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Spinal Muscular Atrophy (SMA) Type II is a neurodegenerative disease that leads to progressive muscle weakness. It prevents children from walking and affects their respiratory function and their activity tolerance, among other health problems. We aimed to assess the activity tolerance showed by a child with SMA using a pediatric gait exoskeleton at home when walking and performing activities.This study presents the case of a 6-year-old boy with SMA Type II and respiratory failure who used a pediatric gait exoskeleton at home for a period of two months. A nursing assessment was done before and during the use of the device to evaluate the child's activity tolerance during the sessions. Nursing interviews, performance, vital signs, fatigue, field notes, and functional scales were analyzed.The nursing assessment showed a good activity tolerance of the child. Performance using the device improved over time; vital signs did not vary significantly during the sessions; fatigue perception decreased over time; and the child reached a higher score on some functional outcomes.A first step has been taken to evaluate the impact of exoskeleton technology in children with SMA Type II from the nursing point of view, exposing the potential of this technology for the care of children with neuromuscular diseases, and the need for more research on the topic.The information in this study will be useful to nurses to know the effects of gait exoskeletons in pediatric care of children with neuromuscular diseases like SMA.

BACKGROUND: Cerebral Palsy (CP) and Spinal Muscular Atrophy (SMA) are common causes of motor disability in childhood. Gait exoskeletons are currently being used as part of rehabilitation for children with walking difficulties. OBJECTIVE: To assess the safety and efficacy and describe the main characteristics of the clinical articles using robot-assisted gait training (RAGT) with exoskeleton for children with CP or SMA. METHODS: A computer search was conducted in five bibliographic databases regarding clinical studies published in the last ten years. In order to be included in this review for further analysis, the studies had to meet the following criteria: (1) assess efficacy or safety of interventions; (2) population had to be children with CP or SMA aged between 3 and 14; (3) exoskeleton must be bilateral and assist lower limbs during walking. RESULTS: Twenty-one articles were selected, of which only five were clinical trials. 108 participants met the inclusion criteria for this study, all with a diagnosis of CP. The evidence level of the selected papers was commonly low. CONCLUSIONS: RAGT therapy seems to be safe for children with CP. However, further investigation is needed to confirm the results related to efficacy. There is no evidence of RAGT therapy for SMA children.

The structures of five linear lipopeptides, thaxteramides A1, A2, B1, B2, and C isolated from the myxobacterium Jahnella thaxteri, were elucidated. They have a C-terminal common tetrapeptidic Tyr-Gly-β-Ala-Tyr core but differ in the stereochemistry of the tyrosine units, methylations, the remaining amino acids, and the N-terminal polyketide. In silico analysis of the genome sequence complemented with feeding experiments revealed two distinct hybrid PKS/NRPS gene clusters. Three semisynthesized cyclic analogues were found to inhibit the growth of Gram-positive bacteria.

Preparations of comfrey (Symphytum officinale L.) roots are used topically to reduce inflammation. Comfrey anti-inflammatory and analgesic properties have been proven in clinical studies. However, the bioactive compounds associated with these therapeutic activities are yet to be identified. An LC&ndash, ESI&ndash, Orbitrap&ndash, MSn metabolite profile of a hydroalcoholic extract of comfrey root guided the identification of 20 compounds, including a new arylnaphthalene lignan bearing a rare &delta, lactone ring, named comfreyn A. Its structure was determined using extensive 2D NMR and ESI&ndash, MS experiments. Additionally, the occurrence of malaxinic acid, caffeic acid ethyl ester, along with the lignans ternifoliuslignan D, 3-carboxy-6,7-dihydroxy-1-(3&prime, 4&prime, dihydroxyphenyl) -naphthalene, globoidnan A and B, and rabdosiin was reported in S. officinale for the first time. These results helped to redefine the metabolite profile of this medicinal plant. Finally, caffeic acid ethyl ester and comfreyn A were found to significantly inhibit E-selectin expression in IL-1&beta, stimulated human umbilical vein endothelial cells (HUVEC), with EC values of 64 and 50 &micro, M, respectively.

In our screening efforts to identify unique scaffolds from myxobacteria for the drug discovery process, we used LC-SPE-NMR-MS techniques to isolate six linear peptides, termed macyranone A-F, from Cystobacter fuscus MCy9118. The macyranones are characterized by a rare 2-methylmalonamide moiety and an α-amino ketone fragment including an α',β'-epoxyketone in macyranone A. Gene disruption experiments confirmed the biosynthetic gene cluster of the macyranones as PKS/NRPS hybrid. Detailed in silico and phylogenetic analysis unraveled that the biosynthesis involves two conspicuous amide bond formations accomplished by an amidotransferase and a unique condensation domain. The gene cluster provides further insights into the formation of the powerful epoxyketone residue involving an acyl-CoA dehydrogenase and an unconventional free-standing thioesterase. Macyranone A was found to inhibit the chymotrypsin-like activity of the yeast 20S proteasome with an IC50 of 5.9 nM and the human constitutive proteasome and immunoproteasome with IC50 values of 21 and 15 nM, respectively. The β5 subunit of the 20S proteasome was characterized as target by X-ray crystallography revealing an irreversible binding mode similar to the natural product epoxomicin. The presence of the methylmalonamide residue facilitates the stabilization of macyranone A with the active β5 subunit of the proteasome. Macyranone A exhibits a potent inhibitory effect against the parasites Trypanosoma brucei rhodesiense and Leishmania donovani with IC50 values of 1.55 and 0.22 μM, respectively.

Cloning and engineering of natural product biosynthetic pathways followed by heterologous expression in a tractable host is a widely used approach for expression and genetic modification of microbial secondary metabolites. Herein, we employed ccdB counterselection combined with oligonucleotide-mediated recombineering to efficiently create point mutations in a complex nonribosomal peptide synthetase (NRPS) from Photorabdus luminescens directing the biosynthesis of luminmides. After in depth analysis of the luminmide production profile from the native NRPS, single and double point mutations were rationally constructed within the adenylation (A) domain from NRPS module 3 which turned out to have a broad substrate tolerance. Expression of mutated versions of the 15.6 kb NRPS gene plu3263 in E. coli led to alterations in luminmide production profiles and allowed to direct the biosynthesis towards certain derivatives. These results demonstrate the suitability of counterselection recombineering for site-directed mutagenesis of complex expression constructs, e.g., genes encoding NRPS biosynthetic pathways in multi-copy plasmids.

Colibactin represents a structurally undefined class of bacterial genotoxin inducing DNA damage and genomic instability in mammalian cells, thus promoting tumour development and exacerbating lymphopenia in animal models. The colibactin biosynthetic gene cluster (clb) has been known for ten years and it encodes a hybrid nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly line. Nevertheless, the final chemical product(s) remain unknown. Previously, we and others reported several colibactin pathway-related metabolites including N-myristoyl-D-asparagine (1) as part of a prodrug precursor that is cleaved from the putative precolibactin to form active colibactin by the peptidase ClbP. Herein, we report two new colibactin pathway-related metabolites (2 and 3) isolated from a clbP mutant of the probiotic E. coli Nissle 1917 strain. Their structures were established by HRMS and NMR. Compound 2 shows an additional 4-aminopenatanoic acid moiety with respect to 1, while 3 is characterized by the presence of an unusual 7-methyl-4-azaspiro[2.4]hept-6-en-5-one residue. Moreover, we propose the biosynthetic pathway towards both intermediates on the basis of extensive gene inactivation and feeding experiments. The identification of 2 and 3 provides further insight into colibactin biosynthesis including the involvement and formation of a rare 1-aminocyclopropanecarboxylic acid unit. Thus, our work establishes additional steps of the pathway forming the bacterial genotoxin colibactin.

Three new siderophores, termed hyalachelins A-C (1-3), were isolated from the terrestrial myxobacterium Hyalangium minutum. Their structures were determined by 2D NMR and HR-MS/MS experiments, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and circular dichroism experiments. Hyalachelins are unusual catecholate-type siderophores that bear a 3,7,8-trihydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid. Their iron chelating activities were evaluated in a CAS assay showing EC50 values of ∼30 μM.

A new linear polyketide, juniperolide A (1), was produced by the terrestrial actinomycete (Lv1-48) isolated from the rhizosphere of the plant Juniperus excelsa. The juniperolide A (1) structure contains a THP unit and a 3-amino-2,3,6-trideoxyhexose as the glycosidic moiety. Mosher's analysis was used for absolute stereochemistry determinations at C-2, C-8, C-20, and C-4', while the relative stereochemistry assignments of the remaining stereocenters were based on ROESY correlations and J-based coupling.

A new sulfated cyclic depsipeptide, termed mutremdamide A, and six new highly N-methylated peptides, termed koshikamides C-H, were isolated from different deep-water specimens of Theonella swinhoei and Theonella cupola. Their structures were determined using extensive 2D NMR, ESI, or CDESI and QTOF-MS/MS experiments and absolute configurations established by quantum mechanical calculations, advanced Marfey's method, and chiral HPLC. Mutremdamide A displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid and a new N(delta)-carbamoyl-beta-sulfated asparagine. Koshikamides C-E are linear undecapeptides, and koshikamides F-H are 17-residue depsipeptides containing a 10-residue macrolactone. Koshikamides F and G differ from B and H in part by the presence of the conjugated unit 2-(3-amino-5-oxopyrrolidin-2-ylidene)propanoic acid. Cyclic koshikamides F and H inhibited HIV-1 entry at low micromolar concentrations while their linear counterparts were inactive. The Theonella collections studied here are distinguished by co-occurrence of mutremdamide A, koshikamides, and theonellamides, the combination of which appears to define a new Theonella chemotype that can be found in deeper waters.

We assessed in vivo the anti-inflammatory activity of two Cat's claw bark extracts, by comparing a spray-dried hydroalcoholic extract against an aqueous freeze-dried extract, to determine which extract was more effective. We used the carrageenan-induced paw edema model in mice. In addition, to assess the molecular mechanism of action, we determined the inhibition of NF-kappa B through the Electrophoretic Mobility Shift Assay (EMSA) and the effects on cycloxygenase-1 and -2. Results showed that the anti-inflammatory activity was significantly higher using the hydroalcoholic compared with the aqueous extract (P

Seven new antibacterials, motualevic acids A-F (1-6) and (4E)-(R)-antazirine (7), have been isolated from the marine sponge Siliquariaspongia sp. and their structures elucidated by spectroscopic methods. Motualevic acids A-D are the first glycyl conjugates of the omega-brominated lipid (E)-14,14-dibromotetradeca-2,13-dienoic acid, and motualevic acid F is the first long-chain 2H-azirine 2-carboxylic acid to be found in nature. Carboxylic acid-containing compounds 1 and 6 inhibit the growth of Staphylococcus aureus and methicillin-resistant S. aureus at 1.2-10.9 microg/mL.