Feasibility and Relevance of an Intervention with Systematic Screening as a Base for Individualized Rehabilitation in Breast Cancer Patients: A Pilot Trial of the ReScreen Randomized Controlled Trial.

Background: A substantial proportion of women with breast cancer (BC) experience a wide range of long-term persistent and troublesome side effects related to the disease and its treatment. The ReScreen randomized controlled trial is conducted aiming to evaluate the effect of early screening of distress followed by individualized rehabilitation after primary BC treatment. Purpose: To examine recruitment, retention, distribution of distress, relevance of intervention and reported problems in a pilot trial of the ReScreen RCT. Patients and methods: Based on international research, a cutoff of ≥7 on the Distress Thermometer was used to identify women in need of extended support. Those who reported high distress were randomized to intervention group (IG, n = 9) or control group (CG, n = 9), while women with low distress formed an observational group (OG, n = 67). Self-reported data was collected at baseline, 2 weeks and 3, 6, 9, and 12 months after start of treatment. The participants were recruited from a BC unit in Sweden. Descriptive statistics were used for analyses. Results: Eighty-five patients consented to participate. The recruitment rate was 73%, answer frequency was 98%, 64%, 95%, and retention rate was 100%, 56%, 91% in the IG, CG and OG, respectively. Few systematic errors were identified. When exploring the distribution of distress, it was evident that the participants scoring ≥7 were fewer (21.2%) than reported in previous studies (34-43%). The most commonly problems reported were in line with previous reports of symptoms, including fatigue and worry. Conclusion: The satisfactory rates of inclusion and data collection and the few systematic errors indicate that the ReScreen study is feasible if well planned and executed. To identify patients in need of extended support, an adjustment of the cutoff in the main study is indicated. Based on self-reported problems, the intervention was found relevant in this context.

Barriers and facilitators for individualized rehabilitation during breast cancer treatment - a focus group study exploring health care professionals' experiences.

BACKGROUND: Breast cancer (BC) and related treatment are associated with the risk of developing a wide range of persistent disabling impairments. Despite extensive research in the field and an enhanced focus on BC rehabilitation, up to 34-43% of these patients are at risk of developing chronic distress. In addition, it is known that these patients repeatedly report unmet needs, which are strongly associated with reduced quality of life. However, despite knowledge that patients' needs for support during BC rehabilitation varies greatly, individualized rehabilitation is often lacking. Therefore, this study aimed to explore health care professionals' (HCPs) experiences of current rehabilitation practice and describe current barriers and facilitators for individualized rehabilitation for patients following BC treatment. METHODS: A total of 19 HCPs were included, representing various professions in BC care/rehabilitation within surgical, oncological and specialized cancer rehabilitation units at a university hospital in Sweden. Five semi structured focus group interviews were conducted and inductively analysed using conventional qualitative content analysis. RESULTS: Three categories were captured: (1) varying attitudes towards rehabilitation; (2) incongruence in how to identify and meet rehabilitation needs and (3) suboptimal collaboration during cancer treatment. The results showed a lack of consensus in how to optimize individualized rehabilitation. It also illuminated facilitators for individualized rehabilitation in terms of extensive competence related to long-term experience of working with patients with BC care/rehabilitation. Further, the analysis exposed barriers such as a great complexity in promoting individualized rehabilitation in a medically and treatment-driven health care system, which lacked structure and knowledge, and overarching collaboration for rehabilitation. CONCLUSION: This study suggests that the cancer trajectory is medically and treatment-driven and that rehabilitation plays a marginal role in today's BC trajectory. It also reveals that structures for systematic screening for needs, evidence-based guidelines for individualized rehabilitation interventions and structures for referring patients for advanced rehabilitation are lacking. To enable optimal and individualized recovery for BC patients', rehabilitation needs to be an integrated part of the cancer trajectory and run in parallel with diagnostics and treatment.

Quality-by-design for biotechnology-related pharmaceuticals.

The following article is a report from a workshop on Quality-by-Design (QbD) held at the 7th European Symposium on Biochemical Engineering Science (7 September 2008, Faro, Portugal).The aim of the workshop was to provide an update on the present status of using QbD in biotechnology-related applications in the pharmaceutical industry. The report summarizes the essential parts of the presentations and covers the industrial, academic, and regulatory aspects of QbD. It concludes with recommendations for further work and development.

Design, synthesis, and multivariate quantitative structure-activity relationship of salicylanilides--potent inhibitors of type III secretion in Yersinia.

Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.

Multivariate design and evaluation of a set of RGRPQ-derived innate immunity peptides.

Oral commensal Streptococcus gordonii proteolytically cleave the salivary PRP-1 polypeptide into an RGRPQ innate peptide. The Arg and Gln termini are crucial for RGRPQ-mediated ammonia production and proliferation by S. gordonii SK12 and adhesion inhibition and desorption by Actinomyces naeslundii T14V, respectively. Here we have applied (i) a multivariate approach using RGRPQ-related peptides varied at amino acids 2, 3, and 4 simultaneously and (ii) size and N- and C-terminal modifications of RGRPQ to generate structure activity information. While the N-terminal arginine motif mediated ammonia production independent of peptide size, other responses required more or less full-length peptide motifs. The motifs for adhesion inhibition and desorption were the same. The adhesion and proliferation motifs required similarly a hydrophobic/low polarity amino acid 4 but differentially a hydrophilic or hydrophobic character of amino acids 2/3, respectively; polar peptides with small/hydrophilic and hydrophilic amino acids 2 and 3, respectively, had high adhesion inhibition/desorption activity, and lipophilic peptides with large/hydrophobic amino acids 2 and 3 had high proliferation activity. Accordingly, while RIWWQ had increased proliferation but abolished adhesion/desorption activity, peptides designed with hydrophilic amino acids 2 and 3 were predicted to behave in the opposite way. Moreover, a RGRPQ mimetic for all three responses should mimic small hydrophilic, large nitrogen-containing, and hydrophobic/low polarity amino acids 2, 3, and 4, respectively. Peptides fulfilling these criteria were 1-1.6-fold improved in all three responses. Thus, both mimetics and peptides with differential proliferation and adhesion activities may be generated for evaluation in biofilm models.

Cadmium in food production systems: a health risk for sensitive population groups.

This paper gives an overview of the cadmium (Cd) situation in agricultural systems and human exposure in Sweden. Cadmium levels in agricultural soils (the plow layer) increase by 0.03% to 0.05% per year. Feed can give substantial contributions of Cd to local agricultural systems. Effects on human kidney function are indicated by some measurements already at today's exposure levels. If food products reach the maximum permissible levels given by the European Union, 10% to 25% of the Swedish population will be exposed to Cd levels above the provisional tolerable weekly intake (PTWI 7 microg Cd kg(-1) body weight). Sensitive groups in the population are individuals with low iron status (mainly women) and kidney disorders. Recent studies indicate that Cd plays a role in osteoporosis and that further research is needed to clarify if Cd is neurotoxic in early developmental stages. Firm actions have to be taken in order to stop a further increase of Cd in agricultural soils. Suggestions for prevention and measures are given in this paper.

Cadmium in food chain and health effects in sensitive population groups.

Even at the low exposure level of cadmium found in this study population living on farms in southern Sweden, there was an indication of effect on biochemical markers of renal function. Women had higher blood cadmium (BCd) and urinary cadmium (UCd) than men, which can be explained by higher absorption of Cd due to low iron status. In the present study, Cd in pig kidneys could not be used to predict human BCd or UCd even though cereals are a substantial part of both the human and the pig diet. The contribution of Cd from locally produced food to the total dietary intake in humans was relatively low and varied and the intake of Cd did not correlate with BCd or UCd. In contrast, Cd levels in pig kidney were significantly related to Cd levels in feed. However, there was no relationship between the locally produced cereals, constituting the main part of the feed, and Cd in pig kidneys. In pig feed, other non-locally produced ingredients contributed to a large part of the Cd in feed. The Cd in non-locally produced feed ingredients reaches the local circulation via excretion in faeces and application of manure to arable soils and will lead to increased levels in the crops. As indicated by experimental data from animals, neurochemical and neurobehavioral effects during development need to be further explored as sensitive endpoints for cadmium toxicity.

Monitoring of cadmium in the chain from soil via crops and feed to pig blood and kidney.

The relationships between cadmium (Cd) levels in soil, feed crops, feed concentrate, pig feed mixture, water, pig blood, and kidney from 49 farms were investigated and the possibility to use pig kidney as a bioindicator of available Cd in the agricultural environment was evaluated. There were correlations between Cd levels in soil and wheat, between wheat and barley, and between feed and kidney. The accumulation ratio between Cd levels in feed and kidney was on average 3. Animals from the same farm, raised in the same environment, given the same feed, and slaughtered at the same age had Cd levels in kidney and blood that could differ several times. This great variation, together with a considerable Cd contribution from nonlocally produced feed ingredients (concentrates), limits the possibilities to use Cd in pig kidney as an indicator of the available Cd in the local environment.

Cadmium in blood and urine--impact of sex, age, dietary intake, iron status, and former smoking--association of renal effects.

We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function.