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The use of immobilized alcohol dehydrogenases (ADHs) offers numerous advantages, especially in the reaction conditions required by industrial applications. Looking for more efficient and cost-effective methods of ADH immobilization, in this study we explored silica-based supports as an alternative to the use of functionalized polymeric resins. Three commercially available ADHs were immobilized by adsorption and covalent bond formation. The obtained supported biocatalysts were applied for the bioreduction of acetophenone and some derivatives with good yields and excellent enantioselectivity. The important intermediate (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol was obtained with a high enantiomeric excess (>99%) by using the highest performing immobilized ADH sample. The reusability of this biocatalyst was investigated in a flow system for five consecutive runs; the experiments showed that the biocatalyst could be recycled without a loss of activity and enantioselectivity. Finally, cross-linking with the glutaraldehyde of the supported biocatalyst was also carried out to prevent the leaching of the enzyme during the catalytic reactions. [ABSTRACT FROM AUTHOR]

Both enantiomers of 1‐(3,5‐bis(trifluoromethyl)phenyl)‐ethanol (BTPE) constitute important building‐blocks for the synthesis of active pharmaceuticals ingredients (APIs). The reduction of 3',5'‐bis(trifluoromethyl)acetophenone (BTAP) performed with soluble and immobilized ketoreductases (KREDs) can be considered as one of the most efficient routes to produce enantiopure BTPE. In the present work, a commercial KRED was employed as biocatalyst after undergoing immobilization processes and it proved to be extremely efficient in the asymmetric synthesis of (S)‐BTPE. The immobilization was studied on a set of different commercially available supports. The best results were obtained with samples immobilized via covalent interaction on short chain amino‐functionalized support. Two reaction parameters, temperature, and solvent were optimized in the biocatalytic reduction of BTAP in batch conditions. A 90 : 10 (v/v) 2‐propanol (IPA): water solvent system and 30 °C proved to be the best reaction conditions in terms of substrate conversion and easy recovery of the product by simple solvent evaporation. Biotransformations were then performed in a flow system under optimized reaction conditions obtaining with most samples complete conversion after 24 hours and excellent enantiomeric excess (>99.9 %). Finally, the reusability of the immobilized biocatalyst was successfully tested in five consecutive reaction cycles, demonstrating the potential of this approach. [ABSTRACT FROM AUTHOR]

To date, studies focusing on oral health in obese adolescents have provided controversial data. The aim of this cross-sectional study was to investigate systemic and oral health parameters in eutrophic and overweight/obese adolescents. In total, 100 adolescents, mean aged 13.33 ± 2.04 years, were divided into two groups: 59 overweight/obese adolescents in the study group (SG) and 41 eutrophic-weight adolescents in the control group (CG). Chi-squared and Fisher exact tests were performed to compare dichotomous and categorical variables between the two groups. The subjects in the SG (mean aged 13.21 ± 2.21) reported a body mass index (BMI) of 29.05 ± 4.09 kg/m2, corresponding to over 95° percentile for both genders, and the subjects in the CG (mean aged 13.49 ± 1.77) reported a BMI of 18.26 ± 4.81 kg/m2, corresponding to 25° percentile for both genders. In the SG, the serum level of 25-hydroxy-vitamin D was significantly lower (p-value < 0.001), whereas fasting blood glucose (p = 0.006), waist circumference, and hip circumference were significantly higher (p-value < 0.001). Plaque Index (PI), Plaque Control Record (PCR), Oral Hygiene Index (OHI), Gingival Index (GI), and Gingival bleeding index (GBI) depicted a significantly worse level of oral health in the SG. Moreover, the number of subjects with caries was significantly higher in the SG. Nutritional and physical activity status according to the Mediterranean Diet Quality Index for children and teenagers (KIDMED test) and the International Physical Activity Questionnaire (IPAQ-Adolescent) were reported to be significanlty better in the CG. In light of our results, obesity and poor oral health coexist in a cohort of adolescents. A screening of oral health status should be considered in obese subjects to focus resources on therapeutic interventions aiming at improving oral health. [ABSTRACT FROM AUTHOR]

In recent years, the immobilization of palladium nanoparticles on solid supports to prepare active and stable catalytic systems has been deeply investigated. Compared to inorganic materials, naturally occurring organic solids are inexpensive, available and abundant. Moreover, the surface of these solids is fully covered by chelating groups which can stabilize the metal nanoparticles. In the present review, we have focused our attention on natural biomaterials-supported metal catalysts applied to the formation of C–C bonds by Mizoroki–Heck, Suzuki–Miyaura and Sonogashira reactions. A systematic approach based on the nature of the organic matrix will be followed: (i) metal catalysts supported on cellulose; (ii) metal catalysts supported on starch; (iii) metal catalysts supported on pectin; (iv) metal catalysts supported on agarose; (v) metal catalysts supported on chitosan; (vi) metal catalysts supported on proteins and enzymes. We will emphasize the effective heterogeneity and recyclability of each catalyst, specifying which studies were carried out to evaluate these aspects. [ABSTRACT FROM AUTHOR]

Four racemic iminoflavan derivatives were synthesized by simple condensation at C‐4 position of flavanone. All new compounds were characterized by using ultraviolet‐visible, infrared, and nuclear magnetic resonance spectroscopic techniques. A chiral chromatographic analysis of racemic mixtures was performed by direct chiral high‐performance liquid chromatography using Chiralcel® OD‐H as chiral stationary phase, and online‐coupled with electronic circular dichroism detector. The correlation of experimental electronic circular dichroism traces with quantum chemical electronic circular dichroism calculations run with time‐dependent density functional theory made it possible to elucidate the absolute configuration for each enantiomer, and to establish the elution order. [ABSTRACT FROM AUTHOR]

Short stature is a frequent disorder in the pediatric population and can be caused by multiple factors. In the last few years, the introduction of Next Generation Sequencing (NGS) in the molecular diagnostic workflow led to the discovery of mutations in novel genes causing short stature including heterozygous mutations in ACAN gene. It encodes for aggrecan, a primary proteoglycan component specific for the structure of the cartilage growth plate, articular and intervertebral disc. We report a novel ACAN heterozygous pathogenic variant in a family with idiopathic short stature, early-onset osteoarthritis and osteoarthritis dissecans (SSOAOD). We also performed a literature review summarizing the clinical characteristic of ACAN 's patients. The probands are two Caucasian sisters with a family history of short stature and osteoarthritis dissecans. They showed dysmorphic features such as mild midface hypoplasia, brachydactyly and broad thumbs, especially the great toes. The same phenotype was presented in the mother who had had short stature and suffered from intervertebral disc disease. DNA sequencing identified a heterozygous pathogenic variation (c.4390delG p.Val1464Ter) in the sisters, with a maternal inheritance. The nonsense mutation, located on exon 12, results in premature truncation and presumed loss of protein function. In terms of treatment, our patients underwent recombinant human growth hormone replacement therapy, associated with gonadotropin releasing hormone therapy, in order to block early growth cessation and therefore reach a better final height. Our case suggests that SSOAOD ACAN related should be considered in the differential diagnosis of children with autosomal dominant short stature and family history of joints disease. [ABSTRACT FROM AUTHOR]

Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6–18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0–0.03) and during OGTT (ISI, 0.654 CI95%-0.11–1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. NCT03261466. [ABSTRACT FROM AUTHOR]

Summary: Context: The Gli‐family of zinc‐finger transcription factors regulates the Sonic Hedgehog (Shh) signalling pathway that plays a key role in early pituitary and ventral forebrain development. Heterozygous GLI2 loss of function mutations in humans have been reported in holoprosencephaly (HPE), HPE‐like phenotypes associated with pituitary anomalies and combined pituitary hormone deficiency with or without other extra‐pituitary findings. Objective: The aim of this study was the search for GLI2 mutations in a cohort of Italian CPHD patients and the assessment of a pathogenic role for the identified variants through in vitro studies. Patients: One hundred forty‐five unrelated CPHD patients diagnosed with or without extra‐pituitary manifestations were recruited from different Italian centres. Methods: The GLI2 mutation screening was carried out through direct sequencing of all the 13 exons and intron‐exon boundaries. Luciferase reporter assays were performed to evaluate the role of the detected missense variants. Results: Five different novel heterozygous non‐synonymous GLI2 variants were identified in five patients. The mutations were three missense (p.Pro386Leu, p.Tyr575His, p.Ala593Val), one frameshift (p.Val1111Glyfs*19) and one nonsense (p.Arg1226X). The latter two mutants are likely pathogenic since they lead to a truncated protein. The in vitro functional study of the plasmids bearing two of the three missense variants (namely p.Tyr575His and p.Ala593Val) revealed a significant reduction in transcriptional activity. Conclusion: In conclusion, the analysis of GLI2 in individuals with CPHD led to the identification of five variations with a likely negative impact on the GLI2 protein, confirming that GLI2 is an important causative gene in CPHD. The functional in vitro study analysis performed on the missense variations were useful to strengthen the hypothesis of pathogenicity. [ABSTRACT FROM AUTHOR]