Essential genes from Arctic bacteria used to construct stable,temperature-sensitive bacterial vaccines

All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 °C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis.     

Arterialized venous flaps: A review of the literature

The arterialized venous flaps are highly regarded in microsurgical and reconstructive surgeries based on advantages of ease of design and harvest without the need to perform deep dissection, no sacrifice of a major artery at the donor site, no limitation of the donor sites, and less donor‐site morbidity. Many experimental investigations and clinical applications have been reported. However, their survivals are still inconsistent, and survival mechanisms remain controversial. In this review, we update the existing problems, experimental studies for survival mechanisms, clinical practices, and methods developed to improve their survivals. © 2010 Wiley‐Liss, Inc. Microsurgery 30:472–478, 2010.     

Alström Syndrome: Mutation Spectrum of ALMS1

Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone‐rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world‐wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.     

Rapid Reduction in Use of Antidiabetic Medication after Laparoscopic Sleeve Gastrectomy: The Newfoundland and Labrador Bariatric Surgery Cohort (BaSCo) Study

Background:

Patients who have undergone bariatric surgery generally need fewer medications as they experience improvement in, or even resolution of, various medical conditions, including type 2 diabetes mellitus, hypertension, and dyslipidemia. Published data on changes in medication use after laparoscopic sleeve gastrectomy, a type of bariatric surgery that is growing in popularity, are limited.

Objective:

To determine whether patients took fewer medications for management of type 2 diabetes, hypertension, and dyslipidemia after laparoscopic sleeve gastrectomy, relative to preprocedure medications.

Methods:

In this prospective, single-centre cohort study, a nurse practitioner used standard medication reconciliation and study data-extraction forms to interview adult patients who had undergone laparoscopic sleeve gastrectomy and determine their medication use and pertinent demographic data. The data were analyzed using generalized estimating equations and standard statistical software. Outcome measures included changes in the use of antidiabetic, antihypertensive, and antilipemic medications at 1, 3, and 6 months after the surgery.

Results:

A total of 65 patients who underwent laparoscopic sleeve gastrectomy between May 2011 and January 2014 met the study inclusion criteria. Before surgery, the 30 patients with type 2 diabetes were taking an average of 1.9 antidiabetic medications. One month after the procedure, 15 (50%) had discontinued all antidiabetic medications, with a further decline at 3 and 6 months (p < 0.001 at each time point). Among the patients who were taking antihypertensives (n = 48) and antilipemics (n = 33) before surgery, the decline in use occurred at a more modest rate, with 6 (12%) and 2 (6%), respectively, discontinuing these medication classes within 1 month, and 12 (25%) (p = 0.001) and 8 (24%) (p = 0.015) having discontinued by 6 months.

Conclusions:

These findings suggest that patients with a history of type 2 diabetes mellitus, hypertension, and/or dyslipidemia who undergo laparoscopic sleeve gastrectomy are less likely to require disease-specific medications shortly after surgery.     

Alternatives to growth hormone stimulation testing in children.

Despite more than 40 years of pediatric growth hormone (GH) replacement, we are still limited in our ability to make a definitive diagnosis of GH deficiency (GHD) in children. Historically, GH stimulation tests (GHSTs) have been used to discriminate between GHD and idiopathic short stature. Over the years, increases in the peak diagnostic GH cutoffs and the proliferation of GH assays have fundamentally changed the nature of the GHST. In our opinion, today's GHSTs lack reproducibility and accuracy, are expensive, and can be dangerous. Moreover, newer diagnostic tools, such as high-resolution neuroimaging, measurements of serum insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, and an increasing number of genetic tests, have emerged. We believe that it is no longer appropriate to use GHSTs to diagnose childhood GHD. Instead, diagnosis should be based on a combination of auxological, biochemical, neuroradiological and genetic considerations. Here, we examine the alternatives to the GHST that are currently available and literature that supports their use. We believe that these alternative methods should replace the GHST.