Rejected

Opioids have long been used to treat acute postsurgical and postprocedural pain; however, opioid-related adverse events (AEs) contribute to poor patient outcomes. In addition, perisurgical exposure to opioids can potentially increase the risk for opioid-use disorder. NSAIDs reduce pain and inflammation by a mechanism different from that of opioid analgesics and may be useful in reducing the need for opioid drugs as part of a multimodal analgesia strategy. We conducted this review to assess the effectiveness and tolerability of adjunctive conventional NSAIDs given systemically in the perioperative setting in terms of opioid-sparing effects observed postoperatively.

Superior mesenteric artery (SMA) syndrome is described as compression of the third part of the duodenum between SMA and aorta with resultant obstruction and dilatation of proximal duodenum and stomach. Virtually, any condition associated with weight reduction may predispose the patient to SMA syndrome. A 17-year-old boy complaining from persistent vomiting, dull abdominal pain, anorexia, and weight loss for long time presented to the pediatric surgery department. Computed tomography (CT) of the abdomen was prescribed to look for the cause of persistent vomiting and bulging of the epigastrium. Contrast Enhanced CT revealed decreased aortomesenteric angle and aortomesenteric distance causing compression of third part of duodenum with resultant marked distension of proximal duodenum, stomach, and even esophagus. The patient underwent laparotomic gasterojujenostomy. SMA syndrome is a rare clinical entity. CT can well delineate this abnormality. SMA syndrome can be treated with both conservative and surgical approaches.

Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients' daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA.Funding: Novartis Pharmaceuticals Corporation.Plain Language Summary: Plain language summary available for this article.

The advantages of continuous adductor canal block (CACB) over single shot ACB (SACB) are still debatable for pain management after total knee arthroplasty (TKA). The aim of this study was to investigate which ACB method provides better pain relief after TKA.

While it is known that thoracic paravertebral blockade (TPVB) could reduce pain undergoing thoracic surgery, it has not been confirmed whether this reduction in pain reduces pulmonary complications in an elderly population.

Chronic neuropathic pain is secondary to other musculoskeletal pain. The following study aimed to determine the frequency of chronic neuropathic pain and its association with depression in the elderly. A crosssectional survey was carried out on 306 participants at the National Institute of Rehabilitation Medicine (NIRM) Hospital, in Islamabad over a period of 6 months from September 2017 to February 2018. Population of ? 60 years of age with chronic pain for >6 months were included, whereas patients with malignant origin of pain, intermittent pain and psychological pain were excluded. Data was collected by using DN4 and DASS Questionnaires were analysed by SPSS. Of the 271 participants with the mean age of 66 } 5.8 years, 216 (79.9%) were male. The frequency of patients suffering from chronic neuropathic pain was 53.9%. Data showed among the elderly a strong association of chronic neuropathic pain with anxiety and stress (P<0.05), but not with depression (P>0.05).

As an important branch of traditional medicines,medicinal marine organisms have many advantages,including biological diversity,remarkable biological activity,especial for the treatment of anti-cancer,anti-virus,anti-coagulation,analgesia,anti-bacterial,cardiovascular and cerebrovascular diseases. In recent years,with the continuous exploration of marine organisms by human beings,many marine organisms with specific biological activities and medicinal prospects have been found,which have attracted great attention around the world and thus called &quot; new hope&quot; to solve human health problems. However,due to the rapid development of modern industry,heavy metal pollution not only poses a great threat to medicinal marine living resources,but also hinders the development of marine biomedical industry and threatens human health. In view of this,this paper introduced the development trend of medicinal marine organisms and the current situation of heavy metal pollution and focusing on the analysis technology and chemical removal technology of heavy metals in medicinal marine organisms,which is to provide reference for the heavy metals control in marine medicines and the development and utilization of marine medicines.

Buprenorphine/samidorphan (BUP/SAM; ALKS 5461) is an investigational opioid system modulator for the adjunctive treatment of patients with major depressive disorder (MDD), who did not respond adequately to prior antidepressant therapy (ADT). FORWARD-2, an open-label extension study, assessed long-term safety and tolerability of adjunctive BUP/SAM treatment in these patients. Patients from four short-term trials and de novo patients were enrolled; all had confirmed MDD and a current major depressive episode lasting 2-24 months. Patients were treated with an established ADT for ≥8 weeks before receiving sublingual, adjunctive BUP/SAM 2/2 mg for up to 52 weeks. Safety (primary objective) was assessed via adverse events (AEs), the Columbia-Suicide Severity Rating Scale, and the Clinical Opiate Withdrawal Scale (COWS). Exploratory evaluation of efficacy was done using the Montgomery-Åsberg Depression Rating Scale (MADRS). Of 1485 patients, 50% completed the study and 11% discontinued due to AEs. AEs of nausea, headache, constipation, dizziness, and somnolence, each occurred in ≥10% of patients. There was no evidence of increased suicidal ideation or behavior. Euphoria-related AEs were uncommon (1.2%). Following abrupt BUP/SAM discontinuation, "drug withdrawal" AEs were infrequent (0.4%), and the incidence of COWS categorical worsening after abrupt drug discontinuation was low (6.5%). Improvements in mean MADRS scores were maintained until study end, suggesting durability of antidepressant effect in patients continuing treatment. BUP/SAM was generally well tolerated, with a low risk of abuse and an AE profile consistent with those seen in placebo-controlled studies. Withdrawal reports were uncommon and of limited clinical impact.

Rutin is a glycone form of the flavonol quercetin and it reduces inflammatory pain in animal models. Therapy with granulocyte colony-stimulating factor (G-CSF) is known by the pain caused as its main side effect. The effect of rutin and its mechanisms of action were evaluated in a model of hyperalgesia induced by G-CSF in mice. The mechanical hyperalgesia induced by G-CSF was reduced by treatment with rutin in a dose-dependent manner. Treatment with both rutin + morphine or rutin + indomethacin, at doses that are ineffectual per se, significantly reduced the pain caused by G-CSF. The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)-ATP-sensitive potassium channel (K) signaling pathway activation is one of the analgesic mechanisms of rutin. Rutin also reduced the pro-hyperalgesic and increased anti-hyperalgesic cytokine production induced by G-CSF. Furthermore, rutin inhibited the activation of the nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), which might explain the inhibition of the cytokine production. Treatment with rutin upregulated the decreased mRNA expression of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) combined with enhancement of the mRNA expression of the Nrf2 downstream target heme oxygenase (HO-1). Intraperitoneal (i.p.) treatment with rutin did not alter the mobilization of neutrophils induced by G-CSF. The analgesia by rutin can be explained by: NO-cGMP-PKG-K channel signaling activation, inhibition of NFκB and triggering the Nrf2/HO-1 pathway. The present study demonstrates rutin as a promising pharmacological approach to treat the pain induced by G-CSF without impairing its primary therapeutic benefit of mobilizing hematopoietic progenitor cells into the blood.

Sinomenine (Sino) is diffusely applied in heal rheumatoid arthritis and neuralgia. Howbeit, the activities of Sino in breast cancer cells remain confused. The research attempted to probe the anti-tumor function of Sino in breast cancer cells and divulge the feasible molecular mechanism. Sion at the 1-16 μM concentrations was exploited for the exposure of MDA-MB-231 or MCF7 cells, and cell growth, migration, invasion, cell cycle-relevant and apoptosis-correlative factors were estimated. Micro RNA (miR)-29 expression was evaluated via enforcing qRT-PCR, and the actions of miR-29 in MDA-MB-231 cells growth, migration and invasion were appraised after the overexpressed or suppressed vectors transfection. The functions of PDCD-4 in JNK and MEK/ERK pathways were estimated by employing western blot. We found that, Sino exposure impeded cell proliferation, provoked cell apoptosis and barricaded cell migration and invasion in MDA-MB-231 and MCF7 cells. Enhancement of miR-29 was observed in Sino-managed cells, and miR-29 overexpression further potentiated the activities of Sino in MDA-MB-231 cells. Additionally, Sino remarkably enhanced PCDC-4 expression via adjusting miR-29 in MDA-MB-231 cells. Beyond that, overexpressed PCDC-4 obstructed JNK and MEK/ERK pathways in MDA-MB-231 cells. Taken together, the explorations unveiled that Sino restrained MDA-MB-231 cells proliferation, migration, invasion, and provoked apoptosis through modulation of miR-29/PDCD-4 axis. Highlight Sino inhibits MDA-MB-231 and MCF7 cells proliferation and provokes apoptosis; Sino restrains MDA-MB-231 and MCF7 cells migration and invasion; Sino ascends miR-29 expression in MDA-MB-231 and MCF7 cells; Sino adjusts cell growth, migration and invasion via modulating miR-29; Sino up-regulates PDCD-4 expression through mediating miR-29; PDCD-4 obstructs JNK and MEK/ERK pathways in MDA-MB-231 cells.