Sociodemographic characteristics associated with a higher wish to complain about health care.

OBJECTIVES: Previous research has shown that patients who are older, less educated, or have lower income are less likely to lodge complaints about health care. This variation may reflect less wish to complain or inequitable access to complaint channels or remedies. We aimed to investigate associations between sociodemographic characteristics and health users' wish to complain. STUDY DESIGN: This was a randomized case vignette survey among 6756 Danish men aged 45-70 years (30% response rate). METHODS: Assuming they received the care in vignettes about prostate cancer (prostate-specific antigen) testing, participants rated their wish to complain on a 5-point Likert scale. Information on sociodemographic characteristics was obtained through self-reports and municipality-level information from national registries. RESULTS: Lower education was associated with an increased wish to complain (mean Likert difference 0.44 [95% CI 0.36-0.51]; P < .001). The wish to complain was higher among unemployed men (difference 0.16 [95% CI 0.04-0.28]; P < .011) and those with a chronic illness (difference 0.06 [95% CI 0.02-0.10]; P < .004). Given the same healthcare scenarios, there was no difference in wish to complain among health users who were retired, living rurally, or from lower income groups. CONCLUSIONS: Health users who are less educated, lower income, elderly, or from rural or minority communities appear to be as likely, or more likely, to wish to complain about health care as others. Yet, younger, well-educated, and higher income citizens are overrepresented in actual complaint statistics. The finding suggests persisting inequalities in the suitability or accessibility of complaint processes for some groups of patients.

The oral communication principle and coming up to informed decision requirements in national screening programs.

OBJECTIVE: Informed consent (IC) principles are often overlooked aspects in debates about national screening programs. This short communication examines the Danish approach to IC in decision-making about screening participation. STUDY DESIGN: A descriptive approach is adopted in linking present screening practices with Danish regulation about IC and international ethical principles. METHODS: To ascertain the extent to which screening procedures come up to IC requirements, the article adopts a review approach by examining relevant Danish national legislation including ministerial orders as well as international ethical codes. RESULTS: The article finds that, although Danish legislation as well as international IC principles generally stipulates a decision-making process requiring oral communication, current procedures largely rely on one-way communication through written information available from leaflets, web sites, etc. Screening programs seem to have established no general formula to qualify healthcare users' understanding of data underlying their choice whether to be screened. CONCLUSION: The deviance from common IC principles may reduce healthcare quality, pose a safety problem, and challenge healthcare users' ability to exercise autonomy.

Mixed reality holograms for heart surgery planning: first user experience in congenital heart disease.

AIMS: Proof of concept and feasibility study for preoperative diagnostic use of mixed reality (MR) holograms of individual 3D heart models from standard cardiac computed tomography angiograms (CTA) images. Optimal repair for complex congenital heart disease poses high demands on 3D anatomical imagination. Three-dimensional printed heart models are increasingly used for improved morphological understanding during surgical and interventional planning. Holograms are a dynamic and interactive alternative, probably with wider applications. METHODS AND RESULTS: A 3D heart model was segmented from CTA images in a patient with double outlet right ventricle and transposition of the great arteries (DORV-TGA). The hologram was visualized in the wearable MR platform HoloLens® for 36 paediatric heart team members who filled out a diagnostic and quality rating questionnaire. Morphological and diagnostic output from the hologram was assessed and the 3D experience was evaluated. Locally developed app tools such as hologram rotation, scaling, and cutting were rated. Anatomy identification and diagnostic output was high as well as rating of 3D experience. Younger and female users rated the app tools higher. CONCLUSION: This preliminary study demonstrates that MR holograms as surgical planning tool for congenital heart disease may have a high diagnostic value and contribute to understanding complex morphology. The first users experience of the hologram presentation was found to be very positive, with a preference among the female and the younger users. There is potential for improvement of the hologram manipulation tools.

Quality of raw and smoked fillets from clinically healthy Atlantic salmon, Salmo salar L., following an outbreak of pancreas disease (PD).

Pancreas disease (PD) is a viral disease of farmed salmonid fish, which causes huge economic losses. Pathological changes in skeletal muscle, pancreas and heart are hallmarks of PD. Stakeholders in the fish-smoking industry have claimed that fillets from PD-affected Atlantic salmon, Salmo salar L., are of poor quality. We therefore examined harvest-ready, clinically healthy Atlantic salmon from a population of fish previously affected by PD. Histopathological changes in skeletal muscle tissues ranged from minor to severe. Fillet quality measurements showed that fish with severe skeletal muscle changes provided a paler raw fillet and a yellowish and harder cold-smoked fillet than normal. PD had no significant effect on fillet gaping, bacteriological quality or off-odour development during storage. An unexpected finding was a significant subendocardial fibrosis in 23% of the PD-affected fish. The latter may indicate susceptibility to stress-related heart failure.

Study of the quality characteristics in cold-smoked salmon (Salmo salar) originating from pre- or post-rigor raw material.

Improved slaughtering procedures in the salmon industry have caused a delayed onset of rigor mortis and, thus, a potential for pre-rigor secondary processing. The aim of this study was to investigate the effect of rigor status at time of processing on quality traits color, texture, sensory, microbiological, in injection salted, and cold-smoked Atlantic salmon (Salmo salar). Injection of pre-rigor fillets caused a significant (P<0.001) contraction (-7.9%± 0.9%) on the caudal-cranial axis. No significant differences in instrumental color (a*, b*, C*, or h*), texture (hardness), or sensory traits (aroma, color, taste, and texture) were observed between pre- or post-rigor processed fillets; however, post-rigor (1477 ± 38 g) fillets had a significant (P>0.05) higher fracturability than pre-rigor fillets (1369 ± 71 g). Pre-rigor fillets were significantly (P<0.01) lighter, L*, (39.7 ± 1.0) than post-rigor fillets (37.8 ± 0.8) and had significantly lower (P<0.05) aerobic plate count (APC), 1.4 ± 0.4 log CFU/g against 2.6 ± 0.6 log CFU/g, and psychrotrophic count (PC), 2.1 ± 0.2 log CFU/g against 3.0 ± 0.5 log CFU/g, than post-rigor processed fillets. This study showed that similar quality characteristics can be obtained in cold-smoked products processed either pre- or post-rigor when using suitable injection salting protocols and smoking techniques.

Effects of phosphates and salt in ground raw and cooked farmed cod (Gadus morhua) muscle studied by the water holding capacity (WHC), and supported by P-NMR measurements.

A model system consisting of ground farmed cod muscle (80%, w/w) and added brine (20%, w/w) with different content and combinations of salt (0% and 3% in brine) and phosphorus compounds (mono-, di-, tri- and hexametaphosphates; 0% and 3% in brine) was used to simulate industrial brining of muscle foods. Individual phosphorus component concentrations and breakdown as function of time (0, 23 h) were analyzed using (31)P-NMR spectroscopy. The effects of salt and phosphate on water holding capacity (WHC) were measured at similar sampling times, and interrelations between phosphorous components determined by NMR and WHC were established. Addition of salt led to a significant increase (+18%) in WHC, and the combined effect of salt and phosphates was even more pronounced (+29%). The positive effect of triphosphate and salt on WHC was also seen after cooking (+36% in raw and +41% in cooked cod muscle, relative to control), although NMR analysis showed a rapid breakdown of di- and triphosphates.

Transcriptome analysis of Schistosoma mansoni larval development using serial analysis of gene expression (SAGE).

SUMMARY: Infection of the snail, Biomphalaria glabrata, by the free-swimming miracidial stage of the human blood fluke, Schistosoma mansoni, and its subsequent development to the parasitic sporocyst stage is critical to establishment of viable infections and continued human transmission. We performed a genome-wide expression analysis of the S. mansoni miracidia and developing sporocyst using Long Serial Analysis of Gene Expression (LongSAGE). Five cDNA libraries were constructed from miracidia and in vitro cultured 6- and 20-day-old sporocysts maintained in sporocyst medium (SM) or in SM conditioned by previous cultivation with cells of the B. glabrata embryonic (Bge) cell line. We generated 21 440 SAGE tags and mapped 13 381 to the S. mansoni gene predictions (v4.0e) either by estimating theoretical 3' UTR lengths or using existing 3' EST sequence data. Overall, 432 transcripts were found to be differentially expressed amongst all 5 libraries. In total, 172 tags were differentially expressed between miracidia and 6-day conditioned sporocysts and 152 were differentially expressed between miracidia and 6-day unconditioned sporocysts. In addition, 53 and 45 tags, respectively, were differentially expressed in 6-day and 20-day cultured sporocysts, due to the effects of exposure to Bge cell-conditioned medium.

Injection-salting and cold-smoking of farmed atlantic cod (Gadus morhua L.) and Atlantic salmon (Salmo salar L.) at different stages of Rigor Mortis: effect on physical properties.

Processing of fish is generally conducted postrigor, but prerigor processing is associated with some potential advantages. The aim of this study was to study how 5 processing regimes of cold-smoked cod and salmon conducted at different stages of rigor influenced yield, fillet shrinkage, and gaping. Farmed cod and salmon was filleted, salted by brine injection of 25% NaCl, and smoked for 2 h at different stages of rigor. Filleting and salting prerigor resulted in increased fillet shrinkage and less increase in weight during brine injection, which in turn was correlated to the salt content of the fillet. These effects were more pronounced in cod fillets when compared to salmon. Early processing reduced fillet gaping and fillets were evaluated as having a firmer texture. In a follow-up trial with cod, shrinkage and weight gain during injection was studied as an effect of processing time postmortem. No changes in weight gain were observed for fillets salted the first 24 h postmortem; however, by delaying the processing 12 h postmortem, the high and rapid shrinking of cod fillets during brine injection was halved.

Cold smoking of Atlantic salmon (Salmo salar) fillets with smoke condensate--an alternative processing technology for the production of smoked salmon.

Two different protocols for the production of cold smoked salmon were investigated. All fillets were dry salted (18 h, 4 degrees C) before being allotted to a smoke condensate/liquid smoke protocol (SCP), which included drenching (1 min) in smoke condensate [1:3 (v/v) smoke:water] and drying (150 min, 28.4 +/- 2.2 degrees C) or a wood chips protocol (WCP) that included drying and smoking in a regular smoking chamber (23 degrees C, 480 min) using wood chips for smoke production. Quality assessments were performed on the smoked fillets at day 0 and after 7, 14, and 31 d of storage (3.4 +/- 0.7 degrees C). Application of the SCP resulted in a significantly higher (P<0.01) processing yield (89.6% +/- 0.7%) as compared to the WCP (88.6% +/- 0.5%). On day 0, the SCP fillets were significantly (P<0.01) less light (L*) and yellow (b*) and had a lower chroma (C*) and hue (h*) compared to the fillets processed with WCP. From 7 d until the end of storage time, small differences in color were observed. After 31 d of storage, the SCP fillets had a significantly higher (P<0.05) intensity of oily texture and lower intensity of salty and smoke taste. Texture profile analysis (TPA) showed few significant differences between the processing protocols, although the WCP fillets were significantly harder than the SCP fillets when recording the force at 60% compression of the fillet height. The use of smoke condensate and drenching technology is a way of producing cold smoked salmon with quality characteristics quite similar to those found in commercial "traditional" products, although processors who want to use this technology have to optimize the drying step and the smoke condensate formulation to their specifications.

Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se?

BACKGROUND: An association between posttransplant lymphoproliferative disorder (PTLD) and cyclosporine A (CsA) and OKT3 has often been postulated on the basis of retrospective studies, although a randomized study with PTLD as the endpoint will probably never be performed. Because focus on PTLD coincided with the use of these drugs, a bias could be suspected. METHODS: In a retrospective, nonrandomized study, we reevaluated all lymphoma-like lesions arising in kidney-transplant patients grafted at our center during 1969 to 1998 and observed up to 2002. Case pathology was reviewed, and an association with Epstein-Barr virus (EBV) infection (and latency pattern) was assessed. RESULTS: We did not find any significant difference in the incidence of PTLDs when comparing the prednisolone/azathioprine, and CsA eras (P=0.89), the periods before or after OKT3 (P=0.61), and those before or after antilymphocyte globulin (ALG) (P=0.22). Occurrence time was shorter in the CsA (P=0.059), OKT3 (P=0.007), and ALG (P=0.007) eras. In the OKT3 era, 182 patients received, and 224 did not receive, OKT3; after the same observation time, there had been eight and five PTLDs, respectively (P=0.34). The use of mycophenolate mofetil (MMF) was associated with a reduction in the number of PTLDs (P=0.01). EBV was detected in 16 of 21 (76%) cases. CONCLUSIONS: We found no evidence to implicate any one drug regime preferentially in the development of PTLDs. The risk of developing PTLD seems to be a result of the whole transplantation process, which includes the antigenicity of the foreign graft, the immunosuppression resulting in inadequate cytotoxic T-cell activity, and the result of EBV infection. An important minority of cases are EBV negative.

Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance, interleukin-18 course, and results of retransplantation.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD, and in whom we were able to perform IL-18 analyses. RESULTS: Patients were followed for up to 7 years after PTLD diagnosis. Treatment consisted of immunosuppression cessation with radiation therapy in cases with overt monomorphic lymphomas. All patients' PTLDs were resolved, and all patients but one (whose graft was removed) demonstrated a period of operational graft tolerance of up to 5 years. Five patients underwent retransplantation without sign of recurrence of the PTLD up to 3 years after transplantation. In the eight patients analyzed, IL-18 increased significantly during PTLD regression and follow-up in those with long-term operational tolerance. CONCLUSION: We report on a series of patients with resolved PTLDs demonstrating long-term recurrence-free survival, of whom most experienced a long period of operational graft tolerance. IL-18 seems to play a role in the resolution of the PTLDs. Five patients underwent retransplantation with standard immunosuppression without recurrence. A previous diagnosis of PTLD should not be regarded as a contraindication for later retransplantation.

Steroid-free immunosuppression in renal transplantation: a long-term follow-up of 100 consecutive patients.

BACKGROUND: Our goal in clinical renal transplantation is to establish a steroid-free immunosuppressive protocol that not only promotes long-term patient and graft survival, but also improves the overall well-being of the patients. METHODS: In a prospective, nonrandomized, clinical study 100 consecutive patients transplanted with first and second grafts were discharged from our center with functioning grafts 1996-1999 and followed for up to 4 1/2 years. Patients received steroid-free immunosuppression with an initial 10-day antithymocyte (ATG) induction and maintenance therapy with cyclosporine (CsA) and mycophenolate mofetil (MMF). No steroids were given. RESULTS: After an observation time of up to 4 1/2 years, 1-, 2-, 3-, and 4-year graft survivals of 97, 96, 90, and 82% were observed, with no correlation to HLA-matching, kidney disease, donor age or type, or number of transplants. Ninety-nine patients (1 died or peritonitis after returning to dialysis) were alive and well. Ninety grafts were functioning well, 9 patients returned to dialysis due to recurrence of hemolytic uremic syndrome, and glomerulonephritis in 2 and chronic rejection in 7 grafts after 7-36 months (3 due to non-compliance after 7-30 months). All 7 children below the age of 15 are alive, with well-functioning grafts, except 1 with recurrence of glomerulonephritis who returned to dialysis after 2 1/2 years. There were 13 acute rejections (13%), 10 early (first 3 months) (10%), and 3 late (6-42 months) (3%). All acute rejection episodes were successfully reversed. No lymphomas were observed. CONCLUSIONS: Our first-line, steroid-free immunosuppressive protocol allows initial graft function, provides a safe level of long-term graft survival and function with a very low rejection rate, gives an acceptable rate of side effects, and possesses the potential for lowering the incidence of chronic rejection over the long-term. Compared with protocols that discontinue steroids after the initial posttransplant period, a steroid-free protocol avoids the increased risk of infection, body disfigurement, and other steroid-induced side-effects in the early posttransplant period. It also avoids the long-term risks of steroid use and the increased risk of rejection when the steriods are withdrawn.

Cancer risk in patients on dialysis and after renal transplantation.

The increased risk of cancer in patients who have had kidney transplants has mainly been attributed to immunosuppressive therapy; however, the prior period of uraemia and dialysis has also been postulated as a cofactor. We analysed cancer risk retrospectively in a cohort of 4178 patients undergoing renal replacement therapy, of whom 3592 were treated with dialysis alone and 1821 later had transplants. We found that excess cancer risk in such patients occurred after transplantation and not during dialysis.

Effect of protective solutes on leakage from and survival of immobilized lactobacillus subjected to drying, storage and rehydration

When lactic acid bacteria are used industrially as fermentation starters it is important to obtain stable and highly viable bacterial cultures. Six strains of Lactobacillus encapsulated in Ca-alginate gel beads were investigated to determine whether dehydration, storage and rehydration may inflict injury. A negative relationship between leakage of lactate dehydrogenase and survival rates was found. Mesophilic lactobacilli showed only negligible leakage compared with thermophilic strains when dehydrated at 30 degrees C to a level of 0.11 g H20 (g dry wt)-1. The choice of an appropriate suspending medium to be introduced before drying was therefore very important for thermophilic lactobacilli in order to increase the survival rates during dehydration, storage and rehydration. The osmoregulatory solutes tested were adonitol, betaine, glycerol and reconstituted non-fat milk solids (NFMS). Less injury was inflected during dehydration for Lactobacillus helveticus with adonitol, glycerol and NFMS. Survival rates for the strains subjected to immobilization, dehydration, storage and rehydration varied with the strain and the protective solute when fluidized-bed drying was used at 5 degrees C to a level as high as 0.34 g H20 (g dry wt)-1. Non-fat milk solids gave the best protection for thermophilic lactobacilli, while adonitol and NFMS were best for mesophilic lactobacilli.

Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol.

BACKGROUND: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD). We tested this paradigm by studying the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. METHODS: EBV serology was performed in 267 consecutive renal transplantations (1990-1997). All were treated with cyclosporine with an initial 10-day antilymphocyte globulin course, supplemented from September 1995 with MMF. In 208 consecutive transplantations after June 1992 aciclovir 3200 mg/day was given for 3 months posttransplantation. RESULTS: After an observation period of up to 7 years we found that: (1) primary or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P<0.00005) and to the incidence of PTLD (P=0.03; P=0.01, if Hodgkin's disease is included); (2) aciclovir protected against PREBV (P<0.00005) and (3) adding mofetil to the immunosuppressive protocol reduced PREBV further (P=0.0001), (4) in 78 transplantations treated with cyclosporine/antilymphocyte globulin/mofetil we observed only 10 acute rejections (P=0.0001), 10 PREBVs (P<0.00005), and no PTLDs compared with the cyclosporine/antilymphocyte globulin group (P=0.04). CONCLUSIONS: Supplemental immunosuppression with mofetil protects against acute rejection. In combination with aciclovir, there is also a reduction in the number of PREBVs, apparently as a result of both direct viral prophylaxis and better rejection control, and in the incidence of EBV-induced PTLD.

Interleukin-10 and posttransplant lymphoproliferative disorder after kidney transplantation.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation, which comprises a morphologically and clinically heterogeneous spectrum of B-lymphocyte diseases. Risk factors include primary or reactivated Epstein-Barr virus (EBV) infection, and the type and duration of immunosuppression. Interleukin-10 (IL-10) is a pleiotropic cytokine, produced primarily by T-helper 2 (Th2) lymphocytes in the later stages of T-cell activation, suggested to play a role in EBV-associated PTLD. We recently reported preliminary findings on IL-10 in relation to the development of PTLD in three kidney transplanted patients. The study now includes nine patients that could be followed before and/or after the occurrence of lymphoma. METHODS: Nine patients with lymphomas (eight PTLDs and one Hodgkin's disease) were diagnosed among 268 consecutive renal transplantations (1990-1997). All were treated with cyclosporine with an initial 10-day course of antilymphocyte globulin, supplemented from 1995 with mycophenolate mofetil. Serum antibodies against EBV were detected using recombinant antigens. A double sandwich enzyme-linked immunosorbent assay using rabbit antibodies to purified human recombinant IL-10 was employed; the assay is specific for human natural and viral IL-10. RESULTS: Three patients experienced primary EBV infection, five reactivated EBV infections, and one did not change EBV status. Three patients had a fulminant course and died with EBV-associated PTLD confirmed post mortem. The other six are alive and are apparently cured. Treatment was immediate discontinuation of immunosuppression (in all PTLDs) and long-term high-dose aciclovir in all but one. Two patients have maintained excellent graft function for 3 and 2 years, respectively, without immunosuppression and are now in a state of operational tolerance. In three of four cases with initial lymphoma, EBV infection (primary or reactivation) preceded the increase in IL-10. In all four cases, the IL-10 increase preceded the PTLD diagnosis. In six cases, IL-10 could be followed after treatment showing either immediate zero or a decrease to zero. CONCLUSION: IL-10 seems to play a role in EBV-associated PTLD. Moreover, IL-10 may have an important role in transplant tolerance by inducing long-lasting anergy to donor- and host-specific alloantigens, perhaps caused by down-regulation of Th1 cytokines in the graft. If substantiated, this may provide new insight into the pathogenesis of PTLD introducing new strategies for prevention and therapy of PTLD, and for the induction of tolerance in transplanted patients.

[The history of transplantation]. / Transplantationens historie.

Transplantation is a young discipline with a long history, of which this paper therefore only describes fragments. The story is created by the pioneers, who made the basis for transplantation. I have focused on those who received the Nobel prize for their work, Carrel (1912), Burnet, Medawar (1960), Snell, Dausset, Benacerraf (1980), Elion, Hitchings (1988), and Thomas and Murray (1990), however many others deserve to be mentioned. Parallelled with the development of transplantation, other disciplines like immunology have grown up. Today we can transplant kidneys, hearts, livers, and bone marrow as a kind of routine. However we do treat on the brink of medicine, and the suppression of the immune apparatus has a prize, which is a tendency to atherosclerosis, virus infections and malignancies.

Demonstration of safety of probiotics -- a review.

Probiotics are commonly defined as viable microorganisms (bacteria or yeasts) that exhibit a beneficial effect on the health of the host when they are ingested. They are used in foods, especially in fermented dairy products, but also in pharmaceutical preparations. The development of new probiotic strains aims at more active beneficial organisms. In the case of novel microorganisms and modified organisms the question of their safety and the risk to benefit ratio have to be assessed. Lactic acid bacteria (LAB) in foods have a long history of safe use. Members of the genera Lactococcus and Lactobacillus are most commonly given generally-recognised-as-safe (GRAS) status whilst members of the genera Streptococcus and Enterococcus and some other genera of LAB contain some opportunistic pathogens. Lactic acid bacteria are intrinsically resistant to many antibiotics. In many cases resistances are not, however, transmissible, and the species are also sensitive to many clinically used antibiotics even in the case of a lactic acid bacteria- associated opportunistic infection. Therefore no particular safety concern is associated with intrinsic type of resistance. Plasmid-associated antibiotic resistance, which occasionally occurs, is another matter because of the possibility of the resistance spreading to other, more harmful species and genera. The transmissible enterococcal resistance against glycopeptide antibiotics (vancomycin and teicoplanin) is particularly noteworthy, as vancomycin is one of the last effective antibiotics left in the treatment of certain multidrug-resistant pathogens. New species and more specific strains of probiotic bacteria are constantly identified. Prior to incorporating new strains into products their efficacy should be carefully assessed, and a case by case evaluation as to whether they share the safety status of traditional food-grade organisms should be made. The current documentation of adverse effects in the literature is reviewed. Future recommendations for the safety of already existing and new probiotics will be given.