DszA Catalyzes C-S Bond Cleavage through N5-Hydroperoxyl Formation.

Due to its detrimental impact on human health and the environment, regulations demand ultralow sulfur levels on fossil fuels, in particular in diesel. However, current desulfurization techniques are expensive and cannot efficiently remove heteroaromatic sulfur compounds, which are abundant in crude oil and concentrate in the diesel fraction after distillation. Biodesulfurization via the four enzymes of the metabolic 4S pathway of the bacterium Rhodococcus erythropolis (DszA-D) is a possible solution. However, the 4S pathway needs to operate at least 500 times faster for industrial applicability, a goal currently pursued through enzyme engineering. In this work, we unveil the catalytic mechanism of the flavin monooxygenase DszA. Surprisingly, we found that this enzyme follows a recently proposed atypical mechanism that passes through the formation of an N5OOH intermediate at the re side of the cofactor, aided by a well-defined, predominantly hydrophobic O2 pocket. Besides clarifying the unusual chemical mechanism of the complex DszA enzyme, with obvious implications for understanding the puzzling chemistry of flavin-mediated catalysis, the result is crucial for the rational engineering of DszA, contributing to making biodesulfurization attractive for the oil refining industry.

Blood cell alterations in Colossoma macropomum juveniles caused by silver nanoparticles.

This study evaluated the median lethal concentration of silver nanoparticles and their effects in fish tambaqui Colossoma macropomum. Therefore, an acute toxicity assay was carried out in completely randomized design evaluating six different concentrations of silver nanoparticles on blood parameters of tambaqui. The silver nanoparticles were produced by chemical reduction with polyvinyl alcohol (AgNP-PVA). The lethal concentration 50% (LC50) was estimated using probit regression. The blood was collected, analyzed and the data were submitted to T-test (dying x surviving fish) and Tukey test (surviving fish). An increase in glucose, hematocrit, total plasma protein, hemoglobin, erythrocytes, leukocytes, monocytes, and neutrophils as well as reduced MCV (mean corpuscular volume) in dying fish compared to surviving fish were observed. Survived fish exposed to 187.5 µg/L showed an increase in hematocrit, MCV, and MCH and a reduction in erythrocytes, total numbers of leukocyte, thrombocyte, lymphocyte, and neutrophil. The fish exposed to concentrations below 125 µg/L, had returned the blood parameter to baselines compared to control. The estimated LC50 was 165.09 µg/L and was classified as highly toxic for the fish tambaqui. In higher concentrations, it causes an acute respiratory toxicity, but in concentrations below 125 µg/L, the fish can adapt to the stressing agent.

Phytoconstituents and Ergosterol Biosynthesis-Targeting Antimicrobial Activity of Nutmeg (Myristica fragans Houtt.) against Phytopathogens.

In recent years, nutmeg (Myristica fragans Houtt.) has attracted considerable attention in the field of phytochemistry due to its diverse array of bioactive compounds. However, the potential application of nutmeg as a biorational for crop protection has been insufficiently explored. This study investigated the constituents of a nutmeg hydroethanolic extract via gas chromatography-mass spectrometry and vibrational spectroscopy. The research explored the extract's activity against phytopathogenic fungi and oomycetes, elucidating its mechanism of action. The phytochemical profile revealed fatty acids (including tetradecanoic acid, 9-octadecenoic acid, n-hexadecanoic acid, dodecanoic acid, and octadecanoic acid), methoxyeugenol, and elemicin as the main constituents. Previously unreported phytochemicals included veratone, gelsevirine, and montanine. Significant radial growth inhibition of mycelia was observed against Botrytis cinerea, Colletotrichum acutatum, Diplodia corticola, Phytophthora cinnamomi, and especially against Fusarium culmorum. Mode of action investigation, involving Saccharomyces cerevisiae labeled positively with propidium iodide, and a mutant strain affected in ERG6, encoding sterol C-24 methyltransferase, suggested that the extract induces a necrotic type of death and targets ergosterol biosynthesis. The evidence presented underscores the potential of nutmeg as a source of new antimicrobial agents, showing particular promise against F. culmorum.

The Challenging World of Simple Inorganic Rings: Revisiting Roesky's Ketone and Roesky's Sulfoxide.

The surprising differences between the experimental solid-state and calculated gas-phase structures of 5-oxo-1,3,2,4-dithiadiazole (Roesky's ketone, 1) and 1-oxo-1,2,4,3,5-trithiadiazole (Roesky's sulfoxide, 2), identified and studied in a series of papers published between 2004 and 2010 but then never satisfactorily explained, have been revisited, making use of the more advanced computational possibilities currently available. The previous calculations' considerable overestimations of the C-S and S-S bond lengths in 1 and 2, respectively, have been partly explained based on the results of periodic calculations and the application of Valence Bond (VB) Theory. In the case of 1, the crystal environment appears to stabilize a structure with a highly polarized C=O bond, which features a C-S bond with considerable double-bond character - an effect which does not exist for the isolated molecule - explaining the much shorter bond in the solid state. For 2, a similar conclusion can be drawn for the S-S distance. For both compounds, though, packing effects are not the sole source of the differences: the inability of Density Functional Theory (DFT) to properly deal with the electronic structures of these apparently simple main-group systems remains a contributing factor.

Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.

Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.

Dream-enactment behaviours during the COVID-19 pandemic: an international COVID-19 sleep study.

There has been increasing concern about the long-term impact of coronavirus disease 2019 (COVID-19) as evidenced by anecdotal case reports of acute-onset parkinsonism and the polysomnographic feature of increased rapid eye movement sleep electromyographic activity. This study aimed to determine the prevalence and correlates of dream-enactment behaviours, a hallmark of rapid eye movement sleep behaviour disorder, which is a prodrome of α-synucleinopathy. This online survey was conducted between May and August 2020 in 15 countries/regions targeting adult participants (aged ≥18 years) from the general population with a harmonised structured questionnaire on sleep patterns and disorders, COVID-19 diagnosis and symptoms. We assessed dream-enactment behaviours using the Rapid Eye Movement Sleep Behaviour Disorder Single-Question Screen with an additional question on their frequency. Among 26,539 respondents, 21,870 (82.2%) answered all items that were analysed in this study (mean [SD] age 41.6 [15.8] years; female sex 65.5%). The weighted prevalence of lifetime and weekly dream-enactment behaviours was 19.4% and 3.1% and were found to be 1.8- and 2.9-times higher in COVID-19-positive cases, respectively. Both lifetime and weekly dream-enactment behaviours were associated with young age, male sex, smoking, alcohol consumption, higher physical activity level, nightmares, COVID-19 diagnosis, olfactory impairment, obstructive sleep apnea symptoms, mood, and post-traumatic stress disorder features. Among COVID-19-positive cases, weekly dream-enactment behaviours were positively associated with the severity of COVID-19. Dream-enactment behaviours are common among the general population during the COVID-19 pandemic and further increase among patients with COVID-19. Further studies are needed to investigate the potential neurodegenerative effect of COVID-19.

Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions.

BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (ß = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

Facilitators of and Barriers to Accessing Hospital Medical Specialty Telemedicine Consultations During the COVID-19 Pandemic: Systematic Review.

BACKGROUND: The COVID-19 pandemic accelerated the digital transition in health care, which required a rapid adaptation for stakeholders. Telemedicine has emerged as an ideal tool to ensure continuity of care by allowing remote access to specialized medical services. However, its rapid implementation has exacerbated disparities in health care access, especially for the most susceptible populations. OBJECTIVE: We aimed to characterize the determinant factors (facilitators and barriers) of access to hospital medical specialty telemedicine consultations during the COVID-19 pandemic and to identify the main opportunities and challenges (technological, ethical, legal, and social) generated by the use of telemedicine in the context of the COVID-19 pandemic. METHODS: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 4 databases (Scopus, Web of Science, PubMed, and Cochrane COVID-19 Study Register) were searched for empirical studies published between January 3, 2020, and December 31, 2021, using established criteria. The protocol of this review was registered and published in PROSPERO (CRD42022302825). A methodological quality assessment was performed, and the results were integrated into a thematic synthesis. The identification of the main opportunities and challenges was done by interpreting and aggregating the thematic synthesis results. RESULTS: Of the 106 studies identified, 9 met the inclusion criteria and the intended quality characteristics. All studies were originally from the United States. The following facilitating factors of telemedicine use were identified: health insurance coverage; prevention of SARS-CoV-2 infection; access to internet services; access to technological devices; better management of work-life balance; and savings in travel costs. We identified the following barriers to telemedicine use: lack of access to internet services; lack of access to technological devices; racial and ethnic disparities; low digital literacy; low income; age; language barriers; health insurance coverage; concerns about data privacy and confidentiality; geographic disparities; and the need for complementary diagnostic tests or the delivery of test results. CONCLUSIONS: The facilitating factors and barriers identified in this systematic review present different opportunities and challenges, including those of a technological nature (access to technological devices and internet services and level of digital literacy), a sociocultural and demographic nature (ethnic and racial disparities, geographic disparities, language barriers, and age), a socioeconomic nature (income level and health insurance coverage), and an ethical and legal nature (data privacy and confidentiality). To expand telemedicine access to hospital-based specialty medical consultations and provide high-quality care to all, including the most susceptible communities, the challenges identified must be thoroughly researched and addressed with informed and dedicated responses.

Optimism and fear of COVID-19 in higher education students: the mediating role of general anxiety.

Higher education students have faced several changes in their lives due to the COVID-19 pandemic. This study aims to explore the effect of dispositional optimism in students' fear of COVID-19 and to test the mediating role of general anxiety in the relationship between optimism and fear. Using an online survey, data were collected during the second wave of the pandemic in Portugal. The sample included 312 higher education students (76% females) aged 18-25 years old, who completed measures of dispositional optimism, general anxiety and fear of COVID-19. The results showed that higher optimism and lower general anxiety reduce fear of COVID-19. Moreover, the link between optimism and fear is fully mediated by general anxiety, showing that optimism reduces fear of COVID-19 indirectly through the reduction of students' anxiety. The role of optimism, anxiety and fear in higher education students is discussed and topics for further research are presented.

The Halogen Bond in Weakly Bonded Complexes and the Consequences for Aromaticity and Spin-Orbit Coupling.

The halogen bond complexes CF3X⋯Y and C2F3X⋯Y, with Y = furan, thiophene, selenophene and X = Cl, Br, I, have been studied by using DFT and CCSD(T) in order to understand which factors govern the interaction between the halogen atom X and the aromatic ring. We found that PBE0-dDsC/QZ4P gives an adequate description of the interaction energies in these complexes, compared to CCSD(T) and experimental results. The interaction between the halogen atom X and the π-bonds in perpendicular orientation is stronger than the interaction with the in-plane lone pairs of the heteroatom of the aromatic cycle. The strength of the interaction follows the trend Cl < Br < I; the chalcogenide in the aromatic ring nor the hybridization of the C−X bond play a decisive role. The energy decomposition analysis shows that the interaction energy is dominated by all three contributions, viz., the electrostatic, orbital, and dispersion interactions: not one factor dominates the interaction energy. The aromaticity of the ring is undisturbed upon halogen bond formation: the π-ring current remains equally strong and diatropic in the complex as it is for the free aromatic ring. However, the spin-orbit coupling between the singlet and triplet π→π* states is increased upon halogen bond formation and a faster intersystem crossing between these states is therefore expected.

Developing a Compost Quality Index (CQI) Based on the Electrochemical Quantification of Cd (HA) Reactivity.

The present work demonstrates the use of Cd2+ as a reactivity probe of the fulvic acids (FAs), humic acids (HAs) and dissolved organic matter (DOM) compost extracts. Significant differences were observed between the extracts, with the HA extract showing the highest reactivity. Comparing the different composts, the largest reactivity variation was again observed for HA then FA and finally DOM extracts. The Cd2+ binding extent was used to calculate the quality of composts and compared with a reference of uncomposted organic fertiliser (FLW), leading to the definition of an operational scale of compost quality. The parameter equivalent mass of fertiliser (mEF) was used for this scale sorted the seven composts from 0.353 to 1.09 kg FLW, for compost of sewage sludge (CSS) and vermicompost of domestic waste (CVDW), respectively. The significance of this parameter was verified through a correlation analysis between binding extent and the effect of compost application on lettuce crop growth in a field trial. The results demonstrate the potentiality of FA and HA extracts as markers of compost bioactivity and the use of Cd2+ as a reactivity probe.

Africanized honeybee (Apis mellifera) semen freezing using Tris-based and Collins extenders.

This study is aimed at evaluating the effect of different extenders on the cryopreservation of semen from Africanized honeybees (A. mellifera). Semen from honeybee drones from 10 different colonies was obtained by endophallus exposure technique and immediately evaluated for motility, viability using fluorescent probes, functional membrane integrity using the water test, and morphology. Samples from each colony were divided in three aliquots and subjected to a dilution ratio of 12:1 (diluent: semen) using Tris, Tris + egg yolk (Tris+EY), and Collins extender. Samples were cryopreserved and stored in liquid nitrogen for one week and then rewarmed and reevaluated. Immediate dilution provoked no significant effect on sperm motility and functional membrane integrity, regardless of the extender used; however, the greatest values (P < 0.05) for normal sperm morphology were found at the use of isolate Tris (69.3 ± 1.9%). After thawing, there were no significant differences among extenders with relation to the preservation of sperm motility, viability, and functional membrane integrity, but the Tris extender provided the highest post-thawing values (P < 0.05) for sperm normal morphology (49.2 ± 4.9%) while the Collins extender provoked the highest amounts (P < 0.05) of curled tail defects (67.5 ± 3.2%). Moreover, the Tris was the only extender at preserving the proportion of normal sperm after thawing similar to what was verified for fresh samples. In summary, we suggest the use of a Tris-based extender for the cryopreservation of Africanized honeybee semen.

Different Enzyme Conformations Induce Different Mechanistic Traits in HIV-1 Protease.

The influence of the dynamical flexibility of enzymes on reaction mechanisms is a cornerstone in biological sciences. In this study, we aim to 1) study the convergence of the activation free energy by using the first step of the reaction catalysed by HIV-1 protease as a case study, and 2) provide further evidence for a mechanistic divergence in this enzyme, as two different reaction pathways were seen to contribute to this step. We used quantum mechanics/molecular mechanics molecular dynamics simulations, on four different initial conformations that led to different barriers in a previous study. Despite the sampling, the four activation free energies still spanned a range of 5.0 kcal ⋅ mol-1 . Furthermore, the new simulations did confirm the occurrence of an unusual mechanistic divergence, with two different mechanistic pathways displaying equivalent barriers. An active-site water molecule is proposed to influence the mechanistic pathway.

Towards the Accurate Thermodynamic Characterization of Enzyme Reaction Mechanisms.

We employed QM/MM molecular dynamics (MD) simulations to characterize the rate-limiting step of the glycosylation reaction of pancreatic α-amylase with combined DFT/molecular dynamics methods (PBE/def2-SVP : AMBER). Upon careful choice of four starting active site conformations based on thorough reactivity criteria, Gibbs energy profiles were calculated with umbrella sampling simulations within a statistical convergence of 1-2 kcal ⋅ mol-1 . Nevertheless, Gibbs activation barriers and reaction energies still varied from 11.0 to 16.8 kcal ⋅ mol-1 and -6.3 to +3.8 kcal ⋅ mol-1 depending on the starting conformations, showing that despite significant state-of-the-art QM/MM MD sampling (0.5 ns/profile) the result still depends on the starting structure. The results supported the one step dissociative mechanism of Asp197 glycosylation preceded by an acid-base reaction by the Glu233, which are qualitatively similar to those from multi-PES QM/MM studies, and thus support the use of the latter to determine enzyme reaction mechanisms.

Effects of rapid fluid infusion on hemoglobin concentration: a systematic review and meta-analysis.

BACKGROUND: Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration. METHODS: Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. RESULTS: Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as "low" for randomized controlled trials (RCTs) and 'low to moderate' for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI - 1.45 to - 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI - 1.69 to - 1.42; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI - 1.03 to - 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb. CONCLUSIONS: Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.

[Fe4S4] cubane in sulfite reductases: new insights into bonding properties and reactivity.

The dissimilatory sulfite reductase enzyme has very characteristic active site where the substrate binds to an iron site, ligated by a siroheme macrocycle and a thiol directly connected to a [Fe4S4] cluster. This arrangement gives the enzyme remarkable efficiency in reducing sulfite and nitrite all the way to hydrogen sulfide and ammonia. For the first time we present a theoretical study where substrate binding modalities and activation are elucidated using active site models containing proton supply side chains and the [Fe4S4] cluster. Density functional theory (DFT) was deployed in conjunction with the energy decomposition scheme (as implemented in AMS), the quantum theory of atoms in molecules (QTAIM), and conceptual DFT (cDFT) descriptors. We quantified the role of the electrostatic interactions inside the active site created by the side chains as well as the influence of the [Fe4S4] cluster on the substrate binding. Furthermore, using conceptual DFT results we shed light of the activation process, thus, laying foundation for further mechanistic studies. We found that the bonding of the ligands to the iron complex is dominated by electrostatic interactions, but the presence of the [Fe4S4] cubane leads to substantial changes in electronic interaction. The spin state of the cubane, however, affects the binding energy only marginally. The conceptual DFT results show that the presence of the [Fe4S4] cubane affects the reactivity of the active site as it is involved in electron transfer. This is corroborated by an increase in the electrophilicity index, thus making the active site more prone to react with the ligands. The interaction energies between the ligand and the siroheme group are also increased upon the presence of the cubane group, thus, suggesting that the siroheme group is not an innocent spectator but plays an active role in the reactivity of the dSIR active site.

Potential of propolis antifungal activity for clinical applications.

The high incidence of skin diseases of microbial origin along with the widespread increase of microbial resistance demand for therapeutic alternatives. Research on natural compounds has been opening new perspectives for the development of new therapies with health-positive impacts. Propolis, a resinous mixture produced by honeybees from plant exudates, is widely used as a natural medicine since ancient times, mainly due to its antimicrobial properties. More recently, antioxidant, anti-tumour, anti-inflammatory, hepatoprotective and immunomodulatory activities were also reported for this natural product, highlighting its high potential pharmacological interest. In the present work, an extensive review of the main fungi causing skin diseases as well as the effects of natural compounds, particularly propolis, against such disease-causing micro-organisms was organized and compiled in concise handy tables. This information allows to conclude that propolis is a highly effective antimicrobial agent suggesting that it could be used as an alternative skin treatment against pathogenic micro-organisms and also as a cosmeceutical component or as a source of bioactive ingredients.

Propolis antibacterial and antioxidant synergisms with gentamicin and honey.

AIMS: Assess the antibacterial and antioxidant effects of ethanol extracts of Portuguese propolis samples when combined with gentamicin, a widely used aminoglycoside antibiotic, or with honey, collected from the same apiary as propolis. METHODS AND RESULTS: Using the agar dilution method and DPPH free radical scavenging assay, antimicrobial and antioxidant synergistic effects between propolis and gentamicin or honey were assessed. Synergism between propolis and gentamicin was observed for all the tested extracts and against all the indicator bacteria, with particular interest against the Methicillin-Resistant Staphylococcus aureus (MRSA) with a threefold decrease of the gentamicin MIC if mixed with 25 µg ml-1 propolis. Likely to propolis and gentamicin, mixtures of sub-MIC concentrations of propolis and honey enhanced the antibacterial action of each individual natural product against the majority of the strains. However, propolis antioxidant capacity decreased along with higher honey content in the mixture. CONCLUSIONS: Propolis has a strong synergistic effect when combined with gentamicin, allowing the reduction of the therapeutic dose of this drug. Propolis and honey mixtures also display a stronger antibacterial effect than the activity exhibited by each sample when tested individually, whereas the high antioxidant capacity of propolis seems to be not affected when in combination with honey. SIGNIFICANCE AND IMPACT OF STUDY: When mixed with honey, propolis antioxidant potential is maintained, or just slightly reduced up to 1:1 dilution, and show synergistic antibacterial effects, allowing to optimize the use of this usually scarce natural resource. Also, considering the antibiotic resistance problem, natural beehive products, alone or in the mixture, are promising alternatives to retard the outbreak of microbial resistance.

Prevalence and Area of Retinal Pigment Epithelium and Outer Retinal Atrophy in Eyes with Non-Exudative Macular Neovascularization.

PURPOSE: The objective of this study wasto assess the prevalence of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in patients with unilateral exudative age-related macular degeneration (AMD) of the fellow eye and establish if the presence of non-exudative macular neovascularization (NE-MNV) influences the prevalence of RPE and outer retinal atrophy in eyes with AMD. METHODS: This is an observational cross-sectional study of 68 patients with unilateral exudative AMD. Demographic and clinical data were collected, and multimodal retinal imaging was performed in all patients. Two groups of patients were defined according to the presence (NE-MNV) or absence (no NE-MNV) of NE-MNV in the study eye. We compared the prevalence of tomographic cRORA and fundus autofluorescence (FAF) geographic atrophy (GA) and differences in cRORA greatest linear diameter (GLD) and GA area between groups. RESULTS: Globally, cRORA was present in 11 eyes (16.2%), FAF GA was present in 10 eyes (14.7%), and NE-MNV was present in 10 eyes (14.7%) of patients with unilateral exudative AMD of the fellow eye. The overall cRORA GLD was 1,950.64 ± 1,428.31 µm, and the mean area of GA was 9.25 ± 7.50 mm2. Regarding comparisons between groups, cRORA was present in 9 eyes (15.5%) without NE-MNV and in 2 eyes (20%) with NE-MNV (p = 0.66). Tomographic signs of atrophy were more frequent in eyes with NE-MNV (50% vs. 24.1% in eyes without NE-MNV; p = 0.008). No significant differences were found in cRORA GLD (p = 0.30) between groups. Eyes with NE-MNV and eyes without NE-MNV had a similar prevalence of FAF GA (2 eyes out of 10 and 8 eyes out of 58, respectively; p = 0.64). Eyes with NE-MNV had a smaller mean area of GA (2.07 ± 0.24 mm2 vs. 11.05 ± 7.34 mm2; p = 0.01). CONCLUSION: In our study, the presence of NE-MNV was not associated with the prevalence of cRORA and/or FAF GA. Nonetheless, eyes with NE-MNV presented smaller areas of GA, which suggests that this type of neovascularization may prevent the progression of RPE and outer retinal atrophy. Longitudinal studies are required to confirm these preliminary results.

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome.

PURPOSE: The aim of this study was to evaluate microvascular abnormalities of patients with Alport syndrome (AS) using optical coherence tomography angiography (OCT-A) quantitative biomarkers. METHODS: This was cross sectional, prospective evaluation of consecutive patients with AS and healthy subjects. AS diagnosis was performed by the genetic test. All participants underwent a retinal vasculature evaluation by spectral-domain optical coherence tomography (SD-OCT) and OCT-A of the macula. Quantitative analysis included whole vascular density, foveal avascular zone area, fractal dimension (FD), and lacunarity (LAC). RESULTS: Ninety-four eyes were included in this study, 45 eyes from patients with AS and 49 eyes from healthy subjects. The pathogenic mutation in the COL4A5 gene on the chromosome X was found in 14 patients; the pathogenic autosomal recessive mutations in the COL4A3 gene were found in 9 patients. Quantitative evaluation demonstrated a significant difference between AS and healthy subjects on LAC of the superficial capillary plexus and deep capillary plexus (DCP) (p < 0.001 and p < 0.001, respectively) and on FD in the DCP (p < 0.001). CONCLUSION: The DCP Alport patients have a higher vessel nonuniformity than DCP of healthy subjects. We hypothesize that endothelial cell lesion in the setting of low resistance at the DCP circuit could lead to long-term structural disorganization.