Chagas disease deaths detected among garbage codes registered in mortality statistics in Brazil: a study from the buRden of ChAgas dISEase in the contemporary world (RAISE) project.

OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.

Therapy of Canine Hyperlipidemia with Bezafibrate.

BACKGROUND: Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs. OBJECTIVE: To assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations. ANIMALS: Forty-six dogs, 26 females and 20 males, mean (±SD) age of 9 (±3) years, with TG ≥150 mg/dL (33 dogs also were hypercholesterolemic [>300 mg/dL]). METHODS: Prospective, uncontrolled clinical trial. Dogs were treated with bezafibrate once daily, using 200 mg tablets at a dosage of 4-10 mg/kg (depending on body weight). Serum TG and CHO concentrations and alanine aminotransferase (ALT) and creatine kinase (CK) activity before and after 30 days of treatment were compared. RESULTS: Sixteen dogs (34.8%) had primary hyperlipidemia, and 30 dogs (65.2%) had secondary hyperlipidemia (including spontaneous hyperadrenocorticism [41.3%, n = 19/46], chronic treatment with glucocorticoids [10.8%, n = 5/46], and hypothyroidism [15.2%, n = 7/46]). After 30 days, serum TG concentration normalized (<150 mg/dL) in 42 dogs (91.3%) and CHO concentration normalized (<270 mg/dL) in 22 of 33 dogs (66.7%). There was no difference in baseline TG concentration between the primary and secondary hyperlipidemia subgroups, but the decrease in TG concentration after treatment was greater in the primary hyperlipidemia subgroup. No adverse effects were observed, but ALT activity decreased significantly after 30 days of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Over 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs.

Decision support system for diabetic retinopathy using discrete wavelet transform.

Prolonged duration of the diabetes may affect the tiny blood vessels of the retina causing diabetic retinopathy. Routine eye screening of patients with diabetes helps to detect diabetic retinopathy at the early stage. It is very laborious and time-consuming for the doctors to go through many fundus images continuously. Therefore, decision support system for diabetic retinopathy detection can reduce the burden of the ophthalmologists. In this work, we have used discrete wavelet transform and support vector machine classifier for automated detection of normal and diabetic retinopathy classes. The wavelet-based decomposition was performed up to the second level, and eight energy features were extracted. Two energy features from the approximation coefficients of two levels and six energy values from the details in three orientations (horizontal, vertical and diagonal) were evaluated. These features were fed to the support vector machine classifier with various kernel functions (linear, radial basis function, polynomial of orders 2 and 3) to evaluate the highest classification accuracy. We obtained the highest average classification accuracy, sensitivity and specificity of more than 99% with support vector machine classifier (polynomial kernel of order 3) using three discrete wavelet transform features. We have also proposed an integrated index called Diabetic Retinopathy Risk Index using clinically significant wavelet energy features to identify normal and diabetic retinopathy classes using just one number. We believe that this (Diabetic Retinopathy Risk Index) can be used as an adjunct tool by the doctors during the eye screening to cross-check their diagnosis.

Proctolin's role in neurally evoked contractions of the locust oviducts.

The effects of proctolin (RYLPT) on neurally evoked contractions of locust oviduct muscle were studied to examine the role of proctolin as a cotransmitter. Increasing the number of stimuli in a burst (from one to 30 stimuli) resulted in an increase in amplitude of contraction of locust oviduct muscle. Proctolin was capable of increasing the amplitude of neurally evoked contractions at lower-stimulus regimes (one- and two-stimulus bursts) but did not do so at higher-stimulus regimes (five- and 10-stimulus bursts). The effects of proctolin were dose dependent within the one- and two-stimulus regimes, with thresholds at 10(-9) M and maxima at 2.5 x 10(-8) M. Addition of proctolin increased the basal tonus and size of a postcontraction relaxation of the oviduct muscle in a dose-dependent manner during all stimulus regimes. However, the effect of proctolin on basal tonus and the postcontraction relaxation was much less at the higher stimulus regimes. Previously, several proctolin analogues have been tested for their ability to antagonize proctolin-induced contractions of the oviduct muscle. Since proctolin is proposed to be a cotransmitter at this neuromuscular junction, one of these analogues, cycloproctolin, was used to antagonize proctolin's effects on neurally evoked contractions. In the presence of the antagonist, the maximum amplitude induced by application of proctolin was decreased by 22.7%, while the proctolin-induced increase in basal tonus was decreased by 45.8%. Finally, the maximum increase in the size of the postcontraction relaxation caused by proctolin was lowered by 32.0%. The results of the present study show that exogenously applied proctolin is an excitant of the oviduct muscle at lower, rather than higher, stimulus regimes, and this latter inaction may be due to the corelease of endogenous proctolin during increased neural stimulation.

Proctolin analogues and a proctolin metabolite as antagonist of the peptide proctolin.

The locust oviduct bioassay was used to assess a variety of proctolin analogues as possible agonists and antagonists of the peptide proctolin. Both [alpha-methyl-L-tyrosine2]proctolin and [N-methyl-L-tyrosine2] proctolin were antagonists of proctolin with thresholds of 5 x 10(-9) M. Interestingly, at these threshold doses the analogues were antagonists when applied along with proctolin, being capable of shifting the dose-response curve for proctolin an order of magnitude to the right. Of the three tripeptides tested Tyr-Arg-Thr and Arg-Tyr-Thr showed no agonistic effects and were incapable of antagonizing proctolin-induced contractions. The third tripeptide, Leu-Pro-Thr, showed minimal agonistic effects and when applied with proctolin, significantly decreased the maximum response and increased the ED50 values of the parent compound. Interestingly, this tripeptide is a degradation product of proctolin. Cycloproctolin possessed no agonistic activity up to 10(-5) M but did antagonize proctolin's response in a dose-dependent manner with 2 x 10(-5) M cycloproctolin shifting the proctolin curve nearly two orders of magnitude to the right. Simultaneous application of 10(-9) M [alpha-methyl-L-tyrosine2]proctolin and 10(-5) M cycloproctolin showed some synergistic effect as the maximum response to the peptide was decreased by 21.6% and the dose-response curve shifted further to the right. These proctolin antagonist will be useful tools for examining the physiological importance of proctolin in insects as well as helping to identify receptor subtypes.

A role for calcium/calmodulin-dependent protein kinase in mediating synaptic modulation by a neuropeptide.

The crayfish neuropeptide DRNFLRFamide (DF2) has previously been shown to increase the amplitude of excitatory post-synaptic potentials (EPSPs) in crayfish muscles by enhancing transmitter release from synaptic terminals [18]. This effect involves at least two types of kinase enzyme: one or more kinases which mediate the initial rise in EPSP amplitude, and protein kinase C (PKC) which prolongs the elevation in EPSP amplitude for several minutes [6,7]. The present investigation was aimed at identifying kinases that participate in the initial response. KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase, delayed the rise in EPSP amplitude induced by DF2. The maximal response to the peptide occurred in about 40 min when KN-62 was present and in 15 min when the inhibitor was absent. KN-62 did not significantly alter EPSP amplitude by itself. KN-04, a structural analog of KN-62 which does not block Ca2+/CaM kinase activity, did not alter EPSP amplitude or the response to the neuropeptide. These data strongly suggest that Ca2+/CaM kinase participates in the initial increase in transmitter release.