An unusually rapid Claisen rearrangement involving ring expansion

A Claisen rearrangement of a partially-fluorinated system involving ring expansion occurred at an unusually low temperature, 100 degreesC lower than a comparable system from the literature

Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo

Methods for measuring gut microbiota biochemical activities in vivo are needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was isolated from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced \u27Microbiota Functional Activity Biosensors\u27 (MFABs) consisting of glycans covalently linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhanced in vivo degradation of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods

Forearm Fracture Nonunion with and without Bone Loss: An Overview of Adult and Child Populations

Nonunion occurs in 2–10% of all forearm fractures due to different mechanical and biological factors, patient characteristics, and surgeon-dependent causes. It is a condition that causes functional and psychosocial disability for the patient because it is a unique anatomical segment in which all the bones and structures involved embody a complex functional unit; therefore, it is a challenge for the orthopedic surgeon. The ultimate goal of the care of these patients is the restoration of function and limitations related to impairment and disability. The aim of this review is to provide an extended description of nonunion forearm fractures, related risk factors, diagnosis, classification systems, and the available evidence for different types of treatment as a tool to better manage this pathology

Conservative Treatment of Chronic Achilles Tendinopathy: A Systematic Review

Achilles tendinopathy is a common musculoskeletal disorder. Athletes, runners and jumpers, and the sedentary are frequently affected. Numerous are the therapeutic choices to manage these kinds of disorders. The aim of this review is to analyze the available literature to document the up-to-date evidence on conservative management of Achilles tendinopathy. A systematic review of two medical electronic databases was performed by three independent authors, using the following inclusion criteria: conservative treatment consisted of pharmacologic, physical therapy without operative treatment, with more of 6 months symptoms and a minimum average of 6-months follow-up. Studies of any level of evidence, reporting clinical results, and dealing with Achilles tendinopathy and conservative treatment were searched for. A total of n = 1228 articles were found. At the end of the first screening, following the previously described selection criteria, we selected n = 94 articles eligible for full-text reading. Ultimately, after full-text reading and a reference list check, we selected n = 29 articles. Achilles tendinopathy is a frequent musculoskeletal disorder and several conservative treatments have been proposed, but no therapy is universally accepted, except for eccentric exercise training, which is the gold standard and a commonly used protocol

Is Supine Position Superior to Prone Position in the Surgical Pinning of Supracondylar Humerus Fracture in Children?

Background: Supracondylar humerus fracture (SCHF) is a frequent injury in pediatric ages. Closed reduction and percutaneous pin fixation is a common treatment of displaced SCHF. Surgery is usually performed in the supine position; otherwise the prone position allows an easier fracture reduction and a safe placement of pins. The aim of study is to compare the clinical and radiographic results of the treatment of displaced SCHF, comparing two different intra-operative positionings. Methods: 59 SCHF affected children were retrospectively divided into supine (Group 1; n = 34) and prone (Group 2; n = 25), according to intraoperative position. All treated subjects were clinically evaluated according to Flynn’s criteria and Mayo Elbow Performance Score, and radiographically, including the measurement of the Baumann angle. Results: Clinically, Group 1, according Flynn’s criteria, had excellent cosmetic outcome in 32 subjects (94.1%). Mean MAYO Score was 96.0 ± 3.8. Group 2, according Flynn’s criteria, had excellent cosmetic outcomes in 23 subjects (92.0%). Mean MAYO Score was 97.8 ± 3.3. Radiographically, mean difference of Baumann’s angle between the injured limb and the normal limb was 5.5° ± 1.0° in Group 1 and 5.1° ± 1.1° in Group 2. Conclusion: Both supine and prone positioning achieved a satisfying outcome with similar results in joint function recovery and complications

Oxy-Cope rearrangements of fluorinated divinylcyclohexanols: a modular method for the construction of selectively fluorinated cyclic ketones

Oxy-Cope rearrangements of fluorinated divinylcyclohexanols afford access to cyclodecenones containing from two to five fluorine atoms

Syntheses of selectively fluorinated cyclodecenones: the first deployment of the neutral oxy-Cope rearrangement in organofluorine chemistry

Metallated haloalkenes were used to open epoxides in moderate to good yield. The homoallylic alcohols obtained underwent Swern oxidation to afford three ??-difluorinated ?,?-enones, which reacted with either vinyllithium, 2-lithio-2H-dihydropyran or another metallated haloalkene to afford substituted trans-1,2-divinylcyclohexanols of different degrees of stability. These intermediates underwent neutral thermal oxy-Cope rearrangements when heated in xylene in Ace(R) tubes. The first-formed enols ketonised without loss of HF to afford a range of cyclodecenones in moderate to good yield; X-ray crystallography was used extensively for product characterisation. All substrates rearranged more rapidly than a cis/trans mixture of 1,2-divinylcyclohexanols

Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Introduction: The Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with âMental Retardation Autosomal Dominant 57' (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies. Methods: We re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and single-cell gel electrophoresis, we investigated the proximity interaction landscape of TLK2 and analysed the effects of p.(Asp551Gly) and a previously reported missense variant (c.1850C>T; p.(Ser617Leu)) on TLK2 interactions, localisation and activity. Results: We identified three new unrelated MRD57 families. Two were sporadic and caused by a missense change (c.1652A>G; p.(Asp551Gly)) or a 39 kb deletion encompassing TLK2, and one was familial with three affected siblings who inherited a nonsense change from an affected mother (c.1423G>T; p.(Glu475Ter)). The clinical phenotypes were consistent with those of previously reported cases. The tested mutations strongly impaired TLK2 kinase activity. Proximal interactions between TLK2 and other factors implicated in neurological disorders, including CHD7, CHD8, BRD4 and NACC1, were identified. Finally, we demonstrated a more relaxed chromatin state in lymphoblastoid cells harbouring the p.(Asp551Gly) variant compared with control cells, conferring susceptibility to DNA damage. Conclusion: Our study identified novel TLK2 pathogenic variants, confirming and further expanding the MRD57-related phenotype. The molecular characterisation of missense variants increases our knowledge about TLK2 function and provides new insights into its role in neurodevelopmental disorders