Gut microbiome composition and functionality impact the responsiveness to a dairy-based product containing galacto-oligosaccharides for improving sleep quality in adults.

Sleep quality and duration can be impacted by diet, and has been linked to gut microbiota composition and function as the result of communication via the microbiota-gut-brain axis. As one strategy to improve sleep quality could be through the modulation of the gut microbiome, we assessed the effects of a dairy-based product containing whey protein, galacto-oligosaccharides, tryptophan, vitamins and minerals after a 3 weeks intervention on gut microbiota composition and (gut-brain related) functions on basis of 67 healthy subjects with moderate sleep disturbances. Associations of the gut microbiota with sleep quality and with response/non-response to the treatment were revealed by shotgun metagenomics sequencing of faecal DNA samples, and subsequent analyses of microbiota taxonomy and generic functionality. A database of manually curated Gut-Brain Modules (GBMs) was applied to analyse specific microbial functions/pathways that have the potential to interact with the brain. A moderate discriminating effect of the DP treatment on gut microbiota composition was revealed which could be mainly attributed to a decrease in Pseudomonas resinovorans, Flintibacter sp. KGM00164, Intestinimonas butyriciproducens, and Flavonifractor plautii. As interindividual variance in microbiota composition could have given rise to a heterogenous responsiveness of the subjects in the intervention group, we zoomed in on the differences between responders and non-responders. A significant difference in baseline microbiota composition between responders and non-responders was apparent, showing lower Bifidobacterium longum and Bifidobacterium adolescentis, and higher Faecalibacterium prausnitzii relative abundances in responders. The findings provide leads with respect to the effectiveness and potential underlying mechanisms of mode of action in sleep improvement that could support future nutritional interventions to aid sleep improvement.

Human milk oligosaccharides, antimicrobial drugs, and the gut microbiota of term neonates: observations from the KOALA birth cohort study.

The infant gut microbiota affects childhood health. This pioneer microbiota may be vulnerable to antibiotic exposures, but could be supported by prebiotic oligosaccharides found in breast milk and some infant formulas. We sought to characterize the effects of several exposures on the neonatal gut microbiota, including human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), and infant/maternal antimicrobial exposures. We profiled the stool microbiota of 1023 one-month-old infants from the KOALA Birth Cohort using 16S rRNA gene amplicon sequencing. We quantified 15 HMOs in breast milk from the mothers of 220 infants, using high-performance liquid chromatography-mass spectrometry. Both breastfeeding and antibiotic exposure decreased gut microbial diversity, but each was associated with contrasting shifts in microbiota composition. Other factors associated with microbiota composition included C-section, homebirth, siblings, and exposure to animals. Neither infant exposure to oral antifungals nor maternal exposure to antibiotics during pregnancy were associated with infant microbiota composition. Four distinct groups of breast milk HMO compositions were evident, corresponding to maternal Secretor status and Lewis group combinations defined by the presence/absence of certain fucosylated HMOs. However, we found the strongest evidence for microbiota associations between two non-fucosylated HMOs: 6'-sialyllactose (6'-SL) and lacto-N-hexaose (LNH), which were associated with lower and higher relative abundances of Bifidobacterium, respectively. Among 111 exclusively formula-fed infants, the GOS-supplemented formula was associated with a lower relative abundance of Clostridium perfringens. In conclusion, the gut microbiota is sensitive to some prebiotic and antibiotic exposures during early infancy and understanding their effects could inform future strategies for safeguarding a health-promoting infant gut microbiota.

Iatrogenic systemic lymphedema following multiple myeloma treatment.

Lymphedema is a debilitating disease characterized by abnormal lymphatic drainage, either due to primary maldevelopment of the lymphatic system or to secondary injury. The clinical features of primary and secondary lymphedema differ, with primary lymphedema more often involving progressive bilateral lower extremity disease as compared to secondary lymphedema characteristically having more localized symptoms related to the origin of injury. This case presentation describes a patient who presented with bilateral lower extremity swelling, left greater than the right, with imaging results to support the diagnosis of lymphedema. During the time he was followed in our clinic, our team witnessed rapid progression of his lymphedema despite compliance with conservative management. We believe that the primary mechanism of systemic damage to our patient's lymphatic system is the lenalidomide and bortezomib therapy prescribed to treat multiple myeloma. This review explores the relationship between lenalidomide, bortezomib, and lymphedema in efforts of understanding this unique pathology of iatrogenic lymphedema mimicking primary nature.

Short chain fatty acids in human gut and metabolic health.

Evidence is accumulating that short chain fatty acids (SCFA) play an important role in the maintenance of gut and metabolic health. The SCFA acetate, propionate and butyrate are produced from the microbial fermentation of indigestible carbohydrates and appear to be key mediators of the beneficial effects elicited by the gut microbiome. Microbial SCFA production is essential for gut integrity by regulating the luminal pH, mucus production, providing fuel for epithelial cells and effects on mucosal immune function. SCFA also directly modulate host metabolic health through a range of tissue-specific mechanisms related to appetite regulation, energy expenditure, glucose homeostasis and immunomodulation. Therefore, an increased microbial SCFA production can be considered as a health benefit, but data are mainly based on animal studies, whereas well-controlled human studies are limited. In this review an expert group by ILSI Europe's Prebiotics Task Force discussed the current scientific knowledge on SCFA to consider the relationship between SCFA and gut and metabolic health with a particular focus on human evidence. Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasing SCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus. Nevertheless, there is an urgent need for well controlled longer term human SCFA intervention studies, including measurement of SCFA fluxes and kinetics, the heterogeneity in response based on metabolic phenotype, the type of dietary fibre and fermentation site in fibre intervention studies and the control for factors that could shape the microbiome like diet, physical activity and use of medication.

Revealing new leads for the impact of galacto-oligosaccharides on gut commensals and gut health benefits through text mining.

Galacto-oligosaccharides (GOS) are linked to various health benefits, such as the relief of symptoms of constipation. Part of the beneficial effects of GOS are thought to be the consequence of their bifidogenic effect, stimulating the growth of several Bifidobacterium species in vivo. However, GOS may exert additional effects by directly stimulating other bacterial species or by effects that bifidobacteria may have on other commensals in the gut. To get a better insight into the potential health effects induced by GOS, a good understanding of the gut ecosystem, the role of GOS and bifidobacteria is important. An increasing number of 16S DNA profiling and metagenomics studies have led to an expanding inventory of genera, species and strains that can be found in the human gut. To investigate the potential connection of these commensals with GOS and bifidobacteria, we have undertaken a text-mining study to chart the literature landscape around these commensals. To this end, we created controlled vocabularies describing GOS, a large set of gut commensals and a number of terms related to gut health, which were used to mine the entire MEDLINE database. Co-occurrence text-mining revealed that a large number of commensals found in the gut have a connection with Bifidobacterium species and with gut health effects. Word frequency analysis provided more insight into the functional nature of these relationships. Combined co-occurrence search results pointed to putative novel health benefits indirectly linked to bifidobacteria and GOS. The potential beneficial effects of GOS on the protection of epithelial function and epithelial barrier impairment and appendicitis are interesting novel leads. The text-mining approach reported here revealed a number of novel leads through which GOS could exert health effects and that could be investigated in dedicated studies.

Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.

BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.

Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment.

In the present double-blind, randomised, parallel intervention study, the effects of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve healthy adult subjects (aged 18-45 years with a normal BMI (18-25 kg/m²)) receiving amoxicillin (AMX) treatment were determined. All the subjects were treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6) or placebo (maltodextrin, n 6) (2·5 g; three times per d) during and 7 d after AMX treatment. Faecal samples were collected twice before starting the treatment and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a disruption of the metabolic activity of the microbiota (increase in succinate, monosaccharide and oligosaccharide levels in the faecal samples) were observed in both groups (P< 0·05). Positive effects of GOS intake were observed on the levels of bifidobacteria, although not found to be significant. Data revealed that the levels of bifidobacteria were higher upon GOS intake than upon placebo intake, especially after AMX treatment. The activity of bifidobacteria and subsequent cross-feeding activity of the microbiota upon GOS intake compared with those upon placebo intake were reflected by the significant increase in butyrate levels (P< 0·05) in the faecal samples after AMX treatment. Despite the small number of subjects, our findings confirm previous results obtained in vitro, namely that GOS intake supports the recovery of the beneficial bifidobacteria and, indirectly, the production of butyrate after AMX treatment.

Evaluation of Epstein-Barr virus-specific immunologic response in solid organ transplant recipients with an enzyme-linked ImmunoSpot assay.

Epstein-Barr virus (EBV) is a γ-herpes virus, responsible for infectious mononucleosis in immunocompetent hosts. Cellular immunity appears rapidly during EBV primary infection, keeping it silent despite long-life persistence in B lymphocytes. Defects of the EBV-specific cellular immunity are supposed to be the basis of post-transplantation lymphoproliferative disorders, promoted by high levels of immunosuppression. We retrospectively reviewed 197 solid organ transplant recipients to investigate EBV-specific lymphocyte responsiveness using Enzyme-linked ImmunoSpot assay (EliSpot), which assesses the EBV-specific interferon (IFN)-γ producing peripheral blood mononuclear cells, and kinetics of EBV infection/reactivation post-transplantation using quantitative real-time polymerase chain reaction (PCR) on whole blood. Overall, 102 of the 197 patients (51.8%) showed EBV responsiveness at the EBV-EliSpot assay: 68 (66.6%) showed a persistently positive EBV response in 3 or more determinations and 34 (33.3%) had transient episodes of nonresponsiveness. Ninety-five (48.2%) patients were persistently EBV nonresponders. EBV-DNAemia data were available for 58 patients: 27.6% presented at least one episode of EBV-DNA occurrence. No differences were found in EBV-EliSpot response stratification between the groups of patients who experienced episodes of EBV reactivation and those without EBV-DNAemia. However, EBV DNAemia peak values tended to be higher in the first year post-transplantation in the group of patients with a persistent positive EBV-specific immune response. EBV viral load quantitation in blood and EliSpot EBV-specific immune response determination may represent a powerful tool for monitoring solid organ transplant recipients, guiding immunosuppression modulation in patients with active EBV replication.

High-throughput analysis of the impact of antibiotics on the human intestinal microbiota composition.

Antibiotic treatments can lead to a disruption of the human microbiota. In this in-vitro study, the impact of antibiotics on adult intestinal microbiota was monitored in a new high-throughput approach: a fermentation screening-platform was coupled with a phylogenetic microarray analysis (Intestinal-chip). Fecal inoculum from healthy adults was exposed in a fermentation screening-platform to seven widely-used antibiotics during 24h in-vitro fermentation and the microbiota composition was subsequently determined with the Intestinal-chip. Phylogenetic microarray analysis was first verified to be reliable with respect to variations in the total number of bacteria and presence of dead (or inactive) cells. Intestinal-chip analysis was then used to identify and compare shifts in the intestinal microbial composition after exposure to low and high dose (1µgml(-1) and 10µgml(-1)) antibiotics. Observed shifts on family, genus and species level were both antibiotic and dose dependent. Stronger changes in microbiota composition were observed with higher doses. Shifts mainly concerned the bacterial groups Bacteroides, Bifidobacterium, Clostridium, Enterobacteriaceae, and Lactobacillus. Within bacterial groups, specific antibiotics were shown to differentially impact related species. The combination of the in-vitro fermentation screening platform with the phylogenetic microarray read-outs has shown to be reliable to simultaneously analyze the effects of several antibiotics on intestinal microbiota.

Selective carbohydrate utilization by lactobacilli and bifidobacteria.

AIM: To evaluate the ability of specific carbohydrates, including commercially available products, to support the growth of representatives of two well-known groups of gut commensals, namely lactobacilli and bifidobacteria. METHODS AND RESULTS: Sixty-eight bacterial strains, representing 29 human-derived lactobacilli and 39 bifidobacteria (both human- and animal-derived), were tested for their ability to metabolize 10 different carbohydrates. Analysis of growth and metabolic activity was performed using a combination of diagnostic parameters, such as final OD600 , final pH, fermentation end products and growth rate. CONCLUSIONS: The data assembled in this study provide significant complementary and comparative information on the growth-promoting properties of a range of carbohydrates, while also investigating interspecies differences between lactobacilli and/or bifidobacteria with regard to their carbohydrate utilization abilities. Galacto-oligosaccharides (GOS) and lactulose were shown to support the most favourable growth characteristics, whereas relatively poor growth of lactobacilli and bifidobacteria was observed on inulin, maltodextrin and polydextrose. GOS/inulin (9 : 1) and fructo-oligosaccharides (FOS)/inulin mixtures supported mostly similar growth abilities to those obtained for GOS and FOS, respectively. Microbial consumption of GOS, as determined by high-performance anion-exchange chromatography with pulsed amperometric detection, was evident for both lactobacilli and bifidobacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may allow for the rational prediction of lactobacilli and/or bifidobacteria to be used in conjunction with prebiotics, such as GOS, as synbiotics.

The lack of cytomegalovirus-specific cellular immune response may contribute to the onset of organ infection and disease in lung transplant recipients.

Cellular immune response has been demonstrated to play a role in the control of human cytomegalovirus (HCMV) replication in organ transplant recipients. Herein, HCMV-specific T-cell response and association to the onset of organ infection/disease were prospectively evaluated by EliSPOT assay in a population of 46 lung transplant (LT) recipients at 1, 3, 6, 9 and 12 months post-transplantation. According to our centre?s practice, a combined prolonged antiviral prophylaxis (HCMV-IG for 12 months and ganciclovir or valganciclovir for 3 weeks from postoperative day 21) was given to all LT recipients. HCMV-DNA was concomitantly detected on bronchoalveolar lavage (BAL) and whole blood by real-time PCR. Approximately one third of patients resulted HCMV persistently non-responder; the rate of HCMV infection, as evaluated by HCMV-DNA positivity, tended to be higher in non-responders. Mean viral load on BAL was significantly higher in non-responders vs other patients (p < 0.001). Temporal profile of infections appeared related to the HCMV responder status with a shorter time to onset of infection post-transplantation and a longer duration in non-responders. The occurrence of organ disease (i.e. pneumonia) tended to be higher in non-responders, with poor prognosis, as death occurred in one of three non-responder patients that developed HCMV pneumonia. The lack of HCMV-specific cellular response can contribute to the onset of organ infection and disease also in patients in which antiviral prophylaxis was adopted; this could be due to the potential occurrence of incomplete control of replication in lungs or a delayed priming of T-cell reconstitution.

No detectable beneficial systemic immunomodulatory effects of a specific synbiotic mixture in infants with atopic dermatitis.

BACKGROUND: In a murine model of allergic inflammation, Bifidobacterium breve M-16V has been shown to reduce IL-4 and IgE by inducing IL-10 and IFN-γ. However, it remains unknown whether this strain has the same effect in humans with allergic disease. OBJECTIVE: To determine the effects of Bifidobacterium breve M-16V combined with a prebiotic oligosaccharide mixture (synbiotic) on atopic markers, ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) and circulating regulatory T cell percentage in infants with atopic dermatitis. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with atopic dermatitis, age <7 months, were randomized to receive an infant formula with Bifidobacterium breve M-16V and a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. At week 0 and 12, plasma levels of IL-5, IgG1, IgG4, CTACK and TARC, ex vivo cytokine responses by PBMCs and percentage of regulatory T cells, were determined. RESULTS: There were no significant differences between the synbiotic and the placebo group in IL-5, IgG1, IgG4, CTACK and TARC levels and ex vivo cytokine production by anti-CD3/anti-CD28-stimulated PBMCs. With allergen-specific stimuli, we found a decreased IL-12p40/70 and IL-12p70 production in response to egg allergen (P = 0.04 and P = 0.01, respectively) and decreased IL-12p70 production in response to peanut allergen (P = 0.003) in the synbiotic compared with the placebo group. Circulating regulatory T cell percentage did not significantly differ between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: This synbiotic mixture has no detectable effect on plasma levels of the analysed atopic disease markers, ex vivo cytokine production and circulating regulatory T cell percentage in infants with atopic dermatitis, besides down-regulation of IL-12 production in egg- and peanut-stimulated PBMCs. These results do not support the use of this synbiotic in clinical practice.

[Interdisciplinary cooperation in occupational health: ethical friction]. / Interdisciplinair werken bij arbeid en gezondheid: ethische fricties.

OBJECTIVE: To investigate which ethical considerations play a role in the assessment of absenteeism due to sickness and of disability, and how these are dealt with. DESIGN: Qualitative, exploratory study. METHOD: We conducted interviews with 32 individual professional practitioners: 8 occupational health physicians, 8 insurance company physicians, 8 general practitioners, and 8 psychologists, with the aid of a semi-structured questionnaire. During the interview we differentiated between 4 clusters of questions referring to the ethical, legal, interdisciplinary, and professional context, respectively. The study revealed only the spectrum of ethical considerations that played a role, and not the representativeness. For this reason the results did not allow for quantitative conclusions. RESULTS: Differences in the manner of thinking and behaving between health-care providers stem from differences in ethical considerations and in background beliefs. These differences hinder effective cooperation within the occupational health sector. CONCLUSION: To improve professional performance and to achieve more responsible decision-making those involved need to be aware of their ethical considerations and background beliefs and to make them explicit, possibly with the aid of a checklist.

Wound healing and regenerative strategies.

Wound healing is a complex biological process that affects multiple tissue types. Wounds in the oral cavity are particularly challenging given the variety of tissue types that exist in close proximity to one another. The goal of regenerative medicine is to facilitate the rapid replacement of lost or damaged tissue with tissue that is functional, and physiologically similar to what previously existed. This review provides a general overview of wound healing and regenerative medicine, focusing specifically on how recent advances in the fields of stem cell biology, tissue engineering, and oral disease could translate into improved clinical outcomes.

Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis.

BACKGROUND: Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. METHODS: In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age <7\ months, were randomized to receive an extensively hydrolyzed formula with Bifidobacterium breve M-16V and a galacto/fructooligosaccharide mixture (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. After 1 year, the prevalence of respiratory symptoms and asthma medication use was evaluated, using a validated questionnaire. Also, total serum IgE and specific IgE against aeroallergens were determined. FINDINGS: Seventy-five children (70.7% male, mean age 17.3 months) completed the 1-year follow-up evaluation. The prevalence of 'frequent wheezing' and 'wheezing and/or noisy breathing apart from colds' was significantly lower in the synbiotic than in the placebo group (13.9%vs 34.2%, absolute risk reduction (ARR) -20.3%, 95% CI -39.2% to -1.5%, and 2.8%vs 30.8%, ARR -28.0%, 95% CI -43.3% to -12.5%, respectively). Significantly less children in the synbiotic than in the placebo group had started to use asthma medication after baseline (5.6%vs 25.6%, ARR -20.1%, 95% CI -35.7% to -4.5%). Total IgE levels did not differ between the two groups. No children in the synbiotic and five children (15.2%) in the placebo group developed elevated IgE levels against cat (ARR -15.2%, 95% CI -27.4% to -2.9%). CONCLUSION: These results suggest that this synbiotic mixture prevents asthma-like symptoms in infants with AD.

Early life: gut microbiota and immune development in infancy.

The immune system of infants is actively downregulated during pregnancy and therefore the first months of life represent a period of heightened susceptibility to infection. After birth, there is an age-dependent maturation of the immune system. Exposure to environmental microbial components is suggested to play an important role in the maturation process. The gastrointestinal tract is the major site of interaction between the host immune system and microorganisms, both commensal as well as potentially pathogenic. It is well established that the mammalian immune system is designed to help protect the host from invading microorganisms and other danger signals. However, recent research is emerging in the field of host-microbe interactions showing that commensal microorganisms (microbiota) are most likely one of the drivers of immune development and, in turn the immune system shapes the composition of the microbiota. Specific early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific view that microbial colonisation plays an important role in regulating and fine-tuning the immune system throughout life. Therefore, the use of pre-, pro- and synbiotics may result in a beneficial microbiota composition that might have a pivotal role on the prevention of several important diseases that develop in early life such as necrotizing enterocolitis and atopic eczema.

Social and psychological factors influenced the course of arm, neck and shoulder complaints.

OBJECTIVE: To investigate the clinical course and prognostic factors of complaints of arm, neck, and shoulder. STUDY DESIGN AND SETTING: A prospective cohort study in physical therapy practice. Participating physiotherapists recruited new consulters with musculoskeletal complaints of the neck and/or upper extremities. Participants filled in questionnaires at baseline, 3 months, and 6 months. The main outcome measure was the persistence of complaints over 6-month follow-up. Possible predictors like social and psychological factors, physical factors, and complaint specific factors were tested in univariate and multivariate logistic regression analyses for repeated measurements. RESULTS: Of the 624 participants at baseline 543 (87%) returned at least one follow-up questionnaire. At 6-month follow-up, 40% had persisting pain and discomfort. Somatization, kinesiophobia, catastrophizing, and a long duration of complaints at baseline were significantly related to the persistence of complaints over 6 months in the total population. In those with paid work (77%), catastrophizing, low decision authority at work, and a long duration of complaints at baseline were significantly related to the persistence of complaints over 6 months. CONCLUSION: 40% of the participants had persisting pain and discomfort after 6 months and mainly social and psychological factors played a role in this course.

Human mesenchymal stem cells derived from bone marrow display a better chondrogenic differentiation compared with other sources.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into several mesodermal lineages. These cells have been isolated from various tissues, such as adult bone marrow, placenta, and fetal tissues. The comparative potential of these cells originating from different tissues to differentiate into the chondrogenic lineage is still not fully defined. The aim of our study was to investigate the chondrogenic potential of MSCs isolated from different sources. MSCs from fetal and adult tissues were phenotypically characterized and examined for their differentiation capacity, based on morphological criteria and expression of extracellular matrix components. Our results show that both fetal and adult MSCs have chondrogenic potential under appropriate conditions. The capacity of bone marrow-derived MSCs to differentiate into chondrocytes was reduced on passaging of cells. MSCs of bone marrow origin, either fetal or adult, exhibit a better chondrogenesis than fetal lung- and placenta-derived MSCs, as demonstrated by the appearance of typical morphological features of cartilage, the intensity of toluidine blue staining, and the expression of collagen type II, IX, and X after culture under chondrogenic conditions. As MSCs represent an attractive tool for cartilage tissue repair strategies, our data suggest that bone marrow should be considered the preferred MSC source for these therapeutic approaches.

Prognostic indicators for non-recovery of non-traumatic complaints at arm, neck and shoulder in general practice--6 months follow-up.

OBJECTIVES: To identify predictors of non-recovery in non-traumatic complaints at the arm, neck and shoulder in general practice 6 months after the first consultation. METHODS: A prospective cohort study was set in 21 Dutch general practices. Consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints and age 18 through 64 yrs entered the cohort. Complaint, patient, physical, psychosocial and work characteristics were investigated as possible predictors of non-recovery at 6 months using multiple logistic regression analyses (backward Wald). RESULTS: At 6 months, 46% of the total population (n = 612) and 42% of the working subpopulation (n = 473) still reported complaints. Complaint characteristics (long duration of the complaint before consultation, recurrent complaint, musculoskeletal comorbidity and complaint mainly located at wrist or hand) were most predictive of non-recovery followed by psychosocial characteristics (more somatization and experiencing less social support). Having a specific diagnosis was associated with recovery. In the working subpopulation, the same variables were predictors of non-recovery. Additionally, low supervisory support was associated with non-recovery. The models correctly classified 72-75% of the patients (explained variance 0.27-0.28). CONCLUSIONS: Besides questions on complaint characteristics, information on somatization and support can help a general practitioner to recognize patients at risk of persistent complaints.

[Limited change in the quality of the social medical guidance and in the satisfaction of sick-listed patients, after collaborative projects between general practitioners and occupational physicians]. / Weinig veranderingen in kwaliteit van sociaal-medische begeleiding en tevredenheid bij patiënten met arbeidsverzuim, na samenwerkingsprojecten voor huis- en bedrijfsartsen.

OBJECTIVE: To evaluate whether regional projects for collaboration between general practitioners (GPs) and occupational physicians (OPs) improved the quality of their social medical guidance (SMG) and the satisfaction of their patients. DESIGN: Evaluation study with before and after measurements with respect to the same GPs and OPs. METHOD: Structured interviews were conducted with 58 GPs and 83 OPs regarding the SMG of their sick-listed patients. Before the project, the SMG of 1109 sick-listed patients was assessed and after the project, 1 or 1.5 years later, the SMG of 1121 sick-listed patients. These patients were sent a questionnaire by means of which their satisfaction could be assessed. RESULTS: After the projects, the quality ofthe diagnosis by the OPs was improved and they also more often adhered to the official guidelines of the KNMG (Royal Netherlands Medical Association) when contacting the GP about a patient. The GPs more often contacted the OP if they needed more information about a patient after reaching a diagnosis. Nevertheless, in half to three-quarters of the patients for whom contact between GPs and OPs was indicated, this contact did not take place. There was no significant increase in patient satisfaction. Before the projects, patients gave their GP a grade of 8.2 on a 10-point scale and after the projects this was 8.5; the OPs were given a grade of 7.5 both times. Further analysis showed that there was no significant relation between the quality ofthe SMG and the patient's satisfaction with the doctor. CONCLUSION: Although there was some improvement in the quality of the SMG, there was still insufficient cooperation between GPs and OPs compared to the guidelines. An increase in patient satisfaction was not demonstrated.