A rare case report of hypertrophic cardiomyopathy induced by catecholamine-producing tumor

RATIONALE: Catecholamine-producing tumors are rare, occurring in less than 0.2% of patients with hypertension, but can have relevant cardiovascular morbidity and mortality. PATIENT CONCERNS: A 37-year-old woman presented with a history of dyspnea, chest pain, palpitations, and paroxysmal hypertension. Electrocardiogram, echocardiogram, and cardiac magnetic resonance showed severe LVH with a prevalent involvement of the anterior portion of interventricular septum. Endomyocardial biopsy found severe hypertrophy with disarray of cardiomyocytes and ultrastructural evidence of contraction and necrosis of myocytes. Hormone investigations revealed high values of 24-hours urinary metanephrines. Abdominal computed tomography (CT) showed an enlarged left adrenal gland with a strong uptake of I-metaiodobenzylguanidine at scintigraphy scan. INTERVENTIONS:Thus, the adrenal tumor was surgically removed. OUTCOMES: At follow-up examination, the patient's metanephrines levels were normalized and the transthoracic echocardiogram showed a reduction of LVH. DIAGNOSIS AND LESSONS: We report a rare case of catecholamine-induced cardiomyopathy due to an adrenal adenoma mixed with nodules enriched in epinephrine-types secreting granules

A Case of Chronic Urticaria Due to Dirofharia Infestation

ABSTRACTUrticaria is one of the most common dermatoallergic conditions occurring mainly in children and adolescents and in atopic individuals. The term of chronic idiopathic urticaria (CIU) is used when the pathophysiological mechanisms remain unclear. Chronic infections and parasitic infestations have been suggested to play an important role in the etiology of CIU. In the present paper, we describe a case of chronic, apparently idiopathic urticaria in an adult woman where Dirofilaria has been recognized to play a pathogenic role in the determination of the cutaneous disease

Modulation of circRNA Metabolism by m6A Modification

N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display “spontaneous” DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Modulation of circRNA Metabolism by m6A Modification

N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation.</p

Subclinical atherosclerosis due to increase of plasma aldosterone concentrations in essential hypertensive individuals

Background and aims: The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension. Methods and results: From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P &lt; 0.05), 24-h urinary albumin excretion (UAE) (38.8 ± vs. 7.6 ± mg/24 h; P &lt; 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P &lt; 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC &lt; 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P &lt; 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (&lt;0.9) in essential hypertensive individuals. Conclusion: Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications