Rejected

Modafinil is a nonamphetamine nootropic drug with an increasingly therapeutic interest due to its different sites of action and behavioral effects in comparison to cocaine or amphetamine. A review of modafinil (and of its prodrug adrafinil and its -enantiomer armodafinil) chemical, pharmacokinetic, pharmacodynamic, toxicological, clinical and forensic aspects was performed, aiming to better understand possible health problems associated to its unconscious and unruled use. Modafinil is a racemate metabolized mainly in the liver into its inactive acid and sulfone metabolites, which undergo primarily renal excretion. Although not fully clarified, major effects seem to be associated to inhibition of dopamine reuptake and modulation of several other neurochemical pathways, namely noradrenergic, serotoninergic, orexinergic, histaminergic, glutamatergic and GABAergic. Due its wake-promoting effects, modafinil is used for the treatment of daily sleepiness associated to narcolepsy, obstructive sleep apnea and shift work sleep disorder. Its psychotropic and cognitive effects are also attractive in several other pathologies and conditions that affect sleep structure, induce fatigue and lethargy, and impair cognitive abilities. Additionally, in health subjects, including students, modafinil is being used off-label to overcome sleepiness, increase concentration and improve cognitive potential. The most common adverse effects associated to modafinil intake are headache, insomnia, anxiety, diarrhea, dry mouth and raise in blood pressure and heart rate. Infrequently, severe dermatologic effects in children, including maculopapular and morbilliform rash, erythema multiforme and Stevens-Johnson Syndrome have been reported. Intoxication and dependence associated to modafinil are uncommon. Further research on effects and health implications of modafinil and its analogs is steel needed to create evidence-based policies.

Up to 74% of people with a history of ankle sprain develop chronic ankle instability (CAI). One commonly reported residual impairment is ankle pain; however, it has not been included in models or inclusion criteria for CAI. We investigated the prevalence of pain in people with CAI and the association between presence of pain and other CAI characteristics.

Marijuana generally refers to the dried mixture of leaves and flowers of the cannabis plant, and the term cannabis is a commonly used to refer to products derived from the Cannabis sativa L. plant. There has been an increasing interest in the potential medicinal use of cannabis to treat a variety of diseases and conditions. This review will provide the latest evidence regarding the medical risks and potential therapeutic benefits of cannabis in managing patients with sleep disorders or those with other medical conditions who commonly suffer with sleep disturbance as an associated comorbidity. Published data regarding the effects of cannabis compounds on sleep in the general population, as well as in patients with insomnia, chronic pain, posttraumatic stress disorder, and other neurological conditions, will be presented. Current trends for marijuana use and its effects on the economy and the implications that those trends and effects have on future research into medical cannabis are also presented.

To determine whether adolescents with generalized hypermobility spectrum disorder/ hypermobile Ehlers-Danlos syndrome (G-HSD/ hEDS) show changes in the level of disability, physical functioning, perceived harmfulness and pain intensity after completing multidisciplinary rehabilitation treatment.

Heme, released from red blood cells in sickle cell disease (SCD), interacts with toll-like receptor 4 (TLR4) to activate NF-κB leading to the production of cytokines and adhesion molecules which promote inflammation, pain, and vaso-occlusion. In SCD, TLR4 inhibition has been shown to modulate heme-induced microvascular stasis and lung injury. We sought to delineate the role of endothelial verses hematopoietic TLR4 in SCD by developing a TLR4 null transgenic sickle mouse. We bred a global deficiency state into Townes-AA mice expressing normal human adult hemoglobin A and Townes-SS mice expressing sickle hemoglobin S. SS- had similar complete blood counts and serum chemistries as SS- mice. However, SS- mice developed significantly less microvascular stasis in dorsal skin fold chambers than SS- mice in response to challenges with heme, lipopolysaccharide (LPS), and hypoxia/reoxygenation (H/R). To define a potential mechanism for decreased microvascular stasis in SS- mice, we measured pro-inflammatory NF-κB and adhesion molecules in livers post-heme challenge. Compared to heme-challenged SS- livers, SS- livers had lower adhesion molecule and cytokine mRNAs, NF-κB phospho-p65, and adhesion molecule protein expression. Furthermore, lung P-selectin and von Willebrand factor immunostaining was reduced. Next, to establish if endothelial or hematopoietic cell TLR4 signaling is critical to vaso-occlusive physiology, we created chimeric mice by transplanting SS- or SS- bone marrow into AA- or AA- recipients. Hemin-stimulated microvascular stasis was significantly decreased when the recipient was AA- . These data demonstrate that endothelial, but not hematopoietic, TLR4 expression is necessary to initiate vaso-occlusive physiology in SS mice.

To analyze the characteristics of right-to-left shunt (RLS) in patients with cryptogenic stroke and migraine by contrast-enhanced transesophageal echocardiography (c-TEE).

Permanent hearing loss after posterior fossa microvascular decompression (MVD) for typical trigeminal neuralgia (TTN) is one of the possible complications of this procedure. Intraoperative brainstem auditory evoked potentials (BAEPs) are used for monitoring the function of cochlear nerve during cerebellopontine angle (CPA) microsurgery. Level-specific (LS)-CE-Chirp® BAEPs are the most recent evolution of classical click BAEP, performed both in clinical studies and during intraoperative neuromonitoring (IONM) of acoustic pathways during several neurosurgical procedures.

Cannabinoids (CBDs) represent a diverse class of chemicals that may be beneficial in the treatment of various skin diseases due to antipruritic, anti-inflammatory, and antinociceptive properties. Although the legal history of these compounds has previously restricted their use and study, it seems likely that CBDs will gain popularity as they become increasingly available. We examined the mechanisms in which CBDs may have potential in the field of dermatology and reviewed the existing literature. We suggest that dermatologists review the existing evidence for CBD use and be ready to discuss it with their patients. The current literature indicates that CBDs may be beneficial in skin disease, particularly in the treatment of acne, chronic pruritus, and atopic dermatitis. Although there is preliminary evidence to suggest that CBDs are beneficial in these conditions, existing studies tend to be small and lacking rigorous design. There is a clear need for high-quality randomized controlled trials to fully evaluate the efficacy and safety of these compounds before their use can be promoted in the treatment of dermatological diseases.

Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups ( = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.