Dengue Virus Serotype 1 Effects on Mosquito Survival Differ among Geographically Distinct Aedes aegypti Populations.

The mosquito Aedes aegypti is distributed worldwide and is recognized as the primary vector for dengue in numerous countries. To investigate whether the fitness cost of a single DENV-1 isolate varies among populations, we selected four Ae. aegypti populations from distinct localities: Australia (AUS), Brazil (BRA), Pakistan (PAK), and Peru (PER). Utilizing simple methodologies, we concurrently assessed survival rates and fecundity. Overall, DENV-1 infection led to a significant decrease in mosquito survival rates, with the exception of the PER population. Furthermore, infected Ae. aegypti from PAK, the population with the lowest infection rate among those tested, exhibited a noteworthy reduction in egg laying. These findings collectively suggest that local mosquito-virus adaptations may influence dengue transmission in endemic settings.

Multi-trait index: selection and recommendation of superior black bean genotypes as new improved varieties.

Common bean provides diet rich in vitamins, fiber, minerals, and protein, which could contribute into food security of needy populations in many countries. Developing genotypes that associate favorable agronomic and grain quality traits in the common bean crop could increase the chances of adopting new cultivars black bean. In this context, the present study aimed at selection of superior black bean lines using multi-variate indexes, Smith-Hazel-index, and genotype by yield*trait biplot analysis. These trials were conducted in Campos dos Goytacazes - RJ, in 2020 and 2021. The experimental design used was randomized blocks, with 28 treatments and three replications. The experimental unit consisted of four rows 4.0 m long, spaced at 0.50 m apart, with a sowing density of 15 seeds per meter. The two central rows were used for the evaluations. The selection of superior genotypes was conducted using the multiple trait stability index (MTSI), multi-trait genotype-ideotype distance index (MGIDI), multi-trait index based on factor analysis and genotype-ideotype distance (FAI-BLUP), Smith-Hazel index, and Genotype by Yield*Trait Biplot (GYT). The multivariate indexes efficiently selected the best black bean genotypes, presenting desirable selection gains for most traits. The use of multivariate indexes and GYT enable the selection of early genotypes with higher grain yields. These lines G9, G13, G17, G23, and G27 were selected based on their performance for multiple traits closest to the ideotype and could be recommended as new varieties.

Detection of Pathogenic Leptospira in Captive Chelonians (Kinosternon scorpioides-Linnaeus, 1766) in the Brazilian Amazon.

Leptospirosis is a zoonosis of great importance for One Health. In this context, the Amazonian biome may harbor numerous hosts for Leptospira spp. that contribute to the maintenance of the pathogen in the environment. Some reptiles, such as chelonians, have been little studied in terms of their involvement with leptospires. The objective of this study was to detect Leptospira spp. DNA in Kinosternon scorpioides turtles kept in captivity in a region of the Brazilian Amazon. A total of 147 samples of blood (n = 40), cloacal fluid (n = 27), cloacal lavage (n = 40), and stomach (n = 40) were collected from 40 chelonians. After DNA extraction, the samples were subjected to amplification of a 331 base pair product of the 16S rRNA gene using the Lep1 and Lep2 primers. PCR products were Sanger sequenced, assembled, and subjected to online blast search and phylogenetic analysis. Of the animals tested, 40% (16/40, 95% confidence interval [CI]: 25-55) had at least one or two samples positive for Leptospira spp. Considering the total number of samples collected, 12.93% (19/147) were positive, being blood clots (27.5%; 11/40), followed by cloacal washings (10%; 4/40), cloacal fluid (11.11%; 3/27) and gastric washings (2.5%; 1/40). Of these, 11 samples were sequenced and showed 99% to 100% identity with Leptospira interrogans sequences, which was confirmed by phylogenetic analysis. This is the first study to detect pathogenic Leptospira DNA in chelonians in a region of the Brazilian Amazon. It has been concluded that K. scorpioides turtles in captivity have been exposed to pathogenic Leptospira.

Spatial analysis of dengue transmission in an endemic city in Brazil reveals high spatial structuring on local dengue transmission dynamics.

In the last decades, dengue has become one of the most widespread mosquito-borne arboviruses in the world, with an increasing incidence in tropical and temperate regions. The mosquito Aedes aegypti is the dengue primary vector and is more abundant in highly urbanized areas. Traditional vector control methods have showing limited efficacy in sustaining mosquito population at low levels to prevent dengue virus outbreaks. Considering disease transmission is not evenly distributed in the territory, one perspective to enhance vector control efficacy relies on identifying the areas that concentrate arbovirus transmission within an endemic city, i.e., the hotspots. Herein, we used a 13-month timescale during the SARS-Cov-2 pandemic and its forced reduction in human mobility and social isolation to investigate the spatiotemporal association between dengue transmission in children and entomological indexes based on adult Ae. aegypti trapping. Dengue cases and the indexes Trap Positive Index (TPI) and Adult Density Index (ADI) varied seasonally, as expected: more than 51% of cases were notified on the first 2 months of the study, and higher infestation was observed in warmer months. The Moran's Eigenvector Maps (MEM) and Generalized Linear Models (GLM) revealed a strong large-scale spatial structuring in the positive dengue cases, with an unexpected negative correlation between dengue transmission and ADI. Overall, the global model and the purely spatial model presented a better fit to data. Our results show high spatial structure and low correlation between entomological and epidemiological data in Foz do Iguaçu dengue transmission dynamics, suggesting the role of human mobility might be overestimated and that other factors not evaluated herein could be playing a significant role in governing dengue transmission.

Wolbachia strains wMel and wAlbB differentially affect Aedes aegypti traits related to fecundity.

Two Wolbachia strains, wMel and wAlbB, have been transinfected into Aedes aegypti mosquitoes for population replacement with the aim of reducing dengue transmission. Epidemiological data from various endemic sites suggest a pronounced decrease in dengue transmission after implementing this strategy. In this study, we investigated the impact of the Wolbachia strains wMel and wAlbB on Ae. aegypti fitness in a common genetic background. We found that Ae. aegypti females infected with the wMel strain exhibited several significant differences compared with those infected with the wAlbB strain. Specifically, wMel-infected females laid significantly fewer eggs, ingested a lower amount of blood, had a reduced egg production rate, and exhibited a decreased Wolbachia density at a later age compared with mosquitoes infected with the wAlbB strain. Conversely, the wAlbB strain showed only mild negative effects when compared with Wolbachia-uninfected specimens. These differential effects on Ae. aegypti fitness following infection with either wMel or wAlbB may have important implications for the success of population replacement strategies in invading native Ae. aegypti populations in endemic settings. Further research is needed to better understand the underlying mechanisms responsible for these differences in fitness effects and their potential impact on the long-term efficacy of Wolbachia-based dengue control programs.IMPORTANCEThe transmission of arboviruses such as dengue, Zika, and chikungunya is on the rise globally. Among the most promising strategies to reduce arbovirus burden is the release of one out of two strains of Wolbachia-infected Aedes aegypti: wMel and wAlbB. One critical aspect of whether this approach will succeed involves the fitness cost of either Wolbachia strains on mosquito life history traits. For instance, we found that wMel-infected Ae. aegypti females laid significantly fewer eggs, ingested a lower amount of blood, had a reduced egg production rate, and exhibited a decreased Wolbachia density at a later age compared with mosquitoes infected with the wAlbB strain. Conversely, the wAlbB strain showed only mild negative effects when compared with Wolbachia-uninfected specimens. These differential effects on mosquito fitness following infection with either wMel or wAlbB may have important implications for the success of population replacement strategies in invading native Ae. aegypti populations.

Illustrated identification key to females of the genus Sabethes Robineau-Desvoidy recorded from Brazil (Diptera: Culicidae), in dichotomous and interactive formats, including an updated list of species and new records for the states.

Female mosquitoes of the genus Sabethes Robineau-Desvoidy, 1827 are implicated in the transmission of several arboviruses, including yellow fever virus. Here, we present an illustrated species identification key for females of the genus Sabethes recorded in Brazil, except Sa. nitidus Theobald, 1901 and Sa. harbachi Nascimento-Pereira, Guimares, Loureno-de-Oliveira & Motta, 2021 as only the males of these species are known. The key is available in dichotomous and interactive formats. An updated list of the Sabethes species of Brazil and new occurrence records for the states of the country are provided. The type localities of four speciesSa. glaucodaemon (Dyar & Shannon, 1925), Sa. amazonicus Gordon & Evans, 1922, Sa. belisarioi Neiva, 1908 and Sa. soperi Lane & Cerqueira, 1942are corrected or restricted.

Optimising the surveillance of Aedes aegypti in Brazil by selecting smaller representative areas within an endemic city.

OBJECTIVES: Arboviruses, such as dengue (DENV), zika (ZIKV), and chikungunya (CHIKV), constitute a growing urban public health threat. Focusing on Aedes aegypti mosquitoes, their primary vectors, is crucial for mitigation. While traditional immature-stage mosquito surveillance has limitations, capturing adult mosquitoes through traps yields more accurate data on disease transmission. However, deploying traps presents logistical and financial challenges, demonstrating effective temporal predictions but lacking spatial accuracy. Our goal is to identify smaller representative areas within cities to enhance the early warning system for DENV outbreaks. METHODS: We created Sentinel Geographic Units (SGUs), smaller areas of 1 km2 within each stratum, larger areas, with the aim of aligning the Trap Positivity Index (TPI) and Adult Density Index (ADI) with their respective strata. We conducted a two-step evaluation of SGUs. First, we examined the equivalence of TPI and ADI between SGUs and strata from January 2017 to July 2022. Second, we assessed the ability of SGU's TPI and ADI to predict DENV outbreaks in comparison to Foz do Iguaçu's Early-Warning System, which forecasts outbreaks up to 4 weeks ahead. Spatial and temporal analyses were carried out, including data interpolation and model selection based on Akaike information criteria (AIC). RESULTS: Entomological indicators produced in small SGUs can effectively replace larger sentinel areas to access dengue outbreaks. Based on historical data, the best predictive capability is achieved 2 weeks after infestation verification. Implementing the SGU strategy with more frequent sampling can provide more precise space-time estimates and enhance dengue control. CONCLUSIONS: The implementation of SGUs offers an efficient way to monitor mosquito populations, reducing the need for extensive resources. This approach has the potential to improve dengue transmission management and enhance the public health response in endemic cities.

DENV-1 Titer Impacts Viral Blocking in wMel Aedes aegypti with Brazilian Genetic Background.

Several countries have been using Wolbachia deployments to replace highly competent native Aedes aegypti populations with Wolbachia-carrying mosquitoes with lower susceptibility to arboviruses such as dengue, Zika, and chikungunya. In Rio de Janeiro, Wolbachia deployments started in 2015 and still present a moderate introgression with a modest reduction in dengue cases in humans (38%). Here, we evaluated the vector competence of wild-type and wMel-infected Ae. aegypti with a Brazilian genetic background to investigate whether virus leakage could contribute to the observed outcomes in Brazil. We collected the specimens in three areas of Rio de Janeiro with distinct frequencies of mosquitoes with wMel strain and two areas with wild Ae. aegypti. The mosquitoes were orally exposed to two titers of DENV-1 and the saliva of DENV-1-infected Ae. aegypti was microinjected into wMel-free mosquitoes to check their infectivity. When infected with the high DENV-1 titer, the presence of wMel did not avoid viral infection in mosquitoes' bodies and saliva but DENV-1-infected wMel mosquitoes produced lower viral loads than wMel-free mosquitoes. On the other hand, wMel mosquitoes infected with the low DENV-1 titer were less susceptible to virus infection than wMel-free mosquitoes, although once infected, wMel and wMel-free mosquitoes exhibited similar viral loads in the body and the saliva. Our results showed viral leakage in 60% of the saliva of wMel mosquitoes with Brazilian background; thus, sustained surveillance is imperative to monitor the presence of other circulating DENV-1 strains capable of overcoming the Wolbachia blocking phenotype, enabling timely implementation of action plans.

Age, sex, and mating status discrimination in the sand fly Lutzomyia longipalpis using near infra-red spectroscopy (NIRS).

BACKGROUND: Understanding aspects related to the physiology and capacity of vectors is essential for effectively controlling vector-borne diseases. The sand fly Lutzomyia longipalpis has great importance in medical entomology for disseminating Leishmania parasites, the causative agent of Leishmaniasis, one of the main neglected diseases listed by the World Health Organization (WHO). In this respect, it is necessary to evaluate the transmission potential of this species and the success of vector control interventions. Near-infrared spectroscopy (NIRS) has been used to estimate the age of mosquitoes in different conditions (laboratory, semi-field, and conservation), taxonomic analysis, and infection detection. However, no studies are using NIRS for sand flies. METHODS: In this study, we developed analytic models to estimate the age of L. longipalpis adults under laboratory conditions, identify their copulation state, and evaluate their gonotrophic cycle and diet. RESULTS: Sand flies were classified with an accuracy of 58-82% in 3 age groups and 82-92% when separating them into young (<8 days) or old (>8 days) insects. The classification between mated and non-mated sandflies was 98-100% accurate, while the percentage of hits of females that had already passed the first gonotrophic cycle was only 59%. CONCLUSIONS: We consider the age and copula estimation results very promising, as they provide essential aspects of vector capacity assessment, which can be obtained quickly and at a lower cost with NIRS.

Blood meals from 'dead-end' vertebrate hosts enhance transmission potential of malaria-infected mosquitoes.

Ingestion of an additional blood meal(s) by a hematophagic insect can accelerate development of several vector-borne parasites and pathogens. Most studies, however, offer blood from the same vertebrate host species as the original challenge (for e.g., human for primary and additional blood meals). Here, we show a second blood meal from bovine and canine hosts can also enhance sporozoite migration in Anopheles stephensi mosquitoes infected with the human- and rodent-restricted Plasmodium falciparum and P. berghei, respectively. The extrinsic incubation period (time to sporozoite appearance in salivary glands) showed more consistent reductions with blood from human and bovine donors than canine blood, although the latter's effect may be confounded by the toxicity, albeit non-specific, associated with the anticoagulant used to collect whole blood from donors. The complex patterns of enhancement highlight the limitations of a laboratory system but are nonetheless reminiscent of parasite host-specificity and mosquito adaptations, and the genetic predisposition of An. stephensi for bovine blood. We suggest that in natural settings, a blood meal from any vertebrate host could accentuate the risk of human infections by P. falciparum: targeting vectors that also feed on animals, via endectocides for instance, may reduce the number of malaria-infected mosquitoes and thus directly lower residual transmission. Since endectocides also benefit animal health, our results underscore the utility of the One Health framework, which postulates that human health and well-being is interconnected with that of animals. We posit this framework will be further validated if our observations also apply to other vector-borne diseases which together are responsible for some of the highest rates of morbidity and mortality in socio-economically disadvantaged populations.

Two year follow-up of distal unruptured intracranial aneurysms treated with a surface modified flow diverter under prasugrel monotherapy.

BACKGROUND: A new generation of modified surface flow diverters (FDs) and monotherapy using new antiplatelets may reduce both ischemic and hemorrhagic complications during the treatment of intracranial aneurysms. Previous preliminary safety analysis of distal unruptured intracranial aneurysms treated with the FD p48 MW HPC (phenox-Wallaby, Bochum, Germany) under antiplatelet monotherapy with prasugrel showed promising results. However, the long term outcomes of distal intracranial aneurysms treated with FDs under antiplatelet monotherapy are not known. METHODS: This was a single center, prospective, pivotal, open single arm study. The primary (safety) endpoint was absence of any new neurological deficits after treatment until the 24 month follow-up. The primary (efficacy) endpoint was the incidence of complete aneurysm occlusion 24 months after treatment. The secondary (efficacy) endpoints were any incidence of aneurysm dome reduction 24 months after treatment. RESULTS: 21 patients harboring 27 distal aneurysms of the anterior circulation were included. No patient had neurologic deficits in the time from treatment to the 24 month follow-up. Complete aneurysm occlusion occurred in 20 (74%) of 27 aneurysms at the 24 month follow-up. Four aneurysms (14.8%) had dome reduction, and three aneurysms (11.1%) remained unchanged. CONCLUSIONS: In this pilot trial, treatment of distal unruptured intracranial aneurysms with an FD under monotherapy with prasugrel, followed by monotherapy with aspirin, appeared to be safe and effective. Randomized studies with long term follow-up are needed to confirm these results.

Climatic seasons and time of the day influence thermoregulation and testicular hemodynamics in Santa Inês rams raised under humid tropical conditions.

This study evaluated the possible association between the diurnal variations of climatic factors during the rainy (RS) or less rainy (LS) seasons on the testicular hemodynamics and thermoregulatory responses of hair sheep rams raised in a humid tropical climate. Santa Inês rams (n = 6) underwent evaluation of general and testicular physiological parameters (heart and respiratory rates, internal and scrotal temperatures, internal-scrotal temperature gradient, scrotal distention, and color Doppler ultrasound evaluation of the spermatic cords and spectral analyses of testicular arteries) over six consecutive weeks per season at three separate times daily (morning = 8:00 a.m., noon = 12:00 p.m., and afternoon = 5:00 p.m.) during the RS and LS. Climatic air temperature and relative humidity data were recorded, and the temperature and humidity index (THI) was calculated. Higher thermal challenge was observed in LS relative to RS (air temperature = 28.0 vs. 30.9 °C; relative humidity = 84.1 vs. 69.9%; THI = 80.0 vs. 82.5; P < 0.05). In both seasons, respiratory rate and internal temperature were normal, demonstrating the animals' adaptability. In RS, however, a higher scrotal temperature was recorded in relation to LS (35.0 vs. 34.7 °C; P < 0.05), with a gradual increase from morning to afternoon. Lower resistivity (0.40 vs. 0.64; P < 0.05) and pulsatility (0.55 vs. 1.14; P < 0.05) indices, and a higher rate of high-velocity blood flow of testicular arteries (71.1 vs. 60.6%; P < 0.05) were observed in RS compared to LS. The lowest correlations between testicular hemodynamic, physiological variables, and environmental parameters (P < 0.05) were observed in the morning. In conclusion, testicular thermoregulation and testicular hemodynamics were influenced by the climatic seasons and time of the day, being more efficient in the LS season and with less interference from environmental factors in the morning.

Aedes aegypti oviposition-sites choice under semi-field conditions.

Vector control is still the recommended approach to avoid arbovirus outbreaks. Herein, we investigate oviposition preferences of Aedes aegypti (Diptera: Culicidae) females under a semi-field structure Rio de Janeiro, Brazil. For that, in Experiment 1, we used two settings: 'Single items', which included as containers drain, beer bottle, bucket, car tyre, water tank, and a potted Peace Lily (Spathiphyllum wallisii) in a saucer with water, or 'Multiple containers', as an urban simulation, in which one drain, two additional beer bottles, and an extra plant pot saucer were added. Experiment 2 (sensory cues) used five variations of potted plant, each one varying in the range of sensory cues known to attract gravid females to oviposition containers. Our results indicate that gravid Ae. aegypti prefer to oviposit close to the ground and in open water containers with organic compounds from plant watering. Domestic large artificial containers containing tap water received significantly fewer eggs, except for the car tyre, which exhibited as many eggs as the potted plant. We also show that visual (potted plant shape) and olfactory clues (odour of the plant or from water containing organic matter) were equally attractive separately as were these stimuli together.

Gut Bacterial Diversity of Field and Laboratory-Reared Aedes albopictus Populations of Rio de Janeiro, Brazil.

BACKGROUND: The mosquito microbiota impacts different parameters in host biology, such as development, metabolism, immune response and vector competence to pathogens. As the environment is an important source of acquisition of host associate microbes, we described the microbiota and the vector competence to Zika virus (ZIKV) of Aedes albopictus from three areas with distinct landscapes. METHODS: Adult females were collected during two different seasons, while eggs were used to rear F1 colonies. Midgut bacterial communities were described in field and F1 mosquitoes as well as in insects from a laboratory colony (>30 generations, LAB) using 16S rRNA gene sequencing. F1 mosquitoes were infected with ZIKV to determine virus infection rates (IRs) and dissemination rates (DRs). Collection season significantly affected the bacterial microbiota diversity and composition, e.g., diversity levels decreased from the wet to the dry season. Field-collected and LAB mosquitoes' microbiota had similar diversity levels, which were higher compared to F1 mosquitoes. However, the gut microbiota composition of field mosquitoes was distinct from that of laboratory-reared mosquitoes (LAB and F1), regardless of the collection season and location. A possible negative correlation was detected between Acetobacteraceae and Wolbachia, with the former dominating the gut microbiota of F1 Ae. albopictus, while the latter was absent/undetectable. Furthermore, we detected significant differences in infection and dissemination rates (but not in the viral load) between the mosquito populations, but it does not seem to be related to gut microbiota composition, as it was similar between F1 mosquitoes regardless of their population. CONCLUSIONS: Our results indicate that the environment and the collection season play a significant role in shaping mosquitoes' bacterial microbiota.

Dengue Exposure and Wolbachia wMel Strain Affects the Fertility of Quiescent Eggs of Aedes aegypti.

(1) Background: The deployment of the bacterium Wolbachia to reduce arbovirus transmission is ongoing in several countries worldwide. When Wolbachia-carrying Aedes aegypti are released and established in the field, females may feed on dengue-infected hosts. The effects of simultaneous exposure on life-history traits of Ae. aegypti to Wolbachia wMel strain and dengue-1 virus DENV-1 remain unclear. (2) Methods: We monitored 4 groups (mosquitoes with either DENV-1 or Wolbachia, coinfected with DENV-1 and Wolbachia, as well as negative controls) to estimate Ae. aegypti survival, oviposition success, fecundity, collapsing and fertility of quiescent eggs for 12 weeks. (3) Results: Neither DENV-1 nor Wolbachia had a significant impact on mosquito survival nor on mosquito fecundity, although the last parameter showed a tendency to decrease with ageing. There was a significant decrease in oviposition success in individuals carrying Wolbachia. Wolbachia infection and storage time significantly increased egg collapse parameter on the egg viability assay, while DENV-1 had a slight protective effect on the first four weeks of storage. (4) Conclusions: Despite limitations, our results contribute to better understanding of the tripartite interaction of virus, bacteria and mosquito that may take place in field conditions and aid in guaranteeing the Wolbachia strategy success.

Egg-laying by female Aedes aegypti shapes the bacterial communities of breeding sites.

BACKGROUND: Aedes aegypti, the main arboviral mosquito vector, is attracted to human dwellings and makes use of human-generated breeding sites. Past research has shown that bacterial communities associated with such sites undergo compositional shifts as larvae develop and that exposure to different bacteria during larval stages can have an impact on mosquito development and life-history traits. Based on these facts, we hypothesized that female Ae. aegypti shape the bacteria communities of breeding sites during oviposition as a form of niche construction to favor offspring fitness. RESULTS: To test this hypothesis, we first verified that gravid females can act as mechanical vectors of bacteria. We then elaborated an experimental scheme to test the impact of oviposition on breeding site microbiota. Five different groups of experimental breeding sites were set up with a sterile aqueous solution of larval food, and subsequently exposed to (1) the environment alone, (2) surface-sterilized eggs, (3) unsterilized eggs, (4) a non-egg laying female, or (5) oviposition by a gravid female. The microbiota of these differently treated sites was assessed by amplicon-oriented DNA sequencing once the larvae from the sites with eggs had completed development and formed pupae. Microbial ecology analyses revealed significant differences between the five treatments in terms of diversity. In particular, between-treatment shifts in abundance profiles were detected, showing that females induce a significant decrease in microbial alpha diversity through oviposition. In addition, indicator species analysis pinpointed bacterial taxa with significant predicting values and fidelity coefficients for the samples in which single females laid eggs. Furthermore, we provide evidence regarding how one of these indicator taxa, Elizabethkingia, exerts a positive effect on the development and fitness of mosquito larvae. CONCLUSIONS: Ovipositing females impact the composition of the microbial community associated with a breeding site, promoting certain bacterial taxa over those prevailing in the environment. Among these bacteria, we found known mosquito symbionts and showed that they can improve offspring fitness if present in the water where eggs are laid. We deem this oviposition-mediated bacterial community shaping as a form of niche construction initiated by the gravid female.

Listen to the shopkeeper.

His mosquito control project heading for failure, a field entomologist recalls how a chance encounter led to a Eureka moment.

Urea Decomposition Mechanism by Dinuclear Nickel Complexes.

Urease is an enzyme containing a dinuclear nickel active center responsible for the hydrolysis of urea into carbon dioxide and ammonia. Interestingly, inorganic models of urease are unable to mimic its mechanism despite their similarities to the enzyme active site. The reason behind the discrepancy in urea decomposition mechanisms between inorganic models and urease is still unknown. To evaluate this factor, we synthesized two bis-nickel complexes, [Ni2L(OAc)] (1) and [Ni2L(Cl)(Et3N)2] (2), based on the Trost bis-Pro-Phenol ligand (L) and encompassing different ligand labilities with coordination geometries similar to the active site of jack bean urease. Both mimetic complexes produced ammonia from urea, (1) and (2), were ten- and four-fold slower than urease, respectively. The presence and importance of several reaction intermediates were evaluated both experimentally and theoretically, indicating the aquo intermediate as a key intermediate, coordinating urea in an outer-sphere manner. Both complexes produced isocyanate, revealing an activated water molecule acting as a base. In addition, the reaction with different substrates indicated the biomimetic complexes were able to hydrolyze isocyanate. Thus, our results indicate that the formation of an outer-sphere complex in the urease analogues might be the reason urease performs a different mechanism.

Lane-Hamilton Syndrome in an Adult With Down Syndrome: A Case Report.

The Lane-Hamilton syndrome (LHS) is an extremely rare association between celiac disease (CD) and idiopathic pulmonary hemosiderosis (IPH), with only a few cases reported in the literature. The authors report a case of a 32-year-old man with Down syndrome who presented to the emergency department with a history of hemoptysis and chronic diarrhea. The complementary investigation revealed iron deficiency anemia and features suggestive of diffuse alveolar hemorrhage on computed tomography (CT) scan of the chest. After excluding all competing diagnosis, the IPH diagnosis was made. The biopsy of the small intestine confirmed CD and the diagnosis of LHS was established. A gluten-free diet and steroids were given to the patient with a very good clinical response. Since there is an established association between IPH and CD, if the diagnosis of IPH is made, it's recommended to screen for CD even in patients without gastrointestinal symptoms.