Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may ...persist in the gut mucosa and elsewhere in individuals on long-term HAART.
We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut).
Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400 mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4(+) T cells carrying HIV-1 proviral DNA was determined.
Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4(+) T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4(+) T-cell counts.
In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4(+) T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4(+) T-cell counts.
This paper presents a QoS-based performance analysis of file systems and distributed object services for Continuous Media (CM) provisioning, as well as the details and implementation experiences of a ...continuous media file system and associated CM servers. For this we have implemented QoS-driven CM servers and the Presto continuous media file system (PFS) in the context of a distributed multimedia application development environment, and validate the performance of PFS against that of the conventional Unix file system through an experimental evaluation. Using our CM server prototype, we next examine the effect of continuous media data delivery on the three different kinds of network protocols such as CORBA, UDP/IP, and TCP/IP, with respect to QoS provisioning and throughput.
There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic ...infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.
Previous studies have extended the traditional framework on occupational disparities in health by examining mortality differentials from a career perspective. Few studies, however, have examined the ...relation between career and mortality in a historical U.S. population. This study explores the relation between occupational career and risk of mortality in old age among 7096 Union Army veterans who fought the American Civil War in the 1860s. Occupational mobility was commonplace among the veterans in the postbellum period, with 54% of them changing occupations from the time of enlistment to 1900. Among veterans who were farmers at enlistment, 46% of them changed to a non-farming occupation by the time of 1900. Results from the Cox Proportional Hazard analysis suggest that relative to the average mortality risk of the sample, being a farmer at enlistment or circa 1900 are both associated with a lower risk of mortality in old age, although the effect is more salient for veterans who were farmers at enlistment. Occupational immobility for manual labors poses a serious threat to chance of survival in old age. These findings still hold after adjusting for the effects of selected variables characterizing risk exposures during early life, wartime, and old age. The robustness of the survival advantage associated with being a farmer at enlistment highlights the importance of socioeconomic conditions early in life in chance of survival at older ages.
Introduction
Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease affecting the axial skeleton, including the sacroiliac joint, which causes vertebral fusion in the advanced stage. ...However, reports of anterior cervical osteophytes compressing the esophagus and causing dysphagia in patients with AS are rare. Here, we present the case of a patient with AS and anterior cervical osteophytes who exhibited rapidly progressing dysphagia after thoracic spinal cord injury (SCI).
Case Presentation
The patient, a 79-year-old man, was previously diagnosed with AS and had syndesmophytes at C2-C7 without dysphagia for several years. In 2020, he began to experience paraplegia, hypesthesia, and bladder and bowel dysfunction after a fall. He also had T9 SCI American Spinal Injury Association Impairment Scale grade A due to a T10 transverse fracture. Four months after SCI, he developed aspiration pneumonia, and a videofluoroscopic swallowing study indicated dysphagia with epiglottic closing problems due to syndesmophytes at the C2-C3 and C3-C4 levels. He received treatment for dysphagia and VitalStim therapy thrice (once daily); however, the recurrent pneumonia and fever continued. He further underwent bedside physical therapy and functional electrical stimulation once daily. However, he died from atelectasis and exacerbation of sepsis.
Discussion and Conclusion
General deterioration of the patient’s physical condition due to SCI, sarcopenic dysphagia, and compression of cervical osteophytes seemed to be involved in rapid exacerbation following SCI. Early screening for dysphagia is vital in bedridden patients with AS or SCI. Additionally, assessment and follow-up are important if the number of rehabilitation treatments or the out-of-bed movement activity decreases because of pressure ulcers.
Electron tomography is a well-established technique for three-dimensional structure determination of (almost) amorphous specimens in life sciences applications. With the recent advances in ...nanotechnology and the semiconductor industry, there is also an increasing need for high-resolution three-dimensional (3D) structural information in physical sciences. In this article, we evaluate the capabilities and limitations of transmission electron microscopy (TEM) and high-angle-annular-dark-field scanning transmission electron microscopy (HAADF-STEM) tomography for the 3D structural characterization of partially crystalline to highly crystalline materials. Our analysis of catalysts, a hydrogen storage material, and different semiconductor devices shows that features with a diameter as small as 1-2 nm can be resolved in three dimensions by electron tomography. For partially crystalline materials with small single crystalline domains, bright-field TEM tomography provides reliable 3D structural information. HAADF-STEM tomography is more versatile and can also be used for high-resolution 3D imaging of highly crystalline materials such as semiconductor devices.
Abstract
The Morel-Lavallee lesion is a closed, internal degloving injury that results when a strong, shearing force is applied parallel to the plane of injury, as is common in vehicular trauma. It ...is an underdiagnosed entity that is often missed during the initial trauma workup as symptoms can be subtle. There are few reports of lesions occurring below the knee. Most cases affect the proximal thigh and trochanter, as these tend to be dependent areas in high velocity trauma. To the best of our knowledge, this is the first literature report of bilateral lower extremity Morel-Lavallee lesions.
Arsenate is an abundant oxyanion that, because of its ability to mimic the phosphate group, is toxic to cells. Arsenate reductase (EC 1.97.1.5; encoded by the arsC gene in bacteria) participates to ...achieve arsenate resistance in both prokaryotes and yeast by reducing arsenate to arsenite; the arsenite is then exported by a specific transporter. The crystal structure of Bacillus subtilis arsenate reductase in the reduced form with a bound sulfate ion in its active site is solved at 1.6-Å resolution. Significant structural similarity is seen between arsenate reductase and bovine low molecular weight protein tyrosine phosphatase, despite very low sequence identity. The similarity is especially high between their active sites. It is further confirmed that this structural homology is relevant functionally by showing the phosphatase activity of the arsenate reductase in vitro. Thus, we can understand the arsenate reduction in the light of low molecular weight protein tyrosine phosphatase mechanism and also explain the catalytic roles of essential residues such as Cys-10, Cys-82, Cys-89, Arg-16, and Asp-105. A "triple cysteine redox relay" is proposed for the arsenate reduction mechanism.
Background Individual studies have suggested the utility of fractional exhaled nitric oxide (F eno ) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients ...with chronic cough. Objective We sought to obtain summary estimates of diagnostic test accuracy of F eno measurement in predicting CVA, EB, or both in adults with chronic cough. Methods Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of F eno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of F eno measurement. Results A total of 15 studies involving 2187 adults with chronic cough were identified. F eno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 95% CI, 0.81-0.88 and 0.72 95% CI, 0.61-0.81, respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 95% CI, 0.77-0.84), and specificity was inconsistent. Conclusions The present meta-analyses indicated the diagnostic potential of F eno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, F eno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of F eno measurement in clinical practice of patients with chronic cough.
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