Rejected

Limited knowledge exists regarding sex differences in prescribing potentially inappropriate medications (PIMs) for various multimorbidity patterns. This study sought to determine sex differences in PIM prescribing in older adults with cardiovascular-metabolic patterns.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a powerful class of inhibitors targeting two isoforms of the family of cyclooxygenase enzymes (COX-1, COX-2). While NSAIDs are widely used in the management of pain, in particular as a treatment for osteo- and rheumatoid arthritis, their long-term use has associated with numerous on- and off-target effects. As the carboxylic acid moiety present in common NSAIDs is responsible for some of their adverse effects, but is not required for their anti-inflammatory activity, we sought to mask this group through direct coupling to glucosamine, which is thought to prevent cartilage degradation. We report herein the conjugation of commonly prescribed NSAIDs to glucosamine hydrochloride and the use of molecular docking to show that addition of the carbohydrate moiety to the parent NSAID can enhance binding in the active site of COX-2. In a preliminary, in vitro screening assay, the diclofenac-glucosamine bioconjugate exhibited 10-fold greater activity towards COX-2, making it an ideal candidate for future in vivo studies. Furthermore, in an intriguing result, we observed that the mefenamic-acid-glucosamine bioconjugate displayed enhanced activity towards COX-1 rather than COX-2.

A 64-year-old man was referred to A&E by his general practitioner with worsening back and acute bilateral leg pain and weakness with urinary retention. His MRI scan demonstrated spinal canal stenosis at the level of L1-L2 and a diagnosis of cauda equina syndrome (CES) was made. CES is a rare neurological condition caused by compression of the central spinal nerves at the termination of the cord. CES is a surgical emergency requiring urgent assessment and treatment. The patient underwent urgent surgical decompression; however, he required a second surgery for further decompression as repeat MRI showed persistent stenosis with further extension. Intraoperative Doppler ultrasonography revealed an intradural lesion, which was surgically excised and found to be a sequestrated lumbar disc in the intrathecal space. The patient showed significant neurological improvement post revision decompression.

The Rotterdam Elderly Pain Observation Scale (REPOS) has not yet been validated for institutionalised cognitively impaired adults. To fill this gap of knowledge, we tested psychometric properties of the REPOS when used for pain assessment in this population.

The aim of this study is to evaluate the effects of successful revision operation on health quality of life(QoL) and functional outcome in humeral nonunion patients.

Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life.

Long pentraxin PTX3, a pattern recognition molecule involved in innate immune responses, is upregulated by pro-inflammatory stimuli, contributors to secondary damage in traumatic brain injury (TBI). We analyzed PTX3 involvement in mice subjected to controlled cortical impact, a clinically relevant TBI mouse model. We measured PTX3 mRNA and protein in the brain and its circulating levels at different time point post-injury, and assessed behavioral deficits and brain damage progression in PTX3 KO mice. PTX3 circulating levels significantly increased 1-3 weeks after injury. In the brain, PTX3 mRNA was upregulated in different brain areas starting from 24 h and up to 5 weeks post-injury. PTX3 protein significantly increased in the brain cortex up to 3 weeks post-injury. Immunohistochemical analysis showed that, 48 h after TBI, PTX3 was localized in proximity of neutrophils, likely on neutrophils extracellular traps (NETs), while 1- and 2- weeks post-injury PTX3 co-localized with fibrin deposits. Genetic depletion of PTX3 did not affect sensorimotor deficits up to 5 weeks post-injury. At this time-point lesion volume and neuronal count, axonal damage, collagen deposition, astrogliosis, microglia activation and phagocytosis were not different in KO compared to WT mice. Members of the long pentraxin family, neuronal pentraxin 1 (nPTX1) and pentraxin 4 (PTX4) were also over-expressed in the traumatized brain, but not neuronal pentraxin 2 (nPTX2) or short pentraxins C-reactive protein (CRP) and serum amyloid P-component (SAP). The long-lasting pattern of activation of PTX3 in brain and blood supports its specific involvement in TBI. The lack of a clear-cut phenotype in PTX3 KO mice may depend on the different roles of this protein, possibly involved in inflammation early after injury and in repair processes later on, suggesting distinct functions in acute phases versus sub-acute or chronic phases. Brain long pentraxins, such as PTX4-shown here to be overexpressed in the brain after TBI-may compensate for PTX3 absence.