miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.

Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long-term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV.

Construct and criterion validity of patient-reported outcomes (PROs) for depression: A clinimetric comparison.

Background: A number of patient-reported outcomes (PROs) have been developed but insufficient attention has been devoted to the assessment of their clinimetric properties. Clinimetrics, the science of clinical measurements, has been considered an emerging approach for evaluating reliability and validity of PROs. This is the first study using clinimetric principles to compare the construct and criterion validity of the Major Depression Inventory (MDI), the Beck Depression Inventory-II (BDI-II), the World Health Organization Well-Being Index (WHO-5), three of the most widely used PROs for the assessment of depression.

COVID-19: Rethinking the nature of viruses.

In this brief essay, we combine biological, historical, philosophical and anthropological perspectives to ask anew the question about the nature of the virus. How should we understand Sars-CoV-2 and why does it matter? The argument we present is that the virus undermines any neat distinction between the natural and the human-made, the biological and the social. Rather, to understand the virus and the pandemic we need to understand both as intimately connected to our own social and historical condition.

Motivational Interviewing Adapted to Group Setting for the Treatment of Relapse in the Behavioral Therapy of Obesity. A Clinical Audit.

Motivational interviewing (MI) is devised to change unhealthy behaviors by increasing motivation. We adapted MI to a group format for the treatment of relapse during the behavioral treatment of obesity and performed a clinical audit to evaluate its effectiveness in stopping weight regain. The program was structured in seven weekly sessions, plus a 6-month follow-up.

Maternal obesity: focus on offspring cardiometabolic outcomes.

Several human and animal studies have demonstrated that cardiometabolic parameters in infancy, childhood, adolescence and even adulthood are negatively influenced by many factors besides energy imbalance. Interestingly, maternal weight excess both before and during pregnancy seems to be a negative determinant of metabolic and cardiovascular outcomes in the offspring. This review includes both human and animal studies and finally highlights the link between maternal obesity and cardiometabolic disorders in offspring.

NAM Therapy-Evidence-Based Results.

Many orthodontists working on patients with cleft lip and palate (CLP) have shown great enthusiasm for presurgical infant orthopedics (PSIO) to improve surgical outcomes with minimal intervention. Even though every clinician aims to use the best treatment modality for their patients, PSIO effects can be confounded by surgical type and timing of the primary repair, as is discussed in many studies. In such cases, one should be cautious when evaluating the particular outcomes for patients with CLP since it is difficult to differentiate the sole effect of an individual surgical or orthodontic intervention.

Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis.

Objectives: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation.

Background: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations.

Review: Danon disease: Review of natural history and recent advances.

Danon disease is a severe multisystem disorder clinically characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation in male patients, and by a milder phenotype (predominantly involving cardiac muscle) in female patients. The disease is inherited as an X-linked dominant trait. The primary deficiency of lysosome-associated membrane protein-2 (LAMP-2) causes disruption of autophagy, leading to an impaired fusion of lysosomes to autophagosomes and biogenesis of lysosomes.

ARNIs: balancing "the good and the bad" of neuroendocrine response to HF.

Background: A new class of drugs-angiotensin receptor, neprylisin inhibitors, ARNI-has shown to be prognostic superior in HFrEF to the sole inhibition of the renin-angiotensin axes with enalapril. The ultimate mechanism of action of ARNIs is unknown.

Aim: We have considered that ARNI exerts a positive modulation of the neuroendocrine balance, with enhancement of the physiological diuresis and dilatation due to neprylisin inhibition by sacubitril.

Androgens in Congenital Adrenal Hyperplasia.

Congenital Adrenal Hyperplasias (CAH) are genetic diseases transmitted in an autosomal recessive way and these diseases affect many aspects of human health. The majority of CAH cases is due to a deficiency in 21-hydroxylase as a result of the existence of mutations in both alleles of the CYP21A2 gene. Since the identification of mild, non-classic forms of this disease, CAH has been recognized to be one of the most common genetic diseases in human beings.

Androgens and Severe Insulin Resistance States: Basic and Clinical Aspects.

Hyperandrogenism with or without polycystic ovary syndrome can be sustained by an extreme form of insulin resistance (IR), and is thus a secondary form of hyperandrogenism, which may be due to a defect in insulin signal transduction or in the adipose tissue. Severe IR due to adipose tissue dysfunction is the most frequent form, which may be the result of a deficiency in the adipose tissue, that is, the lipodystrophies, or to the unrestrained accumulation of adipose tissue. These forms are in some cases produced by a single-gene defect.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 2 of 2-Diagnostic Criteria and Appropriate Utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-Diagnostic criteria and appropriate utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized.

Sacubitril/Valsartan: Updates and Clinical Evidence for a Disease-Modifying Approach.

New therapeutic strategies aimed to tackle the rising socio-economic burden of heart failure (HF) have become an impelling priority. The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides. Sacubitril/valsartan, a first-in-class ARNI, has reduced the primary composite endpoint of cardiovascular death or HF hospitalisation, sudden cardiac death, disease progression and improved quality of life, compared with enalapril, in patients on evidence-based contemporary medical therapy.

The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk.

Context: Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors.

Objectives: To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS).

Design: Cohort study.

Update on polyglucosan storage diseases.

An abnormal structural form of glycogen (with less branching points or amylopectin-like polysaccharide) called polyglucosan (PG) may accumulate in various tissues such as striated and smooth muscles, brain, nerve, liver and skin, and cause a group of nine different genetic disorders manifesting with a variety of clinical phenotypes that affect mainly the nervous system (Lafora disease, adult PG body disease), the heart (glycogen storage disease type XV, hypertrophic cardiomyopathy type 6, PG body myopathy type 1) and the skeletal muscle (glycogen storage disease type IV, glycogen storage disease type VII, PG body myopathy type 2), depending on the organs which are mostly affected by the PG aggregates. The pathological feature of PG storage in tissues is a hallmark of these disorders. Whole-genome sequencing has allowed to obtain a diagnosis in a large number of patients with a previously unrecognized disorder.

Somatic PRKACA Mutations: Association With Transition From Pituitary-Dependent to Adrenal-Dependent Cushing Syndrome.

Context: Prolonged adrenal stimulation by corticotropin, as in long-standing Cushing disease (CD), leads to diffuse to nodular hyperplasia. Adrenal functional autonomy has been described in a subset of patients with CD, leading to the hypothesis of transition from ACTH-dependent to ACTH-independent hypercortisolism.

Objective: With the consideration that the catalytic α subunit of protein kinase A (PKA; PRKACA) somatic mutations are the most common finding in adrenal adenomas associated with ACTH-independent Cushing syndrome, our aim was to analyze PRKACA mutations in adrenals of patients with persistent/long-standing CD.