Ten years of Genome Medicine.

This year marks the 10th anniversary of Genome Medicine. The journal was launched to meet the need in the community for a platform to publish impactful and open science that advances basic and clinical research—using genetic, genomic, omic, and systems approaches—that has the potential to revolutionize the practice of medicine. We have seen the journal evolve along with the changing landscape of health and disease, including the increasing use of genome-scale approaches in medical research and clinical practice, the generation and analysis of patient- and population-level data, and the clinical implementation of these approaches in precision medicine and public health. Genome Medicine, guided by our renowned Section Editors, continues to serve an ever-growing community of interdisciplinary researchers. Here, our Section Editors discuss the major advances in the field and their applications in genomic medicine during the past decade

Easy dual-mode ambient mass spectrometry with Venturi self-pumping, canned air, disposable parts and voltage-free sonic-spray ionization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)An exceptionally easy to assemble source for ambient mass spectrometry is described. Based on Venturi easy ambient sonic-spray ionization (V-EASI), the source was further simplified by the use of a can of compressed air which simultaneously provides solution or solvent Venturi self-pumping and continuous, stable and abundant low-noise ion signal via voltage-free sonic-spraying. Further simplification was also attained by the use of inexpensive and readily commercially available parts: a surgical 2-way catheter, an aerosol can of compressed air, a 30 cm long fused-silica capillary and a hypodermic needle. This 'Spartan' V-EASI source seems to offer one of the easiest and cheapest ways to make ions for ambient desorption/ionization mass spectrometry analysis of both liquid and solid samples.1371125372540Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Brazilian Science Foundation's FINEPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Identification of the Neogenin-Binding Site on the Repulsive Guidance Molecule A

Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the chick retinotectal system. RGMa, one of the 3 isoforms found in mammals, is involved in laminar patterning, cephalic neural tube closure, axon guidance, and inhibition of axonal regeneration. In addition to its roles in the nervous system, RGMa plays a role in enhancing helper T-cell activation. Binding of RGM to its receptor, neogenin, is considered necessary to transduce these signals; however, information on the binding of RGM to neogenin is limited. Using co-immunoprecipitation studies, we have identified that the RGMa region required for binding to neogenin contains amino acids (aa) 259–295. Synthesized peptide consisting of aa 284–293 directly binds to the extracellular domain (ECD) of recombinant neogenin, and addition of this peptide inhibits RGMa-induced growth cone collapse in mouse cortical neurons. Thus, we propose that this peptide is a promising lead in finding reagents capable of inhibiting RGMa signaling

Upper airway dynamics during negative expiratory pressure in apneic and non-apneic awake snorers

BACKGROUND: The ability of negative expiratory pressure (NEP) technique to differentiate between awake snorers with and without obstructive sleep apnea-hypopnea (OSAH) was investigated. METHODS: Forty-eight subjects with sleep disordered breathing (SDB) and 7 healthy subjects, as non-snorer controls, underwent the NEP application of -5 and -7 cmH(2)O in the seated and supine position during wakefulness, after performing a sleep study. The upper airway collapsibility was assessed by computing the volume exhaled during the first 0.5 sec. (V,NEP(0.5)) and 1 sec. (V,NEP(1)) following the NEP start. RESULTS: Patients with severe (AHI ≥ 30) (n = 19) and mild-to-moderate (AHI <30 and >5) (n = 15) OSAH had lower V,NEP(0.5 )(340 ± 88 ml) as compared to snorers (AHI ≤ 5) (n = 14) (427 ± 101 ml; p < 0.01) and controls (n = 7) (492 ± 69 ml; p < 0.001) in the supine position with NEP -5 cmH(2)O. Less significant differences among the different groups were observed for V,NEP(0.5 )in the seated position with NEP -5 cmH(2)O and in both positions with NEP -7 cmH(2)O (only OSAH patients vs controls, p < 0.001). Similar results were obtained for V,NEP(1 )in either position by using both NEP -5 cmH(2)O and -7 cmH(2)O. In spite of this, a substantial overlapping of V,NEP(0.5 )and V,NEP(1 )between snorers and OSAH patients did not allow to identify a reliable diagnostic cut-off level. An inverse correlation with AHI was found for V,NEP(0.5 )in the supine position with NEP -5 cmH(2)O (r(s )= -0.46, p < 0.05) in severe OSAH patients. CONCLUSION: The awake OSAH patients exhibit values of V,NEP(0.5 )and V,NEP(1 )lesser than those of awake snorers. The NEP technique, however, appears to have a limited usefulness as clinical tool for routine screening of the OSAH patients during wakefulness

Five mucosal transcripts of interest in ulcerative colitis identified by quantitative real-time PCR: a prospective study

<p>Abstract</p> <p>Background</p> <p>The cause and pathophysiology of ulcerative colitis are both mainly unknown. We have previously used whole-genome microarray technique on biopsies obtained from patients with ulcerative colitis to identifiy 5 changed mucosal transcripts. The aim of this study was to compare mucosal expressions of these five transcripts in ulcerative colitis patients vs. controls, along with the transcript expression in relation to the clinical ulcerative colitis status.</p> <p>Methods</p> <p>Colonic mucosal specimens from rectum and caecum were taken at ambulatory colonoscopy from ulcerative colitis patients (<it>n </it>= 49) with defined inflammatory activity and disease extension, and from controls (<it>n </it>= 67) without inflammatory bowel disease. The five mucosal transcripts aldolase B, elafin, MST-1, simNIPhom and SLC6A14 were analyzed using quantitative real-time PCR.</p> <p>Results</p> <p>Significant transcript differences in the rectal mucosa for all five transcripts were demonstrated in ulcerative colitis patients compared to controls. The grade of transcript expression was related to the clinical disease activity.</p> <p>Conclusion</p> <p>The five gene transcripts were changed in patients with ulcerative colitis, and were related to the disease activity. The known biological function of some of the transcripts may contribute to the inflammatory features and indicate a possible role of microbes in ulcerative colitis. The findings may also contribute to our pathophysiological understanding of ulcerative colitis.</p

Microbiology of airway disease in a cohort of patients with Cystic Fibrosis

BACKGROUND: Recent reports document an increasing incidence of new Gram-negative pathogens such as Stenotrophomonas maltophilia and Alcaligenes xylosoxidans isolated from patients with Cystic Fibrosis, along with an increase in common Gram-negative pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex. Furthermore, the increase in multidrug-resistance of such organisms makes the therapeutic management of these patients more problematic. Therefore, careful isolation and identification, and accurate studies of susceptibility to antibiotics are critical for predicting the spread of strains, improving therapeutic measures and facilitating our understanding of the epidemiology of emerging pathogens. The first aim of this study was to determine the incidence and the prevalence of colonization by Gram-negative organisms isolated from respiratory samples of Cystic Fibrosis patients in the Regional Referral Cystic Fibrosis Centre of Naples; the second was to evaluate the spectrum of multidrug-resistance of these organisms. METHODS: Patients (n = 300) attending the Regional Cystic Fibrosis Unit were enrolled in this study over 3 years. Sputum was processed for microscopic tests and culture. An automated system, Phoenix (Becton Dickinson, Sparks, Maryland, USA), was used for phenotypic identification of all strains; the API 20 NE identification system (bioMérieux, Marcy l'Etoile, France) was used when the identification with the Phoenix system was inaccurate. A PCR-RFLP method was used to characterize the organisms in the Burkholderia cepacia complex. A chemosusceptibility test on microbroth dilutions (Phoenix) was used. Primary outcomes such as FEV1 were correlate with different pathogens. RESULTS: During the period of study, 40% of patients was infected by Pseudomonas aeruginosa, 7% by Burkholderia cepacia complex, 11% by Stenotrophomonas maltophilia and 7% by Alcaligenes xylosoxidans. Of the strains isolated, 460 were multidrug-resistant. Multiresistant were Pseudomonas aeruginosa and Burkholderia cepacia complex. CONCLUSION: The results confirm previously reported data; in particular, they show an increase the isolation of non-fermentative Gram-negative bacteria in Cystic Fibrosis patients. They also demonstrate increased resistance to antibiotics. Beta-lactams are rarely effective, with exception of ceftazidime, which is the most efficacious agent against multiresistant strains. Aminoglycosides and quinolones are poorly efficacious

Operative versus non-operative management of pediatric medial epicondyle fractures: a systematic review

There is ongoing debate about the management of medial epicondyle fractures in the pediatric population. This systematic review evaluated non-operative versus operative treatment of medial epicondyle fractures in pediatric and adolescent patients over the last six decades. A systematic review of the available literature was performed. Frequency-weighted mean union times were used to compare union rates for closed versus open treatments. Moreover, functional outcomes and range-of-motion variables were correlated with varying treatment modalities. Any complications, including ulnar nerve symptoms, pain, instability, infection, and residual deformity, were cataloged. Fourteen studies, encompassing 498 patients, met the inclusion/exclusion criteria. There were 261 males and 132 female patients; the frequency-weighted average age was 11.93 years. The follow-up range was 6–216 months. Under the cumulative random effects model, the odds of union with operative fixation was 9.33 times the odds of union with non-operative treatment (P &lt; 0.0001). There was no significant difference between operative and non-operative treatments in terms of pain at final follow-up (P = 0.73) or ulnar nerve symptoms (P = 0.412). Operative treatment affords a significantly higher union rate over the non-operative management of medial epicondyle fractures. There was no difference in pain at final follow-up between operative and non-operative treatments. As surgical indications evolve, and the functional demands of pediatric patients increase, surgical fixation should be strongly considered to achieve stable fixation and bony union

Role of lipid apheresis in changing times

During the last decades, LDL-apheresis was established as an extracorporeal treatment option for patients with severe heterozygous or homozygous familial hypercholesterolemia (FH) that is resistant to conventional treatment strategies such as diet, drugs, and changes in lifestyle. Nearly half a century ago, the first LDL-apheresis treatment was performed by plasma exchange in a child with homozygous FH