"I am not pain, I have pain": A pilot study examining iRest yoga nidra as a mind-body intervention for persistent pain.

Purpose: This pilot study was the first of its kind to examine the experiences of people with persistent pain engaging in a six-week iRest for Pain group program as part of multidisciplinary pain care.

Method: The present study used a qualitative, phenomenological design and reflexive thematic analysis to gain an understanding of the firsthand experience of patients who participated in the iRest for Pain group program. This program was offered in a specialist outpatient pain management service within a regional public hospital in Victoria, Australia.

A Quantitative Trait Locus with a Major Effect on Root-Lesion Nematode Resistance in Barley.

Although the root-lesion nematode is known to affect barley ( L.), there have been no reports on the genetic control of resistance in barley. In this research, resistance was assessed for a panel of 46 barley mapping parents and for two mapping populations (Arapiles/Franklin and Denar/Baudin).

SAR studies toward discovery of emvododstat (PTC299), a potent dihydroorotate dehydrogenase (DHODH) inhibitor.

Dihydroorotate dehydrogenase (DHODH) is the enzyme that catalyzes a rate-determining step during the de novo synthesis of uridine, an important source of cellular pyrimidine nucleotides. Ability to modulate the activity of this enzyme may be used to control diseases associated with rapid, out-of-control cell growth in oncology, immunology, and virology. Emvododstat (PTC299) is a tetrahydro-β-carboline DHODH inhibitor discovered through the GEMS technology (Gene Expression Modulation by Small-Molecules).

Emvododstat, a Potent Dihydroorotate Dehydrogenase Inhibitor, Is Effective in Preclinical Models of Acute Myeloid Leukemia.

Blocking the pyrimidine nucleotide synthesis pathway by inhibiting dihydroorotate dehydrogenase (DHODH) results in the cell cycle arrest and/or differentiation of rapidly proliferating cells including activated lymphocytes, cancer cells, or virally infected cells. Emvododstat (PTC299) is an orally bioavailable small molecule that inhibits DHODH. We evaluated the potential for emvododstat to inhibit the progression of acute myeloid leukemia (AML) using several and models of the disease.

A QTL on the Ca7 chromosome of chickpea affects resistance to the root-lesion nematode .

Unlabelled: The root-lesion nematode Sher & Allen, 1953 is a damaging parasite of many crop plants, including the grain legume chickpea ( L.). Within cultivated chickpea, there are no known sources of strong resistance to , but some cultivars have partial resistance.

Radiotherapeutic Management of Synchronous Prostate and Rectal Cancers Using Proton Beam Therapy.

Treatment of synchronous prostate and rectal cancers is a rare yet challenging problem with compounded toxicities. We report a case of a 65-year-old man who underwent proton beam therapy (PBT) with concurrent capecitabine and hormonal therapy for his synchronously found prostate (intermediate-risk) and rectal (cT2, N2b, stage IIIB) cancers; he also received low anterior resection. Before PBT, the patient experienced hematochezia.

SMN protein is required throughout life to prevent spinal muscular atrophy disease progression.

Spinal muscular atrophy (SMA) is caused by the loss of the survival motor neuron 1 (SMN1) gene function. The related SMN2 gene partially compensates but produces insufficient levels of SMN protein due to alternative splicing of exon 7. Evrysdi™ (risdiplam), recently approved for the treatment of SMA, and related compounds promote exon 7 inclusion to generate full-length SMN2 mRNA and increase SMN protein levels.

Preclinical and Early Clinical Development of PTC596, a Novel Small-Molecule Tubulin-Binding Agent.

PTC596 is an investigational small-molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical anticancer activity, and its pharmacokinetic-pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma.

DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes.

Dihydroorotate dehydrogenase (DHODH) catalyzes a rate-limiting step in de novo pyrimidine nucleotide synthesis. DHODH inhibition has recently been recognized as a potential new approach for treating acute myeloid leukemia (AML) by inducing differentiation. We investigated the efficacy of PTC299, a novel DHODH inhibitor, for myelodysplastic syndrome (MDS).

The combination of the tubulin binding small molecule PTC596 and proteasome inhibitors suppresses the growth of myeloma cells.

The novel small molecule PTC596 inhibits microtubule polymerization and its clinical development has been initiated for some solid cancers. We herein investigated the preclinical efficacy of PTC596 alone and in combination with proteasome inhibitors in the treatment of multiple myeloma (MM). PTC596 inhibited the proliferation of MM cell lines as well as primary MM samples in vitro, and this was confirmed with MM cell lines in vivo.

The complete mitochondrial genome of .

Based on PacBio assembly, we report the first complete mitochondrial genome of (460,333 bp) containing nine large chloroplast-derived sequences (1.9-17.3 kb) across the mitogenome.

Chloroplast genome data of and and their phylogenetic relationships.

and are domesticated plants in the family Cucurbitaceae. They are mainly cultivated in the tropical and subtropical regions of Asia. The chloroplast genomes of many Cucurbitaceae species were sequenced to examine gene content and evolution.

Efficacy of the novel tubulin polymerization inhibitor PTC-028 for myelodysplastic syndrome.

Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors.

De novo assemblies of Luffa acutangula and Luffa cylindrica genomes reveal an expansion associated with substantial accumulation of transposable elements.

Luffa spp. (sponge gourd or ridge gourd) is an economically important vegetable crop widely cultivated in China, India and Southeast Asia. Here, we employed PacBio long-read single-molecule real-time (SMRT) sequencing to perform de novo genome assemblies of two commonly cultivated Luffa species, L.

Chemical modifications of G418 (geneticin): Synthesis of novel readthrough aminoglycosides results in an improved in vitro safety window but no improvements in vivo.

G418 is currently the most potent and active aminoglycoside to promote readthrough of eukaryotic nonsense mutations. However, owing to its toxicity G418 cannot be used in vivo to study readthrough activity A robust and scalable method for selective derivatization of G418 was developed to study the biological activity and toxicity of a series of analogs. Despite our synthetic efforts, an improvement in readthrough potency was not achieved.

Implementation of a Community Walking Program (Walk On!) for Functionally-Limited Older Adults.

Background: Walking interventions improve physical function, reduce fall risk, and prevent mobility disability-even in those with compromised walking ability. However, most prior studies have been conducted in controlled research settings, with no dissemination of an evidence-based walking program for older adults who have mobility limitations and/or are socially isolated.

Objectives: This study reports data on the feasibility and acceptability of a community-based walking program (Walk On!) for older adults who are functionally limited, and assesses changes in physical function among attendees.

Resistance of Wheat Genotypes to Root-Lesion Nematode () Can be Used to Predict Final Nematode Population Densities, Crop Greenness, and Grain Yield in the Field.

The root-lesion nematode is a major pathogen of wheat () in many regions globally. Resistance of wheat genotypes to can be determined from final nematode population densities in glasshouse experiments but combining results across multiple experiments presents challenges. Here, we use a factor analytic method for multiexperiment analysis of final population densities of for 1,096 unique wheat genotypes in 22 glasshouse experiments.

Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that is broadly chemoresistant, due in part to biophysical properties of tumor stroma, which serves as a barrier to drug delivery for most classical chemotherapeutic drugs. The goal of this work is to evaluate the preclinical efficacy and mechanisms of PTC596, a novel agent with potent anticancer properties and desirable pharmacologic properties . We assessed the pharmacology, mechanism, and preclinical efficacy of PTC596 in combination with standards of care, using multiple preclinical models of PDA.

Effect of an Energy-Restricted, Nutritionally Complete, Higher Protein Meal Plan on Body Composition and Mobility in Older Adults With Obesity: A Randomized Controlled Trial.

Background: Increasing protein content of the diet might be an effective strategy to preserve muscle mass in older adults undergoing caloric restriction, thereby preserving muscle function.

Methods: Ninety-six older adults (70.3 ± 3.

The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential.

Nonsense mutations, resulting in a premature stop codon in the open reading frame of mRNAs are responsible for thousands of inherited diseases. Readthrough of premature stop codons by small molecule drugs has emerged as a promising therapeutic approach to treat disorders resulting from premature termination of translation. The aminoglycoside antibiotics are a class of molecule known to promote readthrough at premature termination codons.

Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties.

PTC299 was identified as an inhibitor of VEGFA mRNA translation in a phenotypic screen and evaluated in the clinic for treatment of solid tumors. To guide precision cancer treatment, we performed extensive biological characterization of the activity of PTC299 and demonstrated that inhibition of VEGF production and cell proliferation by PTC299 is linked to a decrease in uridine nucleotides by targeting dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme for pyrimidine nucleotide synthesis. Unlike previously reported DHODH inhibitors that were identified using enzyme assays, PTC299 is a more potent inhibitor of DHODH in isolated mitochondria suggesting that mitochondrial membrane lipid engagement in the DHODH conformation is required for its optimal activity.