Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility.

Cardiac myosin activation has been shown to be a viable approach for the treatment of heart failure with reduced ejection fraction. Here, we report the discovery of nelutroctiv (), a selective cardiac troponin activator intended for patients with cardiovascular conditions where cardiac contractility is reduced. Discovery of nelutroctiv began with a high-throughput screen that identified compound , a muscle selective cardiac sarcomere activator devoid of phosphodiesterase-3 activity.

Value of high-speed videoendoscopy as an auxiliary tool in differentiation of benign and malignant unilateral vocal lesions.

Purpose: The study aimed to assess the relevance of objective vibratory parameters derived from high-speed videolaryngoscopy (HSV) as a supporting tool, to assist clinicians in establishing the initial diagnosis of benign and malignant glottal organic lesions.

Methods: The HSV examinations were conducted in 175 subjects: 50 normophonic, 85 subjects with benign vocal fold lesions, and 40 with early glottic cancer; organic lesions were confirmed by histopathologic examination. The parameters, derived from HSV kymography: amplitude, symmetry, and glottal dynamic characteristics, were compared statistically between the groups with the following ROC analysis.

High-Speed Videoendoscopy Enhances the Objective Assessment of Glottic Organic Lesions: A Case-Control Study with Multivariable Data-Mining Model Development.

Unlabelled: The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using high-speed videolaryngoscopy (HSV).

Methods: Case-control study including 100 patients with unilateral vocal fold lesions in comparison to 38 normophonic subjects. Quantitative assessment with the determination of vocal fold oscillation parameters was performed based on HSV kymography.

Phenylalanine hydroxylase deficiency treatment and management: A systematic evidence review of the American College of Medical Genetics and Genomics (ACMG).

Purpose: Elevated serum phenylalanine (Phe) levels due to biallelic pathogenic variants in phenylalanine hydroxylase (PAH) may cause neurodevelopmental disorders or birth defects from maternal phenylketonuria. New Phe reduction treatments have been approved in the last decade, but uncertainty on the optimal lifespan goal Phe levels for patients with PAH deficiency remains.

Methods: We searched Medline and Embase for evidence of treatment concerning PAH deficiency up to September 28, 2021.

Catalytic Properties of Two Complexes of chromium(III) and cobalt(II) with Nitrilotriacetate, Dipicolinate, and 4-Acetylpyridine.

In this paper, a synthesis of two innovative coordination compounds, based on chromium(III) and cobalt(II) ions with N,O-donor ligands (nitrilotriacetate, dipicolinate) and 4-acetylpyridine, is reported. The obtained metal-organic compounds were structurally characterized using the single-crystal X-ray diffraction (XRD) method. The well-defined chromium(III) and cobalt(II) complexes were used as precatalysts in the oligomerization reaction of 2-chloro-2-propen-1-ol and 2-propen-1-ol with methylaluminoxane (MMAO) as an activator.

Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors.

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable.

Assessment of Vocal Fold Stiffness by Means of High-Speed Videolaryngoscopy with Laryngotopography in Prediction of Early Glottic Malignancy: Preliminary Report.

One of the most important challenges in laryngological practice is the early diagnosis of laryngeal cancer. Detection of non-vibrating areas affected by neoplastic lesions of the vocal folds can be crucial in the recognition of early cancerogenous infiltration. Glottal pathologies associated with abnormal vibration patterns of the vocal folds can be detected and quantified using High-speed Videolaryngoscopy (HSV), also in subjects with severe voice disorders, and analyzed with the aid of computer image processing procedures.

An evidence-based practice guideline of the National Society of Genetic Counselors for telehealth genetic counseling.

There are currently no practice guidelines available for genetic counseling using telehealth modalities. This evidence-based practice guideline was developed in response to increasing use of alternative service delivery models for genetic counseling, specifically telephone and video-based genetic counseling (telehealth genetic counseling or THGC). A recent systematic evidence review (SER) compared outcomes of THGC with in-person genetic counseling and found that for the majority of studied outcomes, THGC was a non-inferior and comparable service delivery model.

Isolated Severe Dysphonia as a Presentation of Post-COVID-19 Syndrome.

This is the first study assessing the clinical management of severe, isolated dysphonia during post-COVID-19 syndrome. One hundred and fifty-eight subjects met the inclusion criteria for the post-COVID-19 condition as specified by the WHO. Six patients were diagnosed with isolated severe dysphonia, constituting 3.

Trends in guideline implementation: an updated scoping review.

Background: Guidelines aim to support evidence-informed practice but are inconsistently used without implementation strategies. Our prior scoping review revealed that guideline implementation interventions were not selected and tailored based on processes known to enhance guideline uptake and impact. The purpose of this study was to update the prior scoping review.

The uptake and utility of genetic testing and genetic counseling for hypertrophic cardiomyopathy-A systematic review and meta-analysis.

Genetic testing and genetic counseling are routinely indicated for patients with hypertrophic cardiomyopathy (HCM); however, the uptake and utility of these services is not entirely understood. This systematic review and meta-analysis summarizes the uptake and utility of genetic counseling and genetic testing for patients with HCM and their at-risk family members, as well as the impact of genetic counseling/testing on patient-reported outcomes (PROs). A systematic search was performed through March 12, 2021.

Observational study of population genomic screening for variants associated with endocrine tumor syndromes in a large, healthcare-based cohort.

Background: In current care, patients' personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants.

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies.

Purpose: Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.

Diagnostic validity and clinical utility of genetic testing for hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Objective: This study summarises the diagnostic validity and clinical utility of genetic testing for patients with hypertrophic cardiomyopathy (HCM) and their at-risk relatives.

Methods: A systematic search was performed in PubMed (MEDLINE), Embase, CINAHL and Cochrane Central Library databases from inception through 2 March 2020. Subgroup and sensitivity analyses were prespecified for individual sarcomere genes, presence/absence of pathogenic variants, paediatric and adult cohorts, family history, inclusion of probands, and variant classification method.