Rejected

Understanding postoperative opioid use patterns among different populations is key to developing opioid stewardship programs.

Pathological myocardial hypertrophy in response to an increase in left ventricular (LV) afterload may ultimately lead to heart failure. Cell surface receptors bridge the interface between the cell and the ECM in cardiac myocytes and cardiac fibroblasts, and have been suggested to be important mediators of pathological myocardial hypertrophy. We identify for the first time that integrin α11 (α11) is preferentially upregulated amongst integrin beta 1 heterodimer-forming α subunits in response to increased afterload induced by aortic banding (AB) in wild type mice (WT). Mice were anesthetized in a chamber with 4% isoflurane and 95% oxygen before being intubated and ventilated with 2.5% isoflurane and 97% oxygen. For pre- and post-operative analgesia, animals were administered 0.02 mL buprenorphine (0.3 mg/mL) subcutaneously. Surprisingly, mice lacking α11 develop myocardial hypertrophy following AB comparable to WT. In the mice lacking α11, we further show a compensatory increase in the expression of another mechanoreceptor, syndecan-4, following AB compared to WT AB mice, indicating that syndecan-4 compensated for lack of α11. Intriguingly, mice lacking mechanoreceptors α11 and syndecan-4 show ablated myocardial hypertrophy following AB compared to WT mice. Expression of the main cardiac collagen isoforms col1a2 and col3a1 was significantly reduced in AB mice lacking mechanoreceptors α11 and syndecan-4 compared to WT AB.

The SARS-CoV-2 virus has infected more than 235 million people since it was accepted as a pandemic in March 2020. Although a milder disease is seen in the pediatric age group, the extent of lung damage and its long-term effects are still unknown. In this study, persistent respiratory symptoms and pulmonary function tests were investigated in children with COVID-19. Fifty children with a confirmed diagnosis of COVID-19 were included in the study. Patients were evaluated for ongoing respiratory symptoms and pulmonary function tests 3 months after infection. Patients with and without persistent symptoms were compared in terms of demographic, clinical, laboratory, and radiological characteristics and also disease severity. Three months after infection, persistent respiratory symptoms were found to be present in 28% of patients; cough, chest pain and tightness, dyspnea, and exertional dyspnea were the most common symptoms. Three patients had an obstructive deficit, and one had a restrictive deficit. Four patients had impaired diffusing capacity of the lungs for carbon monoxide (DLCO). A significant decrease in FEV1/FVC and an increase in lung clearance index were found in the patients with persistent respiratory symptoms. Persistent respiratory symptoms were present in 50% of patients who had severe disease and 12.5% with non-severe disease. DLCO was also significantly lower in the severe disease group.   Conclusions: Our study suggests that the persistence of respiratory symptoms is not related to the severity of acute COVID-19 in children. The inflammatory process due to COVID-19 may continue regardless of its severity, and consequently, peripheral airways may be affected. What is Known: • As compared with adults, children with COVID-19 exhibit a milder disease course and lower mortality rates. However, due to the lack of follow-up studies on children, the long-term effects of their contracting the disease are unknown. What is New: • Although COVID-19 has been thought to have a milder course in children, respiratory system symptoms persist in approximately 30% of patients 3 months after infection. The persistent respiratory symptoms suggest that the inflammatory process due to COVID-19 may continue in some children, even if the clinical findings at admission are not severe, and that the peripheral airways may be affected accordingly.

Cepharanthine is an alkaloid that isolated from Stephania cepharantha Hayata, however，its analgesic properties are unclear and the molecular targets that mediating Cepharanthine-induced analgesia are not explored yet. In the current study, mice pain models including hot plate, acetic acid-induced writhing and formalin tests were conducted to evaluate the antinociceptive actions of Cepharanthine. [H]-ligand competitive binding assay was applied to determine the binding affinity and selectivity of Cepharanthine at κ, μ and δ opioid receptors. Cepharanthine-induced constipation was investigated using the small intestinal transit test. The results showed that intraperitoneal injection of Cepharanthine produced potent antinociception with an ED value of 24.5 mg/kg in the acetic acid-induced writhing test. In the formalin test, Cepharanthine produced moderate antinociception with the maximum analgesic activity of 42.6 ± 11.3% in phase I and 60.1 ± 7.7% in phase Ⅱ, respectively. Cepharanthine had no effects in the hot plate test. In vitro radioligand binding assay, Cepharanthine exhibited a high affinity for μ opioid receptors with a Ki value of 80 nM, without binding to κ and δ opioid receptors. Correspondingly, Cepharanthine-mediated antinociceptive effects were antagonized by pretreatment with opioid receptor antagonist naloxone. Cepharanthine also decreased the small intestine propulsion rates in the small intestinal transit test. Together, this study firstly demonstrates that Cepharanthine produces potent antinociception in acetic acid-induced visceral pain and moderate antinociception in formalin-induced inflammatory pain, and its mechanism of action may be through activation of μ opioid receptors.

The broad distribution of voltage-gated potassium channels (VGKCs) in the human body makes them a critical component for the study of physiological and pathological function. Within the KCNQ family of VGKCs, these aqueous conduits serve an array of critical roles in homeostasis, especially in neural tissue. Moreover, the greater emphasis on genomic identification in the past century has led to a growth in literature on the role of the ion channels in pathological disease as well. Despite this, there is a need to consolidate the updated findings regarding both the pharmacotherapeutic and pathological roles of KCNQ channels, especially regarding neural plasticity and motor disorders which have the largest body of literature on this channel. Specifically, KCNQ channels serve a remarkable role in modulating the synaptic efficiency required to create appropriate plasticity in the brain. This role can serve as a foundation for clinical approaches to chronic pain. Additionally, KCNQ channels in motor disorders have been utilized as a direction for contemporary pharmacotherapeutic developments due to the muscarinic properties of this channel. The aim of this study is to provide a contemporary review of the behavior of these channels in neural plasticity and motor disorders. Upon review, the behavior of these channels is largely dependent on the physiological role that KCNQ modulatory factors (i.e., pharmacotherapeutic options) serve in pathological diseases.

The COVID-19 pandemic has a substantial impact on the physical and mental health status of patients with COVID-19. This study's objective was to evaluate the factors associated with mental health in patients isolated with COVID-19.

The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the potential therapeutic efficacy of KD in epilepsy, depression, migraine, Alzheimer's disease and Parkinson's disease. In our opinion, KD should be considered as an adjuvant therapeutic option for some neurological diseases.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) share common culprit foods and potential pathophysiological factors. However, how diet may contribute to disease course and whether this differs between both entities is unclear. We therefore investigated the association of dietary indices with intestinal inflammation and gastrointestinal symptoms in both IBD and IBS patients. Food frequency questionnaires from 238 IBD, 261 IBS and 195 healthy controls (HC) were available to calculate the overall diet quality by the Dutch Healthy Diet-Index 2015 (DHD-2015) and its inflammatory potential by the Adapted Dietary Inflammatory Index (ADII). Intestinal inflammation and symptoms were evaluated by faecal calprotectin and the Gastrointestinal Symptom Rating Scale, respectively. The DHD-2015 was lower in IBD and IBS versus HC ( < 0.001), being associated with calprotectin levels in IBD (b = -4.009, = 0.006), and with abdominal pain (b = -0.012, = 0.023) and reflux syndrome (b = -0.016, = 0.004) in IBS. ADII scores were comparable between groups and were only associated with abdominal pain in IBD (b = 0.194, = 0.004). In this side-by-side comparison, we found a lower diet quality that was differentially associated with disease characteristics in IBD versus IBS patients. Longitudinal studies are needed to further investigate the role of dietary factors in the development of flares and predominant symptoms.