Rejected

Back pain is a prevalent health problem. Research often focuses on adults. Evidence on the long-term course of back pain in older patients is limited. A prospective cohort study (BACE) was conducted in a primary care setting in the Netherlands. We aim to investigate the 5-year course and medical consumption of older adults (>55 years) presenting with back pain in general practice.

The purpose of our study was to compare magnetic resonance arthrography (MRA) as a diagnostic modality against the gold standard of wrist arthroscopy in the evaluation of chronic wrist pain.

Trigeminal neuralgia (TN) is a common cranial nerve disease. Inflammation is suggested in many recent studies to be involved in neuropathic pain, but its role in TN remains unclear so far. Therefore, the current study aimed to explore the relationship of inflammation with TN.

Opioids are commonly used after posterior spinal instrumented fusion (PSIF) for adolescent idiopathic scoliosis (AIS). Prescription opioids use can potentially lead to misuse, abuse, dependence, and overdose death. Prolonged opioid use has not been extensively studied in the postoperative AIS population. The purpose of this study is to identify risk factors associated with prolonged opioid use after PSIF for AIS.

The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

Studies with non-human primates have suggested an excitatory influence of the thalamus on the cerebral cortex, with the centromedian-parafascicular complex (CM-Pf) being particularly involved in processes of sensory event-driven attention and arousal. To define the involvement of the human CM-Pf in bottom-up and top-down auditory attention, we simultaneously recorded cortical EEG activity and intracranial local field potentials (LFPs) via electrodes implanted for deep brain stimulation for the treatment of neuropathic pain. The patients (N = 6) performed an auditory three-class oddball paradigm with frequent standard stimuli and two types of infrequent deviant stimuli (target and distractor). We found a parietal P3b to targets and a central P3a to distractors at the scalp level. Subcortical recordings in the CM-Pf revealed enhanced activation to targets compared to standards. Interarea-correlation analyses showed that activation in the CM-Pf predicted the generation of longer latency P3b scalp potentials specifically in the target condition. Our results provide first direct human evidence for a functional temporal relationship between target-related activation in the CM-Pf and an enhanced cortical target response. These results corroborate the hypothetical model of a cortico-basal ganglia loop system that switches from top-down to bottom-up mode in response to salient, task-relevant external events that are not predictable.

To compare and predict kinesiophobia and fear avoidance beliefs between athletes with gastrocnemius myofascial pain syndrome (MPS) and healthy athletes.