Prevention of heartworm infection in dogs using a combination of moxidectin, imidacloprid and praziquantel: evidence from a randomized clinical trial.

The aim of this study was to evaluate the efficacy of a topical combination of moxidectin 3.5%, imidacloprid 10% and praziquantel 10% for the prevention of Dirofilaria immitis (Leidy, 1856) infection in dogs. For this purpose, a randomized and controlled clinical trial was conducted between August 2021 and October 2022, in the municipality of Goiana, state of Pernambuco, north-eastern Brazil, where heartworm is highly prevalent. Of the 213 dogs initially sampled (baseline), 68 (31.9%) were positive for adult antigens (SNAP 4Dx Plus, Idexx) and/or microfilariae (modified Knott's test). On day 0, 140 negative dogs were randomly included in the treatment and control groups, 70 animals each. During the study, 60 dogs (34 treated and 26 untreated) were removed for different reasons. At the end of the study (day 360 ± 2), 36 treated and 44 untreated were sampled and included in the efficacy calculation. The efficacy against the development of adults and microfilariae was 84.7%, with only one treated dog being positive for adult antigens but negative for microfilariae. On the other hand, eight untreated dogs were positive for adult antigens and/or microfilariae, resulting in a significant difference in the number of positives between groups (Chi-square test = 4.706, df = 1, P = 0.0301). Remarkably, the efficacy against the appearance of D. immitis microfilariae was 100% (i.e., all treated dogs negative) and three untreated dogs were positive for microfilariae. The topical combination of moxidectin 3.5%, imidacloprid 10% and praziquantel 10% significantly reduced the risk of D. immitis infection in treated dogs as compared with untreated dogs, in a highly endemic area in north-eastern Brazil.

Seasonal dynamics of Amblyomma cajennense (Fabricius, 1787) sensu stricto in a degraded area of the Amazon biome, with notes on Rickettsia amblyommatis infection.

BACKGROUND: The tick Amblyomma cajennense sensu stricto (A. cajennense s.s.) frequently parasitizes animals and humans in the Amazon biome, in addition to being a vector of Rickettsia amblyommatis. In the present study, we evaluated both the population dynamics of A. cajennense s.s. in a degraded area of the Amazon biome and the presence of rickettsial organisms in this tick population. METHODS: The study was carried out in a rural area of the Santa Inês municipality (altitude: 24 m a.s.l.), Maranhão state, Brazil. Ticks were collected from the environment for 24 consecutive months, from June 2021 to May 2023. The region is characterized by two warm seasons: a rainy season (November-May) and a dry season (June-October). We characterized the temporal activity of A. cajennense s.s. on the vegetation by examining questing activity for each life stage (larvae, nymphs, adults [males and females]) in relation to the dry and rainy season. Ticks collected in this study were randomly selected and individually tested by a TaqMan real-time PCR assay that targeted a 147-bp fragment of the rickettsial gltA gene. RESULTS: Overall, 1843 (62.4%) adults (52.6% females, 47.4% males), 1110 (37.6%) nymphs and 398 larval clusters were collected. All adult females and nymphs were morphologically identified as A. cajennense s.s. Larval activity was observed from April to December, with a peak from June to September (dry season); nymph abundance peaked from September to November (transition period between dry and rainy seasons); and adult ticks were abundant from October to May (spring/summer/early autumn). The infection rate by R. amblyommatis in A. cajennense s.s. ticks was at least 7% (7/99). CONCLUSION: Our data suggest a 1-year generation pattern for A. cajennense s.s., with a well-defined seasonality of larvae, nymphs and adults in the Amazon biome. Larvae predominate during the dry season, nymphs are most abundant in the dry-rainy season transition and adults are most abundant in the rainy season. The presence of R. amblyommatis in adult ticks suggests that animals and humans in the study region are at risk of infection by this species belonging to the spotted fever group of Rickettsia.

Análisis de la experiencia del uso de cánula nasal de alto flujo como terapéutica en neumonía por SARS-CoV-2 / Analysis of the experience of the use of high-flow nasal cannula as therapeutics in SARS-CoV-2 pneumonia

RESUMEN Introducción: Durante la pandemia por SARS-CoV-2, la cánula nasal de alto flujo (CNAF) se usó como soporte en espera de Unidad de terapia intensiva (UTI) o como alternativa a la ventilación invasiva. Objetivos: Primario: Determinar si la cánula nasal de alto flujo evita la intubación oro traqueal. Secundarios: Analizar predictores de éxito al inicio de la cánula nasal de alto flujo y análisis descriptivo de la muestra. Materiales y métodos: Estudio observacional descriptivo retrospectivo. Se incluyeron pacientes mayores de 16 años positivos para SARS-CoV-2, atendidos en guardia y unidad de terapia intensiva, que utilizaron cánula nasal de alto flujo entre octubre de 2020 y marzo 2021. Se recolectaron datos en planillas individuales, analizadas por un profesional externo. Resultados: Se incluyeron en el trabajo 72 pacientes (de 16 a 88 años), 20 mujeres y 52 hombres. El 50 % de la muestra evitó la intubación orotraqueal. El IROX inicio grupo "éxito" vs. grupo "fracaso", p = 0,006. Comparación Irox 12 h grupo "éxito" vs. grupo "fracaso" p < 0,001. Comparación "tiempo desde ingreso a inicio de cánula nasal de alto flujo" grupo "éxito" vs. grupo "fracaso", p = 0,133. Comparación "Delta IROX" grupo "éxito" vs grupo "fracaso" p = 0,092. Conclusión: Se evitó la intubación orotraqueal en el 50 % de los casos. El IROX de inicio y el IROX a las 12 h del uso de cánula nasal de alto flujo fue estadísticamente significativo, lo que es un buen predictor del éxito en esta población. La fecha de inicio de síntomas y el uso de cánula nasal de alto flujo y el delta del IROX durante las pri meras 12 h no fue estadísticamente significativo para el éxito de la terapia. Estos datos son una herramienta útil con el objeto de generar protocolos de selección de pacientes para esta patología.

ABSTRACT Introduction: During the SARS-CoV-2 pandemic, the high flow nasal cannula (HFNC) was used as support while waiting for the Intensive Care Unit (ICU) or as an alternative to invasive ventilation. The objective of this work is the description and analysis of the use of CNAF in our population. Objectives: Primary: Determine if HFNC prevents orotracheal intubation. Secondary: Analyze predictors of success at the start of CNAF and a descriptive analysis of the sample Materials and method: Retrospective descriptive observational study. Patients over 16 years of age positive for SARS-CoV-2, treated in Guard and ICU were included. who used CNAF between October 2020 and March 2021 Data was collected in individual forms, analyzed by an external professional. Results: The study included 72 patients (16 to 88 years old), 20 women and 52 men; 50 % of the sample avoided orotracheal intubation. Start IROX, group "success" vs. group "failure" p = 0.006. Comparison Irox.12 h group "success" vs. group "failure" p < 0.001. Comparison "Time from admission to start of CNAF" group "success" vs. group "failure" p = 0.133. Comparison "Delta IROX" group "success" vs. group "failure" p = 0.092. Conclusion: HFNC avoided orotracheal intubation in the 50 % of the cases. The initial IROX and the IROX 12 hours after the use of HFNC were statistically significant, which is a good predictor of success in this population. The date of onset of symptoms and the use of FNAF and IROX delta during the first 12 hours were not statistically significant for the success of the therapy. These data are a useful tool for generating patient selection protocols for this pathology.

Vector-borne pathogens of zoonotic concern in dogs from a Quilombola community in northeastern Brazil.

Canine vector-borne pathogens (CVBPs) comprise a group of disease agents mainly transmitted by ticks, fleas, mosquitoes and sand flies. In this study, we assessed the presence of CVBPs in an Afro-descendent community (Quilombola) of northeastern, Brazil. Dog blood samples (n = 201) were collected and analyzed by rapid test for the detection of antibodies against Leishmania spp., Anaplasma spp., Ehrlichia spp. and Borrelia burgdorferi sensu lato (s.l.), and antigens of Dirofilaria immitis. In addition, polymerase chain reactions were performed for Anaplasmataceae, Babesia spp., Hepatozoon spp., Rickettsia spp. and B. burgdorferi s.l. Overall, 66.7% of the dogs scored positive to at least one pathogen at serological and/or molecular methods. Antibodies against Ehrlichia spp. were the most frequently detected (57.2%; n = 115/201), followed by Anaplasma spp. (8.5%; n = 17/201), Leishmania spp. (8.5%; n = 17/201) and B. burgdorferi s.l. (0.5%; n = 1/201). For D. immitis, 11 out of 201 (5.5%) animals scored positive. At the molecular analysis, 10.4% (n = 21/201) of the samples scored positive for Babesia spp./Hepatozoon spp., followed by Anaplasmataceae (5.0%; n = 10/201) and Rickettsia spp. (3.0%; n = 6/201). All samples were negative for B. burgdorferi s.l. Our data demonstrated the presence of CVBPs in the studied population, with a high seropositivity for Ehrlichia spp. In addition, considering the detection of zoonotic pathogens in dogs and their relationship with people from Quilombola communities, effective control strategies are advocated for minimizing the risk of infection in this socially vulnerable human population and their pets.

Molecular epidemiology and prevalence of babesial infections in dogs in two hyperendemic foci in Brazil.

Babesial parasites are some of the most ubiquitous blood pathogens and consequently have considerable worldwide veterinary impact. Dogs living in the tropics are highly exposed to babesial parasites, particularly to Babesia vogeli. Limited data on the seroprevalence and molecular prevalence of Babesia spp. in dogs are available in Latin America. We conducted a cross-sectional study combining serological and molecular tests to estimate the seroprevalence and molecular epidemiology of Babesia spp. infections in dogs in two hyperendemic foci in Brazil. A total of 630 privately owned dogs (417 from Goiana municipality, Pernambuco state, north-eastern Brazil, and 213 from São Joaquim de Bicas municipality, Minas Gerais state, south-eastern Brazil) were sampled and molecularly and serologically tested for Babesia spp. Overall, 519 dogs (82.4%) presented detectable IgG antibodies against Babesia spp., and seropositivity was significantly higher in dogs older than 1 year. Molecularly, 34 dogs (5.4%) were positive for a ~ 200 bp fragment of the 18S rRNA gene of Babesia spp. and 88 (14.0%) for a longer fragment (~ 450 bp) of the same gene of Babesia spp. and other protozoa. The 18S rRNA gene sequences generated herein corresponded to B. vogeli (n = 52) or Hepatozoon canis (n = 20). This study confirms a high level of exposure to B. vogeli in two areas of Brazil and highlights that most of the dogs living in these areas are infected during the course of their life, reflected by increased seroprevalence in older dogs. Increased awareness and prevention of tick-borne protozoa infections in dogs from Brazil and Latin America are urgently needed.

Spray-dried bacterial cellulose nanofibers: A new generation of pharmaceutical excipient intended for intestinal drug delivery.

Defibrillation of bacterial cellulose by ultra-refining was efficient to release nanofibers (BCNF) which were spray dried with the matrices formers mannitol (MN), maltodextrin or hydroxypropylmethylcellulose. The best microsystem comprised the association of BCNF and MN, so the selected microparticles were loaded with diclofenac sodium or caffeine. Depending on the proportion of BCNF, the nanofibers collapse promoted by spray drying can occur onto surface or into microparticles core, leading to different release behaviors. Samples showed pH-dependent drug release, so the microsystem developed with the lowest BCNF concentration showed important trend to gastroresistance. Caffeine was spray dried as a free drug and for this reason it was devoid of any control over release rates. The set of results showed BCNF can be considered an interesting and potential pharmaceutical excipient for lipophilic drugs. Beyond that, BCNF association with MN can lead to novel enteric drug delivery systems based on natural polymers.

Evaluation of the causal effects between dopamine infusion changeover and fluctuations in mean arterial pressure in neonates.

OBJECTIVE: To evaluate whether changing dopamine infusions every 12 hours and preparing these infusions 30 min before administration reduces blood pressure fluctuations in preterm and term neonates. DESIGN: This was a retrospective study using data from live patients on the neonatal unit and prospective study exploring stability of infusions in a laboratory-based neonatal ward simulation. SETTING: Single-centre study in a tertiary neonatal surgical unit in a university teaching hospital. PATIENTS: Neonates who received more than one subsequent dopamine infusion and had invasive arterial blood pressure monitoring, during their admission in the neonatal unit, were included. INTERVENTIONS: As part of the Quality Improvement project, the standard operating procedure (SOP) was changed, and dopamine infusions were prepared by nursing staff and left to rest for 30 min before administering to the neonate. Additionally, infusions were replaced every 12 hours. MAIN OUTCOME MEASURES: The percentage change in mean arterial pressure (MAP) and the percentage loss in the drug concentration during infusion during changeover. RESULTS: Our findings indicate that up to 15% of the initial dopamine concentration is lost after 24 hours. This results in a sharp variation in the dopamine concentration during infusion changeover that correlates with observed rapid fluctuations in MAP. In changing the SOP, no significant difference in the concentration of dopamine and MAP were observed over 12 hours. CONCLUSIONS: Delaying administration of dopamine infusions by 30 min after preparation combined with changing infusions 12 hourly has reduced MAP fluctuations. Therefore, the risks associated with MAP fluctuations, including intraventricular haemorrhages, are reduced.

A novel unbalanced translocation between the short arms of chromosomes 6 and 16 in a newborn girl: Clinical features and management.

The reporting of previously undescribed genetic mutations and resulting clinical phenotypes guides management and enables a more accurate prognosis for clinicians treating newborns with similar features. Previous cases of 6p deletions and 16p duplications have been described as separate entities. This patient presents with both and has a unique phenotype.

Recognising early meningitis: a missed opportunity to diagnose meningitis.

There are ∼250 cases of neonatal bacterial meningitis each year in the UK. Clinical evaluation of signs and symptoms of meningitis is challenging, particularly, during the neonatal period. Although uncommon, it is recognised that bacterial meningitis can be present in a child with an apparently normal cerebrospinal fluid (CSF) initially.We report the case of a newborn baby girl who was admitted with concerns regarding 2 dusky episodes. She underwent blood tests, a lumbar puncture and was started on intravenous antibiotics. With negative cultures, normal blood results and following a significant clinical improvement, antibiotics were discontinued after 48 hours and the baby was discharged home. She re-presented to the children's emergency department 7 hours later with a history of an apnoeic episode. A second CSF sample was suggestive of bacterial meningitis. We will discuss the published literature and the potential drawbacks of lumbar punctures and ways to diagnose meningitis early.

High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process?

During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1ß, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures.

High-throughput analysis of calcium signalling kinetics in astrocytes stimulated with different neurotransmitters.

Astrocytes express a wide range of receptors for neurotransmitters and hormones that are coupled to increases in intracellular Ca(2+) concentration, enabling them to detect activity in both neuronal and vascular networks. There is increasing evidence that astrocytes are able to discriminate between different Ca(2+)-linked stimuli, as the efficiency of some Ca(2+) dependent processes--notably release of gliotransmitters--depends on the stimulus that initiates the Ca(2+) signal. The spatiotemporal complexity of Ca(2+) signals is substantial, and we here tested the hypothesis that variation in the kinetics of Ca(2+) responses could offer a means of selectively engaging downstream targets, if agonists exhibited a "signature shape" in evoked Ca(2+) response. To test this, astrocytes were exposed to three different receptor agonists (ATP, glutamate and histamine) and the resultant Ca(2+) signals were analysed for systematic differences in kinetics that depended on the initiating stimulus. We found substantial heterogeneity between cells in the time course of Ca(2+) responses, but the variation did not correlate with the type or concentration of the stimulus. Using a simple metric to quantify the extent of difference between populations, it was found that the variation between agonists was insufficient to allow signal discrimination. We conclude that the time course of global intracellular Ca(2+) signals does not offer the cells a means for distinguishing between different neurotransmitters.