The longitudinal dispositions of people diagnosed with adjustment or severe stress disorders.

BACKGROUND: Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that gap, the present article documents the service use and diagnostic outcomes of people with adjustment or stress-related disorders presenting at Singapore's largest psychiatric emergency department. METHODS: Administrative data from 2014 to 2021 was retrieved to follow a group of 683 service users whose first-ever psychiatric presentation in 2014 warranted a diagnosis of adjustment or stress-related disorder. People were grouped a priori depending on whether different diagnoses were recorded within 7 days, 9 months, after 9 months or not at all. Survival curves characterized conversion to other diagnoses and engagement with healthcare services. Service use outcomes include the number of hospitalizations, outpatient appointments, emergency department visits, and prescriptions. RESULTS: Sixty-one percent (n = 417) never received another diagnosis over the 8-year period. This group used emergency services most and received the most pharmacotherapy shortly after their first visit. Of those who received another diagnosis, depression, personality disorders, and psychotic disorders were the most common. Those who received another diagnosis within 7 days (n = 70, 10%) received it on their first day of hospitalization (IQR 1-1), making the most use of inpatient services. The group who received another diagnosis within 9 months (n = 105, 15%) did so after 42 days (IQR 26-84) and had the highest relative number of deaths. Those who received another diagnosis after 9 months (n = 91, 13%) did so after 1,134 days (IQR 613-1,823) and had the longest period of engagement but made the least use of any psychiatric service, potentially suggesting a group whose early index diagnosis heralded vulnerability to future disorders. CONCLUSIONS: A large group of service users with acute stress or adjustment disorders will likely never be given another psychiatric diagnosis and appear to disengage following an initial period of high-intensity service use. The group that received a different diagnosis after the 9-month mark had prolonged contact with services but low intensity of service use and may represent a target for preventative intervention to help them improve their stress-managing skills and avoid developing other disorders.

Intramedullary nail: the past, present and the future - a review exploring where the future may lead us.

BACKGROUND: Intramedullary nails (IMNs) are the current gold standard treatment for long bone diaphyseal and selected metaphyseal fractures. The design of IMNs has undergone many revisions since its invention in the 16th century, with a dramatic increase in novel designs in recent years aiming to further improve intramedullary fixation techniques. AIMS: To map the evolution of IMNs in orthopedic surgery, discuss the limitations and complications of current IMNs and identify novel IMNs that may influence future design innovations. METHODS: We undertook a scoping review on the status of orthopedic IMNs by reviewing Google Scholar with the following keywords. Publications and patents selected for retrieval were initially assessed on the title and abstract by five independent reviewers. 52 papers were retrieved for complete text examination, and secondary references were checked from these papers. The results were discussed within the research group and consensus was obtained describing novel IMNs. RESULTS: Novel IMN designs include growth factor and/or antimicrobial coatings targeting fracture healing and perioperative infection risk, respectively; minimally invasive expandable IMNs to avoid the need for interlocking screws; and novel materials such as carbon fiber for their theoretically superior biomechanical properties and avoidance of artifact on CT and MRI imaging. CONCLUSION: The novel IMNs proposed in recent years collectively aim to improve intramedullary fixation techniques by reducing operative time and radiation exposure, improving fracture healing or monitoring bone cancer progression. However, more research and development are necessary to solve these complex problems.

Potential role of ZEB1 as a DNA repair regulator in colorectal cancer cells revealed by cancer-associated promoter profiling.

Besides being a key contributor to epithelial­to­mesenchymal transition (EMT) activation and stemness maintenance, zinc finger E-box binding homeobox 1 (ZEB1) is also a crucial inducer of chemoresistance and radioresistance. Unlike the clear mechanism that mediates its effect on EMT and dedifferentiation, the mechanism of how ZEB1 promotes chemo- and radio-resistance remains to be elucidated. It has been previously reported that ZEB1 promotes DNA double-strand break clearance by enhancing the deubiquitylating activity of ubiquitin-specific peptidase (USP)7 on checkpoint kinase 1, which is an important step during DNA repair. It was hypothesized that as a transcriptional suppressor, ZEB1 may be involved in an unbalanced DNA damage response (DDR) by affecting other key components. Therefore, in the present study, the target gene occupancy of ZEB1 was mapped in colorectal cancer cells using the ChIP-on-chip method, revealing positive intervals enriched along the three DDR-associated genes: USP17, chromodomain helicase DNA-binding protein 1-like and double homeobox 4. The E-boxes identified in the binding regions and the enhanced mRNA expression of the three genes following the knockdown of ZEB1 supported the identification of these three genes as downstream target genes of ZEB1. Furthermore, ZEB1 knockdown initiated a chemosensitization effect, induced G1/S arrest and increased apoptosis, which functionally validated the three ZEB1 downstream targets. In summary, the present study identified three DDR-associated genes as ZEB1 downstream targets, and demonstrated that their suppression by ZEB1 contributes to ZEB1-mediated chemoresistance.