Caloric restriction in humans reveals immunometabolic regulators of health span.

The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.

DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components.

DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput transcriptomic and proteomic approaches. DNAJC17-depleted cells transcriptome highlighted genes involved in general functional categories, mainly related to gene expression. Conversely, DNAJC17 interactome can be classified in very specific functional networks, with the most enriched one including proteins involved in splicing. Furthermore, several splicing-related interactors, were independently validated by co-immunoprecipitation and in vivo co-localization. Accordingly, co-localization of DNAJC17 with SC35, a marker of nuclear speckles, further supported its interaction with spliceosomal components. Lastly, DNAJC17 up-regulation enhanced splicing efficiency of minigene reporter in live cells, while its knockdown induced perturbations of splicing efficiency at whole genome level, as demonstrated by specific analysis of RNAseq data. In conclusion, our study strongly suggests a role of DNAJC17 in splicing-related processes and provides support to its recognized essential function in early development.

Cor triatriatum associated with degenerative aortic insufficiency in an adult patient.

Cor triatriatum is a rare cardiac anomaly which can be congenital or acquired in origin. Congenital cor triatriatum is due to an alteration of the common pulmonary vein resorption and therefore the left atrium is divided into two chambers, a proximal one, in communication with the pulmonary veins, and a distal one, in communication with the mitral valve orifice. The diagnosis is usually made at birth, but in rare cases, when the communication between the two chambers is wide and the patient is asymptomatic, the lesions may be diagnosed incidentally during a routine echocardiographic examination. We report a 32-year-old man, admitted to our hospital with a diagnosis of aortic insufficiency, in whom echocardiography revealed the presence of cor triatriatum. The patient underwent aortic valve replacement and resection of the atrial membrane. Histology of the aortic valve revealed myxoid degeneration of the spongiosa.

[Analysis of risk factors in patients undergoing closed heart mitral commissurotomy]. / Analisi dei fattori di rischio in pazienti sottoposti a commissurotomia mitralica a cuore chiuso.

The aim of this study was to analyse the risk factors in patients undergoing closed heart commissurotomy (CHC). From 1956 to 1978 a total of 630 patients with severe mitral stenosis underwent CHC at this Institute. The study was performed on a sample of 100 patients. Follow-up was performed using data taken from the Institute archives, questionnaires sent to the doctors in charge, telephone interviews or visits to outpatient clinics by the Institute's medical staff. The mortality rate 30 days after surgery was 2.9%. Re-CHC was necessary in 11 patients after a mean interval of 7.2 years. The overall probability of survival was 83%, 71%, 48% an 33% respectively at 10, 20, 30 and 40 years. Survival free from mitral re-operation at 10, 20, 30 and 40 years was 76%, 39%, 29% and 11% respectively. The probability of incidence for central and peripheral thromboembolism was 38%, 26%, 11% and 4% at 10, 20, 30 and 40 years. Mitral valve replacement surgery (MVR) was performed in a total of 64 patients. Operative mortality was 0.6% (1 patient). The mean duration of follow-up in patients undergoing post-CHC MVR was 10 years. The probability os survival in overall terms and free of cardiac decompensation was 79 and 53% respectively. From this study it is clear the CHC is a surgical procedure that offers excellent long-term results with a low incidence od thromboembolic events, very low costs and a good quality of life. CHC currently represents a valid alternative o mitral valve replacement in selected patients.

[Quality of life in patients undergoing mitral valve substitution]. / Qualità di vita in pazienti sottoposti ad intervento di sostituzione valvolare mitralica.

AIM: The aim of the present study was to evaluate the quality of life after mitral valve replacement through the analysis of behavioural, psychological, functional, economic and working changes, as well as alterations in social and sexual life after surgery. SETTING: The study was performed before and after surgery in a cardiological ward. POPULATION: The population studied included 206 patients undergoing mitral valve replacement surgery. Results were compared with a control population of patients suffering from mitral valve disease and receiving medical therapy. METHOD: All patients were asked by medical staff to compile a series of five self-evaluation questionnaires: General Well-Being Schedule, Physical Symptoms Distress Index B, Social Participation, Sexual Satisfaction Unified Test and Work Performance and Satisfaction. RESULTS: Our results showed a significant improvement in the perception of quality of life after mitral valve replacement. In particular, the state of general well-being improved significantly with a clear reduction in symptoms. This was accompanied by a reduction in sexual activity and no change in social life or working capacity. Data obtained in the group of patients operated showed a significant improvement in the perception of the quality of life and psycho-physical well-being compared to patients receiving medical treatment alone. CONCLUSIONS: From this study it can be seen that patients undergoing mitral valve replacement surgery experience a marked improvement in the quality of life compared to pre-operative conditions and to the group of patients receiving medical therapy for mitral valve diseases. The use of specific working and social rehabilitation programmes can certainly optimise the results also with regard to affective relations.

[Ambulatory phlebectomy with Müller procedure in the treatment of lower limb varices. Indications, technique and long-term results]. / La flebectomia ambulatoriale sec. Müller nel trattamento delle varici degli arti inferiori. Indicazioni, tecnica e risultati a distanza.

The authors report the results of more than five years experience of phlebectomies, according to Müller's method, performed both in general anesthesia during stripping operations and in local practice. The results confirmed the validity of this complementary surgical treatment for its radicality, execution simpleness and best respect for aesthetics.

[Placebo effect and arterial pressure]. / Effetto placebo e pressione arteriosa.

The aim of the present single blind study was the assessment of the effect of placebo on office (OBP) and 24-hour ambulatory (ABP) blood pressure in patients with mild and moderate essential hypertension (WHO stage I). Ten patients (6 males, 4 females, age 51 +/- 9 years) underwent both OBP and ABP measurements at the beginning and the end of a 2-week placebo treatment. The comparison of the results of the first (OBP 156/100 +/- 15/6 mmHg, day ABP 155/96 +/- 12/7 mmHg, night ABP 139/81 +/- 21/10 mmHg) and the second sets of measurements (OBP 152/98 +/- 22/7 mmHg, day ABP 147/90 +/- 15/7 mmHg, night ABP 134/79 +/- 18/7 mmHg) did not show a statistically significant drop in OBP and night ABP, while there was a statistically significant (p < 0.05) decrease in day ABP. Thus, the effect of placebo can influence day ABP measurements, even when OBP is not decreased by placebo administration. Possible explanations involve alerting reactions to the first ABP monitorings in selected patients with mild and even moderate hypertension.