Scalable multiplexing for parallel imaging with interleaved optical coherence tomography

We demonstrate highly parallel imaging with interleaved optical coherence tomography (iOCT) using an in-house-fabricated, air-spaced virtually-imaged phased array (VIPA). The air-spaced VIPA performs spectral encoding of the interferograms from multiple lateral points within a single sweep of the source and allows us to tune and balance several imaging parameters: number of multiplexed points, ranging depth, and sensitivity. In addition to a thorough discussion of the parameters and operating principles of the VIPA, we experimentally demonstrate the effect of different VIPA designs on the multiplexing potential of iOCT. Using a 200-kHz light source, we achieve an effective A-scan rate of 3.2-MHz by multiplexing 16 lateral points onto a single wavelength sweep. The improved sensitivity of this system is demonstrated for 3D imaging of biological samples such as a human finger and a fruit fly.OCIS codes: (110.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (110.6880) Three-dimensional image acquisition, (250.7260) Vertical cavity surface emitting lasers     

A pragmatic randomised controlled trial on routine iron prophylaxis during pregnancy in Maputo,Mozambique (PROFEG): rationale,design, and success

The effects of prophylactic iron during pregnancy on maternal and child health in developing settings with endemic malaria and high prevalence of HIV remain unclear. This paper describes the rationale, implementation and success of a pragmatic randomised controlled trial comparing routine iron supplementation vs. screening and treatment for anaemia during pregnancy. The setting was two health centres in Maputo, Mozambique. Pregnant women (≥12‐week gestation; ≥18 years old; and not with a high‐risk pregnancy, n = 4326) were recruited. The main outcomes are preterm delivery and low birthweight. The women were randomly assigned to one of two iron administration policies: a routine iron group (n = 2184) received 60 mg of ferrous sulphate plus 400 μg of folic acid daily while a selective iron group (n = 2142) had screening and treatment for anaemia and a daily intake of 1 mg of folic acid. The recruitment, follow‐up, and collection of follow‐up data were successful; both groups were similar to each other in all the trial stages. Collection of delivery data was challenging and data on about 40% of births is missing. These are currently being traced through different hospitals and health centres. The compliance of the study personnel and the women with regard to regular measurement of haemoglobin and intake of the iron and folic acid tablets was high and similar in both trial arms. Taking into account the various constraints encountered, the stages of the present trial prior to delivery were carried out well.     

Fecal Microbiota Composition Differs Between Children With β-Cell Autoimmunity and Those Without

The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects. To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing. Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with β-cell autoimmunity. In addition, a dearth of the two most dominant Bifidobacterium species, Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with β-cell autoimmunity. We did not find increased fecal calprotectin or IgA as marker of inflammation in children with β-cell autoimmunity. Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.Type 1 diabetes (T1D) is caused by the destruction of the pancreatic β-cells in genetically susceptible individuals. The disease is considered to be immune mediated, and the appearance of circulating autoantibodies against β-cells is seen years before the diagnosis along with a significant reduction in β-cell mass (1,2). Environmental factors associated with the activation of the gut immune system, such as early exposure to dietary antigens (cow’s milk and gluten), have been associated with the induction of this process (3–5). The role of the gut immune system in the pathogenesis of T1D has been supported by studies showing an immunological link between the pancreas and the gastrointestinal tract. It has been demonstrated that oral antigens are capable of activating antigen-specific T cells in pancreatic lymph nodes (6) and that the interaction between endothelium and T cells is controlled by shared homing receptors in inflamed islets and in the gut (7). The development of autoimmune diabetes in animal models is regulated by factors affecting the function of the gut immune system, such as dietary factors and microbial stimuli, which further affect the intestinal mucosal barrier and immune responsiveness (8). The effects of intestinal microbes may not be restricted to barrier mechanisms, but gut microbiota seems to play a key role in the regulation of the T-cell populations in the gut, including regulatory T cells, T helper 1, and T helper 17 cells (9).Several animal studies indicate that alterations in the intestinal microbiota are associated with the development of autoimmune diabetes. Nonobese diabetic mice lacking MyD88, an essential signal transducer in Toll-like receptor signaling, did not have development of diabetes (10), which emphasizes the role of intestinal microbiota as a regulator of autoimmune diabetes. There are differences in the gut microbiota between bio-breeding (BB) diabetes-prone (DP), and diabetes-resistant rats before the diagnosis of diabetes. Antibiotics also can prevent autoimmune diabetes in BB-DP rats (11). Furthermore, it has been reported that stool from BB diabetes-resistant rats contained more probiotic-like bacteria, whereas Bacteroides, Eubacterium, and Ruminococcus were more prevalent in BB-DP rats (12). Lactobacillus johnsonii prevented diabetes when administered to BB-DP rats (13). There are only a few studies of the intestinal microbiota in relation to T1D in humans, but the results of a follow-up study including four children with development of T1D suggested that the Bacteroidetes-to-Firmicutes ratio increased over time in those children with eventual progression to clinical T1D, whereas it decreased in children who remained nondiabetic (14).The aim of this study was to compare the composition of the gut microbiota between children with β-cell autoimmunity and autoantibody-negative children matched for age, sex, HLA risk genotype, and early feeding history using pyrosequencing as the method of choice.     

Human Cases of Methicillin-Resistant Staphylococcus aureus CC398, Finland

Nationwide surveillance identified 10 human isolates of methicillin-resistant Staphylococcus aureus clonal complex (CC) 398. Further typing in comparison with animal isolates identified 4 clusters: 1 related to a horse epidemic and 3 to persons who had no direct contact with animals or each other. These findings may indicate unrecognized community transmission.     

Prostate cancer survival in Trinidad: Is PSA a prognostic factor?

Background:

Prostate cancer is the most common malignancy among men in the western hemisphere, including Trinidad and Tobago. The aim of this study is to describe the epidemiological features of prostate cancer among patients admitted to a tertiary level teaching hospital during 2002 to 2005. We assessed the long-term survival of patients with prostate cancer and the epidemiology of the disease.

Methods:

We reviewed the admissions data for the period 2002–2005. Demographic, clinical and outcomes (survival or death) data were collected and analysed, using SPSS version 16. Statistical analysis included Kaplan-Mier survival analysis, Cox regression models and the log-rank test. A p value of <0.05 was considered statistically significant.

Results:

Of the 1250 cases reviewed, 242 participants were selected. Patients of African ancestry, older than 60 years and a Gleason score greater than 7 had an increased risk of mortality. Patients with prostate-specific antigen (PSA) ≥100 ng/L had a 3-fold increased risk of mortality. Survival rates declined between 2002 and 2005.

Conclusion:

This is the first study of its kind to demonstrate survival rates among patients with prostate cancer in Trinidad. The following epidemiological features were identified: average age of occurrence of 71 years, ethnic disparity with higher occurrence in African men than all other ethnic groups and a PSA of >100 ng/dL. These features were associated with a 3-fold higher risk of death. A Gleason score of 8 to 10 was also associated with lower survival rates.     

Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo.

Although total hip replacement (THR) is amongst the most successful and beneficial medical procedures to date, long-term outcomes continue to suffer from aseptic loosening secondary to peri-prosthetic osteolysis. Extensive research over the last two decades has elucidated a central mechanism for osteolysis in which wear debris generated from the implant stimulates inflammatory cells to promote osteoclastogenesis and bone resorption. The cytokine tumor necrosis factor alpha (TNFalpha) has been demonstrated to be central to this process and is considered to be a leading target for intervention. Unfortunately, even though FDA approved TNF antagonists are available (etanercept), currently there are no reliable outcome measures that can be used to evaluate the efficacy of a drug to prevent peri-prosthetic osteolysis. To the end of developing an effective outcome measure, we evaluated the progression of lesion size in 20 patients with established peri-acetabular osteolysis (mean=29.99 cm(3), range=2.9-92.7 cm(3)) of an uncemented primary THR over 1-year, using a novel volumetric computer tomography (3D-CT) technique. We also evaluated polyethylene wear, urine N-telopeptides and functional assessments (WOMAC, SF-36 and Harris Hip Score) for comparison. At the time of entry into the study baseline CT scans were obtained and the patients were randomized to etanercept (25 mg s.q., twice/week) and placebo in a double-blinded fashion. CT scans, urine and functional assessments were also obtained at 6 and 12 months. No serious adverse drug related events were reported, but one patient had to have revision surgery before completion of the study due to aseptic loosening. No remarkable differences between the groups were observed. However, the study was not powered to see significant drug effects. 3D-CT data from the 19 patients was used to determine the mean increase in lesion size over 48 weeks, which was 3.19 cm(3) (p<0.0013). Analysis of the urine N-telopeptides and functional assessment data failed to identify a significant correlation with wear or osteolysis. In conclusion, volumetric CT was able to measure progression of osteolysis over the course of a year, thus providing a technology that could be used in therapeutic trials. Using the data from this pilot we provide a model power calculation for such a trial.     

Magnetic resonance imaging of the hip with a pelvic phased-array surface coil: a technical note

Objective. The aim of this study was to assess the capability of high-resolution images obtained with a commercially available pelvic phased-array surface coil to demonstrate normal hip anatomy. Design. We retrospectively analyzed the oblique coronal magnetic resonance (MR) images of hips of 36 consecutive patients acquired on a 1.5-T clinical imager using a pelvic phased-array coil as a receiver, a 16–20 cm field of view, and 5 mm slice thickness. Patients. Thirty-six patients were studied, age 15–81 years. There were 20 males and 16 females. Results and conclusions. The articular cartilage, cortex, superior labrum, and iliofemoral ligament were well visualized on proton density weighted fat saturation (PDF) images. The femoral and obturator vessels, obturator nerve, and various muscles were easily seen on T1-weighted images. High-resolution imaging of the hip is achievable in a reasonable amount of time using newer phased-array surface coils and may play an increasing role in the future evaluation of hip disorders.     

Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects. METHODS: Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA. RESULTS: Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels. CONCLUSIONS: There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.