Interestingly, the clinicopathologic characteristics of K19-expressing HCCs were similar in both cohorts, although we found that K19 positivity increased from 18.2% in cohort 1 to 28.7% in cohort 2. Because K19-positive tumor

cells were not diffusely present, the expression frequencies of K19 in cohort 1, using 2-mm core microarrays, may have been somewhat underestimated, despite the fact that we used a lower cut-off value of 1% for the tissue microarray cases, compared to the 5% cut-off value for the whole tissue sections of cohort 2. The histologic features, such as the presence of fibrous stroma and the lack of tumor capsules, were recognized in K19-positive HCCs of both cohorts, and vascular invasion and high serum AFP levels were also common AZD1208 research buy features. In addition, although statistical significance was not reached,

these tumors were more frequent in younger and female patients, compared to K19-negative HCCs, were larger in size, and were more frequently multiple. The immunostaining patterns of K19 were variable, in contrast to CD133, XL765 datasheet c-kit, and EpCAM; K19 expression was observed in both tumor cells with typical hepatocyte-like features and in the slightly smaller cells, which were located at the periphery or within the cell nests. However, the latter group of K19-expressing cells could not be readily identified by H&E stain, and these tumors could not be classified as the recently described combined hepatocellular-cholangiocarcinoma with stem cell features. K19 positivity in HCCs was associated with a decreased disease-free survival in the second cohort after both univariable and multivariable analyses, therefore showing that K19 is a significant independent prognostic factor, which is in line with previous studies regarding MCE the prognostic significance of K19 expression in HCCs.3, 21

The molecular features that explain the aggressive behavior of HCCs with high K19 expression are still unclear, and, to our knowledge, this is the first study that compares the differences between K19-high and K19-low HCCs with regard to the expression of EMT and invasion-related molecules. The mRNA levels of K19 were well correlated with K19 protein expression detectable by immunohistochemistry, and HCCs with high K19 mRNA levels were significantly associated with up-regulated EMT and invasion-associated genes (e.g., snail, twist, uPAR, and MMP2). In addition, K19 protein expression was significantly related with vimentin, S100A4, uPAR, and ezrin expression, and Snail and MMP2 expression and loss of E-cadherin were also more frequent in K19-expressing HCCs, although not statistically significantly. Fibrous stroma was more frequently observed in HCCs expressing any of the four stemness markers, and fibrous capsules were less common in these tumors.

Interestingly, the clinicopathologic characteristics of K19-expressing HCCs were similar in both cohorts, although we found that K19 positivity increased from 18.2% in cohort 1 to 28.7% in cohort 2. Because K19-positive tumor

cells were not diffusely present, the expression frequencies of K19 in cohort 1, using 2-mm core microarrays, may have been somewhat underestimated, despite the fact that we used a lower cut-off value of 1% for the tissue microarray cases, compared to the 5% cut-off value for the whole tissue sections of cohort 2. The histologic features, such as the presence of fibrous stroma and the lack of tumor capsules, were recognized in K19-positive HCCs of both cohorts, and vascular invasion and high serum AFP levels were also common learn more features. In addition, although statistical significance was not reached,

these tumors were more frequent in younger and female patients, compared to K19-negative HCCs, were larger in size, and were more frequently multiple. The immunostaining patterns of K19 were variable, in contrast to CD133, BGB324 concentration c-kit, and EpCAM; K19 expression was observed in both tumor cells with typical hepatocyte-like features and in the slightly smaller cells, which were located at the periphery or within the cell nests. However, the latter group of K19-expressing cells could not be readily identified by H&E stain, and these tumors could not be classified as the recently described combined hepatocellular-cholangiocarcinoma with stem cell features. K19 positivity in HCCs was associated with a decreased disease-free survival in the second cohort after both univariable and multivariable analyses, therefore showing that K19 is a significant independent prognostic factor, which is in line with previous studies regarding medchemexpress the prognostic significance of K19 expression in HCCs.3, 21

The molecular features that explain the aggressive behavior of HCCs with high K19 expression are still unclear, and, to our knowledge, this is the first study that compares the differences between K19-high and K19-low HCCs with regard to the expression of EMT and invasion-related molecules. The mRNA levels of K19 were well correlated with K19 protein expression detectable by immunohistochemistry, and HCCs with high K19 mRNA levels were significantly associated with up-regulated EMT and invasion-associated genes (e.g., snail, twist, uPAR, and MMP2). In addition, K19 protein expression was significantly related with vimentin, S100A4, uPAR, and ezrin expression, and Snail and MMP2 expression and loss of E-cadherin were also more frequent in K19-expressing HCCs, although not statistically significantly. Fibrous stroma was more frequently observed in HCCs expressing any of the four stemness markers, and fibrous capsules were less common in these tumors.

He was there front-row center, which wouldn’t be so remarkable except that he was 94 years old and still telling me jokes. After a year of hematology fellowship at Georgetown, I stayed true to my childhood dream and applied for a position Erastin ic50 in clinical practice with a prestigious group of Washington internists. I was deeply disappointed to find that they selected someone else, presumably on the grounds that they needed a cardiologist more than a hematologist. In my disappointment, Rath took me under his wing and encouraged me to stay

at Georgetown with the terse statement, “You can always go into practice.” As further inducement, he doubled my salary from $6,000 to $12,000 a year. Charlie was generous of spirit, but not so generous of Tamoxifen in vitro money. At Georgetown University Hospital, I was an instructor and then assistant professor of medicine and also head of hematology research. I spent 50% of my time teaching, 50% seeing patients, and the other 50% doing research. I was spread very thin

and my math wasn’t very good either. Two things became apparent to me. First, I was not the triple-threat academician that I was supposed to be and, second, that I enjoyed seeing patients in a hospital setting and I gradually lost my desire to go into private practice. Nonetheless, the pace of my position and the frustration over being unable to fulfill my research responsibilities was getting to me. Then, in 1969, I received another life-changing communication. It was a call from Paul Holland and Paul Schmidt at the NIH Blood Bank informing me that the Australia antigen MCE I had studied was now known to be associated with HBV and that they would like me to

return to the NIH to pursue studies of transfusion-associated hepatitis (TAH). I jumped at the opportunity and have never looked back. I was married in 1965 during my hematology fellowship to Barbara Bailey, a woman I had met during my fellowship at the NIH. It was a good marriage, but, sadly, ended after 12 years. However, two joyous events emerged from that marriage: the birth of my son, Mark, now an M.D./Ph.D. embarking on his own research career and the subsequent birth of my daughter, Stacey, currently a teacher in Colorado. My children have been wonderful from day one and are a source of great pride. They have given me four grandchildren, one of whom was born prematurely at the Hep-DART meeting on Kauai, weighing only 1 pound, 15 ounces. Miraculously, he is now age 10 and will soon be attending his third Hep-DART meeting. In 1984, I met a collaborator who has never entered the lab or participated in a study, but who has collaborated intensely in my life. I speak of my current wife, Diane, who has put up with the long hours and anxiety-ridden deadlines incumbent on a research career and who has done so with grace and elegance. She has been my staunchest advocate and has had more faith in me than I have had in myself.

If MOH shares some neurophysiological features with addiction, long-lasting functional alterations of the mesocorticolimbic dopamine system related to medication

overuse should be present. We collected functional magnetic resonance imaging data during the execution of a decision-making under risk paradigm in 8 MOH patients immediately after beginning medication withdrawal, in 8 detoxified MOH patients at 6 months after beginning medication withdrawal, in 8 chronic migraine patients, and in 8 control subjects. Our results revealed that MOH patients present: (1) reduced Tamoxifen concentration task-related activity in the substantia nigra/ventral tegmental area complex and increased activity in the ventromedial prefrontal cortex, when compared with controls; (2) reduced activity in the substantia nigra/ventral tegmental area complex, when compared with chronic migraine patients; (3) increased activity in the ventromedial prefrontal cortex, when compared with detoxified MOH patients. Our study showed that MOH patients present dysfunctions

in the mesocorticolimbic dopamine circuit, in particular in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental area complex. The ventromedial prefrontal selleck chemical cortex dysfunctions seem to be reversible and attributable to the acute/chronic headache, whereas the substantia nigra/ventral tegmental area complex dysfunctions are persistent and possibly related to medication medchemexpress overuse. These dysfunctions might be the expression of long-lasting neuroadaptations related to the overuse of medications and/or a pre-existing neurophysiological condition leading to vulnerability to medication overuse. The observed persistent dysfunctions in the midbrain dopamine suggest that MOH may share some neurophysiological

features with addiction. “
“Objective.— Examine whether acceptance and commitment additive therapy is effective in reducing the experience of sensory pain, disability, and affective distress because of chronic headache in a sample of outpatient Iranian females. Background.— Chronic headaches have a striking impact on sufferers in terms of pain, disability, and affective distress. Although several Acceptance and Commitment Therapy outcome studies for chronic pain have been conducted, their findings cannot be completely generalized to chronic headaches because headache-related treatment outcome studies have a different emphasis in both provision and outcomes. Moreover, the possible role of Iranian social and cultural contexts and of gender-consistent issues involved in Acceptance and Commitment Therapy outcomes deserve consideration. Methods.— This study used a randomized pretest–post-test control group design.

Conclusions:  The H. pylori-infected children have a lower Bifidobacterium microflora in gut. The probiotics-containing yogurt can offer benefits to restore Bifidobacterium spp./E. coli ratio in children and suppress the H. pylori load with increment of serum IgA but with reduction in IL-6 in H. pylori-infected children. “
“The envisaged roles and partly understood LY294002 purchase functional properties of Helicobacter pylori protein HP0986 are

significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 Buparlisib gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were

incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study

its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent MCE公司 manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF-κB, subcellular localization, and seropositivity data point to a significant role of HP0986 in gastroduodenal inflammation. We propose to name the HP0986 gene/protein as ‘TNFR1 interacting endonuclease A (TieA or tieA)’. Helicobacter pylori infection is characterized by the infiltration of mononuclear and polymorphonuclear cells into the gastric mucosa in addition to the accumulation of various cytokines, including IL1β, IL6, IL-8, and TNFα secreted by gastric epithelial and immune cells [1, 2].

However, considerable expenses and use of uncommon parameters reduce practical utility. A few years later, the Forns’ score (age, GGT, cholesterol, platelets, and prothrombin)5 and the APRI index (AST and platelets)6 overcame these drawbacks by use of only standard laboratory tests in the development of their predictive models. Subsequent models

include the ELF-score,7 the Hepascore8 and the Fibrometer.9 Validation of these models selleck compound in cohorts of CHC patients revealed reliable information on liver fibrosis in about one-third of patients. Still, the APRI and the Forns’ score, although slightly less accurate, offer the benefit of simplicity for use.10,11 Chronic hepatitis B (CHB) is the most frequent infectious cause of CLD worldwide. More than 400 million people are chronically infected with HBV. The virus is responsible for more than 300 000 cases of liver cancer every year and for similar numbers of gastrointestinal hemorrhage and ascites.12 Predictive models designed especially

for CHB patients have been proposed Selleckchem MAPK Inhibitor Library by the Shanghai Liver Fibrosis Group (SLFG),13 Hui et al.14 and Mohamadnejad et al.15 But few of these models mentioned above have been widely validated and implemented in clinical practice. The aim of the present study was to generate a simple, noninvasive model for predicting liver fibrosis in patients with chronic HBV infection based on routine laboratory markers and compare its diagnostic value with that of some typical models, in order to provide references for introducing the noninvasive predictive model into clinical management of patients with chronic HBV infection. A total of 386 patients was selected in the training cohort from a total of 513 consecutive chronic HBV

carriers who underwent a percutaneous liver biopsy in the hospitals of the SLFG13 from 1999 to 2001. Chronic HBV carriers were defined as persons who had positive hepatitis B surface antigen (HBsAg) for at least 6 months before enrolling.16 Exclusion criteria included co-infection with medchemexpress HIV or HCV, alcohol consumption >30 g/day, other causes of chronic liver disease, previous antiviral treatment, and insufficient biopsy samples. Another group of 146 consecutive chronic HBV carriers who underwent a liver biopsy in three hospitals (Renji Hospital, Shanghai; Southeast Hospital, Zhangzhou, Fujian Province; and Taizhou People’s Hospital, Jiangsu Province) between 2005 and 2007 were prospectively enrolled in the validation cohort, using the same criteria. The study was approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine. Informed consent to participate in the study was obtained from each patient. All patients received a liver biopsy directed by ultrasonography within 1 week after inclusion.

Preliminary results of the study are now available CAL-101 mw [48]. This retrospective

study involved PUPs with haemophilia A who were diagnosed between 2006 and 2011 in participating centres of the eastern German network for coagulation disorders (Kompetenznetzwerk hämorrhagische Diathese Ost; KHDO). By means of a detailed questionnaire developed specifically for study purposes, information collected from patients’ medical charts included: age at diagnosis and at start of prophylaxis; FVIII gene mutation; type of FVIII product; body weight relative to FVIII dose; number of exposure days to FVIII products until inhibitor formation; presence of danger signals; details of immune tolerance induction (ITI)

therapy. All 12 KHDO centres that treat children participated in the study and the number of patients treated per centre ranged from 1 to 24. During the study period 67 patients were newly diagnosed with haemophilia A, of whom 33 had severe, 4 moderate, 20 mild and 10 subclinical disease. The analysis centred around patients with severe haemophilia as this is the group at greatest risk of developing inhibitors. Among the 33 patients with severe haemophilia, eight had been treated with the historical FVIII prophylaxis regimen (30 U kg−1 2–3× per week) none of whom developed an inhibitor. Twenty-five patients had been treated with the low-dose 上海皓元医药股份有限公司 regimen (25 U kg−1 1× per week) of whom 9 (36%) developed an inhibitor (five high-responding, four Maraviroc manufacturer low-responding). At the time of investigation (July 2012), 27 of the 33 patients with severe haemophilia had had more than 100 exposure days to FVIII concentrates; three patients had <20 exposure days and the remaining three patients had between 20 and 100 exposure days. In order to identify possible strategies to avoid inhibitor development, the characteristics of patients with severe haemophilia A treated with prophylaxis (n = 33)

were examined based on the presence or absence of inhibitors (Table 5). In both groups, prophylaxis had been initiated at an early age – slightly earlier in patients with than without inhibitors (11.5 vs. 15 months) – although the range was broad in both groups. The FVIII dose at the start of once-weekly prophylaxis was the same in patients with or without inhibitors. In patients treated with the historical prophylaxis regimen, the FVIII dose was slightly lower in patients with than without inhibitors (22 vs 28 IU kg−1), but the clinical significance of this difference remains uncertain. Overall, 14 PUPs with severe haemophilia received plasma-derived products and 19 received recombinant products. All nine patients who developed inhibitors had been treated with recombinant FVIII (rFVIII) concentrates.

3A). To determine whether C/EBPβ functioned to prevent RALA hepatocyte death from TNFα, the effect of C/EBPβ overexpression on TNFα-induced apoptosis in RALA hepatocytes BMN 673 supplier with an inhibition of NF-κB activation was assessed. Cells infected with the C/EBPβ-expressing

adenovirus WT-C/EBPβ alone or coinfected with WT-C/EBPβ and either Ad5LacZ or Ad5IκB expressed increased levels of C/EBPβ compared with cells infected with Ad5LacZ alone (Fig. 3B). Cells were coinfected with Ad5IκB and either Ad5LacZ as a control or WT-C/EBPβ and treated with TNFα. When compared with Ad5IκB/Ad5LacZ-coinfected cells, the amount of cell death after TNFα treatment was significantly decreased in Ad5IκB/WT-C/EBPβ–coinfected cells at 6 and 12 hours by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Fig. 3C). The ability of C/EBPβ expression to block cell death from TNFα was confirmed by fluorescence microscopic studies of Idasanutlin concentration cells costained with acridine orange/ethidium bromide to quantify the numbers of apoptotic and necrotic cells. As previously established, death from NF-κB inactivation and TNFα was predominantly apoptotic, and no significant increase occurred in

the numbers of necrotic cells (data not shown). The marked increase in apoptotic cells with TNFα administration was significantly reduced by adenoviral expression of C/EBPβ (Fig. 3D). Thus, the NF-κB–dependent increase in C/EBPβ in TNFα-treated RALA hepatocytes is a mechanism

of cellular resistance to TNFα-induced apoptosis. The sensitization of hepatocytes to TNFα toxicity by NF-κB inhibition occurs through caspase-dependent apoptosis.17, 33 The ability of C/EBPβ to function as a caspase inhibitor suggested that the mechanism of C/EBPβ’s inhibition of TNFα-induced apoptosis may be through blocking caspase activation. Adenoviral expression of C/EBPβ significantly decreased levels of activity of the initiator caspase 8 in both untreated and TNFα-treated cells in which NF-κB was inhibited by Ad5IκB (Fig. 4A). Inhibition of caspase 8 by C/EBPβ prevented TNFα-induced activation of the mitochondrial death pathway as WT-C/EBPβ decreased 上海皓元医药股份有限公司 the amount of truncated Bid that translocated to the mitochondria and blocked the cytochrome c release from mitochondria into cytoplasm that occurred in Ad5IκB/Ad5LacZ-coinfected cells (Fig. 4B). In contrast, levels of cytochrome oxidase, a mitochondrial protein not released during apoptosis, were equivalent in Ad5LacZ- and WT-C/EBPβ–infected cells after TNFα treatment and indicated equal protein loading (Fig. 4B). As a result of the inhibition of cytochrome c release, downstream effector caspase 3 and caspase 7 activation was blocked in cells overexpressing C/EBPβ as detected by decreases in the active, cleaved caspase forms on immunoblots (Fig. 4C).

3A). To determine whether C/EBPβ functioned to prevent RALA hepatocyte death from TNFα, the effect of C/EBPβ overexpression on TNFα-induced apoptosis in RALA hepatocytes Wnt inhibitor with an inhibition of NF-κB activation was assessed. Cells infected with the C/EBPβ-expressing

adenovirus WT-C/EBPβ alone or coinfected with WT-C/EBPβ and either Ad5LacZ or Ad5IκB expressed increased levels of C/EBPβ compared with cells infected with Ad5LacZ alone (Fig. 3B). Cells were coinfected with Ad5IκB and either Ad5LacZ as a control or WT-C/EBPβ and treated with TNFα. When compared with Ad5IκB/Ad5LacZ-coinfected cells, the amount of cell death after TNFα treatment was significantly decreased in Ad5IκB/WT-C/EBPβ–coinfected cells at 6 and 12 hours by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Fig. 3C). The ability of C/EBPβ expression to block cell death from TNFα was confirmed by fluorescence microscopic studies of Pexidartinib ic50 cells costained with acridine orange/ethidium bromide to quantify the numbers of apoptotic and necrotic cells. As previously established, death from NF-κB inactivation and TNFα was predominantly apoptotic, and no significant increase occurred in

the numbers of necrotic cells (data not shown). The marked increase in apoptotic cells with TNFα administration was significantly reduced by adenoviral expression of C/EBPβ (Fig. 3D). Thus, the NF-κB–dependent increase in C/EBPβ in TNFα-treated RALA hepatocytes is a mechanism

of cellular resistance to TNFα-induced apoptosis. The sensitization of hepatocytes to TNFα toxicity by NF-κB inhibition occurs through caspase-dependent apoptosis.17, 33 The ability of C/EBPβ to function as a caspase inhibitor suggested that the mechanism of C/EBPβ’s inhibition of TNFα-induced apoptosis may be through blocking caspase activation. Adenoviral expression of C/EBPβ significantly decreased levels of activity of the initiator caspase 8 in both untreated and TNFα-treated cells in which NF-κB was inhibited by Ad5IκB (Fig. 4A). Inhibition of caspase 8 by C/EBPβ prevented TNFα-induced activation of the mitochondrial death pathway as WT-C/EBPβ decreased 上海皓元 the amount of truncated Bid that translocated to the mitochondria and blocked the cytochrome c release from mitochondria into cytoplasm that occurred in Ad5IκB/Ad5LacZ-coinfected cells (Fig. 4B). In contrast, levels of cytochrome oxidase, a mitochondrial protein not released during apoptosis, were equivalent in Ad5LacZ- and WT-C/EBPβ–infected cells after TNFα treatment and indicated equal protein loading (Fig. 4B). As a result of the inhibition of cytochrome c release, downstream effector caspase 3 and caspase 7 activation was blocked in cells overexpressing C/EBPβ as detected by decreases in the active, cleaved caspase forms on immunoblots (Fig. 4C).

pylori eradication rates between probiotic and DNA Damage inhibitor placebo group (45.5 vs 37.5%; p = NS) [71]. In a study of our group, aimed to evaluate the efficacy of probiotics to reduce antibiotic side effects, we found no differences in the eradication rates according to the presence/absence of the probiotic: treatment was successful in 17 of 20 patients supplemented

with L. reuteri ATCC 55730 (SD2112) as compared to 16 of 20 patients in the placebo group (85 vs 80%; p = NS) [72]. Recently, in a double-blind placebo-controlled randomized clinical trial performed in 66 children no difference was found with respect to H. pylori eradication rates between children receiving standard triple therapy supplemented with L. rhamnosus GG or placebo (69 vs 68%; p = NS) [77]. Pooled data, derived from children and adults’ studies selleck chemicals on more than 1900 treated patients, show eradication

rates of 82.5% (95%CI: 80.1–84.7%) in patients with probiotic supplementation as compared to 73.7% (95%CI: 71–76.4%) in patients receiving placebo (RR: 1.11; 95%CI: 1.07–1.17). These data do not represent convincing evidence to support the use of probiotics as an adjunct with the aim of increasing the H. pylori eradication rate. Nevertheless, further studies are needed to clarify their role in this particular issue. The major limit to establish whether a probiotic is able to significantly increase the eradication rate is represented by the power of the study. Indeed, due to the high eradication rates that we mostly achieve with standard antibiotic treatment, to detect a 10% increase in eradication (secondary to the use of a probiotic strain), given a power of al least 80% and an alpha error level of 5%, 150 patients in each arm are needed to be enrolled. In our own experience on 40 adults, we were able to demonstrate a favorable effect of L. reuteri ATCC 55730 (SD2112) on dyspeptic symptoms

induced by H. pylori [56]. In this study, L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale (GSRS) as compared to pre-treatment value (7.9 ± 4.1 vs 11.8 ± 8.5; p < .05) that was not observed MCE公司 in patients receiving placebo (9.7 ± 8.7 vs 11.4 ± 9.7; p < NS) [56]. Not all probiotic strains are able do decrease dyspeptic symptoms [53] suggesting that the effect is strain specific. No data are available in the pediatric age. Bacterial resistance and antibiotic’ side-effects represent the most frequent cause for anti-H. pylori treatment failure in clinical practice [9]. Several studies evaluated whether probiotic supplementation might help to prevent or reduce drug-related side effects during H. pylori eradication therapy in adults [61,63,64,66,68,69,72–75,78–80]. All showed that diarrhea, nausea and taste disturbances were significantly reduced by probiotics and overall they were superior to placebo for side effect prevention.