Oleamide, a Sleep-Inducing Supplement, Upregulates Doublecortin in Hippocampal Progenitor Cells via PPARα.

BACKGROUND: Doublecortin (DCX), a microtubule associated protein, has emerged as a central biomarker of hippocampal neurogenesis. However, molecular mechanisms by which DCX is regulated are poorly understood. OBJECTIVE: Since sleep is involved with the acquisition of memory and oleamide or 9-Octadecenamide (OCT) is a sleep-inducing supplement in human, we examined whether OCT could upregulate DCX in hippocampal progenitor cells (HPCs). METHODS: We employed real-time PCR, western blot, immunostaining, chromatin immunoprecipitation, lentiviral transduction in HPCs, and the calcium influx assay. RESULTS: OCT directly upregulated the transcription of Dcx in HPCs via activation of peroxisome proliferator-activated receptor α (PPARα), a lipid-lowering transcription factor. We observed that, HPCs of Ppara-null mice displayed significant impairment in DCX expression and neuronal differentiation as compared to that of wild-type mice. Interestingly, treatment with OCT stimulated the differentiation process of HPCs in wild-type, but not Ppara-null mice. Reconstruction of PPARα in mouse Ppara-null HPCs restored the expression of DCX, which was further stimulated with OCT treatment. In contrast, a dominant-negative mutant of PPARα significantly attenuated the stimulatory effect of OCT on DCX expression and suppressed neuronal differentiation of human neural progenitor cells. Furthermore, RNA microarray, STRING, chromatin immunoprecipitation, site-directed mutagenesis, and promoter reporter assay have identified DCX as a new target of PPARα. CONCLUSION: These results indicate that OCT, a sleep supplement, directly controls the expression of DCX and suggest that OCT may be repurposed for stimulating the hippocampal neurogenesis.

Radiographic findings predictive of irreducibility and surgical resection in ileocolic intussusception.

BACKGROUND: Ileocolic intussusception is a common cause of intestinal obstruction in young children. Radiographs may be of limited value in the diagnosis of intussusception and are sometimes utilized primarily to exclude pneumoperitoneum before therapeutic enema reduction. OBJECTIVE: The goal of this study was to determine if radiographic findings in ileocolic intussusception can offer prognostic information regarding the outcome of therapeutic air enema and, for those requiring surgical intervention, surgical outcomes and/or complications. MATERIALS AND METHODS: A single institution retrospective study was performed including all enemas for intussusception performed during a 5-year period from September 2012 to August 2017. Radiographs obtained before therapeutic enema, including our institution radiographs, outside facility radiographs, or scout images obtained during fluoroscopy or computed tomography (CT), were independently scored by two pediatric radiologists for normal bowel gas pattern, soft-tissue mass, paucity of bowel gas, meniscus sign and bowel obstruction. The reviewers were blinded to enema and surgical outcomes at the time of review. Differences were resolved by consensus. Cases were excluded in which there was no adequate pre-procedure radiograph. In total, 182 cases were reviewed. The medical records were reviewed for enema and surgical outcomes. RESULTS: Radiographic findings included normal bowel gas pattern in 13%, soft-tissue mass in 26%, paucity of bowel gas in 65%, meniscus sign in 12% and obstruction in 10% of the cases, with 17.5% of patients having more than one finding. In patients with bowel obstruction on radiographs, there was a statistically significant decrease in success of therapeutic enema (83% vs. 21%, P=0.0001), increase in complicated surgical reductions (47% vs. 4%, P=0.0012), and increase in bowel resection (42% vs. 4%, P=0.003) compared to patients with normal bowel gas pattern. CONCLUSION: Radiographs can offer prognostic information regarding the potential for therapeutic enema success, as well as potential surgical outcomes in patients failing enema reduction. Particularly, bowel obstruction significantly decreases the success of therapeutic enema and increases the need for bowel resection.

Top Ten Things Palliative Care Clinicians Should Know About Caring for Hindus.

Hinduism is one of the five major world religions with >1 billion followers worldwide and encompasses a diversity of belief systems. As of 2010, an estimated 1.8 million Hindus lived in the United States, and this number is expected to increase to 4.8 million by 2050, making the United States home to the largest Hindu population outside of South Asia. As this population continues to grow, it will become increasingly important that clinicians of all disciplines develop a basic understanding of their beliefs and practices to address their palliative care needs. This article highlights 10 considerations for Hindu patients and their families relevant to inpatient care, symptom management, and advance care planning.

Cinnamon and its Metabolite Protect the Nigrostriatum in a Mouse Model of Parkinson's Disease Via Astrocytic GDNF.

Glial cell line-derived neurotrophic factor (GDNF) has potent neurotrophic effects and is known to promote the dopaminergic (DA) neuronal survival in cellular and animal models of Parkinson's disease (PD). However, long-term ectopic GDNF delivery is associated with long lasting adverse side effects in PD patients. Therefore, finding safer and effective ways to elevate endogenous GDNF levels is an active area of research. This study underlines the importance of sodium benzoate (NaB), a metabolite of commonly-used spice cinnamon, a food-additive and an FDA-approved drug against hyperammonemia, in stimulating GDNF in primary mouse and human astrocytes. Presence of cAMP response element (CRE) in the Gdnf gene promoter, recruitment of CREB to the Gdnf promoter by NaB and abrogation of NaB-mediated GDNF expression by siRNA knockdown of CREB suggest that NaB induces the transcription of Gdnf via CREB. Finally, oral administration of NaB and cinnamon itself increased the level of GDNF in vivo in the substantia nigra pars compacta (SNpc) of normal as well as MPTP-intoxicated mice. Accordingly, cinnamon and NaB treatment protected tyrosine hydroxylase positive neurons in the SNpc and fibers in the striatum, normalized striatal neurotransmitters, and improved locomotor activities in MPTP-intoxicated Gfapcre mice, but not GdnfΔastro mice lacking GDNF in astrocytes. These findings highlight the importance of astroglial GDNF in cinnamon- and NaB-mediated protection of the nigrostriatum in MPTP mouse model of PD and suggest possible therapeutic potential of cinnamon and NaB in PD patients. Graphical abstract Cinnamon metabolite sodium benzoate (NaB) activates cAMP-response element-binding (CREB) via protein kinase A (PKA) in astrocytes. Activated CREB then binds to cAMP-response element (CRE) present in GDNF gene promoter to stimulate the transcription of GDNF in astrocytes. This astrocytic GDNF leads to nigral trophism and protects dopaminergic neurons from MPTP insult.