Stochasticity of flow through microcirculation as a regulator of oxygen delivery

<p>Abstract</p> <p>Objective</p> <p>Observations of microcirculation reveal that the blood flow is subject to interruptions and resumptions. Accepting that blood randomly stops and resumes, one can show that the randomness could be a powerful means to match oxygen delivery with oxygen demand.</p> <p>Method</p> <p>The ability of the randomness to regulate oxygen delivery is based on two suppositions: (a) the probability for flow to stop does not depend on the time of uninterrupted flow, thus the number of interruptions of flow follows a Poisson distribution; (b) the probability to resume the flow does not depend on the time for flow being interrupted; meaning that time spent by erythrocytes at rest follows an exponential distribution. Thus the distribution of the time to pass an organ is a compound Poisson distribution. The Laplace transform of the given distribution gives the fraction of oxygen that passes the organ.</p> <p>Result</p> <p>Oxygen delivery to the tissues directly depends on characteristics of the irregularity of the flow through microcirculation.</p> <p>Conclusion</p> <p>By variation of vasomotion activity it is possible to change delivery of oxygen to a tissue by up to 8 times.</p

Determination of monolayer-protected gold nanoparticle ligand–shell morphology using NMR

It is accepted that the ligand shell morphology of nanoparticles coated with a monolayer of molecules can be partly responsible for important properties such as cell membrane penetration and wetting. When binary mixtures of molecules coat a nanoparticle, they can arrange randomly or separate into domains, for example, forming Janus, patchy or striped particles. To date, there is no straightforward method for the determination of such structures. Here we show that a combination of one-dimensional and two-dimensional NMR can be used to determine the ligand shell structure of a series of particles covered with aliphatic and aromatic ligands of varying composition. This approach is a powerful way to determine the ligand shell structure of patchy particles; it has the limitation of needing a whole series of compositions and ligands' combinations with NMR peaks well separated and whose shifts due to the surrounding environment can be large enough

Exploitation of TerraSAR-X Data for Land use/Land Cover Analysis Using Object-Oriented Classification Approach in the African Sahel Area, Sudan.

Recently, object-oriented classification techniques based on image segmentation approaches are being studied using high-resolution satellite images to extract various thematic information. In this study different types of land use/land cover (LULC) types were analysed by employing object-oriented classification approach to dual TerraSAR-X images (HH and HV polarisation) at African Sahel. For that purpose, multi-resolution segmentation (MRS) of the Definiens software was used for creating the image objects. Using the feature space optimisation (FSO) tool the attributes of the TerraSAR-X image were optimised in order to obtain the best separability among classes for the LULC mapping. The backscattering coefficients (BSC) for some classes were observed to be different for HH and HV polarisations. The best separation distance of the tested spectral, shape and textural features showed different variations among the discriminated LULC classes. An overall accuracy of 84 % with a kappa value 0.82 was resulted from the classification scheme, while accuracy differences among the classes were kept minimal. Finally, the results highlighted the importance of a combine use of TerraSAR-X data and object-oriented classification approaches as a useful source of information and technique for LULC analysis in the African Sahel drylands

The Ethnomedicine of the Haya people of Bugabo ward, Kagera Region, north western Tanzania

\ud The Kagera region, in north western Tanzania, is endowed with a strong culture of traditional medicine that is well supported by a rich diversity of medicinal plants. However, most of the plants in this region have not been documented nor evaluated for safety and efficacy. As an initiative in that direction, this study documented the knowledge on medicinal plant use by traditional healers of Bugabo Ward in Bukoba District. Key informants were selected with the help of local government officials and information on their knowledge and use of plants for therapeutic purposes was gathered using a semi-structured interview format. In this study 94 plant species representing 84 genera and 43 families were found to be commonly used in the treatment of a variety of human ailments. The family Asteraceae had the highest number of species being used as traditional medicines. The study revealed that Malaria is treated using the highest number of different medicinal species (30), followed by skin conditions (19), maternal illnesses and sexually transmitted diseases (14), respiratory diseases (11) and yellow fever, Herpes simplex and peptic ulcers (10). Majority of the species are used to treat less than five different diseases/conditions each and leaves were the most commonly used part, comprising 40% of all the reports on use of plant parts. Trees comprised the most dominant growth form among all plants used for medicinal purposes in the study area. Bugabo Ward has a rich repository of medicinal plants and this reinforces the need for an extensive and comprehensive documentation of medicinal plants in the area and a concomitant evaluation of their biological activity as a basis for developing future medicines.\u

Expression Profiling of CYP1B1 in Oral Squamous Cell Carcinoma: Counterintuitive Downregulation in Tumors

Oral Squamous Cell Carcinoma (OSCC) has a very flagitious treatment regime. A prodrug approach is thought to aid in targeting chemotherapy. CYP1B1, a member of cytochrome P450 family, has been implicated in chemical carcinogenesis. There exists a general accordance that this protein is overexpressed in a variety of cancers, making it an ideal candidate for a prodrug therapy. The activation of the prodrug facilitated by CYP1B1 would enable the targeting of chemotherapy to tumor tissues in which CYP1B1 is specifically overexpressed as a result reducing the non-specific side effects that the current chemotherapy elicits. This study was aimed at validating the use of CYP1B1 as a target for the prodrug therapy in OSCC. The expression profile of CYP1B1 was analysed in a panel of 51 OSCC tumors, their corresponding normal tissues, an epithelial dysplasia lesion and its matched normal tissue by qRT-PCR, Western blotting and Immunohistochemistry. CYP1B1 was found to be downregulated in 77.78% (28/36) tumor tissues in comparison to their corresponding normal tissues as well as in the epithelial dysplasia lesion compared to its matched normal tissue at the transcriptional level, and in 92.86% (26/28) of tumor tissues at the protein level. This report therefore clearly demonstrates the downregulation of CYP1B1 at the transcriptional and translational levels in tumor tissues in comparison to their corresponding normal tissues. These observations indicate that caution should be observed as this therapy may not be applicable universally to all cancers and also suggest the possibility of a prophylactic therapy for oral cancer

Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases

<p>Abstract</p> <p>Background</p> <p>Hepato-biliary tract lithiasis is common and present either as pain or as asymptomatic on abdominal ultrasonography for other causes. Although the DNA of <it>Helicobacter </it>species are identified in the gallbladder bile, tissue or stones analyzed from these cases, still a causal relationship could not be established due to different results from different geographical parts.</p> <p>Methods</p> <p>A detailed search of pubmed and pubmedcentral was carried out with key words <it>Helicobacter </it>and gallbladder, gallstones, hepaticolithiasis, cholelithiasis and choledocholithiasis, benign biliary diseases, liver diseases. The data was entered in a data base and meta analysis was carried out. The analysis was carried out using odds ratio and a fixed effect model, 95% confidence intervals for odds ratio was calculated. Chi square test for heterogeneity was employed. The overall effect was calculated using Z test.</p> <p>Results</p> <p>A total of 12 articles were identified. One study used IgG for diagnosis while others used the PCR for Ure A gene, 16 S RNA or Cag A genes. A couple of studies used culture or histopathology besides the PCR. The cumulative results show a higher association of <it>Helicobacter </it>with chronic liver diseases (30.48%), and stone diseases (42.96%)(OR 1.77 95% CI 1.2–2.58; Z = 2.94, p = 0.003), the effect of each could not be identified as it was difficult to isolate the effect of helicobacter due to mixing of cases in each study.</p> <p>Conclusion</p> <p>The results of present meta analysis shows that there is a slight higher risk of cholelithiasis and benign liver disease (OR 1.77), however due to inherent inability to isolate the effect of stone disease from that of other benign lesions it is not possible to say for sure that <it>Helicobacter </it>has a casual relationship with benign biliary disease or stone disease or both.</p

A mutant O-GlcNAcase enriches Drosophila developmental regulators

YesProtein O-GlcNAcylation is a reversible post-translational modification of serines/threonines on nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is essential for early embryogenesis. Drosophila melanogaster OGT/supersex combs (sxc) is a polycomb gene, null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities of the O-GlcNAcylated proteins involved, and the underlying mechanisms linking these phenotypes to embryonic development, are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is hampered by the low stoichiometry of this modification and limited enrichment tools. Using a catalytically inactive bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing Drosophila embryo, identifying, amongst others, known regulators of Hox genes as candidate conveyors of OGT function during embryonic development.Wellcome Trust Investigator Award (110061); MRC grant (MC_UU_12016/5); and Royal Society Research Grant

Non-alcoholic beverages and risk of bladder cancer in Uruguay

BACKGROUND: Bladder cancer is the fourth most frequent malignancy among Uruguayan men. A previous study from Uruguay suggested a high risk of bladder cancer associated with maté drinking. We conducted an additional case-control study in order to further explore the role of non-alcoholic beverages in bladder carcinogenesis. METHODS: In the time period 1996–2000, 255 incident cases with transitional cell carcinoma of the bladder and 501 patients treated in the same hospitals and in the same time period were frequency matched on age, sex, and residence. Both cases and controls were face-to-face interviewed on occupation, tobacco smoking, alcohol drinking and intake of maté, coffee, tea, and soft drinks. Statistical analysis was carried out by unconditional multiple logistic regression. RESULTS: Ever maté drinking was positively associated with bladder cancer (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2–3.9) and the risk increased for increasing duration and amount of maté drinking. Both coffee and tea were strongly associated with bladder cancer risk (OR for coffee drinking 1.6, 95% CI 1.2–2.3; OR for tea drinking 2.3, 95% CI 1.5–3.4). These results were confirmed in a separate analysis of never-smokers. CONCLUSION: Our results suggest that drinking of maté, coffee and tea may be risk factors for bladder carcinoma in Uruguay

Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study

BackgroundActivity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort.MethodsPatients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy.ResultsSeventeen patients completed the program with average participation duration of 21.3&nbsp;weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1&nbsp;N to 21.2&nbsp;N over 20&nbsp;weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline.ConclusionsA weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI

Genetic Determinants of Variability in Glycated Hemoglobin (HbA1c) in Humans: Review of Recent Progress and Prospects for Use in Diabetes Care

Glycated hemoglobin A1c (HbA1c) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA1c represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA1c levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genome-wide analyses. Here I review current research aimed at discovering genetic determinants of HbA1c levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis