Background & Aims: Several lines of evidence support a role for Toll-like receptor (TLR) signaling to protect the intestine from pathogenic infection. We hypothesized that TLR signaling at the level ...of the intestinal epithelium is critical for mucosal immune responses. Methods: We generated transgenic mice that express a constitutively active form of TLR4 in the intestinal epithelium (V-TLR4 mice). Lamina propria cellularity was evaluated by immunostaining and flow cytometry. Immunoglobulin (Ig) A levels in the stool and serum were measured by enzyme-linked immunosorbent assay. Chemokine and cytokine expression were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results: V-TLR4 transgenic mice reproduced normally and had a normal life span. Constitutive activity of TLR4 in the intestinal epithelium promoted recruitment of B cells and an increase in fecal IgA levels. Intestinal epithelial cells of V-TLR4 mice expressed higher levels of CCL20 and CCL28, chemokines known to be involved in B-cell recruitment, and of a proliferation-inducing ligand (APRIL), a cytokine that promotes T-cell-independent class switching of B cells to IgA. The changes in B-cell numbers and IgA levels were blocked by simultaneous expression in intestinal epithelial cells of M3, a herpes virus protein that binds and inhibits multiple chemokines. Conclusions: TLR signaling in the intestinal epithelial cells significantly elevated the production of IgA in the intestine. This effect was mediated by TLR-induced expression of a specific set of chemokines and cytokines that promoted both recruitment of B cells into the lamina propria and IgA class switching of B cells.
Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer's and Parkinson's diseases. In these clinical conditions ...the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases. However, the difficulty to investigate biochemical processes directly in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory responses have been identified in different body fluids, such as blood, cerebrospinal fluid, and tears. In addition, progress in micro and nanotechnology has enabled the development of biosensing platforms capable of detecting in real-time, multiple biomarkers in clinically relevant samples. Biosensing technologies are approaching maturity where they will become deployed in community settings, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight both clinical and recent technological advances toward the development of multiplex-based solutions for effective neuroinflammatory and neurodegenerative disease diagnostics and monitoring.
Abstract
Context
Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been ...reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear.
Objective
To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.
Methods
We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.
Results
KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004).
Conclusion
The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.
The impact of KCNJ5 somatic mutations on hypertension remission after adrenalectomy brings new insight into the postoperative follow-up of patients with PA.
In order to better understand the enzootiology of trypanosomiasis caused by
Trypanosoma evansi in the Brazilian Pantanal we examined domestic and wild mammals by microhematocrit centrifuge technique ...(MHCT), immunofluorescence antibody test (IFAT) and polymerase chain reaction (PCR).
T. evansi infection was detected in all species sampled with exception of the sheep and the feral pig. High parasitemias were observed in capybaras (5/24), coatis (18/115), horses (31/321) and dogs (3/112). Among these species, only the capybaras did not develop anemia. Low parasitemias, only detected by PCR, were found in buffaloes (18/43), bovines (29/331), marsupials (1/4), small rodents (14/67), bats (7/18), and one armadillo (1/8). The highest prevalence of
T. evansi infection was recorded in horses (73%), although no neurological signs in infected horses were observed. Diagnosis through standard parasitological tests and IFAT should be used with caution since they may overlook comprovedly infected horses. The relationship between ranch management and
T. evansi infection in horse was investigated. The importance of other transmission mechanisms apart from the tabanids and reservoir hosts are discussed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Determining the reservoir hosts for parasites is crucial for designing control measures, but it is often difficult to identify the role that each host species plays in maintaining the cycle of ...infection in the wild. One way to identify potential maintenance hosts is to estimate key parameters associated with transmission and pathogenicity. Here we assess the potential for three native rodent species of the Brazilian Pantanal (
Clyomys laticeps,
Thrichomys pachyurus and
Oecomys mamorae) to act as reservoir or maintenance hosts of
Trypanosoma evansi, an important parasite of domestic livestock. By analyzing blood parameters of naturally infected wild-caught rodents of these species, we compared their levels of parasitemia and anemia due to
T. evansi infection with literature values for other host species infected by this parasite. We also analyzed levels of these blood parameters relative to infection by
Trypanosoma cruzi, the causative agent of Chagas disease in humans, for which wild rodents are already thought to be important reservoir species. All three species showed low impacts of the two trypanosomes on their blood parameters compared to other species, suggesting that they experience a low virulence of trypanosome infection under natural conditions in the Pantanal and might act as maintenance hosts of trypanosome infections. The low parasitemia of trypanosome infections suggests that these rodents play a secondary role in the transmission cycle compared to other species, especially compared to the capybara (
Hydrochaeris hydrochaeris) which also experiences low pathogenicity due to infection despite much higher levels of parasitemia.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Magnetotactic bacteria produce magnetosomes, which are magnetic particles enveloped by biological membranes, in a highly controlled mineralization process. Magnetosomes are used to navigate in ...magnetic fields by a phenomenon called magnetotaxis. Two levels of organization and control are recognized in magnetosomes. First, magnetotactic bacteria create a spatially distinct environment within vesicles defined by their membranes. In the vesicles, the bacteria control the size, composition and purity of the mineral content of the magnetic particles. Unique crystal morphologies are produced in magnetosomes as a consequence of this bacterial control. Second, magnetotactic bacteria organize the magnetosomes in chains within the cell body. It has been shown in a particular case that the chains are positioned within the cell body in specific locations defined by filamentous cytoskeleton elements. Here, we describe an additional level of organization of the magnetosome chains in uncultured magnetotactic cocci found in marine and freshwater sediments. Electron microscopy analysis of the magnetosome chains using a goniometer showed that the magnetic crystals in both types of bacteria are not oriented at random along the crystal chain. Instead, the magnetosomes have specific orientations relative to the other magnetosomes in the chain. Each crystal is rotated either 60°, 180° or 300° relative to their neighbors along the chain axis, causing the overlapping of the (1 1 1) and Formula in text capping faces of neighboring crystals. We suggest that genetic determinants that are not present or active in bacteria with magnetosomes randomly rotated within a chain must be present in bacteria that organize magnetosomes so precisely. This particular organization may also be used as an indicative biosignature of magnetosomes in the study of magnetofossils in the cases where this symmetry is observed.
An evaluation was made on how the landscape and cattle ranching affect the transmission cycles and the patterns of tripanosomatid infection (
Trypanosoma cruzi and
Trypanosoma evansi) of small wild ...mammals in the Pantanal. This region comprises a large natural environment with a multiplicity of habitats, wide variety of biodiversity besides the presence of livestock.
T. cruzi and
T. evansi infections were evaluated by parasitological and serological methods in one preserved and one cattle ranching area. The diversity of the small mammal fauna showed to be the same in the two studied areas, however, their relative abundance was different. Distinct enzootiological scenarios of both trypanosomatids could be observed. Transmission of
T. cruzi occurred mainly in forested areas, in the two study areas, while
T. evansi occurred dispersed among all habitats studied in the unpreserved area. The arboreal rodent
Oecomys mamorae, the most abundant species in both areas, displayed high
T. cruzi and
T. evansi serum prevalence and parasitemias. Also, the caviomorph rodent
Thrichomys pachyurus was shown to be an important host due to its expressive relative abundance, prevalence of infection by both trypanosomatid species and a broad range use of habitats. The role of the small mammal fauna in the transmission cycle of both trypanosomes species seems to be distinct according to land use since we found a broad range of
T. evansi infected hosts in the preserved area in contrast to cattle ranching area and a half number of the rodents species infected with
T. cruzi in unpreserved in comparison to protect area. The present study showed that cattle ranching in this study area did not enhance overall prevalence of
T. cruzi infection among small wild mammals. Together with the observation that small mammals diversity in FA is similar to RN area suggest that ranching activity may also not necessarily conduct to biodiversity loss or risk of Chagas disease.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA subtypes include bilateral hyperplasia and unilateral PA, typically aldosterone-producing adenomas. Adrenal ...venous (AV) sampling (AVS) is a key step to define PA subtype and guide PA management. According current PA guidelines, most PA patients should undergo AVS, which is a challenging procedure, especially in terms of successfully cannulating the right AV. The aim of this study was to report a single tertiary center experience with AVS in PA patients. We retrospectively evaluated 84 AVS from 1984 to 2019. Sequential AVS was performed by an experienced interventional radiologist. AV and inferior vena cava (IVC) samples were obtained under cosyntropin continuous infusion. Successful catheterization was defined by a selectivity index SI= AV/IVC cortisol (C) concentrations ≥5. Unilateral disease was defined by a lateralization index LI= aldosterone (A)/C ratio in the dominant AV divided by A/C in the non-dominant AV ≥4. The relative aldosterone secretion index (RASI= A/C ratio in AV divided by A/C in IVC) was calculated in each side. A RASI <1 was defined as contralateral suppression (CS). In patients with unsuccessful AV catheterization (mostly right AV) or undetermined LI (3-4), CS was used to indicate adrenalectomy. The biochemical cure of PA after adrenalectomy was defined as the gold standard parameter to confirm unilateral disease. Successful bilateral AV catheterization was achieved in 75% of the cases. After 2015, the use of intra-procedural rapid cortisol assay improved angiographer experience and increased AVS successful rate from 52 to 80%. LI revealed unilateral and bilateral aldosterone excess in 68 and 32% of the cases, respectively. A LI ≥4 had a sensitivity of 100% and specificity of 98% to define unilateral PA among patients with successful catheterization. In addition, RASI in the non-dominant AV was significantly lower in unilateral PA according the LI when compared to bilateral cases 0.12 (0.03 to 1.18) vs. 1.1 (0.04 to 4.56), p= 0.0001. RASI in the non-dominant AV was inversely correlated with LI (r= -0.81, p= 0.0001). A CS index ≤0.5 had a high sensitivity (90%) and specificity (94%) to define unilateral aldosterone excess. In conclusion, the LI is the most valuable parameter in AVS for PA subtyping. Additionally, CS (cut-off of 0.5) is very useful to define lateralization and can be used in cases of borderline LI or unsuccessful AV catheterization.CAPES Grant to Freitas TC.
We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015-2016 (refs.
...). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below -2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between -1 and -2 s.d. in any domain (scores <85-70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
