Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis

Dysfunction of mitochondrial respiration is an increasingly recognized cause of isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes mitochondrial translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs∗8) frameshift and a paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for the latter change. In both humans and yeast, MTO1 increases the accuracy and efficiency of mtDNA translation by catalyzing the 5-carboxymethylaminomethylation of the wobble uridine base in three mitochondrial tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably combined reduction in mtDNA-dependent respiratory chain activities. Reduced respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA. Conversely, defective respiration of a yeast mto1Δ strain failed to be corrected by an Mto1Pro622∗ variant, equivalent to human MTO1Arg620Lysfs∗8, whereas incomplete correction was achieved by an Mto1Ala431Thr variant, corresponding to human MTO1Ala428Thr. The respiratory yeast phenotype was dramatically worsened in stress conditions and in the presence of a paromomycin-resistant (PR) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation was impaired in the mutant yeast strains

Utilità della ripresa fotografica a colori della papilla ottica nel glaucoma cronico semplice: nostre considerazioni su casi particolari

Scopo del presente lavoro è di evidenziare l’utilità clinica della fotografia della papilla ottica nella gestione del follow-up di pazienti affetti da glaucoma cronico semplice, soprattutto in casi clinici particolari. Presso il centro Glaucoma della II Divisione della Clinica Oculistica dell’Università “La Sapienza” di Roma, gli Autori hanno eseguito la ripresa fotografica in gruppi di pazienti affetti da glaucoma cronico semplice o in accertamento diagnostico che presentano malformazioni papillari, aree di atrofia corioretinica peripapillare, dischi ottici con rapporto cup/disk alterato ( 0,3), asimmetrie significative del rapporto cup/disk (> 0,2) o semplicemente perchè monoculi o di giovane età. Spesso i pazienti presentano contemporaneamente più criteri di inclusione, rafforzando la necessità di eseguire in questi casi tale indagine. In ognuno di questi gruppi è presente una problematica clinica, per la quale lo studio dello stato papillare gioca un ruolo fondamentale. La fotografia della papilla ottica consente di documentare lo stato attuale papillare e di effettuare una valutazione obiettiva da parte di più operatori, rappresentando un indispensabile ausilio per il monitoraggio cronologico del paziente. L’analisi fiotografica della papilla ottica si pone alla stregua delle più moderne metodiche di indagine dello stato papillare per la semplicità di esecuzione, l’economicità, la ripetibilità e la non invasività; inoltre rappresenta la base di un’ulteriore analisi morfometrica. In conclusione, la fotografia della papilla ottica è una pratica estensibile all’intera popolazione glaucomatosa, o quanto meno a casi particolari, che alla utilità clinica associa la possibilità di effettuare un’opera di educazione sanitaria specifica, migliora il rapporto “paziente-malattia” e agevola anche la compliance terapeutica

Brain tissue oxygenation monitoring in subarachnoid hemorrhage for the detection of delayed ischemia: a systematic review and meta-analysis

Introduction: Subarachnoid hemorrhage (SAH) is a severe subtype of stroke which can be caused by the rupture of an intracranial aneurysm. Following SAH, about 30% of patients develop a late neurologic deterioration due to a delayed cerebral ischemia (DCI). This is a metanalysis and systematic review on the association between values of brain tissue oxygenation (PbtO2) and DCI in patients with SAH. Evidence acquisition: The protocol was written according to the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and approved by the International Prospective Register of Systematic Reviews (PROSPERO registration number CRD42021229338). Relevant literature published up to August 1, 2022 was systematically searched throughout the databases MEDLINE, WEB OF SCIENCE, SCOPUS. A systematic review and metanalysis was carried out. The studies considered eligible were those published in English; that enrolled adult patients (≥18years) admitted to neurointensive care units with aneurysmal SAH (aSAH); that reported presence of multimodality monitoring including PbtO2 and detection of DCI during the period of monitoring. Evidence synthesis: We founded 286 studies, of which six considered eligible. The cumulative mean of PbtO2was 19.5 mmHg in the ischemic group and 24.1mmHg in the non ischemic group. The overall mean difference of the values of PbtO2 between the patients with or without DCI resulted significantly different (-4.32 mmHg [IC 95%: -5.70, -2.94], without heterogeneity, I2 = 0%, and a test for overall effect with P<0.00001). Conclusions: PbtO2 values were significantly lower in patients with DCI. Waiting for definitive results, monitoring of PbtO2 should be considered as a complementary parameter for multimodal monitoring of the risk of DCI in patients with SAH

Personality features of obese women in relation to binge eating and night eating

Personality traits can affect eating behaviors, the development of obesity as well as obesity treatment failure. We investigated the personality characteristics and their relation with disordered eating in 586 obese women consecutively seeking treatment at eight Italian medical centers (age, 47.7\ub19.8 years) and 185 age-matched, normal weight women without symptoms of eating disorders (Eating Attitude Test<20). The assessment included anthropometry, the Temperament and Character Inventory (TCI), the Binge Eating Scale (BES) and the Night Eating Questionnaire (NEQ). Logistic regression analyses were carried out in different models with BES score 6527 and NEQ 6530 as dependent variables and TCI scores as independent factors. Personality traits of obese individuals included significantly lower self-directedness and cooperativeness on TCI. BES and NEQ scores were higher in obese women, and values above the defined cut-offs were present in 77 and 18 cases (14 with high BES), respectively. After controlling for age and BMI, high BES values were associated with high novelty seeking and harm avoidance and low self-directedness, the last two scales being also associated with high NEQ. We conclude that personality traits differ between obese patients seeking treatment and controls, and the presence of disordered eating is associated with specific personality characteristic

Validation of the Italian Yale Food Addiction Scale in postgraduate university students

This study was aimed to examine the structural and construct validity of the Italian version of the Yale Food Addiction Scale in a multisite sample of postgraduate students

Mutations in APOPT1, Encoding a Mitochondrial Protein, Cause Cavitating Leukoencephalopathy with Cytochrome c Oxidase Deficiency

Contains fulltext : 137503.pdf (publisher's version ) (Open Access)Cytochrome c oxidase (COX) deficiency is a frequent biochemical abnormality in mitochondrial disorders, but a large fraction of cases remains genetically undetermined. Whole-exome sequencing led to the identification of APOPT1 mutations in two Italian sisters and in a third Turkish individual presenting severe COX deficiency. All three subjects presented a distinctive brain MRI pattern characterized by cavitating leukodystrophy, predominantly in the posterior region of the cerebral hemispheres. We then found APOPT1 mutations in three additional unrelated children, selected on the basis of these particular MRI features. All identified mutations predicted the synthesis of severely damaged protein variants. The clinical features of the six subjects varied widely from acute neurometabolic decompensation in late infancy to subtle neurological signs, which appeared in adolescence; all presented a chronic, long-surviving clinical course. We showed that APOPT1 is targeted to and localized within mitochondria by an N-terminal mitochondrial targeting sequence that is eventually cleaved off from the mature protein. We then showed that APOPT1 is virtually absent in fibroblasts cultured in standard conditions, but its levels increase by inhibiting the proteasome or after oxidative challenge. Mutant fibroblasts showed reduced amount of COX holocomplex and higher levels of reactive oxygen species, which both shifted toward control values by expressing a recombinant, wild-type APOPT1 cDNA. The shRNA-mediated knockdown of APOPT1 in myoblasts and fibroblasts caused dramatic decrease in cell viability. APOPT1 mutations are responsible for infantile or childhood-onset mitochondrial disease, hallmarked by the combination of profound COX deficiency with a distinctive neuroimaging presentation