Subcellular Level Spatial Transcriptomics with PHOTON.

The subcellular localization of RNA is closely linked to its function. Many RNA species are partitioned into organelles and other subcellular compartments for storage, processing, translation, or degradation. Thus, capturing the subcellular spatial distribution of RNA would directly contribute to the understanding of RNA functions and regulation.

Evolutionary fingerprints of EMT in pancreatic cancers.

Mesenchymal plasticity has been extensively described in advanced and metastatic epithelial cancers; however, its functional role in malignant progression, metastatic dissemination and therapy response is controversial. More importantly, the role of epithelial mesenchymal transition (EMT) and cell plasticity in tumor heterogeneity, clonal selection and clonal evolution is poorly understood. Functionally, our work clarifies the contribution of EMT to malignant progression and metastasis in pancreatic cancer.

Photoselective sequencing: microscopically guided genomic measurements with subcellular resolution.

In biological systems, spatial organization and function are interconnected. Here we present photoselective sequencing, a new method for genomic and epigenomic profiling within morphologically distinct regions. Starting with an intact biological specimen, photoselective sequencing uses targeted illumination to selectively unblock a photocaged fragment library, restricting the sequencing-based readout to microscopically identified spatial regions.

In situ genome sequencing resolves DNA sequence and structure in intact biological samples.

Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei.

Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins.

ADP-ribosylation of proteins can profoundly impact their function and serves as an effective mechanism by which bacterial toxins impair eukaryotic cell processes. Here, we report the discovery that bacteria also employ ADP-ribosylating toxins against each other during interspecies competition. We demonstrate that one such toxin from Serratia proteamaculans interrupts the division of competing cells by modifying the essential bacterial tubulin-like protein, FtsZ, adjacent to its protomer interface, blocking its capacity to polymerize.

The bacterial replisome has factory-like localization.

DNA replication is essential to cellular proliferation. The cellular-scale organization of the replication machinery (replisome) and the replicating chromosome has remained controversial. Two competing models describe the replication process: In the track model, the replisomes translocate along the DNA like a train on a track.

The Replisomes Remain Spatially Proximal throughout the Cell Cycle in Bacteria.

The positioning of the DNA replication machinery (replisome) has been the subject of several studies. Two conflicting models for replisome localization have been proposed: In the Factory Model, sister replisomes remain spatially co-localized as the replicating DNA is translocated through a stationary replication factory. In the Track Model, sister replisomes translocate independently along a stationary DNA track and the replisomes are spatially separated for the majority of the cell cycle.

Transcription leads to pervasive replisome instability in bacteria.

The canonical model of DNA replication describes a highly-processive and largely continuous process by which the genome is duplicated. This continuous model is based upon reconstitution and ensemble experiments. Here, we characterize the replisome-complex stoichiometry and dynamics with single-molecule resolution in bacterial cells.

A randomized study to compare ramp versus burst antitachycardia pacing therapies to treat fast ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators: the PITAGORA ICD trial.

Background: In patients with implantable cardioverter-defibrillators (ICDs), antitachycardia pacing (ATP) is highly effective in terminating fast ventricular tachycardias (FVTs) and lowers the use of high-energy shocks, without increasing the risk of arrhythmia acceleration or syncope.

Methods And Results: The aim of the PITAGORA ICD trial was to randomly compare 2 ATP strategies (88% coupling interval burst versus 91% coupling interval ramp, both 8 pulses) in terms of ATP efficacy, arrhythmia acceleration, and syncope. Two hundred six ICD patients (83% male, 67+/-11 years) were enrolled.

A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat atrial fibrillation in patients paced for sinus node disease: the Prevention Investigation and Treatment: A Group for Observation and Research on Atrial arrhythmias (PITAGORA) trial.

Background: Rhythm control is an important goal in the treatment of recurrent atrial tachyarrhythmias (AT). The PITAGORA study was a randomized trial in patients paced for sinus node disease (SND), designed to test the noninferiority of class IC antiarrhythmic drugs (AADs) to amiodarone in terms of a primary end point composed of death, permanent AT, cardiovascular hospitalization, atrial cardioversion, or AAD change.

Methods: Randomization was stratified to assign 2 patients to amiodarone and 2 patients to class IC AADs: propafenone or flecainide.

A case of lumbar sciatica in a patient with spondylolysis and spondylolysthesis and underlying misdiagnosed brucellar discitis.

We report the case of a patient affected by vertebral pain refractory to conventional analgesic therapy with a diagnosis of spondylolysthesis and also the affects of a misdiagnosed brucellar spondylodiscitis. The absence of a positive response to conventional analgesics, a suggestive medical history (epidemiologic data still show a high incidence of Brucella infections for the Province of Catania), radiological findings and microbiological tests led to the correct diagnosis of algic syndrome in a patient affected by brucellar spondylodiscitis with the concomitant presence of retroperitoneal muscular abscess, and a previously diagnosed spondylolysthesis. All symptoms improved after correct antibrucellar antibiotic therapy and surgical drainage of the retroperitoneal abscess.

Osteoporotic vertebral compression fracture pain (back pain): our experience with balloon kyphoplasty.

Aim: The aim of this study is to evaluate the safety and effectiveness of antalgic and functional results after interdisciplinary approach and treatment of vertebral compression fractures (VCF) with percutaneous balloon kyphoplasty (KP) by the pain medicine specialist.

Methods: Between April and December 2004, after informed consent, 13 patients have been treated for a total amount of 15 KP. For L5 - T11 level spinal anesthesia was performed, above T11 local infiltration was used.

Continuous intrathecal baclofen administration by a fully implantable electronic pump for severe spasticity treatment: our experience.

Aim: With this 8-month study, we wanted to evaluate the efficacy of continuous intrathecal baclofen infusion delivery by a programmable pump for severe spasticity according to patient selection criteria, implantation technique and related parameters, and outcome after the initial follow-up period.

Methods: Intrathecal baclofen infusion was initiated in 30 patients within 24 h after a test dose of the agent resulted positive in spinal anaesthesia. During the procedure and the follow-up period, the following parameters were measured: incidence of anaesthesiological or surgical complications and adverse events, postdural puncture headache, prolonged motor block, difficulty in wound healing, infection, necessity to remove the pump; clinical response as measured on the Ashworth and spasms scales, quality of sleep, autonomy, quality of life and pain before and after intrathecal baclofen therapy.

Randomized comparison between Ramp and Burst+ atrial antitachycardia pacing therapies in patients suffering from sinus node disease and atrial fibrillation and implanted with a DDDRP device.

Aims: Atrial tachycardia and flutter frequently occur in association with atrial fibrillation and may be treated by overdrive pacing in patients who receive pacemakers with antitachycardia pacing (ATP) capabilities. The PITAGORA trial was a multi-centre, randomized, cross-over study aimed at comparing two different ATP modes for atrial tachyarrhythmia (AT) termination in patients suffering from sinus node disease (SND).

Methods And Results: One hundred and seventy-six patients (72 M, age 71+/-9 years) received a Medtronic AT500 pacemaker.

Design and rationale of a randomized study to compare amiodarone and Class IC anti-arrhythmic drugs in terms of atrial fibrillation treatment efficacy in patients paced for sinus node disease: the PITAGORA trial.

Aims: Many sinus node disease (SND) patients suffer from atrial fibrillation (AF). Anti-arrhythmic drugs (AADs) are the therapeutic mainstay for AF prophylaxis. The PITAGORA trial has a multicentre, prospective, randomized, single blind design to compare amiodarone with Class IC AADs in patients who have an AF history and are paced for SND.

Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial.

Aims: This multicentre prospective randomised trial was undertaken to evaluate the usefulness of an electrophysiological study (EPS)-guided/implantable cardioverter defibrillator (ICD) strategy in patients at high risk of sudden death (SD) early after myocardial infarction (MI). Previous studies have shown the benefits of such a strategy only in high-risk patients late after MI.

Methods And Results: We enrolled 143 survivors of acute MI (<1 month) with left ventricular ejection fraction < or = 35% and either frequent (> or =10/h) premature ventricular complexes (PVCs), or depressed heart rate variability (SDNN < 70 ms) or abnormal signal-averaged ECG, who were able to tolerate optimised beta-blocker therapy (68 +/- 40 mg/day of metoprolol).

Left ventricular function in acute hypothyroidism: a Doppler echocardiography study.

Background: Acute changes in cardiac parameters may occur after L-thyroxine withdrawal in patients totally thyroidectomized for thyroid cancer. The literature data regarding cardiac function in acute hypothyroidism are limited and discordant.

Methods: In order to evaluate the effects of acute hypothyroidism on cardiac function, 20 athyreotic patients (3 males, 17 females, mean age 46.

Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism.

Background: The concentration of peroxynitrite in the brain increases after central nervous system injuries. The authors hypothesized that propofol, because of its particular chemical structure, mitigates the effects of peroxynitrite-mediated oxidative stress and apoptosis by the induction of heme oxygenase (HO)-1 in primary cultured astroglial cells.

Methods: Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (3 mm SIN-1) in the presence or absence of propofol (40 microm, 80 microm, 160 microm, and 1 mm).

[Spasticity in multiple sclerosis].

Already in 1860, the great neurologist Charcot described the symptom spasticity in patients affected by "sclerose en plaque". Spasticity is one of the most common symptoms of multiple sclerosis MS). The consequences of spasticity are very disadvantages because it hinders the functional mobility and overburden disability.

Preclinical thalassemic cardiopathy: a study by acoustic densitometry.

Background: The cardiac function in thalassemia major has never been studied at ultrasonic backscatter techniques. We assessed the utility of acoustic densitometry in thalassemic patients without clinical or echocardiographic signs of heart failure.

Methods: Three groups of subjects with comparable age, sex and body surface area were analyzed: 25 with beta-thalassemia major (group A), 14 with thalassemia intermedia (group B) and 10 healthy subjects (group C).

Dual chamber pacing with optimal AV delay in congestive heart failure: a randomized study.

Aim: A prospective randomized trial was set up to evaluate contractile parameters and quality of life in patients with congestive heart failure.

Methods And Results: We describe the results from 38 patients in sinus rhythm and with chronic heart failure due to congestive cardiomyopathy, prospectively randomized to optimal medical therapy (Group 1, 19 patients) or optimal medical therapy plus dual chamber pacemaker programmed to optimal AV delay (Group 2, 19 patients). At a 6 month follow-up, 7/19 patients in Group 1 had died compared with 5/19 patients in Group 2.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study].

Background: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire.

Which strategy is "best" after myocardial infarction? The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator Trial: rationale and study design.

The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator (BEST-ICD) Trial is a multicenter prospective randomized trial that started in June 1998, in 95 centers in Italy and Germany. The trial will test the hypothesis whether, in high-risk post myocardial infarction (MI) patients already treated with beta blockers, electrophysiologic study (EPS)-guided therapy (including the prophylactic implantation of implantable cardioverter defibrillator [ICD] in inducible patients) will improve survival compared with conventional therapy. Patients eligible for the study are survivors of recent MI (> or = 5 and < or = 21 days), aged < or = 80 years, with left ventricular ejection fraction < or = 35% and > or = 1 of the following additional risk factors: (1) ventricular premature beats > or = 10/hour; (2) decreased heart rate variability (standard deviation of unusual RR intervals < 70 msec); and (3) presence of ventricular late potentials.