Rejected

To determine the postdrome's prevalence and characterize its clinical manifestations, to assess the impact of these symptoms on the patients' activities of daily living, work activity and quality of life and to assess the factors that influence the postdrome's frequency and duration.

The best medical treatment (BMT) for most patients with early stage of peripheral arterial occlusive disease (PAOD) is often limited to gait training and pharmacological therapy besides endovascular surgery. The application of remote ischemic conditioning (RIC) has been described as a promising experimental strategy for the improvement of therapeutic outcome in cardiovascular disease but has not proven beneficial effects in clinical practice and treatment of PAOD yet.

To evaluate computerized dynamic visual acuity (DVA) test findings among patients with migraine and to determine whether self-motion sensitivity and visually induced migraine symptoms that are seen in migraine patients can be explained by DVA results.

Routine opioid use in surgical patients has received attention given the opioid epidemic and a renewed focus on the dangers and drawbacks of opioids in the postoperative setting. Little is known about opioid use in bariatric surgery, especially in the inpatient setting. We hypothesize that a standardized opioid-sparing protocol reduces postoperative inpatient opioid use in bariatric surgery patients.

Left/right judgment task performance (LRJT) is impaired in severe neuropathic pain conditions. However, comparison of LRJT performance in patients with carpal tunnel syndrome (CTS) with a control group with similar cognitive functions has not been investigated.

Prognosis following surgical rotator cuff repair (RCR) is often established through the assessment of non-modifiable biomedical factors such as tear size. This understates the complex nature of recovery following RCR. There is a need to identify modifiable psychosocial and sleep-related variables, and to find out whether changes in central pain processing influence prognosis after RCR. This will improve our knowledge on how to optimise recovery, using a holistic rehabilitation approach.

The lack of effective treatment for neurological disorders has encouraged the search for novel therapeutic strategies. Remarkably, neuroinflammation provoked by the activated microglia is emerging as an important therapeutic target for neurological dysfunction in the central nervous system. In the pathological context, the hyperactivation of microglia leads to neuroinflammation through the release of neurotoxic molecules, such as reactive oxygen species, proteinases, proinflammatory cytokines and chemokines. Cannabidiol (CBD) is a major pharmacologically active phytocannabinoids derived from L. CBD has promising therapeutic effects based on mounting clinical and preclinical studies of neurological disorders, such as epilepsy, multiple sclerosis, ischemic brain injuries, neuropathic pain, schizophrenia and Alzheimer's disease. A number of preclinical studies suggested that CBD exhibited potent inhibitory effects of neurotoxic molecules and inflammatory modulators, highlighting its remarkable therapeutic potential for the treatment of numerous neurological disorders. However, the molecular mechanisms of action underpinning CBD's effects on neuroinflammation appear to be complex and are poorly understood. This review summarises the anti-neuroinflammatory activities of CBD against various neurological disorders with a particular focus on their main molecular mechanisms of action, which were related to the downregulation of NADPH oxidase-mediated ROS, TLR4-NFκB and IFN-β-JAK-STAT pathways. We also illustrate the pharmacological action of CBD's derivatives focusing on their anti-neuroinflammatory and neuroprotective effects for neurological disorders. We included the studies that demonstrated synergistic enhanced anti-neuroinflammatory activity using CBD and other biomolecules. The studies that are summarised in the review shed light on the development of CBD, including its derivatives and combination preparations as novel therapeutic options for the prevention and/or treatment of neurological disorders where neuroinflammation plays an important role in the pathological components.

Ion channels are targets of considerable therapeutic interest to address a wide variety of neurological indications, including pain perception. Current pharmacological strategies have focused mostly on small molecule approaches which can be limited by selectivity requirements within members of a channel family or superfamily. Therapeutic antibodies have been proposed, designed and characterized to alleviate this selectivity limitation, however there are no FDA-approved therapeutic antibody-based drugs targeting ion channels on the market to date. Here, in an effort to identify novel classes of engineered ion channel modulators for potential neurological therapeutic applications, we report the generation and characterization of six (EC < 25nM) Cys-loop receptor family monoclonal antibodies with modulatory function against rat and human glycine receptor alpha 1 (GlyRa1) and/or GlyRa3. These antibodies have activating (; positive modulator) or inhibiting (; negative modulator) profiles. Moreover, GlyRa3 selectivity was successfully achieved for two of the three positive modulators identified. When dosed intravenously, the antibodies achieved sufficient brain exposure to cover their calculated EC values. When compared head-to-head at identical exposures, the GlyRa3-selective antibody showed a more desirable safety profile over the non-selective antibody, thus demonstrating, for the first time, an advantage for GlyRa3-selectivity. Our data show that ligand-gated ion channels of the glycine receptor family within the CNS can be functionally modulated by engineered biologics in a dose-dependent manner and that, despite high protein homology between the alpha subunits, selectivity can be achieved within this receptor family resulting in future therapeutic candidates with more desirable drug safety profiles. We present immunization and multi-platform screening approaches to generate a diverse library of functional antibodies (agonist, potentiator or inhibitory) raised against human glycine receptors (GlyRs). We also demonstrate the feasibility of acquiring alpha subunit selectivity, a desirable therapeutic profile. When tested , these tool molecules demonstrated an increased safety profile in favor of GlyRa3-selectivity. To our knowledge, these are the first reported functional GlyR antibodies that may open new avenues to treating CNS diseases with subunit selective biologics.

To investigate the technological innovation, safety, operational advantages, and clinical application value of direct percutaneous computed tomography (CT)-guided enterostomy.

Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural invasion (PNI). OSCC has higher rates of PNI than other cancer subtypes, with PNI present in 80% of tumors. Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co-opt different components of the neurotrophin pathway in metastasis, PNI, and pain.