Rejected

In view of postsynaptic density 95kDA (PSD95) tethers neuronal NO synthase (nNOS) to N-methyl-d-aspartate receptor (NMDAR), the PSD95-nNOS complex represents a therapeutic target of neuropathic pain. This study therefore sought to explore the ability of PCC-0105002, a novel PSD95-nNOS small molecule inhibitor, to alter pain sensitivity in rodent neuropathic pain models. Firstly, the IC of PCC-0105002 for PSD95 and NOS1 binding activity was determined using an AlphaScreen assay kit. Then, we examined the effects of PCC-0105002 in the mouse formalin test and in the rat spinal nerve ligation (SNL) model, and explored the ability of PCC-0105002 to mediate analgesia and to effect motor coordination in a rota-rod test. Moreover, the mechanisms whereby PCC-0105002 mediates analgesia was explored via western blotting, Golgi staining, and co-immunoprecipitation experiments in dorsal horn. The outcomes indicated that PCC-0105002 exhibited dose-dependent attenuation of phase II pain-associated behaviors in the formalin test. The result indicated that PCC-0105002 disrupted the PSD95-nNOS interaction with IC of 1.408 μM. In the SNL model, PCC-0105002 suppressed mechanical allodynia, thermal hyperalgesia, and abnormal dorsal horn wide dynamic range neuron discharge. PCC-0105002 mediated an analgesic effect comparable to that of MK-801, while it was better able to enhance motor coordination as compared with MK-801. Moreover, PCC-0105002 altered signaling downstream of NMDAR and thus functionally and structurally attenuating synaptic plasticity through respective regulation of the NR2B/GluR1/CaMKIIα and Rac1/RhoA pathways. These findings suggest that the novel PSD95-nNOS inhibitor PCC-0105002 is an effective agent for alleviating neuropathic pain, and that it produces fewer motor coordination-associated side effects than do NMDAR antagonists.

The association of arterial tortuosity and connective tissue diseases is widely reported in the literature, but only a few studies were based on a quantitative evaluation of this arterial phenotype, and none of the latter examined the intracranial vasculature. The aim of this study was to evaluate the degree of intracranial arterial tortuosity in patients with Marfan syndrome and those with Loeys-Dietz syndrome, and to assess its usefulness in the differential diagnosis.

To evaluate the findings of magnetic resonance imaging (MRI) of the ipsilateral hip(s) as part of the workup of men with chronic orchialgia (CO).

Avian schistosomes, the causative agents of human cercarial dermatitis (or swimmer's itch), die in mammals but the mechanisms responsible for parasite elimination are unknown. Here we examined the role of reactive nitrogen species, nitric oxide (NO) and peroxynitrite, in the immune response of mice experimentally infected with Trichobilharzia regenti, a model species of avian schistosomes remarkable for its neuropathogenicity.

To evaluate the effect of Brief Guided Imagery (BGI) on patients suffering chronic, fibromyalgia-related pain.

Hospitalized newborn infants may require analgesia and sedation either for the management of procedural pain, during or after surgery, and other painful conditions. The benefits and harms of opioids administered at different doses and routes of administration have been reported in numerous trials and systematic reviews. The use of alpha-2-agonists such as clonidine and dexmedetomidine in newborn infants is more recent, and they might be prescribed to reduce the total amount of opioids which are thought to have more side effects. Moreover, alpha-2-agonists might play an important role in the management of agitation and discomfort.

Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity.

Emergency medical services regularly encounter severe burns. As standards of care are relatively well-established regarding their hospital management, prehospital care is comparatively poorly defined. The aim of this study was to describe burned patients taken care of by our physician-staffed emergency medical service (PEMS).

Chronic non-cancer pain is common and long-term opioid therapy is frequently used in its management. While opioids can be effective, they are also associated with significant harm and misuse, and clinicians must weigh any expected benefits with potential risks when making decisions around prescribing. This review aimed to summarise controlled trials and systematic reviews that evaluate patient-related, provider-related, and system-related factors supporting responsible opioid prescribing for chronic non-cancer pain. A scoping review methodology was employed, and six databases were searched. Thirteen systematic reviews and nine controlled trials were included for analysis, and clinical guidelines were reviewed to supplement gaps in the literature. The majority of included studies evaluated provider-related factors, including prescribing behaviours and monitoring for misuse. A smaller number of studies evaluated system-level factors such as regulatory measures and models of healthcare delivery. Studies and guidelines emphasise the importance of careful patient selection for opioid therapy, development of a treatment plan, and cautious initiation and dose escalation. Lower doses are associated with reduced risk of harm and can be efficacious, particularly when used in the context of a multimodal interdisciplinary pain management program. Further research is needed around many elements of responsible prescribing, including instruments to monitor for misuse, and the role of policies and programs.