A distinct clade of Bifidobacterium longum in the gut of Bangladeshi children thrives during weaning.

The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development.

The histone deacetylase inhibitor, entinostat (MS-275), induces the odontogenic differentiation of an odontoblast-like cell line in the absence of an osteoblast mineralization medium.

The aim of this study was to determine whether histone deacetylase inhibitors (HDACi), including entinostat (MS-275), valproic acid (VPA), trichostatin A (TSA), and sodium butyrate (NaB), promoted the odontogenic differentiation of the odontoblast-like cell line, MDPC-23 in the absence of an osteoblast mineralization medium. The cells were cultured in basal medium (Dulbecco's modified Eagle medium) with and without (controls) the inhibitors. The cell viability and migration were assessed using the cell proliferation reagent WST-1 and a scratch wound healing assay, respectively. The mRNA expression levels of bone morphogenetic protein (Bmp)-2 and -4, collagen 1 alpha 1 (Col1α1), osteocalcin (Oc), dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp), runt-related transcription factor 2 (Runx2), Krueppel-like factor 5 (Klf5), and Msh homeobox 1 (Msx1) were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Alizarin red and alkaline phosphatase assays were performed to determine the extent of mineralization in the culture systems. No significant differences in cell numbers were observed between the controls and the MS-275-, VPA-, and NaB-treated cells; however, a significant difference was observed with TSA (concentration, 1000 nM). The scratch wound healing assay showed no effect of cell migration in the MS-275 (1.0 µM)-treated cells when compared with the controls at 24 h. Furthermore, MS-275, VPA, and NaB increased the mRNA expression levels of Bmp-2 and -4, Oc, and Runx2 followed by the mineralization of the cells. Only MS-275 significantly increased the expression levels of Dmp1, Dspp, Klf5, and Msx1 in the cells. These findings indicated that MS-275 may be considered as a reliable candidate for the odontogenic differentiation of dental pulp cells.

Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers.

Bacteriophage therapy is a commonly used treatment for Staphylococcus aureus infections in countries of the former Soviet Union, using both single phages and phage cocktails. The scarce data available on Eastern phage cocktails prompted an investigation into commercially-available Pyophage cocktails from two different manufacturers used to treat skin and wound infections. Comparison of the metagenomic composition of two Pyophage products from Georgia and Russia revealed substantial differences in phage-types targeting Escherichia, Enterococcus, Salmonella, Pseudomonas aeruginosa and Proteus, therefore indicating multiple strategies for composing phage cocktails against these bacterial pathogens. Closely-related Kayvirus-like Myoviruses were, however, a shared component against S. aureus within all products, except for the inclusion of a secondary S. aureus Podovirus in one Microgen cocktail. Metagenomic analysis also revealed the presence of several probable prophage sequences but detected no genetic safety risks in terms of virulence factors or antibiotic resistance genes. The safety of broad-spectrum cocktails was tested by comparing the effects of nasal and oral exposure to Eliava Pyophage, a monospecies counterpart and placebo in healthy human carriers of S. aureus. The lack of adverse effects in any treatment groups supports the clinical safety of S. aureus phages administered as a single phage or as phage cocktail.

Bangladeshi children with acute diarrhoea show faecal microbiomes with increased Streptococcus abundance, irrespective of diarrhoea aetiology.

We report streptococcal dysbiosis in acute diarrhoea irrespective of aetiology. Compared with 20 healthy local controls, 71 Bangladeshi children hospitalized with acute diarrhoea (AD) of viral, mixed viral/bacterial, bacterial and unknown aetiology showed a significantly decreased bacterial diversity with loss of pathways characteristic for the healthy distal colon microbiome (mannan degradation, methylerythritol phosphate and thiamin biosynthesis), an increased proportion of faecal streptococci belonging to the Streptococcus bovis and Streptococcus salivarius species complexes, and an increased level of E. coli-associated virulence genes. No enteropathogens could be attributed to a subgroup of patients. Elevated lytic coliphage DNA was detected in 2 out of 5 investigated enteroaggregative E. coli (EAEC)-infected patients. Streptococcal outgrowth in AD is discussed as a potential nutrient-driven consequence of glucose provided with oral rehydration solution.

Long-Term Gastrointestinal Consequences are Frequent Following Sporadic Acute Infectious Diarrhea in a Tropical Country: A Prospective Cohort Study.

BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD), though reported from the temperate countries, have not been studied in the tropics; PI-malabsorption syndrome (MAS), which mimics PI-IBS, is reported from the tropics. No report till date on PI-IBS excluded PI-MAS. We studied: (i) the frequency of continuing bowel dysfunction after acute gastroenteritis (AG), (ii) its predictors, and (iii) PI-MAS among patients with PI-IBS. METHODS: 345 consecutive subjects each, with AG and age- and gender-matched healthy controls were followed up 3-monthly for 12 months using a translated-validated questionnaire and functional gastrointestinal disorders (FGIDs) were diagnosed by Rome III criteria. Symptom duration >3 months but <6 months was diagnosed as chronic bowel dysfunction (CBD) and dyspeptic symptoms, respectively. MAS was diagnosed if 2/3 tests (D-xylose H2 breath test, Sudan III-stained stool microscopy, and duodenal histology) were abnormal. Fecal microbiological studies were performed in 245/345 (71%) patients. RESULTS: AG patients more often developed PI-IBS and PI-FD than controls (16.5 vs. 2.6% and 7.4 vs. 0.6%, respectively; p<0.001). Presence of FD was a risk factor for PI-IBS and IBS for PI-FD. On multivariate analysis, dyspeptic symptoms, CBD, and weight loss were the risk factors for PI-FGIDs. The frequency of PI-IBS following Vibrio cholera and other bacterial infection was comparable. Malabsorption was present among 2/23 (9%) patients with PI-IBS. CONCLUSION: FGIDs are common after AG; dyspeptic symptoms, CBD, and weight loss were risk factors for PI-FGIDs. Vibrio cholerae infection caused PI-FGID, which was never reported. About 9 % patients fulfilling the criteria for PI-IBS had PI-MAS.

What happened to Koch's postulates in diarrhoea?

In 1890, Robert Koch has formulated postulates describing what criteria a parasite has to fulfil to qualify as an aetiological agent for an infectious disease. Since then Koch's postulates have experienced reformulations by nearly every generation of microbiologists reflecting new discoveries changing the understanding of infectious diseases pathogenesis. The latest addition to this discussion is the role of the host commensal microbiota in turning infections into disease. After an overview of the historical developments of the postulates, data on diarrhoea aetiology from Bangladesh with respect to Koch's postulates were analysed. In countries with a low environmental hygiene standard, some recognized bacterial enteropathogens appear as a necessary, but not sufficient condition for diarrhoea. The possibility emerges that the loss of a physiological commensal gut microbiota equilibrium ('dysbiosis') is an important co-factor for some bacterial pathogens to induce diarrhoea. Koch's hypothesis '1 pathogen + 1 host = 1 disease' is therefore better formulated as 'X (pathogen/s) + Y (local milieu) + Z (individual host susceptibility) = disease'.

Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh.

A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes.

Overexpression of microRNA-542-3p attenuates the differentiating capacity of endometriotic stromal cells.

Aim: Endometriosis is defined as the presence of endometrial glandular and stromal cells outside of the uterine cavity. A previous study reported that microRNA (miR)-542-3p plays a critical role in eutopic endometrial decidualization. This study aims to clarify the potential role of miR-542-3p and the target gene, IGFBP-1 (insulin-like growth factor-binding protein 1), in the impairment of the decidualizing capacity of human ectopic endometrial stromal cells (HEcESCs). Methods: In vitro analysis of primary undifferentiated and decidualizing human eutopic endometrial stromal cells (HEuESCs) and HEcESCs was conducted. The primary HEuESCs or HEcESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP) and medroxyprogesterone acetate (MPA). Results: The morphological and biological differentiating capacities of the HEcESCs were markedly impaired. In contrast to the HEuESCs, the HEcESCs that were treated with the decidual stimulus retained the mesenchymal phenotype and capacity for migration. The down-regulation of miR-542-3p in the HEcESCs treatment with 8-bromo-cAMP and MPA was much weaker than that of the HEuESCs. High expression of miR-542-3p led to a significant decrease in the expression of IGFBP1 in the HEcESCs. Conclusion: Impairment of the differentiating capacity by the overexpression of miR-542-3p could influence the capacity for migration and invasion of endometriotic cells in an ectopic environment.

Anti-rotavirus protein reduces stool output in infants with diarrhea: a randomized placebo-controlled trial.

BACKGROUND & AIMS: Rotavirus infection is a leading cause of morbidity and mortality in children younger than 5 years of age. Current treatment options are limited. We assessed the efficacy of a llama-derived, heavy-chain antibody fragment called anti-rotavirus protein (ARP1), in modifying the severity and duration of diarrhea in male infants with rotavirus infection. METHODS: We performed a double-blind, placebo-controlled trial of 176 male infants (6-24 months old) with severe rotavirus-associated diarrhea at Dhaka Hospital, Bangladesh. The infants were randomly assigned to groups given oral ARP1 (15-30 mg/kg/day, n = 88) or placebo (maltodextrin, n = 88) for a maximum of 5 days. The primary outcomes were severity (stool output) and duration of diarrhea and fecal excretion of rotavirus. Secondary outcomes were intake of oral rehydration salt solution, severity of vomiting, and serum levels of rotavirus-specific IgA. RESULTS: In infants with only rotavirus infection, total cumulative stool output was 305.47 g/kg body weight among those given placebo (n = 63) and 237.03 g/kg body weight among those given ARP1 (n = 61) (a difference of 68.44 g/kg body weight or 22.5%; 95% confidence interval: 18.27-118.59 g/kg body weight; P =.0079). There was a significant reduction in rate of stool output (g/kg/d) in the ARP1 group compared with the placebo group (61%; P = .002). ARP1 had no significant effect in infants with concomitant infections or on any other measured outcomes. No adverse events could be linked to ARP1. CONCLUSIONS: In a placebo-controlled trial, ARP1 reduced stool output in male infants with severe rotavirus-associated diarrhea. Clinicaltrials.gov number: NCT01259765.

Effect of housing construction material on childhood acute respiratory infection: a hospital based case control study in Bangladesh.

Despite several studies conducted to investigate housing factors, the effects of housing construction materials on childhood ARI symptoms in Bangladesh remain unclear. Hence, the study aimed to measure such a correlation among children under the age of five. A hospital-based case-control study was conducted, involving 221 cases and 221 controls from January to April 2023. Bivariate and multivariate binary logistic regression was performed to measure the degree of correlation between housing construction materials and childhood ARI symptoms. Households composed of natural floor materials had 2.7 times (95% confidence interval 1.27-5.57) and households composed of natural roof materials had 1.8 times (95% confidence interval 1.01-3.11) higher adjusted odds of having under-five children with ARI symptoms than household composed of the finished floor and finished roof materials respectively. Households with natural wall type were found protective against ARI symptoms with adjusted indoor air pollution determinants. The study indicates that poor housing construction materials are associated with an increased risk of developing ARI symptoms among under-five children in Bangladesh. National policy regarding replacing poor housing materials with concrete, increasing livelihood opportunities, and behavioral strategies programs encouraging to choice of quality housing construction materials could eliminate a fraction of the ARI burden.

Estimating the potato farming efficiency: A comparative study between stochastic frontier analysis and data envelopment analysis.

BACKGROUND: The government of Bangladesh has been trying to encourage potato consumption to reduce pressure on rice consumption and earn foreign currency along with ensuring zero hunger that helps to achieve the Sustainable Development Goal. It is necessary to use farmers' resources and current technology more efficiently to meet the demand. Therefore, the authors aimed to evaluate the farm-level efficiency of potato farming in Bangladesh. METHODS AND MATERIALS: The Cobb-Douglas Stochastic Frontier Analysis (SFA) and the input-oriented Data Envelopment Analysis (DEA) methods are used to compute farm-level technical, allocative, and economic efficiencies and inefficiency of potato farming. The primary data were collected through interviews of 300 potato farmers from Munshigonj, Rangpur, Dinajpur, and Joypurhat districts of Bangladesh. RESULTS: The findings revealed that the efficiency score of the SFA model is higher than the DEA model, which implies that the SFA frontier fits better than the DEA frontier. In the case of DEA, variable returns to scale (VRS) technical efficiency (TE) enveloped data more closely than constant returns to scale (CRS) TE. Results of efficiency suggest significant economic, technical, and allocative inefficiencies in potato farming and there is a scope to increase potato production levels through efficiency improvement. Inefficiency analysis shows that infrastructure and socio-economic factors jointly influence potato production variability. CONCLUSIONS: The authors suggest for using the SFA to find efficiencies in the agriculture sector. To achieve efficiency in potato production, the government needs to pay attention for improving the allocative and economic efficiencies along with emphasizing to choose the appropriate technology and efficient use of resources for the scale of operation.

Yield performance and trait correlation of BARI released sweet potato varieties studied under several districts of Bangladesh.

A study was carried out in five sweet potato growing regions of Bangladesh, each characterized by suitable agro-ecologies, in order to demonstrate the most favorable varietal performance and trait correlations. A completely randomized block design with three replications was used to compare the varietal performance of BARI (Bangladesh Agricultural Research Institute) released sweet potato varieties (viz. BARI Mistialu-9, BARI Mistialu-10, BARI Mistialu-12, BARI Mistialu-15 and BARI Mistialu-17). During the 2021-22 cropping season, sweet potato varieties were tested in five districts of Bangladesh, namely Gazipur, Bogura, Jamalpur, Jashore, and Chattogram. The findings revealed that the BARI Mistialu-12 variety exhibited remarkable attributes, including a high marketable storage root yield of 39.88 t/ha. Additionally, it demonstrated exceptional performance in various yield components such as vine length, average storage root weight, and dry weight of the root. Furthermore, a positive correlation was observed between several traits and yield, as well as yield-attributing characteristics. This correlation suggests that enhancing these traits could potentially contribute to an overall increase in the storage root yield of sweet potatoes.

Anti-parasitic drug discovery against Babesia microti by natural compounds: an extensive computational drug design approach.

Tick-borne Babesiosis is a parasitic infection caused by Babesia microti that can infect both animals and humans and may spread by tick, blood transfusions, and organ transplantation. The current therapeutic options for B. microti are limited, and drug resistance is a concern. This study proposes using computational drug design approaches to find and design an effective drug against B. microti. The study investigated the potentiality of nine natural compounds against the pathogenic human B. microti parasite and identified Vasicinone and Evodiamine as the most promising drugs. The ligand structures were optimized using density functional theory, molecular docking, molecular dynamics simulations, quantum mechanics such as HOMO-LUMO, drug-likeness and theoretical absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetics characteristics performed. The results showed that Vasicinone (-8.6 kcal/mol and -7.8 kcal/mol) and Evodiamine (-8.7 kcal/mol and -8.5 kcal/mol) had the highest binding energy and anti-parasitic activity against B. microti lactate dehydrogenase and B. microti lactate dehydrogenase apo form. The strongest binding energy was reported by Vasicinone and Evodiamine; the compounds were evaluated through molecular dynamics simulation at 100 ns, and their stability when they form complexes with the targeted receptors was determined. Finally, the pkCSM web server is employed to predict the ADMET qualities of specific molecules, which can help prevent negative effects that arise from taking the treatment. The SwissADME web server is used to assess the Lipinski rule of five and drug-likeness properties including topological polar surface area and bioavailability. The Lipinski rule is used to estimate significant drug-likeness. The theoretical pharmacokinetics analysis and drug-likeness of the selected compounds are confirmed to be accepted by the Lipinski rule and have better ADMET features. Thus, to confirm their experimental value, these mentioned molecules should be suggested to carry out in wet lab, pre-clinical, and clinical levels.

Influence of Helicobacter pylori infection on gastric acid secretion in pre-school Bangladeshi children.

BACKGROUND: The effect of Helicobacter pylori (H. pylori) infection on gastric acid secretion (GAS) is poorly defined in children. OBJECTIVE: To determine whether H. pylori infection is associated with abnormal GAS in children. METHODS: We studied 30 H. pylori-infected children (identified by a positive urea breath test) and 30 noninfected children of both sexes, aged 2-5 years. Gastric pH and GAS were measured before and 8 weeks after the completion of a 2-week course of anti- H. pylori therapy (omeprazole, clarithromycin, and amoxicillin). Gastric acid output (GAO) was quantified during a 1-h basal period (GAO-B) (mmol/h) and a 1-hour stimulated period (GAO-S) (mmol/hour) following subcutaneous administration of pentagastrin (6 µg/kg). RESULTS: A significantly greater number of infected children had a high gastric pH (>4.0, p = 0.03) compared with the noninfected group. GAO-B and GAO-S in H. pylori-infected children were significantly lower, around 50%, compared with children without H. pylori infection. H. pylori-eradication therapy resulted in a rise of both the mean GAO-B (paired t-test before vs. after therapy; 0.28 ± 0.40 vs. 0.62 ± 1.0, p = 0.12) and GAO-S (before vs. after therapy; 2.0 ± 1.4 vs. 3.4 ± 2.5, p = 0.001), with values reaching equivalence to those in the H. pylori-negative children (0.71 ± 0.56 for BAO, 3.3 ± 2.0 for SAO, p = NS). CONCLUSION: The results suggest that the gastric barrier is compromised in children with H. pylori infection in Bangladesh. Improvement of GAO following anti- H. pylori therapy suggests a causal link between H. pylori infection and depressed GAO in this population.

Antinociceptive, antidiarrheal, and neuropharmacological activities of Barringtonia acutangula.

CONTEXT: Barringtonia acutangula (L.) Gaertn. (Lecythidaceae) has been used in folk medicine in the treatment of arthralgia, chest pain, dysmenorrhea, inflammation, hemorrhoids, diarrhea, and also in psychological disorders. OBJECTIVE: To investigate the antinociceptive, antidiarrheal, and neuropharmacological effect of the methanol extract of B. acutangula leaves and seeds in mice. MATERIALS AND METHODS: The extracts (200 and 400 mg/kg; p.o.) were tested for antinociceptive activity by acetic acid-induced writhing, hot plate and tail immersion models; castor oil- and magnesium sulphate-induced diarrheal models were used to evaluate antidiarrheal activity whereas hole cross and open field models were employed for testing neuropharmacological activity. RESULTS: Both extracts exhibited significant antinociceptive effect (p < 0.001) in acetic acid and heat induced pain models in a dose-dependent manner. The extracts prolonged the latency period to the thermal stimuli in both hot plate and tail immersion test. The extracts also showed significant inhibition of defecation (p < 0.001, 0.01) in both diarrheal models. Again, the spontaneous motor activity was decreased (p < 0.001) by the extracts in both hole cross and open field test. DISCUSSION AND CONCLUSION: The results of this study suggest that the methanol extracts of B. acutangula leaves and seeds possess good antinociceptive, antidiarrheal, and central nervous system (CNS) depressant activities. This study validates the use of this plant in traditional medicine.

Corrigendum: A Long Time Constant May Endorse Sharp Waves and Spikes Over Sharp Transients in Scalp Electroencephalography: A Comparison of After-Slow Among Different Time Constants Concordant With High-Frequency Activity Analysis.

[This corrects the article DOI: 10.3389/fnhum.2021.748893.].

A Long Time Constant May Endorse Sharp Waves and Spikes Over Sharp Transients in Scalp Electroencephalography: A Comparison of After-Slow Among Different Time Constants Concordant With High-Frequency Activity Analysis.

Objective: To clarify whether long time constant (TC) is useful for detecting the after-slow activity of epileptiform discharges (EDs): sharp waves and spikes and for differentiating EDs from sharp transients (Sts). Methods: We employed 68 after-slow activities preceded by 32 EDs (26 sharp waves and six spikes) and 36 Sts from 52 patients with partial and generalized epilepsy (22 men, 30 women; mean age 39.08 ± 13.13 years) defined by visual inspection. High-frequency activity (HFA) associated with the apical component of EDs and Sts was also investigated to endorse two groups. After separating nine Sts that were labeled by visual inspection but did not fulfill the amplitude criteria for after-slow of Sts, 59 activities (32 EDs and 27 Sts) were analyzed about the total area of after-slow under three TCs (long: 2 s; conventional: 0.3 s; and short: 0.1 s). Results: Compared to Sts, HFA was found significantly more with the apical component of EDs (p < 0.05). The total area of after-slow in all 32 EDs under TC 2 s was significantly larger than those under TC 0.3 s and 0.1 s (p < 0.001). Conversely, no significant differences were observed in the same parameter of 27 Sts among the three different TCs. Regarding separated nine Sts, the total area of after-slow showed a similar tendency to that of 27 Sts under three different TCs. Significance: These results suggest that long TC could be useful for selectively endorsing after-slow of EDs and differentiating EDs from Sts. These findings are concordant with the results of the HFA analysis. Visual inspection is also equally good as the total area of after-slow analysis.

Changing Epidemiology of Acute Respiratory Infections in Under-Two Children in Dhaka, Bangladesh.

Objectives: Risk factors for acute respiratory infections (ARIs) in community settings are not fully understood, especially in low-income countries. We examined the incidence and risk factors associated with ARIs in under-two children from the Microbiota and Health study. Methods: Children from a peri-urban area of Dhaka (Bangladesh) were followed from birth to 2 years of age by both active surveillance of ARIs and regular scheduled visits. Nasopharyngeal samples were collected during scheduled visits for detection of bacterial facultative respiratory pathogens. Information on socioeconomic, environmental, and household conditions, and mother and child characteristics were collected. A hierarchical modeling approach was used to identify proximate determinants of ARIs. Results: Of 267 infants, 87.3% experienced at least one ARI episode during the first 2 years of life. The peak incidence of ARIs was 330 infections per 100 infant-years and occurred between 2 and 4 months of age. Season was the main risk factor (rainy monsoon season, incidence rate ratio [IRR] 2.43 [1.92-3.07]; cool dry winter, IRR 2.10 [1.65-2.67] compared with hot dry summer) in the first 2 years of life. In addition, during the first 6 months of life, young maternal age (<22 years; IRR 1.34 [1.01-1.77]) and low birth weight (<2,500 g; IRR 1.39 [1.03-1.89]) were associated with higher ARI incidence. Conclusions: Reminiscent of industrialized settings, cool rainy season rather than socioeconomic and hygiene conditions was a major risk factor for ARIs in peri-urban Bangladesh. Understanding the causal links between seasonally variable factors such as temperature, humidity, crowding, diet, and ARIs will inform prevention measures.

The Influence of FUT2 and FUT3 Polymorphisms and Nasopharyngeal Microbiome on Respiratory Infections in Breastfed Bangladeshi Infants from the Microbiota and Health Study.

Acute respiratory infections (ARIs) are one of the most common causes of morbidity and mortality in young children. The aim of our study was to examine whether variation in maternal FUT2 (α1,2-fucosyltransferase 2) and FUT3 (α1,3/4-fucosyltransferase 3) genes, which shape fucosylated human milk oligosaccharides (HMOs) in breast milk, are associated with the occurrence of ARIs in breastfed infants as well as the influence of the nasopharyngeal microbiome on ARI risk. Occurrences of ARIs were prospectively recorded in a cohort of 240 breastfed Bangladeshi infants from birth to 2 years. Secretor and Lewis status was established by sequencing of FUT2/3 genes. The nasopharyngeal microbiome was characterized by shotgun metagenomics, complemented by specific detection of respiratory pathogens; 88.6% of mothers and 91% of infants were identified as secretors. Maternal secretor status was associated with reduced ARI incidence among these infants in the period from birth to 6 months (incidence rate ratio [IRR], 0.66; 95% confidence interval [CI], 0.47 to 0.94; P = 0.020), but not at later time periods. The nasopharyngeal microbiome, despite precise characterization to the species level, was not predictive of subsequent ARIs. The observed risk reduction of ARIs among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. However, we found no evidence that modulation of the nasopharyngeal microbiome influenced ARI risk. IMPORTANCE The observed risk reduction of acute respiratory infections (ARIs) among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. Respiratory pathogens were only weak modulators of risk, and the nasopharyngeal microbiome did not influence ARI risk, suggesting that the associated protective effects of human milk oligosaccharides (HMOs) are not conveyed via changes in the nasopharyngeal microbiome. Our observations add to the evidence for a role of fucosylated HMOs in protection against respiratory infections in exclusively or predominantly breastfed infants in low-resource settings. There is no indication that the nasopharyngeal microbiome substantially modulates the risk of subsequent mild ARIs. Larger studies are needed to provide mechanistic insights on links between secretor status, HMOs, and risk of respiratory infections.

Sleep is associated with reduction of epileptiform discharges in benign adult familial myoclonus epilepsy.

To clarify the effects of sleep on cortical irritability in benign adult familial myoclonus epilepsy (BAFME), we retrospectively compared epileptiform discharges of electroencephalographies (EEGs) between awake and sleep periods in 5 patients (mean age: 49.6 ±â€¯20.3 years). We also analyzed polysomnography (PSG) of 1 patient. Epileptiform discharges were significantly more frequent during the awake period (1.3 ±â€¯1.2/min) than those during light sleep stages (0.02 ±â€¯0.04/min) (P < 0.05). Regarding PSG analysis, epileptiform discharges were also reduced during all sleep stages compared to those during awake periods. Our study suggests a relative reduction in cortical irritability during sleep in BAFME.