Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

BackgroundSystemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.MethodsIn this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.ResultsOne hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).ConclusionsOral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART

Transitioning from Episodic to Sustained Care in Humanitarian Service

Background: Humanitarian missions serve populations needing care and usually provide short term interventions. Traditionally, care provided through humanitarian agencies like VOSH International has been episodic, consisting of a short-term mission placing a team in country for several days. There have been discussions that episodic care is a short term measure which impedes the systematic development of a long term solution to providing the necessary health care. The move toward sustained care is a step in the direction of improving the public health in developing countries. Method: A survey instrument was mailed to the 26 VOSH chapters in the United States and Canada. Results were tabulated and analyzed. Results: Sixteen completed surveys were returned for a response rate of 62%. In a one-year period, missions were carried out in 13 countries. There is a strong tendency toward continuity of care with 81% of respondents returning to locations of previous missions and 69% targeting the same population base. There is also a trend toward providing sustained care (such as establishment of a fixed clinical facility) with half responding affirmatively. Nineteen percent of chapters have been involved in the development or enhancement of departments, schools or colleges of optometry in the developing world. Conclusion: It is exhibited in this study that most teams return to the same areas for future missions and collaborate with other partners with different expertise to create an ongoing presence. This model provides acute care for those needing immediate attention but also enhances the local infrastructure to develop a plan for long term care of this population. This allows for the opportunity to address immediate concerns, build rapport with the community, and use that goodwill and expertise to create long term change. While episodic humanitarian missions have made a profound impact, transitioning from episodic to sustained care improves overall quality of care, expanded services and long-term impact

Viscous damping of nanobeam resonators: humidity, thermal noise and the paddling effect

The nanobeam resonator is the key mechanical component in the nano-electromechanical system. In addition to its high frequency originating from its low dimension, the performance is significantly influenced by the circumstances, especially at nanoscale where a large surface area of the material is exposed. Molecular dynamics simulations and theoretical analysis are used for a quantitative prediction on the damping behavior, such as the critical damping condition and lifetime, of nanobeam resonators that directly maps the fluid-structure properties and interaction information into dynamical behaviors. We show here how the humidity defines the critical damping condition through viscous forces, marking the transition from under-damping to over-damping regime at elevated humidity. Novel phenomena such as the thermal fluctuation and paddling effects are also discussed.Comment: 15 pages, 5 figure

Travel Illness Outbreak Investigation and Treatment among Interprofessional Health Team Members in Guatemala

Purpose: Americans travel each year and acquire illnesses. Gastrointestinal illness is a common self-reported illness and has many associated risk factors. Students from a medical school in Virginia traveled to Guatemala to provide medical care. Overall, 1,250 patients were seen by the student doctors. An outbreak investigation was initiated when members of the medical team began experiencing illness. Methods: Food and water safety was inspected and inquiries were made about the health of other travelers staying at the same host. Furthermore, a voluntary brief survey was completed after returning to the United States. The index patient had seen a patient in the clinic with similar symptoms. An incubation period of 24-36 hours was established. Results: After an adequate kitchen inspection including both food and water distribution, it was determined the illness was being spread from person to person. The survey was administered to 93 travelers and 69 completed the survey. Symptoms were reported by 74% of survey respondents. There was no correlation to consumption of food and water. Conclusions: Prevention measures such as hand hygiene practices should be emphasized to prevent spread of the illness among medical travelers. Limitations include recall bias

Palladium-catalyzed heteroallylation of unactivated alkenes – synthesis of citalopram

A palladium-catalyzed difunctionalization of unactivated alkenes with tethered nucleophiles is reported. The versatile reaction occurs with simple allylic halides and can be carried out under air. The methodology provides rapid access to a wide array of desirable heterocyclic targets, as illustrated by a concise synthesis of the widely prescribed antidepressant citalopram

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Anatomy of the high-frequency ambient seismic wave field at the TCDP borehole.

International audienceThe Taiwan Chelungpu-fault Drilling Project (TCDP) installed a vertical seismic array between 950 and 1270 m depth in an active thrust fault environment. In this paper we analyze continuous noise records of the TCDP array between 1 and 16 Hz. We apply multiple array processing and noise correlation techniques to study the noise source process, properties of the propagation medium, and the ambient seismic wave field. Diurnal amplitude and slowness patterns suggest that noise is generated by cultural activity. The vicinity of the recording site to the excitation region, indicated by a narrow azimuthal distribution of propagation directions, leads to a predominant ballistic propagation regime. This is evident from the compatibility of the data with an incident plane wave model, polarized direct arrivals of noise correlation functions, and the asymmetric arrival shape. Evidence for contributions from scattering comes from equilibrated earthquake coda energy ratios, the frequency dependent randomization of propagation directions, and the existence of correlation coda waves. We conclude that the ballistic and scattered propagation regime coexist, where the first regime dominates the records, but the second is weaker yet not negligible. Consequently, the wave field is not equipartitioned. Correlation signal-to-noise ratios indicate a frequency dependent noise intensity. Iterations of the correlation procedure enhance the signature of the scattered regime. Discrepancies between phase velocities estimated from correlation functions and in-situ measurements are associated with the array geometry and its relative orientation to the predominant energy flux. The stability of correlation functions suggests their applicability in future monitoring efforts

Synthesis of DNA fragments in yeast by one-step assembly of overlapping oligonucleotides

Here it is demonstrated that the yeast Saccharomyces cerevisiae can take up and assemble at least 38 overlapping single-stranded oligonucleotides and a linear double-stranded vector in one transformation event. These oligonucleotides can overlap by as few as 20 bp, and can be as long as 200 nucleotides in length. This straightforward scheme for assembling chemically-synthesized oligonucleotides could be a useful tool for building synthetic DNA molecules

Dietary plasma proteins attenuate the innate immunity response in a mouse model of acute lung injury

We examined whether oral plasma protein supplements affect the innate immune response in a model of acute lung inflammation. Mice were fed diets supplemented with 8% spray-dried plasma (SDP) or 2% plasma Ig concentrate (IC) from day 19 (weaning) until day 34. The mice were challenged with intranasal lipopolysaccharide (LPS) at day 33 (and killed 24 h later for cytokine and leucocyte analyses) or at day 34 (and killed 6 h later for cytokine determinations). In bronchoalveolar lavage fluid (BALF), LPS increased the number of leucocytes by twenty-sevenfold, an effect that was partly prevented by both SDP and IC, and by twentyfold the percentage of activated monocytes, which was partly prevented by SDP. In the lung tissue, LPS increased the infiltrated leucocytes, and this effect was prevented in part by SDP. In unchallenged mice, both SDP and IC diets reduced the percentage of resident neutrophils and monocytes (P,0·05). In the blood, both SDP and IC completely prevented LPS-dependent monocyte activation (CD14þ; P,0·05). LPS dramatically increased the concentration of cytokines (TNF-a, IL-1a, IL-6, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor) and chemokines (CXCL1, CCL2, CCL3 and CCL4) in BALF. The acute response of cytokine production was reduced by 20-80% by both SDP and IC. For chemokines, plasma supplements had no effect on LPS-induced CXCL1 expression but significantly reduced CCL2, CCL3 and CCL4 production (P,0·05). The results support the view that dietary plasma proteins can be used to attenuate endotoxin-associated lung inflammation

Water vapor in the starburst galaxy NGC 253: A new nuclear maser?

22 GHz water vapor emission was observed toward the central region of the spiral starburst galaxy NGC 253. Monitoring observations with the 100-m telescope at Effelsberg and measurements with the BnC array of the VLA reveal three distinct velocity components, all of them blueshifted with respect to the systemic velocity. The main component arises from a region close to the dynamical center and is displaced by <1 arcsec from the putative nuclear continuum source. The bulk of this maser component is spread over an area not larger than 70 x 50 mas. Its radial velocity may be explained by masing gas that is part of a nuclear accretion disk or of a counterrotating kinematical subsystem or by gas that is entrained by the nuclear superwind or by an expanding supernova shell. A weaker feature, located 5 arcsec to the northeast, is likely related to an optically obscured site of massive star formation.Comment: 6 pages, 4 Postscript figures, A&A Main Journa