Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca2+]i distribution in human iPSC-derived cardiomyocytes.

Mutations in ubiquitously expressed presenilin genes (PSENs) lead to early-onset familial Alzheimer's disease (FAD), but patients carrying the mutation also suffer from heart diseases. To elucidate the cardiac myocyte specific effects of PSEN ΔE9, we studied cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) from patients carrying AD-causing PSEN1 exon 9 deletion (PSEN1 ΔE9). When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP3Rs) by 2-ABP. The SR Ca2+ leak did not affect electrophysiological properties of the hiPSC-CMs, but according to experiments and in silico simulations the leak induces a diastolic buildup of [Ca2+] near the perinuclear SR and reduces the releasable Ca2+ during systole. This demonstrates that PSEN1 ΔE9 induced SR Ca2+ leak has specific effects in iPSC-CMs, reflecting their unique structural and calcium signaling features. The results shed light on the physiological and pathological mechanisms of PSEN1 in cardiac myocytes and explain the intricacies of comorbidity associated with AD-causing mutations in PSEN1.

Head and Neck Restoration in Scar Alopecia: Hair Transplantation in Scalp, Eyebrows, Beard and Mustache.

BACKGROUND: Surgical management of hair loss has become an increasingly challenging procedure, when dealing with scar alopecia. We investigated the efficacy of hair transplantation in patients with head and neck scar alopecia. METHODS: From 2016 to 2018 in Shiraz, Iran, all patients with scar alopecia in head and neck were evaluated for efficacy of follicular unit extraction (FUE), follicular unit transplantation (FUT) or a combination of two methods from donor sites in scalp and beard various hair-grafts were compared. RESULTS: Fifty-six patients were enrolled. Most of them were between 31 and 40 yr old (48.3%) and male (71.4%). Trauma, burn, surgical excision of adjacent skin, radiotherapy and leishmaniasis were the registered causes. Scars were visible in scalp (39.3%), beard (28.6%), eyebrow (21.4%), and moustache (10.7%) regions. FUE (87.5%), FUT (10.7%) and a combination (1.8%) were the used methods. One-hair-grafts were used in eyebrows (100%), moustache (100%), beard (88%) and scalp (7.9%), while 2-hair-grafts in beard (6%) and scalp (47.4%) and 3-haired grafts in beard (6%) and scalp (44.7%) transplantations. CONCLUSION: In head and neck scar alopecia, hair transplantation was selected based on type and depth of scar. FUE was targeted when huge grafts were not needed, including beard, moustache, and eyebrow, while FIT was used when extensive scars were present in scalp. One-hair-grafts were mostly applied for eyebrow, moustache and beard, 2-hair- and 3-hair- grafts for beard and scalp transplantation. These findings can be added to the literature when FUE, FIT, or their combination are targeted in hair restoration of scar alopecia in head and neck.

Genetic Polymorphisms of Cytochrome p450 (2C9) Enzyme in Patients with Type 2 Diabetes Mellitus in Turkmen and Fars Ethnic Groups.

BACKGROUND: Cytochrome P450 2C9 (CYP450 2C9) has an important role in metabolic processes. Mutations in CYP450 2C9 genes may affect the catalytic activity of this enzyme. The aim of the present study is to assess the genetic polymorphisms of Cytochrome P450 (2C9) enzyme in Turkmen and Fars ethnic groups with type 2 diabetes compared with controls. METHODS: A total of 336 Turkmen and 336 Fars type 2 diabetic patients and 336 healthy Turkmen and Fars individuals were included in this study. Genomic DNA was extracted from whole blood samples and then the CYP2C9 genotyping was done using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. RESULTS: The CYP2C9*1, CYP2C9*2 and CYP2C9*3 allele frequencies in type 2 diabetic patients were 85.27%, 11.68%, and 3.05%, and in control were 87.13%, 8.56%, and 4.31%, respectively. We found significant differences between allele distribution of 2C9 in type 2 diabetic patients and controls. CYP2C9*2 and CYP2C9*3 allele frequency was significantly different in Turkmen and Fars type 2 diabetic compared to two ethnic controls. The CYP2C9*1/*1 and CYP2C9*1/*2 genotypes frequencies in type 2 diabetic Turkmen showed significant differences compared to Turkmen control. There were significant differences in the genotype frequency of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, and CYP2C9*2/*3 between type 2 diabetic Fars and Fars controls. Two diabetic ethnic groups showed statistically significant differences in frequencies of CYP2C9*2/*2 and CYP2C9*2/*3 genotypes. CONCLUSION: Our study suggests that diabetic patients with mutant CYP2C9 polymorphism may show different antidiabetic drug metabolism compared to the wild-type allele. In this regard, determination of CYP2C9 alleles and genotypes can be a useful tool for the treatment of diabetic patients with antidiabetic drugs because it may assist physicians' to determine optimal dosage and efficiency of drugs metabolized by this polymorphic enzyme.