Rejected

Six kuwanon derivatives (A/B/C/E/H/J) extracted from the roots of L. were evaluated to determine their cyclooxygenase (COX)-1 and 2 inhibitory effects. Cyclooxygenase (COX) is known as the target enzyme of nonsteroidal anti-inflammatory drugs (NSAIDs), which are the most widely used therapeutic agents for pain and inflammation. Among six kuwanon derivatives, kuwanon A showed selective COX-2 inhibitory activity, almost equivalent to that of celecoxib, a known COX inhibitor. Kuwanon A showed high COX-2 inhibitory activity (IC = 14 μM) and a selectivity index (SI) range of >7.1, comparable to celecoxib (SI > 6.3). To understand the mechanisms underlying this effect, we performed docking simulations, fragment molecular orbital (FMO) calculations, and pair interaction energy decomposition analysis (PIEDA) at the quantum-mechanical level. As a result, kuwanon A had the strongest interaction with Arg120 and Tyr355 at the gate of the COX active site (-7.044 kcal/mol) and with Val89 in the membrane-binding domain (-6.599 kcal/mol). In addition, kuwanon A closely bound to Val89, His90, and Ser119, which are residues at the entrance and exit routes of the COX active site (4.329 Å). FMO calculations and PIEDA well supported the COX-2 selective inhibitory action of kuwanon A. It showed that the simulation and modeling results and experimental evidence were consistent.

Crohn's disease (CD) is an inflammatory bowel disease that typically affects the distal part of the gastrointestinal tract (GI) such as the terminal ileum and colon. However, it can affect the upper GI tract, potentially resulting in complications such as strictures, but discussion of the management of such effects is limited in the surgical literature.

Disseminated peritoneal coccidioidomycosis in the setting of early pregnancy after fertility treatment is rare and can present as a diagnostic challenge. A 39-year-old underwent ovarian stimulation with clomiphene citrate followed by HCG trigger and intrauterine insemination. She developed persistent abdominal pain, ascites and episodes of fever in early pregnancy, and eventually underwent a diagnostic laparoscopy for worsening clinical presentation. Operative findings were notable for peritoneal studding, infracolic omentum inflammation, bowel adhesions to the abdominal wall and normal-appearing uterus and adnexa. The pathology results indicated peritoneal infection. Hormonal changes associated with fertility treatment and immune tolerance in pregnancy may increase the risk for disseminated peritoneal coccidioidomycosis. A high index of suspicion and a multidisciplinary team are important for the diagnostic workup and treatment plan of disseminated peritoneal coccidioidomycosis.

The design of some knee replacements includes the use of a mobile polyethylene bearing which can potentially dislocate away from the main bearing surfaces. This is particularly the case in unicompartmental or partial knee replacements (UKRs), and the most widely used UKR currently has this feature. Bearing dislocations are typically very painful and disabling, but not always, as in the case we present.

To explore the application value of the pressing acupuncture therapy (PAT) combined with auricular pressure beans in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS).

Intracranial cavernous malformations (CMs) are benign vascular malformations that arise mostly within the brain parenchyma, but occasionally from the dura mater. Here, we report an extremely rare case of a 29-year-old pregnant woman presenting with hemorrhage in a dural-based CM at the temporal convexity. She presented with headache at 38 weeks of pregnancy. Imaging showed a hemorrhagic mass lesion in the left temporal lobe. Consciousness was clear, with no apparent neurological symptoms or headache. Her baby was delivered by emergency Caesarean section. Magnetic resonance (MR) imaging revealed an enhanced lesion around the hematoma and flow void appearances. Cerebral angiography confirmed the left middle meningeal artery feeding the lesion with apparent contrast medium pooling. Surgical removal of the lesion as a single block was performed. Histological examinations were consistent with CM. The lesion was located outside the brain and attached to the dura mater of the convexity, so the final diagnosis was dural-based CM. The patient was discharged home with her baby without any neurological deficits, and no recurrence has been seen for 2 years. Dural-based CM at the temporal convexity was detected, presenting as headache induced by hemorrhage during pregnancy. The relationship between bleeding of the lesion and pregnancy remains unclear, but female hormones and vascular growth factors during pregnancy can induce morphological changes and angiogenesis in CMs.

Deutetrabenazine is approved to treat tardive dyskinesia (TD) in adults and is titrated weekly by 6 mg/day, from 12 to 48 mg/day, based on dyskinesia control and tolerability. This analysis compared the safety of deutetrabenazine during titration versus maintenance.

Diabetic neuropathic pain (DNP) is a common diabetic complication that currently lacks an efficient therapy. The aim of the current work was to uncover the anti-allodynic and neuroprotective effects of memantine in a model of mouse diabetic neuropathy and its ameliorative effect on the high-mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-k B (NF-kB) inflammatory axis. Diabetes was prompted by an alloxan injection (180 mg/kg) to albino mice. On the ninth week after diabetes induction, DNP was confirmed. Diabetic mice were randomly allocated to two groups (six mice each); a diabetes mellitus (DM) group and DM+memantine group (10 mg/kg, daily) for five weeks. DNP-related behaviors were assessed in terms of thermal hyperalgesia and mechanical allodynia by hot-plate and von Frey filaments. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the spinal glutamate, interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α). The spinal levels of N-methyl-D-aspartate type 1 receptor (NMDAR1), HMGB1, TLR4, and phosphorylated NF-kB were assessed using Western blotting. Histopathological investigation of the spinal cord and sciatic nerves, together with the spinal cord ultrastructure, was employed for assessment of the neuroprotective effect. Memantine alleviated pain indicators in diabetic mice and suppressed excessive NMDAR1 activation, glutamate, and pro-inflammatory cytokine release in the spinal cord. The current study validated the ability of memantine to combat the HMGB1/TLR4/NF-kB axis and modulate overactive glutamate spinal transmission, corroborating memantine as an appealing therapeutic target in DNP.

Migraine is one of the most disabling types of headache. It affects 4-6% of men and 13-18% of women; more than 80% of them are under 30 years. Many theories to explain mechanism of migraine are present; role of serum magnesium is one of them. This Cross-sectional analytical study was designed to see serum magnesium level status of migraine patients in Bangladesh and to find out any relation. The study was carried out in Outpatient Department of Neurology of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2017 to September 2018. Seventy (70) patients between 18-60 years of both sexes with headache fulfilling the criteria for migraine were enrolled as migraine group. Patients with headache who did not fulfill the criteria of migraine enrolled as non migraine group. Patients were included in both groups after exclusion of structural lesions, magnesium containing drug intake, pregnancy, menstruation, alcoholism, renal or GIT problems. Serum magnesium levels were studied in both groups and compared with each other. All related factors such as age, sex, family history of migraine, occupation were assessed. Fifty one (51) of 70 patients (72.85%) was female and 19(27.15%) were male in migraine group. Thirty eight (54.28%) of cases were between 18 and 30 years old. Thirty nine (55.71%) of migraine patients had history of similar headache in their family. Severe headache in 51.43% of migraine patients and 30% had more than three attacks per month. Mean serum magnesium level was 1.70 mg/dl in migraine group and 1.85 mg/dl in non migraine group (p=0.001). Serum magnesium level was also lower in severe migraine headache in comparison to mild to moderate headache (p=0.01). No significant difference was found in serum magnesium level compared according to age, sex, frequency of attack and presence or absence of aura. The study concludes that serum magnesium in migraine patients was significantly lower than non migraine group. It was also lower in migraine patient having severe headache in comparison with mild to moderate headache, though in both conditions they were within normal range.

Ectopic pregnancy is commonly considered in the differential diagnosis for first-trimester vaginal bleeding and acute abdominal pain in women of reproductive age. Negative human chorionic gonadotropin (hCG) tests have been considered the gold standard to rule out this life-threatening diagnosis and appropriately rising hCG levels are thought to exclude it as well. In the unique case reported here, pathology confirmed ectopic pregnancy is identified in the setting of a negative serum hCG test. The patient was a 23-year-old woman (with one living child and one earlier miscarriage) who presented to the emergency department (ED) with sudden onset of abdominal pain, vaginal bleeding and syncope. She was tachycardic but normotensive and had both a negative serum hCG test and a negative urine hCG test. Imaging demonstrated a hemoperitoneum and right adnexal mass. She was taken for emergency exploratory surgery. The right fallopian tube had a tubal mass consistent with an ectopic pregnancy as well as 500 mL of blood. Pathology confirmed the ectopic pregnancy. A literature review revealed only two prior documented cases of pathology-confirmed ectopic pregnancy in the setting of a negative serum hCG test. The patient had experienced an abortion two months earlier without a documented intrauterine pregnancy. Her hCG levels were followed to <5 mIU/mL and she had not yet had return of menses at the time of her presentation. Perhaps a chronic ectopic could explain this unusual case. This case highlights that an ectopic pregnancy should never be excluded from the differential diagnosis in a woman of reproductive age.