Rejected

Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100-200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.

The successful clinical application of patient-specific personalized medicine for the management of low back patients remains elusive. This study aimed to classify chronic nonspecific low back pain (NSLBP) patients using our previously developed and validated wearable inertial sensor (SHARIF-HMIS) for the assessment of trunk kinematic parameters. One hundred NSLBP patients consented to perform repetitive flexural movements in five different planes of motion (PLM): 0° in the sagittal plane, as well as 15° and 30° lateral rotation to the right and left, respectively. They were divided into three subgroups based on the STarT Back Screening Tool. The sensor was placed on the trunk of each patient. An ANOVA mixed model was conducted on the maximum and average angular velocity, linear acceleration and maximum jerk, respectively. The effect of the three-way interaction of Subgroup by direction by PLM on the mean trunk acceleration was significant. Subgrouping by STarT had no main effect on the kinematic indices in the sagittal plane, although significant effects were observed in the asymmetric directions. A significant difference was also identified during pre-rotation in the transverse plane, where the velocity and acceleration decreased while the jerk increased with increasing asymmetry. The acceleration during trunk flexion was significantly higher than that during extension, in contrast to the velocity, which was higher in extension. A Linear Discriminant Analysis, utilized for classification purposes, demonstrated that 51% of the total performance classifying the three STarT subgroups (65% for high risk) occurred at a position of 15° of rotation to the right during extension. Greater discrimination (67%) was obtained in the classification of the high risk vs. low-medium risk. This study provided a smart "sensor-based" practical methodology for quantitatively assessing and classifying NSLBP patients in clinical settings. The outcomes may also be utilized by leveraging cost-effective inertial sensors, already available in today's smartphones, as objective tools for various health applications towards personalized precision medicine.

Ginger has a pain-reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX-pathways, antioxidant activity, inibition of the transcription factor nf-kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10-year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long-term therapy.

Crohn's disease (CD) and ulcerative colitis (UC) are associated with considerable direct healthcare costs. There have been few comprehensive analyses of all IBD- and non-IBD comorbidities that determine direct costs in this population.

The reversible cerebral vasoconstriction syndrome (RCVS) is a common cause of thunderclap headache. Many trigger factors, such as the intake of vasoactive and less commonly immunosuppressive medication have previously been described. This article reports the first case of the occurrence of RCVS after the intake of ustekinumab in a female patient with a history of Crohn's disease.

The aim of this study was to evaluate the effects of photobiomodulation therapy (PBM) and ozone applications on patients' quality of life after gingivectomy and gingivoplasty. In this study, 36 patients with chronic inflammatory gingival enlargement underwent gingivectomy and gingivoplasty. The groups were randomly divided into control (n = 12), PBM (n = 12) and ozone (n = 12) groups. GaAlAs diode laser 810 nm wavelength at a non-contact and continuous mode with a power of 0.3 W and a density of 4 J/cm used for PBM for 1 min. Ozone was applied for 1 min for every 5 mm in contact mode at power level 9 using probe number 3. PBM and ozone applications were performed immediately after the operation, on the 3rd and 7th days. Pain assessment was performed at 3rd, 7th, 14th and 28th days after gingivectomy and gingivoplasty by using visual analogue scale (VAS). Oral Health Impact Profile (OHIP-14) records were obtained from the patients before gingivectomy and gingivoplasty and postoperative 7th and 14th days. OHIP-14 questions were also evaluated individually. VAS pain levels of the control group measured on the 3rd day were higher than the PBM group and on the 7th day were found to be significantly higher than both groups (p < 0.05). The total OHIP-14 score of the control group on the 7th postoperative day was found to be higher than the PBM group (p < 0.05). The mean score obtained from the third question of OHIP-14 at 7th and 14th day of the PBM group was found to be lower than the control and ozone groups (p < 0.05). The PBM and ozone applications after gingivectomy and gingivoplasty reduce the pain levels of patients and have a positive effect on patients' quality of life.

Somatic symptoms including pain are everyday human experiences. They usually result from a complex interaction of stimuli, interpretation and reaction, and are not necessarily proportional to structural damage. Persistent functional somatic symptoms can be associated with a significant impairment of quality of life and functioning, even without mental or somatic comorbidity. Dysfunctional experiences, expectancies and behavior, not only by patients but also by physicians, can increase the risk of chronification. From the outset, management should be graded with respect to the severity and biopsychosocial aspects, with thorough but cautious diagnostics and with psychoeducative, active and coping-oriented treatment.

Pain management after total knee arthroplasty (TKA) is important as acute postoperative pain can affect patient's ability to walk and participate in rehabilitation required for good functional outcome. This is achieved by effective intra-operative and post-operative analgesia to facilitate early recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) are analgesic regimens and commonly used for effective post-operative analgesia after TKA. Our aim was to compare the efficacy and outcomes of these two methods, combined and independently.

Oxycodone is an opioid with strong analgesic effects widely used to treat acute and chronic pain. Interpretation of oxycodone concentrations in postmortem cases is complicated due to tolerance and overlapping concentrations for fatal and non-fatal levels. In this study, our aim was to develop and validate a method for oxycodone and its three metabolites: noroxycodone, oxymorphone, and noroxymorphone in postmortem femoral blood. Our goal was to define reference concentrations for intoxications and non-intoxications, and investigate metabolic ratios in different causes of death. A rapid LC-MS-MS method using protein precipitated postmortem blood was developed. LLOQ was 0.005 μg/g blood for all analytes, ULOQ was 1.0 μg/g for oxycodone and noroxycodone, and 0.25 μg/g for oxymorphone and noroxymorphone. The method displayed high precision (3.3-7.7%) and low bias (-0.3-12%). In total, 192 cases were analysed and concentrations ranged from 0.005-13 μg/g for oxycodone, 0.005-2.0 μg/g for noroxycodone, 0.005-0.24 μg/g for oxymorphone, and 0.005-0.075 μg/g for noroxymorphone. We found a significant difference in oxycodone concentration between the cases where oxycodone contributed and those where it did not. In spite of that, we do not recommend the use of a specific blood concentration to distinguish fatal intoxications. Instead, the percentiles from our dataset suggest that concentrations greater than 0.2 μg/g are likely to have contributed to toxicity, but that concentrations as high as 0.3 might be tolerated without toxic effects. In addition, we also found that a low noroxycodone/oxycodone ratio could point towards an acute fatal intoxication. In conclusion, the oxycodone concentration alone may not be sufficient to diagnose a fatal intoxication.