Limosilactobacillus fermentum CECT5716: Clinical Potential of a Probiotic Strain Isolated from Human Milk.

Breastfeeding provides the ideal nutrition for infants. Human milk contains a plethora of functional ingredients which foster the development of the immune system. The human milk microbiota predominantly contributes to this protective effect. This is mediated by various mechanisms, such as an antimicrobial effect, pathogen exclusion and barrier integrity, beneficial effects on the gastrointestinal microbiota, vitamin synthesis, immunity enhancement, secreted probiotic factors, and postbiotic mechanisms. Therefore, human milk is a good source for isolating probiotics for infants who cannot be exclusively breastfed. One such probiotic which was isolated from human milk is Limosilactobacillus fermentum CECT5716. In this review, we give an overview of available interventional studies using Limosilactobacillus fermentum CECT5716 and summarise preclinical trials in several animal models of different pathologies, which have given first insights into its mechanisms of action. We present several randomised clinical studies, which have been conducted to investigate the clinical efficacy of the Limosilactobacillus fermentum CECT5716 strain in supporting the host's health.

The effect of graded motor imagery training on pain, functional performance, motor imagery skills, and kinesiophobia after total knee arthroplasty: randomized controlled trial.

Background: The aim was to investigate the effect of graded motor imagery (GMI) added to rehabilitation on pain, functional performance, motor imagery ability, and kinesiophobia in individuals with total knee arthroplasty (TKA). Methods: Individuals scheduled for unilateral TKA were randomized to one of two groups: control (traditional rehabilitation, n = 9) and GMI (traditional rehabilitation + GMI, n = 9) groups. The primary outcome measures were the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were knee range of motion, muscle strength, the timed up and go test, mental chronometer, Movement Imagery Questionnaire-3, lateralization performance, Central Sensitization Inventory, Pain Catastrophizing Scale, and Tampa Kinesiophobia Scale. Evaluations were made before and 6 weeks after surgery. Results: Activity and resting pain were significantly reduced in the GMI group compared to the control group (P < 0.001 and P = 0.004, respectively). Movement Imagery Questionnaire-3 scores and accuracy of lateralization performance also showed significant improvement (P = 0.037 and P = 0.015, respectively). The Pain Catastrophizing Scale and Tampa Kinesiophobia Scale scores were also significantly decreased in the GMI group compared to the control group (P = 0.039 and P = 0.009, respectively). However, GMI did not differ significantly in WOMAC scores, range of motion, muscle strength, timed up and go test and Central Sensitization Inventory scores compared to the control group (P > 0.05). Conclusions: GMI improved pain, motor imagery ability, pain catastrophizing, and kinesiophobia in the acute period after TKA.

Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy.

BACKGROUND: Antibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region. METHODS: The prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre. RESULTS: A result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect. CONCLUSION: This study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

Probiotics added to maternal nutrition affect infantile colic symptoms and fecal microbiota profile: a single-blind randomized controlled study.

BACKGROUND: Infantile colic has a multifactorial etiology; although various treatments have been attempted to manage and alleviate its symptoms, a solution is lacking, adversely affecting mothers and their babies. Recent studies have suggested that dysbiosis may play a role in the pathogenesis of infantile colic and that modulating the gut microbiota, including the use of probiotics, may aid its management. PURPOSE: This single-blind randomized controlled study evaluated the effect of probiotics (Actiregularis, 5×106) added to the diet of mothers on infantile colic symptoms and neonatal gut microbiota content. METHODS: A probiotic drink containing the Actiregularis (5× 106) strain was added to the diet of mothers in the experimental group once daily for 15 consecutive days. Stool samples were collected from each infant twice, on days 0 and 15, and fecal 16s rRNA gene sequencing and compositional-based metabolomic analyses were performed. The mothers recorded the babies' crying frequency and severity for 15 days using a daily form created by the researchers. This study was registered at ClinicalTrials.gov (ID: NCT04374955). RESULTS: Infants whose mothers were supplemented with Actiregularis for 15 days showed a decreased frequency (P= 0.00) and intensity (P<0.001) of crying as well as a significantly increased bacterial diversity in the stools (P=0.017). This variety was substantially affected by the addition of probiotic products. The greatest species diversity was observed in the group treated with probiotics, while the least diversity was observed in the control group (Shannon, P=0.0043; Simpson, P=0.017). CONCLUSION: Babies treated with Actiregularis added to their mother's diet for 15 days showed decreased crying frequency and intensity and increased bacterial diversity and density.

Beneficial Effects of Limosilactobacillus fermentum CECT 5716 Administration to Infants Delivered by Cesarean Section.

Cesarean section (CS) disrupts the natural microbiota colonization process in infants, which might compromise immune system maturation, leading to a higher risk of infections. We evaluated the effect of the probiotic Limosilactobacillus (L.) fermentum CECT 5716 on the incidence of gastrointestinal and respiratory infections in the CS infant subgroups (n = 173) of three randomized clinical trials in which this probiotic strain was demonstrated to be safe and effective for preventing infections. Therefore, the data for the CS infants were extracted to obtain the incidence rate ratio (IRR) and 95% CI for gastrointestinal and respiratory infections for each study and were then combined to obtain a pooled IRR and 95% CI using the generic inverse variance method. There was a significant reduction of 73% in the incidence of gastrointestinal infections in CS infants receiving L. fermentum CECT 5716 compared with those receiving the control formula [n = 173, IRR: 0.27 (0.13, 0.53), p = 0.0002]. Regarding respiratory infections, although pooled results showed a reduction of 14% in the probiotic group, the difference was not statistically significant [n = 173, IRR (95% CI): 0.86 (0.67, 1.11), p = 0.25]. In conclusion, the administration of L. fermentum CECT 5716 to CS-born infants protects them from gastrointestinal infections by reducing the risk by up to 73% in this population.

Gut immune homeostasis: the immunomodulatory role of Bacillus clausii, from basic to clinical evidence.

INTRODUCTION: The gut microbiota affects the development of the gut immune system in early life. Perturbations to microbiota structure and composition during this period can have long-term consequences on the health of the individual, through its effects on the immune system. Research in the last few decades has shown that probiotic administration can reverse these effects in strain- and environment-specific ways. Bacillus clausii (B. clausii) has been in use for many decades as a safe and efficacious probiotic, but its mode of action has not yet been completely elucidated. AREAS COVERED: In this review, we discuss how the gut immune system works, the factors that affect its functioning, and the plethora of research highlighting its role in various diseases. We also discuss the known modes of action of Bacillus probiotics, and highlight the preclinical and clinical evidence that reveal how B. clausii acts to bolster gut defense. EXPERT OPINION: We anticipate that the treatment and/or prevention of dysbiosis will be central to managing human health and disease in the future. Discovering the pathophysiology of autoimmune diseases, infections, allergies, and some cancers will aid our understanding of the key role played by microbial communities in these diseases.

Liver Abscess in a Cyanotic Newborn.

Umbilical venous catheterisation is a common bedside procedure in the neonatal intensive care unit (NICU). Complications including thrombus formation, thromboembolism, vessel perforation, haemorrhage, and central line-associated bloodstream infection can be seen after the procedure. Pyogenic liver abscess is a rare but life-threatening complication of umbilical venous catheterisation. A male infant with cyanotic congenital heart disease was admitted to NICU. An umbilical venous catheter (UVC) was inserted. Abdominal X-ray showed an improperly positioned UVC, it was removed and replaced with a newer one. On the seventh day, the infant had abdominal distension and his clinical condition deteriorated. Abdominal ultrasonography (US) revealed a hepatic abscess. US-guided percutaneous abscess drainage was performed. Empiric antibiotic treatment was initiated and culture revealed Staphylococcus. The patient was followed by serial US and the lesion was completely resolved after three weeks. In conclusion, clinical worsening associated with gastrointestinal symptoms in a cyanotic infant with UVC should raise suspicion for liver abscess. Key Words: Neonate, Hepatic abscess, Umbilical venous catheter, Cyanotic heart disease.

Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey.

OBJECTIVES: The aim of this point prevalence survey was to evaluate the consumption, indications and strategies of antifungal therapy in the paediatric population in Turkey. METHODS: A point prevalence study was performed at 25 hospitals. In addition to general data on paediatric units of the institutes, the generic name and indication of antifungal drugs, the presence of fungal isolation and susceptibility patterns, and the presence of galactomannan test and high-resolution computed tomography (HRCT) results were reviewed. RESULTS: A total of 3338 hospitalised patients were evaluated. The number of antifungal drugs prescribed was 314 in 301 patients (9.0%). Antifungal drugs were mostly prescribed in paediatric haematology and oncology (PHO) units (35.2%), followed by neonatal ICUs (NICUs) (19.6%), paediatric services (18.3%), paediatric ICUs (PICUs) (14.6%) and haematopoietic stem cell transplantation (HSCT) units (7.3%). Antifungals were used for prophylaxis in 147 patients (48.8%) and for treatment in 154 patients (50.0%). The antifungal treatment strategy in 154 patients was empirical in 77 (50.0%), diagnostic-driven in 29 (18.8%) and targeted in 48 (31.2%). At the point of decision-making for diagnostic-driven antifungal therapy in 29 patients, HRCT had not been performed in 1 patient (3.4%) and galactomannan test results were not available in 12 patients (41.4%). Thirteen patients (8.4%) were receiving eight different antifungal combination therapies. CONCLUSION: The majority of antifungal drugs for treatment and prophylaxis were prescribed in PHO and HSCT units (42.5%), followed by ICUs. Thus, antifungal stewardship programmes should mainly focus on these patients within the availability of diagnostic tests of each hospital.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

Kawasaki disease in a 9-year old girl presenting with febrile cholestasis: case report and review of literature.

Kawasaki disease is a systemic vasculitis that develops during childhood, especially in those younger than 5 years. Gastrointestinal involvement does not belong to the classic diagnostic criteria. We reported here, a 9-year old girl who presented with febrile cholestasis, and developed a medium right coronary artery aneurysm despite intravenous immunoglobulin administration on the 9th day of fever. Hepatobiliary ultrasonographic evaluation revealed normal findings. Seroimmunologic markers of cholestasis were negative. Her clinical feature was ameliorated shortly after a second dose of intravenous immunoglobulin administration. We consider that a high index of suspicion of Kawasaki disease could prevent delayed diagnosis and complications.

Bacterial agents causing meningitis during 2013-2014 in Turkey: A multi-center hospital-based prospective surveillance study.

This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections.

Antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

Health care-associated infection surveillance in a tertiary neonatal intensive care unit: A prospective clinical study after moving to a new building.

BACKGROUND: There are very few prospective clinical studies on neonatal health care-associated infection (HAI) surveillance. HAI surveillance helps reduce not only mortality, but also morbidity, length of hospital stay, and health care costs. METHODS: This prospective clinical study covered a period of 12 months in a tertiary neonatal intensive care unit (NICU). HAI rates were calculated using different denominators: number of patients hospitalized in the NICU, number of patient-days, and number of specific device-days. RESULTS: The HAI rate was 18%, and the incidence density was 17/1,000 patient-days. The most common HAI was bloodstream infection (n = 34; 50%). The most common pathogen was coagulase-negative staphylococci (CoNS; 54.9%) in gram-positive bacteria and in general. Methicillin resistance was 96.4% for CoNS. Klebsiella spp (13.7%) was the most common gram-negative bacteria. Extended-spectrum ß-lactamase positivity was 14.3% for Klebsiella spp and 25% for Escherichia coli. HAI-related mortality was 0.3%. CONCLUSIONS: NICUs should perform their own HAI surveillance with prospective clinical design. Attention paid to handwashing, disinfection and sanitizing, complying with the terms of asepsis, extending in-service training, increasing the number of medical staff, preventing frequent changes in health care staff positions, and improving physical environmental conditions in NICUs might eventually decrease HAI rates.

Unilateral Spinal Anesthesia Experience in a Supercentenarian.

Improvement of living and socioeconomic conditions, developments, and innovations in medicine and technology has prolonged of life expectancy. We provided spinal anesthesia for a 111-year-old woman requiring internal fixation of a fractured femur. The operation lasted 75 minutes. After surgery, the patient was monitored in the intensive care unit overnight. The patient was discharged from the intensive care unit after 24-hour monitoring without any complications. She was discharged from the hospital on postoperative day 2.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting / O Lactobacillus reuteri DSM 17938 reduz a diarreia infecciosa aguda no cuidado pediátrico ambulatorial

OBJECTIVE: Two randomized controlled clinical trials have shown thatLactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea.METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1 × 108 CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded.RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15 h, 60.4 ± 24.5 h [95% CI: 51.0-69.7 h] vs. 74.3 ± 15.3 h [95% CI: 68.7-79.9 h], p < 0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48 h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79,p < 0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted.CONCLUSION:L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

OBJETIVO: Dois ensaios clínicos randomizados controlados demonstraram que oLactobacillus (L) reuteri DSM 17938 reduz a duração de diarreia em crianças hospitalizadas devido a diarreia infecciosa aguda. Este é o primeiro ensaio que avalia a eficácia do L. reuteri DSM 17938 em crianças com diarreia infecciosa aguda no ambulatório.MÉTODOS: Ensaio clínico multicêntrico, randomizado, único cego, com grupos paralelos e controlado em crianças com diarreia aguda. Foram inscritas 64 crianças internadas na clínica ambulatorial. O grupo probiótico recebeu 1 × 108 CFU L. reuteri DSM 17938 por cinco dias, além de uma solução de reidratação oral (SRO), e o segundo grupo foi tratado apenas com SRO. O desfecho principal foi a duração da diarreia (em horas). O desfecho secundário foi o número de crianças com diarreia em cada um dos cinco dias da intervenção. Os eventos adversos também foram registrados.RESULTADOS: A duração média da diarreia foi significativamente reduzida no grupoL. reuteri em comparação com o grupo de controle (aproximadamente 15 horas; 60,4 ± 24,5 horas [51,0-69,7 horas, IC de 95%] em comparação com 74,3 ± 15,3 horas [68,7-79,9 horas, IC de 95%], p < 0,05). O percentual de crianças com diarreia foi menor no grupo L. reuteri (13/29; 44,8%) após 48 horas do que no grupo de controle (27/31; 87%) (RR: 0,51; 0,34-0,79; IC de 95%, < 0,01). A partir da 72a hora de intervenção, não havia diferença entre os dois grupos no percentual de crianças com diarreia. Nenhum efeito adverso com relação ao L. reuteri foi observado.CONCLUSÃO: O L. reuteri DSM 17938 é eficaz, seguro e bem tolerado por crianças com diarreia infecciosa aguda no ambulatório.

Children with breakthrough varicella infection requiring hospitalization in Turkey (VARICOMP Study 2008-2013).

INTRODUCTION: Varicella in previously immunized individuals, known as "breakthrough varicella". While the majority of breakthrough cases are mild, some may be severe, requiring hospitalization in previously healthy children or children with an underlying condition. METHODS: This report, as a part of the prospective national pediatric varicella hospitalizations study (including 29 centers, represent 50% of pediatric population) in Turkey, is aimed to evaluate breakthrough varicella infection requiring hospitalization before the routine use of single-dose live varicella vaccine in national program from 2008 to 2013 (<10% of the pediatric age group received a single-dose vaccine). RESULTS: In the time period, 1939 children were hospitalized due to varicella infection in Turkey; 36 children (20 boys, 16 girls, mean age 68.0+37.6 months, all received single dose live varicella vaccine) with breakthrough varicella infection. Breakthrough varicella infection might be severe in previously healthy children (61.1%) and children with immune-compromising conditions (38.9%). The time elapsed between vaccination and hospitalization was approximately 5 years, and neurological complications, mainly encephalitis and meningitis, were the most common reason for hospitalization in previously healthy children. CONCLUSION: Pediatric breakthrough varicella requiring hospitalization have been seen in Turkey, is mainly observed in previously healthy children at 5 years after a single-dose varicella vaccine. The varicella vaccine has been implemented as part of the National Immunization Program in Turkey in 2013 (a single dose at age 12 months). Further surveillance in the same settings could evaluate the effectiveness of national immunization with single-dose varicella vaccine at 12 months of age and potential need for second dose of vaccine.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting.

OBJECTIVE: Two randomized controlled clinical trials have shown that Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea. METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1×10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded. RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15h, 60.4±24.5h [95% CI: 51.0-69.7h] vs. 74.3±15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted. CONCLUSION: L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

Foreword: all things considered about probiotics, prebiotics and intestinal microbiota in children - from bench to bedside.

There are numerorus published and ongoing experimental/clinical studies about probiotics and prebiotics, intestinal microbiota and nutrition. Three years ago, at the first International Symposium of Probiotics Prebiotics in Paediatrics in Istanbul (2012) we highlighted the 'paediatric perspective' on these issues and brought together more than 40 global key opinion leaders and 400 attendants to have a chance to extensively discuss the past, present and the future. In 2014, the second state of art congress, held in Antalya, aimed to discuss the gut microbiota and microbiotics and their impact through lifespan. Selected papers of this conference are presented in this special issue 'prebiotics and probiotics in paediatrics' of Beneficial Microbes. A summary of the conference results is provided below.

Probiotics for the prevention of pediatric upper respiratory tract infections: a systematic review.

BACKGROUND: Acute upper respiratory tract infections (URTIs) contribute substantially to pediatric morbidity and mortality worldwide. Prevention of these infections in childhood is a very important public health challenge. Previous systematic reviews, including both adult and childhood populations, have reported that probiotics seem promising, but with modest evidence. This study aimed to focus on prophylactic probiotic use in the prevention of URTIs in childhood. METHODS: Relevant trials on two databases were identified in a systematic review, from inception to June 2014. Study selection, data extraction and quality assessment were carried out by two reviewers. In this review, the effects of probiotics, particularly the Lactobacillus and Bifidobacterium strains, on the incidence and symptom scores of URTI in otherwise healthy children were evaluated for the first time. This review comprises 14 randomized controlled trials (RCTs) applied to a pediatric population with high-quality methodology. RESULTS: This systematic review suggests that probiotics in immunocompetent children have a modest effect both in diminishing the incidence of URTIs and the severity of the infection symptoms. CONCLUSIONS: At least one beneficial effect of prophylactic probiotic was observed in the majority of RCTs. Even a minimal reduction of 5 - 10% in the incidence of URTIs would have an important clinical and economic mpact on societies. Furthermore, the long-term administration of probiotics appeared to have a good safety profile in childhood and none of the studies reported any serious adverse events related to the probiotic strain.

The protective effect of Capparis ovata on 6-mercaptopurine-induced hepatotoxicity and oxidative stress in rats.

Capparis ovata is a member of Capparidacaeae family has been used in phytomedicine with a lot of positive effects such as an antioxidative, antihyperlipidemic, anti-inflammatory, and antihepatotoxic agent. The aim of this study was to research the protective effect of C. ovata on 6-mercaptopurine (6-MP) induced to hepatotoxicity and oxidative stress in rats. The rats were divided into 4 groups: control, 6-MP, C. ovataovate, and 6-MP + C. ovata. A complete blood count was performed, liver function test and antioxidant enzymes levels such as superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde were measured in blood before and after a 14-day test period. White blood cell and platelet counts were lower in the 6-MP group than other 3 groups (P < 0.005). Hepatic transaminase levels were higher in 6-MP group than the 3 groups (P < 0.05). Superoxide dismutase, glutathione peroxidase, and CAT levels were lower and malondialdehyde was higher in blood samples in 6-MP group than other 3 groups (P < 0.005). In conclusion, our tests were showed that C. ovata may be useful in patients receiving 6-MP therapy to prevent hepatotoxicity and in order to maintain uninterrupted therapy possibly reducing the risk of relapse. Although additional studies ensure that Capparis does not affect 6-MP antileukemic activity. We believe these results are important contribution to the literature.