Familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program

Self-organization of developing embryo using scale-invariant approach

<p>Abstract</p> <p>Background</p> <p>Self-organization is a fundamental feature of living organisms at all hierarchical levels from molecule to organ. It has also been documented in developing embryos.</p> <p>Methods</p> <p>In this study, a scale-invariant power law (SIPL) method has been used to study self-organization in developing embryos. The SIPL coefficient was calculated using a centro-axial skew symmetrical matrix (CSSM) generated by entering the components of the Cartesian coordinates; for each component, one CSSM was generated. A basic square matrix (BSM) was constructed and the determinant was calculated in order to estimate the SIPL coefficient. This was applied to developing <it>C. elegans </it>during early stages of embryogenesis. The power law property of the method was evaluated using the straight line and Koch curve and the results were consistent with fractal dimensions (fd). Diffusion-limited aggregation (DLA) was used to validate the SIPL method.</p> <p>Results and conclusion</p> <p>The fractal dimensions of both the straight line and Koch curve showed consistency with the SIPL coefficients, which indicated the power law behavior of the SIPL method. The results showed that the ABp sublineage had a higher SIPL coefficient than EMS, indicating that ABp is more organized than EMS. The fd determined using DLA was higher in ABp than in EMS and its value was consistent with type 1 cluster formation, while that in EMS was consistent with type 2.</p

Quantifying Heterogeneity in Host-Vector Contact: Tsetse (Glossina swynnertoni and G. pallidipes) Host Choice in Serengeti National Park, Tanzania

Identifying hosts of blood-feeding insect vectors is crucial in understanding their role in disease transmission. Rhodesian human African trypanosomiasis (r-HAT or ‘sleeping sickness’) caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies, is commonly associated with wilderness areas of east and southern Africa. Such areas hold a diverse range of species which form communities of hosts for disease maintenance. The relative importance of different wildlife hosts remains unclear. This study quantified tsetse feeding preferences in a wilderness area of great host species richness, Serengeti National Park, Tanzania, assessing tsetse feeding and host density contemporaneously. Glossina swynnertoni and G.pallidipes were collected from six study sites. Bloodmeal sources were identified through matching Cytochrome B sequences amplified from bloodmeals from fed flies to published sequences. Densities of large mammal species in each site were quantified, and feeding indices calculated to assess the relative selection or avoidance of each host species by tsetse. The host species most commonly identified in G. swynnertoni bloodmeals, warthog (94/220), buffalo (48/220) and giraffe (46/220), were found at relatively low densities (3-11/km2) and fed on up to 15 times more frequently than expected by their relative density. Wildebeest, zebra, impala and Thomson’s gazelle, found at the highest densities, were never identified in bloodmeals. Commonly identified hosts for G. pallidipes were buffalo (26/46), giraffe (9/46) and elephant (5/46). This study is the first to quantify tsetse host range by molecular analysis of tsetse diet with simultaneous assessment of host density in a wilderness area. Although G.swynnertoni and G.pallidipes can feed on a range of species, they are highly selective. Many host species are rarely fed on, despite being present in areas where tsetse are abundant. These feeding patterns, along with the ability of key host species to maintain and transmit T.b.rhodesiense, drive the epidemiology of r-HAT in wilderness areas

Dendritic branching of pyramidal cells in the visual cortex of the nocturnal owl monkey: A fractal analysis

The branching structure of neurones is thought to influence patterns of connectivity and how inputs are integrated within the arbor. Recent studies have revealed a remarkable degree of variation in the branching structure of pyramidal cells in the cerebral cortex of diurnal primates, suggesting regional specialization in neuronal function. Such specialization in pyramidal cell structure may be important for various aspects of visual function, such as object recognition and color processing. To better understand the functional role of regional variation in the pyramidal cell phenotype in visual processing, we determined the complexity of the dendritic branching pattern of pyramidal cells in visual cortex of the nocturnal New World owl monkey. We used the fractal dilation method to quantify the branching structure of pyramidal cells in the primary visual area (V1), the second visual area (V2) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively), which are often associated with color processing. We found that, as in diurnal monkeys, there was a trend for cells of increasing fractal dimension with progression through these cortical areas. The increasing complexity paralleled a trend for increasing symmetry. That we found a similar trend in both diurnal and nocturnal monkeys suggests that it was a feature of a common anthropoid ancestor

Identifying diabetic patients with cardiac autonomic neuropathy by heart rate complexity analysis

BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes has been called a "silent killer", because so few patients realize that they suffer from it, and yet its effect can be lethal. Early sub clinical detection of CAN and intervention are of prime importance for risk stratification in preventing sudden death due to silent myocardial infarction. This study presents the usefulness of heart rate variability (HRV) and complexity analyses from short term ECG recordings as a screening tool for CAN. METHODS: A total of 17 sets of ECG recordings during supine rest were acquired from diabetic subjects with CAN (CAN+) and without CAN (CAN-) and analyzed. Poincaré plot indexes as well as traditional time and frequency, and the sample entropy (SampEn) measure were used for analyzing variability (short and long term) and complexity of HRV respectively. RESULTS: Reduced (p > 0.05)_Poincaré plot patterns and lower (p < 0.05) SampEn values were found in CAN+ group, which could be a practical diagnostic and prognostic marker. Classification Trees methodology generated a simple decision tree for CAN+ prediction including SampEn and Poincaré plot indexes with a sensitivity reaching 100% and a specificity of 75% (percentage of agreement 88.24%). CONCLUSION: Our results demonstrate the potential utility of SampEn (a complexity based estimator) of HRV in identifying asymptomatic CAN

Fractal analysis: Pitfalls and revelations in neuroscience

Fractal analysis has become a popular method in all branches of scientific investigation including ecology, physics and medicine. The method is often used to determine effects such as impact of cattle grazing, the distribution of stars within a galaxy or whether tissue is pathological. However several aspects of fractal analysis are not often considered when interpreting results communicated in the literature. These include the concept that no presentation of any pattern on a computer, even for an ideal fractal, is truly fractal. Pre-processing that is also required, such as scanning of images and resizing play a role in the variation of the final fractal dimension. In addition D is also a function of the fractal analysis method used and how the final fractal dimension is determined. To obtain a better overview of the effects of the steps involved in fractal analysis and the utility of this method, this chapter describes, using biological material from neuroscience, a non fractal based method, Sholl analysis and continues by discussing various processing options and the results obtained using fractal analysis. The effect of different fractal analysis methods, different computer applications of the same method, scale and resolution as well as regression analysis, which is for most methods the final step in determining D are discussed. This provides a platform for a better understanding of fractal analysis in research fields other than physics and mathematics and a more meaningful interpretation of results

Risk stratification of cardiac autonomic neuropathy based on multi-lag Tone-Entropy

Cardiac autonomic neuropathy (CAN) is an irreversible condition affecting the autonomic nervous system, which leads to abnormal functioning of the visceral organs and affects critical body functions such as blood pressure, heart rate and kidney filtration. This study presents multi-lag Tone-Entropy (T-E) analysis of heart rate variability (HRV) at multiple lags as a screening tool for CAN. A total of 41 ECG recordings were acquired from diabetic subjects with definite CAN (CAN+) and without CAN (CAN-) and analyzed. Tone and entropy values of each patient were calculated for different beat sequence lengths (len: 50-900) and lags (m: 1-8). The CAN- group was found to have a lower mean tone value compared to that of CAN+ group for all m and len, whereas the mean entropy value was higher in CAN- than that in CAN+ group. Leave-one-out (LOO) cross-validation tests using a quadratic discriminant (QD) classifier were applied to investigate the performance of multi-lag T-E features. We obtained 100 % accuracy for tone and entropy with len = 250 and m = {2, 3} settings, which is better than the performance of T-E technique based on lag m = 1. The results demonstrate the usefulness of multi-lag T-E analysis over single lag analysis in CAN diagnosis for risk stratification and highlight the change in autonomic nervous system modulation of the heart rate associated with cardiac autonomic neuropathy

Association of cardiovascular risk using non-linear heart rate variability measures with the framingham risk score in a rural population

Cardiovascular risk can be calculated using the Framingham cardiovascular disease (CVD) risk score and provides a risk stratification from mild to very high CVD risk percentage over 10 years. This equation represents a complex interaction between age, gender, cholesterol status, blood pressure, diabetes status, and smoking. Heart rate variability (HRV) is a measure of how the autonomic nervous system (ANS) modulates the heart rate. HRV measures are sensitive to age, gender, disease status such as diabetes and hypertension and processes leading to atherosclerosis. We investigated whether HRV measures are a suitable, simple, noninvasive alternative to differentiate between the four main Framingham associated CVD risk categories. In this study we applied the tone-entropy (T-E) algorithm and complex correlation measure (CCM) for analysis of HRV obtained from 20 min. ECG recordings and correlated the HRV score with the stratification results using the Framingham risk equation. Both entropy and CCM had significant analysis of variance (ANOVA) results [F (172, 3) = 9.51; <0.0001]. Bonferroni post hoc analysis indicated a significant difference between mild, high and very high cardiac risk groups applying tone-entropy (p < 0.01). CCM detected a difference in temporal dynamics of the RR intervals between the mild and very high CVD risk groups (p < 0.01). Our results indicate a good agreement between the T-E and CCM algorithm and the Framingham CVD risk score, suggesting that this algorithm may be of use for initial screening of cardiovascular risk as it is noninvasive, economical and easy to use in clinical practice