The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study

Purpose: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. Methods: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. Results: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p?p?=?0.022), age (HR 1.03, p?p?p?=?0.038), peripheral artery disease (HR 1.83, p?=?0.025) and amputation (HR 4.1, p?=?0.009) at baseline were significant predictors of overall mortality. Conclusions: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality     

Can long-term bisphosphonate use causes low-energy fractures? A case report

Bisphosphonates are inorganic pyrophosphate analog which accumulate on the bone surface, cause osteoclast apoptosis, and inhibit bone resorption. The nitrogen-containing bisphosphonates continue to be the drug of choice for the treatment of osteoporosis in both men and women. Although histomorphometric studies including bone biopsies have not shown any evidence of microcracks, recent studies have revealed that potent bisphosphonates are responsible for the oversuppression of bone turnover leading to microdamages, reduced bone strength, and increased fracture risk. There are individual cases reporting atypical femoral fractures and severely suppressed bone turnover along with long-term (≥5 years) use of biphosphonates. In this study, we report on a 74-year-old woman with a history of continuous alendronate use for nearly 16 years who presented to the emergency department with right proximal humerus and left femur fracture.     

The Generation of Zebrafish Mariner Model Using the CRISPR/Cas9 System

Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as a powerful tool for gene function studies and has great potential for gene therapy. Although CRISPR/Cas9 has been widely used in many research fields, only a few successful zebrafish models have been established using this technology in hearing research. In this study, we successfully created zebrafish mariner mutants by targeting the motor head domain of Myo7aa using CRISPR/Cas9. The CRISPR/Cas9-generated mutants showed unbalanced swimming behavior and disorganized sterocilia of inner ear hair cells, which resemble the phenotype of the zebrafish mariner mutants. In addition, we found that CRISPR/Cas9-generated mutants have reduced number of stereociliary bundles of inner ear hair cells and have significant hearing loss. Furthermore, phenotypic analysis was performed on F0 larvae within the first week post fertilization, which dramatically shortens data collection period. Therefore, results of this study showed that CRISPR/Cas9 is a quick and effective method to generate zebrafish mutants as a model for studying human genetic deafness. Anat Rec, 303:556–562, 2020. © 2019 American Association for Anatomy     

Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy

Adenosine deaminase 2 (ADA2) deficiency due to CECR1 mutations is a recently defined disorder that involves systemic inflammation and vasculopathy often associated with polyarteritis nodosa. We report on a 5-year-old girl with a severe vasculopathy who carried two novel mutations in CECR1. Conclusion: Identification of CECR1 mutations in patients with vasculopathy may lead to earlier diagnosis of ADA2 deficiency.     

Placebo effect in burning mouth syndrome: a systematic review

Placebo controls play a critical role in the evaluation of any pharmacotherapy. This review surveys the placebo arm in 12 randomized controlled trials (RCTs) investigating burning mouth syndrome (BMS) and documents a positive placebo response in 6 of them. On average, treatment with placebos produced a response that was 72% as large as the response to active drugs. The lack of homogeneity in the use of placebos adds to the difficulty in comparing results and aggregating data. Future RCTs investigating BMS would benefit from larger sample sizes, adequate follow‐up periods, and use of a standard placebo.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).