An arrhythmic storm: a potential complication on opening the umbrella for percutaneous closure of interatrial communications

Interatrial communications (ICs) have been linked to paradoxic embolism, which may be prevented using both surgical and percutaneous interventions. The case of a 61-year-old woman with a history of transient cerebral ischemic attack who developed repetitive ventricular arrhythmias and an intermittent left branch bundle block immediately after percutaneous closure of an IC is described. Transthoracic echocardiography showed that the device had migrated into the left ventricular outflow tract, and the patient consequently underwent emergency cardiac surgery to retrieve the device and repair the IC. In conclusion, percutaneous transcatheter closure of ICs is more rapid and less invasive compared with surgery, but nevertheless may be associated with significant short-term morbidity.     

Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis

BACKGROUND: Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. AIM OF THE STUDY: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. RESULTS: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of L-arginine to L-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC(25) values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. CONCLUSION: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.     

Advances in Alport syndrome diagnosis using next-generation sequencing

Alport syndrome (ATS) is a hereditary nephropathy often associated with sensorineural hypoacusis and ocular abnormalities. Mutations in the COL4A5 gene cause X-linked ATS. Mutations in COL4A4 and COL4A3 genes have been reported in both autosomal recessive and autosomal dominant ATS. The conventional mutation screening, performed by DHPLC and/or Sanger sequencing, is time-consuming and has relatively high costs because of the absence of hot spots and to the high number of exons per gene: 51 (COL4A5), 48 (COL4A4) and 52 (COL4A3). Several months are usually necessary to complete the diagnosis, especially in cases with less informative pedigrees. To overcome these limitations, we designed a next-generation sequencing (NGS) protocol enabling simultaneous detection of all possible variants in the three genes. We used a method coupling selective amplification to the 454 Roche DNA sequencing platform (Genome Sequencer junior). The application of this technology allowed us to identify the second mutation in two ATS patients (p.Ser1147Phe in COL4A3 and p.Arg1682Trp in COL4A4) and to reconsider the diagnosis of ATS in a third patient. This study, therefore, illustrates the successful application of NGS to mutation screening of Mendelian disorders with locus heterogeneity.     

Noninvasive fetal sex determination in maternal plasma: a prospective feasibility study

PurposeTo prospectively validate a protocol for noninvasive fetal sex determination in maternal plasma and demonstrate its applicability to clinical practice.MethodsPeripheral blood from 404 pregnant women undergoing prenatal invasive testing was collected from 6 to 23 weeks of gestation. Real-time PCR was performed for the SRY gene and multicopy DYS14 marker sequence located within the TSPY gene by the TaqMan minor groove binder probe assay as a first-line test. Owing to a false-positive result, amplification of repetitive motifs of the DAZ gene region was also tested as a second-line test performed in the last 232 patients enrolled in our series. A diagnostic algorithm was designed using a combination of these three markers. Fetal gender determined by noninvasive prenatal diagnosis (NIPD) was compared with that diagnosed by quantitative fluorescent PCR after invasive testing or ultrasound.ResultsA single false-positive result was obtained in the first 172 pregnancies. Reporting criteria were modified in the subsequent 232 pregnancies, giving an overall sensitivity and specificity of 100% (95% CI 99.8–100%) and 99.5% (95% CI 98.1–100%), respectively. Pregnancy outcome was obtained in all cases, including 221 male-bearing and 183 female-bearing pregnancies.ConclusionNIPD for fetal sex determination in maternal plasma is highly accurate and clinically applicable if robust reporting criteria are applied.     

Serum paraoxonase activity is associated with variants in the PON gene cluster and risk of Alzheimer disease

Previous studies have shown association of single nucleotide polymorphisms (SNPs) in 3 contiguous genes (PON1, PON2, and PON3) encoding paraoxonase with risk of Alzheimer disease (AD). We evaluated the association of serum paraoxonase activity measured by phenyl acetate (PA) and thiobutyl butyrolactone (TBBL) with risk of AD and with 26 SNPs spanning the PON gene cluster in 266 AD cases and 306 sibling controls from the MIRAGE study. The odds of AD (adjusted for age, gender, and ethnicity) increased 20% for each standard deviation decrease in PA or TBBL activity. There were association signals with activity in all 3 genes. Haplotypes including SNPs spanning the PON genes were generally more significant than haplotypes comprising SNPs from 1 gene. Significant interactions were observed between SNP pairs located across the PON cluster with either serum activity measure as the outcome, and between several PON SNPs and PA activity with AD status as the outcome. Our results suggest that low serum paraoxonase activity is a risk factor for AD. Furthermore, multiple variants in PON influence serum paraoxonase activity and their effects may be synergistic.     

Reorganization of multi-muscle and joint withdrawal reflex during arm movements in post-stroke hemiparetic patients

ObjectivesTo investigate the behavior of the nociceptive withdrawal reflex (NWR) in the upper limb during reaching and grasping movements in post-stroke hemiparetic patients.MethodsEight patients with chronic stroke and moderate motor deficits were included. An optoelectronic motion analysis system integrated with a surface EMG machine was used to record the kinematic and EMG data. The NWR was evoked through a painful electrical stimulation of the index finger during a movement which consisted of reaching out, picking up a cylinder, and returning it to the starting position.ResultsWe found that: (i) the NWR is extensively rearranged in hemiparetic patients, who were found to present different kinematic and EMG reflex patterns with respect to controls; (ii) patients partially lose the ability to modulate the reflex in the different movement phases; (iii) the impairment of the reflex modulation occurs at single-muscle, single-joint and multi-joint level.ConclusionsPatients with chronic and mild-moderate post-stroke motor deficits lose the ability to modulate the NWR dynamically according to the movement variables at individual as well as at multi-muscle and joint levels.SignificanceThe central nervous system is unable to use the NWR substrate dynamically and flexibly in order to select the muscle synergies needed to govern the spatio–temporal interaction among joints.     

Gait Pattern in Inherited Cerebellar Ataxias

Our aim was to perform a comprehensive analysis of the global and segmental features of gait in patients with genetically confirmed inherited ataxias. Sixteen patients with autosomal dominant (spinocerebellar ataxia, SCA1 or 2) or recessive (Friedreich's ataxia, FRDA) ataxia were studied. We used a motion analysis system to record gait kinematic and kinetic data. We measured the mean values of global (time-distance parameters, COM displacement, support moment) and segmental gait parameters (joint displacement and inter-joint coordination), as both discrete and continuous variables, and their variability and correlations with International Cooperative Ataxia Rating Scale (ICARS) scores. We found a marked difference in all global gait parameters between the ataxic patients and the controls and close correlations between longer stride and stance duration and lower gait, posture and total ICARS scores. The only difference between the two patient groups was a shorter step length in the FRDA patients. As regards the segmental features, we found a significantly different waveform shape for all continuous kinematic and kinetic measures between the ataxic patients and the healthy controls, but only minor differences for the discrete measures. Intersegmental coordination evaluated using the continuous relative phase method revealed an irregular alternating joint behaviour without clear evidence of the synchronous pattern of alternating proximal/distal joint seen in healthy subjects. For almost all gait parameters we observed a markedly higher intra-subject variability in the ataxic patients versus the controls, which was strongly related to the clinical ICARS scores. Patients with chronic, progressive inherited ataxias lose the ability to "stabilize" a walking pattern that can be repeated over time. The most peculiar aspect of the gait of inherited ataxia patients, regardless the different genetic forms, seems to be the presence of increased variability of all global and segmental parameters rather than an invariant abnormal gait pattern.