Early treatment may prevent or delay the onset of type 2 diabetes mellitus (T2DM) in individuals who are at high risk. Lifestyle interventions and the hypoglycemic drug metformin have been shown to reduce T2DM incidence. The effectiveness of such interventions may be enhanced by targeting environmental factors such as the intestinal microbiota, which has been proven to predict the response to lifestyle interventions and play a part in mediating the glucose-lowering effects of metformin. Shifts in the intestinal microbiota “towards a more balanced state” may promote glucose homeostasis by regulating short-chain fatty acids’ production. This study aimed to investigate the safety and effect of a multi-strain probiotic on glycemic, inflammatory, and permeability markers in adults with prediabetes and early T2DM and to assess whether the probiotic can enhance metformin’s effect on glycaemia. A randomised controlled pilot study was conducted in 60 adults with a BMI ≥ 25 kg/m2 and with prediabetes or T2DM (within the previous 12 months). The participants were randomised to a multi-strain probiotic (L. plantarum, L. bulgaricus, L. gasseri, B. breve, B. animalis sbsp. lactis, B. bifidum, S. thermophilus, and S. boulardii) or placebo for 12 weeks. Analyses of the primary outcome (fasting plasma glucose) and secondary outcomes, including, but not limited to, circulating lipopolysaccharide, zonulin, and short chain fatty acids and a metagenomic analysis of the fecal microbiome were performed at baseline and 12 weeks post-intervention. The results showed no significant differences in the primary and secondary outcome measures between the probiotic and placebo group. An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group. Probiotics may act as an adjunctive to metformin by increasing the production of butyrate, which may consequently enhance glucose management.

At the time of birth, humans experience an induced pro-inflammatory beneficial event. The mediators of this encouraged activity, is a fleet of bacteria that assault all mucosal surfaces as well as the skin. Thus initiating effects that eventually provide the infant with immune tissue maturation. These effects occur beneath an emergent immune system surveillance and antigenic tolerance capability radar. Over time, continuous and regulated interactions with environmental as well as commensal microbial, viral, and other antigens lead to an adapted and maintained symbiotic state of tolerance, especially in the gastrointestinal tract (GIT) the organ site of the largest microbial biomass. However, the perplexing and much debated surprise has been that all microbes need not be targeted for destruction. The advent of sophisticated genomic techniques has led to microbiome studies that have begun to clarify the critical and important biochemical activities that commensal bacteria provide to ensure continued GIT homeostasis. Until recently, the GIT and its associated micro-biometabolome was a neglected factor in chronic disease development and end organ function. A systematic underestimation has been to undervalue the contribution of a persistent GIT dysbiotic (a gut barrier associated abnormality) state. Dysbiosis provides a plausible clue as to the origin of systemic metabolic disorders encountered in clinical practice that may explain the epidemic of chronic diseases. Here we further build a hypothesis that posits the role that subtle adverse responses by the GIT microbiome may have in chronic diseases. Environmentally/nutritionally/and gut derived triggers can maintain microbiome perturbations that drive an abnormal overload of dysbiosis. Live probiotic cultures with specific metabolic properties may assist the GIT microbiota and reduce the local metabolic dysfunctions. As such the effect may translate to a useful clinical treatment approach for patients diagnosed with a metabolic disease for end organs such as the kidney and liver. A profile emerges that shows that bacteria are diverse, abundant, and ubiquitous and have significantly influenced the evolution of the eukaryotic cell.

The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system.

We describe the case of a child with severely unintelligible speech, referred to our clinic after unsuccessful therapy elsewhere. Thomas's speech was char-acterized by deapicalization and velodorsal articulations, together with hypernasality. Unusually, Thomas was also able to produce a small number of items normally. His speech was investigated by videofluorography as previous impressionistic transcription had been inconclusive. Thomas's history suggested that these speech characteristics were learned behaviour, adopted because of irritation in the upper oro-pharynx. Previous therapy had concentrated on articulatory drills with little success. A new strategy of a contextually embedded, meaning-based approach to speech remediation was undertaken, and within a short time Thomas was using mainly intelligible speech with age-appropriate phonological patterns.

Objectives/Hypothesis To determine whether the severity of obstructive sleep apnea (OSA) is affected by weight gain velocity (WGV) in adolescents with Down syndrome. Study Design Retrospective case series. Methods We performed a retrospective case series of children with Down syndrome, aged 9–19, referred for polysomnography (PSG) due to suspected OSA at an academic children's hospital. We determined the velocity (slope of change) of yearly weight gain using a mixed effect linear regression model. Subsequently, we determined if velocity of yearly weight gain was greater in adolescents with severe OSA (apnea‐hypopnea index > 10). Significance was set at P < .05. Results A total of 77 adolescents with Down syndrome were identified. The average age was 12.5 years (standard deviation = 3.1); 44 (57%) were male and 46 (60%) were Hispanic. The majority, 51 (66%) had severe OSA. The velocity of yearly weight gain prior to PSG in Down syndrome adolescents was similar regardless of OSA severity (mean diff in weight gain at PSG between severe and nonsevere OSA = −1.42, 95% confidence interval = −5.8 to 2.9, P = .52). Down syndrome adolescents with severe OSA weighed more at PSG (58.4 kg vs. 40.9 kg, P < .001) and all years prior to PSG. These findings remained even when controlling for age at PSG. Conclusions Severe OSA in adolescents with Down syndrome is associated with weight. There was no significant difference in WGV in children with Down syndrome with or without severe OSA. Level of Evidence 3 Laryngoscope, 131:2598–2602, 2021