Retinoblastoma in Ceara: An epidemiological study in a Brazilian pediatric oncology referral center

ABSTRACT Purpose: Although Brazil has a high prevalence of retinoblastoma, there is a lack of epidemiological data on the disease. Thus, in this study, we aimed to evaluate the epidemiological profile of patients diagnosed with retinoblastoma in the ophthalmology department of a pediatric tertiary referral hospital in Ceara, Brazil. Methods: A descriptive and cross-sectional study was conducted by retrospectively analyzing the clinical and socioeconomic data from the medical records of pediatric patients followed-up at the hospital between 2007 and 2021. Retinoblastoma was diagnosed on the basis of a fundoscopic or histopathologic examination. Results: The data of 105 patients were included in the study, and the mean patient age at the time of diagnosis was 1.7 years. Most of the patients were women (50.5%) and hailed from rural areas (57.4%), which was associated with a higher tumor stage. Of the 150 patients, 57.1% initially presented with leukocoria. Ocular hyperemia was associated with more advanced stages of retinoblastoma (p=0.004). Bilateral involvement was observed in 25.7% of the patients and at a significantly younger age (p=0.009). The presence of retinal detachment, vascularized lesions, and vitreous seeds significantly increased the likelihood of requiring enucleation. Discussion: This study presents an epidemiological description of retinoblastoma in Brazil, which highlights the significance of early detection. Delayed diagnosis is associated with a poorer visual prognosis and higher mortality rate, particularly in patients with unilateral disease. Risk factors for a more severe disease were retinal detachment, vascularized lesions, and vitreous seeds. The correlation between histopathological features and clinical outcomes was limited. Conclusion: Further studies are required to assess the influence of ocular hyperemia, fundoscopic assessment, and histopathologic findings on the prognosis of retinoblastoma. Moreover, it is critical to devise interventions to reduce the time-to-diagnosis in rural areas.

Intraocular pressure modulation with thermal stimuli

ABSTRACT Purpose: This study aimed to determine whether early-stage intraocular pressure can be modulated using a thermal face mask. Methods: In this prospective clinical study, healthy participants were randomized on a 1:1:1 allocation ratio to three mask groups: hypothermic (G1), normothermic (G2), and hyperthermic (G3). After randomization, 108 eyes from 108 participants were submitted to clinical evaluations, including measurement of initial intraocular pressure (T1). The thermal mask was then applied for 10 minutes, followed by a second evaluation of intraocular pressure (T2) and assessment of any side effects. Results: The hypothermic group (G1) showed a significant reduction in mean intraocular pressure between T1 (16.97 ± 2.59 mmHg) and T2 (14.97 ± 2.44 mmHg) (p<0.001). G2 showed no significant pressure difference between T1 (16.50 ± 2.55 mmHg) and T2 (17.00 ± 2.29 mmHg) (p=0.054). G3 showed a significant increase in pressure from T1 (16.53 ± 2.69 mmHg) to T2 (18.58 ± 2.95 mmHg) (p<0.001). At T1, there was no difference between the three study groups (p=0.823), but at T2, the mean values of G3 were significantly higher than those of G1 and G2 (p<0.00). Conclusion: Temperature was shown to significantly modify intraocular pressure. Thermal masks allow the application of temperature in a controlled, reproducible manner. Further studies are needed to assess the duration of these effects and whether they are reproducible in patients with pathologies that affect intraocular pressure.

A Comprehensive Compilation of Spectral Libraries for Petroleum Hydrocarbons (PHC) Encompassing VNIR-SWIR-TIR Ranges.

Remote detection and mapping of surface materials using optical sensors relies predominantly on analyzing multispectral and hyperspectral imagery employing classification algorithms. The classification process involves comparing the spectra of individual pixels within the image to spectra from reference databases, commonly referred to as spectral libraries. Here, we introduce a comprehensive compilation of spectral libraries specifically tailored for petroleum hydrocarbons (PHC), meticulously crafted under controlled laboratory conditions. This compilation includes reference spectral libraries for various PHC forms, including crude oils, mineral substrate-PHC mixtures (comprising crude oils and fuels), oil-film on water, and oil-water emulsions. Data collection was conducted within the visible, near, and shortwave IR (VNIR-SWIR - 0.35-2.5 µm) spectra and thermal IR (TIR - 3-15 µm) range. The openly accessible spectral libraries presented herein support the scientific community and industry in characterizing field samples or spectral data from onshore and offshore sites. Furthermore, these libraries are instrumental in developing and applying classification algorithms designed for processing spectral images captured by cameras coupled to multiple platforms (e.g., tripods, drones, airborne, orbital satellites).

Major recent failures in Brazilian mine waste containment facilities, current cases of maximum emergency level and imminent risk of rupture, and a brief sustainability analysis.

Waste is the materials left over after the processing of ores. Significant disasters involving waste disposal structures have occurred in Brazil in recent years and caused severe damage by contaminating soil, rivers and coastal areas, destroying native fauna and flora, interrupting the water supply and compromising its potability, putting the population's health, livelihoods and economy at risk, as well as causing 289 irreparable human deaths. Regulatory laws have become stricter, and since 2019, after the tailings dam tragedies occurred in 2015 and 2019 in Mariana and Brumadinho, in Minas Gerais, the operation of  upstream-raised tailings dams has been prohibited in Brazil. In 2022, a waste slide from a sterile pile at the Pau Branco Mine in Nova Lima promoted a dike overflow. There was the death of five people whose car was buried by a landslide on a hillside. New strategies and technologies, such as reprocessing and recycling, can be tested to ascertain whether they can help improve practices in tailings management. Indeed, mining companies' corporate responsibility and sustainability practices need to be evaluated to verify whether they better match expectations. On the other hand, more specific and detailed regulations and resolutions are required to ensure the safe monitoring and management of sterile waste piles. This paper presents a review of the facts, a discussion of the literature (mainly on recent tailings dam disasters), the current situation of mining-containing waste structures in Brazil, a brief sustainability analysis and perspectives aimed at preventing/minimising catastrophes in the future.

Retinoblastoma in Ceara: An epidemiological study in a Brazilian pediatric oncology referral center.

PURPOSE: Although Brazil has a high prevalence of retinoblastoma, there is a lack of epidemiological data on the disease. Thus, in this study, we aimed to evaluate the epidemiological profile of patients diagnosed with retinoblastoma in the ophthalmology department of a pediatric tertiary referral hospital in Ceara, Brazil. METHODS: A descriptive and cross-sectional study was conducted by retrospectively analyzing the clinical and socioeconomic data from the medical records of pediatric patients followed-up at the hospital between 2007 and 2021. Retinoblastoma was diagnosed on the basis of a fundoscopic or histopathologic examination. RESULTS: The data of 105 patients were included in the study, and the mean patient age at the time of diagnosis was 1.7 years. Most of the patients were women (50.5%) and hailed from rural areas (57.4%), which was associated with a higher tumor stage. Of the 150 patients, 57.1% initially presented with leukocoria. Ocular hyperemia was associated with more advanced stages of retinoblastoma (p=0.004). Bilateral involvement was observed in 25.7% of the patients and at a significantly younger age (p=0.009). The presence of retinal detachment, vascularized lesions, and vitreous seeds significantly increased the likelihood of requiring enucleation. DISCUSSION: This study presents an epidemiological description of retinoblastoma in Brazil, which highlights the significance of early detection. Delayed diagnosis is associated with a poorer visual prognosis and higher mortality rate, particularly in patients with unilateral disease. Risk factors for a more severe disease were retinal detachment, vascularized lesions, and vitreous seeds. The correlation between histopathological features and clinical outcomes was limited. CONCLUSION: Further studies are required to assess the influence of ocular hyperemia, fundoscopic assessment, and histopathologic findings on the prognosis of retinoblastoma. Moreover, it is critical to devise interventions to reduce the time-to-diagnosis in rural areas.

Brazilian Thoracic Society recommendations for the diagnosis and monitoring of asbestos-exposed individuals.

Asbestos was largely used in Brazil. It is a mineral that induces pleural and pulmonary fibrosis, and it is a potent carcinogen. Our objective was to develop recommendations for the performance of adequate imaging tests for screening asbestos-related diseases. We searched peer-reviewed publications, national and international technical documents, and specialists' opinions on the theme. Based on that, the major recommendations are: Individuals exposed to asbestos at the workplace for ≥ 1 year or those with a history of environmental exposure for at least 5 years, all of those with a latency period > 20 years from the date of initial exposure, should initially undego HRCT of the chest for investigation. Individuals with pleural disease and/or asbestosis should be considered for regular lung cancer monitoring. Risk calculators should be adopted for lung cancer screening, with a risk estimate of 1.5%.

Forty years of a Postgraduate Program in Cardiology at a Brazilian public university: indicators of its graduates.

PURPOSE: To evaluate the profile of graduates of the Postgraduate Program (PGP) in Cardiology of a public federal university, according to sociodemographic factors and professional trajectory. METHODS: The variables were collected from databases from the observed institution and digital platforms. The analysis of differences between the various levels of degrees was carried out in three cohorts: the entire historical series (graduates from 1978-2021), the first 20 years (1978-1997) and the second 20 years (1998-2018). RESULTS: The results demonstrated that most students from the PGP completed a PhD and are men over 30 years old, they came from public universities and the Southeast region. In the first 20 years, significant differences were observed in the distribution of masters and doctors working professionally at the institution analyzed, as well as in the age of the students. In the 20 years of the second half, there were differences between masters and PhD working professionally in the institution itself, as they came from private universities, they are women and PhD. CONCLUSIONS: The changes in the profile of masters and PhD that graduated from this PGP in cardiology reflect transformations that occurred in the job market and academy over the decades.

Intraocular pressure modulation with thermal stimuli.

PURPOSE: This study aimed to determine whether early-stage intraocular pressure can be modulated using a thermal face mask. METHODS: In this prospective clinical study, healthy participants were randomized on a 1:1:1 allocation ratio to three mask groups: hypothermic (G1), normothermic (G2), and hyperthermic (G3). After randomization, 108 eyes from 108 participants were submitted to clinical evaluations, including measurement of initial intraocular pressure (T1). The thermal mask was then applied for 10 minutes, followed by a second evaluation of intraocular pressure (T2) and assessment of any side effects. RESULTS: The hypothermic group (G1) showed a significant reduction in mean intraocular pressure between T1 (16.97 ± 2.59 mmHg) and T2 (14.97 ± 2.44 mmHg) (p<0.001). G2 showed no significant pressure difference between T1 (16.50 ± 2.55 mmHg) and T2 (17.00 ± 2.29 mmHg) (p=0.054). G3 showed a significant increase in pressure from T1 (16.53 ± 2.69 mmHg) to T2 (18.58 ± 2.95 mmHg) (p<0.001). At T1, there was no difference between the three study groups (p=0.823), but at T2, the mean values of G3 were significantly higher than those of G1 and G2 (p<0.00). CONCLUSION: Temperature was shown to significantly modify intraocular pressure. Thermal masks allow the application of temperature in a controlled, reproducible manner. Further studies are needed to assess the duration of these effects and whether they are reproducible in patients with pathologies that affect intraocular pressure.

Exploring the osteogenic potential of semisynthetic triterpenes from Combretum leprosum: An in vitro and in silico study.

Combretum leprosum Mart. is a plant of the Combretaceae family, widely distributed in the Northeast region of Brazil, popularly used as an anti-inflammatory agent, and rich in triterpenes. This study evaluated in vitro and in silico potential osteogenic of two semisynthetic triterpenes (CL-P2 and CL-P2A) obtained from the pentacyclic triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene (CL-1) isolated from C. leprosum. Assays were carried out in cultured murine osteoblasts (OFCOL II), first investigating the possible toxicity of the compounds on these cells through viability assays (MTT). Cell proliferation and activation were investigated by immunohistochemical evaluation of Ki-67, bone alkaline phosphatase (ALP) activity, and mineralization test by Von Kossa. Molecular docking analysis was performed to predict the binding affinity of CL-P2 and CL-P2A to target proteins involved in the regulation of osteogenesis, including: bone morphogenetic protein 2 (BMP-2), proteins related to Wingless-related integration (WNT) pathway (Low-density lipoprotein receptor-related protein 6-LRP6 and sclerostin-SOST), and receptor activator of nuclear factor (NF)-kB-ligand (RANK-L). Next, Western Blot and immunofluorescence investigated BMP-2, WNT, RANK-L, and OPG protein expressions in cultured murine osteoblasts (OFCOL II). None of the CL-P2 and CL-P2A concentrations were toxic to osteoblasts. Increased cell proliferation, ALP activity, and bone mineralization were observed. Molecular docking assays demonstrated interactions with BMP-2, LRP6, SOST, and RANK-L/OPG. There was observed increased expression of BMP-2, WNT, and RANK-L/OPG proteins. These results suggest, for the first time, the osteogenic potential of CL-P2 and CL-P2A.

Psycho-physio-neurological correlates of qualitative attention, emotion and flow experiences in a close-to-real-life extreme sports situation: low- and high-altitude slackline walking.

It has been indicated that extreme sport activities result in a highly rewarding experience, despite also providing fear, stress and anxiety. Studies have related this experience to the concept of flow, a positive feeling that individuals undergo when they are completely immersed in an activity. However, little is known about the exact nature of these experiences, and, there are still no empirical results to characterize the brain dynamics during extreme sport practice. This work aimed at investigating changes in psychological responses while recording physiological (heart rate-HR, and breathing rate-BR) and neural (electroencephalographic-EEG) data of eight volunteers, during outdoors slackline walking in a mountainous environment at two different altitude conditions (1 m-low-walk- and 45 m-high-walk-from the ground). Low-walk showed a higher score on flow scale, while high-walk displayed a higher score in the negative affect aspects, which together point to some level of flow restriction during high-walk. The order of task performance was shown to be relevant for the physiological and neural variables. The brain behavior during flow, mainly considering attention networks, displayed the stimulus-driven ventral attention network-VAN, regionally prevailing (mainly at the frontal lobe), over the goal-directed dorsal attention network-DAN. Therefore, we suggest an interpretation of flow experiences as an opened attention to more changing details in the surroundings, i.e., configured as a 'task-constantly-opened-to-subtle-information experience', rather than a 'task-focused experience'.

ß-Alanine Plus Sodium Bicarbonate Co-Supplementation Does Not Decrease Neuromuscular Fatigue in Swimming.

This study aimed to investigate the effects of chronic ß-alanine (ßA) plus acute sodium bicarbonate (SB) co-supplementation on neuromuscular fatigue during high-intensity intermittent efforts in swimming. Eleven regional and national competitive-level young swimmers performed a neuromuscular fatigue assessment before and immediately after two 20 × 25-m front crawl maximal efforts every 90 s, performed at pre- and post-4-week co-supplementation. Neuromuscular fatigue was evaluated by percutaneous electrical stimuli through the twitch interpolation technique on the triceps brachii and quadriceps femoris. Performance was defined by the mean time of the 20 efforts and blood samples to lactate concentrations were collected every four efforts. Participants supplemented 3.2-6.4 g·day-1 of chronic ßA or placebo (PL) during four weeks, and acute 0.3 g·kg-1 of SB or PL 60 min before the second assessment (allowing ßA+SB and PL+PL groups). No statistical changes were found in neuromuscular fatigue of triceps brachii. In the quadriceps femoris, a main effect of time was found in potentiated twitch delta values in pooled groups, showing a statistical increase of 19.01% after four weeks (Δ = 13.05 [0.35-25.75] N; p = 0.044), without time × group interactions. No statistical difference was found in the swimming performance. Blood lactate increased by 25.06% only in the ßA+SB group (Δ = 6.40 [4.62-8.18] mM; p Bonf < 0.001) after the supplementation period. In conclusion, 4-week ßA and SB co-supplementation were not able to reduce neuromuscular fatigue levels and improve performance in highintensity intermittent efforts, but statistically increased blood lactate levels.

Prevalence and clinico-pathology of PSOROPTIC mange in buffaloes of the Amazon region.

Scabies is an important skin disease in several species of domestic and wild animals; however, few reports in Brazil have emphasized its occurrence in buffaloes. This article describes the epidemiological, clinical and pathological aspects and diagnosis of psoroptic mange in buffaloes in a property in the municipality of Castanhal, PA, Amazon region. Of the 41 buffaloes examined, 38 males and females of the Murrah, Baio, Mediterranean and Carabao breeds and their crossbreeds, aged between 2 and 20 years, had a history of pruritus. Clinical examination was performed to map the lesions, skin scrapings were collected to identify the mites, and a biopsy was performed for histopathological examination. Clinical signs, from mild to severe intensity, varied according to the system of creation and handling of the animals and were more severe in buffaloes raised in bays than those raised under a collective regime (pastures and collective troughs). The characteristic clinical signs were intense itching, extensive areas of alopecia, periocular edema, and thickening of the epidermis with exudative crusts covering the face, chamfer, neck, scapular region, back, base of the horn, thoracic and pelvic limbs and chest. The behavior of rubbing the affected regions of the body against structures (troughs, fence posts, gates) or with the horns was frequently observed and provided relief from itching. In the most severe cases, mites were also noted in the crusts, which were identified as Psoroptes natalensis. Histological skin lesions exhibited alterations consistent with immune-mediated dermatitis, which is typical of hypersensitivity to mite-derived allergens.

Sleep "ON", sleep better! Positive effects of levodopa on sleep behaviour in people with Parkinson's disease.

People with Parkinson's disease experience reduced sleep quality compared with their peers. Levodopa may have a direct effect on sleep macrostructure or may improve sleep by enhancing nocturnal motor performance. Therefore, it is important to understand the acute effects of withdrawing levodopa on sleep measures in Parkinson's disease. The purpose of this study was to compare the estimated objective and subjective sleep measures of people with Parkinson's disease sleeping under (ON-night) versus without (OFF-night) the effects of the last daily dopaminergic medication before going to bed. A total of 23 people with Parkinson's disease were instructed to wear an actigraphy device for 4 consecutive nights to objectively measure the sleep behaviour. Subjective sleep measure was assessed each morning using a Likert scale. Participants slept for 3 nights on ON-night and 1 night on OFF-night. They were instructed not to take their last dose of levodopa before going to bed in OFF-night. Sleeping in ON- versus OFF-night increased total sleep time (7.8%, p = 0.032) and sleep efficiency (3.7%, p = 0.019), and decreased duration and number of wakes after sleep onset (22.3%, p = 0.050; and 29.2%, p = 0.013, respectively). However, subjective sleep analysis indicated no significant differences between the two conditions. From a clinical point of view, our results suggest that sleeping on ON-night resulted in an improvement in estimated objective sleep measures compared with sleeping on OFF-night. From a methodological point of view, our findings emphasize the importance of relying on objective sleep measurements to accurately assess OFF-night sleep behaviour in people with Parkinson's disease.

Parasitic Granulomatous Dermatitis Caused by Pelodera spp. in Buffalo on Marajó Island, Pará.

This is the first report of parasitic granulomatous dermatitis caused by Pelodera spp. in a buffalo. The affected buffalo was about seven years old, was a female of the Murrah breed and belonged to a property located on Marajó Island in the State of Pará. During the clinical examination, the animal was in a standing position and presented several multifocal nodular and placoid masses throughout the body, mostly on the forelimbs, hindlimbs, abdomen, mammary glands, perineum, vulva and tail. These masses were also observed on the nasal mucosa, head, neck, back and chest. On macroscopic examination, the skin had several multifocal-to-coalescent sessile nodular and placoid lesions. Histopathology of the skin showed a marked reduction in the number of hair follicles. In the superficial dermis, there was significant multifocal-to-coalescent inflammatory infiltration, consisting of macrophages, epithelioid macrophages, lymphocytes, plasma cells and multinucleated giant cells. In the remaining hair follicles, there were numerous cross and longitudinal sections of small rhabditoid nematodes characterized by a thin cuticle, platymyarian musculature, an intestinal tract, a rhabditiform esophagus and lateral alae (morphologically compatible with Pelodera spp.). The diagnosis of parasitic dermatitis was confirmed by histopathological skin lesions associated with the presence of intralesional rhabditiform larvae morphologically compatible with Pelodera spp.

Cutaneous Mucormycosis in Buffalos in the Brazilian Amazon Biome.

This is the first description of cutaneous mucormycosis in buffalo in the Brazilian Amazon biome. All buffalo showed apathy, inappetence, weight loss, reluctance to move, and prolonged sternal decubitus. Of the four affected animals, two died 15 and 30 days after the appearance of clinical signs. In the initial phase, the skin lesions were rounded areas with dry central regions, sensitive to palpation, with protruding edges and diameters ranging from 8 cm to 15 cm. These areas of necrosis were isolated or coalescing and present mainly on the limbs and sides. In an advanced stage of the disease, there was detachment of the skin from the necrotic areas with extensive wound formation, which sometimes exposed the subcutaneous tissue. The histopathology of the skin showed a multifocal inflammatory infiltrate composed of intact and degenerated eosinophils surrounded by epithelioid macrophages. At the center of these areas was a focally extensive area of epidermal ulceration characterized by intact and degenerated neutrophils, the necrosis of epithelial cells, and the accumulation of fibrin and erythrocytes. The mycological culture was positive for Rhizopus sp. The diagnosis of cutaneous dermatitis caused by Rhizopus sp. was based on clinical signs, macroscopic and histopathological findings, and the identification of the fungus by mycological and molecular techniques.

Operational criteria application does not change clinicians' opinion on the diagnosis of mental disorder: a pre- and post-intervention validity study.

Objective: Our objective was to check if the ICD-10 operational criteria application changes non-operational, prototype-based diagnoses obtained in a real-life scenario. Methods: Psychiatry residents applied the diagnostic criteria of the ICD-10 as a "diagnostic test" to five outpatient patients they were already following who had a prototype-based diagnosis. Tests were used to ascertain whether changes in opinion were significant and if any of the diagnostic groups were more prone to change than others. The present paper is part of the study with UTN U1111-1260-1212. Results: Seventeen residents reviewed their last five case files, retrieving 85 diagnostic pairs of non-operational-based vs. operational-based diagnoses. The Stuart-Maxwell test did not indicate a significant opinion change (χ2 = 5.25, p = 0.39; power = 0.94) besides 30% of diagnostic changes. Despite not being statistically significant, 20.2% of all evaluations resulted in a change that would affect treatment choices. Using ICD-10 operational criteria slightly increased the number of observed diagnoses, but probably without clinical relevance. None of the non-operational diagnoses have a higher tendency to change with operational criteria application (χ2 = 11.6, p = 0.07). The female gender was associated with a higher diagnostic change tendency. Conclusion: Applying ICD-10 operational criteria as a diagnostic test does not induce a statistically significant diagnostic opinion change in residents and no diagnostic group seems more sensible to diagnostic change. Gender-related differences in diagnostic opinion changes might be evidence of sunk cost bias. Although not statistically significant, using operational criteria after diagnostic elaboration might help to deal with subjects without adequate treatment response.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil.

BACKGROUND OBJECTIVES: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. METHODS: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. RESULTS: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. INTERPRETATION CONCLUSION: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil's phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.

Immunometabolic crosstalk in Aedes fluviatilis and Wolbachia pipientis symbiosis.

Wolbachia pipientis is a maternally transmitted symbiotic bacterium that mainly colonizes arthropods, potentially affecting different aspects of the host's physiology, e.g., reproduction, immunity, and metabolism. It has been shown that Wolbachia modulates glycogen metabolism in mosquito Aedes fluviatilis (Ae. fluviatilis). Glycogen synthesis is controlled by the enzyme GSK3, which is also involved in immune responses in both vertebrate and invertebrate organisms. Here we investigated the mechanisms behind immune changes mediated by glycogen synthase kinase ß (GSK3ß) in the symbiosis between Ae. fluviatilis and W. pipientis using a GSK3ß inhibitor or RNAi-mediated gene silencing. GSK3ß inhibition or knockdown increased glycogen content and Wolbachia population, together with a reduction in Relish2 and gambicin transcripts. Furthermore, knockdown of Relish2 or Caspar revealed that the immunodeficiency pathway acts to control Wolbachia numbers in the host. In conclusion, we describe for the first time the involvement of GSK3ß in Ae. fluviatilis immune response, acting to control the Wolbachia endosymbiotic population.

Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights.

Flavor esters are organic compounds widely used in the food industry to enhance the aroma and taste of products. However, most chemical processes for the production of these flavoring compounds use toxic organic solvents. Some organic solvents derived from petroleum can leave behind residual traces in food products, which may raise concerns about potential health risks and contamination. In this study, we employ Eversa Transform 2.0, a commercial lipase derived from the lipase from Thermomyces lanuginosus, to produce geranyl butyrate in aqueous media. The chemical process was optimized using the Taguchi method, and a conversion of 93% was obtained at the optimal reaction conditions of: 1:5 molar ratio (v/v), 15% biocatalyst load (w/w), at 50 °C, in 6 h. Classic (molecular dynamics) and quantum (density functional theory) simulations unveiled amino acid residues involved in the stabilization of the enzyme-substrate complex. Detailed QM/MM mechanistic studies identified the nucleophilic attack of the deacylation reaction as the rate-limiting step of the entire mechanism, which has a free energy barrier of 14.0 kcal/mol.