Search

The reuse of well-established medicines using computational modeling has gained a lot of attention due to its tremendous benefits. Based on this perspective, a new method for linking known medicines to diseases is proposed. The creation of a new treatment or medicine can be financially and temporally costly and the reuse of medicines is one possibility to accelerate this process efficiently. The main purpose of the reuse of medicines is to reduce some stages of the development of new medicines, motivating the proposition of several methods nowadays. In this work, a new method is developed aiming to connect known medicines to diseases based on available networks of protein interactions and available lists of medicines that affect protein action. The concepts of multiplex networks are used to connect subgraphs of vertices that represent medicines and proteins. The core of the procedure is determined by a weighting strategy constructed to define precisely the more relevant connections. The method was compared to other network link methods in the literature and a case study was presented and evaluated by the proposed method.

The present case is the first description of a co-infection with canine distemper virus (CDV) and canine adenovirus type 1 (CAdV-1) in a free-living hoary fox pup from Brazil. The animal was found and rescued with poor body condition, dehydration, incoordination, ataxia, excessive vocalization, and "blue eyes" phenomenon. Despite the efforts, euthanasia was elected due to worsening clinical signs and poor prognosis. Pathologic examination revealed a mild, acute, random, necrotizing hepatitis, acute bronchopneumonia, hydrocephalus, corneal edema with epithelium degeneration, and acidophilic intracytoplasmatic inclusion bodies in different epithelial cells types with rare syncytial. Through immunohistochemistry, CDV antigen was observed in the tongue, trachea, lungs, liver, spleen, stomach, intestine and urinary bladder. Adenovirus antigen was identified in the nucleus of scattered hepatocytes. Polymerase chain reaction and sequencing demonstrated high similarity with CAdV-1 and wild-type strain of CDV close related to Brazilian viral lineages isolated from domestic dogs. Disease surveillance in wildlife animals is essential to assess possible conservation threats and consider the implementation of mitigation or control measures., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Dengue is the most prevalent arboviral disease in humans in tropical and subtropical regions, especially in urban areas, and can cause major epidemics. Although a self-limiting illness, it may sometimes have serious hemorrhagic manifestations, and the outcome of dengue hemorrhagic fever has similar clinical manifestations as in other infections, which could result in death. Therefore, autopsy procedures are required under certain circumstances such as in hemorrhagic fevers, sometimes to confirm or to clarify the diagnosis that may have epidemiological consequences. Normally, the Immunohistochemistry Laboratory of the Pathology Center of Adolfo Lutz Institute receives autopsy samples from different hospitals in Sao Paulo State to confirm a previous diagnosis, especially hemorrhagic fever of infectious etiology. For this diagnosis, we have been using a mouse polyclonal antibody to dengue virus that often does not provide a clear conclusion, because of background staining or no relevant immunostaining, which hampers the histopathological analysis. Accordingly, in the present study, anti-DENV-NS1 monoclonal antibody (4H2) was tested to determine its accuracy in immunohistochemical analysis. Twenty-four autopsy cases of hemorrhagic febrile syndrome showing histopathological alterations compatible with dengue disease were studied: twenty cases were confirmed by RT-PCR for DENV-2 and in four by RT-PCR for yellow fever virus. Samples from autopsied cases of deaths caused by other infectious diseases (two meningitis C and two severe acute respiratory syndrome caused by influenza A H1N1) were included as negative control cases. Positive immunostaining for DENV-NS1 was detected in 16/20 (80%) liver samples and 11/15 (73%) spleen samples from autopsied hemorrhagic dengue patients, whereas the polyclonal antibody detected DENV antigens in 12/20 (60%) liver and in 6/15 (40%) spleen samples from the same cases. Positive results were not obtained with liver biopsy samples from yellow fever or Neisseria meningitides and Flu-A cases. 4H2 mAb recognizes the native protein of the four DENV serotypes in infected cells and did not cross-react with native ZIKV- or CHKV-infected cells by immunohistochemical assay, so it is a useful tool for differential histopathological conclusion of acute febrile hemorrhagic deaths., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Introduction: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation., Methods: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant)., Results: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection., Conclusion: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

Background: Health-related quality of life (HRQoL) is determined by multiple factors that include components such as spirituality and religiousness (S/R). Even though various systematic reviews have investigated the association between S/R and improved health outcomes in the most different groups, healthy young individuals are seldom addressed., Objective: To assess the association between S/R and HRQoL among young, healthy individuals., Methods: Systematic review of papers published in the last ten years and indexed in four academic research databases (PubMed, Web of Science, Cochrane Library, and Scopus) and two gray literature databases. Inclusion criteria were studies assessing S/R and HRQoL using validated instruments and assessing healthy adults (i.e., non-clinical patients, not belonging to any specific group of chronic diseases), aged between 18 and 64 years old., Results: Ten out of 1,952 studies met the inclusion criteria: nine cross-sectional and one longitudinal cohort study, in which 89% of the participants were college students. Nine studies report a positive association between S/R and HRQoL, while one study did not report any significant association. The main HRQoL domains associated with S/R were the psychological, social relationships, and environment domains, while the S/R most influent facets/components were optimism, inner strength, peace, high control, hope, and happiness., Conclusions: Higher S/R levels among healthy adult individuals were associated with higher HRQoL levels, suggesting the S/R can be an important strategy to deal with adverse environmental situations even among those without chronic diseases, enhancing the wellbeing of individuals. Registration of systematic review: PROSPERO-CRD42018104047., (© 2021. The Author(s).)

Although pain is a frequent complaint of patients with chronic kidney disease who undergo hemodialysis, few studies have assessed the functional interference of pain in activities of daily living (ADLs). Hence, the aim of this study was to evaluate the prevalence, location, intensity, and functional interference of pain in ADLs of chronic kidney disease patients undergoing hemodialysis and to estimate the association of specific pain sites with severe functional interference by pain in ADLs. This cross-sectional study included patients with chronic kidney disease undergoing hemodialysis. The prevalence, intensity, and functional interference of pain in ADLs were assessed using the brief pain inventory. Poisson regression was used to calculate the prevalence ratio. A total of 65 patients participated in the study. The overall prevalence of pain was 89.23%; the prevalence of headache was 18.46% and that of pain in the trunk was 55.38%, upper limbs was 35.38%, and lower limbs was 60.00%. The prevalence of moderate and severe pain at the time of hemodialysis was 13.85% and 21.54%, respectively. A high prevalence of severe functional interference of pain in general activity (61.54%), mobility (56.92%), and disposition (55.38%) was observed. Pain is a frequent complaint in patients undergoing hemodialysis, mainly musculoskeletal and intradialytic, and it interferes with ADLs and incapacitates the patient. Pain was highly prevalent in the upper and lower limbs and the trunk. Furthermore, a higher prevalence of severe pain at the time of hemodialysis and functional interference of pain, mainly in general activity, mobility, and disposition, were observed.

Aims: To assess the presence of pain, its location, intensity, and effects on the daily activities of patients with chronic kidney disease (CKD) undergoing hemodialysis (HD)., Participants/subjects: Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD)., Design: A systematic review., Methods: We carried out search for articles published until December 2020, including publications in Portuguese, English, and Spanish during the past 15 years (2005-2020), using the Embase, SciELO, PubMed, and Web of Science databases. The following information was collected: type of pain, pain treatment, pain assessment instrument, prevalence of pain, location, and influence of pain on quality of life., Results: Twenty-five studies were selected for a systematic review. These studies involved a total of 98,162 adult and elderly patients with CKD who were undergoing HD. There was a high prevalence of pain in patients with CKD on HD. The most frequent sites of pain were the head, back, bones, chest, and the upper and lower limbs. The presence of acute, chronic, neuropathic pain, and myalgia was also reported in the studies. In addition, there was a higher frequency of moderate and severe pain, which influenced daily activities, the ability to walk, mood, relationships with other people, sleep, and work in patients on dialysis., Conclusions: The analyzed studies suggest that acute and chronic pain is a prevalent complaint in adults and elderly patients undergoing HD. There was a higher frequency of moderate and severe pain in different parts of the body, and pain interfered with everyday activities., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study presents an overview of the accuracy of cone beam computed tomography (CBCT) compared with micro-computed tomography (μCT) in the assessment of root canal morphology of extracted human permanent teeth. A database search in PubMed, PubMed Central, Embase, Scopus, Opengrey, Scielo and Virtual Health Library was conducted which compared root canal morphology of extracted human permanent teeth on the accuracy of CBCT with μCT. In accordance with PRISMA statement guidelines, data were extracted on study characteristics, target mediators, sampling and assay techniques and the parameters associated with obtaining the image and ability to identify the root canal morphology. Amongst 2734 records, ten fulfilled the inclusion criteria. Four studies compared the accuracy of CBCT and μCT in the assessment of root canal morphology using Vertucci's classification, with at least one CBCT group or subgroup of each study presented high agreement compared to the μCT. Six studies assessed more detailed root canal morphology, including two articles that found a lack of agreement between these imaging systems. Risk of bias was deemed low in three studies, moderate in four and high in three. CBCT can be as accurate as μCT in the assessment of several morphological features of extracted human permanent teeth; however there are some exceptions related to the more detailed morphological aspects. Voxel size likely influences the ability to detect these features, though the different aspects of exposure setting used in studies components may be confounding factors. CBCT may be considered for the assessment of root canal morphology ex-vivo.

Aims: There is a pancreatic islet adaptation in obese subjects, resulting in insulin resistance and diabetes type 2. We studied the effect of intermittent fasting (IntF) on the islet structure of diet-induced obese (DIO) mice., Methods: Three-month-old male mice fed a control diet (C, 10% Kcal fat) or a high-fat diet (HF, 50% Kcal fat) for two months (n = 20 each group). Then, half of each group did IntF (alternating 24 h fed/24 h fast), continuing in their diets four more weeks: C, C-IntF, HF, HF-IntF. Islets were prepared to microscopy or isolated for molecular analysis., Results: HF group (vs. C group) showed hyperglycemia, hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, glucose intolerance, insulin resistance, and islet hypertrophy with a consequent higher both the alpha-cell and beta-cell masses. In the HF group (vs. C), there was low PDX1 (pancreatic and duodenal homeobox 1), and IntF did not alter PDX1. There was a low p-AKT/AKT ratio (protein kinase B), and IntF enhanced it. Also, tumor suppressor p53 was increased, and IntF decreased it. IL (interleukin) -6 was higher in the HF group (vs. C), and HF-IntF (vs. C-IntF). Any significant change in NFkB was seen among groups., Conclusions: IntF improves pancreatic islet structure in DIO mice, even with continued HF diet intake, primarily considering on the alpha- and beta-cell masses regulation, then improving insulin signaling and decreasing cell apoptosis. Future research should explore whether the shortening of the IntF extend could maintain the benefits observed in the long term., Competing Interests: Declaration of competing interest There are no potential conflicts of interest in this work., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Laser irradiation modifies the topography and composition of dentin surface aiming to increase the retention of bonded posts. Objective: To assess the effect of dentin irradiation with Er,Cr:YSGG or diode lasers on the bond strength of fiber posts using self-adhesive resin cement. Materials and methods: Sixty bovine root canals were root-canal treated, post spaces were prepared, and subsequently fiber posts were cemented. The samples were distributed according to the surface treatment: distilled water (control), Er,Cr:YSGG (1.5 W, 20 sec), or diode (1.5 W, 20 sec) lasers. Bond strengths were assessed by pull-out ( n  = 10) or push-out testing ( n  = 10). Pearson's correlation was calculated. Failure mode after testing and the depth of tags in the dentinal tubules were analyzed by confocal laser microscopy. Data were submitted to analysis of variance and Tukey's test. A p  < 0.05 was considered significant. Results: In the push-out test, Er,Cr:YSGG laser had significantly different higher values (5.43 ± 0.10 MPa) compared to the control (4.79 ± 0.05 MPa). Diode laser values were not significantly different from the other groups (5.12 ± 0.27 MPa). In the pull-out test, there were no significant differences between Er,Cr:YSGG (6.86 ± 2.16 MPa) and diode (8.43 ± 1.77 MPa) lasers, and both had significant differences compared to the control (4.18 ± 1.29 MPa). No correlation was found. Adhesive failures were predominant in all groups, and no significant differences in tag penetration among the groups were found. Conclusions: The Er,Cr:YSGG laser increases the bond strength of resin cement and fiber post to dentin in both tests, compared to control group without laser treatment. Diode laser only enhanced bonding for pull-out test.

Background: Menopause and deficiency in vitamin D (VD) are two health problems usually associated with aging women. Objective: We aimed to study inflammation in visceral adipose tissue when bilateral ovariectomy is combined with dietary restriction in VD. Methods: We studied 60 female C57BL/6 mice 3 months of age. Half of the animals had bilateral ovariectomy (Ovx group, n  = 30) and half a sham procedure (Control [C] group, n  = 30), and half of each Ovx or C group were fed a standard diet containing VD or a diet restricted in VD (D-) for an additional 12 weeks. Therefore, four groups were formed ( n  = 15 each group): C, C(D-), Ovx, and Ovx(D-). After sacrifice, the periovarian adipose tissue (PAT) was investigated. Results: In PAT, we observed different levels of hypertrophied adipocytes, enhanced proinflammatory cytokines, activation of inflammatory markers, and components of the extracellular signal-regulated kinase. The most affected PAT was seen in the Ovx(D-) group, followed by the Ovx group, the C(D-) group, and the C group (the least altered). Conclusion: The results demonstrate that ovariectomy and dietary restriction of VD are inducers of adverse effects on mouse visceral adipose tissue. When combined, these insults might enhance PAT inflammation.

Aims: A prevalence of vitamin D deficiency has been reported in association with the postmenopause. Thus, we aimed to experimentally study the effect of the vitamin D deficiency and ovariectomy, alone or combined, in the liver damage., Main Methods: Three-months-old female mice C57BL/6 with bilateral ovariectomy (Ovx group, n = 30) or a sham procedure (n = 30) were separated feeding control diet (C, n = 15) or a diet restricted in vitamin D (D-, n = 15) during additional 12 weeks., Key Findings: Body mass (BM) and blood pressure (BP) were higher in Ovx than in C animals, but highest in Ovx (D-) that also showed glucose intolerance/ insulin resistance. Plasmatic lipids, alanine aspartase transferase, and hepatic steatosis were increased because of the combination of Ovx and D-. However, D- had little implication in the changes of the BM and BP, but affected hepatic steatosis. Gene and protein expressions demonstrated an impaired glucose uptake in the liver because of Ovx and D-, and an increase in lipogenesis and decrease in beta-oxidation in the liver associated more to the Ovx, but also evident in D-. Also, interleukin 6 and tumor necrosis factor alpha showed an enhancement due to dietary restriction of vitamin D., Significance: The findings demonstrated that ovariectomy and dietary restriction of vitamin D are inducers of harmful effects on the liver of mice, enhancing lipogenesis and inflammation and compromising beta-oxidation. The treatment of vitamin D deficiency is simple and not costly and can reduce the impact of menopause on metabolism and especially the liver., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The study was conducted to understand better the mechanisms involved in liver changes when there is a combination of diet-induced obesity (DIO) and vitamin D deficiency (VDD). After 8 wk of feeding a control diet (C group) or a high-fat diet (HF), both with vitamin D, and counterpart groups without vitamin D (VitD- groups), we found in plasma: higher alanine aminotransferase, and aspartate aminotransferase in the VitD- groups, and more elevated total cholesterol in the HF group. Compared to their counterparts, HF and HF/VitD- showed hyperinsulinemia and higher hepatic triglycerides and steatosis. The protein expressions of markers linked with the vitamin D action were altered by VDD (vitamin D receptor VDR, 25-hydroxyvitamin D-24-hydroxylase CYP24A1, CYP27B1, and CYP2R1). The hepatic lipogenesis and fatty acid synthesis were enhanced by VDD (peroxisome proliferator-activated receptor PPARγ, sterol regulatory element-binding proteins SREBP1c, carbohydrate-responsive element-binding protein ChREBP, and fatty acid synthase FAS), but markers of beta-oxidation were reduced (PPARα and phosphoenolpyruvate carboxykinase PEPCK). In conclusion, the study provides convincing new evidence that there is an additive and adverse effect on the liver caused by the combination of VDD and DIO. The essence of these changes in the liver is in an increased lipogenesis and a reduced beta-oxidation, which predisposes to the accumulation of fat in the liver, accompanied by IR. The worsening of the pathogenesis of NAFLD may tilt to more severe stages of liver disease.

Aims: The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE)., Methods: Four-months old C57BL/6 female mice (wild-type, wt, n=20), and ApoE female mice (n=20), were submitted to OVX or a surgical procedure without ovary removal (SHAM) and formed four groups (n=10/group): SHAM/wt, SHAM/ApoE, OVX/wt, and OVX/ApoE., Key Findings: OVX led to greater body mass, plasma triglycerides (TG) and total cholesterol, and resulted in insulin resistance and altered RAAS gene expressions in the heart tissue. The gene expression of angiotensin-converting enzyme (ACE)-2 was lower in OVX/wt than in SHAM/wt (P=0.0004), Mas receptor (MASr) was lower in OVX/wt compared to SHAM/wt (P<0.0001). Also, angiotensin II receptor type 1 (AT1r) was higher in OVX/wt than in SHAM/wt (P=0.0229), and AT2r was lower in OVX/wt than in SHAM/wt (P=0.0121). OVX and ApoE deficiency showed interaction potentializing the insulin resistance, increasing TG levels and altering ACE and MASr gene expressions. ACE gene expression was higher in OVX/ApoE than in OVX/wt (P<0.0001), and MASr gene expression was lower in OVX/ApoE than in OVX/wt (P<0.0001)., Significance: The impact of OVX on local RAAS cascade in the heart of ApoE deficient animals, besides the metabolic changes culminating with insulin resistance, involves an upregulation of renin, ACE, and AT1r gene expressions. The findings may contribute to clarify the mechanisms of development of postmenopausal hypertension and the link between RAAS and apolipoprotein E., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recent surveys of the copepod fauna associated with the sponge Ircinia felix (Porifera, Dictyoceratida) in Brazil resulted in the discovery of a new siphonostomatoid species belonging to a recently erected genus of Asterocheridae. Setacheres portobarrensis sp. nov. possesses a 21-segmented antennule, with 3 free distal segments, after the aesthetasc. The third exopodal segment of leg 3 shows a distal seta instead of a spine as in some other congeners. The new species shows several unique features on the third endopodal segment of the antenna, the mandibular stylet, the inner lobe of the maxillule, and setules and spinules located in specific regions of legs 1 to 4. Setacheres portobarrensis sp. nov. follows the same distributional pattern as its congeners, and this is the first record of a siphonostomatoid copepod associated with Ircinia felix.

The objective of this study was to evaluate the antibacterial effect and the ultrastructural alterations of diode laser with different wavelengths (808nm and 970nm) and its association with irrigating solutions (2.5% sodium hypochlorite and 2% chlorhexidine) in root dentin contaminated by a five days biofilm. Thirteen uniradicular teeth were sectioned into 100 dentin intraradicular blocks. Initially, the blocks were immersed for 5min in 17% EDTA and washed with distilled water for 5min, then samples were sterilized for 30min at 120°C. The dentin samples were inoculated with 0.1mL of E. faecalis suspension in 5mL BHI (Brain Heart Infusion) and incubated at 37°C for 5days. After contamination, the specimens were distributed into ten groups (n=10) according to surface treatment: GI - 5mL NaOCl 2.5%, GII - 5mL NaOCl 2.5%+808nm diode (0.1W for 20s), GIII - 5mL NaOCl 2.5%+970nm diode (0.5W for 4s), GIV - 808nm diode (0.1W for 20s), GV - 970nm diode (0.5W for 4s), GVI - CHX 2%, GVII - CHX 2%+808nm diode (0.1W for 20s), GVIII - CHX 2%+970nm diode (0.5W for 4s), GIX - positive control and GX - negative control. Bacterial growth was analyzed by turbidity and optical density of the growth medium by spectrophotometry (nm). Then, the specimens were processed for analysis ultrastructural changes of the dentin surface by SEM. The data was subject to the One-way ANOVA test. GI (77.5±12.1), GII (72.5±12.2), GIII (68.7±8.7), GV (68.3±8.7), GVI (62.0±5.5) and GVII (67.5±3.3) were statistically similar and statistically different from GIV (58.8±25.0), GVIII (59.2±4.0) and control groups (p<0.05). SEM analysis showed a modified amorphous organic matrix layer with melted intertubular dentin when dentin samples were irradiated with 970nm diode laser; erosion of the intertubular dentin in blocks submitted to 808nm diode laser irradiation; and an increased erosion of the intertubular dentin when 2.5% NaOCl was associated to the different wavelengths lasers. All the therapeutic protocols were able to reduce the bacterial contingent in dentin blocks, and the association of diode laser and solutions did not significantly improve the reduction of the bacterial contingent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Scope: To investigate the impact of vitamin D deficiency on insulin resistance and abnormal glucose homeostasis in obesity., Methods and Results: Sixty male C57BL/6 mice (3 months old) were fed a control diet (C-10% energy as fat) or a high-fat diet (HF-50% energy as fat), with or without vitamin D, for 8 weeks. There was no difference in body mass between the HF and HF/VitD- groups. Vitamin D deficiency (VitD) in the diet-induced obese mice increased hyperinsulinemia (p = 0.04), hyperleptinemia (p = 0.0002), insulin resistance (HOMA-IR, p = 0.04), and islet changes, including alpha and beta cell disarray. In the insulin signaling pathway, insulin receptor substrate 2 expression was upregulated in the C/VitD- group (p = 0.001) and downregulated in the HF/VitD- group (p = 0.009). Interestingly, forkhead box protein O1 expression was higher in the HF/VitD- group than in the HF group (p = 0.03), and pancreatic and duodenal homeobox 1 expression was lower in the HF/VitD-group than in the HF group (p = 0.025), indicating that the HF diet and vitamin D deficiency influenced the downregulation of the expression of these proteins (two-way ANOVA, p < 0.0001)., Conclusion: Vitamin D deficiency exacerbated the adverse structural and physiological remodeling of pancreatic islets due to obesity, contributing to abnormal glucose homeostasis., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gitelman's Syndrome (GS) is a rare autosomal recessive salt-wasting nephropathy, classically characterized by hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and low blood pressure. Fatigue, muscle weakness and muscle paralysis are common symptoms. Besides the typical electrolyte disturbances, others laboratory findings include hyperreninemia and secondary hyperaldosteronism. Bilateral nephrocalcinosis may occur. The treatment consists of potassium replacement and use of aldosterone antagonists. The best approach to pregnant women with GS is yet to be defined. However, we emphasize the need for ions supplementation, weight control as a clinical tool for assessing the water balance, and frequent monitoring of the fetus and amniotic fluid levels. The surgical risk associated with cesarean section in a patient with GS is not yet defined. Despite the risks related to symptomatic episodes of hypokalemia/hypomagnesemia, GS has a good prognosis when treated properly. Pregnancy imposes the need for more intensive control of the disease, but has a good prognosis for the mother and neonate.

Introduction: This paper proposes a new methodology to simultaneously select the most relevant SNPs markers for the characterization of any measurable phenotype described by a continuous variable using Support Vector Regression with Pearson Universal kernel as fitness function of a binary genetic algorithm. The proposed methodology is multi-attribute towards considering several markers simultaneously to explain the phenotype and is based jointly on statistical tools, machine learning and computational intelligence., Results: The suggested method has shown potential in the simulated database 1, with additive effects only, and real database. In this simulated database, with a total of 1,000 markers, and 7 with major effect on the phenotype and the other 993 SNPs representing the noise, the method identified 21 markers. Of this total, 5 are relevant SNPs between the 7 but 16 are false positives. In real database, initially with 50,752 SNPs, we have reduced to 3,073 markers, increasing the accuracy of the model. In the simulated database 2, with additive effects and interactions (epistasis), the proposed method matched to the methodology most commonly used in GWAS., Conclusions: The method suggested in this paper demonstrates the effectiveness in explaining the real phenotype (PTA for milk), because with the application of the wrapper based on genetic algorithm and Support Vector Regression with Pearson Universal, many redundant markers were eliminated, increasing the prediction and accuracy of the model on the real database without quality control filters. The PUK demonstrated that it can replicate the performance of linear and RBF kernels.

Background: Structure identification of dynamic models for complex biological systems is the cornerstone of their reverse engineering. Biochemical Systems Theory (BST) offers a particularly convenient solution because its parameters are kinetic-order coefficients which directly identify the topology of the underlying network of processes. We have previously proposed a numerical decoupling procedure that allows the identification of multivariate dynamic models of complex biological processes. While described here within the context of BST, this procedure has a general applicability to signal extraction. Our original implementation relied on artificial neural networks (ANN), which caused slight, undesirable bias during the smoothing of the time courses. As an alternative, we propose here an adaptation of the Whittaker's smoother and demonstrate its role within a robust, fully automated structure identification procedure., Results: In this report we propose a robust, fully automated solution for signal extraction from time series, which is the prerequisite for the efficient reverse engineering of biological systems models. The Whittaker's smoother is reformulated within the context of information theory and extended by the development of adaptive signal segmentation to account for heterogeneous noise structures. The resulting procedure can be used on arbitrary time series with a nonstationary noise process; it is illustrated here with metabolic profiles obtained from in-vivo NMR experiments. The smoothed solution that is free of parametric bias permits differentiation, which is crucial for the numerical decoupling of systems of differential equations., Conclusion: The method is applicable in signal extraction from time series with nonstationary noise structure and can be applied in the numerical decoupling of system of differential equations into algebraic equations, and thus constitutes a rather general tool for the reverse engineering of mechanistic model descriptions from multivariate experimental time series.

Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being the dominant feature. However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, exhibiting later a pattern of cercarial shedding and histopatopathological picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its internal defense system. Snails previously inoculated with irradiated miracídia (Group I); treated with S. mansoni antigens (Group II) or with a non-related parasite antigen (Group III) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of antigen injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with Capillaria hepatica. However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located elsewhere within the snail body.

Present report demonstrates that repeated radiation of Schistosoma mansoni-infected Biomphalaria glabrata, totaling 15,000 rads, caused a sudden, albeit transient, suppression of cercarial shedding. Initially, sporocysts practically disappeared from the snail tissues. The more resistant developing cercariae presented nuclear clumping and vacuolation, before undergoing lysis. No host tissue reaction was evident at any time. Thirty-four days after the last irradiation, the snails resumed cercarial elimination. By that time numerous sporocysts and developing cercariae were detected, disseminated throughout snail tissues in a pattern similar to that of a highly malignant neoplasm, with no signs of host cellular reactions, which on the other hand were present in non-irradiated infected controls. The region of the ovo-testis was apparently destroyed after radiation, but returned to its normal appearance around 40 days after the last radiation. Ionizing radiation affected both host and parasite in S. mansoni-infected Biomphalaria glabrata, but the resulting impressive changes were soon reversed.

A comparative histopathological study of three snails species--Biomphalaria glabrata, B. tenagophila and B. straminea--which had been infected with Schistosoma mansoni miracidia revealed similar qualitative features; consisting of areas of sporocyst proliferation and differentiation associated with reactive host reaction, at the time they were actively eliminating great number of cercariae. However, in specimens that were exposed to miracidia but failed to eliminate cercariae later on, different histopathological pictures were observed in different snail species. While B. glabrata exhibited frequent focal (granulomatous) proliferation of amebocytes in several organs, B. tenagophila and B. straminea only rarely showed such reactive changes, suggesting that the mechanism of resistance to miracidial infection probably follows different pathways in the snail species studied.