Antonio Gramsci and Irredentism. Historical-ideological roots of an attempted meeting with Fiume legionaries

In April 1921 Antonio Gramsci, co-founder of the Italian Communist Party, tried to meet Gabriele D?Annunzio, leader of the irredentist Fiume Endeavour. Though the attempt could apparently seem in contradiction with the internationalist tradition of Marxist ideology, it was perfectly coherent with the dialectical conception of the national problem, formalized by Gramsci in his early works and his Quaderni del carcere

Different approaches for bladder neck dissection during robot-assisted radical prostatectomy: the Aalst technique

ABSTRACT Introduction: Bladder neck dissection is one of the most delicate surgical steps of robotic-assisted radical prostatectomy (RARP) [1, 2], and it may affect surgical margins rate and functional outcomes [3, 4]. Given the relationship between outcomes and surgical experience [5–7], it is crucial to implement a step-by-step approach for each surgical step of the procedure, especially in the most challenging part of the intervention. In this video compilation, we described the techniques for bladder neck dissection utilized at OLV Hospital (Aalst, Belgium). Surgical Technique: We illustrated five different techniques for bladder neck dissection during RARP. The anterior technique tackles the bladder neck from above until the urethral catheter is visualized, and then the dissection is completed posteriorly. The lateral and postero-lateral approaches involve the identification of a weakness point at the prostate-vesical junction and aim to develop the posterior plane – virtually until the seminal vesicles – prior to the opening of the urethra anteriorly. Finally, we described our techniques for bladder neck dissection in more challenging cases such as in patients with bulky middle lobes and prior surgery for benign prostatic hyperplasia. All approaches follow anatomic landmarks to minimize positive surgical margins and aim to preserve the bladder neck in order to promote optimal functional recovery. All procedures were performed with DaVinci robotic platforms using a 3-instruments configuration (scissors, fenestrated bipolar, and needle driver). As standard protocol at our Institution, urinary catheter was removed on postoperative day two [8]. Conclusions: Five different approaches for bladder neck dissection during RARP were described in this video compilation. We believe that the technical details provided here might be of help for clinicians who are starting their practice with this surgical intervention

Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres

Cells respond to DNA double-strand breaks (DSBs) and uncapped telomeres by recruiting checkpoint and repair factors to the site of lesions. Single-stranded DNA (ssDNA) is an important intermediate in the repair of DSBs and is produced also at uncapped telomeres. Here, we provide evidence that binding of the checkpoint protein Rad9, through its Tudor domain, to methylated histone H3-K79 inhibits resection at DSBs and uncapped telomeres. Loss of DOT1 or mutations in RAD9 influence a Rad50-dependent nuclease, leading to more rapid accumulation of ssDNA, and faster activation of the critical checkpoint kinase, Mec1. Moreover, deletion of RAD9 or DOT1 partially bypasses the requirement for CDK1 in DSB resection. Interestingly, Dot1 contributes to checkpoint activation in response to low levels of telomere uncapping but is not essential with high levels of uncapping. We suggest that both Rad9 and histone H3 methylation allow transmission of the damage signal to checkpoint kinases, and keep resection of damaged DNA under control influencing, both positively and negatively, checkpoint cascades and contributing to a tightly controlled response to DNA damage

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

RNAi Screening Implicates a SKN-1-Dependent Transcriptional Response in Stress Resistance and Longevity Deriving from Translation Inhibition

Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other functions in response to stress. Here we used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1-dependent or other mechanisms. These genes correspond to multiple cellular processes, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be important for DR-induced lifespan extension. One model postulates that these effects derive from reduced energy needs, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factor RNAi robustly induces SKN-1 target gene transcription and confers skn-1-dependent oxidative stress resistance. The accompanying increases in longevity are mediated largely through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which is required for longevity that derives from reduced IIS. Our results indicate that the SKN-1 detoxification gene network monitors various metabolic and regulatory processes. Interference with one of these processes, translation initiation, leads to a transcriptional response whereby SKN-1 promotes stress resistance and functions together with DAF-16 to extend lifespan. This stress response may be beneficial for coping with situations that are associated with reduced protein synthesis

Antonio Gramsci and Irredentism. Historical-ideological roots of an attempted meeting with Fiume legionaries

In April 1921 Antonio Gramsci, co-founder of the Italian Communist Party, tried to meet Gabriele D’Annunzio, leader of the irredentist Fiume Endeavour. Though the attempt could apparently seem in contradiction with the internationalist tradition of Marxist ideology, it was perfectly coherent with the dialectical conception of the national problem, formalized by Gramsci in his early works and his Quaderni del carcere.Nell’aprile del 1921, il fondatore del Partito comunista d’Italia Antonio Gramsci tentò di effettuare un incontro con Gabriele D’Annunzio, leader della spedizione irredentista di Fiume. Il tentativo di apertura sembra apparentemente contraddittorio con la tradizione internazionalista dell’elaborazione ideologica marxista, eppure esso è del tutto coerente con l’impostazione dialettica della questione nazionale proposta da Gramsci dagli scritti politici giovanili ai Quaderni del carcere