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Hallux valgus is a challenging pathology characterized by a valgus deformity in the metatarsophalangeal area of the first ray. The aim of this study was to analyze the influence of first metatarsal osteotomy on the relationship between midfoot bones in patients with hallux valgus. The sample consisted of patients from the orthopedics and traumatology outpatient clinic who underwent surgical treatment for hallux valgus. Preoperative and postoperative X-rays were compared regarding the width of the midfoot and the tarsometatarsal joint. The sample consisted of 17 women, with 22 feet assessed in each group. The distance from the medial cuneiform to the cuboid, the distance from the intermediate cuneiform to the cuboid, the distance between the first and fifth metatarsals, and the distance between the second and fifth metatarsals reduced significantly between pre- and postoperative assessments. Hallux valgus correction through osteotomy of the first metatarsal leads to a structural change in the midfoot. Further studies should determine whether these changes persist over time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chagas disease (CD) is a typical tropical illness caused by Trypanosoma cruzi . The objective of this study was to assess the prevalence of Chagas disease in communities in two states of the Brazilian Amazon. Data collection occurred in July in the Alto Juruá region of Acre and in December in the communities of Humaitá, Amazonas, in 2019. A total of 477 participants were included in the study. In the communities of Alto Juruá, triatomine collections and analyses of T. cruzi infection were also carried out. All confirmed cases were found in the state of Acre, resulting in a total prevalence of 1.67. Of these eight cases, seven underwent ECG, all of which were concluded as normal by the physician team's cardiologists. Seventeen triatomine bugs, all belonging to the Rhodnius genus, were captured. The natural infection rate by T. cruzi was 25% in the Nova Cintra community and 66.67% in the Boca do Moa community (Alto Juruá). This research found that more than 1% of the studied population exhibited positive serological results for Chagas disease in the riverine communities during the study period, representing a small portion of cases among those who have not yet been diagnosed.

Anxiety, a state related to anticipatory fear, can be adaptive in the face of environmental threats or stressors. However, anxiety can also become persistent and manifest as anxiety- and stress-related disorders, such as generalized anxiety or post-traumatic stress disorder (PTSD). In rodents, systemic administration of glucocorticoids (GCs) or short-term restraint stress induces anxiety-like behaviors and dendritic branching within the basolateral complex of the amygdala (BLA) ten days later. Additionally, increased arousal-related memory retention mediated by elevated GCs requires concomitant noradrenaline (NE) signaling, both acting in the BLA. It is unknown whether GCs and NE play a role in the delayed acute stress-induced effects on behavior and BLA dendritic plasticity. Here, inhibiting corticosterone (CORT) elevation during 2 h of restraint stress prevents stress-induced increases in delayed anxiety-like behavior and BLA dendritic spine density in rats. Also, we show that the delayed acute stress-induced effects on behavior and morphological alterations are critically dependent on genomic glucocorticoid receptor (GR) actions in the BLA. Unlike CORT, the pharmacological enhancement of NE signaling in the BLA was insufficient to drive delayed anxiety-related behavior. Nonetheless, the delayed anxiety-like behavior ten days after acute stress requires NE signaling in the BLA during stress exposure. Therefore, we define the essential roles of two stress-related hormones for the late stress consequences, acting at two separate times: CORT, via GR, immediately during stress, and NE, via beta-adrenoceptors, during the expression of delayed anxiety., Competing Interests: None., (© 2023 The Authors.)

Background: Within the endocrine-paracrine signalling network at the maternal-foetal interface, the activin-inhibin-follistatin system modulates extravillous trophoblast invasion, suggesting a potential role in preeclampsia pathogenesis. This study aimed to compile the evidence published in the last decade regarding the variation in maternal serum activins, inhibin- and follistatin-related proteins in preeclamptic pregnancies compared to healthy pregnancies, and to discuss their role in predicting and understanding the pathophysiology of preeclampsia., Material and Methods: A scoping review was conducted in MEDLINE, EMBASE and LILACS databases to identify studies published within the last ten years (2012-2022)., Results: Thirty studies were included. None of the studies addressed maternal serum changes of isoforms different from activin A, inhibin A, follistatin, and follistatin-like 3. Sixteen studies evaluated the potential of these isoforms in predicting preeclampsia through the area under the curve from a receiver operating characteristic curve., Conclusions: In preeclampsia, inhibin A is upregulated in all trimesters, whereas activin A increases exclusively in the late second and third trimesters. Serum follistatin levels are reduced in women with preeclampsia during the late second and third trimesters. However, changes in follistatin-like 3 remain inconclusive. Inhibin A and activin A can potentially serve as biomarkers of early-onset preeclampsia based on the outcomes of the receiver operating characteristic curve analysis. Further investigations are encouraged to explore the feasibility of quantifying maternal serum levels of activin A and inhibin A as a clinical tool in early preeclampsia prediction., (© 2023 Jorge A. Barrero et al., published by Sciendo.)

Competing Interests: JS, YW were employed by UCB Biosciences Inc. LC was employed by 17-09, LLC.

In the field of interventional neuroradiology, antiplatelet agents are commonly used to prepare patients before the implantation of permanent endovascular materials. Among the available drugs, clopidogrel is the most frequently used one, but resistance phenomena are considered to be relatively common. Prasugrel and ticagrelor were recently added to the pharmacologic arsenal, but the safety of these agents in patients undergoing neurointerventional procedures is still a subject of discussion. The cumulative experience with both drugs is less extensive than that with clopidogrel, and the experience with patients in the neurology field is less extensive than in the cardiology domain. In the present article, we provide a narrative review of studies that investigated safety issues of oral P2Y12 inhibitors in interventional neuroradiology and discuss potential routes for future research., (© 2021 by American Journal of Neuroradiology.)

The persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.

Rationale: Studies point out a higher prevalence of posttraumatic stress disorder (PTSD) in individuals with diabetes mellitus. It is known that glucocorticoid (GR) and mineralocorticoid (MR) receptors are implicated in fear memory processes and PTSD. However, there is no preclinical studies addressing the involvement of these receptors on abnormal fear memories related to diabetic condition., Objectives: By inducing a contextual conditioned fear memory, we generate a suitable condition to investigate the extinction and the generalization of the fear memory in streptozotocin-induced diabetic (DBT) rats alongside the expression of the cytosolic and nuclear GR and MR in the hippocampus (HIP) and prefrontal cortex (PFC). Moreover, we investigated the involvement of the MR or GR on the acquisition of fear memory extinction and on the generalization of this fear memory. When appropriate, anxiety-related behavior was evaluated., Methods: Male Wistar rats received one injection of steptozotocin (i.p.) to induce diabetes. After 4 weeks, the animals (DBTs and non-DBTs) were subjected to a conditioned contextual fear protocol., Results: The expression of MR and GR in the HIP and PFC was similar among all the groups. The single injection of MR agonist was able to facilitate the acquisition of the impaired fear memory extinction in DBTs animals together with the impairment of its generalization. However, the GR antagonism impaired only the generalization of this fear memory which was blocked by the previous injection of the MR antagonist. All treatments were able to exert anxiolytic-like effects., Conclusions: The results indicate that MR activation in DBT animals disrupts the overconsolidation of aversive memory, without discarding the involvement of emotional behavior in these processes.

The objectives of this study were to evaluate the occurrence of microorganisms, the antimicrobial susceptibility profile, and the presence of multidrug resistant (MDR) bacteria in the urine of clinically healthy dogs and dogs with cystitis. The urine was collected through cystocentesis. Subsequently, culture and antimicrobial susceptibility tests were performed. The isolates were classified based on their resistance profile, to evaluate the presence of MDR bacteria. Statistical analyses were performed using the chi-squared or Fisher's exact tests. Bacterial isolates were present in 24.39% of the dogs in the control group, and 60.27% of the dogs in the cystitis group. The cystitis group was associated with a higher risk of bacterial isolates than the control group (odds ratio = 7.5; 95% confidence interval = 2.81-22.40). The main isolates were Staphylococcus spp., Escherichia coli , Proteus spp., and Enterobacter spp. in both groups. A high percentage of isolates were resistant to ampicillin in both groups. The lowest resistance presented by the isolates in both groups was to meropenem. Only the resistance to quinolones was different between the groups. The proportions of MDR isolates were 70% (7/10) and 65.91% (29/44) in the control and cystitis groups, respectively. The results showed the presence of MDR bacteria in the urine of both the healthy dogs, and the dogs with cystitis. The drug resistance was high, reinforcing the importance of establishing an effective treatment approach against urinary tract infections in pets, to minimize the spread of bacterial resistance and its impact on public health., Competing Interests: The authors declare no conflict of interest.

We evaluated the distribution of piroplasmids in equids from the Mato Grosso state in Midwestern Brazil using molecular methods and the interspecific genetic diversity. For this, 1,624 blood samples of equids from 973 farms were examined by PCR, using primer pairs that amplify a fragment of the genes rap-1 and ema-1 of Babesia caballi and Theileria equi, respectively. For molecular characterization and phylogenetic studies, 13 and 60 sequences of the rap-1 and ema-1 genes, respectively, were used to build a dendogram using maximum parsimony. B. caballi and T. equi were detected in 4.11% and 28.16% of the farms, respectively, and molecular prevalence was 2.74% for B. caballi and 25.91% for T. equi. The location of the farms and animals raised in the Pantanal ecoregion influence the probability of equids testing positive for B. caballi and T. equi . Moreover, age and herd purpose were variables significantly associated with T . equi infection. The sequences of B. caballi presented 1.95% intraspecific variability, contrasting with 2.99% in T. equi. Dendrograms for both species demonstrated the presence of subgroups with high values of support of branches. However, it is not possible to associate these groups with geographic origin and/or ecoregion.

Introduction: This article reports, for the first time, the occurrence of Panstrongylus megistus in the Brazilian Western Amazon., Methods: Specimens of P. megistus were collected in the cities of Rio Branco, Acre and Extrema, Rondônia., Results: The number of triatomine species in the State of Acre increased from eight to nine and in Rondônia from seven to eight. This was also the first report of P. megistus in the Brazilian Western Amazon., Conclusion: The occurrence of P. megistus in the Western Amazon evidences an epidemiological alert, since it is an important vector of T. cruzi., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states., Methods: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP. RNA from post-mortem samples of the entire lateral ventricular choroid plexus was extracted from 6 healthy controls (Ctrl), 7 patients with advanced (Braak and Braak stage III-VI) Alzheimer's disease (AD), 4 with frontotemporal dementia (FTD) and 3 with Huntington's disease (HuD). Statistics and agglomerative clustering were accomplished with MathWorks, MatLab; and gene set annotations by comparing input sets to GeneGo ( http://www.genego.com ) and Ingenuity ( http://www.ingenuity.com ) pathway sets. Bonferroni-corrected hypergeometric p-values of < 0.1 were considered a significant overlap between sets., Results: Pronounced differences in gene expression occurred in CP of advanced AD patients vs. Ctrls. Metabolic and immune-related pathways including acute phase response, cytokine, cell adhesion, interferons, and JAK-STAT as well as mTOR were significantly enriched among the genes upregulated. Methionine degradation, claudin-5 and protein translation genes were downregulated. Many gene expression changes in AD patients were observed in FTD and HuD (e.g., claudin-5, tight junction downregulation), but there were significant differences between the disease groups. In AD and HuD (but not FTD), several neuroimmune-modulating interferons were significantly enriched (e.g., in AD: IFI-TM1, IFN-AR1, IFN-AR2, and IFN-GR2). AD-associated expression changes, but not those in HuD and FTD, were enriched for upregulation of VEGF signaling and immune response proteins, e.g., interleukins. HuD and FTD patients distinctively displayed upregulated cadherin-mediated adhesion., Conclusions: Our transcript data for human CP tissue provides genomic and mechanistic insight for differential expression in AD vs. FTD vs. HuD for stromal as well as epithelial components. These choroidal transcriptome characterizations elucidate immune activation, tissue functional resiliency, and CSF metabolic homeostasis. The BCSFB undergoes harmful, but also important functional and adaptive changes in neurodegenerative diseases; accordingly, the enriched JAK-STAT and mTOR pathways, respectively, likely help the CP in adaptive transcription and epithelial repair and/or replacement when harmed by neurodegeneration pathophysiology. We anticipate that these precise CP translational data will facilitate pharmacologic/transgenic therapies to alleviate dementia.

Schizophrenia (SCZ), bipolar disorder (BD) and recurrent major depressive disorder (rMDD) are common psychiatric illnesses. All have been associated with lower cognitive ability, and show evidence of genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism. Disrupted in schizophrenia 1 (DISC1) protein directly interacts with a large set of proteins (DISC1 Interactome) that are involved in brain development and signaling. Modulation of DISC1 expression alters the expression of a circumscribed set of genes (DISC1 Regulome) that are also implicated in brain biology and disorder. Here we report targeted sequencing of 59 DISC1 Interactome genes and 154 Regulome genes in 654 psychiatric patients and 889 cognitively-phenotyped control subjects, on whom we previously reported evidence for trait association from complete sequencing of the DISC1 locus. Burden analyses of rare and singleton variants predicted to be damaging were performed for psychiatric disorders, cognitive variables and personality traits. The DISC1 Interactome and Regulome showed differential association across the phenotypes tested. After family-wise error correction across all traits (FWER across ), an increased burden of singleton disruptive variants in the Regulome was associated with SCZ (FWER across P=0.0339). The burden of singleton disruptive variants in the DISC1 Interactome was associated with low cognitive ability at age 11 (FWER across P=0.0043). These results identify altered regulation of schizophrenia candidate genes by DISC1 and its core Interactome as an alternate pathway for schizophrenia risk, consistent with the emerging effects of rare copy number variants associated with intellectual disability.

In order to assess the effects of Fe-enrichment on the growth and domoic acid (DA) production of the toxigenic diatom Pseudo-nitzschia multiseries , static cultures that received the addition of different iron (Fe) concentrations were maintained for 30 days. Intra- and extracellular DA concentrations were evaluated over time, and growth and chain-formation were compared to those of non-toxic diatoms, Bacillaria sp. Growth rates of P. multiseries (μ = 0.45-0.73 d -1 ) were similar among cultures containing different Fe concentrations. Likewise, the similar incidence and length of P. multiseries stepped cell chains (usually 2-4; up to 8-cell long) among the treatments reinforces that the cultures were not growth-inhibited under any condition tested, suggesting an efficient Fe acquisition mechanism. Moreover, DA concentrations were significantly higher under the highest Fe concentration, indicating that Fe is required for toxin synthesis. Bacillaria sp. reached comparable growth rates under the same Fe concentrations, except when the dissolved cell contents from a P. multiseries culture was added. The 50-70% reduction in cell density and 70-90% decrease in total chlorophyll-a content of Bacillaria sp. at early stationary growth phase indicates, for the first time, an allelopathic effect of undetermined compounds released by Pseudo-nitzschia to another diatom species., Competing Interests: The authors declare no conflict of interest.

N-methyl-D-aspartate-receptors (NMDARs) are ionotropic glutamate receptors that function in synaptic transmission, plasticity and cognition. Malfunction of NMDARs has been implicated in a variety of nervous system disorders, making them attractive therapeutic targets. Overexpression of functional NMDAR in non-neuronal cells results in cell death by excitotoxicity, hindering the development of cell-based assays for NMDAR drug discovery. Here we report a plate-based, high-throughput approach to study NMDAR function. Our assay enables the functional study of NMDARs with different subunit composition after activation by glycine/D-serine or glutamate and hence presents the first plate-based, high throughput assay that allows for the measurement of NMDAR function in glycine/D-serine and/or glutamate sensitive modes. This allows to investigate the effect of small molecule modulators on the activation of NMDARs at different concentrations or combinations of the co-ligands. The reported assay system faithfully replicates the pharmacology of the receptor in response to known agonists, antagonists, positive and negative allosteric modulators, as well as the receptor's sensitivity to magnesium and zinc. We believe that the ability to study the biology of NMDARs rapidly and in large scale screens will enable the identification of novel therapeutics whose discovery has otherwise been hindered by the limitations of existing cell based approaches.

More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of Plasmodium falciparum malaria. Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin. Lack of PfHRP2 protein through deletion of the pfhrp2 gene leads to false-negative RDT results for P. falciparum. We have evaluated the extent of pfhrp2 and pfhrp3 gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012. Pfhrp2 and pfhrp3 gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil. In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for pfhrp2 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of pfhrp2 gene deletion was only 3.3% (2 out of 60 patients). In isolates from Para state, all parasites were pfhrp2-positive. In contrast, we detected high proportions of isolates from all 3 states that were pfhrp3-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples). In Bolivia, only one of 25 samples (4%) tested had deleted pfhrp2 gene, while 68% (17 out of 25 samples) were pfhrp3-negative. Among the isolates tested, P. falciparum pfhrp2 gene deletions were present mainly in those from Acre State in the Brazilian Amazon. These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor pfhrp2 gene deletions in this and other parts of the Amazon region.

Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (1), was isolated from the AcOEt fraction (Kd-AC). The BuOH-soluble fraction afforded quercetin 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (2) and the new kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside-7-O-β-d-glucopyranoside (3), named daigremontrioside. The crude extract, Kd-AC fraction, flavonoids 1 and 2 were evaluated using acyclovir-sensitive strains of HSV-1 and HSV-2. Kd-AC was highly active against HSV-1 (EC 50  = 0.97 μg/ml, SI > 206.1) and HSV-2 (EC 50  = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti-HSV-1 (EC 50  = 7.4 μg/ml; SI > 27 and EC 50  = 5.8 μg/ml; SI > 8.6, respectively) and anti-HSV-2 (EC 50  = 9.0 μg/ml; SI > 22.2 and EC 50  = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity., (© 2016 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: The morbidity and mortality profile in a given region reflects its quality of life and provides tools for improving public health policies in that region., Methods: A cross-sectional epidemiological study was performed using secondary mortality data collected from the Monte Negro municipality of the Brazilian Western Amazon from 2000 to 2011. These data were compared with data from similar municipalities in other Brazilian macro-regions. Data were obtained through the Departamento de Informática do Sistema Único de Saúde (DATASUS) information system., Results: The number of deaths reported over the study period was 606. The most common cause of death was external causes of morbidity and mortality [International Classification of Diseases (ICD)-10 chapter 20], followed by diseases of the circulatory system (ICD-10 chapter 9). Among the causes of death according to age group, infectious and parasitic diseases were the most common for 2- to 9-year-old children; external causes of disease were the most prevalent for 10- to 59-year-old people; and circulatory diseases prevailed in individuals over 60 years of age. Eleven percent of deaths were due to unknown causes., Conclusions: These results point to a fragility in the public policies for prevention and awareness of this problem. Infectious and parasitic diseases contribute only 4.5% of deaths, but had the third highest Disability-Adjusted Life Year score (1,190 days). Improving support to the Estratégia Saúde da Família (Family Health Strategy) program and implementing a death verification service would significantly aid in reducing the occurrence of non-transmissible chronic diseases and clarifying unknown causes of death.

In this study, we identified the phlebotomine sandfly vectors involved in the transmission of American Cutaneous Leishmaniasis (ACL) in Assis Brasil, Acre, Brazil, which is located on the Brazil-Peru-Bolivia frontier. The genotyping of Leishmania in phlebotomines was performed using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. A total of 6,850 sandflies comprising 67 species were captured by using CDC light traps in rural areas of the municipality. Three sandfly species were found in the state of Acre for the first time: Lutzomyia georgii, Lu. complexa and Lu. evangelistai. The predominant species was Lu. auraensis/Lu. ruifreitasi and Lu. davisi (total 59.27%). 32 of 368 pools were positive for the presence of Leishmania DNA (16 pools corresponding to Lu. davisi, and 16 corresponding to Lu. auraensis/Lu. ruifreitasi), with a minimal infection prevalence of 1.85% in Lu. davisi and 2.05% in Lu. auraensis/Lu. ruifreitasi. The Leishmania species found showed maximum identity with L. (Viannia) guyanensis and L. (V.) braziliensis in both phlebotomine species. Based on these results and similar scenarios previously described along the Brazil/Peru/Bolivia tri-border, the studied area must take into consideration the possibility of Lu. davisi and Lu. auraensis/Lu. ruifreitasi as probable vectors of ACL in this municipality.

Introduction: This paper reports, for the first time, the presence of Rhodnius stali in the state of Acre and in the Brazilian Amazon., Methods: Specimens of R. stali were collected by the Federal University of Acre in Rio Branco., Results: The number of Triatominae species in the State of Acre increased from five to six. This was also the first report of R. stali in the Brazilian Amazon., Conclusions: The occurrence of R. stali is worrisome, since this species has been found naturally infected by Trypanosoma cruzi and there has been evidence of its domiciliation capabilities.

Background: Until recently, Amblyomma cajennense (Fabricius, 1787) was considered to represent a single tick species in the New World. Recent studies have split this taxon into six species. While the A. cajennense species complex or A. cajennense (sensu lato) (s.l.) is currently represented by two species in Brazil, A. cajennense (sensu stricto) (s.s.) and Amblyomma sculptum Berlese, 1888, their geographical distribution is poorly known., Methods: The distribution of the A. cajennense (s.l.) in Brazil was determined by morphological examination of all lots of A. cajennense (s.l.) in two large tick collections of Brazil, and by collecting new material during three field expeditions in the possible transition areas between the distribution ranges of A. cajennense (s.s.) and A. sculptum. Phylogenetic analysis inferred from the ITS2 rRNA gene was used to validate morphological results. Morphological description of the nymphal stage of A. cajennense (s.s.) is provided based on laboratory-reared specimens., Results: From the tick collections, a total 12,512 adult ticks were examined and identified as 312 A. cajennense (s.s.), 6,252 A. sculptum and 5,948 A. cajennense (s.l.). A total of 1,746 ticks from 77 localities were collected during field expeditions, and were identified as 249 A. cajennense (s.s.), 443 A. sculptum, and 1,054 A. cajennense (s.l.) [these A. cajennense (s.l.) ticks were considered to be males of either A. cajennense (s.s.) or A. sculptum]. At least 23 localities contained the presence of both A. cajennense (s.s.) and A. sculptum in sympatry. DNA sequences of the ITS2 gene of 50 ticks from 30 localities confirmed the results of the morphological analyses. The nymph of A. cajennense (s.s.) is morphologically very similar to A. sculptum., Conclusion: Our results confirmed that A. cajennense (s.l.) is currently represented in Brazil by only two species, A. cajennense (s.s.) and A. sculptum. While these species have distinct distribution areas in the country, they are found in sympatry in some transition areas. The current distribution of A. cajennense (s.l.) has important implications to public health, since in Brazil A. sculptum is the most important vector of the bacterium Rickettsia rickettsii, the etiological agent of Brazilian spotted fever.

INTRODUCTION Mansonella ozzardi is a widely distributed filaria worm in the Amazon region. This study aimed to determine the prevalence of M. ozzardi infection in riverine communities of Lábrea municipality, Amazonas State, Brazil. METHODS A diagnostic blood filtration method in a polycarbonate membrane was used. RESULTS M. ozzardi was found in 50.3% of the sample, with the highest prevalence in farmers/fishermen (69.4%; χ 2 = -19.14, p<0.001). The prevalence was higher in longer-term residents (≥11 years; 60.2%). CONCLUSIONS M. ozzardi infection rates are high near the Purus River, much greater than those previously reported based on diagnosis using thick blood smears.

This study had the aim of ascertaining the sandfly fauna and possible presence of Leishmania in these insects, collected in caves in the state of Rondônia, Brazil. Collections were conducted in eight caves located in two different areas of this state. Leishmania in the sandflies collected was detected using the polymerase chain reaction (PCR). This was the first study on sandflies from caves in Rondônia and, among the total of 1,236 individuals collected, 24 species and 10 genera were identified. The species Evandromyia georgii was collected for the first time in Rondônia and the most abundant species were Trichophoromyia ubiquitalis with 448 individuals (36.2%), followed by T. octavioi with 283 (22.9%) and E. georgii with 179 (14.5%). For the PCR, 17 pools were analyzed and five pools were positive (forT. auraensis in three pools and for Nyssomyia shawi and N. antunesi in one pool each). The kDNA region was amplified and the presence of Leishmania DNA was confirmed. The sandfly fauna in these caves can be considered diverse in comparison with similar studies in other regions. It may be that some species use caves as a temporary shelter and breeding site, while other species live exclusively in this environment. The detection of Leishmania DNA indicates that this pathogen is circulating in cave environments and that further studies are needed in order to ascertain the risks of infection by leishmaniasis in these locations with high touristic potential.

Unlabelled: To evaluate the physicochemical characteristics of lyophilized bovine grafts manufactured on a semi-industrial scale (Orthogen; Baumer S/A*) in accordance with a protocol previously developed by the authors., Methods: The lyophilized bovine bone grafts were characterized by means of scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffractometry (XRD), thermogravimetric (TG) analysis, differential exploratory scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy., Results: Ca was the main component (60%) found in the samples, followed by P (28%) and O (5%). The mean (sd) pore size was 316 μm (146.7), ranging from 91.2 to 497.8 μm, and 333.5 μm (304.8), ranging from 87.2 to 963.9 μm, at 50x and 150x magnification, respectively. The hydroxyapatite peaks were at 26°C and 32°C, and mass losses were observed between 250°C and 640°C, corresponding to organic material and water. Two temperature transitions (45.67°C and 91.89°C) showed denaturation of type 1 collagen and dehydration of hydroxyapatite., Conclusion: The physicochemical assessment of lyophilized bovine bone grafts in accordance with the protocol developed at semi-industrial scale confirmed that this product presents excellent biocompatibility, with characteristics similar to natural bone.

Trichophoromyia ruifreitasi sp. n. is described as a new species of sand fly from the genus Trichophoromyia Barretto. This description is supported with illustrations and photographs that detail the morphological characteristics of male specimens collected in the municipality of Assis Brasil, Acre State, Brazilian Amazon. This species is similar to Trichophoromyia auraensis (Mangabeira), but the two species can be easily differentiated by the distribution of setae on their parameres, and by the presence of a dorsal lobe in the parameres of the new species.

Spectroscopic and chromatographic techniques can be used together to evaluate hydrocarbon inputs to coastal environments such as the Paranaguá estuarine system (PES), located in the SW Atlantic, Brazil. Historical inputs of aliphatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs) were analyzed using two sediment cores from the PES. The AHs were related to the presence of biogenic organic matter and degraded oil residues. The PAHs were associated with mixed sources. The highest hydrocarbon concentrations were related to oil spills, while relatively low levels could be attributed to the decrease in oil usage during the global oil crisis. The results of electron paramagnetic resonance were in agreement with the absolute AHs and PAHs concentrations measured by chromatographic techniques, while near-infrared spectroscopy results were consistent with unresolved complex mixture (UCM)/total n-alkanes ratios. These findings suggest that the use of a combination of techniques can increase the accuracy of assessment of contamination in sediments., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Mucosal leishmaniosis (ML) is a severe clinical form of leishmaniosis. Complex factors related to the parasite and the host are attributed to the development of mucosal lesions. Leishmania RNA virus 1 (LRV1) can disrupt immune response, and may be the main determinant of severity of the disease; it should be investigated., Objective: To study the existence of clinical differences between patients with ML with endosymbiosis by LRV1 and. those without it., Methods: A cross-sectional cohort study with clinical evaluation, polymerase chain reaction (PCR) detection of Leishmania, species classification, and search of LRV1 was performed. Only patients with confirmed diagnosis of ML by positive PCR and with nasal mucosa injuries were included in this analysis., Results: Out of 37 patients, 30 (81.1%) were diagnosed with Leishmania braziliensis, five (13.5%) with Leishmania guyanensis, and two (5.4%) with mixed infection of L. braziliensis and L. guyanensis. LVR1 virus was present in 26 (70.3%) of the cases., Conclusion: Correlation between clinical phenotype and presence of LRV1 was not observed, although the frequency of the virus is two-fold higher in mucosal lesions than that found in the literature on skin lesions in the same geographical area., (Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Background: In recent years there has been changes in the social and geographic profile of acquired immunodeficiency syndrome (AIDS). The aim of this study was to evaluate the internalization of AIDS in the state of Rondônia, Brazil., Findings: In Rondônia, 1473 AIDS cases were reported, with an average annual incidence of 15.8/100,000 persons (42.7 % women). The most common mode of viral transmission was sexual (96.5 %), and the majority of the individuals had not completed their primary education (64.8 %). There was heterogeneity in relation to case distribution, involving almost all of the municipalities in the state. The average annual mortality rate was 2.5/100,000 persons., Conclusion: Rondônia has a higher incidence of AIDS than the national average and the northern region. Efforts to provide access to treatment and follow-up of these individuals should be implemented, prioritizing areas where the incidence is higher and decentralizing the treatment of patients with AIDS in the state.

Introduction: This paper reports, for the first time, the presence of Rhodnius montenegrensis in the State of Acre, Brazil., Methods: Two female R. montenegrensis were collected in a dwelling in the rural area of Rio Branco, Acre, Brazil., Results: The occurrence of this species was confirmed, and the number of Triatominae species in the State of Acre increased from four to five., Conclusions: Further studies should be performed to reach a clearer understanding of the ecology of this arthropod, its possible role in transmitting Chagas' disease and rangeliosis, and its current geographical distribution in the region.

Introduction: The use of the Self-Image Form (SIF) expands the identification of active leprosy cases to neighbors of index cases., Methods: The SIF was used to screen two groups: case (neighbors of index cases of leprosy) and control (individuals residing next to houses without leprosy) group. A specialist investigated suspected leprosy cases for disease confirmation., Results: New cases of leprosy were diagnosed in the case group (n = 7, 8.6%), but not the control group., Conclusions: The new surveillance strategy is inexpensive, efficient, and feasible within a primary health strategy. Future studies can help improve the use of the SIF.

Introduction: Toxoplasma gondii infection is widely prevalent in humans and other animals worldwide. Information on the prevalence of T. gondii infection is scarce in some regions of Brazil, including riverside communities along the Amazon River basin., M Methods: The prevalence of T. gondii in 231 people, aged 1-85 years, who were living in four riverside communities along the Purus River, Lábrea, State of Amazonas, Brazil, was determined. Antibodies against T. gondii were assayed using a commercial enzyme-linked immunosorbent assay (ELISA) kit. The hearts and brains of 50 chickens, which were raised free-range in the communities, were pooled according to the community of origin and bioassayed in mice. The isolates were genotyped using polymorphisms at 12 nuclear markers (SAG1, 5' and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3)., Results: The overall seroprevalence of T. gondii was 56.7% (131/231). IgG antibodies were presented by 117 (89.3%) and IgM by 14 (10.7%) of the 131 positive individuals. No association between age group and gender with prevalence was observed (chi-square test, p > 0.05); however, the comparison between localities showed that the seroprevalence of T. gondii was significantly lower among the individuals living in the Boca do Ituxi (p < 0.05) community. Five isolates of T. gondii were obtained in the mouse bioassay, and genotyping revealed two complete genotypes that had not been described previously and three mixed isolates., Conclusions: These results support previous findings that T. gondii population genetics are highly diverse in Brazil and that T. gondii infection is active in these riverside communities.

Vast amounts of bioactivity data have been generated for small molecules across public and corporate domains. Biological signatures, either derived from systematic profiling efforts or from existing historical assay data, have been successfully employed for small molecule mechanism-of-action elucidation, drug repositioning, hit expansion and screening subset design. This article reviews different types of biological descriptors and applications, and we demonstrate how biological data can outlive the original purpose or project for which it was generated. By comparing 150 HTS campaigns run at Novartis over the past decade on the basis of their active and inactive chemical matter, we highlight the opportunities and challenges associated with cross-project learning in drug discovery., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The progressive aggregation of Amyloid-β (Aβ) in the brain is a major trait of Alzheimer's Disease (AD). Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP). Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A) recently implicated with AD through genome wide association studies (GWAS) and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.

Background: The Amazon is one of the regions who have the highest rates of infection by the hepatitis B virus in the world. Objectives This study aimed to evaluate the epidemiological data and spatial distribution of hepatitis B cases reported between 2002 and 2012 in the Brazilian State of Rondônia., Methods: Social and clinical data of these individuals were studied through the Information System for Notifiable Diseases (SINAN), including the following variables: gender, age group, vaccination, contact with a known patient with HBV, exposure to risk factors, source of infection, and clinical status., Results: There were 7,132 cases reported in Rondônia, with an average incidence rate of 42/100,000 inhabitants per year. The municipalities with the highest incidence rates were Monte Negro (187.6/100,000 inhabitants) and Ariquemes (157.2/100,000 inhabitants). The 20-39 year-old age group had the highest number of cases (n = 3,834), and 69.9% of patients were likely infected via sexual contact. Regarding the clinical disease status, most of the patients (80.7%) were in the chronic phase., Conclusions: There was a recent 402% increase in the diagnosis of hepatitis B, which is likely owing to the improvements in the public diagnostic system. This highlights the need for public policies to prevent and control the disease.

This study aims to analyze factors associated with sick leave rates among workers in the meat, fish, and seafood industries in Brazil. The study analyzed all sick leave benefits granted by the country's social security system to workers in these industries in 2008. Incidence of sick leave per 10 thousand jobs was stratified by sex, age, diagnosis, job position, State, and nature and length of benefits. The study analyzed 31,913 sick leaves, with an annual incidence of 788.7. Meat processing and packaging showed the highest incidence, and fish and seafood processing and packaging showed the longest mean length of sick leave. Women showed a higher sick leave incidence, while men received longer average sick leaves. Injuries, musculoskeletal disorders, and mental disorders accounted for 67.2% of sick leaves. The most common diagnoses were lower back pain, first-trimester bleeding in pregnancy, and depression. The data suggest poor job protection and adverse working conditions in these industries.

Introduction: Hepatic capillariosis, caused by Capillaria hepatica (Calodium hepaticum) (Bancroft, 1893), Travassos, 1915 (Nematoda, Trichinelloidea, Capillariidae), is a common zoonosis in rodents but is rare in humans. Seventy-two cases in humans have been reported worldwide since the first case was described by MACARTHUR in 192417,27. This study aimed to determine the prevalence of Capillaria hepatica in humans and rodents in an urban area of Porto Velho, the capital of Rondônia, in Brazil., Methods: After conducting a census of the area, 490 residents were randomly selected, and, after signing a term of consent, provided blood samples that were screened for anti-Capillaria hepatica antibodies. Simultaneously, rats were captured to assess the prevalence of this parasite in rodents by histopathological examination in liver sections., Results: A prevalence of 1.8% was found among residents who had specific antibodies at a dilution of 1:150, indicating exposure to parasite eggs; 0.8% of the subjects also had positive titers at a dilution of 1:400, indicating true infection. The prevalence in rats was 2%., Conclusions: The prevalence of infection with this parasite among humans and rats was low. While the prevalence encountered among humans was within the limits reported in the literature, the prevalence among rodents was much lower.

Mosquito nets treated with long-lasting insecticide (LLINs), when used in compliance with guidelines of the World Health Organization, may be effective for malaria vector control. In 2012, approximately 150,000 LLINs were installed in nine municipalities in the state of Rondônia. However, no studies have assessed their impact on the reduction of malaria incidence. This study analyzed secondary data of malaria incidence, in order to assess the impact of LLINs on the annual parasite incidence (API). The results showed no statistically significant differences in API one year after LLIN installation when compared to municipalities without LLINs. The adoption of measures for malaria vector control should be associated with epidemiological studies and evaluations of their use and efficiency, with the aim of offering convincing advantages that justify their implementation and limit malaria infection in the Amazon Region.

Objective: Riverine communities in Rondônia State are exposed to high selenium (Se) content in their diet because of the high-selenium soils identified in the Amazon. However, the Amazonian population has a high mercury (Hg) exposure because this metal accumulates in the soil. Because children are more vulnerable to Hg toxicity, the aim of this study was to evaluate and correlate Se status and hair Hg levels in riverine children (aged 3-9 y) living in two different locations in Rondônia State: Demarcação area (DA) and Gleba do Rio Preto (GRP)., Methods: Se levels were assessed using hydride generation quartz tube atomic absorption spectroscopy; total hair Hg levels were assessed using cold vapor atomic absorption spectrometry. Dietary intake was evaluated through a 24-h food record and a food frequency questionnaire., Results: Forty-two children participated in this study. Eighty-four percent of the children from DA showed low plasma Se. Conversely, all children from GRP presented plasma Se levels above the reference values. Forty-five percent of the children from DA presented low erythrocyte levels, and 55% of the children from GRP showed concentration in erythrocyte above the reference values. The mean Se intake was 41.8 μg/d in DA and 179.0 μg/d in GRP. High hair Hg levels were observed in children from both the DA and GRP (3.57 ± 1.86 and 6.24 ± 5.89, respectively)., Conclusions: Children from both riverine communities are likely to present altered Se status according to their dietary intake. Additionally, these children are highly exposed to Hg, mainly through fish consumption, and the toxicity of this metal may cause metabolic damage., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Blood samples were collected from 99 domestic dogs from the urban and rural areas of the Lábrea municipality, state of Amazonas, Brazil. Canine serum samples were tested by immunofluorescence assay against Rickettsia spp., which revealed that only 3.0% (1/33) and 7.6% (5/66) of the dogs from urban and rural areas, respectively, reacted positively to at least one Rickettsia species. DNA was extracted from canine blood and tested by a battery of PCR assays targeting protozoa of the genera Babesia and Hepatozoon, and bacteria of the genera Rickettsia and Ehrlichia and family Anaplasmataceae. All samples were negative in the PCR assays targeting the genera Babesia, Hepatozoon, Ehrlichia and Rickettsia. For Anaplasmataceae, 3% (1/33) and 39.4% (26/66) of the urban and rural dogs, respectively, yielded amplicons that generated DNA sequences 100% identical to the corresponding sequence of Wolbachia endosymbiont of Dirofilaria immitis. Because of these results, all canine DNA samples were further tested in a PCR assay targeting filarial nematodes, which was positive for 18.2% (6/33) and 57.6% (38/66) urban and rural dogs, respectively. Filarial-PCR products generated DNA sequences 100% identical to D. immitis. While tick-borne infections were rare in Lábrea, D. immitis infection rates were among the highest reported in South America.

Introduction: Malaria is one of the major parasitic diseases in the State of Rondônia, located in the western Brazilian Amazon. The basic treatment scheme for this disease is chloroquine and primaquine. This study evaluated the epidemiological profile of malaria in Rondônia between 2008 and 2012., Methodology: The epidemiological data were provided by the Health Surveillance Agency from the State of Rondônia, and socioeconomic indicators were obtained from the Brazilian Institute of Geography and Statistics, Department of Informatics of the Unified Health System, and from the National Institute for Space Research. The analyzed variables included year of diagnosis, gender, age group, main activity performed in the 15 days previous to the diagnosis, parasite species, level of parasitemia, number of relapse/recrudescence cases, and socioeconomic and environmental data for Rondônia., Results: A total of 238,626 cases of malaria were recorded in Rondônia during the study period. Of this total, 65.6% were men and the most prevalent age group was 20-39 years. Plasmodium vivax was the most common parasite (89.8%), followed by Plasmodium   falciparum (9.4%). An average of 30.9% of the individuals who were tested presented with relapse/recrudescence malaria. The API value was highest in 2008 and lowest in 2012, corresponding to 42.3 cases and 19.2 cases per 1,000 inhabitants, respectively., Conclusions: A 58% reduction in the number of malaria cases and a 36.2% reduction in the number of relapse/recrudescence malaria cases were observed, due to increases in the economy, improvements in the health system, and reduction of deforestation in this region.

Background/objectives: Mucosal leishmaniasis (ML) is a progressive disease that affects cartilage and bone structures of the nose and other upper respiratory tract structures. Complications associated with ML have been described, but there is a lack of studies that evaluate the structural changes of the nose and paranasal sinuses in ML using radiological methods. In this study, we aimed to assess the opacification of the paranasal sinuses in patients with treated ML and any anatomical changes in the face associated with ML using multidetector computed tomography scans (MDCT) of the sinuses. We compared the findings with a control group., Methodology/principal Findings: We evaluated 54 patients with treated ML who underwent CT scans of the sinuses and compared them with a control group of 40 patients who underwent orbital CT scans. The degree of sinus disease was assessed according to the Lund-Mackay criteria. Forty of the 54 patients with a history of ML (74.1%) had a tomographic score compatible with chronic sinusitis (Lund-Mackay ≥4). CT scans in the leishmaniasis and control groups demonstrated significant differences in terms of facial structure alterations. Patients from the ML group showed more severe levels of partial opacification and pansinus mucosal thickening (42.6%) and a greater severity of total opacification. Patients from the ML group with a Lund-Mackay score ≥4 presented longer durations of disease before treatment and more severe presentations of the disease at diagnosis., Conclusion/significance: CT scans of the sinuses of patients with ML presented several structural alterations, revealing a prominent destructive feature of the disease. The higher prevalence in this study of chronic rhinosinusitis observed in CT scans of patients with treated ML than in those of the control group suggests that ML can be considered a risk factor for chronic rhinosinusitis in this population (p<0.05).

The wealth of bioactivity information now available on low-molecular weight compounds has enabled a paradigm shift in chemical biology and early phase drug discovery efforts. Traditionally chemical libraries have been most commonly employed in screening approaches where a bioassay is used to characterize a chemical library in a random search for active samples. However, robust curating of bioassay data, establishment of ontologies enabling mining of large chemical biology datasets, and a wealth of public chemical biology information has made possible the establishment of highly annotated compound collections. Such annotated chemical libraries can now be used to build a pathway/target hypothesis and have led to a new view where chemical libraries are used to characterize a bioassay. In this article we discuss the types of compounds in these annotated libraries composed of tools, probes, and drugs. As well, we provide rationale and a few examples for how such libraries can enable phenotypic/forward chemical genomic approaches. As with any approach, there are several pitfalls that need to be considered and we also outline some strategies to avoid these.