Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.

The activity of the aryl hydrocarbon receptor in T cells tunes the gut microenvironment to sustain autoimmunity and neuroinflammation.

Multiple sclerosis (MS) is a T cell-driven autoimmune disease that attacks the myelin of the central nervous system (CNS) and currently has no cure. MS etiology is linked to both the gut flora and external environmental factors but this connection is not well understood. One immune system regulator responsive to nonpathogenic external stimuli is the aryl hydrocarbon receptor (AHR). The AHR, which binds diverse molecules present in the environment in barrier tissues, is a therapeutic target for MS. However, AHR's precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that in a mouse model of MS, T cell-specific Ahr knockout leads to recovery driven by a decrease in T cell fitness. At the mechanistic level, we demonstrate that the absence of AHR changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota, while simultaneously identifying new potential molecular targets for the treatment of MS and other autoimmune diseases.

The hypothalamic-pituitary-adrenal axis activity in archers: cortisol release, stress, anxiety and success.

BACKGROUND: Archery is a unique sport requiring simultaneous physical and psychological focusing for precisely hitting the small, distant target. Thus, in this sport, the effects of stress and anxiety on success might be more pronounced as a slight deviation in aiming may translate into a large error in meeting the target. Therefore, the current study aimed to assess the interrelationship between anxiety, cortisol awakening response (CAR), cortisol levels during the shooting period, and success in professional male archers during a national tournament. METHODS: Archers (16-20 years old, male, N.=20) shooting with recurve bow participated in the current study during the indoor archery championship. For the assessment of CAR, salivary samples were collected at 0- (wake up), 30-, 45- and 60-min postawakening on three consecutive days, namely qualification, individual elimination, and team shooting days. On the first two days of the shootings (i.e., qualification and elimination), shooting salivary samples were collected at 30 and 15 minutes before the shootings, at half-time and just after the shootings. State and trait anxiety inventory were filled in on the day of registration (the day before qualification shootings). RESULTS: CAR, measured as the area under the curve (AUC), was higher on the elimination day (P=0.038) compared to the qualification day. Shooting cortisol levels were also higher on the elimination day compared to the qualification day (P=0.004). Archers having high rankings on qualification day also had higher success rates on elimination day (r=0.963, P<0.001). CONCLUSIONS: Moderately increased state anxiety, higher CAR, and elevated shooting cortisol levels appear to be the integral components of the elimination stage during a real competition in archery. Thus, assessment of secretion dynamics of cortisol appears to be a valuable objective tool for understanding the neuroendocrine control during the competition days.

Subfunctionalization of Paralog Transcription Factors Contributes to Regulation of Alkaloid Pathway Branch Choice in Catharanthus roseus.

Catharanthus roseus produces a diverse range of specialized metabolites of the monoterpenoid indole alkaloid (MIA) class in a heavily branched pathway. Recent great progress in identification of MIA biosynthesis genes revealed that the different pathway branch genes are expressed in a highly cell type- and organ-specific and stress-dependent manner. This implies a complex control by specific transcription factors (TFs), only partly revealed today. We generated and mined a comprehensive compendium of publicly available C. roseus transcriptome data for MIA pathway branch-specific TFs. Functional analysis was performed through extensive comparative gene expression analysis and profiling of over 40 MIA metabolites in the C. roseus flower petal expression system. We identified additional members of the known BIS and ORCA regulators. Further detailed study of the ORCA TFs suggests subfunctionalization of ORCA paralogs in terms of target gene-specific regulation and synergistic activity with the central jasmonate response regulator MYC2. Moreover, we identified specific amino acid residues within the ORCA DNA-binding domains that contribute to the differential regulation of some MIA pathway branches. Our results advance our understanding of TF paralog specificity for which, despite the common occurrence of closely related paralogs in many species, comparative studies are scarce.

Effects of Complement Regulators and Chemokine Receptors in Type 2 Diabetes.

CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diabetes and its complications. The stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) are chemokine proteins. We aimed to investigate the relation of CD55 and CD59 expression levels and polymorphisms of SDF-1 and CXCR-4 with type 2 diabetes mellitus (T2DM) and its complications. Seventy-five T2DM patients and 73 controls were enrolled. Expression levels of CD55 and CD59 were measured by FACS Calibur; qRT-PCR was used to determine SDF-1 and CXCR-4 gene polymorphisms. CD55 and CD59 expressions in patients with nephropathy, retinopathy and cardiovascular disease were significantly lower than controls. Frequency of CXCR-4 T allele carrying was high in patients and created 1.6 fold risk for the disease (p = .07). CXCR-4 a allele carriers had decreased nephropathy; although there was no statistical significance in carrying CXCR-4 T allele, presence of nephropathy was approximately 2 times higher (p = .254). The nephropathy risk increased 10-fold in CXCR-4 TT genotype carriers (p = .02). All SDF-1 CC genotype carriers had retinopathy, so, it was considered that the CC genotype was effective in retinopathy development (p = .031). For the presence of cardiovascular disease, significant difference was observed for SDF-1 genotypes. Increased cardiovascular risk of 5- and 1.9-fold in SDF-1 T (p = .007) and CXCR-4 T (p = .216) allele carriers, respectively, was observed. We suggest that CD55 and CD59 protein levels and SDF-1 and CXCR-4 have predictive importance in process, complications and tendency of T2DM.

Prevalence of common mental disorders among Syrian refugee children and adolescents in Sultanbeyli district, Istanbul: results of a population-based survey.

AIMS: Research demonstrates elevated levels of common mental disorders among Syrian refugees, but the majority of studies have, to date, focused on adult populations. This study aims to estimate the prevalence of depression, anxiety and post-traumatic stress disorder (PTSD) among Syrian children and adolescents living in Sultanbeyli district of Istanbul, Turkey. METHODS: A population-based survey among Syrian children and adolescents aged 8-17 years living in Sultanbeyli district was conducted in 2019, as part of an all-age survey of disability. 80 clusters of 50 participants (all-ages) were selected from the local municipality's refugee registration database using probability proportionate to size sampling. Children aged 8-17 years were assessed for symptoms of common mental disorders using the Child Revised Impact of Event Scale (CRIES-8) and abbreviated versions of the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Child Anxiety Related Disorders (SCARED). RESULTS: Of the 852 participants, 23.7% (95% CI 19.9-27.2) screened positive for symptomatic depression, PTSD and anxiety. The prevalence estimates for depression, PTSD and anxiety were 12.5% (95% CI 9.8-15.6), 11.5% (95% CI 9.1-14.4) and 9.2% (95% CI 6.8-12.1), respectively. Depression and PTSD were significantly more common in older adolescents, whilst anxiety and PTSD were significantly more common in girls. Depression was more common in children from poorer households and those who had received no education. Children coming from larger households were less likely to show symptoms of PTSD. CONCLUSIONS: Syrian refugee children and adolescents are vulnerable to common mental disorders, and culturally appropriate prevention and intervention support are needed for this population.

Hepatoprotective potential of Ferula communis extract for carbon tetrachloride induced hepatotoxicity and oxidative damage in rats.

We investigated the hepatoprotective potential of Ferula communis extract for CCI4 induced liver damage. We used six groups of rats: group 1, untreated control; group 2, CCl4 treated (hepatotoxic); group 3, treated with 150 mg/kg F. communis; group 4, treated with 300 mg/kg F. communis; group 5, treated with CCl4 + 150 mg/kg F. communis; and group 6, treated with CCl4 + 300 mg/kg F. communis. Liver damage was produced by injection of 1 ml/kg CCI4 twice/week. Extracts of F. communis, 150 and 300 mg/kg/day, were administered for 8 weeks. The effects of F. communis were assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and total bilirubin (T-BIL) levels, and the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver. The histology and immunohistochemistry of liver tissue were evaluated using hematoxylin and eosin staining, and caspase 3 and 8-OHdG immunostaining. F. communis extract produced significant reductions in elevated levels of ALT, AST, GGT and T-BIL and increased levels of GPx and SOD in rats treated with CCl4. F. communis extract decreased CCl4 induced 8-OHdG formation and caspase 3 activation significantly in hepatocytes, especially at the 150 mg/kg dose. Our findings demonstrate the potential efficacy of F. communis for attenuating CCl4 induced hepatotoxicity and oxidative damage.

Increased serum leptin levels are associated with metabolic syndrome and carotid intima media thickness in premenopausal systemic lupus erythematosus patients without clinical atherosclerotic vascular events.

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3 ± 6.7, 32.7 ± 9.3 and 29.9 ± 5.6 years, respectively. The mean disease duration, SLICC (Systemic Lupus International Collaborating Clinics damage index) and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 ± 54.9 months, 0.16 ± 0.48 and 1.18 ± 1.5, respectively, and were similar between MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001; p = 0.002, p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p = 0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA) scores were significantly higher in SLE MetS+ than SLE MetS- ( p = 0.018; p = 0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025). Conclusions In premenopausal women with SLE without a history of CVD, CIMT values were increased and related to MetS. Leptin was increased in patients with MetS and correlated with CIMT values.

Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants.

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25-0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23-0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11-4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89-1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89-1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol 2018;771-781.

Pancreatic involvement in cystic fibrosis.

Cystic fibrosis (CF) is an important genetic disorder that usually manifests in early childhood. Better understanding and improved care of CF patients in our current practice with pancreatic enzyme replacement therapy and nutritional support has enabled physicians to see them more frequently from any age groups. After the lungs, pancreas is the most important organ involved with CF. Its most frequently affected component is the exocrine pancreas while endocrine functions may also be deranged. Parenchymal damage as acute or chronic pancreatitis may also develop. Herein, we aimed to outline the types of the disease, clinical picture, diagnosis and genetic aspect of the CF linked with the pancreatic involvement.

Cathelicidin and human ß-defensin 2 in bronchoalveolar lavage fluid of children with pulmonary tuberculosis.

BACKGROUND: The antimicrobial peptide cathelicidin LL-37/hCAP-18 and human ß-defensins (hBD) are key factors in innate immune responses of the respiratory tract. OBJECTIVE: To determine LL-37 and hBD-2 concentrations in the bronchoalveolar lavage (BAL) fluid of paediatric patients (aged <16 years) with pulmonary tuberculosis (TB) and to compare these with concentrations in healthy children. METHODS: We measured peptide concentrations using an immunosorbent assay (ELISA). RESULTS Forty TB patients and 40 healthy controls were enrolled in the study (mean age 9.2 ± 4.7 and 8.3 ± 4.2 years, respectively, P = 0.97). The two groups exhibited no statistically significant difference in terms of sex, body mass index, relative weight or 25-hydroxyvitamin D levels. The mean BAL LL-37 level of the TB group was significantly higher than that of the control group (0.95 ± standard deviation [SD] 1.33 vs. 0.35 ± SD 0.51 ng/ml, P = 0.01, t = 2.54). The hBD-2 level was also higher in the TB group; however, the difference was not statistically significant (0.30 ± SD 0.58 vs. 0.14 ± SD 0.30 ng/ml, P = 0.11). There was no correlation between LL-37, hBD-2 and 25-hydroxyvitamin D levels. CONCLUSIONS Our data suggest that LL-37 and hBD-2 may play an important role in TB pathogenesis in children. To our knowledge, this is the first study on BAL LL-37 and hBD-2 concentrations in children with pulmonary TB.

[The treatment of female urinary incontinence]. / Le traitement de l'incontinence urinaire chez la femme.

Urinary incontinence isn't a fatality anymore. This pathology, which handicaps a large majority of the female population, should be treated in a global approach of the pelvic floor pathologies. Up to 25% of women over 65 years will suffer from urinary incontinence but age is not a discriminating factor in the appearance of this pathology. Comportemental and physiotherapeutical treatments are primordial. In case of lack of good results, surgery may offer good results in urinary incontinence and pharmacological treatment for urge urinary incontinence. In this text, the most common treatment options will be discussed.

Evaluation of nutrient equivalency of microbial phytase in hens in late lay given maize-soybean or distiller's dried grains with solubles (DDGS) diets.

1. An experiment was conducted with 360 Lohmann LSL-Classic White Leghorn layers (64 weeks old) to evaluate the effects of supplementation of microbial phytase on production, egg quality, bone, selected manure parameters and feed costs. 2. Experimental diets were formulated as follows: (1) maize-soybean (CS), (2) CS+300 units of phytase (FTU)/kg diet which was formulated to recoup only calcium and available phosphorus equivalency for phytase (CS+PHYCa+P), (3) CS+300 FTU/kg diet which was formulated to recoup total nutrient equivalency for phytase (CS+PHYtotal), (4) CS+100 g/kg distiller's dried grains with solubles (DDGS), (5) DDGS+300 FTU/kg diet which was formulated to recoup only calcium and available phosphorus equivalency for phytase (DDGS+PHYCa+P), or (6) DDGS+300 FTU/kg diet which was formulated to recoup total nutrient equivalency for phytase (DDGS+PHYtotal). 3. Each dietary treatment was assigned to 4 replicate groups with 3 cages and 5 hens per cage. The hens were provided with feed and water ad libitum. The experiment lasted for 8 weeks. 4. CS+PHYCa+P, CS+PHYtotal, DDGS+PHYCa+P and DDGS+PHYtotal diets supplemented with phytase provided similar percentage egg production, egg weight, egg mass, exterior egg quality, initial and final body weight compared with phytase-free diets. 5. However, supplementation of phytase to the experimental diets and calculation of the total nutrient equivalency for enzyme caused increased feed intake and decreased feed conversion ratio and Haugh unit. 6. No differences in manure dry matter, crude ash, total nitrogen, tibia crude ash, calcium and phosphorus contents were found among the experimental diets. On the other hand, manure total phosphorus content was significantly decreased in the DDGS diet and diets supplemented with phytase in comparison to the CS diet. 7. It was concluded that the addition of microbial phytase to the CS-based diets or diets with DDGS of hens in late lay and using Ca and available P equivalency of enzyme in feed; formulation may provide an economic benefit and decrease the amount of phytate P excretion in the manure without compromising production and egg quality parameters.

IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses.

BACKGROUND: IL-10-producing regulatory B cells suppress immune responses, and lack of these cells leads to exacerbated symptoms in mouse models of chronic inflammation, transplantation, and chronic infection. IgG4 is a blocking antibody isotype with anti-inflammatory potential that is induced in human high-dose antigen tolerance models. OBJECTIVE: We sought to characterize human inducible IL-10-secreting B regulatory 1 (BR1) cells and to investigate their immunoregulatory capacity through suppression of cellular immune responses and production of anti-inflammatory immunoglobulins. METHODS: Highly purified IL-10-secreting B cells were phenotypically and functionally characterized by means of whole-genome expression analysis, flow cytometry, suppression assay, and antibody production. B cells specific for the major bee venom allergen phospholipase A2 (PLA) were isolated from beekeepers who displayed tolerance to bee venom antigens and allergic patients before and after specific immunotherapy. RESULTS: Human IL-10+ BR1 cells expressed high surface CD25 and CD71 and low CD73 levels. Sorting of CD73-CD25+CD71+ B cells allowed enrichment of human BR1 cells, which produced high levels of IL-10 and potently suppressed antigen-specific CD4+ T-cell proliferation. IgG4 was selectively confined to human BR1 cells. B cells specific for the major bee venom allergen PLA isolated from nonallergic beekeepers show increased expression of IL-10 and IgG4. Furthermore, the frequency of IL-10+ PLA-specific B cells increased in allergic patients receiving allergen-specific immunotherapy. CONCLUSION: Our data show the characterization of IL-10+ BR1 cells and in vivo evidence for 2 essential features of allergen tolerance: the suppressive B cells and IgG4-expressing B cells that are confined to IL-10+ BR1 cells in human subjects.

Effects of inulin supplementation on selected faecal characteristics and health of neonatal Saanen kids sucking milk from their dams.

Fifty newborn Saanen kids were used to study the effects of inulin supplementation on faecal score, faecal pH, selected faecal bacterial population, BW, body temperature, haematological traits, selected health parameters and the incidence of diarrhoea. Kids were sorted by parity of their dams and multiple birth (twin or triplet) and assigned to one of the two groups (control: CG, and experimental: EG) at birth. Each group consisted of 25 kids. The groups were similar with regard to sex and birth weight. All kids were fed colostrum for the first 3 days after birth, and then the kids in EG were adapted to inulin supplementation by an increased dosage from day 4 to 7. Each kid in EG was supplemented with 0.2 g, 0.3 g, 0.4 g, 0.5 g and 0.6 g inulin on day 4, 5, 6, 7 and from day 8 to 28, respectively, whereas the kids in CG did not receive inulin. Faecal score and faecal bacterial population were not affected by inulin supplementation (P > 0.05). There were differences in faecal pH on day 14 (P = 0.01) and 28 (P<0.05), whereas no difference in faecal pH on day 21 (P > 0.05) was detected between groups. No differences (P > 0.05) in BW and haematological traits were found between groups. Body temperature did not differ on day 14 and 21 (P > 0.05), whereas there was a difference in body temperature on day 28 (P = 0.01) between groups. The numbers of kids with pneumonia and kids treated for pneumonia and diarrhoea were similar for CG and EG. Kid losses during the study were the same for CG and EG. The incidence of diarrhoea was not affected by inulin supplementation (P > 0.05). Inulin supplemented to kids did not adversely affect faecal score. The effect of inulin on faecal pH was not consistent. The results of our study suggested that daily dose (0.6 g) of inulin might not be enough to observe effects of it. Our data will be useful to determine the dose and timing of inulin supplementation in future studies investigating the effects of inulin on the parameters associated with performance and health status in kids and other young ruminants.

Peripheral immune response in pulmonary tuberculosis.

Cellular immune response and delayed-type hypersensitivity reactions are considered to play a major role in the immunopathogenesis of pulmonary tuberculosis (PTB). But the exact mechanism is still to be clarified. Th1 cells are mainly involved in cellular immune responses in PTB and provide a normal healing process with minimal or no sequela whereas Th2 cell and CD8(+) T lymphocyte responses may lead to more severe type of disease. In this study, we investigated the peripheral blood immune responses in PTB. The study group consisted of acid fast positive young male soldiers with PTB and a negative HIV serology. The control group included healthy young volunteer male soldiers without a history of PTB. Intracytoplasmic cytokine content of CD8(+) T cells and lymphocytes, including IL-2, IL-4, IL-5, IL-10 and IFN-gamma were determined by flow cytometry, and IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha serum levels were measured by cytometric bead array (CBA). No difference was observed between the percentages of T, B, NK cells and HLA-DR expression in both groups, however, the number of CD3(+)HLA-DR(+) activated T cell percentages was higher in PTB group as compared to healthy subjects. IL-2, IL-4, IL-5, IL-10 contents of lymphocytes and IFN-gamma(+)CD8(+) T cells were found to be significantly lower in PTB patients when compared with healthy subjects, and in parallel, serum IL-2, IL-4, IL-5 and TNF-alpha levels were also significantly lower in PTB patients. In conclusion we suggest that, CD8(+) T cells producing both Th1 and Th2 type cytokines, may play important role in the peripheral immune response to mycobacteria.

Frontiers in clinical immunology 2008.

In recent years, investigations in immunology have led to progress in clinical medicine, including understanding transplant rejection, autoimmune diseases, immune deficiencies, inflammation, transplantation, cancer and the development of new vaccines. At a meeting recently held on the Mediterranean shore, advances in several facets of clinical immunology were the focus of discussion. Here, we highlight some of the debates that reflected advances in a variety of human immune disorders.

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

Natural killer cells in allergic inflammation.

Natural killer (NK) cells are large granular lymphocytes of the innate immune system that exert a potent function against infected and tumor cells. Although NK cells were originally defined by their capacity to lyse target cells and produce interferon-gamma without prior activation, recent studies showed that NK cells also display a potent regulatory function. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, producing cytokines and providing costimulation to cells of the adaptive immune system. NK cells play important roles in viral infections, autoimmunity, pregnancy, cancer and bone marrow transplantation, but little is known about the role of NK cells in allergy. Recent developments in the understanding of the role of human NK cells in allergy are overviewed.

Open intramedullary Kirschner wire versus screw and plate fixation for unstable forearm fractures in children.

PURPOSE: To compare the outcomes of intramedullary Kirschner wire versus screw and plate fixation for unstable forearm fractures in children aged older than 10 years. METHODS: Records of 32 children aged 10 to 15 (mean, 12) years with displaced fractures of the radius and ulna were retrospectively reviewed. 17 boys and 4 girls underwent intramedullary Kirschner wiring, whereas 10 boys and one girl underwent plating. All patients had been initially treated with closed reduction and casting. Indications for surgical intervention were fractures with angulation of >10 degrees and total displacement. Patients were followed up for a mean of 24 (range, 13-40) months. Angulation and range of movements of the elbow, wrist, and forearm, as well as clinical and cosmetic results were compared. RESULTS: Both treatments achieved excellent clinical outcomes, but intramedullary Kirschner wiring resulted in better cosmesis, shorter operating times, easier hardware removal, and lower implant costs. CONCLUSION: Intramedullary Kirschner wiring is a better option than plating for the treatment of unstable forearm fractures in older children.