Perception of unfamiliar caregivers during sickness - Using the new Caregiver Perception Task (CgPT) during experimental endotoxemia.

Social withdrawal is a well-established part of sickness behavior, but in some contexts sick animals might gain from keeping close instead of keeping away. For instance, sick individuals are more willing to be near known individuals who can provide care and safety (close others) compared to when healthy. Yet, interactions with some strangers might also be beneficial (i.e., healthcare professionals), but it is not known how sickness interplay with social behavior towards such individuals. Here, we assessed if sickness affects perception of caregivers, and developed a new task, the Caregiver Perception Task (CgPT). Twenty-six participants performed the CgPT, once after an injection of lipopolysaccharide (LPS, 0.8 ng/kg body weight, n = 24), and once after an injection of saline (n = 25), one hour and forty-five minutes post-injection. During the task, participants watched short video clips of three types of caregivers: a healthcare professional taking care of a sick individual, a healthcare professional not taking care of a sick individual, and a non-healthcare professional taking care of their sick adult child or partner. After each video clip, the likability, trustworthiness, professionalism, and willingness to interact with and receive care from the caregiver were rated on visual analogue scales. Results showed that participants injected with saline rated healthcare professionals who did not take care of a sick individual less positively on all aspects compared to healthcare professionals who took care of a sick individual. Moreover, compared to saline, LPS increased the participants' willingness to receive care from healthcare professionals and non-healthcare professionals providing care, but not from healthcare professionals not providing care. Thus, our results indicate that sick individuals may approach unknown individuals with potential to provide care and support.

The walking sick: Perception of experimental sickness from biological motion.

Identification of sick conspecifics allows for avoidance of infectious threats, and is therefore an important behavioral defense against diseases. Here, we investigated if humans can identify sick individuals solely from biological motion and posture (using point-light displays). Additionally, we sought to determine which movements and sickness parameters would predict such detection. We collected video clips and derived point-light displays (one stride presented in a loop) of sick walkers (injected with lipopolysaccharide at 2.0 ng/kg body weight) and the same walkers when healthy (injected with saline). We then presented these displays to two groups, one group classified each walker as sick or healthy (study 1, n = 106), and the other group scored the walkers' health on a visual analogue scale (study 2, n = 106). The raters were able to identify sick individuals above chance, and rated sick walkers as having worse health, both from observing video clips and point-light displays. Furthermore, both sickness detection and worse apparent health were predicted by inflammation-induced increase in rigidity and slower walking, but not other cues. Altogether, these findings indicate that biological motion can serve as a sickness cue, possibly allowing humans to identify sick conspecifics from a distance, and thereby allowing for disease avoidance.

Increased abdominal fat mass and high fat consumption in young school children with congenital heart disease: results from a case-control study.

BACKGROUND: We have previously found that infants with complex congenital heart disease (CHD) experience growth failure despite high-energy dietary supplementation. This is a follow-up and comparison with healthy controls at 9 years of age regarding body composition and macronutrient intake, especially in relationship to the diet provided during infancy. METHODS: Anthropometric changes in 10 children with CHD at 12 months and at 4 and 9 years of age were analysed as Z-scores. To assess body composition and food intake at 9 years of age, a dual-energy X-ray absorptiometry scan and a 3-day food diary were completed and compared with age- and gender-matched controls using Wilcoxon's signed-rank test for matched pairs. RESULTS: Growth changes from 12 months to 9 years, converted to Z-scores for weight for height and height for age, were significantly different within the group of children with complex CHD, although no growth differences were seen in comparison with healthy controls at 9 years of age. However, the children with CHD had statistically higher abdominal fat mass index and higher daily intake of fat, particularly from saturated fatty acid in g kg-1 compared to controls. CONCLUSIONS: At 9 years of age, children with complex CHD with growth failure and high fat intake in infancy have normalised growth but increased abdominal fat mass and higher intake of saturated fatty acid compared to their peers. Nutritional monitoring in early childhood may detect unhealthy diet quality and prevent later health risks in this group.

Changes in attitudes, intended behaviour, and mental health literacy in the Swedish population 2009-2014: an evaluation of a national antistigma programme.

OBJECTIVE: Public stigma of mental illness is still a major problem where numerous population studies during the last decade have mainly shown no improvements. A Swedish national antistigma campaign has been running 2010-2014. The aim of this study was to investigate changes in public stigma during this period as compared to baseline in 2009. METHODS: Yearly population surveys were made between 2009 and 2014 including assessments of mental health literacy, attitudes, and intended future behaviour. Two surveys were made, one including a nationally representative sample and one including a representative sample from three original campaign regions. Multiple regression analyses, also including age, gender, education, and familiarity with mental illness were made to investigate yearly changes in public stigma compared to baseline. RESULTS: Mental health literacy improved significantly in the campaign regions between 2009 and 2014, as did intended future behaviour. Attitudes toward mental illness also improved significantly. Improvements were also shown in the national population surveys, but the time pattern of these compared to that of the original campaign regions indicated that these changes took place mainly after the campaign had been extended to a further five Swedish regions. CONCLUSION: The results of our surveys suggest that a campaign primarily based on social contact theory and involving people with lived experience of mental illness may, even in a rather short-term perspective, have a significant positive impact on mental health literacy, attitudes, and intentions of social contact with people with mental illness.

Dietary intake in infants with complex congenital heart disease: a case-control study on macro- and micronutrient intake, meal frequency and growth.

BACKGROUND: Children with severe congenital heart disease (CHD) need considerable nutritional support to reach normal growth. The actual intake of macro- and micronutrients in outpatient CHD infants over a 6-month period in infancy is not described in the literature. The present study aimed to prospectively investigate the distribution between macro- and micronutrient intake, meal frequency and growth in children with CHD. METHODS: At 6, 9 and 12 months of age, a 3-day food diary and anthropometric data were collected in 11 infants with severe CHD and 22 healthy age- and feeding-matched controls. Macro- and micronutrient intake, meal frequency and growth were calculated. RESULTS: Compared to the healthy controls, CHD infants had a statistically significantly higher intake of fat at 9 months of age (4.8 versus 3.6 g kg(-1) day(-1) ), a higher percentage energy (E%) from fat, (40.6% versus 34.5%) and a lower E% from carbohydrates (46.1% versus 39.6%) at 12 months of age, and a lower intake of iron (7.22 versus 9.28 mg day(-1) ) at 6 months of age. Meal frequency was significantly higher at 6 and 9 months of age (P < 0.01). Mean Z-score weight for height, weight for age and body mass index for age were significant lower (P < 0.01) at all time points. CONCLUSIONS: Despite a higher intake of energy from fat and a higher meal frequency, the intake does not meet the needs for growth, and the results may indicate a low intake of micronutrients in CHD infants.

Alemtuzumab (anti-CD52 monoclonal antibody) as single-agent therapy in patients with relapsed/refractory chronic lymphocytic leukaemia (CLL)-a single region experience on consecutive patients.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is used in patients with refractory chronic lymphocytic leukaemia (CLL). We report results in health care with alemtuzumab on consecutive, advanced-stage patients from a well-defined geographical region. Records from 1,301 patients (Stockholm-Cancer-Registry 1991-2010) identified 56 relapsed/refractory patients treated with alemtuzumab. Median age was 69 years, 88 % had advanced Rai-stage with median 3 prior therapies. One fourth had bulky lymphadenopathy and 73 % were refractory to purine analogues. Median treatment length was 11.6 weeks. Median cumulative dose was 930 mg, significantly higher (p = 0.0277) for responders. Overall response-rate (ORR) was 43 %; 32.5 %, 50 % and 87.5 % in the Refractory, Purine analogue relapsed and Relapsed/Other subgroup, respectively. Response rate was significantly associated with subgroup (p = 0.0104). Good performance status (PS) was associated with better response rate (p = 0.0227). Median time-to-treatment-failure (TTF) (months) was 7.8 months, significantly (p < 0.0001) longer for responders (13.4) Major infections occurred in 36 %. Median overall survival was 22.5 months (range 0.4-74.3). Positive predictive factors were good PS (p < 0.0001) and fewer previous therapies (p = 0.0038). Twenty percent were retreated with alemtuzumab with an ORR of 54.5 %, and a TTF of 7.1 months. A high cumulative dose/longer duration of therapy and a relatively high response rate was observed compared to previous reports. Optimal patient identification and management may result in avoidance of early discontinuation and possibly better outcomes.

Landlords' experiences of housing tenants suffering from severe mental illness: a Swedish empirical study.

The aim of this Swedish study was to describe landlords' experiences of having tenants suffering from severe mental illness. Sixteen landlords working in private and public housing agencies participated in open in-depth interviews. Data were subjected to a thematic latent content analysis. The results showed that having tenants with severe mental illness entails being confronted with various difficult circumstances, ranging from mismanagement of apartments to sensitivity among neighbours as well as issues regarding provocative behaviour. It involved providing assistance that was far beyond their professional obligations and to be neglected by the community-based psychiatric service system when in need of help. In order to support landlords and to prevent evictions of individuals with severe mental illness, community-based psychiatric services need to be more pro-active in their attempts to achieve collaboration with the parties at hand.

Sex identification and PIT-tagging: tools and prospects for studying intersexual differences in freshwater fishes.

This study evaluated a technique to allow the long-term monitoring of individual fishes of known sex in the wild using sex confirmation in close proximity to the reproductive period combined with individual tagging. Hundreds of partially migratory roach Rutilus rutilus were tagged with passive integrated transponders (PIT) following sex determination in spring and various performance measures were compared with fish tagged outside the reproductive period in autumn. Short-term survival was >95% for R. rutilus sexed and tagged under natural field conditions. Total length (LT ) did not affect the probability of survival within the size range tagged (119-280 mm), nor were there differences in timing of migration the following season between individuals sexed and tagged in spring and individuals tagged in autumn (i.e. outside the reproductive period). Also, a similar per cent of R. rutilus sexed and tagged in spring and tagged in autumn migrated the following season (34·5 and 34·7%). Moreover, long-term recapture data revealed no significant differences in body condition between R. rutilus individuals sexed and tagged in spring, individuals tagged in autumn and unmanipulated individuals. The observed sex ratio of recaptured fish did not differ from the expected values of equal recapture rates between males and females. Hence, there is no observable evidence for an adverse effect of tagging close to the reproductive period and therefore this method is suitable for studying intersexual differences and other phenotypic traits temporarily expressed during reproduction at the individual level in fishes.

Manifestations of acute appendicitis: a prospective study on acute abdominal pain.

BACKGROUND/AIMS: The aim of this prospective study was to identify the clinical symptoms and signs most important for the prediction of appendicitis among patients with acute abdominal pain. METHODS: Clinical findings in 2,478 patients admitted to the emergency department of Mora Hospital from February 1997 to June 2000, with acute abdominal pain of up to 7 days' duration, were registered in a database. The medical records were reviewed after 1 year. RESULTS: A total of 432 patients were suspected of having appendicitis and in 221 this diagnosis was confirmed. Some 53 patients, with another preliminary diagnosis, were eventually found to suffer from appendicitis, making a total of 274 patients with appendicitis. Appendectomy was performed in 316 patients and was negative in 14%. Clinical diagnosis of appendicitis had a sensitivity of 0.81, a specificity of 0.90, a positive predictive value of 0.51, a positive likelihood ratio of 8.1, and a diagnostic accuracy of 0.89. The highest odds ratios were found for isolated tenderness in the right iliac fossa (3.29), rebound tenderness (3.00), right-sided rectal tenderness (2.53), migration of pain to the right iliac fossa (2.18), and local guarding (2.11). CONCLUSION: Clinical findings indicating localised inflammation in the right iliac fossa were reliable in predicting acute appendicitis. The patients' history of pain combined with a careful clinical examination still plays an important role in detecting appendicitis among patients with acute abdominal pain.

Partial migration in fishes: causes and consequences.

Partial migration, where only some individuals from a population migrate, has been widely reported in a diverse range of animals. In this paper, what is known about the causes and consequences of partial migration in fishes is reviewed. Firstly, the ultimate and proximate drivers of partial migration are reflected upon: what ecological factors can shape the evolution of migratory dimorphism? How is partial migration maintained over evolutionary timescales? What proximate mechanisms determine whether an individual is migratory or remains resident? Following this, the consequences of partial migration are considered, in an ecological and evolutionary context, and also in an applied sense. Here it is argued that understanding the concept of partial migration is crucial for fisheries and ecosystem managers, and can provide information for conservation strategies. The review concludes with a reflection on the future opportunities in this field, and the avenues of research that are likely to be fruitful to shed light on the enduring puzzle of partial migration in fishes.

Partial migration in fishes: definitions, methodologies and taxonomic distribution.

Partial migration, where populations are composed of both migratory and resident individuals, is extremely widespread across the animal kingdom. Researchers studying fish movements have long recognized that many fishes are partial migrants, however, no detailed taxonomic review has ever been published. In addition, previous work and synthesis has been hampered by a varied lexicon associated with this phenomenon in fishes. In this review, definitions and important concepts in partial migration research are discussed, and a classification system of the different forms of partial migration in fishes introduced. Next, a detailed taxonomic overview of partial migration in this group is considered. Finally, methodological approaches that ichthyologists can use to study this fascinating phenomenon are reviewed. Partial migration is more widespread amongst fishes than previously thought, and given the array of techniques available to fish biologists to study migratory variation the future of the field looks promising.

How do eating disorder patients eat after treatment? Dietary habits and eating behaviour three years after entering treatment.

OBJECTIVE: Improvements in psychological symptoms and weight have often been demonstrated following eating disorder (ED) treatment, but it is not clear to what extent eating behaviour itself is normalised. This cross-sectional study aimed to investigate dietary habits and eating behaviour in ED patients three years after entering treatment. METHOD: ED patients (N=70) were divided into those who had recovered (N=36), and those who still suffered from bulimic (N=18) or anorexic (N=16) psychopathology. Patients were compared to a female normal control group of similar age (N=61), and assessments were made on a dietary questionnaire, as well as the BDI, EDI-2, SASB and SCL-90. RESULTS: With some notable exceptions eating patterns in recovered patients resembled those of controls. Dieting was most evident in recovered and current bulimic patients, while restrictive eating and vegetarianism was found in recovered or current anorexic patients. A majority of the patients with ongoing EDs avoided fatty foods. DISCUSSION: Risk behaviours such as restrictive eating, dieting and food avoidance, may have an important impact on relapse rates, and it may therefore be imperative to continue to monitor eating behaviour in ED patients following treatment termination to ensure better long-term outcome.

Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST).

BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.

Anastomotic-vaginal fistula (AVF) after anterior resection of the rectum for cancer--occurrence and risk factors.

OBJECTIVE: The aim of the study was to assess recto-vaginal fistula (RVF) after anterior resection of the rectum for cancer with regard to occurrence and risk factors. METHOD: All female patients [median age 69.5 years, Union Internationale centre le Cancer (UICC) cancer stage IV in 10%] who developed a symptomatic RVF (n = 20) after anterior resection of the rectum for cancer from three separate cohorts of patients were identified and compared with those who developed conventional symptomatic leakage (n = 32), and those who did not leak (n = 338). Patient demography and perioperative data were compared between these three groups. Fourteen patient-related and surgery-related variables thought to be possible risk factors for RVF (anastomotic-vaginal fistula) were analysed. RESULTS: Symptomatic anastomotic leakage occurred in 52 (13.3%) of 390 patients. Twenty (5.1%) had an anastomotic-vaginal fistula (AVF) and 32 (8.2%) conventional leakage (CL). Patients with AVF required unscheduled re-operation and defunctioning stoma as often as those with CL. AVF was diagnosed later and more often after discharge from hospital compared with CL. Patients with AVF had lower anastomoses and decreased BMI compared with those with CL. Risk factors for AVF in multivariate analysis were anastomosis < 5 cm above the anal verge (P = 0.001), preoperative radiotherapy (P = 0.004), and UICC cancer stage IV (P = 0.005). Previous hysterectomy was a risk factor neither for AVF nor for CL. CONCLUSION: Anastomotic-vaginal fistula forms a significant part of all symptomatic leakages after low anterior resection for cancer in women. Although diagnosed later, the need for abdominal re-operation and defunctioning stoma was not different from patients with CL. Risk factors for AVF included low anastomosis, preoperative radiotherapy and UICC cancer stage IV.

Generation of a dendritic cell-based vaccine in chronic lymphocytic leukaemia using CliniMACS platform for large-scale production.

We previously demonstrated that dendritic cells (DC) that have endocytosed apoptotic bodies of autologous leukemic cells (Apo-DC) can boost antileukemic T-cell responses. In this study, we report a description of the production procedure and product specification of the Apo-DC vaccine preparations for clinical use. Enriched populations of CD14+ monocytic precursors and CD19+ leukaemic cells were obtained using CliniMACS technology from a single leukapheresis product. Apoptotic bodies were obtained by irradiating (5 Gy) CD19+ selected B cells. DC were generated ex vivo by culturing monocytes with granulocyte macrophage colony-stimulating factor and interleukin-4. Following coculture with apoptotic bodies, DCs were matured with tumour necrosis factor-alpha. The mean percentage of CD14+ cells in the peripheral blood as well as in the leukapheresis product of the patients (n = 10) was approximately 2% (range, 0.8-3.3). Immunomagnetic selection using the CD14 reagent yielded a CD14+ population that was 91 +/- 2.2% (mean +/- SEM) pure. Immunomagnetic selection of CD19 expressing cells yielded a population that was 100 +/- 0.03% pure. Cell viability immediately after selection was 97% and 98% after 7 days of culture. The Apo-DC cellular vaccine product showed a mature phenotype, with a high rate of endocytosis (84%) of apoptotic leukemic B-cells. In conclusion, despite significant variability in the circulating monocyte frequency of the chronic lymphocytic leukaemia patients, our method permitted the production of a DC vaccine with high reproducibility and conforming with recommended quality standards.

Molecular analysis of commensal host-microbial relationships in the intestine.

Human beings contain complex societies of indigenous microbes, yet little is known about how resident bacteria shape our physiology. We colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the normal mouse and human intestinal microflora. Global intestinal transcriptional responses to colonization were observed with DNA microarrays, and the cellular origins of selected responses were established by laser-capture microdissection. The results reveal that this commensal bacterium modulates expression of genes involved in several important intestinal functions, including nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and postnatal intestinal maturation. These findings provide perspectives about the essential nature of the interactions between resident microorganisms and their hosts.

Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC).

BACKGROUND: Circulating myeloma cells (CMC), exhibiting the same immunoglobulin heavy-chain gene rearrangements as the plasma cells, are part of the myeloma clone. In this study, we evaluated the effect of idiotype (Id) vaccination on CMC. PATIENTS AND METHODS: Eleven patients were immunized with the autologous Id in combinations with granulocyte-macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id-specific T cells were monitored by proliferation assay, enzyme-linked immunospot (interferon-gamma) assay, and quantitative real-time PCR for cytokines. Regulatory T (T(reg)) cells were analyzed by flow cytometry. RESULTS: CMC were detected in 9 of 11 patients at start of vaccination. In four patients, CMC declined and two had a complete molecular remission. Further two patients had stable levels of CMC during follow-up, while in three patients CMC progressively increased. Six patients had a vaccine-induced Id-specific T-cell response. A significant correlation was observed between reduced/stable levels of CMC and the Id-specific T cells (P < 0.02). The frequency of T(reg) cells was decreased in immune responders, but increased in immune nonresponders (P < 0.05). No significant change in the serum M-protein concentration was, however, observed in any patient. CONCLUSION: Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells. Further studies are warranted to analyze the clinical significance of CMC and clinical effects of Id vaccination.