Triphasic Computed Tomography Enterography with Polyethylene Glycol to Detect Renal Cell Carcinoma Metastases to the Small Bowel

Enteroclysis was first used to diagnose small bowel obstruction in 1996. However, nasojejunal intubation required during enteroclysis causes discomfort to the patient. Triphasic computed tomography (CT) enterography, a noninvasive procedure that does not require intubation, was found to be an efficient method to diagnose small bowel lesions. We describe our experience of using triphasic CT enterography with polyethylene glycol (PEG) for diagnosing renal cell carcinoma (RCC) metastases to the small intestine. RCC can metastasize to many organs and can cause variable clinical presentations. We report the case of a 56-year-old man with RCC who had psoas muscle involvement and lung metastasis. The patient presented with melena and intermittent abdominal pain. Two conventional CT and small bowel series examinations had shown no obstructive lesion in the small intestine. However, triphasic CT enterography with PEG detected two enhanced masses suggestive of small bowel metastasis. The patient underwent laparotomy and segmental resection of the jejunum with primary anastomosis. Histologic examination was compatible with RCC. This is the first report where RCC metastasis to the small bowel was diagnosed using triphasic CT enterography. Our study emphasizes the importance of triphasic CT enterography in cases of obscure gastrointestinal bleeding, especially in patients suspected of having small bowel metastasis

αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis

The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer

Purpose: Previous studies have reported conflicting results in the associations of testosterone replacement therapy (TTh) and statins use with prostate cancer (PCa). However, the combination of these treatments with PCa stage and grade at diagnosis and prostate cancer-specific mortality (PCSM) and by race/ethnicity remains unclear. Methods: We identified non-Hispanic White (NHW, N = 58,576), non-Hispanic Black (NHB, n = 9,703) and Hispanic (n = 4,898) men diagnosed with PCa in SEER-Medicare data 2007–2011. Pre-diagnostic prescription of TTh and statins was ascertained for this analysis. Multivariable-adjusted logistic and Cox proportional hazards models were used to evaluate the association of TTh and statins use with PCa stage and grade and PCSM. Results: 22.5% used statins alone, 1.2% used TTh alone, and 0.8% used both. TTh and statins were independently, inversely associated with PCa advanced stage and high grade. TTh plus statins was associated with 44% lower odds of advanced stage PCa (OR 0.56, 95% CI 0.35–0.91). As expected, similar inverse associations were present in NHWs as the overall cohort is mostly comprised NHW men. In Hispanic men, statin use with or without TTh was inversely associated with aggressive PCa. Conclusions: Pre-diagnostic use of TTh or statins, independent or in combination, was inversely associated with aggressive PCa, including in NHW and Hispanics men, but was not with PCSM. The findings for use of statins with aggressive PCa are consistent with cohort studies. Future prospective studies are needed to explore the independent inverse association of TTh and the combined inverse association of TTh plus statins on fatal PCa

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

<p>Abstract</p> <p>Background</p> <p>To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages.</p> <p>Method</p> <p>Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF₂).</p> <p>Results</p> <p>There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment.</p> <p>Conclusions</p> <p>Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation.</p

Deqi sensations without cutaneous sensory input: results of an RCT

<p>Abstract</p> <p>Background</p> <p>Deqi is defined in relation to acupuncture needling as a sensory perception of varying character. In a recently published sham laser validation study, we found that subjects in the verum and the sham laser group experienced deqi sensations. Therefore, we aim to further analyze whether the perceptions reported in the two study arms were distinguishable and whether expectancy effects exhibited considerable impact on our results.</p> <p>Methods</p> <p>A detailed re-analysis focusing on deqi sensations was performed from data collected in a previously published placebo-controlled, double-blind, clinical cross-over trial for a sham laser evaluation. Thirty-four healthy volunteers (28 ± 10.7 years; 16 women, 18 men) received two laser acupuncture treatments at three acupuncture points LI4 (hégu), LU7 (liéque), and LR3 (táichong); once by verum laser and once using a sham device containing an inactive laser in randomized order. Outcome measures were frequency, intensity (evaluated by visual analogue scale; VAS), and quality of the subjects' sensations perceived during treatments (assessed with the "acupuncture sensation scale").</p> <p>Results</p> <p>Both, verum and the sham laser acupuncture result in similar deqi sensations with regard to frequency (p-value = 0.67), intensity (p-value = 0.71) and quality (p-values between 0.15 - 0.98). In both groups the most frequently used adjectives to describe these perceptions were "spreading", "radiating", "tingling", "tugging", "pulsing", "warm", "dull", and "electric". Sensations reported were consistent with the perception of deqi as previously defined in literature. Subjects' conviction regarding the effectiveness of laser acupuncture or the history of having received acupuncture treatments before did not correlate with the frequency or intensity of sensations reported.</p> <p>Conclusions</p> <p>Since deqi sensations, described as sensory perceptions, were elicited without any cutaneous sensory input, we assume that they are a product of non-specific effects from the overall treatment procedure. Expectancy-effects due to previous acupuncture experience and belief in laser acupuncture do not seem to play a major role in elicitation of deqi sensations. Our results give hints that deqi might be a central phenomenon of awareness and consciousness, and that its relevance should be taken into account, even in clinical trials. However, further research is required to understand mechanisms underlying deqi.</p

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Self-Organization of Muscle Cell Structure and Function

The organization of muscle is the product of functional adaptation over several length scales spanning from the sarcomere to the muscle bundle. One possible strategy for solving this multiscale coupling problem is to physically constrain the muscle cells in microenvironments that potentiate the organization of their intracellular space. We hypothesized that boundary conditions in the extracellular space potentiate the organization of cytoskeletal scaffolds for directed sarcomeregenesis. We developed a quantitative model of how the cytoskeleton of neonatal rat ventricular myocytes organizes with respect to geometric cues in the extracellular matrix. Numerical results and in vitro assays to control myocyte shape indicated that distinct cytoskeletal architectures arise from two temporally-ordered, organizational processes: the interaction between actin fibers, premyofibrils and focal adhesions, as well as cooperative alignment and parallel bundling of nascent myofibrils. Our results suggest that a hierarchy of mechanisms regulate the self-organization of the contractile cytoskeleton and that a positive feedback loop is responsible for initiating the break in symmetry, potentiated by extracellular boundary conditions, is required to polarize the contractile cytoskeleton

Biomechanical analysis of the lumbar spine on facet joint force and intradiscal pressure - a finite element study

<p>Abstract</p> <p>Background</p> <p>Finite element analysis results will show significant differences if the model used is performed under various material properties, geometries, loading modes or other conditions. This study adopted an FE model, taking into account the possible asymmetry inherently existing in the spine with respect to the sagittal plane, with a more geometrically realistic outline to analyze and compare the biomechanical behaviour of the lumbar spine with regard to the facet force and intradiscal pressure, which are associated with low back pain symptoms and other spinal disorders. Dealing carefully with the contact surfaces of the facet joints at various levels of the lumbar spine can potentially help us further ascertain physiological behaviour concerning the frictional effects of facet joints under separate loadings or the responses to the compressive loads in the discs.</p> <p>Methods</p> <p>A lumbar spine model was constructed from processes including smoothing the bony outline of each scan image, stacking the boundary lines into a smooth surface model, and subsequent further processing in order to conform with the purpose of effective finite element analysis performance. For simplicity, most spinal components were modelled as isotropic and linear materials with the exception of spinal ligaments (bilinear). The contact behaviour of the facet joints and changes of the intradiscal pressure with different postures were analyzed.</p> <p>Results</p> <p>The results revealed that asymmetric responses of the facet joint forces exist in various postures and that such effect is amplified with larger loadings. In axial rotation, the facet joint forces were relatively larger in the contralateral facet joints than in the ipsilateral ones at the same level. Although the effect of the preloads on facet joint forces was not apparent, intradiscal pressure did increase with preload, and its magnitude increased more markedly in flexion than in extension and axial rotation.</p> <p>Conclusions</p> <p>Disc pressures showed a significant increase with preload and changed more noticeably in flexion than in extension or in axial rotation. Compared with the applied preloads, the postures played a more important role, especially in axial rotation; the facet joint forces were increased in the contralateral facet joints as compared to the ipsilateral ones at the same level of the lumbar spine.</p

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort

BACKGROUND: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. METHODS: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. FINDINGS: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. INTERPRETATION: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. FUNDING: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore