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0001), had a beneficial effect on the evolution of MFA. Conclusion This is the first longitudinal study describing women with MFA. The radiological evolution of MFA seamed favorable and similar to that expected for a single FA. We identified factors influencing the evolution of the disease, including progestin treatments such as lynestrenol, which could have a beneficial effect. Our cohort should be followed further in order to expand our knowledge of MFA, especially concerning the risk of breast cancer.Objective Despite its increasing use in neonates, the literature on the use of vasopressin (VP) in neonates is limited. The aim of this study is to evaluate the systemic and pulmonary effects of VP in neonates and to assess its safety among them. Study design This retrospective study enrolled all neonates in two level III neonatal intensive care units in Winnipeg, Manitoba, who had received VP therapy between 2011 and 2016. Infants with congenital malformations/chromosomal disorders were excluded. The changes in cardiovascular and pulmonary parameters were collected from patient charts. The primary outcome was the mean blood pressure (MBP) post-VP initiation. Secondary outcomes included systolic blood pressure (SBP) and diastolic blood pressure (DBP), vasoactive inotropic score (VIS), pH, urine output, lactate, base deficit (BD), mean airway pressure (MAP), and oxygen requirement. Results A total of 33 episodes from 26 neonates were analyzed. The postnatal age at VP initiation was 14 days (interquartile range [IQR] 4-25), and the median starting dose was 0.3 mU/kg/min (IQR 0.2-0.5). MBP improved significantly after VP initiation from 28 to 39 mm Hg 24 hours after VP initiation (p less then 0.001). Similar changes are observed with SBP and DBP. VIS declined from 15 to 6 at 24 hours, while pH, lactate, BD, and oxygen requirement improved significantly. While urine output marginally improved, there were no changes to MAP 24 hours post-VP initiation. Hyponatremia was observed in 21 episodes (64%) and severe hyponatremia in 7 episodes (33%). Conclusion VP appears to be a promising rescue therapy in catecholamine resistant shock or refractory pulmonary hypertension in neonates.The rising costs of new medicinal products are a challenge to the economic sustainability of national healthcare systems in ensuring patients' access to therapies. European Union (EU) and US legislators have provided regulatory pathways aimed at simplifying Marketing Authorization (MA) applications for new medicinal products in cases when safety and efficacy profiles can be derived from the data of already-marketed products. In this review, we discuss the different regulatory pathways towards the MA of new medicinal products containing old drug substances and intended to improve the therapeutic value of a treatment, to obtain a new therapeutic indication (drug repositioning), or to ensure the same therapeutic value of a reference product at lower costs.Osteoarthritis (OA) is a debilitating disease with no effective disease-modifying therapies. Among the challenges for developing treatment is achieving targeted drug delivery to affected joints. This has contributed to the failure of several drug candidates for the treatment of OA. Over the past 20 years, significant advances have been made in antisense oligonucleotide (ASO) technology for achieving targeted delivery to tissues and cells both in vitro and in vivo. Since ASOs are able to bind specific gene regions and regulate protein translation, they are useful for correcting aberrant endogenous mechanisms associated with certain diseases. ASOs can be delivered locally through intra-articular injection, and can enter cells through natural cellular uptake mechanisms. Despite this, ASOs have yet to be successfully tested in clinical trials for the treatment of OA. Recent chemical modification to ASOs have further improved cellular uptake and reduced toxicity. Among these are locked nucleic acid (LNA)-based ASOs, which have shown promising results in clinical trials for diseases such as hepatitis and dyslipidemia. Recently, LNA-based ASOs have been tested both in vitro and in vivo for their therapeutic potential in OA, and some have shown promising joint-protective effects in preclinical OA animal models. In order to accelerate the testing of ASO therapies in a clinical trial setting for OA, further investigation into delivery mechanisms is required. In this review article, we discuss opportunities for viral-, particle-, biomaterial-, and chemical modification-based therapies, which are currently in preclinical testing. VP16 We also address potential roadblocks in the clinical translation of ASO-based therapies for the treatment of OA, such as the limitations associated with OA animal models and the challenges with drug toxicity. Taken together, we review what is known and what would be useful to accelerate translation of ASO-based therapies for the treatment of OA.Background The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. Methods We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. Results The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. Conclusion As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.