Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

Background Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. Conclusions We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.

Milk flow-dependent vacuum loss in high-line milking systems: effects on milking characteristics and teat tissue condition

To study the effects of a milking system that partially compensates for milk flow-dependent vacuum loss compared with a standard (high-line) milking unit in a tie-stall barn, milk flow and vacuum patterns were recorded in 10 cows during machine milking with 2 milking systems in a crossover design for 7 d each. Before and after each treatment period postmilking teat condition was recorded by ultrasound cross-sectioning. Additionally, 2 methods to measure teat tissue condition were compared: longitudinal teat ultrasound cross-sectioning and teat tissue density measurements with the spring-loaded caliper (cutimeter method). The partial compensation of milk flow-dependent vacuum loss caused an elevation of the peak flow rate (4.74+/-0.08 vs. 4.29+/-0.07 kg/min) and a shorter duration of plateau (1.57+/-0.06 vs. 1.96+/-0.07 min) compared with the standard milking system. Total milk yield, duration of incline and decline of milk flow, average milk flow, time until peak flow rate, main milking time, and total milking time did not differ between treatments (overall means: 13.75+/-0.17 kg; 0.65+/-0.01 min; 2.88+/-0.09 min; 2.82+/-0.05 kg/min; 1.65+/-0.03 min; 5.23+/-0.09 min, and 5.30+/-0.10 min, respectively). The vacuum drop in the short milk tube during periods of high milk flow was less in the compensating vacuum than in the standard milking system (11+/-1.1 vs. 15+/-0.7 kPa). Teat measures as determined by ultrasound remained unchanged over the entire experimental period with both milking systems. Postmilking teat tissue measures including their recovery within 20 min after the end of milking show a correlation (0.85 and 0.71, respectively) between the methods used (ultrasound and cutimeter method). In conclusion, a more constant vacuum at the teat tip (within the short milk tube) during periods of high milk flow affected milk flow patterns, mainly increasing peak flow rate. However, the reduced vacuum loss did not increase the overall speed of milking. In addition, effects of higher vacuum stability on teat condition and udder health were not obvious.

T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity

BACKGROUND: Quinolones are widely used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2-3% of treated patients. OBJECTIVE: To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX). METHODS: We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones (TCC). RESULTS: The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX- and MXFX-specific CD4(+)/CD8(+) T cell receptor (TCR) alphabeta(+) TCC were generated to investigate the nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross-reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross-reactivity and clones showing a broad cross-reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)-peptide complex, as glutaraldehyde-fixed Ag-presenting cells (APC) could present the drug and washing quinolone-pulsed APC removed the drug, abrogating the reactivity of quinolone-specific TCC. CONCLUSION: Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent.

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Inducible nitric oxide synthase and nitrotyrosine in listeric encephalitis: a cross-species study in ruminants

Listeria monocytogenes (LM) is a Gram-positive facultative intracellular bacterium that causes fatal meningoencephalitis in humans and ruminants. A current paradigm predicts that intracellular bacteria are controlled by nitric oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase (iNOS). The ability of macrophages (Mphi) to express iNOS shows extreme interspecies variability. Here the expression of iNOS and synthesis of NO was studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed by a subset of Mphi in cerebral microabscesses in all three species. The level of iNOS expression and the density of cells per lesion expressing iNOS was highest in cattle, intermediate in sheep, and lowest in goats. The accumulation of nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions of cattle but not in those of small ruminants. The density of iNOS-expressing cells in lesions was inversely correlated with the number of bacteria. No species differences were observed in regard to reactive oxygen intermediate (ROI) production by stimulated granulocytes, using the flow cytometric dihydrorhodamine-123 (DHR) method indicating ROI generation. Thus, the marked species differences in iNOS expression, NT accumulation, and LM content in lesions of ruminants with listeric encephalitis are explained by different amounts of ROI produced. It suggests that variations in the ability of Mphi to synthesize NO are of pathophysiological significance in listeriosis.

Hop-to-Hop Reliability in IP-Based Wireless Sensor Networks - A Cross-Layer Approach

To interconnect a wireless sensor network (WSN) to the Internet, we propose to use TCP/IP as the standard protocol for all network entities. We present a cross layer designed communication architecture, which contains a MAC protocol, IP, a new protocol called Hop-to-Hop Reliability (H2HR) protocol, and the TCP Support for Sensor Nodes (TSS) protocol. The MAC protocol implements the MAC layer of beacon-less personal area networks (PANs) as defined in IEEE 802.15.4. H2HR implements hop-to-hop reliability mechanisms. Two acknowledgment mechanisms, explicit and implicit ACK are supported. TSS optimizes using TCP in WSNs by implementing local retransmission of TCP data packets, local TCP ACK regeneration, aggressive TCP ACK recovery, congestion and flow control algorithms. We show that H2HR increases the performance of UDP, TCP, and RMST in WSNs significantly. The throughput is increased and the packet loss ratio is decreased. As a result, WSNs can be operated and managed using TCP/IP.

Flow disturbances in stent-related coronary evaginations: a computational fluid-dynamic simulation study

Aims: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. Methods and results: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross ectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. Conclusions: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

High-resolution glacial and deglacial record of atmospheric methane by continuous-flow and laser spectrometer analysis along the NEEM ice core

The Greenland NEEM (North Greenland Eemian Ice Drilling) operation in 2010 provided the first opportunity to combine trace-gas measurements by laser spectroscopic instruments and continuous-flow analysis along a freshly drilled ice core in a field-based setting. We present the resulting atmospheric methane (CH4) record covering the time period from 107.7 to 9.5 ka b2k (thousand years before 2000 AD). Companion discrete CH4 measurements are required to transfer the laser spectroscopic data from a relative to an absolute scale. However, even on a relative scale, the high-resolution CH4 data set significantly improves our knowledge of past atmospheric methane concentration changes. New significant sub-millennial-scale features appear during interstadials and stadials, generally associated with similar changes in water isotopic ratios of the ice, a proxy for local temperature. In addition to the midpoint of Dansgaard–Oeschger (D/O) CH4 transitions usually used for cross-dating, sharp definition of the start and end of these events brings precise depth markers (with ±20 cm uncertainty) for further cross-dating with other palaeo- or ice core records, e.g. speleothems. The method also provides an estimate of CH4 rates of change. The onsets of D/O events in the methane signal show a more rapid rate of change than their endings. The rate of CH4 increase associated with the onsets of D/O events progressively declines from 1.7 to 0.6 ppbv yr−1 in the course of marine isotope stage 3. The largest observed rate of increase takes place at the onset of D/O event #21 and reaches 2.5 ppbv yr−1.

Opportunistic Routing for Multi-flow Video Dissemination over Flying Ad-Hoc Networks

A reliable and robust routing service for Flying Ad-Hoc Networks (FANETs) must be able to adapt to topology changes. User experience on watching live video sequences must also be satisfactory even in scenarios with buffer overflow and high packet loss ratio. In this paper, we introduce a Cross-layer Link quality and Geographical-aware beaconless opportunistic routing protocol (XLinGO). It enhances the transmission of simultaneous multiple video flows over FANETs by creating and keeping reliable persistent multi-hop routes. XLinGO considers a set of cross-layer and human-related information for routing decisions, as performance metrics and Quality of Experience (QoE). Performance evaluation shows that XLinGO achieves multimedia dissemination with QoE support and robustness in a multi-hop, multi-flow, and mobile network environments.

Performance analysis of a miniature turbine generator for intracorporeal energy harvesting

Replacement intervals of implantable medical devices are commonly dictated by battery life. Therefore, intracorporeal energy harvesting has the potential to reduce the number of surgical interventions by extending the life cycle of active devices. Given the accumulated experience with intravascular devices such as stents, heart valves, and cardiac assist devices, the idea to harvest a small fraction of the hydraulic energy available in the cardiovascular circulation is revisited. The aim of this article is to explore the technical feasibility of harvesting 1 mW electric power using a miniature hydrodynamic turbine powered by about 1% of the cardiac output flow in a peripheral artery. To this end, numerical modelling of the fluid mechanics and experimental verification of the overall performance of a 1:1 scale friction turbine are performed in vitro. The numerical flow model is validated for a range of turbine configurations and flow conditions (up to 250 mL/min) in terms of hydromechanic efficiency; up to 15% could be achieved with the nonoptimized configurations of the study. Although this article does not entail the clinical feasibility of intravascular turbines in terms of hemocompatibility and impact on the circulatory system, the numerical model does provide first estimates of the mechanical shear forces relevant to blood trauma and platelet activation. It is concluded that the time-integrated shear stress exposure is significantly lower than in cardiac assist devices due to lower flow velocities and predominantly laminar flow.

Vascular turbine powering a cardiac pacemaker: an in-vivo case study

Background: Today’s medical devices are powered by batteries with a limited energy storage capacity. Depleted batteries have to be replaced, exposing the patients to the risk of adverse events. Thus, a method for harvesting energy inside the body is desirable since it would allow building devices without batteries. Methods: A miniaturized intravascular Tesla turbine was implanted as an arteriovenous shunt between the common carotid artery and external jugular vein of a pig. The harvested energy was used to power a custom-built temporary cardiac pacemaker. Results: At a flow rate of ~150 ml/min, an output power of 0.4 mW was measured. Successful ventricular pacing was performed. Conclusion: Harvesting energy from the circulation using an intravascular turbine is technically feasible and provides enough energy to power a cardiac pacemaker.

Virtopsy: postmortem minimally invasive angiography using cross section techniques--implementation and preliminary results.

Postmortem investigation is increasingly supported by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). This led to the idea to implement a noninvasive or minimally invasive autopsy technique. Therefore, a minimally invasive angiography technique becomes necessary, in order to support the vascular cross section diagnostic. Preliminary experiments investigating different contrast agents for CT and MRI and their postmortem applicability have been performed using an ex-vivo porcine coronary model. MSCT and MRI angiography was performed in the porcine model. Three human corpses were investigated using minimally invasive MSCT angiography. Via the right femoral artery a plastic tube was advanced into the aortic arch. Using a flow adjustable pump the radiopaque contrast agent meglumine-ioxithalamate was injected. Subsequent MSCT scanning provided an excellent anatomic visualization of the human arterial system including intracranial and coronary arteries. Vascular pathologies such as calcification, stenosis and injury were detected. Limitations of the introduced approach are cases of major vessel injury and cases that show an advanced stage of decay.