Articulating Video Stylet Compared to Other Techniques for Endotracheal Intubation in Normal Airways: A Simulation Study in Consultants with No Prior Experience.

Simulation for airway management allows for acquaintance with new devices and techniques. Endotracheal intubation (ETI), most commonly performed with direct laryngoscopy (DL) or video laryngoscopy (VLS), can be achieved also with combined laryngo-bronchoscopy intubation (CLBI). Finally, an articulating video stylet (ProVu) has been recently introduced. A single-center observational cross-sectional study was performed in a normal simulated airway scenario comparing DL, VLS-Glidescope, VLS-McGrath, CLBI and ProVu regarding the success rate (SR) and corrected time-to-intubation (cTTI, which accounts for the SR). Up to three attempts/device were allowed (maximum of 60 s each). Forty-two consultants with no experience with ProVu participated (15 ± 9 years after training completion). The DL was significantly faster (cTTI) than all other devices (p = 0.033 vs. VLSs, and p < 0.001 for CLBI and Provu), no differences were seen between the two VLSs (p = 0.775), and the VLSs were faster than CLBI and ProVu. Provu had a faster cTTI than CLBI (p = 0.004). The DL and VLSs showed similar SRs, and all the laryngoscopes had a higher SR than CLBI and ProVu at the first attempt. However, by the third attempt, the SR was not different between the DL/VLSs and ProVu (p = 0.241/p = 0.616); ProVu was superior to CLBI (p = 0.038). In consultants with no prior experience, ProVu shows encouraging results compared to DL/VLSs under simulated normal airway circumstances and further studies are warranted.

A survey to evaluate knowledge, attitudes, and practices associated with the risk of foodborne infection in a sample of Sicilian general population.

Although foodborne infections contracted at home are frequent diseases worldwide, there is a general lack of information. Main purpose of this cross-sectional study was to evaluate knowledge, attitudes, and practices (KAP) of a sample of the general Sicilian population about the risk of contracting foodborne diseases. It was carried out through a web-based questionnaire to a Sicilian population sample. The questionnaire collected socio-demographic data, health issues, KAP and self-reported diseases. Scores were calculated for summarizing the results. A total of 373 subjects participated into the study. Overall, 65.15% of the participants were females, 48.26% of all respondents were aged between 18 and 29 years and over one-third were students (34.58%). At least one episode of vomiting/diarrhoea in the previous 3 months was reported by 119 respondents. Practices were associated with knowledge (R2 = 0.02; p < 0.01) and attitudes (R2 = 0.13; p < 0.001) although with low degree of correlation. A lower practice score was statistically significantly associated with both onset of foodborne transmitted infections in participants and among the cohabitants of participants. Our results confirm that foodborne disease can be strongly associated with food handling at home and with unsafe practices. Specific education on food safety could help to reduce the risk but the adoption of good practices of food manipulation is the real key to assure a reduction in food outbreaks in residences.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

Application of pyrosequencing to the identification of sequence variations in the cystic fibrosis transmembrane conductance regulator gene.

BACKGROUND: A high number of mutations associated with cystic fibrosis have been identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of which are rare and, therefore, hamper extensive molecular diagnosis. In couples undergoing prenatal diagnosis where no mutation is found in one or both partners, additional analysis of intragenic polymorphisms may allow for the identification of fetal alleles associated with cystic fibrosis. METHODS: We developed novel, rapid and accurate assays for CFTR genotype determination using pyrosequencing technology; a simple, automated and reliable technique with low cost. RESULTS: Assays were optimized for the identification of the seven most frequent CFTR mutations (p.DeltaF508, p.N1303K, p.G542X, c.2183AA>G, c.1717-1G>A, p.W1282X, p.R1162X) in the Italian population and two common intragenic polymorphisms (rs213950 and rs1800136). Blind validation on 15 known control samples, typed for each sequence variation, allowed correct identification of all 135 genotypes. CONCLUSIONS: We demonstrated that this procedure is highly specific for the identification of individual CFTR sequence variations associated with cystic fibrosis, allowing both population screening and prenatal diagnosis.

The rare G93D mutation causes a slowly progressing lower motor neuron disease.

We describe an ALS family with the rare SOD1 G93D mutation. Three members of the family developed ALS at an age ranging from 45 to 71 years. In all cases pyramidal signs were not evident. Two members of the family were obligate gene carriers, and died at 56 and 81years, respectively, without developing ALS signs or symptoms. The mutation was found in the DNA extracted from the hair bulbs in the two deceased obligate carriers and in another family member who died at 80 years of age without any sign of the disease. This study shows that SOD1 G93D mutation causes a slowly developing lower motor neuron disease with a reduced penetrance.

Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data.

BACKGROUND: The cause of sporadic ALS is currently unknown. Despite evidence for a role for genetics, no common genetic variants have been unequivocally linked to sporadic ALS. We sought to identify genetic variants associated with an increased or decreased risk for developing ALS in a cohort of American sporadic cases. METHODS: We undertook a genome-wide association study using publicly available samples from 276 patients with sporadic ALS and 271 neurologically normal controls. 555 352 unique SNPs were assayed in each sample using the Illumina Infinium II HumanHap550 SNP chip. FINDINGS: More than 300 million genotypes were produced in 547 participants. These raw genotype data are freely available on the internet and represent the first publicly accessible SNP data for ALS cases. 34 SNPs with a p value less than 0.0001 (two degrees of freedom) were found, although none of these reached significance after Bonferroni correction. INTERPRETATION: We generated publicly available genotype data for sporadic ALS patients and controls. No single locus was definitively associated with increased risk of developing disease, although potentially associated candidate SNPs were identified.

Wounds Difficult to Heal: An Effective Treatment Strategy.

OBJECTIVE: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore a relevant social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery. PATIENTS AND METHODS: Patients (n=100) with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet concentrate (LPC) and hyaluronic acid (HIAFF, Hyalofill-F® ) as a scaffold. RESULTS: After 2 months, a 49% reduction in wound area was observed in the second group and in about 65% wound reduction was achieved in 15 days (4 LPC dressings). In contrast, patients treated by conventional therapies, showed a longer healing time and a greater percentage of failures. Morphometric analysis of biopsy samples obtained from the edge as well as from the bottom of the lesions obtained from the LPC group, detected an abundant presence of neoformed capillaries, characterized by a cubic, "reactive endothelium", close to the site of LPC infiltration. CONCLUSION: These results suggest that healing was promoted not only by limiting bacterial infections but also by the release of chemotactic and proangiogenic factors from leukocytes and platelets, improving the neoformation of capillaries.

Surgical treatment of spontaneous common carotid dissection: a case report.

BACKGROUND: Cervical carotid dissection is more common in extracranical vessel: internal carotid artery dissection (ICAD) is typical, vertebral artery dissection is uncommon, common carotid artery dissection (CCAD) is rare and even a more rare cause of ischemic stroke. Cervical artery dissections account up to 20-25% of ischemic strokes in young patients. Isolated and spontaneous common carotid artery dissection without aortic damage is unique. Indeed in the Literature 8 cases were identified. MRI and CTA were the most commonly used for diagnosis and follow-up. CASE REPORT: A 67-year-old came to our observation reporting burning pain in the right latero-cervical region in supine position, irradiated in the temporal region and recurrent episodes of migraine with aura (scintillating scotoma), in the last 3 months. The last Doppler Ultrasound control, performed after the onset of symptoms, showed an highlighted dissection wall with double lumen at the origin of the bulb and the internal carotid artery on the right. Aortic arch arteriography confirmed the diagnosis. The patient underwent surgery (longitudinal arteriotomy, removing four miointimal flaps, fastening the distal common carotid artery with 3 Kunlin's points). RESULTS: Any neurological or vascular problems after surgery were noticed. DISCUSSION AND COMMENTS: The pathogenesis can be related to a combination of an intrinsic weakness in the arterial wall and an external trigger. The diagnosis of CAD is made with MRI (78.0%), conventional angiography (31.1%), CTA (14.7%), and ultrasound (11.3%). CONCLUSION: No evidence-based guidelines exists for treatment of CCAD. In our patient surgical CEA treatment was the optimal solution.

FUS mutations in sporadic amyotrophic lateral sclerosis.

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease.

Serological and genetic factors in early recurrence of IgA nephropathy after renal transplantation.

BACKGROUND: The relative role of IgA anomalies and genetic factors in IgA nephropathy (IgAN) recurrence after transplantation has never been investigated in a single cohort. METHODS: Sixty-one transplanted patients who had IgAN as an original disease (30 with biopsy-proved early recurrence, median 2.9 yr post-transplant), and 120 controls, were investigated for aberrantly glycosylated IgA1, IgA binding to mesangial matrix, macromolecular IgA (IgA/fibronectin and uteroglobulin/IgA/fibronectin complexes), and polymorphisms of cytokines [tumor necrosis factor alpha (TNFalpha), interleukin 10 (IL-10), IL-6, interferon gamma and transforming growth factor beta 1] and renin-angiotensin system (angiotensinogen converting enzyme, angiotensin II receptor 1, and angiotensinogen) genes. RESULTS: At multivariate logistic regression analysis, recurrence showed a border-line association with aberrantly glycosylated IgA1 [odds ratio (OR) 8.172, p = 0.077], and was significantly less frequent in carriers of -308 AG/AA TNF-alpha"high producer" genotype (OR 0.125, p = 0.036) and -1082, -819, -592 ACC/ATA IL-10 "low producer" (OR 0.038, p = 0.009) genotypes. CONCLUSION: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.

Low renin-angiotensin system activity gene polymorphism and dysplasia associated with posterior urethral valves.

PURPOSE: Obstructive uropathies, including posterior urethral valves (PUVs) and kidney hypodysplasia, are the most frequent cause of renal failure in children. The role of renin-angiotensin system genes in renal and urinary tract development has been observed in experimental models. The aim of this study was to investigate the distribution of angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin receptor type 1 (ATR1) genetic polymorphisms in children affected by chronic renal failure due to renal hypodysplasia associated with posterior urethral valves or without urethral abnormalities. MATERIALS AND METHODS: The study included 50 children (21 with hypodysplasia associated with PUVs, 7 with obstructive uropathy and 22 with pure hypodysplasia) and 50 healthy subjects matched for sex and geographic origin. ACE ID, AGT TC and ATR1 AC gene polymorphisms were assayed in all patients with standard polymerase chain reaction techniques. RESULTS: ACE II was expressed more in patients with PUVs compared to those with other dysplasias and controls (43% vs 7% and 10%, respectively, chi-square test p <0.05), while ATR1 AA was significantly less represented in patients with hypodysplasia compared to controls (38% vs 56%, chi-square test p <0.05). ACE DD and AGT genotypes were not distributed differently in patients with PUVs compared to those with other dysplasias and controls. CONCLUSIONS: To our knowledge this is the first report associating severe congenital uropathies and renal hypodysplasia with decreased renin-angiotensin system activity associated with the ACE II genotype and a possible functional imbalance among ATR1 receptors.

Chromosomal instability and APC gene mutations in human sporadic colorectal adenomas.

The mechanisms by which adenomatous polyposis coli (APC) gene mutations contribute to colorectal tumourigenesis and progression are still not fully understood. Using in vitro mouse embryonic stem cells, APC mutations have been proposed to dysregulate the interactions between kinetochores and microtubules during mitosis, leading to chromosomal instability (CIN) and aneuploidy. A link between APC mutations and aneuploidy in vivo among human sporadic colorectal adenomas has not been reported previously and was therefore investigated in the present series of 61 adenomas. Multi-parameter flow cytometry, based on scattering and fluorescence from the DNA-specific 4,6-diamidino-2-phenylindole-2-hydrochloride (DAPI) dye, which separates epithelial from stromal lymphocyte nuclei, was used to evaluate the DNA index (DI) and to sort epithelial nuclei. Additionally, DNA extracted from these sorted nuclei was used to analyse APC mutations by DNA sequencing. Aneuploidy was present in 20 of 61 adenomas (33%), with 15 of these 20 cases (75%) having a near-diploid DI (DI different from 1 and less than 1.3). APC mutations were detected in 19 adenomas (31%): 12 were within or downstream of the mutation cluster region (MCR), roughly defined by codons 1200-1500, and seven were upstream of the MCR. Overall, the prevalence of aneuploidy in APC wild-type and mutated adenomas was 26% and 47%, respectively, and no statistically significant association was found between APC status and DI (p = 0.142). However, when APC mutations were subdivided into two groups, ie occurring within/downstream of the MCR and upstream of the MCR, the association of APC mutations within and downstream of the MCR with aneuploidy was statistically significant (p = 0.017). In conclusion, the present data suggest that the type of APC mutation may play a role in the origin of CIN in vivo in human sporadic colorectal adenomas and that APC mutations within and downstream of the MCR, and large-scale chromosomal alterations, may co-operate in the progression of a subgroup of adenomas.