Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis

Povidone-iodine Irrigation - A Possible Alternative To Lead Extraction

Pocket infection and erosion remain the commonest (class 1) indication for pacemaker (PM) or implantable cardiac defibrillator (ICD) lead extraction. However, tranvenous lead extraction is not without significant risk of serious complications, particularly in patients with chronically implanted leads or ICD leads specifically. The paucity of cardiologists adequately experienced to undertake this high-risk procedure also means that its availability is limited to relatively few specialist institutions, yet more conservative 'lead-preserving' treatment options have not been well-reported. We describe the first reported case of a chronically eroded and infected ICD generator, managed conservatively with 5-days of povidone-iodine closed irrigation, followed by re-implantation of a new ICD on the contralateral side. With satisfactory long-term follow-up, this successfully averted the need for lead extraction in our elderly patient. We advocate the need for formal prospective evaluation of conservative therapeutic strategies of PM and ICD pocket infections. Although not gold standard, it provides an important therapeutic alternative in resource-limited areas

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles

High-resolution Near-Infrared Images and Models of the Circumstellar Disk in HH 30

We present Hubble Space Telescope (HST) Near-Infrared Camera and Multi-object Spectrometer (NICMOS) observations of the reflection nebulosity associated with the T Tauri star HH 30. The images show the scattered light pattern characteristic of a highly inclined, optically thick disk with a prominent dustlane whose width decreases with increasing wavelength. The reflected nebulosity exhibits a lateral asymmetry in the upper lobe on the opposite side to that reported in previously published Wide Field Planetary Camera 2 (WFPC2) images. The radiation transfer model which most closely reproduces the data has a flared accretion disk with dust grains larger than standard interstellar medium grains by a factor of approximately 2.1. A single hotspot on the stellar surface provides the necessary asymmetry to fit the images and is consistent with previous modeling of the light curve and images. Photometric analysis results in an estimated extinction of Av>~80; however, since the photometry measures only scattered light rather than direct stellar flux, this a lower limit. The radiative transfer models require an extinction of Av = 7,900.Comment: Accepted for publication in Ap.

Patient and physician preferences for surgical and adjuvant treatment options for rectal cancer

Hypothesis Patients and their clinicians hold varying preferences for surgical and adjuvant treatment therapies for rectal cancer. Design Preferences were determined using the Prospective Measure of Preference. Setting Royal Prince Alfred and St Vincent\u27s hospitals in Sydney, Australia. Participants Patients with colorectal cancer were interviewed during their postoperative hospital stay, and physicians were asked to complete a mailed survey. Main Outcome Measures The Prospective Measure of Preference method produces 2 outcome measures of preference: willingness to trade and prospective measure of preference time trade-off. Results Patients\u27 strongest preference was to avoid a stoma: more than 60% would give up a mean of 34% of their life expectancy to avoid this surgical option. This was followed by treatment options involving chemoradiotherapy, where more than 50% would give up a mean of almost 25% of their life to avoid treatment. Surgeons held stronger preferences against all adjuvant options compared with oncologists (P ≤ .01). Conclusions Patients had strong preferences against all treatment options, and these preferences frequently differed from those of physicians. These results highlight the importance of determining patients\u27 own preferences in the clinical encounter. Furthermore, the diversity of preferences of clinical subspecialists emphasizes the need for multidisciplinary treatment planning to ensure a balanced approach to treatment decision making for patients with rectal cancer

How Frustrated Strings Would Pull the Black Holes from the Centers of Galaxies

Recently Pen and Spergel (1997) have shown that a universe whose energy density is dominated by a frustrated network of non-Abelian TeV-scale cosmic strings could account for a broad class of cosmological observations. In this paper we consider the effects of such a string network on the massive black holes widely believed to inhabit the centers of many galaxies. As these black holes traverse the universe together with their host galaxies, they would intersect a large number of string segments. We argue that such segments would become stuck to the black hole, and be stretched by the hole's motion. Stretching the strings would cause significant deceleration of the black holes. Although the black holes would probably not be removed from the galaxies completely, they would be noticeably displaced from the galactic center of mass -- by at least 5kpc. This displacement seems to be is contradiction to the observational evidence.Comment: 9 pages, 2 figures, accepted for publication in Phys. Rev.

Oleoyl Coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in Mycobacteria

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria

1950: Abilene Christian College Bible Lectures - Full Text

Introduction We offer with interest and pleasure another volume of a great series of discourses delivered at Abilene Christian College. The following were given in February, 1950. The first of these Lectureships was held in the year 1919, and was published by the Firm Foundation Publishing House in book form. With little exception they have appeared each year since that time. The printing was done by others a few times. Those who are fortunate enough to have a complete set of these fine gospel sermons are possessed of a treasure in religious literature. Only a few of the later years can now be supplied. The rest are numbered among the “rare books” and we frequently have calls for them, but of course cannot supply them. Any reader having a copy for sale is requested to write the office of the Firm Foundation at Austin, Texas. The “Lectureship” of Abilene Christian College has become a great annual affair to the churches of Christ; thousands are in attendance, many of them coming from Canada and other countries besides all over the United States. This annual “mass meeting” must not be understood to be a “Convention” of the churches of Christ. We have no such conventions and do not endorse them. The Lectureship is simply a feature in the work of Abilene Christian College, a series of gospel sermons to which friends and patrons of the school and others are invited. It is our hope that the contents of this book may enrich the life, and strengthen the faith of the reader. G. H. F. SHOWALTER Austin, Texas August 20, 195

Chemoselective sequential click ligations directed by enhanced reactivity of an aromatic ynamine

Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 +2] cycloaddition (“click”) reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups