow cells indicated that p53 was redundant in khat-mediated cell death in vitro. We suggest that analysis of isoform patterns and p53 PTMs are useful for elucidation of biological effects of complex plant extracts, and that p53 protein analysis is particularly useful in the search for new chemical probes and experimental cancer therapeutics.publishedVersio

Current Status of Intravesical Therapies for Bladder Pain Syndrome (BPS): A Narrative Review of Emerging Evidence

Bladder pain syndrome (BPS) is a complex condition, which can have debilitating sequelae for patients. Many elements of BPS remain poorly understood including pathophysiology, diagnosis and treatment. Navigating patient care can therefore be challenging for the clinician. Management mandates a multidisciplinary and symptom-based approach. Intravesical treatments such as instillation therapies remain a cornerstone of most treatment algorithms and there are a range of agents that can be selected. This review offers an up-to-date evaluation of the evidence for these intravesical treatments.publishedVersio

Management of Bladder Pain Syndrome (BPS): A Practical Guide

Bladder pain syndrome (BPS) is a prevalent and pervasive disease. The physical and psychological sequelae can be very burdensome for the patient, and the condition represents a real challenge for the clinician as well. With no simple pathognomonic test, finding harmony in navigating patient care can be demanding. Diagnosis and management rely upon a multidisciplinary and holistic approach. Treatment options include conservative measures and pharmacotherapies as well as bladder instillation therapies. Ultimately, surgery may be offered but only in cases of refractory disease. This article offers a pragmatic guide for clinicians managing this challenging disease.publishedVersio

Patient-reported outcomes after curative treatment for prostate cancer with prostatectomy, primary radiotherapy or salvage radiotherapy

Trials reporting adverse health outcomes (AHOs) in terms of patient-reported outcome measures (PROMs) after contemporary curative treatment of prostate cancer (PC) are hampered by study heterogeneity and lack of new treatment techniques. Particularly, the evidence regarding toxicities after radiotherapy (RT) with the volumetric arc therapy (VMAT) technique is limited, and comparisons between men treated with surgery, primary radiotherapy (PRT) and salvage radiotherapy (SRT) are lacking. The aim of the study was to evaluate change in PROMs 3 months after treatment with robotic-assisted laparoscopic prostatectomy (RALP), PRT and SRT administered with VMAT

Nurses’ and occupational therapists’ experiences of conducting a home-based psychosocial intervention following stroke: a qualitative process evaluation

Background: Persons with stroke are susceptible to psychosocial problems, and express disappointment at how health care professionals fail to meet their psychosocial needs following discharge to home. The responsibility of nurses and occupational therapists in stroke rehabilitation is to assist the persons and their families during the recovery and adjustment process. A home-based dialogical intervention aiming to enhance psychosocial support was therefore developed and tested in a randomized controlled trial. This study is a part of the process evaluation conducted alongside the trial. The aim was to explore the nurses’ and occupational therapists’ experiences of conducting the intervention. Methods: Eighteen nurses and four occupational therapists participated in six focus groups to explore their experiences when providing the intervention. The themes discussed in the focus groups were the aspects that facilitated the delivering of the intervention and the challenges they encountered during the study period. The interviews were analysed using qualitative content analysis. Results: The analysis generated two themes. The theme Developing a supportive relationship to facilitate the adjustment process following stroke had two subthemes: Getting personally involved and Handling challenges. This theme reveals how the nurses and occupational therapists experienced their relationship with the persons with stroke and potential threats which challenged them while conducting the intervention. The theme Developing professional skills in providing psychosocial support had two subthemes: Becoming confident in conducting dialogues and Integrating psychosocial topics. This theme reveals the aspects that the nurses and occupational therapists perceived as facilitating the development of their professional skills in conducting the dialogues. Conclusion: Delivering the psychosocial intervention was perceived as deeply meaningful and increased the nurses’ and occupational therapists’ understanding of how to support stroke survivors to live with the consequences of stroke. However, balancing the professional and the personal relationship was challenging. A basic educational programme, training, supervision and having dedicated time were crucial elements to instil confidence in professionals conducting theme-based dialogues to promote post-stroke psychosocial well-being. Individual clinical experience and knowledge of stroke care were considering important to enable professionals to integrate psychosocial rehabilitation into community health care.publishedVersio

The Longitudinal Course of Prospectively Recorded Patient-reported Outcomes in Prostate Cancer Patients Treated with Surgery and Salvage Radiotherapy

Background - Patient-reported outcome measures (PROMs) after prostate cancer (PC) treatment, including both radical prostatectomy (RP) and salvage radiation therapy (SRT), are under-reported. Objective - To investigate PROMs longitudinally from before SRT until 18 mo after SRT for men treated with contemporary treatment modalities. Design, setting, and participants - This prospective, longitudinal cohort study included 120 men (whole cohort) treated with SRT administered with volumetric modulated arc radiotherapy from 2016 to 2021 at the University Hospital of North Norway. The whole cohort was followed from before SRT until 18 mo after SRT. A subcohort of 48 men was followed from before RP until 18 mo after SRT. Outcome measurements and statistical analysis - PROMs were collected with the Expanded Prostate Cancer Index-26 (EPIC-26), covering symptoms of urinary incontinence, urinary irritative, bowel, sexual, and hormonal domains. The domain scores were inquired before RP, 3 mo after RP, before SRT, at SRT termination, and 3 and 18 mo after SRT. We used linear mixed models with repeated measurements design to assess changes in PROMs throughout the treatment period. Results and limitations - The median age before SRT was 63 yr. For the whole cohort, all five domains worsened at 3 and 18 mo after SRT compared with those before SRT. The estimated mean changes from before SRT to 18 mo after SRT are as follows: urinary incontinence –13.1, urinary irritative function –10.4, bowel –16.8, sexual function –9.1, and hormonal function –20.2 (at clinically important levels for all domains but sexual). For the subcohort, the mean urinary incontinence, bowel, sexual, and hormonal functions were significantly worsened 3 and 18 mo after SRT compared with those before RP at clinically important levels. Conclusions - Men treated for PC report particular increased severity of urinary, bowel, sexual, and hormonal symptoms after SRT compared with baseline status

Discrimination of grade 2 and 3 cervical intraepithelial neoplasia by means of analysis of water soluble proteins recovered from cervical biopsies

<p>Abstract</p> <p>Background</p> <p>Cervical intraepithelial neoplasia (CIN) grades 2 and 3 are usually grouped and treated in the same way as "high grade", in spite of their different risk to cancer progression and spontaneous regression rates. CIN2-3 is usually diagnosed in formaldehyde-fixed paraffin embedded (FFPE) punch biopsies. This procedure virtually eliminates the availability of water-soluble proteins which could have diagnostic and prognostic value.</p> <p>Aim</p> <p>To investigate whether a water-soluble protein-saving biopsy processing method followed by a proteomic analysis of supernatant samples using LC-MS/MS (LTQ Orbitrap) can be used to distinguish between CIN2 and CIN3.</p> <p>Methods</p> <p>Fresh cervical punch biopsies from 20 women were incubated in RPMI1640 medium for 24 hours at 4°C for protein extraction and subsequently subjected to standard FFPE processing. P16 and Ki67-supported histologic consensus review CIN grade (CIN2, n = 10, CIN3, n = 10) was assessed by independent gynecological pathologists. The biopsy supernatants were depleted of 7 high abundance proteins prior to uni-dimensional LC-MS/MS analysis for protein identifications.</p> <p>Results</p> <p>The age of the patients ranged from 25-40 years (median 29.7), and mean protein concentration was 0.81 mg/ml (range 0.55 - 1.14). After application of multistep identification criteria, 114 proteins were identified, including proteins like vimentin, actin, transthyretin, apolipoprotein A-1, Heat Shock protein beta 1, vitamin D binding protein and different cytokeratins. The identified proteins are annotated to metabolic processes (36%), signal transduction (27%), cell cycle processes (15%) and trafficking/transport (9%). Using binary logistic regression, Cytokeratin 2 was found to have the strongest independent discriminatory power resulting in 90% overall correct classification.</p> <p>Conclusions</p> <p>114 proteins were identified in supernatants from fresh cervical biopsies and many differed between CIN2 and 3. Cytokeratin 2 is the strongest discriminator with 90% overall correct classifications.</p

Perceived study-induced influence on the control group in a randomized controlled trial evaluating a complex intervention to promote psychosocial well-being after stroke: a process evaluation

Background A commonly applied control condition in trials evaluating complex interventions in rehabilitation research is “usual care.” The main challenge is to ensure that the control group receives genuine usual care as delivered in everyday clinical practice. The assessment interviews and dialogues with the data collectors may influence the control group participants’ reflections on their condition and adjustments. This represents a threat to the internal validity of the trial. Thus, the aim of this study was to explore the perceived study-induced influence of assessment interviews on the adjustment of the members of a control group in a randomized clinical trial. The aim of the trial was to test a dialogue-based psychosocial intervention aiming at promoting the psychosocial well-being and adjustment of stroke survivors. Methods Fifteen participants in the control group of a multicenter stroke rehabilitation trial participated in narrative semi-structured interviews. Ricoeur’s interpretation theory guided the analysis. Results The perceived study-induced influence of the assessment interviews on the adjustment process of members of the control group varied considerably. The results demonstrated that the assessment interviews facilitated some participants’ feelings of control and their ability to cope. Other participants’ statements indicate that they relied on their existing personal capacity to cope and adjust and that the assessment interviews did not make any difference either on their coping ability or on their process of adjustment. Five themes were identified that described the perceived study-induced influence of the assessment interviews in the control group. The themes illustrated that the assessments served as a safety net, enhanced awareness and understanding, encouraged seeking support, allowed the opportunity to vent disappointment, or did not make any difference either way. Conclusions RCT assessment interviews may influence the adjustment process and represent a serious problem in measuring interventions over time in trials of complex interventions in rehabilitation research. To uphold rigor and stringency, the usual care control conditions should be thoroughly assessed and described. Informing participants only about the treatment they were allocated to receive might counteract the potential to dilute the difference between the two arms of the trial

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019)Swiss National Science Foundation | Ref. 200021_16959

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (nee European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60% from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).Peer reviewe