Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases.

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(?). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.

Long-Term Outcomes 10 Years after Laparoscopic Sleeve Gastrectomy: a Single Center Retrospective Analysis.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed bariatric procedure in the world. The aim of the study was to evaluate outcomes after 10 years. METHODS: Patients who underwent LSG between 2005 and 2010 in a single center were retrospectively assessed, focusing mainly on the percentage of excess weight loss (%EWL) after 10 years. Inadequate weight loss was defined as a %EWL < 50% or the need to perform a revisional bariatric surgery. RESULTS: Overall, 149 patients underwent LSG, with a median preoperative body mass index of 42.0 ± 6.5 kg/m2. Ten patients (6.7%) underwent previous bariatric procedure. Patients eating behavior was described as volume eaters in 73 (49%), sweet eaters in 11 (7.4%) and both volume and sweet eaters in 65 (43.6%). Six patients died during follow-up and 25 patients were lost to follow-up, leaving 118 (79%) patients who completed full follow-up. Thirty-five patients (23.5%) needed a revisional bariatric surgery. For the 83 remaining patients, the mean %EWL was 35.9% at 10 years, only 23 of 83 patients (27.7%) had a %EWL ≥ 50%. Thus 80.5% patients (95/118) experienced inadequate weight loss 10 years after LSG. A lower %EWL after 1 year was predictive for inadequate weight loss after 10 years. CONCLUSION: Ten years after LSG, the rate of inadequate weight loss was high, reaching 80% of patients. Thirty percent of patients required a revisional bariatric procedure. New studies must try to identify patients who are good candidates for LSG and strategies to improve long-term outcomes.

A cross-sectional study on the personality traits of episodic and chronic migraine patients.

BACKGROUND: Migraine, is a common neurological disorder that may be associated with certain personality traits. This study aims to identify and compare the personality traits accompanying the clinical and sociodemographic profiles in migraine groups. METHODS: The study included a cohort of chronic, episodic migraine (CM - EM) and healthy controls (HC). Migraine was diagnosed according to the International Classification of Headache Disorders-3ß criteria. Age, gender, migraine-related disease duration, number of days with a headache each month, and headache intensity of the patients were recorded. The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) was used to determine personality traits. RESULTS: The study groups were similar in terms of sociodemographic characteristics (70 CM, 70 EM, and 70 HC). The visual analog scale (VAS) score was significantly higher in CM (p < 0.05). No statistically significant difference was found between the groups concerning symptoms of migraine such as osmophobia, photophobia, phonophobia, and nausea (p > 0.05). When the personality traits were examined, the mean scores of the MMPI test results of migraine patients were found to be higher than healthy controls in line personality disorders (p < 0.05 for all personality traits). In CM patients, the 'hysteria' score was found to be higher in subgroup evaluation (p < 0.05). CONCLUSION: EM and CM patients had more evidence of personality disorders than healthy controls. CM patients had higher hysteria scores than EM patients. In addition to pain treatment, determining personality traits and providing appropriate management with a multidisciplinary approach can benefit both in terms of treatment, cost, and time.

A giant parastomal hernia in a high risk patient: preparation to make surgery worthwhile.

BACKGROUND: Parastomal hernia (PH) is a frequent and well-known complication of stoma placement. Most PHs are asymptomatic and those who are not are usually well tolerated by patients. Thus, watchful waiting is a common practice. Nevertheless, this management policy is associated with a risk of complications and with an inevitable risk of hernia enlargement, complicating its subsequent surgery. Moreover, PH can affect body image and alter the quality of life. METHODS: We herein present a complex case of a 67-year-old man with multiple comorbidities, who presented with an uncommon, below knee, giant PH, which was managed in a two-steps surgery by a multidisciplinary team comprising a senior digestive surgeon, experienced in abdominal wall repair, cardiologist, pulmonologist, anesthesiologist, psychiatrist, dietitian and physiotherapist. RESULT: Treatment started with 8 months hygienic measures comprising smoking cessation, strict control of diabetes and hypertension, a strict diet, and a physical fitness and pulmonary rehabilitation program. Two steps surgery started by colostomy transposition along with pre-peritoneal mesh repair to the right side and the second step consisted of a prophylactic PH repair using a Key-hole preperitoneal polypropelene mesh. CONCLUSION: PH is a common and sometimes inevitable complication of stoma creation. The success achieved by operating a heavily morbid patient, is only possible through the combined efforts of the multidisciplinary team and a preoperative rigorous management.

A novel bilayer zein/MMT nanocomposite incorporated with H. perforatum oil for wound healing.

Recently, layered structures composed of nanofibers have gained attention as a novel material to mimic skin tissue in wound healing applications. The aim of this study is to develop a novel hybrid bilayer material composed of zein based composite film and nanofiber layers as a wound dressing material. The upper layer was composed of H. perforatum oil incorporated zein film including MMT and the bottom layer was comprised of 3D electrospun zein/MMT nanofibers to induce wound healing with the controlled release of H. perforatum oil. The bilayer composites were characterized in terms of mechanical test, WVP, water uptake and surface wettability. Antimicrobial activity of the wound dressings against microorganisms were investigated by disc diffusion method. In vitro cytotoxicity of monolayer film and bilayer structure was performed using WST-1 assay on HS2 keratinocyte and 3T3 cell lines. Results indicated that the prepared monolayer films showed appropriate mechanical and gas barrier properties and surface wettability for wound healing. Controlled release of H. perforatum oil was obtained from fabricated membranes up to 48 h. Bilayer membranes showed antimicrobial activity against E. coli, S. aureus, and C. albicans and did not show any toxic effect on NIH3T3 mouse fibroblast and HS2 keratinocyte cell lines. In vitro scratch assay results indicated that H. perforatum oil had a wound healing effect by inducing fibroblast migration. The proliferation study supported these results by increasing fibroblast proliferation on H. perforatum oil loaded bilayer membranes.

In vitro evaluation of Spirulina platensis extract incorporated skin cream with its wound healing and antioxidant activities.

CONTEXT: Algae have gained importance in cosmeceutical product development due to their beneficial effects on skin health and therapeutical value with bioactive compounds. Spirulina platensis Parachas (Phormidiaceae) is renowned as a potential source of high-value chemicals and recently used in skincare products. OBJECTIVE: This study develops and evaluates skin creams incorporated with bioactive S. platensis extract. MATERIALS AND METHODS: Spirulina platensis was cultivated, the aqueous crude extract was prepared and in vitro cytotoxicity of S. platensis extract in the range of 0.001-1% concentrations for 1, 3 and 7 d on HS2 keratinocyte cells was determined. Crude extracts were incorporated in skin cream formulation at 0.01% (w/w) concentration and in vitro wound healing and genotoxicity studies were performed. Immunohistochemical staining was performed to determine the collagen activity. RESULTS: 0.1% S. platensis extract exhibited higher proliferation activity compared with the control group with 198% of cell viability after 3 d. Skin cream including 1.125% S. platensis crude extract showed enhanced wound healing effect on HS2 keratinocyte cell line and the highest HS2 cell viability % was obtained with this concentration. The micronucleus (MN) assay results indicated that S. platensis extract incorporated creams had no genotoxic effect on human peripheral blood cells. Immunohistochemical analysis showed that collagen 1 immunoreactivity was improved by increased extract concentration and it was strongly positive in cells treated with 1.125% extract incorporated skin cream. CONCLUSIONS: The cell viability, wound healing activity and genotoxicity results showed that S. platensis incorporated skin cream could be of potential value in cosmeceutical and biomedical applications.

Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material.

Recent studies in wound dressing applications offer new therapies and promote wound healing process. The aim of this study was to develop Hypericum perforatum (St John's Wort) oil incorporated chitosan films for wound dressing applications. H. perforatum oil as a potential therapeutic agent was encapsulated in chitosan film to achieve a better wound dressing material. Oil incorporated chitosan films were successfully prepared by solvent casting method in different oil concentrations (0.25-1.5%v/v). Water vapor permeability (WVP), mechanical test, swelling behavior and surface hydrophobicity were performed in order to characterize the prepared films. Antimicrobial test was performed by disc diffusion method and the growth inhibition effects of the films including different amount of H. perforatum oil were investigated on Escherichia coli and Staphylococcus aureus. WVP increased with oil incorporation and the highest value was obtained for 0.25% oil concentration.The highest strain value was obtained in 0.25% oil content films although tensile stress decreased with increasing oil content. H. perforatum oil incorporated films had antimicrobial effect on both microorganisms. Chitosan based films had no cytotoxic effects on NIH3T3fibroblast cells and provided a good surface for cell attachment and proliferation. The results showed that the H. perforatum incorporated chitosan films seems to be a potential and novel biomaterial for wound healing applications.