Pneumococcal carriage and serotype distribution in children with nephrotic syndrome.

BACKGROUND: Patients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS. METHODS: Pneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR. RESULTS: The pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all). CONCLUSIONS: The pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS.

Screening for functional gastrointestinal disorders in preterm infants up to 12 months of corrected age: a prospective cohort study.

Functional gastrointestinal disorders (FGIDs) are characterized by a variety of symptoms that are frequently age-dependent, chronic, or recurrent and are not explained by structural or biochemical abnormalities. There are studies in the literature reporting different results regarding the relationship between prematurity and FGIDs. The main objective of this study was to compare the frequency of FGIDs between preterm and term infants. The secondary objective was to evaluate whether there was any association between neonatal characteristics and development of FGIDs. A multicenter prospective cohort study that included preterm infants born before 37 weeks of gestation and healthy term infants was carried out. At 1, 2, 4, 6, 9, and 12 months of age, infants were assessed for the presence of FGIDs using the Rome IV criteria. In preterm infants, an additional follow-up visit was made at 12 months corrected age. 134 preterm and 104 term infants were enrolled in the study. Infantile colic, rumination syndrome, functional constipation, and infant dyschezia were more common in preterm infants. Incidence of other FGIDs (infant regurgitation, functional diarrhea and cyclic vomiting syndrome) were similar among preterm and term infants. Preterm infants who are exclusively breastfeed in the first 6 months of life have a lower incidence of infantile colic (18.8% vs 52.1%, p = 0.025). In terms of chronological age, FGIDs symptoms started later in preterm infants; this difference was statistically significant for infantile colic and regurgitation (median age 2 months vs 1 month, p < 0.001).   Conclusions: Preterm infants have a higher prevalence of FGIDs compared with term controls. Therefore, especially if they have gastrointestinal complaints, they should be screened for FGIDs. Possibly due to maturational differences, the time of occurrence of FGIDs may differ in preterm infants. Infantile colic incidence decreases with exclusive breastfeeding. What is Known: • The functional gastrointestinal disorders are a very common in infancy. • Data on preterm infants with FGIDs are currently very limited. What is New: • Preterm infants have a higher incidence of infantile colic, rumination syndrome, functional constipation and infant dyschezia when compared to term infants. • Preterm infants who are exclusively breastfed during the first 6 months of life experience a lower incidence of infantile colic.

Young children's sleep patterns and problems in paediatric primary healthcare settings: a multicentre cross-sectional study from a nationally representative sample.

Studies describing paediatric sleep patterns are needed by taking culture into consideration. The aim of this study was to identify parent-reported sleep-wake patterns in young children and explore possible factors influencing sleep problems. The mothers of 2,434 young children enrolled from well-child outpatient clinics in Turkey completed an online survey including sociodemographic variables, Brief Infant Sleep Questionnaire, Edinburgh Postnatal Depression Scale and Generalised Anxiety Disorder scales. Overall, young children in Turkey go to bed late (10:00 p.m.), awaken twice per night for 30 min, and obtain 11.5 h of total sleep, showing no sex-specific differences. Distinct night-time sleep patterns emerged after 18 months of age. Importantly, although currently breastfed healthy children were 3.8-times less likely to sleep through the night, total sleep duration and exclusive breastfeeding duration were higher in children who were not sleeping through the night. Overall, bedsharing was identified in 11.5%, and only room sharing was reported in 52.9%. Parental perception of a child's sleep as problematic was 35.8%. Mothers with higher educational attainment were more likely to perceive their children's sleep as a problem. Maternal depressive and anxious symptoms and a history of excessive infant crying were the determinants predicting the likelihood of both parent-perceived sleep problems and poor sleepers. The present analysis of sleep structure in infancy and toddlerhood provides reference data for well-child visits. These findings highlight the importance of considering maternal anxiety, depression and behaviour management techniques to cope with fussy infants in addressing childhood behavioural sleep problems.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.

Unintentional Exposure of an Infant to Synthetic Cannabinoid (Bonzai) Related to the Parent's Use.

The increase of available synthetic cannabinoids poses an emerging public health threat worldwide. Synthetic cannabinoid use has been mainly reported in adolescent cases in pediatric practices; there are few reported cases involving infants affected by unintentional use. In this case report, we present the youngest age of synthetic cannabinoid bonzai exposure in the literature, discussing a 3-month-old child affected by exposure to the parents' use of bonzai in the home environment. Because unintentional exposure to synthetic cannabinoids like bonzai might be encountered, pediatric emergency teams should be aware of this condition and child protection teams should be informed of suspicions of child negligence and abuse as a part of the medical approach.

Clostridium difficile Colitis Prevention and Treatment.

Clostridium difficile (C. diff) is the most common causative agent of antibiotic-associated diarrhea and colitis. This spore-forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, the use of probiotics, especially Saccharomyces boulardii, and more recently of fecal microbiota transplantation have become valid forms of prevention and/or therapy and are here critically examined.

[Meningitis Due to Streptococcus pneumoniae Serotype 24B in a Patient with Cochlear Implant Previously Vaccinated with the Pneumococcal Vaccine]. / Pnömokok Asili Koklear Implantli Hastada Streptococcus pneumoniae Serotip 24B'ye Bagli Menenjit.

Streptococcus pneumoniae is a major cause of bacterial meningitis in children. It can progress and carries a serious risk of mortality and morbidity despite effective treatment. Cochlear implantation is a fairly successful procedure for restoring hearing in cases of sensorineural hearing loss. Moreover, patients with cochlear implants are at increased risk of contracting pneumococcal meningitis compared to the general population. The development of meningitis is associated with pathogens in the middle ear that contaminate the cerebrospinal fluid (CSF), as a result of congenital anomalies in the cochlea, and the cochlear implant. A 4-year-old girl presented to our clinic with fever, vomiting, and weakness. A physical examination showed an axillary temperature of 38.3°C, heart rate of 134/min, respiration rate of 50 breaths/minute, and arterial blood pressure of 120/88 mmHg. The patient also had a neck stiffness and her Kernig and Brudzinski signs were positive. It was discovered that the patient had undergone cochlear implantation approximately five months prior due to bilateral congenital sensorineural hearing loss. She had also received the Haemophilus influenzae type b and PCV-13 vaccines in line with the national immunization calendar. Her laboratory findings showed a leukocyte count of 21.900/mm3 (neutrophils 90% and lymphocytes 10%) and her procalcitonin level was 1.22 ng/ml. An uncountable number of neutrophils was identified in her cerebrospinal fluid, which led to the initial diagnosis of meningitis. There was also 1 mg/dl of glucose (blood glucose, 102 mg/dl) and 706 mg/dl of protein in her cerebrospinal fluid. Empirically, vancomycin (60 mg/kg/day) and ceftriaxone (100 mg/kg/day) were started. Following 5 days of antibiotic treatment, penicillin-susceptible S.pneumoniae was yielded in her CSF culture and identified as serotype 24B. S.pneumoniae with the same antibiotic sensitivity was also identified in her blood culture. Since rhinorrhea was observed on day 16 of hospitalization, she underwent an operation to repair the fistula tract. A computerized tomography cranial scan was performed after the development of acute mental fog at postoperative day 3 and showed brain edema and a thrombus in the right middle cerebral artery. The patient died on day 42 of hospitalization due to multiple organ failure. To our knowledge, this is the first case of meningitis reported in our country associated with S.pneumoniae serotype 24B in a patient with a cochlear implant. While there has been a decrease in the prevalence of invasive pneumococcal disease with routine administration of the pneumococcal conjugate vaccine, a relative increase has been observed in its non-vaccine serotypes. This is relevant not only to patients with more risk factors, such as a cochlear implant, but also those who are at lower risk for pneumococcal infection.

Menstruation-related headache in adolescents: Point prevalence and associated factors.

BACKGROUND: The aim of this study was to investigate the prevalence of menstruation-related headache and the impact of associated factors in adolescents. METHODS: This cross-sectional study was conducted in seven randomly selected high schools, and 3,886 girls attending those schools were invited to take part. After the consent of the school principals, a final total of 2,485 girls (63.9%) were involved in the study. A specific questionnaire was distributed to adolescent girls (14-19 years old). The first part of the survey investigated the features of menstruation (age at first menstruation, duration of period, pad fully soaked per day). The last part of the questionnaire surveyed the presence of headache during the menstrual period. The severity of headache was measured using a visual analog scale. Last, participants were requested to complete the Beck Depression Inventory (BDI). The prevalence of menstruation-related headache and associated factors were studied. RESULTS: Mean subject age was 15.89 ± 1.07 years (range, 14-19 years) and mean age at menarche was 12.96 ± 1.09 years old. The prevalence of menstruation-related headache was 25.9% (n = 646). Onset of menstruation at <12 years of age, longer duration of menstruation period, dysmenorrhea, daily consumption of coffee and cola and smoking significantly affected the frequency of menstruation-related headache. Mean BDI score was 21.68 ± 13.65 and was significantly associated with menstruation headache. CONCLUSION: Menstruation-related headache is a common problem in adolescent girls. It might be associated with different comorbidities such as depression. Accordingly, a multidisciplinary treatment approach must be considered to improve the quality of life.

Human mature milk zearalenone and deoxynivalenol levels in Turkey.

INTRODUCTION: Zearalenone (ZEA) and deoxynivalenol (DON) are toxic fungal secondary metabolites, found mainly in contaminated food, that are associated with serious health problems. It is important to identify undesirable toxins and metabolites that may be present in human milk. The aim of this study was to evaluate human milk ZEA and DON levels, total daily intake of ZEA and DON; and their possible relationship with maternal dietary habits. METHODS: We enrolled 90 lactating mothers who had 7- to 90-day-old babies. A dietary questionnaire was completed by each of the mothers. Human milk samples were obtained from 90 mothers, and human milk ZEA and DON levels were evaluated with the solid-phase direct enzyme immunoassay. The total daily intake (TDI) was calculated for the 63 exclusively breastfed infants. RESULTS: ZEA was detected in all human milk samples; median was 173.8 ng/L (35.7-682 ng/L). The calculated median TDI for ZEA was 33.0 ng/kg body weight (bw) (10.4-120.5 ng/kg) among exclusively breast-fed infants, none of them had a TDI that was above the previously defined threshold levels. Human milk ZEA levels were associated with the maternal consumption of meat, fish, dry fig, dried apricot, flaked red spice and spice. The median DON levels was 3924 ng/L (400-14997 ng/L). The median TDI of DON was 750 ng/kg (240-2774 ng/kg) among exclusively breastfed infants and 36% out of them, the TDI for DON was above the previously defined threshold level. Human milk DON levels were associated with the maternal meat consumption. CONCLUSIONS: Our findings are indicative of dietary exposure to mycotoxins during the pregnancy and lactation periods in nursing mothers. Further, the excessive TDI values for DON observed in 36% of the exclusively breastfed infants point to the need for further regulations and recommendations on the dietary habits of pregnant/nursing mothers in order to avoid exposure to potential mycotoxins.

Evaluation of Screen Time in Children Under Five Years Old.

INTRODUCTION: Due to the rapid advancement of technology, there has been a noteworthy increase in the diversity and abundance of activities involving children. The most effective methods to enhance and facilitate children's media interactions are to minimize, reduce, use with caution, and establish healthy patterns. We aimed to evaluate media exposure of children below five years of age. MATERIAL AND METHODS: This is a prospective, observational, cross-sectional study that was conducted between December 2017 and September 2019 in Eskisehir, Türkiye. To assess the frequency of electronic device usage among children under the age of five, including televisions, laptops, tablets, and mobile phones, as well as its impact on their sleep patterns and physical measurements, and to evaluate families' understanding of the terms "screen time" and "back screen time," we developed a questionnaire. RESULTS: We analyzed a total of 731 questionnaires: 334 (45.7%) were girls, 397 (54.3%) were boys, and the mean age was 33.55±16.37 months. Upon examining the technical equipment accessible to the children in our study, we found that 98.6% possessed a television, 96.9% owned a mobile phone, 54% had a laptop, 49.5% had a tablet, and 34.1% possessed a gaming console. The study revealed the following proportions of electronic devices in children's rooms: 13% televisions, 11.9% tablets, 7.4% laptops, and 7% mobile phones. There has been a substantial increase in the amount of time they spend watching television and playing computer games among children who have at least one sibling. There was a statistically significant disparity between the television viewing periods and the body mass index of children older than two years old. Additionally, we have seen a significant disparity in the presence of media devices in children's bedrooms and the subsequent impact on their sleep duration and patterns throughout both nighttime and daytime. Around 65.8% of parents did not know of the concept of screen time, while 88.4% of parents did not know of the concept of back screen time. DISCUSSION: Parental compliance with the current guidelines for screen time is insufficient, among parents with children under the age of five, even though exposure to screens begins in the first months of life. Our analysis highlighted the necessity for parents to establish and enforce a unified and logical media usage policy for all children residing in the household. It is crucial to allocate sufficient time during the routine healthcare visit to discuss these recommendations.

Composition of Microbiota in Transient and Mature Human Milk: Significant Changes in Large for Gestational Age Group.

The composition of the human milk (HM) microbiota and, consequently, the microorganisms that are passed on to the infant through breastfeeding, can be influenced by various factors such as the mother's health and diet, gestational age, delivery mode, lactation stage, method of infant feeding, and geographical location. The aim of the Human Milk-Gest Study was to compare the microbiota of transient (postpartum 7-15 days) and mature HM (postpartum 45-90 days) of 44 mothers, and to investigate any potential changes associated with preterm birth, mode of delivery, and birth weight in relation to gestational age. The data were classified into five study groups: normal spontaneous delivery-term (NS-T) newborns, cesarean delivery-term (CS-T) newborns, preterm (PT) newborns (with a gestational age of less than 37 weeks), small for gestational age (SGA) newborns, and large for gestational age (LGA) newborns. An analysis of differential abundance was conducted using ANCOM-BC to compare the microbial genera between transient and mature HM samples as well as between other study groups. A significant difference was detected between HM samples at different sampling times and between the study groups (p < 0.01). In transient HM samples, Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the NS-T, CS-T, PT, and SGA groups. In mature HM samples, Burkholderiaceae_uc, Ralstonia, Pelomonas, and Klebsiella were significantly dominant in the LGA group compared to the NS-T, CS-T, and PT groups, while Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the SGA group. Differences were also detected between the transient and mature HM samples in the CS-T, PT, SGA, and LGA groups, but no differences occurred in the NS-T groups. In conclusion, we showed that Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group in transient HM and continued in mature HM. The body mass index (BMI) of the mothers in the LGA group was not >30 at conception, however, the maternal BMI at birth and maternal weight gain during pregnancy were higher than in the other groups. The nutritional composition of HM is specifically designed to meet infant nutritional requirements during early life. Evaluating the effects of HM microbiota on infant microbiota composition and short- and long-term health effects in larger studies would be useful.

Comparison of Bordetella pertussis Antibody Levels in Pregnant Women and Umbilical Cord Blood: A Multicenter Study.

BACKGROUND: In countries where pertussis vaccination is not administered during pregnancy, the determination of pertussis antibody levels in pregnant women is very important in terms of knowing the current seroepidemiology and potential strategies for immunizations. METHODS: We included 396 pregnant women who were admitted to 4 different obstetrics and gynecology clinics. Anti-Bordetella pertussis toxin (PT) IgG and anti-Bordetella pertussis filamentous hemagglutinin IgG levels in maternal and cord blood pairs were determined by the ELISA method. RESULTS: Venous blood serum anti-PT level was below 5 IU/mL in 58.8%, 5-40 IU/mL in 34.8%, 40-100 IU/mL in 5.1% and >100 IU/mL in 1.3% of pregnant women. Cord blood serum anti-PT level was below 5 IU/mL in 47.7%, 5-40 IU/mL in 44.5%, 40-100 IU/mL in 6.8% and >100 IU/mL in 1% of pregnant women. In our study, the anti-PT level was found below 40 IU/mL in 93.6% of pregnant women and 92.2% of cord blood. Our study found the anti-filamentous hemagglutinin level below 40 IU/mL in 81% of pregnant women and 66.2% of cord blood. CONCLUSIONS: Although it is known that pertussis causes serious morbidity and mortality in young infants all over the world and that the most effective and reliable way to prevent it is vaccination of pregnant women, it is a remarkable contradiction that pertussis vaccination rates and therefore seropositivity rates in pregnant women are very low.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

Serum and urinary leptin and ghrelin in children with nephrotic syndrome.

OBJECTIVE: The aim of the present study was to evaluate the serum and urinary levels of leptin and ghrelin in children with primary idiopathic nephrotic syndrome (NS), to compare these results between patients during the relapse and remission phase and to evaluate the possible role of leptin and ghrelin in the pathogenesis of NS. PATIENTS AND METHODS: Forty-nine children with primary idiopathic NS (25 children with relapse and 24 children in remission), who were followed up at the Pediatric Nephrology Unit, enrolled. Twenty-eight age- and sex-matched healthy children served as controls. Serum and urinary leptin levels were determined by immunoenzymatic ELISA, and serum and urinary ghrelin levels were determined by the RIA method. RESULTS: The serum leptin levels were significantly lower in the children with NS during the relapse phase than in the children with NS during remission or in the controls (1.42±0.34 ng/dl and 3.60±0.70 ng/ml; p<0.01, 1.42±0.34 ng/ml and 5.27±4.67 ng/ml; p<0.001, respectively). The urinary leptin excretion levels were significantly higher in the relapse group than in the controls (0.40±0.11 ng/ml and 0.12±0.06 ng/ml, p<0.01, respectively). The serum ghrelin levels were similar between the study groups (p>0.05). The urinary ghrelin excretion levels were significantly higher in the relapse group than in the remission group and the controls (965.0 pg/ml [93-3711] and 679.7 pg/ml [93-3783], p<0.05; 965.0 pg/ml [93-3711] and 387.7 pg/ml [114-1214], p<0.001, respectively). The urinary ghrelin levels were also significantly higher in the remission group than in the controls (679.7 pg/ml [93-3783] and 387.7 pg/ml [114-1214]), p<0.01, respectively). The serum leptin levels were positively correlated with the serum albumin levels (r=0.440, p<0.05) and were negatively correlated with the serum triglyceride levels during the relapse phase. The urinary leptin and ghrelin levels were positively correlated with proteinuria in the relapse group. CONCLUSIONS: We propose that leptin plays a role in the pathophysiology of NS and is associated with proteinuria, hypoproteinemia and hyperlipidemia. The significant urinary excretion of ghrelin in children with NS is possibly due to underlying pathophysiological changes, and normal serum ghrelin levels might be associated with an unknown compensatory mechanism.

Functional effects of human milk oligosaccharides (HMOs).

Human milk oligosaccharides (HMOs) are the third most important solid component in human milk and act in tandem with other bioactive components. Individual HMO levels and distribution vary greatly between mothers by multiple variables, such as secretor status, race, geographic region, environmental conditions, season, maternal diet, and weight, gestational age and mode of delivery. HMOs improve the gastrointestinal barrier and also promote a bifidobacterium-rich gut microbiome, which protects against infection, strengthens the epithelial barrier, and creates immunomodulatory metabolites. HMOs fulfil a variety of physiologic functions including potential support to the immune system, brain development, and cognitive function. Supplementing infant formula with HMOs is safe and promotes a healthy development of the infant revealing benefits for microbiota composition and infection prevention. Because of limited data comparing the effect of non-human oligosaccharides to HMOs, it is not known if HMOs offer an additional clinical benefit over non-human oligosaccharides. Better knowledge of the factors influencing HMO composition and their functions will help to understand their short- and long-term benefits.

Effects of synbiotic supplementation on intestinal microbiota composition in children and adolescents with exogenous obesity: (Probesity-2 trial).

INTRODUCTION: Gut microbiota manipulation may be a potential therapeutic target to reduce host energy storage. There is limited information about the effects of probiotics/synbiotics on intestinal microbiota composition in children and adolescents with obesity. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic on intestinal microbiota composition in children and adolescents with exogenous obesity. METHOD: Children with exogenous obesity were managed with a standard diet and increased physical activity and were randomly allocated into two groups at a ratio of 1:1; the 1st group received synbiotic supplementation (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus. rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 × 109 CFU/sachet) and fructo-oligosaccharides (FOS; 625 mg/sachet) for 12 weeks; the 2nd group received placebo once daily for 12 weeks. Fecal samples were obtained before and at the end of the 12-week intervention to characterize the changes in the gut microbiota composition. Detailed metagenomic and bioinformatics analyses were performed. RESULTS: Before the intervention, there were no significant differences in alpha diversity indicators between the synbiotic and placebo groups. After 12 weeks of intervention, the observed taxonomic units and Chao 1 were lower in the synbiotic group than at baseline (p < 0.001 for both). No difference for alpha diversity indicators was observed in the placebo group between baseline and 12 weeks of intervention. At the phylum level, the intestinal microbiota composition of the study groups was similar at baseline. The major phyla in the synbiotic group were Firmicutes (66.7%) and Bacteroidetes (18.8%). In the synbiotic group, the Bacteroidetes phylum was higher after 12 weeks than at baseline (24.0% vs. 18.8%, p < 0.01). In the synbiotic group, the Firmicutes/Bacteroidetes ratio was 3.54 at baseline and 2.75 at 12 weeks of intervention (p < 0.05). In the placebo group, the Firmicutes/Bacteroidetes ratio was 4.70 at baseline and 3.54 at 12 weeks of intervention (p < 0.05). After 12 weeks of intervention, the Firmicutes/Bacteroidetes ratio was also lower in the synbiotic group than in the placebo group (p < 0.05). In the synbiotic group, compared with the baseline, we observed a statistically significant increase in the genera Prevotella (5.28-14.4%, p < 0.001) and Dialister (9.68-13.4%; p < 0.05). Compared to baseline, we observed a statistically significant increase in the genera Prevotella (6.4-12.4%, p < 0.01) and Oscillospira (4.95% vs. 5.70%, p < 0.001) in the placebo group. In the synbiotic group, at the end of the intervention, an increase in Prevotella, Coprococcus, Lachnospiraceae (at the genus level) and Prevotella copri, Coprococcus eutactus, Ruminococcus spp. at the species level compared to baseline (predominance of Eubacterium dolichum, Lactobacillus ruminis, Clostridium ramosum, Bulleidia moorei) was observed. At the end of the 12th week of the study, when the synbiotic and placebo groups were compared, Bacteroides eggerthi species were dominant in the placebo group, while Collinsella stercoris species were dominant in the synbiotic group. CONCLUSION: This study is the first pediatric obesity study to show that a synbiotic treatment is associated with both changes intestinal microbiota composition and decreases in BMI. Trial identifier: NCT05162209 (www. CLINICALTRIALS: gov).

Drug Repurposing of FDA Compounds against α-Glucosidase for the Treatment of Type 2 Diabetes: Insights from Molecular Docking and Molecular Dynamics Simulations.

Type 2 diabetes mellitus is a chronic health problem that can be controlled by slowing one's carbohydrate metabolism by inhibiting α-glucosidase, an enzyme responsible for carbohydrate degradation. Currently, drugs for type 2 diabetes have limitations in terms of safety, efficiency, and potency, while cases are rapidly increasing. For this reason, the study planned and moved towards drug repurposing by utilizing food and drug administration (FDA)-approved drugs against α-glucosidase, and investigated the molecular mechanisms. The target protein was refined and optimized by introducing missing residues, and minimized to remove clashes to find the potential inhibitor against α-glucosidase. The most active compounds were selected after the docking study to generate a pharmacophore query for the virtual screening of FDA-approved drug molecules based on shape similarity. The analysis was performed using Autodock Vina (ADV)-based on binding affinities (-8.8 kcal/mol and -8.6 kcal/mol) and root-mean-square-deviation (RMSD) values (0.4 Å and 0.6 Å). Two of the most potent lead compounds were selected for a molecular dynamics (MD) simulation to determine the stability and specific interactions between receptor and ligand. The docking score, RMSD values, pharmacophore studies, and MD simulations revealed that two compounds, namely Trabectedin (ZINC000150338708) and Demeclocycline (ZINC000100036924), are potential inhibitors for α-glucosidase compared to standard inhibitors. These predictions showed that the FDA-approved molecules Trabectedin and Demeclocycline are potential suitable candidates for repurposing against type 2 diabetes. The in vitro studies showed that trabectedin was significantly effective with an IC50 of 1.263 ± 0.7 µM. Further investigation in the laboratory is needed to justify the safety of the drug to be used in vivo.

Effects of Multispecies Synbiotic Supplementation on Anthropometric Measurements, Glucose and Lipid Parameters in Children With Exogenous Obesity: A Randomized, Double Blind, Placebo-Controlled Clinical Trial (Probesity-2 Trial).

Studies on the effects of synbiotics on obesity in children are limited. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic during 12 weeks on anthropometric measurements, glucose metabolism and lipid parameters in 61 children with exogenous obesity. All children were treated with a standard diet and increased physical activity and received once daily a synbiotic supplement (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium and fructo-oligosaccharides) or daily placebo for 12 weeks. At baseline, no statistically significant differences existed in anthropometric measurements, glucose and lipid parameters between both groups. We observed changes for anthropometric measures (% reduction comparing to baseline) in both synbiotic and placebo groups. After 12 weeks; changes (% reduction comparing to baseline) in weight (p < 0.01), BMI (p < 0.05), waist circumference (p < 0.05) and waist circumference to height ratio (p < 0.05) were significantly higher in the children receiving the synbiotic supplement. There is no difference in glucose metabolism, lipid parameters, presence of non-alcoholic fatty liver disease between both groups after 12 weeks. The daily intake of a multispecies synbiotic in addition to diet and increased physical activity did improve anthropometric measurements: body weight, BMI, waist circumference and waist/height ratio. The supplementation of this synbiotic is an efficient weight-loss strategy above diet and exercise in pediatric obesity (Trial identifier: NCT05162209).

Human Milk Virome Analysis: Changing Pattern Regarding Mode of Delivery, Birth Weight, and Lactational Stage.

The human milk (HM) microbiota is a significant source of microbes that colonize the infant gut early in life. The aim of this study was to compare transient and mature HM virome compositions, and also possible changes related to the mode of delivery, gestational age, and weight for gestational age. Overall, in the 81 samples analyzed in this study, reads matching bacteriophages accounted for 79.5% (mainly Podoviridae, Myoviridae, and Siphoviridae) of the reads, far more abundant than those classified as eukaryotic viruses (20.5%, mainly Herpesviridae). In the whole study group of transient human milk, the most abundant families were Podoviridae and Myoviridae. In mature human milk, Podoviridae decreased, and Siphoviridae became the most abundant family. Bacteriophages were predominant in transient HM samples (98.4% in the normal spontaneous vaginal delivery group, 92.1% in the premature group, 89.9% in the C-section group, and 68.3% in the large for gestational age group), except in the small for gestational age group (only ~45% bacteriophages in transient HM samples). Bacteriophages were also predominant in mature HM; however, they were lower in mature HM than in transient HM (71.7% in the normal spontaneous vaginal delivery group, 60.8% in the C-section group, 56% in the premature group, and 80.6% in the large for gestational age group). Bacteriophages still represented 45% of mature HM in the small for gestational age group. In the transient HM of the normal spontaneous vaginal delivery group, the most abundant family was Podoviridae; however, in mature HM, Podoviridae became less prominent than Siphoviridae. Myoviridae was predominant in both transient and mature HM in the premature group (all C-section), and Podoviridae was predominant in transient HM, while Siphoviridae and Herpesviridae were predominant in mature HM. In the small for gestational age group, the most abundant taxa in transient HM were the family Herpesviridae and a species of the genus Roseolovirus. Bacteriophages constituted the major component of the HM virome, and we showed changes regarding the lactation period, preterm birth, delivery mode, and birth weight. Early in life, the HM virome may influence the composition of an infant's gut microbiome, which could have short- and long-term health implications. Further longitudinal mother-newborn pair studies are required to understand the effects of these variations on the composition of the HM and the infant gut virome.