The effectiveness of structured physical activity on agitation in people with dementia: a rapid review.

OBJECTIVES: Managing agitation and other behaviours that challenge is a significant dementia care challenge. The priority is to find effective non-pharmacological interventions as drug treatments can have significant side effects. This review evaluates the effectiveness of structured physical activity on agitation in dementia. METHOD: Our rapid review searched four electronic databases, Cochrane CENTRAL, MEDLINE, CINAHL and Embase, for interventional studies using a structured physical activity programme in people with dementia and studied the effect of this activity on behaviours that challenge. Study quality was assessed using CASP criteria and data was narratively synthesised. RESULTS: We included 13 studies in this review (four rated as high quality), involving a total of 1546 participants. Results were analysed according to exercise type, frequency and intensity of the intervention. Exercise is effective in reducing agitation and studies with higher adherence to exercise demonstrated more positive effects on agitation and behaviours that challenge. CONCLUSION: Physical activity can be effective in reducing agitation in older adults with dementia. Further research is needed to clarify the type of intervention that is most beneficial. Strategies to make physical activity more acceptable and available to people with dementia need to be established.

Predictors of Psychedelic Experience: A Thematic Analysis.

Research on the therapeutic potential of psychedelic substances is expanding. A limitation within this field is the unpredictability of individual responses to psychedelics. Better understanding of factors predicting psychedelic experience is essential to clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. This study aimed to (a) identify factors that produce positive and adverse psychedelic experience, and (b) compare these potential predictors across four psychedelic substances. A thematic analysis was conducted on twenty-two first-person reports of psychedelic use (six per substance), sourced from the Erowid database. This revealed three external predictors (nature, music, and preparation) and three internal predictors (understanding, mind-set, and motivation). Each factor identified contained two sub-themes that further elucidated meaning and impact. Nature and music emerged as potential tools for de-escalating adverse reactions to psychedelics. Substance-specific perceptual and sensorial effects were also examined. Finally, the importance of, and interrelationship between, preparation, mind-set, understanding, and motivation was examined as common themes that emerged. The broader clinical and sociological implications are discussed, with reference to developing harm reduction frameworks. These findings constitute an early step in developing a more nuanced understanding of factors shaping psychedelic experience.

Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.

Background: The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer. Patients and methods: Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS). Results: Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months. Conclusion: Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. Clinical trial information: NCT02549430.

The influence of wind farm development on the hydrochemistry and ecology of an upland stream.

Despite perceptions of pristine condition, upland environments are increasingly subject to a range of anthropogenic pressures including air pollution, climate change, land-use change and evolving land management strategies. Although they have received little attention to date, the large-scale development of upland wind farms also has the potential to disturb vegetation and soils, alter hydrology and water quality and, thus, impact freshwater ecosystems. This paper presents the findings of a 5-year study of the impacts of wind farm construction on the freshwater environment. Data on water quality, invertebrate and fish populations were collected for 2 years before construction and for the following 3 years covering the construction period and the initial period of the farm's operation. In contrast to previous studies, the impacts of the wind farm development were assessed for a suite of potentially affected hydrochemical variables using a before-after-control-impact (BACI) analysis that allowed separation of construction effects from spatial and temporal variability in hydroclimatological conditions, thereby providing an improved, more robust evidence base. There was a small but significant negative effect of construction on pH, alkalinity (Alk) and acid neutralising capacity (ANC) in the upper part of the treatment catchment, which was where the wind farm was situated. The effects were more marked under higher flow conditions. It is hypothesised that this reflects changes in hydrological processes with increased near-surface runoff or organic acid mobilisation. There was no indication that either invertebrate community structure or fish densities were impacted by construction and the resulting effects on water quality.

Investigation of the impact of feeding Lactobacillus plantarum CRL 1815 encapsulated in microbially derived polymers on the rat faecal microbiota.

AIMS: The aim of this study was to evaluate the impact of the administration of microencapsulated Lactobacillus plantarum CRL 1815 with two combinations of microbially derived polysaccharides, xanthan : gellan gum (1%:0·75%) and jamilan : gellan gum (1%:1%), on the rat faecal microbiota. METHODS AND RESULTS: A 10-day feeding study was performed for each polymer combination in groups of 16 rats fed either with placebo capsules, free or encapsulated Lact. plantarum or water. The composition of the faecal microbiota was analysed by fluorescence in situ hybridization and temporal temperature gradient gel electrophoresis. Degradation of placebo capsules was detected, with increased levels of polysaccharide-degrading bacteria. Xanthan : gellan gum capsules were shown to reduce the Bifidobacterium population and increase the Clostridium histolyticum group levels, but not jamilan : gellan gum capsules. Only after administration of jamilan : gellan gum-probiotic capsules was detected a significant increase in Lactobacillus-Enterococcus group levels compared to controls (capsules and probiotic) as well as two bands were identified as Lact. plantarum in two profiles of ileum samples. CONCLUSIONS: Exopolysaccharides constitute an interesting approach for colon-targeted delivery of probiotics, where jamilan : gellan gum capsules present better biocompatibility and promising results as a probiotic carrier. SIGNIFICANCE AND IMPACT OF STUDY: This study introduces and highlights the importance of biological compatibility in the encapsulating material election, as they can modulate the gut microbiota by themselves, and the use of bacterial exopolysaccharides as a powerful source of new targeted-delivery coating material.

Staphylococcus aureus infections after liver transplantation.

BACKGROUND: More data on the risk factors and outcomes after Staphylococcus aureus infections in liver transplantation are needed. METHODS: Liver recipients with S. aureus infections (cases) were retrospectively identified and compared to gender-, age-, and transplant type-matched (1:2) non-S. aureus-infected controls. Risk factors associated with S. aureus infections were identified by conditional logistic regression analysis. RESULTS: We evaluated 51 patients (median age 52 years). First S. aureus infections developed at a median time of 29 days after transplantation, with 52.94% of them in the first month; 88.24% were nosocomial, 41.18% were polymicrobial, and 47.06% were caused by methicillin-resistant S. aureus (MRSA). Surgical site infections represented 58.82% and bacteremia 23.53%. By univariate analysis, patients with S. aureus infections were intubated more frequently (odds ratio [OR] 26.92, 95% confidence interval [CI] 3.23-3,504.15, p = 0.0006), had a central line (OR 11.69, 95% CI 1.42-95.9, p = 0.02), or recent surgery (OR 26.92, 95% CI 3.23-3,504.15, p = 0.0006) compared with controls. By multivariate analysis, subjects who underwent surgery within 2 weeks prior to infection had a 26.9 times higher risk of developing S. aureus infection (95% CI 3.23-3,504.15, p = 0.0006); these results were adjusted for matched criteria. S. aureus infections did not affect graft or patient survival, but the study was not powered for such outcomes. CONCLUSION: Only recent surgical procedure was found to be a significant independent risk factor for S. aureus infections after liver transplantation.

Investigation of the faecal microbiota of geriatric cats.

AIMS: Aim of the study was to investigate the faecal microbiota of geriatric cats, as aging affects the nutrient digestibility and metabolic function of the feline intestine. METHODS AND RESULTS: Twenty geriatric cats were randomly assigned to two groups that were fed different foods. Coriobacteriaceae, Clostridium cluster XIV, bifidobacteria and lactic acid bacteria were the dominant faecal bacterial groups, accounting for c. 40% of total bacteria. Clostridium cluster IX was less predominant (0.5% of total bacteria), while the remaining bacterial populations enumerated only accounted for 0.2% of total bacteria. Highly diverse microbial profiles were demonstrated for geriatric cats with denaturing gradient gel electrophoresis, although a few common bands were evident. Some differences were seen in the feline faecal microbiota between animal groups at the same time or over time for individual animals. However, no obvious clustering based on animal group or sample time was indicated. CONCLUSIONS: Geriatric cats harboured a complex faecal microbiota and c. 41% of total bacteria have been detected with the probes employed. SIGNIFICANCE AND IMPACT OF THE STUDY: First molecular-based study examining faecal microbiota of geriatric felines. Knowledge of the microbiota associated with ageing in cats may allow improved development of foods specific for the needs of senior cats.

Physiological and bifidogenic effects of prebiotic supplements in infant formulae.

OBJECTIVES: This randomized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides (GOS), oligofructose, and long-chain inulin (fructooligosaccharides, FOS) in formula. METHODS: Subjects were randomized to Orafti Synergy1 (50 oligofructose:50 FOS) 0.4 g/dL or 0.8 g/dL, GOS:FOS (90:10) 0.8 g/dL, or a standard formula according to Good Clinical Practice guidelines. A breast-fed group was included for comparison. Outcome parameters were weight, length, intake, stool characteristics, crying, regurgitation, vomiting, adverse events, and fecal bacterial population counts. Statistical analyses used nonparametric tests. RESULTS: During the first month of life, weight, length, intake, and crying increased significantly in all of the groups. Regurgitation and vomiting scores were low and similar. Stool frequency decreased significantly and similarly in all of the formula groups but was lower than in the breast-fed group. All of the prebiotic groups maintained soft stools, only slightly harder than those of breast-fed infants. The standard group had significantly harder stools at weeks 2 and 4 compared with 1 (P < 0.001 and P = 0.0279). The total number of fecal bacteria increased in all of the prebiotic groups (9.82, 9.73, and 9.91 to 10.34, 10.38, and 10.37, respectively, log10 cells/g feces, P = 0.2298) and more closely resembled the breast-fed pattern. Numbers of lactic acid bacteria, bacteroides, and clostridia were comparable. In the SYN1 0.8 g/dL and GOS:FOS groups, Bifidobacterium counts were significantly higher at D14 and 28 compared with D3 and were comparable with the breast-fed group. Tolerance and growth were normal. CONCLUSIONS: Stool consistency and bacterial composition of infants taking SYN1 0.8 g/dL or GOS:FOS-supplemented formula were closer to the breast-fed pattern. There was no risk of dehydration.

Survivability of a probiotic Lactobacillus casei in the gastrointestinal tract of healthy human volunteers and its impact on the faecal microflora.

AIM: The aim of this study was to measure the gastrointestinal survival of Lactobacillus casei and its impact on the gut microflora in healthy human volunteers. METHODS AND RESULTS: Twenty healthy volunteers took part in a double-blind placebo-controlled probiotic feeding study (10 fed probiotic, 10 fed placebo). The probiotic was delivered in two 65 ml aliquots of fermented milk drink (FMD) daily for 21 days at a dose of 8.6 +/- 0.1 Log(10)Lact. casei CFU ml(-1) FMD. Faecal samples were collected before, during and after FMD or placebo consumption, and important groups of faecal bacteria enumerated by fluorescent in situ hybridization (FISH) using oligonucleotide probes targeting the 16S rRNA. The fed Lact. casei was enumerated using selective nutrient agar and colony identity confirmed by pulsed field gel electrophoresis. Seven days after ingestion of FMD, the Lact. casei was recovered from faecal samples taken from the active treatment group at 7.1 +/- 0.4 Log(10) CFU g(-1) faeces (mean +/- SD, n = 9) and numbers were maintained at this level until day 21. Lact. casei persisted in six volunteers until day 28 at 5.0 +/- 0.9 Log(10) CFU g(-1) faeces (mean +/- SD, n = 6). Numbers of faecal lactobacilli increased significantly upon FMD ingestion. In addition, the numbers of bifidobacteria were higher on days 7 and 21 than on days 0 and 28 in both FMD fed and placebo fed groups. Consumption of Lact. casei had little discernible effect on other bacterial groups enumerated. CONCLUSIONS: Daily consumption of FMD enabled a probiotic Lact. casei strain to be maintained in the gastrointestinal tract of volunteers at a stable relatively high population level during the probiotic feeding period. SIGNIFICANCE AND IMPACT OF THE STUDY: The study has confirmed that this probiotic version of Lact. casei survives well within the human gastrointestinal tract.

Molecular characterisation of the gut microflora of healthy and inflammatory bowel disease cats using fluorescence in situ hybridisation with special reference to Desulfovibrio spp.

Inflammatory bowel disease (IBD) is a common cause of chronic large bowel diarrhoea in cats. Although the aetiology of IBD is unknown, an immune-mediated response to a luminal antigen is thought to be involved. As knowledge concerning the colonic microflora of cats is limited and requires further investigation, the purpose of this study was to determine the presence of specific bacterial groups in normal and IBD cats, and the potential role they play in the health of the host. Total bacterial populations, Bacteroides spp., Bifidobacterium spp., Clostridium histolyticum subgp., Lactobacillus-Enterococcus subgp. and Desulfovibrio spp. were enumerated in 34 healthy cats and 11 IBD cats using fluorescence in situ hybridisation. The study is one of the first to show the presence of Desulfovibrio in cats. Total bacteria, Bifidobacterium spp. and Bacteroides spp. counts were all significantly higher in healthy cats when compared with IBD cats, whereas Desulfovibrio spp. (producers of toxic sulphides) numbers were found to be significantly higher in colitic cats. The information obtained from this study suggests that modulation of bacterial flora by increasing bifidobacteria and decreasing Desulfovibrio spp. may be beneficial to cats with IBD. Dietary intervention may be an important aspect of their treatment.

Prebiotics and resistance to gastrointestinal infections.

Acute gut disorder is a cause for significant medicinal and economic concern. Certain individual pathogens of the gut, often transmitted in food or water, have the ability to cause severe discomfort. There is a need to manage such conditions more effectively. The route of reducing the risk of intestinal infections through diet remains largely unexplored. Antibiotics are effective at inhibiting pathogens; however, these should not be prescribed in the absence of disease and therefore cannot be used prophylactically. Moreover, their indiscriminate use has reduced effectiveness. Evidence has accumulated to suggest that some of the health-promoting bacteria in the gut (probiotics) can elicit a multiplicity of inhibitory effects against pathogens. Hence, an increase in their numbers should prove effective at repressing pathogen colonisation if/when infectious agents enter the gut. As such, fortification of indigenous bifidobacteria/lactobacilli by using prebiotics should improve protection. There are a number of potential mechanisms for lactic acid bacteria to reduce intestinal infections. Firstly, metabolic endproducts such as acids excreted by these micro-organisms may lower the gut pH to levels below those at which pathogens are able to effectively compete. Also, many lactobacilli and bifidobacteria species are able to excrete natural antibiotics, which can have a broad spectrum of activity. Other mechanisms include an improved immune stimulation, competition for nutrients and blocking of pathogen adhesion sites in the gut. Many intestinal pathogens like type 1 fimbriated Escherichia coli, salmonellae and campylobacters utilise oligosaccharide receptor sites in the gut. Once established, they can then cause gastroenteritis through invasive and/or toxin forming properties. One extrapolation of the prebiotic concept is to simulate such receptor sites in the gut lumen. Hence, the pathogen is 'decoyed' into not binding at the host mucosal interface. The combined effects of prebiotics upon the lactic acid flora and anti-adhesive strategies may lead towards new dietary interventions against food safety agents.

Total laparoscopic hysterectomy versus total abdominal hysterectomy for obese women with endometrial cancer.

Obesity is common in endometrial cancer and surgery for these patients is challenging. We compared total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) with respect to feasibility (operating time, estimated blood loss, length of hospital stay, and conversion to laparotomy) and safety (perioperative morbidity and mortality) in a retrospective analysis of 78 morbidly obese patients with endometrial cancer. Analysis is based on the intention to treat. The intention to treat was TLH in 47 patients and it could be successfully completed in 42 patients (89.4%). The mean weight for all patients was 118.7 kg, with patients in the TLH group weighing more and having higher ASA scores. Mean operating time and estimated blood loss were similar in both groups. Mean postoperative hospital stay was 4.4 (+/-3.9) days in the TLH group and 7.9 (+/-3.0) days in the TAH group (P < 0.0001). Wound infections occurred in 15 of 31 patients (48.4%) in the TAH group and in 1 of 47 patients (2.1%) in the TLH group. All other morbidity, as well as patterns of recurrence and survival were similar in both groups. These data justify a prospective randomized trial comparing TLH with TAH for the treatment of endometrial cancer.

Early-onset neonatal group B streptococcal infection in London: 1990-1999.

OBJECTIVE: To identify the incidence of early-onset group B streptococcal infection and to describe the antecedent maternal risk factors, in order to provide data to inform the design of interventional strategies that could be introduced in the UK to reduce the burden of this infection. DESIGN: A retrospective study with review of case notes of mothers and babies. SETTING: Seven maternity units in London during 1990-1999. Population All cases of proven early-onset neonatal group B streptococcal infection. METHODS: Identification of presence of risk factors that could be used to select women for the offer of intrapartum antibiotic prophylaxis. MAIN OUTCOME MEASURES: Incidence and case-fatality rate of invasive early-onset group B infection. RESULTS: One hundred and forty cases were identified among a birth cohort of 198,388 live births, an incidence of 0.71 per 1000 live births. Twenty-two babies died, a case-fatality rate of 15.6% or 1.1 per 100,000 live births. Women of black ethnic origin, and those who had had a previously affected infant, multiple pregnancy, preterm delivery, prolonged rupture of membranes or intrapartum fever all had a significantly increased risk of delivering an infected infant. CONCLUSIONS: These data suggest that the incidence of early-onset group B streptococcal infection in these London centres is sufficiently high to warrant administration of intrapartum antibiotics to at-risk women.

Group B streptococcal disease in UK and Irish infants younger than 90 days.

The incidence, morbidity, and mortality of group B streptococcal disease in the UK and Republic of Ireland are largely unknown. Between Feb 1, 2000, and Feb 28, 2001, we identified cases of invasive group B streptococcal disease in infants younger than 90 days through surveillance involving paediatricians, microbiologists, and parents. 568 cases were identified, equivalent to a total incidence of 0.72 per 1000 live-births (95% CI 0.66-0.78); the incidence for early-onset disease (n=377) was 0.48 per 1000 (0.43-0.53), and for late-onset disease (n=191) was 0.24 per 1000 (0.21-0.28). Risk factors were identifiable for 218 (58%) cases of early-onset disease. 53 infants died (overall 9.7%). We have established the minimum current burden of group B streptococcal disease in UK and Irish infants. This information will assist in the formulation of guidelines for prevention of this disease.

Quantifying the effects of forestry practices on the recovery of upland streams and lochs from acidification.

Trends in long-term chemistry data are presented for 37 acidified upland streams and lochs, located in four areas (A, B, C and D) across Scotland, to provide a comparison between recovery rates of moorland catchments and forest catchments at different stages of the management cycle. For all sites, non-marine sulfate (nm-SO(4)) showed a significant decline in annual median concentrations, the greatest decline being in streams draining felled catchments, which showed a 50% greater decline than catchments with moorland or young, aggrading forests. A similar pattern was found for chloride (Cl) concentrations in Area C, which reflected the reduced interception of sea-salt aerosols following clearfelling. However, high elevation moorland sites in Area D also revealed significant declines in Cl while trends in aggrading forest sites in this area were insignificant. Alkalinity (ALK) and pH increased more at sites where felling had taken place than at moorland or young forest sites while aggrading forest catchments appeared to be most resistant to changes in pH and ALK. Associated with these acid-base changes was a corresponding decline in labile aluminium (Al-L) concentrations. The pattern of nitrate (NO(3)) change was especially affected by the timing of felling in forested catchments. Large negative trends in NO(3) at stream sites were associated with felling during the early part of the study period. This downward trend was further enhanced as NO(3) concentrations fell below pre-felling levels as the second rotation crop became established. Few forest sites showed significant increases in NO(3) due to felling in the latter part of the study period. Most moorland loch sites showed a small but significant increase in NO(3,) probably in response to similar increases in N deposition and/or climatic impacts. Dissolved organic carbon (DOC) increased significantly at both forest and moorland sites, however, the extent of these increasing trends appeared to be positively correlated with absolute DOC concentrations. Despite the complex response of streams and lochs during the various stages of the forest cycle, especially for NO(3), both forest and moorland catchments showed generally similar and rapid responses to reductions in S deposition. Nevertheless, forested sites are still more acid and have higher concentrations of toxic forms of Al than moorland sites. Although the proposed emission reductions in Europe are likely to result in a continuing decline in S and N loadings to catchments, the continuing policy of planting second rotation forests in these acidified catchments may, in the long-term, delay or halt chemical and biological recovery. However, in the short-term, any increase in the uptake of N deposition by aggrading forests should help to counteract the acidifying effects of a small increase in the interception of S and N compounds.

Long-term trends in pH, aluminium and dissolved organic carbon in Scottish fresh waters; implications for brown trout (Salmo trutta) survival.

Over the past 30 years upland streams and lochs in Scotland have shown significant signs of recovery from acidification, particularly in terms of declining concentrations of non-marine sulphate (nm-SO(4)). Long-term index sites in central and southwest Scotland reveal a significant decline in the concentration of biologically important components, notably acidity (H(+)) and labile (toxic) forms of aluminium (Al-L), whilst dissolved organic carbon (DOC) and complexed forms of aluminium (AL-NL) have increased significantly. Although these improvements should increase the probability of brown trout survival, and have resulted in increased acid neutralising capacity (ANC) in fishless streams to values close to current critical limits, there is still a relatively poor correlation between ANC and current fish status. Site to site variability appears to be linked to the relative contribution of (H(+)), Al-L and DOC within the critical ANC (ANC(CRIT)) range. It is proposed that ANC(CRIT) should cover a range of ANC values as a function of Al-L concentration. Based on field studies an empirical range of critical ANC values are suggested which better predict the presence of a sustainable brown trout population.

Application of molecular biological methods for studying probiotics and the gut flora.

Increasingly, the microbiological scientific community is relying on molecular biology to define the complexity of the gut flora and to distinguish one organism from the next. This is particularly pertinent in the field of probiotics, and probiotic therapy, where identifying probiotics from the commensal flora is often warranted. Current techniques, including genetic fingerprinting, gene sequencing, oligonucleotide probes and specific primer selection, discriminate closely related bacteria with varying degrees of success. Additional molecular methods being employed to determine the constituents of complex microbiota in this area of research are community analysis, denaturing gradient gel electrophoresis (DGGE)/temperature gradient gel electrophoresis (TGGE), fluorescent in situ hybridisation (FISH) and probe grids. Certain approaches enable specific aetiological agents to be monitored, whereas others allow the effects of dietary intervention on bacterial populations to be studied. Other approaches demonstrate diversity, but may not always enable quantification of the population. At the heart of current molecular methods is sequence information gathered from culturable organisms. However, the diversity and novelty identified when applying these methods to the gut microflora demonstrates how little is known about this ecosystem. Of greater concern is the inherent bias associated with some molecular methods. As we understand more of the complexity and dynamics of this diverse microbiota we will be in a position to develop more robust molecular-based technologies to examine it. In addition to identification of the microbiota and discrimination of probiotic strains from commensal organisms, the future of molecular biology in the field of probiotics and the gut flora will, no doubt, stretch to investigations of functionality and activity of the microflora, and/or specific fractions. The quest will be to demonstrate the roles of probiotic strains in vivo and not simply their presence or absence.