Pharmacokinetics and safety of erenumab in pediatric patients with migraine: A phase I, randomized, open-label, multiple-dose study.

Erenumab, a fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, is efficacious and safe for prevention of attacks of migraine in adults. This phase I, randomized, open-label, multiple-dose study evaluated the safety, tolerability, and pharmacokinetics (PK) of erenumab in children and adolescents with migraine. The initial treatment phase lasted 12 weeks, followed by an optional 40-week extension phase for adolescents.

A case of non-mosaic X trisomy (65,XXX) in a Thoroughbred mare confirmed by cytogenetic and molecular analysis.

A 9-year-old Thoroughbred mare with normal external genitalia and regular oestrus symptoms was gynecologically examined prior to insemination. This primary examination revealed the presence of a hypoplastic uterus and the lack of normal ovaries, and the mare was therefore subjected to more detailed diagnostics, including endocrinological, genetic, and clinical tests. Diagnostic imaging with the use of ultrasonography and endoscopy confirmed the underdevelopment of internal genitalia.

Multiplanar (4-Dimension) Breast Augmentation-A Personal Surgical Concept for Dynamic Implant-Tissue Interaction Providing Sustainable Shape Stability.

Background: In esthetic breast augmentation long-term shape stability and natural appearance remain an ongoing challenge. The authors found that to reduce the incidence of secondary deformity and increase the natural feel and appearance, a standard multiplanar procedure combining a subfascial and dual plane approach with fasciotomies will provide long-term stability and esthetic quality.

Patients And Methods: The technique involves a submuscular dissection, release of the infranipple portion of the pectoralis muscle combined with the wide subfascial release of the breast gland, and scoring of the deep plane of the superficial glandular fascia.

Accessible Tutoring Platform Using Audio-Tactile Graphics Adapted for Visually Impaired People.

One of the problems faced by people with blindness is access to materials presented in graphical form. There are many alternative forms of providing such information, but they are very often ineffective or have certain limitations. The development of mobile devices and touch sensors enabled the development of new tools to support such people.

Age at League Entry and Early All-Cause Mortality among National Football League Players.

Background: A growing body of research suggests that American football players are exposed to higher cumulative head impact risk as competition level rises. Related literature finds that head impacts absorbed by youth, adolescent, and emerging adult players are associated with elevated risk of long-term health problems (e.g.

Pharmacokinetics, Tolerability, and Safety of Single and Multiple Omecamtiv Mecarbil Doses in Healthy Japanese and Caucasian Subjects.

Background And Objectives: Omecamtiv mecarbil (OM) is a cardiac myosin activator under development for the treatment of heart failure. The pharmacokinetics of single and multiple doses of OM were investigated in healthy Japanese subjects in two clinical studies.

Methods: Study 1 (n = 36) evaluated the bioavailability and pharmacokinetics after intravenous infusion (15 mg/h for 4 h) and an oral modified release (MR) tablet in healthy Japanese and Caucasian subjects using 25 mg single and multiple doses and 50 mg single dose.

Relative Bioavailability of Omecamtiv Mecarbil Pediatric Minitablet Formulations in Healthy Adult Subjects.

Background And Objective: Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets.

Effect of Varying Degrees of Hepatic Impairment on the Pharmacokinetics of Omecamtiv Mecarbil.

Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator under investigation for the treatment of heart failure with reduced ejection fraction. OM is primarily eliminated via metabolism mediated by multiple cytochrome P450 enzymes. This phase 1 single-dose, multicenter, open-label, nonrandomized study evaluated the pharmacokinetics (PK) of OM and major metabolites M3 and M4, safety, and tolerability following oral administration of a single dose of 25-mg MR tablet in subjects with mild (n = 6) or moderate (n = 6) hepatic impairment (according to Child-Pugh classification) versus subjects with normal hepatic function (n = 6).

Switchability and minimal effect of food on pharmacokinetics of modified release tablet strengths of omecamtiv mecarbil, a cardiac myosin activator.

Omecamtiv mecarbil (OM) is a cardiac myosin activator in clinical development for the treatment of heart failure. The effect of food on the pharmacokinetics (PK) of 25, 37.5, and 50 mg strength modified release (MR) tablets and the bioequivalence of two 25 mg tablets versus one 50 mg MR tablet were evaluated in two open-label, randomized, cross-over studies in healthy subjects.

Pharmacokinetics, Disposition, and Biotransformation of [C]Omecamtiv Mecarbil in Healthy Male Subjects after a Single Intravenous or Oral Dose.

Omecamtiv mecarbil (OM) is a novel cardiac myosin activator that is currently in clinical development for the treatment of heart failure. The absorption and disposition of [C]OM (60 µCi) were studied after a single intravenous infusion (35 mg over 1 hour) or oral solution dose (35 mg) in 14 healthy male subjects. Mean recovery of the administered [C]OM dose was 85.

The equine graying with age mutation of the STX17 gene: A copy number study using droplet digital PCR reveals a new pattern.

The equine graying with age causative mutation in the syntaxin-17 gene (STX17) has been known for over a decade, but proper genotyping of this variant remains challenging due to its molecular character (4.6-kb tandem duplication). Precise information on gray mutation status is important for horse breeders and veterinarians, since gray homozygous horses are more prone to developing aggressive melanoma tumors than heterozygotes.

Computer aided math learning as a tool to assess and increase motivation in learning math by visually impaired students.

Purpose: Effective teaching and learning mathematics is important to achieve good results during an academic and professional career. This is especially difficult for visually impaired students because of difficulties in managing structural information included in maths formulae.

Methods: The extended multimedia alternative method, including the problem of decomposition and knowledge vector, were presented and compared to the classical teaching method.

Computer-aided therapeutic diagnosis for anorexia.

Background: Anorexia nervosa is a clinical disorder syndrome of the wide spectrum without a fully recognized etiology. The necessary issue in the clinical diagnostic process is to detect the causes of this disease (e.g.

Association of Professional Football Cumulative Head Impact Index Scores With All-Cause Mortality Among National Football League Players.

Importance: Long-term adverse health outcomes, particularly those associated with repetitive head impacts, are of growing concern among US-style football players in the US and Canada.

Objective: To assess whether exposure to repetitive head impacts during a professional football career is associated with an increase in the risk of all-cause mortality.

Design, Setting, And Participants: This retrospective cohort study included 13 912 players in the 1969 to 2017 National Football League (NFL) seasons.

Electromagnetic compatibility issues in hybrid wired and wireless industrial networks.

Industrial networks are currently the only communication means designed for real-time systems used in industry. Networked control systems (NCS) are still important and commonly used type of such systems operating on shop floor. As a computerized node of NCS, a programmable logic controller (PLC) is usually used.

Genes encoding equine β-lactoglobulin (LGB1 and LGB2): Polymorphism, expression, and impact on milk composition.

β-lactoglobulin is one of the most abundant milk whey proteins in many mammal species, including the domestic horse. The aim of this study was to screen for polymorphism in the equine LGB1 and LGB2 gene sequences (all exons, introns, and 5'-flanking region) and to assess potential relationship of particular genotypes with gene expression levels (measured in milk somatic cells) and milk composition traits (protein, fat, lactose, and total β-lactoglobulin content). Direct DNA sequencing analysis was performed for twelve horse breeds: Polish Primitive Horse (PPH), Polish Coldblood Horse (PCH), Polish Warmblood Horse (PWH), Silesian, Hucul, Fjording, Haflinger, Shetland Pony, Welsh Pony, Arabian, Thoroughbred, and Percheron-and revealed the presence of 83 polymorphic sites (47 and 36 for LGB1 and LGB2 genes, respectively), including eight that were previously unknown.

Application of droplet digital PCR in diagnosing of X monosomy in mares.

Background: X monosomy is the most common disorder of sex development in horses. Although cytogenetic analysis is still the gold standard in the diagnosis of equine X monosomy, novel molecular techniques are being sought to quickly and reliably detect this chromosome abnormality.

Objectives: The goal of this study was to evaluate the usefulness of a novel variant of the PCR technique-namely, droplet digital PCR (ddPCR)-in the detection of X monosomy in mares.

Is Obesity Protective in Thoracoabdominal Penetrating Trauma?

The incidence of obesity has been increasing in the United States, and the medical care of obese patients after injury is complex. Obesity has been linked to increased morbidity after blunt trauma. Whether increased girth protects abdominal organs from penetrating injury or complicates management from obesity-associated medical comorbidities after penetrating injury has not been well defined.

and genotypes reveal discrepancies in officially recorded coat colors of Hucul horses.

Although only a few specific pigmentation types are allowed within the Hucul horse registry, accurate determination of particular coat colors can be uncertain due to the presence of variation in color shades and segregation of multiple dun dilution variants. Herein, we genotyped the previously identified polymorphisms within two coat color loci TBX3 (T-box 3) and ASIP (Agouti Signaling Protein) in 462 Hucul individuals and compared the genotype predicted phenotypes with observed pigmentation types provided in the Polish Horse Breeders Association database. We identified disagreement between the predicted and recorded coat color in 157 horses (34%).

Factors influencing the process of learning mathematics among visually impaired and blind people.

Effective instruction and comprehension of mathematics are important for achieving academic and professional success but are especially difficult for visually impaired individuals because of the inherent difficulty in managing structural information included in math formulae. An evaluation of an alternative for computer-aided math instruction and comprehension among visually impaired students was developed, and the evaluation included seven detailed categories of factors: behavioral, emotional, cognitive, social, distracting, motivational, and modeling factors. Then, the proposed method was used to compare the alternative teaching method, including problem decomposition and vector knowledge, to the classical teaching method with a teacher.

5'-flanking variants of equine casein genes (CSN1S1, CSN1S2, CSN2, CSN3) and their relationship with gene expression and milk composition.

Genes encoding casein proteins are important candidates for milk composition traits in mammals. In the case of the domestic horse, our knowledge of casein genes is limited mainly to coding sequence variants. This study involved screening for polymorphism in 5'-flanking regions of four genes encoding equine caseins (CSN1S1, CSN1S2, CSN2, and CSN3) and making a preliminary assessment of their effect on the gene expression (on the mRNA and protein levels) and milk composition traits in selected horse breeds.

Characterization of the Polish Primitive Horse (Konik) maternal lines using mitochondrial D-loop sequence variation.

The Polish Primitive Horse (PPH, Konik) is a Polish native horse breed managed through a conservation program mainly due to its characteristic phenotype of a primitive horse. One of the most important goals of PPH breeding strategy is the preservation and equal development of all existing maternal lines. However, until now there was no investigation into the real genetic diversity of 16 recognized PPH dam lines using mtDNA sequence variation.

Tutoring math platform accessible for visually impaired people.

Background: There are many problems with teaching and assessing impaired students in higher education, especially in technical science, where the knowledge is represented mostly by structural information like: math formulae, charts, graphs, etc. Developing e-learning platform for distance education solves this problem only partially due to the lack of accessibility for the blind.

Method: The proposed method is based on the decomposition of the typical mathematical exercise into a sequence of elementary sub-exercises.