This case report describes a 65-year-old female with iatrogenic opioid use disorder for chronic lower back pain, who developed Takotsubo cardiomyopathy on multiple occasions following buprenorphine induction. This patient had three opioid transfers to buprenorphine, over 4 years, two of which were complicated by Takotsubo cardiomyopathy. In the transfer where she did not develop Takotsubo cardiomyopathy, she was treated with high doses of the centrally acting agonist, clonidine (three times a day, total of 600 mcg/day), up to and including the day of her transfer. This case highlights the potential consequences of a precipitated withdrawal with buprenorphine in an opioid transfer and its possible prevention with clonidine. To our knowledge, this is the first description of the recurrent Takotsubo cardiomyopathy in an opioid transfer setting. Given that buprenorphine is a partial agonist, in the presence of a full opioid agonist, it can precipitate withdrawal within minutes to hours of its administration. Selleck CDK inhibitor Opioid withdrawal can result in a sympathetic overdrive. Although complications of opioid withdrawal are extensively documented, cardiotoxicity is uncommon. As the use of buprenorphine and its new injectable formulations rise, it is important for prescribers to be aware of this life threatening complication. The prophylactic administration of clonidine can be considered to reduce the risk of cardiotoxicity, as well as manage opioid withdrawal symptoms.

To review reverse cardiac remodeling and guideline-directed medical and device therapy (GDMT) within the context of recent data on combined angiotensin receptor/neprilysin inhibitor (ARNI) therapy.

Preliminary data suggested that ARNI therapy led to significant reversal of deleterious cardiac remodeling. More definitive data regarding impact of ARNI therapy on remodeling parameters are now available from two prospective trials, PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure) and EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction). Both studies demonstrated marked improvements in biomarker and echocardiographic parameters of reverse cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Much of the observed clinical benefit of sacubitril/valsartan therapy in patients with reduced ejection fraction (HFrEF). Much of the observed clinical benefit of sacubitril/valsartan therapy in patients with HFrEF is likely related to significant reverse cardiac remodeling. Ongoing trials will assess the role for ARNI therapy in patients with heart failure with preserved ejection fraction (HFpEF) and in the post-myocardial infarction setting. Future studies should comprehensively assess predictors of response to ARNI therapy.Bioactivity guided separation of Walsura trichostemon stem methanolic extract led to the isolation of four new dammarane (1-4) and two new apotirucallane triterpenoids (5-6), together with one limonoid (7), 11,25-dideacetyltrichostemonate, 12β, 20S, 24R-trihydroxydammar-25-en-3-one and 12β, 20S, 25-trihydroxydammar-23-en-3-one. Compounds 1-7 showed in vitro inhibitory activity on the proliferation of A549, human lung adenocarcinoma cell line.I investigated the causative agents of licorice-induced pseudoaldosteronism, which is a frequent side effect of Japanese traditional Kampo medicines. Glycyrrhizin (GL), the main ingredient of licorice, is absorbed after being metabolized to glycyrrhetinic acid (GA) by intestinal bacteria, and then metabolized in liver to 3-monoglucuronyl-glycyrrhetinic acid (3MGA). In normal condition, 3MGA is excreted into bile via a multidrug resistance-related protein (Mrp) 2, therefore, 3MGA does not appear in blood circulation. However, under the dysfunction of Mrp2, 3MGA appears in the blood circulation and is excreted into the urine by not glomerular filtration but tubular secretion via organic anion transporter (OAT) 1 and 3. At this time, 3MGA inhibits type 2 11β-hydroxysteroid dehydrogenase (11βHSD2) in tubular cells to cause pseudoaldosteronism. Since GA is not the substrates of these transporters, GA cannot inhibit 11βHSD2 in tubular cells. Therefore, it was considered that 3MGA was the causative agents of licoricsociated with low plasma renin activity, plasma aldosterone levels, and serum potassium levels. It is highly probable that compound 3 is the true causative agent of pseudoaldosteronism.

Constipation is a common problem in children with spastic cerebral palsy (sCP) with a prevalence that reaches 75%. We hypothesized that treating constipation in those children will improve their health and shorten time spent in daily care. Our aim was to evaluate the efficacy and safety of oral magnesium sulfate for treating chronic constipation in children with sCP.

A prospective, double-blinded randomized control trial was carried out involving 100 children aged 2-12years with sCP (level III-V of the Gross Motor Functional Classification system) and chronic constipation. They were followed up in the Pediatric neurology clinic, Children’s hospital, Ain Shams University, May 2017- January 2019. The intervention group (O-Mg) received oral magnesium sulfate 1mL/kg/day daily for 1month compared to the placebo. Outcome measures were constipation improvement and decrease in bowel evacuation time after 1month.

Initially, weekly bowel movements, constipation scores and stool consistency were comparable in both evacuation attempts.Current methods of CRISPR-Cas9-mediated site-specific mutagenesis create deletions and small insertions at the target site which are repaired by imprecise non-homologous end-joining. Targeting of the Cas9 nuclease relies on a short guide RNA (gRNA) corresponding to the genome sequence approximately at the intended site of intervention. We here propose an improved version of CRISPR-Cas9 genome editing that relies on two complementary guide RNAs instead of one. Two guide RNAs delimit the intervention site and allow the precise deletion of several nucleotides at the target site. As proof of concept, we generated heterozygous deletion mutants of the kcng4b, gdap1, and ghitm genes in the zebrafish Danio rerio using this method. A further analysis by high-resolution DNA melting demonstrated a high efficiency and a low background of unpredicted mutations. The use of two complementary gRNAs improves CRISPR-Cas9 specificity and allows the creation of predictable and precise mutations in the genome of D. rerio.