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.

Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals.

Coronaviruses such as SARS-CoV-2 encode a conserved papain-like protease (PLpro) that is crucial for viral replication and immune evasion, making it a prime target for antiviral drug development. In this study, three surface pockets on SARS-CoV-2 PLpro that may function as sites for allosteric inhibition were computationally identified. To evaluate the effects of these pockets on proteolytic activity, 52 residues were separately mutated to alanine. In Pocket 1, located between the Ubl and thumb domains, the introduction of alanine at T10, D12, T54, Y72, or Y83 reduced PLpro activity to <12% of that of WT. In Pocket 2, situated at the interface of the thumb, fingers, and palm domains, Q237A, S239A, H275A, and S278A inactivated PLpro. Finally, introducing alanine at five residues in Pocket 3, between the fingers and palm domains, inactivated PLpro: S212, Y213, Y251, K254, and Y305. Pocket 1 has a higher druggability score than Pockets 2 and 3. MD simulations showed that interactions within and between domains play critical roles in PLpro activity and thermal stability. The essential residues in Pockets 1 and 2 participate in a combination of intra- and inter-domain interactions. By contrast, the essential residues in Pocket 3 predominantly participate in inter-domain interactions. The most promising targets for therapeutic development are Pockets 1 and 3, which have the highest druggability score and the largest number of essential residues, respectively. Non-competitive inhibitors targeting these pockets may be antiviral agents against COVID-19 and related coronaviruses.

Assessing the global prevalence of wild birds in trade.

Trade represents a significant threat to many wild species and is often clandestine and poorly monitored. Information on which species are most prevalent in trade and potentially threatened by it therefore remains fragmentary. We used 7 global data sets on birds in trade to identify species or groups of species at particular risk and assessed the extent to which they were congruent in terms of the species recorded in trade. We used the frequency with which species were recorded in the data sets as the basis for a trade prevalence score that was applied to all bird species globally. Literature searches and questionnaire surveys were used to develop a list of species known to be heavily traded to validate the trade prevalence score. The score was modeled to identify significant predictors of trade. Although the data sets sampled different parts of the broad trade spectrum, congruence among them was statistically strong in all comparisons. Furthermore, the frequency with which species were recorded within data sets was positively correlated with their occurrence across data sets, indicating that the trade prevalence score captured information on trade volume. The trade prevalence score discriminated well between species identified from semi-independent assessments as heavily or unsustainably traded and all other species. Globally, 45.1% of all bird species and 36.7% of globally threatened bird species had trade prevalence scores ≥1. Species listed in Appendices I or II of CITES, species with large geographical distributions, and nonpasserines tended to have high trade prevalence scores. Speciose orders with high mean trade prevalence scores included Falconiformes, Psittaciformes, Accipitriformes, Anseriformes, Bucerotiformes, and Strigiformes. Despite their low mean prevalence score, Passeriformes accounted for the highest overall number of traded species of any order but had low representation in CITES appendices. Geographical hotspots where large numbers of traded species co-occur differed among passerines (Southeast Asia and Eurasia) and nonpasserines (central South America, sub-Saharan Africa, and India). This first attempt to quantify and map the relative prevalence in trade of all bird species globally can be used to identify species and groups of species that may be at particular risk of harm from trade and can inform conservation and policy interventions to reduce its adverse impacts.

Análisis de la prevalencia mundial de aves silvestres en el mercado Resumen El mercado representa una amenaza importante para muchas especies silvestres y a menudo es clandestino y mal vigilado. Por ello, la información sobre las especies más presentes en el mercado y bajo amenaza potencial todavía está fragmentada. Utilizamos siete conjuntos de datos mundiales sobre aves comercializadas para identificar especies o grupos de especies bajo riesgo especial y evaluamos hasta qué punto eran congruentes en cuanto a las especies registradas en el comercio. Utilizamos la frecuencia con la que las especies se registraban en los conjuntos de datos como base para una puntuación de prevalencia del comercio que se aplicó a todas las especies de aves a nivel mundial. Para validar la puntuación de prevalencia del comercio, realizamos búsquedas bibliográficas y cuestionarios para elaborar una lista de especies que se sabe son objeto de comercio intenso. Modelamos la puntuación para identificar los predictores significativos del mercado. Aunque los conjuntos de datos muestrearon partes distintas del amplio espectro del mercado, la congruencia entre ellos fue estadísticamente robusta en todas las comparaciones. Además, la frecuencia con la que se registraron las especies dentro de los conjuntos de datos se correlacionó positivamente con su presencia en todos los conjuntos de datos, lo que indica que la puntuación de prevalencia del mercado captó información sobre el volumen de este. La puntuación de prevalencia del mercado distinguió entre las especies identificadas a partir de evaluaciones semiindependientes como objeto de comercio intenso o insostenible y todas las demás especies. A nivel mundial, el 45.1% de todas las especies de aves y el 36.7% de las especies de aves amenazadas mundialmente tenían puntuaciones de prevalencia del mercado ≥1. Las especies incluidas en los Apéndices I o II de CITES, las especies con una amplia distribución geográfica y los no paseriformes tendieron a tener puntuaciones elevadas de prevalencia del mercado. Los órdenes de especies con puntuaciones medias de prevalencia del mercado elevadas fueron Falconiformes, Psittaciformes, Accipitriformes, Anseriformes, Bucerotiformes y Strigiformes. A pesar de su baja puntuación media de prevalencia, los Passeriformes representaron el mayor número total de especies comercializadas de todos los órdenes, pero tuvieron una baja representación en los apéndices de CITES. Los puntos calientes geográficos en los que coexisten un gran número de especies comercializadas difieren entre los paseriformes (Sudeste Asiático y Eurasia) y los no paseriformes (centro de Sudamérica, África subsahariana e India). Este primer intento de cuantificar y cartografiar la prevalencia relativa en el comercio de todas las especies de aves a escala mundial puede utilizarse para identificar especies y grupos de especies que pueden correr un riesgo especial de sufrir daños a causa del comercio y puede servir de base para intervenciones políticas y de conservación destinadas a reducir sus efectos adversos.

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.

Cardiac remodeling and inflammation detected by magnetic resonance imaging in COVID-19 survivors.

Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19. Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity. Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced. Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high.

Epidemiology, ventilation management and outcomes of COVID-19 ARDS patients versus patients with ARDS due to pneumonia in the Pre-COVID era.

BACKGROUND: Ventilation management may differ between COVID-19 ARDS (COVID-ARDS) patients and patients with pre-COVID ARDS (CLASSIC-ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC-ARDS also exist in COVID-ARDS. METHODS: Individual patient data analysis of COVID-ARDS and CLASSIC-ARDS patients in six observational studies of ventilation, four in the COVID-19 pandemic and two pre-pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator-free days and alive (VFD-60) at day 60. RESULTS: This analysis included 6702 COVID-ARDS patients and 1415 CLASSIC-ARDS patients. COVID-ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60-day mortality and less VFD-60 in both groups. Higher PEEP had an association with less VFD-60, but only in COVID-ARDS patients. CONCLUSIONS: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID-ARDS and CLASSIC-ARDS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.

Bioactive Compounds in Citrus Species with Potential for the Treatment of Chronic Venous Disease: A Review.

Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds in the Citrus genus, exploring their therapeutic potential in CVD treatment and addressing the gap in current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological effects of Citrus-derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among Citrus compounds. The review highlights the Citrus genus as a rich source of pharmacologically active compounds, notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective properties. Some of these compounds have been integrated into existing therapies, underscoring their potential for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more than 85% structural similarity. Citrus-derived bioactive compounds offer promising therapeutic potential for managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident. This review underlines the importance of advancing our understanding of these natural compounds and encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity method's introduction provides a novel approach to exploring the chemical diversity within the Citrus genus, opening new pathways for pharmacological research.

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.

Adherence to low tidal volume in the transition to spontaneous ventilation in patients with acute respiratory failure in intensive care units in Latin America (SPIRAL): a study protocol.

OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.

Residues in the fructose-binding pocket are required for ketohexokinase-A activity.

Excessive fructose consumption is a primary contributor to the global surges in obesity, cancer, and metabolic syndrome. Fructolysis is not robustly regulated and is initiated by ketohexokinase (KHK). In this study, we determined the crystal structure of KHK-A, one of two human isozymes of KHK, in the apo-state at 1.85 Å resolution, and we investigated the roles of residues in the fructose-binding pocket by mutational analysis. Introducing alanine at D15, N42, or N45 inactivated KHK-A, whereas mutating R141 or K174 reduced activity and thermodynamic stability. Kinetic studies revealed that the R141A and K174A mutations reduced fructose affinity by 2- to 4-fold compared to WT KHK-A, without affecting ATP affinity. Molecular dynamics simulations provided mechanistic insights into the potential roles of the mutated residues in ligand coordination and the maintenance of an open state in one monomer and a closed state in the other. Protein-protein interactome analysis indicated distinct expression patterns and downregulation of partner proteins in different tumor tissues, warranting a reevaluation of KHK's role in cancer development and progression. The connections between different cancer genes and the KHK signaling pathway suggest that KHK is a potential target for preventing cancer metastasis. This study enhances our understanding of KHK-A's structure and function and offers valuable insights into potential targets for developing treatments for obesity, cancer, and metabolic syndrome.

Prostaglandin E2 is an unreliable biomarker for inflammation in castrated piglets: a randomized controlled trial assessing pharmaceutical drug efficiency.

OBJECTIVE: To investigate the effect of intranasal (IN) flunixin meglumine (FM) and intra-inguinal (IG) lidocaine on castration inflammation using prostaglandin E2 (PGE2) concentration as a biomarker. METHODS: This randomized controlled trial was conducted in March 2022. Blood was collected at -24, 1, and 24 hours postcastration for PGE2 quantification from 195 piglets that received 1 of 8 treatments: (1) saline (1.5 mL) applied IG and IN (0.2 mL) followed by surgical castration (n = 24); (2) saline (1.5 mL) IG and IN (0.2 mL) followed by sham castration (25); (3) lidocaine (20 mg/kg or 1.5 mL) IG followed by surgical castration (24); (4) lidocaine (20 mg/kg or 1.5 mL) IG followed by sham castration (25); (5) FM (2.2 mg/kg) IN followed by surgical castration (25); (6) FM (2.2 mg/kg) IN followed by sham castration (24); (7) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by surgical castration (24); and (8) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by sham castration (24). RESULTS: Prostaglandin E2 concentrations did not increase following the castration procedure and were not an effective biomarker of castration inflammation. Piglets that received lidocaine demonstrated no difference in PGE2 levels across all time points. Piglets administered FM had lower PGE2 concentrations at 1 hour and 20 minutes postdrug administration in both the sham and castrated piglets. CONCLUSIONS: Prostaglandin E2 was not an effective biomarker to quantify castration inflammation. Flunixin meglumine was able to reduce PGE2 concentration in piglets regardless of castration procedure, but lidocaine had no impact. Decreased PGE2 levels in FM-treated pigs are likely associated with the drug's ability to mitigate a noncastration-associated inflammatory process occurring independent of the castration procedure. CLINICAL RELEVANCE: Flunixin meglumine reduced circulating PGE2 concentration in the blood, regardless of the castration procedure, indicating a potential for the drug to mitigate an inflammatory process unrelated to castration.

Boosting immunity: synergistic antiviral effects of luteolin, vitamin C, magnesium and zinc against SARS-CoV-2 3CLpro.

SARS-CoV-2 was first discovered in 2019 and has disseminated throughout the globe to pandemic levels, imposing significant health and economic burdens. Although vaccines against SARS-CoV-2 have been developed, their long-term efficacy and specificity have not been determined, and antiviral drugs remain necessary. Flavonoids, which are commonly found in plants, fruits, and vegetables and are part of the human diet, have attracted considerable attention as potential therapeutic agents due to their antiviral and antimicrobial activities and effects on other biological activities, such as inflammation. The present study uses a combination of biochemical, cellular, molecular dynamics, and molecular docking experiments to provide compelling evidence that the flavonoid luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one) has antiviral activity against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) that is synergistically enhanced by magnesium, zinc, and vitamin C. The IC50 of luteolin against 2 µM 3CLpro is 78 µM and decreases 10-fold to 7.6 µM in the presence of zinc, magnesium, and vitamin C. Thermodynamic stability analyses revealed that luteolin has minimal effects on the structure of 3CLpro, whereas metal ions and vitamin C significantly alter the thermodynamic stability of the protease. Interactome analysis uncovered potential host-virus interactions and functional clusters associated with luteolin activity, supporting the relevance of this flavone for combating SARS-CoV-2 infection. This comprehensive investigation sheds light on luteolin's therapeutic potential and provides insights into its mechanisms of action against SARS-CoV-2. The novel formulation of luteolin, magnesium, zinc, and vitamin C may be an effective avenue for treating COVID-19 patients.

3-chymotrypsin-like protease in SARS-CoV-2.

Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is a highly pathogenic human coronavirus that has caused the coronavirus disease 2019 (COVID-19) pandemic. It has led to a global viral outbreak with an exceptional spread and a high death toll, highlighting the need for effective antiviral strategies. 3-Chymotrypsin-like protease (3CLpro), the main protease in SARS-CoV-2, plays an indispensable role in the SARS-CoV-2 viral life cycle by cleaving the viral polyprotein to produce 11 individual non-structural proteins necessary for viral replication. 3CLpro is one of two proteases that function to produce new viral particles. It is a highly conserved cysteine protease with identical structural folds in all known human coronaviruses. Inhibitors binding with high affinity to 3CLpro will prevent the cleavage of viral polyproteins, thus impeding viral replication. Multiple strategies have been implemented to screen for inhibitors against 3CLpro, including peptide-like and small molecule inhibitors that covalently and non-covalently bind the active site, respectively. In addition, allosteric sites of 3CLpro have been identified to screen for small molecules that could make non-competitive inhibitors of 3CLpro. In essence, this review serves as a comprehensive guide to understanding the structural intricacies and functional dynamics of 3CLpro, emphasizing key findings that elucidate its role as the main protease of SARS-CoV-2. Notably, the review is a critical resource in recognizing the advancements in identifying and developing 3CLpro inhibitors as effective antiviral strategies against COVID-19, some of which are already approved for clinical use in COVID-19 patients.

The Combination of Enzymes and Conidia of Entomopathogenic Fungi against Aphis gossypii Nymphs and Spodoptera frugiperda Larvae.

The slow action of fungi is one of the biggest challenges in using entomopathogenic fungi. A promising alternative to reduce the time of action is to combine conidia with extracellular enzymes. This study aimed to characterize the production of Pr1 subtilisin protease and lipases by Beauveria bassiana and Metarhizium anisopliae in different culture media and to evaluate the efficiency of the enzymatic treatment against Aphis gossypii and Spodoptera frugiperda. The isolates were cultivated in five different liquid cultures, and, after 7 days, the culture was filtered and centrifuged, and the activity of the Pr1 and lipases was measured. The fungi cultured in a Luria-Bertani broth medium had the highest activity of proteases and lipases. The mortality of A. gossypii nymphs treated with conidia 7 days after the treatment was 39% (JEF-410), 76.5% (JEF-492), 74.8% (ERL-836), and 70.9% (JEF-214). The B. bassiana JEF-410 supernatant combined with conidia increased the fungal virulence at day 5 and day 6 after treatment. When S. frugiperda larvae were treated with B. bassiana JEF-492 conidia combined with its supernatant, the time of infection was shorter compared to the larvae treated with conidia only. Once the supernatant was incubated at 37 °C, the relative activity decreased from 100% to 80% after 2 h and to 45% after 24 h. The results suggest that the supernatant of entomopathogenic fungi may be formulated and used as a biopesticide in an efficient strategy for the biological control of pests.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.