Connective tissue progenitor cell growth characteristics on textured substrates

Growth characteristics of human connective tissue progenitor (CTP) cells were investigated on smooth and textured substrates, which were produced using MEMS (microelectromechanical systems) fabrication technology. Human bone marrow derived cells were cultured for 9 days under conditions promoting osteoblastic differentiation on polydimethylsiloxane (PDMS) substrates comprising smooth (non-patterned) surfaces (SMOOTH), 4 different cylindrical post micro-textures (POSTS) that were 7–10 μm high and 5, 10, 20, and 40 μm diameter, respectively, and channel micro-textures (CHANNELS) with curved cross-sections that were 11 μm high, 45 μm wide, and separated by 5 μm wide ridges. Standard glass-tissue culture surfaces were used as controls. Micro-textures resulted in the modification of CTP morphology, attachment, migration, and proliferation characteristics. Specifically, cells on POSTS exhibited more contoured morphology with closely packed cytoskeletal actin microfilaments compared to the more random orientation in cells grown on SMOOTH. CTP colonies on 10 μm-diameter POSTS exhibited higher cell number than any other POSTS, and a significant increase in cell number (442%) compared to colonies on SMOOTH (71%). On CHANNELS, colonies tended to be denser (229%) than on POSTS (up to 140% on 10 μm POSTS), and significantly more so compared to those on SMOOTH (104%)

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded PTFE Propaten Graft in a Chronic Canine Femoral Artery Bypass Model

Background: Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Methods: Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. Results: All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P 0.05). Conclusions: Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency

Post microtextures accelerate cell proliferation and osteogenesis

AbstractThe influence of surface microtexture on osteogenesis was investigated in vitro by examining the proliferation and differentiation characteristics of a class of adult stem cells and their progeny, collectively known as connective tissue progenitor cells (CTPs). Human bone marrow-derived CTPs were cultured for up to 60days on smooth polydimethylsiloxane (PDMS) surfaces and on PDMS with post microtextures that were 10μm in diameter and 6μm in height, with 10μm separation. DNA quantification revealed that the numbers of CTPs initially attached to both substrates were similar. However, cells on microtextured PDMS transitioned from lag phase after 4days of culture, in contrast to 6days for cells on smooth surfaces. By day 9 cells on the smooth surfaces exhibited arbitrary flattened shapes and migrated without any preferred orientation. In contrast, cells on the microtextured PDMS grew along the array of posts in an orthogonal manner. By days 30 and 60 cells grew and covered all surfaces with extracellular matrix. Western blot analysis revealed that the expression of integrin α5 was greater on the microtextured PDMS compared with smooth surfaces. Real time reverse transcription-polymerase chain reaction revealed that gene expression of alkaline phosphatase had decreased by days 30 and 60, compared with that on day 9, for both substrates. Gene expression of collagen I and osteocalcin was consistently greater on post microtextures relative to smooth surfaces at all time points

Magnetic and Electric Dipole Constraints on Extra Dimensions and Magnetic Fluxes

The propagation of charged particles and gauge fields in a compact extra dimension contributes to $g-2$ of the charged particles. In addition, a magnetic flux threading this extra dimension generates an electric dipole moment for these particles. We present constraints on the compactification size and on the possible magnetic flux imposed by the comparison of data and theory of the magnetic moment of the muon and from limits on the electric dipole moments of the muon, neutron and electron.Comment: 11 pages, 5 figures, revtex

Efficacy and Safety of Antioxidant Treatment With α-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy

Objective: To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). Research Design and Methods: In a multicenter randomized double-blind parallel-group trial, 460 diabetic patients with mild-to-moderate DSPN were randomly assigned to oral treatment with 600 mg ALA once daily (n = 233) or placebo (n = 227) for 4 years. Primary end point was a composite score (Neuropathy Impairment Score [NIS]–Lower Limbs [NIS-LL] and seven neurophysiologic tests). Secondary outcome measures included NIS, NIS-LL, nerve conduction, and quantitative sensory tests (QSTs). Results: Change in primary end point from baseline to 4 years showed no significant difference between treatment groups (P = 0.105). Change from baseline was significantly better with ALA than placebo for NIS (P = 0.028), NIS-LL (P = 0.05), and NIS-LL muscular weakness subscore (P = 0.045). More patients showed a clinically meaningful improvement and fewer showed progression of NIS (P = 0.013) and NIS-LL (P = 0.025) with ALA than with placebo. Nerve conduction and QST results did not significantly worsen with placebo. Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not differ between the groups. The rates of serious adverse events were higher on ALA (38.1%) than on placebo (28.0%). Conclusions: Four-year treatment with ALA in mild-to-moderate DSPN did not influence the primary composite end point but resulted in a clinically meaningful improvement and prevention of progression of neuropathic impairments and was well tolerated. Because the primary composite end point did not deteriorate significantly in placebo-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded PTFE Propaten Graft in a Chronic Canine Femoral Artery Bypass Model

Background: Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Methods: Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. Results: All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P 0.05). Conclusions: Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency

Genetics and the Archaeology of Ancient Israel

This paper is a call for DNA testing on ancient skeletal materials from the southern Levant to begin to database genetic information of the inhabitants of this crossroads region. Archaeologists and biblical historians view the earliest presence in the region of a group that called itself Israel in the Iron I period, traditionally dated to ca. 1200-1000 BCE. These were in villages in the varied hill countries of the region, contemporary with urban settlements in the coastal plains, inland valleys, and central Hill Country attributed to varied indigenous groups collectively called Canaanite. The remnants of Egyptian imperial presence in the region lasted until around 1150 BCE, postdating the arrival of an immigrant group from the Aegean called the Philistines ca. 1175 BCE. The period that follows the Iron I in the southern Levant is marked by the development of territorial states throughout the region, ca. 1000-800 BCE. These patrimonial kingdoms, including the United Kingdom of Israel and the divided kingdoms of northern Israel and Judah, coalesced varied peoples under central leadership and newly founded administrative and religious bureaucracies. Ancient DNA testing will give us a further refined understanding of the individuals who peopled the region of the southern Levant throughout its varied archaeological and historic periods, and put forward scientific data that will support, refute, or nuance our socio-historic reconstruction of ancient group identities. These social identities may or may not map onto genetic data, and without sampling of ancient DNA we may never know. A database of ancient DNA will also allow for comparisons with modern DNA samples collected throughout the greater region and the Mediterranean littoral, giving a more robust understanding of the long historical trajectories of regional human genetics and the genetics of varied ancestral groups of today’s Jewish populations and other cultural groups in the modern Middle East and Mediterranean

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID