EClinicalMedicine
August 2024
Background: Prior data indicate limited ethnoracial diversity in studies testing psychedelic-assisted treatments. Regulatory approval for psychedelic treatments may be imminent given growing evidence for safety and efficacy in a variety of psychiatric conditions. Data on racial and ethnic inclusion rates in clinical psychedelic studies since 2018 have not been systematically reported to date.
View Article and Find Full Text PDFBackground: Prior studies have failed to show differences in functional outcomes for patient-reported sling use after rotator cuff repair. Temperature-sensing devices are used to more accurately measure brace adherence. The purposes of this study were to quantify actual sling adherence and its predictors and to establish whether increased sling adherence is associated with improved functional and image-based outcomes.
View Article and Find Full Text PDFBackground: Perioperative education and socioeconomic factors influence patient behavior. Recent evidence has suggested that sling compliance is associated with improved outcomes after shoulder surgery; it is important to investigate factors that influence sling compliance.
Purpose: To determine the associations between postoperative sling wear and patients' understanding of sling necessity, postoperative home assistance, and social deprivation.
Fibroadipogenic progenitor (FAP) cells are implicated as a major source of fatty infiltration (FI) in murine rotator cuff (RC) injury, but FAP cell response after RC tear in a rabbit model is unknown. This study determined whether changes in FAP cell count after an RC tear predate muscle degeneration in a clinically relevant rabbit model. We hypothesized increases in FAP cell count correlate temporally with RC degeneration.
View Article and Find Full Text PDFThe downregulation of sclerostin in osteocytes mediates bone formation in response to mechanical cues and parathyroid hormone (PTH). To date, the regulation of sclerostin has been attributed exclusively to the transcriptional downregulation of the gene hours after stimulation. Using mouse models and rodent cell lines, we describe the rapid, minute-scale post-translational degradation of sclerostin protein by the lysosome following mechanical load and PTH.
View Article and Find Full Text PDFBack in 2003, we published 'MAX' randomization, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. 'MAX' randomization saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an α-helix, as in zinc-finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple contiguous codons in a non-degenerate manner.
View Article and Find Full Text PDFBackground: Traditional perinatal practices may protect against postnatal common mental disorders (CMD) in non-Western societies.
Aims: To evaluate the association between perinatal practices and postnatal CMD in rural Ethiopia.
Method: A population-based sample of 1065 women was followed up from pregnancy until 2 months postpartum.
Background: Although maternal common mental disorder (CMD) appears to be a risk factor for infant undernutrition in South Asian countries, the position in sub-Saharan Africa (SSA) is unclear
Methods: A population-based cohort of 1065 women, in the third trimester of pregnancy, was identified from the demographic surveillance site (DSS) in Butajira, to investigate the effect of maternal CMD on infant undernutrition in a predominantly rural Ethiopian population. Participants were interviewed at recruitment and at two months post-partum. Maternal CMD was measured using the locally validated Self-Reported Questionnaire (score of > or = six indicating high levels of CMD).
A dual-peak LPFG (long-period fibre grating), inscribed in an optical fibre, has been employed to sense DNA hybridization in real time, over a 1 h period. One strand of the DNA was immobilized on the fibre, while the other was free in solution. After hybridization, the fibre was stripped and repeated detection of hybridization was achieved, so demonstrating reusability of the device.
View Article and Find Full Text PDFObjectives: To examine the impact of antenatal psychosocial stressors, including maternal common mental disorders (CMD), upon low birth weight, stillbirth and neonatal mortality, and other perinatal outcomes in rural Ethiopia.
Methods: A population-based sample of 1065 pregnant women was assessed for symptoms of antenatal CMD (Self-Reporting Questionnaire-20: SRQ-20), stressful life events during pregnancy (List of Threatening Experiences: LTE) and worry about the forthcoming delivery. In a sub-sample of 654 women from six rural sub-districts, neonatal birth weight was measured on 521 (79.
Nuclear transfer stem cells hold considerable promise in the field of regenerative medicine and cell-based drug discovery. In this study, a total of 29 oocytes were obtained from three young (20-24 years old) reproductive egg donors who had been successful in previous cycles. These oocytes, deemed by intended parents to be in excess of their reproductive needs, were donated for research without financial compensation by both the egg donor and intended parents after receiving informed consent.
View Article and Find Full Text PDFBackground: The cultural validity of instruments to detect perinatal common mental disorders (CMD) in rural, community settings has been little-investigated in developing countries.
Methods: Semantic, content, technical, criterion and construct validity of the Edinburgh Postnatal Depression Scale (EPDS) and Self-Reporting Questionnaire (SRQ) were evaluated in perinatal women in rural Ethiopia. Gold-standard measure of CMD was psychiatric assessment using the Comprehensive Psychopathological Rating Scale (CPRS).
Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability.
View Article and Find Full Text PDFWe have successfully linked protein library screening directly with the identification of active proteins, without the need for individual purification, display technologies or physical linkage between the protein and its encoding sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping gene libraries that encode zinc finger proteins, randomized variously at the three principal DNA-contacting residues. Expression and screening of the libraries against five possible target DNA sequences generated data points covering a potential 40,000 individual interactions.
View Article and Find Full Text PDFImpaired infant growth, a major problem in South Asia, may require interventions to improve maternal mental health in addition to current interventions targeting infant nutrition
View Article and Find Full Text PDFA simple protein-DNA interaction analysis has been developed using both a high-affinity/high-specificity zinc finger protein and a low-specificity zinc finger protein with nonspecific DNA binding capability. The latter protein is designed to mimic background binding by proteins generated in randomized or shuffled gene libraries. In essence, DNA is immobilized onto the surface of microplate wells via streptavidin capture, and green fluorescent protein (GFP)-labeled protein is added in solution as part of a crude cell lysate or protein mixture.
View Article and Find Full Text PDFScanning oligodeoxynucleotide (ODN) arrays appear promising in vitro tools for the prediction of effective antisense reagents but their usefulness has not yet been reported in mammalian systems. In this study, we have evaluated the use of scanning ODN arrays to predict efficacious antisense ODNs targeting the human epidermal growth factor receptor (EGFR) mRNA in a human epidermoid cancer cell line and in primary human glioma cells. Hybridisation accessibility profile of the first 120nt in the coding region of the human EGFR mRNA was determined by hybridising a radiolabelled EGFR transcript to a scanning array of 2684 antisense sequences ranging from monomers to 27-mers.
View Article and Find Full Text PDFAmino acid substitution plays a vital role in both the molecular engineering of proteins and analysis of structure-activity relationships. High-throughput substitution is achieved by codon randomisation, which generates a library of mutants (a randomised gene library) in a single experiment. For full randomisation, key codons are typically replaced with NNN (64 sequences) or NN(G)(CorT) (32 sequences).
View Article and Find Full Text PDFAntisense oligonucleotides (AODNs) can selectively inhibit oncogene expression by Watson-Crick hybridisation to target mRNA and are being increasingly considered for use in combination with conventional drugs for potential anticancer therapy. Combination therapy of AODNs and cytotoxic agents using biodegradable polymeric delivery systems potentially offers several advantages including site-specific or organ-directed targeting, protection from digesting enzymes, and improved pharmacokinetics/pharmacodynamics resulting from sustained delivery of the entrapped drugs. Using a model AODN targeting the epidermal growth factor receptor (that is over-expressed in several cancers including breast and brain cancer) and the commonly used cytotoxic agent, 5-fluorouracil (5-FU), we have examined the use of poly (lactide-co-glycolide) (P(LA-GA)) microsphere formulations for co-delivery of these agents.
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