Rejected

Antagonists for the serotonin receptor 2B (5-HT) have clinical applications towards migraine, anxiety, irritable bowl syndrome, and MDMA abuse; however, few selective 5-HT antagonists have been identified. Previous studies from these labs identified a natural product, 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 2) as the first non-nitrogenous ligand for the 5-HT receptor. Studies on 5-HPEC optimization led to the identification of 5-hydroxy-2-(3-phenylpropyl)chromone (5-HPPC, 3), which showed a tenfold improvement in binding affinity over 2 at 5-HT. This study aimed to further improve receptor pharmacology of this unique scaffold. Guided by molecular modeling studies modifications at the C-3' and C-4' positions of 3 were made to probe their effects on ligand binding affinity and efficacy. Among the derivatives synthesized 5-hydroxy-2-(3-(3-cyanophenyl)propyl)chromone (5-HCPC, 3d) showed the most promise with a multifold improvement in binding affinity (pK = 7.1 ± 0.07) over 3 with retained antagonism.

To identify the mechanisms underlying the development of infection-driven autoimmune cytopenias.

Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions in pediatric gastroenterology. They account for 50% of all pediatric gastroenterology clinic visits. The pathophysiology of FAPDs is poorly understood, but there is growing understanding of the role of food and the patient's nutritional state in both their treatment and prognosis. Clinic-based studies have shown a higher prevalence of FAPDs, and worse prognosis among obese children with FAPDs. We aimed to assess the nutritional status of children with FAPD to determine if there is increased prevalence of FAPDs in obese or underweight patients. We conducted a cross sectional study of schoolchildren in Colombia. We enrolled 1030 patients from five schools and screened them for FAPDs using Rome IV criteria. Data on weight, height, abdominal circumference and BMI were collected for each child. Cases (FAPDs) were compared with a control group of enrolled children who did not meet diagnostic criteria for any functional gastrointestinal disorders (FGID). We diagnosed 58 (5.8%) children with FAPDs based on Rome IV criteria. When we compared to participants who were not diagnosed with FGIDs by screening, there was no statistically significant difference in children who were obese (OR 0.34 CI: 0.03-1.34, = 0.124) or overweight (OR 1.00 CI: 0.46-2.02, = 0.984) or those with increased abdominal circumference (OR 0.94, CI: 0.10-3.90, = 0.943). FAPDs are not more common among obese children compared with healthy controls at a community level. Obese children may have been overrepresented in previous studies which were done at a clinical level due to comorbidities and a more severe phenotype that makes them more likely to consult. Nutritional status is not a useful predictor for the occurrence of FAPDs in children in the general population.

Osteoarthritis (OA) is a chronic degenerative joint disease and is considered as the most common cause of pain and disability. To the best of our knowledge, it is generally observed that there is a lack of evidence on the effects of low-level laser therapy (LLLT) on inflammatory cytokines in OA. The present review aims to appraise the current evidence of efffects of LLLT on inflammatory cytokines in OA of the knee. Medical databases such as Medline, PubMed, EMBASE, PEDro CINAHL, Web of Science, Cochrane register, and Google reference were searched from its inception to June 2019. Articles that meet the inclusion criteria: subjects (animals-Wistar rats) induced with OA; rats with age group of 50-90 days; weight of 150-300 g; finding the effects of LLLT; reporting inflammatory cytokines; and articles written in English were included. The reviewers assessed the methodological quality of the primary studies. Data of inflammatory cytokines IL-1β, IL-6, TNF-α, and MMP-13 were extracted for analysis. The Q (x) test and I statistics analysis were performed to find the heterogeneity evaluation. Standard mean difference (SMD) and its 95% confidence interval (CI) were used to synthesize the data. Two hundred eleven potential articles were identified and 186 articles were excluded based on the selection criteria. The rest of the 25 articles were read and 8 articles were selected for further study. From the study, it is observed that the laser therapy group had mild to moderate improvement than control group in IL-1β, TNF-α, and MMP-13 (IL-1β; SMD 1.21 [95% CI – 0.278, 2.704], TNF-α; SMD 5.19 [95% CI 2.413, 7.961], and MMP-13 SMD – 1.45 [95% CI – 5.121, 2.211]), while IL-6 [SMD 3.11 (95% CI 0.662, 5.549] did not show any considerable improvement after laser therapy. The present review provides the evidence of LLLT-dependent reduction of IL-1β, TNF-α, and MMP-13, and its ability to modulate proliferation of inflammatory cells, which makes LLLT a suitable treatment for OA. Though the included studies showed a high heterogeneity in treatment parameter, the beneficial effect of LLLT on changes in inflammatory cytokines, such as IL-6, seems to be unaffected.

Objectives Pediatric chronic abdominal pain (CAP) is typically managed in primary care settings, although specialty referrals may help patients access the full range of biopsychosocial treatment options. We investigated patterns of specialty referral (gastroenterology or mental health) among children with CAP seen in an academic pediatric primary care clinic. Methods We retrospectively identified patients age 4-17 years visiting our primary care clinic in 2016-2017 for abdominal pain, identified using International Classification of Diseases (ICD) codes. We excluded patients whose symptoms did not persist for 3 months or who were referred to a specialist before their symptoms had persisted for 3 months. Referral outcomes were assessed through December 2018. Results Of 320 patients with qualifying ICD codes, 253 were excluded because their symptoms did not persist for 3 months; 31 had already been referred to a specialist within 3 months of pain onset; and one chart could not be accessed. Of the remaining 34 patients (22/12 girls/boys, median age 10 years) 10 (29%) were referred to a gastroenterologist and none were referred to mental health specialists. No clinical or demographic factors reached statistically significant associations with gastroenterology referral, although pain duration was shorter among patients who were referred. Conclusions Children with CAP managed in our primary care clinic were seldom referred to specialists after their pain persisted over 3 months. Increasing focus on cognitive-behavioral therapies for chronic pain, and the low specialty referral rate, indicates that primary care practices should be prepared to offer these treatment modalities to children with CAP.

Ketorolac is a nonsteroidal anti-inflammatory drug used as part of multimodal analgesia in women undergoing cesarean delivery. The lowest effective dose of ketorolac that best optimizes analgesia without increasing side effects is unclear. We performed this retrospective study to compare the analgesic efficacy of 15 mg or 30 mg ketorolac administered intra-operatively to our obstetric population.

Abdominal hysterectomy is one of the most commonly performed gynecologic surgical procedures and is frequently associated with moderate to severe pain. The present study compared the effects of morphine and ketamine on postoperative analgesia, hemodynamic stability, and postoperative adverse effects in patients who underwent abdominal hysterectomy.

The purpose of this study was to determine the efficacy and safety of embolization treatment in pelvic venous disorders in women refluxing in the ovarian and or internal iliac veins in women with chronic pelvic pain.

Aneurysmal bone cysts are rare benign bone lesions. Location in the sacrum is unusual. Symptoms are nonspecific. After an injury, pain develops and complications of adjacent structures can be triggered by the associated oedema. Radiological presentation is usually characteristic but must be confirmed by biopsy and a differential diagnosis must be made with other tumours. Treatment in long bones is based in curettage and refill with bone replacement material. In the sacrum, neurological complications can develop with selective arterial embolisation being an alternative in their management. We describe the case of a 71-year-old male patient with sacral aneurysmal bone cysts and a history of chronic lymphoid leukaemia and benign prostatic hyperplasia. The report includes the clinical presentation, imaging findings and outcome after treatment with selective arterial embolisation. This case highlights the therapeutic options and difficulties encountered in the management of these lesions when located in the sacrum, which complicates their usual treatment. Selective arterial embolisation is a therapeutic option in patients with sacral aneurysmal bone cysts, allowing less aggressive treatments and favourable results.

Intracranial subdural hematoma is a rare, but potentially lethal complication of neuraxial procedures. Considering the high frequency of neuraxial techniques in the obstetric population, parturients are more susceptible to this fearful complication. The diagnosis is often masked and delayed because it shares similar clinical characteristics with posdural puncture headache, with headache being the most common symptom. This case report describes a timely diagnosis and successful management of an intracranial subdural hematoma, after unintentional dural puncture during labour epidural analgesia. Postpartum headache following epidural analgesia, remains a clinical challenge for the caring team, requiring a close follow-up and awareness for non-benign causes that require prompt management, avoiding devastating consequences.