Bioassay-Guided Fractionation of Pittosporum angustifolium and Terminalia ferdinandiana with Liquid Chromatography Mass Spectroscopy and Gas Chromatography Mass Spectroscopy Exploratory Study.

Bioprospecting native Australian plants offers the potential discovery of latent and novel bioactive compounds. The promising cytotoxic and antibacterial activity of methanolic extracts of Pittosporum angustifolium and Terminalia ferdinandiana led to further fractionation and isolation using our laboratory's bioassay-guided fractionation protocol. Hence, the aim of this study was to further evaluate the bioactivity of the fractions and subfractions and characterize bioactive compounds using liquid chromatography mass spectroscopy (LC-MS/MS) and gas chromatography MS (GC-MS). Compounds tentatively identified in P. angustifolium Fraction 1 using LC-ESI-QTOF-MS/MS were chlorogenic acid and/or neochlorogenic acid, bergapten, berberine, 8'-epitanegool and rosmarinic acid. GC-MS analysis data showed the presence of around 100 compounds, mainly comprising carboxylic acids, sugars, sugar alcohols, amino acids and monoalkylglycerols. Furthermore, the fractions obtained from T. ferdinandiana flesh extracts showed no cytotoxicity, except against HT29 cell lines, and only Fraction 2 exhibited some antibacterial activity. The reduced bioactivity observed in the T. ferdinandiana fractions could be attributed to the potential loss of synergy as compounds become separated within the fractions. As a result, the further fractionation and separation of compounds in these samples was not pursued. However, additional dose-dependent studies are warranted to validate the bioactivity of T. ferdinandiana flesh fractions, particularly since this is an understudied species. Moreover, LC-MS/GC-MS studies confirm the presence of bioactive compounds in P. angustifolium Fraction 1/subfractions, which helps to explain the significant acute anticancer activity of this plant. The screening process designed in this study has the potential to pave the way for developing scientifically validated phytochemical/bioactivity information on ethnomedicinal plants, thereby facilitating further bioprospecting efforts and supporting the discovery of novel drugs in modern medicine.

Clinical correlates of pain in adults with hard-to-heal leg ulcers: a cross-sectional study.

OBJECTIVE: Pain is a complex symptom associated with hard-to-heal (chronic) leg ulcers that is often poorly managed. The objective of this study was to gain greater understanding by investigating relationships between physical and psychosocial factors, and pain severity in adults with hard-to-heal leg ulcers. METHOD: A secondary analysis of data collected for a longitudinal, observational study of adults with hard-to-heal leg ulcers was undertaken. Data were collected over a 24-week period, including variables relating to sociodemographics, clinical variables, medical status, health, ulcer and vascular histories, and psychosocial measures. Multiple linear regression modelling was used to determine the independent influences of these variables on pain severity, as measured with a Numerical Rating Scale (NRS). RESULTS: Of 142 participants who were recruited, 109 met the inclusion criteria for this study, of whom: 43.1% had venous ulcers; 41.3% had mixed ulcers; 7.3% had arterial ulcers; and 8.3% had ulcers from some other cause. The final model explained 37% (adjusted r2=0.370) of the variation in the pain NRS scores. Controlling for analgesic use, salbutamol use (p=0.005), clinical signs of infection (p=0.027) and ulcer severity (p=0.001) were significantly associated with increased pain, while the presence of diabetes (p=0.007) was significantly associated with a decrease in pain. CONCLUSION: Pain is a highly complex and pervasive symptom associated with hard-to-heal leg ulcers. Novel variables were identified as being associated with pain in this population. The model also included wound type as a variable; however, despite being significantly correlated to pain at the bivariate level of analysis, in the final model, the variable did not reach significance. Of the variables included in the model, salbutamol use was the second most significant. This is a unique finding that, to the authors' knowledge, has not been previously reported or studied. Further research is required to better understand these findings and pain in general.

Rapid progression of cervical squamous cell carcinoma with delayed treatment in pregnancy.

•Delayed treatment of cervical cancer in pregnancy can result in progression.•Surveillance of cervical cancer in pregnancy with pelvic MRIs every 6 weeks.•Comprehensive multidisciplinary care is essential in setting of treatment delays.

A ruptured vulvar labial artery pseudoaneurysm causes a secondary postpartum hemorrhage: A case report.

BACKGROUND: Postpartum hemorrhage is the most common cause of maternal morbidity in the United States. However, secondary postpartum hemorrhage is rare and includes pseudoaneurysms, which represent only 3.3% of all cases of secondary postpartum hemorrhage. Vulvar labial artery pseudoaneurysm had never been reported in the literature. CASE: This is a case of ruptured vulvar labial pseudoaneurysm leading to secondary postpartum hemorrhage. Computerized tomography angiography showed it to be located in a distal branch of the vulvar labial artery. This location is unique, although there are reported cases of pseudoaneurysms in the uterine artery. The patient was successfully treated with arterial embolization. CONCLUSION: Recognition of a ruptured pseudoaneurysm as the cause of postpartum hemorrhage allows for its proper management by arterial embolization.

Congenital Diaphragmatic Hernia Presenting in a 7-Day-Old Infant.

A 7-day-old male infant presented to the emergency room after respiratory distress was noted at an outpatient well child check. On exam, he was observed to have tachypnea, increased work of breathing, and decreased breath sounds on the left side of the chest. On chest X-ray, he was found to have a left-sided congenital diaphragmatic hernia. The infant was transported to a tertiary care facility where the defect was repaired without complication. Interestingly, the mother had a history of a normal antenatal ultrasound, completed at 19 + 2 weeks of gestational age. This case report summarizes the challenges of diagnosing late-presenting congenital diaphragmatic hernia, associated malformations, possible etiologies, and prognosis.

Toll-like receptor 2 mediates vascular contraction and activates RhoA signaling in vascular smooth muscle cells from STZ-induced type 1 diabetic rats.

Increased vascular smooth muscle cell (VSMC) contraction is an early and critical contributor to the pathogenesis of vascular dysfunction in diabetes; however, knowledge regarding the underlying mechanisms is scarce. Toll-like receptor 2 (TLR2), a well-known component of the innate immunity, is expressed in VSMC and recently has been identified to be systemically activated in diabetes. Whether TLR2 is locally activated in the diabetic blood vessels and have effect on contraction is not known. In the current study, we examined the role of TLR2 in increased vascular contraction in diabetes. Utilizing rat model of type 1 diabetes (induced by streptozotocin (STZ)), we demonstrated that aortas from STZ-diabetic rats exhibit increased expression of TLR2 and its adaptor protein, myeloid differentiation primary response 88 (MyD88), as well as enhanced protein-protein interaction between TLR2 and MyD88, suggesting a TLR2 signaling activation. Blockade of TLR2 in intact aortas using anti-TLR2 antibody attenuated increased vascular contraction in STZ-diabetic rat as assessed by wire myograph. Activation of TLR2 by specific ligand in primary aortic VSMC cultures triggered activation of RhoA which was exacerbated in cells from STZ-diabetic rats than control rats. Activation of RhoA was accompanied by phosphorylation and therefore activation of its downstream targets myosin phosphatase target subunit I and myosin light chain (markers of VSMC contraction). Taken together, these results provide evidence for the role of TLR2 in increased contraction in diabetic blood vessels that involves RhoA signaling. Thus, targeting vascular TLR2 offers a promising drug target to treat vascular dysfunction in diabetes.