Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Dimensional analysis of MINMOD leads to definition of the disposition index of glucose regulation and improved simulation algorithm

BACKGROUND: Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) together with its mathematical model, the minimal model (MINMOD), have become important clinical tools to evaluate the metabolic control of glucose in humans. Dimensional analysis of the model is up to now not available. METHODS: A formal dimensional analysis of MINMOD was carried out and the degree of freedom of MINMOD was examined. Through re-expressing all state variable and parameters in terms of their reference scales, MINMOD was transformed into a dimensionless format. Previously defined physiological indices including insulin sensitivity, glucose effectiveness, and first and second phase insulin responses were re-examined in this new formulation. Further, the parameter estimation from FSIVGTT was implemented using both the dimensional and the dimensionless formulations of MINMOD, and the performances were compared utilizing Monte Carlo simulation as well as real human FSIVGTT data. RESULTS: The degree of freedom (DOF) of MINMOD was found to be 7. The model was maximally simplified in the dimensionless formulation that normalizes the variation in glucose and insulin during FSIVGTT. In the new formulation, the disposition index (Dl), a composite parameter known to be important in diabetes pathology, was naturally defined as one of the dimensionless parameters in the system. The numerical simulation using the dimensionless formulation led to a 1.5–5 fold gain in speed, and significantly improved accuracy and robustness in parameter estimation compared to the dimensional implementation. CONCLUSION: Dimensional analysis of MINMOD led to simplification of the model, direct identification of the important composite factors in the dynamics of glucose metabolic control, and better simulations algorithms

Allergic rhinitis in northern vietnam: increased risk of urban living according to a large population survey

<p>Abstract</p> <p>Background</p> <p>Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.</p> <p>Results</p> <p>Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.</p> <p>Conclusions</p> <p>Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.</p

Temporal bone verrucous carcinoma: outcomes and treatment controversy

Verrucous carcinoma is a rare tumor that presents in the head and neck with the most common sites being the oral cavity and larynx. Fourteen cases of verrucous carcinoma of the temporal bone have been described in literature; this study aims to examine treatment outcomes and discuss the controversy surrounding postoperative radiation. The study design included a literature review along with individual case report in the setting of a tertiary care medical center. Outcome analysis of all cases of verrucous carcinoma of the temporal bone, which are documented in the English literature, and presentation of a single patient report including gross, histologic and radiologic analyses were performed. The longest recorded survival for verrucous carcinoma of the temporal bone occurs in patients treated with surgery alone. Poorer outcomes for patients treated with adjuvant (chemo)radiation may be due to more advanced stage of disease at the time of treatment. Early reports of radiation leading to tumor dedifferentiation or early recurrence are not supported by more recent studies. Whether adjuvant radiation therapy is indicated in verrucous carcinoma of the temporal bone remains controversial

The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer

MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor

Molecular and electronic structure of terminal and alkali metal-capped uranium(V) nitride complexes

Determining the electronic structure of actinide complexes is intrinsically challenging because inter-electronic repulsion, crystal field, and spin–orbit coupling effects can be of similar magnitude. Moreover, such efforts have been hampered by the lack of structurally analogous families of complexes to study. Here we report an improved method to U≡N triple bonds, and assemble a family of uranium(V) nitrides. Along with an isoelectronic oxo, we quantify the electronic structure of this 5f1 family by magnetometry, optical and electron paramagnetic resonance (EPR) spectroscopies and modelling. Thus, we define the relative importance of the spin–orbit and crystal field interactions, and explain the experimentally observed different ground states. We find optical absorption linewidths give a potential tool to identify spin–orbit coupled states, and show measurement of UV···UV super-exchange coupling in dimers by EPR. We show that observed slow magnetic relaxation occurs via two-phonon processes, with no obvious correlation to the crystal field

Exercise and the Prevention of Oesophageal Cancer (EPOC) study protocol: a randomized controlled trial of exercise versus stretching in males with Barrett's oesophagus

<p>Abstract</p> <p>Background</p> <p>Chronic gastro-oesophageal reflux disease and excessive body fat are considered principal causes of Barrett's oesophagus (a metaplastic change in the cells lining the oesophagus) and its neoplastic progression, oesophageal adenocarcinoma. Metabolic disturbances including altered levels of obesity-related cytokines, chronic inflammation and insulin resistance have also been associated with oesophageal cancer development, especially in males. Physical activity may have the potential to abrogate metabolic disturbances in males with Barrett's oesophagus and elicit beneficial reductions in body fat and gastro-oesophageal reflux symptoms. Thus, exercise may be an effective intervention in reducing oesophageal adenocarcinoma risk. However, to date this hypothesis remains untested.</p> <p>The 'Exercise and the Prevention of Oesophageal Cancer Study' will determine whether 24 weeks of exercise training will lead to alterations in risk factors or biomarkers for oesophageal adenocarcinoma in males with Barrett's oesophagus. Our primary outcomes are serum concentrations of leptin, adiponectin, tumour necrosis factor-alpha, C-reactive protein and interleukin-6 as well as insulin resistance. Body composition, gastro-oesophageal reflux disease symptoms, cardiovascular fitness and muscular strength will also be assessed as secondary outcomes.</p> <p>Methods/Design</p> <p>A randomized controlled trial of 80 overweight or obese, inactive males with Barrett's oesophagus will be conducted in Brisbane, Australia. Participants will be randomized to an intervention arm (60 minutes of moderate-intensity aerobic and resistance training, five days per week) or a control arm (45 minutes of stretching, five days per week) for 24 weeks. Primary and secondary endpoints will be measured at baseline (week 0), midpoint (week 12) and at the end of the intervention (week 24).</p> <p>Discussion</p> <p>Due to the increasing incidence and very high mortality associated with oesophageal adenocarcinoma, interventions effective in preventing the progression of Barrett's oesophagus are urgently needed. We propose that exercise may be successful in reducing oesophageal adenocarcinoma risk. This primary prevention trial will also provide information on whether the protective association between physical activity and cancer is causal.</p> <p>Trial Registration</p> <p>ACTRN12609000401257</p

fMRI scanner noise interaction with affective neural processes

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes