Spatial Analysis Spotlighting Early Childhood Leprosy Transmission in a Hyperendemic Municipality of the Brazilian Amazon Region

Background

More than 200,000 new cases of leprosy were reported by 105 countries in 2011. The disease is a public health problem in Brazil, particularly within high-burden pockets in the Amazon region where leprosy is hyperendemic among children.

Methodology

We applied geographic information systems and spatial analysis to determine the spatio-temporal pattern of leprosy cases in a hyperendemic municipality of the Brazilian Amazon region (Castanhal). Moreover, we performed active surveillance to collect clinical, epidemiological and serological data of the household contacts of people affected by leprosy and school children in the general population. The occurrence of subclinical infection and overt disease among the evaluated individuals was correlated with the spatio-temporal pattern of leprosy.

Principal Findings

The pattern of leprosy cases showed significant spatio-temporal heterogeneity (p<0.01). Considering 499 mapped cases, we found spatial clusters of high and low detection rates and spatial autocorrelation of individual cases at fine spatio-temporal scales. The relative risk of contracting leprosy in one specific cluster with a high detection rate is almost four times the risk in the areas of low detection rate (RR = 3.86; 95% CI = 2.26–6.59; p<0.0001). Eight new cases were detected among 302 evaluated household contacts: two living in areas of clusters of high detection rate and six in hyperendemic census tracts. Of 188 examined students, 134 (71.3%) lived in hyperendemic areas, 120 (63.8%) were dwelling less than 100 meters of at least one reported leprosy case, 125 (66.5%) showed immunological evidence (positive anti-PGL-I IgM titer) of subclinical infection, and 9 (4.8%) were diagnosed with leprosy (8 within 200 meters of a case living in the same area).

Conclusions/Significance

Spatial analysis provided a better understanding of the high rate of early childhood leprosy transmission in this region. These findings can be applied to guide leprosy control programs to target intervention to high risk areas.     

Acute intracerebroventricular insulin microinjection after nitric oxide synthase inhibition of renal sodium handling in rats

The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Recent and growing evidence suggests that insulin or a nonapeptide-derived from the C-terminus of the insulin beta-chain may influence many brain functions. However, there is little information on the insulin-activated neural pathways regulating urinary sodium excretion. Also, we examined the influence of nitric oxide synthase activity by chronic oral administration of N(omega)-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, after previous i.c.v. administration of insulin to unanesthetized, unrestrained rats that were randomly assigned to one of seven separated groups: (a) i.c.v. 0.15 M NaCl-injected (n = 11) and i.c.v. 126 ng (n = 11) insulin-injected rats; (b) i.c.v. insulin-injected in systemic L-NAME-treated (n = 10) and vehicle-treated insulin-injected rats (n = 10); and (c) subcutaneously (SC) insulin-injected rats (n = 5). We showed that centrally administered insulin produced increase in the urinary output of sodium (from 0.15 M NaCl: 855.6 +/- 85.1 Delta%.min(-1) to 126 ng insulin: 2055 +/- 310.6 Delta%.min(-1)) and potassium (126 ng: from 0.15 M NaCl: 460.4 +/- 100 Delta%.min(-1) to 126 ng insulin: 669 +/- 60.8 Delta%.min(-1)). The urinary sodium excretion response to i.c.v. 126 ng insulin microinjection was significantly abolished by previous systemic treatment of animals with 15 mg/kg/day L-NAME (from vehicle + 126 ng insulin: 1935 +/- 258.3 Delta%. min(-1) to L-NAME + 126 ng insulin: 582.3 +/- 69.6 Delta%. min(-1)). In addition, we showed that insulin-induced natriuresis occurred by increasing post-proximal tubule sodium rejection (FEPP(Na)), despite an unchanged glomerular filtration rate (C(Cr)). The current data suggests the novel concept that CNS NO-dependent neural pathways may play an instrumental role on efferent insulin-sensitive nerve activity from periventricular region. Speculatively, it seems interesting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature, and that defects in this efferent signal could result in insulin central resistance, inability of renal tubules to handle the hydro electrolyte balance and hypertension.     

Reproducibility of an incremental treadmill VO(2)max test with gas exchange analysis for runners

The evaluation of performance through the application of adequate physical tests during a sportive season may be a useful tool to evaluate training adaptations and determine training intensities. For runners, treadmill incremental VO(2)max tests with gas exchange analysis have been widely used to determine maximal and submaximal parameters such as the ventilatory threshold (VT) and respiratory compensation point (RCP) running speed. However, these tests often differ in methodological characteristics (e.g., stage duration, grade, and speed increment size), and few studies have examined the reproducibility of their protocol. Therefore, the aim of this study was to verify the reproducibility and determine the running speeds related to maximal and submaximal parameters of a specific incremental maximum effort treadmill protocol for amateur runners. Eleven amateur male runners underwent 4 repetitions of the protocol (25-second stages, each increasing by 0.3 km·h in running speed while the treadmill grade remained fixed at 1%) after 3 minutes of warm-up at 8-8.5 km·h. We found no significant differences in any of the analyzed parameters, including VT, RCP, and VO(2)max during the 4 repetitions (p > 0.05). Further, the results related to running speed showed high within-subject reproducibility (coefficient of variation < 5.2%). The typical error (TE) values for running speed related to VT (TE = 0.62 km·h), RCP (TE = 0.35 km·h), and VO(2)max (TE = 0.43 km·h) indicated high sensitivity and reproducibility of this protocol. We conclude that this VO(2)max protocol facilitates a clear determination of the running speeds related to VT, RCP, and VO(2)max and has the potential to enable the evaluation of small training effects on maximal and submaximal parameters.     

One operational definition by population: the need for local evaluations of frailty

Frailty is a health problem that increases the probability of developing adverse health outcomes in the elderly. A frequently used way to operationalize frailty is the construction of a frailty index, which is built from the addition of several health deficits that describe biological aging. However, there is no consensus about the number of health deficits for building a frailty index and about which deficits must be chosen. This lack of a standardized frailty index is assumed to be an obstacle for the advancement of research on frailty. The focus of the present article is to propose a theoretically plausible alternative way of operationalizing frailty by means of frailty indexes composed of deficits selected at a local level. These deficits would therefore be different for each given population. This "anthropological approach" is on the opposite side from current trends in frailty research, which is characterized by the search for a standardized operational definition of frailty. The anthropological approach would generate more reliable data by taking into account the specificity of the population to be studied for selecting frailty deficits. In this approach, emotions, motives, and beliefs are as important to determine individuals' health vulnerability as chronic diseases and physical function. Physiological anthropologists are well positioned to contribute to research on frailty by carrying out studies on the selection of the best deficits to operationalize frailty in different populations, with different socio-cultural determinants of health, and living in different environmental life spaces.     

Astrocyte proliferation following stroke in the mouse depends on distance from the infarct

Reactive gliosis is a hallmark of brain pathology and the injury response, yet the extent to which astrocytes proliferate, and whether this is central to astrogliosis is still controversial. We determined the fraction of mature astrocytes that proliferate in a mouse stroke model using unbiased stereology as a function of distance from the infarct edge. Cumulatively 11.1±1.2% of Aldh1l1(+) astrocytes within 400 μm in the cortical penumbra incorporate BrdU in the first week following stroke, while the overall number of astrocytes does not change. The number of astrocytes proliferating fell sharply with distance with more than half of all proliferating astrocytes found within 100 μm of the edge of the infarct. Despite extensive cell proliferation primarily of microglia and neutrophils/monocytes in the week following stroke, few mature astrocytes re-enter cell cycle, and these are concentrated close to the infarct boundary.     

Pivotal role of Toll-like receptors 2 and 4, its adaptor molecule MyD88, and inflammasome complex in experimental tubule-interstitial nephritis

Tubule-interstitial nephritis (TIN) results in decreased renal function and interstitial inflammation, which ultimately leads to fibrosis. Excessive adenine intake can cause TIN because xanthine dehydrogenase (XDH) can convert this purine into an insoluble compound, which precipitates in the tubuli. Innate immune sensors, such as Toll-like receptors (TLR) and inflammasome complex, play a crucial role in the initiation of inflammation. The aim of this study was to evaluate the roles of TLR-2 and -4, Myd88 and inflammasome complex in an experimental model of TIN. Here, we show that wild-type (WT) mice fed adenine-enriched food exhibited significant renal dysfunction and enhanced cellular infiltration accompanied by collagen deposition. They also presented higher gene and protein expression of pro-inflammatory cytokines. In contrast, TLR-2, -4, MyD88, ASC and Caspase-1 KO mice showed renoprotection associated with expression of inflammatory molecules at levels comparable to controls. Furthermore, treatment of WT animals with allopurinol, an XDH inhibitor, led to reduced levels of uric acid, oxidative stress, collagen deposition and a downregulation of the NF-kB signaling pathway. We concluded that MyD88 signaling and inflammasome participate in the development of TIN. Furthermore, inhibition of XDH seems to be a promising way to therapeutically target the developing inflammatory process.     

Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease

Background

Uremic solute concentration increases as Glomerular Filtration Rate (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR) and the concentrations of several small water-soluble and protein-bound uremic solutes (MW<500Da). Since also middle molecular weight proteins have been associated with mortality and cardiovascular damage in Chronic Kidney Disease (CKD), we investigated the association between several eGFR formulae and the concentration of Low Molecular Weight Proteins (LMWP) (MW>500Da).

Materials and Methods

In 95 CKD-patients (CKD-stage 2–5 not on dialysis), associations between different eGFR-formulae (creatinine, CystatinC-based or both) and the natural logarithm of the concentration of several LMWP’s were analyzed: i.e. parathyroid hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, retinol binding protein (RbP), immunoglobin light chains kappa and lambda (Ig-κ and Ig-λ), beta-2-microglobulin (β₂M), myoglobin and fibroblast growth factor-23 (FGF-23)).

Results

The regression coefficients (R²) between eGFR, based on the CKD-EPI-Crea-CystC-formula as reference, and the examined LMWP’s could be divided into three groups. Most of the LMWP’s associated weakly (R² <0.2) (FGF-23, leptin, IL-6, TNF-α, Ig-κ, Ig-λ) or intermediately (R² 0.2–0.7) (RbP, myoglobin, PTH). Only β₂M and CystC showed a strong association (R² >0.7). Almost identical R²-values were found per LMWP for all eGFR-formulae, with exception of CystC and β₂M which showed weaker associations with creatinine-based than with CystC-based eGFR.

Conclusion

The association between eGFR and the concentration of several LMWP’s is inconsistent, with in general low R²-values. Thus, the use of eGFR to evaluate kidney function does not reflect the concentration of several LMWP’s with proven toxic impact in CKD.     

In Silico and Quantitative Analyses of the Putative FLC-like Homologue in Coffee (Coffea arabica L.)

The sequential pattern of coffee flowering is a major constraint that directly affects productivity, increases harvest costs, and generates a final product of lower quality for mixing dry fruits with ripe and unripe ones. The objective of this work was to identify and analyze one of the main genes involved in flowering regulation, FLOWERING LOCUS C (FLC) in coffee (Coffea arabica L.). The identification of this gene was conducted in silico using a coffee EST database (CAFEST) and bioinformatics tools. Quantitative PCR results suggest that the identified CaFLC-like homologue is directly involved in flowering regulation in coffee. This expands our knowledge on evolutionary conservation of flowering pathways in dicot species. The functional studies of CaFLC-like with mutants of a more tractable species will lead to a better understanding of the molecular regulation as well as the specific functions of each gene flowering during floral induction in coffee.