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Irineu Ribeiro De Melo Jnr,1 Wilson Takashi Hida,1– 3 Bernardo Kaplan Moscovici,4,5 Cesar Vilar,1,2 Antonio Francisco Pimenta Motta,1 Andre Lins de Medeiros,1 Mario Augusto Pereira Dias Chaves,1 Jonathan Clive Lake,1 Walton Nose,4 Pedro Carlos Carricondo3 1Department of Ophthalmology, Hospital Oftalmológico De Brasília, Brasília, DF, Brazil; 2Department of Ophthalmology, Renato Ambrosio Eye Research Center, Brasília, DF, Brazil; 3Department of Ophthalmology, University of Sao Paulo, São Paulo, SP, Brazil; 4Department of Ophthalmology, Federal University of Sao Paulo UNIFESP, São Paulo, SP, Brazil; 5Department of Ophthalmology, Hospital Visão Laser, Santos, SP, BrazilCorrespondence: Bernardo Kaplan Moscovici, Email bernardokaplan@yahoo.com.brPurpose: Validate a novel approach for assessing residual astigmatism’s impact on visual acuity in pseudophakic patients using defocus curves and spherical equivalent compensation.Materials and Methods: Thirteen patients over 40 with cataracts and normal ophthalmological examinations were enrolled in a prospective, non-randomized cohort study. The defocus curve method was employed, wherein visual acuity was measured with spherical lenses ranging from − 2.50 to +2.50 diopters in 0.5 diopter increments based on subjective refraction. Cylindrical lenses (+1, +2, and +3 diopters) were introduced at each spherical diopter’s 90° and 180° axes. Curves’ results were compared at each defocus point to assess the impact of astigmatism. The Kruskal–Wallis test was used to determine if astigmatism significantly affected visual acuity post-phacoemulsification surgery with intraocular lens implantation.Results: Significant p-values were observed only for defocus curve points of − 0.5, 0, +0.5, and +1, indicating rejection of the hypothesis of no difference between the 90° and 180° groups at these points. Although statistical significance was not achieved, the against-the-rule (ATR) group was inclined toward improved near and intermediate visual acuity. In contrast, the with-the-rule (WTR) group tended to enhance distance visual acuity and myopic tolerance.Conclusion: This novel methodology is both reproducible and valuable. It offers potential insight into residual astigmatism tolerance in pseudophakic patients. Its application may aid in surgical planning and intraocular lens decision-making.Keywords: cataract, astigmatism, visual acuity, treatment result

Understanding circadian clock mechanisms is fundamental in order to counteract the harmful effects of clock malfunctioning and associated diseases. Biochemical, genetic and systems biology approaches have provided invaluable information on the mechanisms of the circadian clock, from which many mathematical models have been developed to understand the dynamics and quantitative properties of the circadian oscillator. To better analyze and compare quantitatively all these circadian cycles, we propose a method based on a previously proposed circadian cycle segmentation into stages. We notably identify a sequence of eight stages that characterize the progress of the circadian cycle. Next, we apply our approach to an experimental dataset and to five different models, all built with ordinary differential equations. Our method permits to assess the agreement of mathematical model cycles with biological properties or to detect some inconsistencies. As another application of our method, we provide insights on how this segmentation into stages can help to analyze the effect of a clock gene loss of function on the dynamic of a genetic oscillator. The strength of our method is to provide a benchmark for characterization, comparison and improvement of new mathematical models of circadian oscillators in a wide variety of model systems., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Circadian clocks form a fundamental mechanism that promotes the correct behavior of many cellular and molecular processes by synchronizing them on a 24 h period. However, the circadian cycles remain difficult to describe mathematically. To overcome this problem, we first propose a segmentation of the circadian cycle into eight stages based on the levels of expression of the core clock components CLOCK:BMAL1, REV-ERB and PER:CRY. This cycle segmentation is next characterized through a piecewise affine model, whose analytical study allows us to propose an Algorithm to generate biologically-consistent circadian oscillators. Our study provides a characterization of the cycle dynamics in terms of four fundamental threshold parameters and one scaling parameter, shows robustness of the circadian system and its period, and identifies critical points for correct cycle progression., Competing Interests: Declarations. Conflict of interest: The authors declare no Conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brazil is one of the world's largest beer producers and also a major food producer. These activities generate a large amount of residues which, if disposed of inappropriately, can have adverse effects on the environment. The objective of this research was to evaluate the potential of using these residues for both mushroom cultivation (traditional use) and the production of mycelium-based composites (innovative use). Mushroom production (Pleurotus sajor-caju) was conducted using only brewer's spent grains (fresh and dried) and also mixed with banana leaves (1:1) or peach palm leaves (1:1), which are residues widely available in the northern region of Santa Catarina, Brazil. The productivity of mushrooms cultivated using fresh and dried brewer's spent grains did not exhibit a statistically significant difference, indicating that this residue can be utilized shortly after its generation in the industrial process, thereby reducing costs associated with production. Combining brewer's spent grains with banana or peach palm leaves resulted in enhanced mushroom production (0.41 and 0.38 g day -1 , respectively) compared to using the leaves as a sole substrate. The mushrooms produced contain sugars and a minimal sodium content, and are considered a source of phosphorus. In addition, no toxic elements (Hg and Pb) were present. The mycelium-based composites produced using the residual substrate (after the mushroom harvest) exhibited better mechanical properties (compressive strength = 0.04 MPa, density = 242 kg m -3 , and low humidity sorption) than those produced using fresh substrate. The results demonstrate the synergistic effect of combining the two approaches under investigation. The use of brewer´s spent enhance the mushroom productivity and the residual substrate enhance the mechanical properties of mycelium-based composites. The compressive strength, density, and air humidity sorption properties are essential for determining the potential applications of mycelium-based composites. The use of brewer's spent grains mixed with banana leaves demonstrated significant promise for mushroom production and subsequent application in the development of mycelium-based composites. These sequential approaches contribute to waste valorization and the rational utilization of natural resources, as the mycelium-based composites are considered for substitution of synthetic materials, thereby promoting sustainability for future generations., (© 2024. The Author(s).)

Avian influenza virus (AIV) is a significant threat to the poultry industry, necessitating rapid and accurate diagnosis. The current AIV diagnostic process relies on virus identification via real-time reverse transcription-polymerase chain reaction (rRT-PCR). Subsequently, the virus is further characterized using genome sequencing. This two-step diagnostic process takes days to weeks, but it can be expedited by using novel sequencing technologies. We aim to optimize and validate nucleic acid extraction as the first step to establishing Oxford Nanopore Technologies (ONT) as a rapid diagnostic tool for identifying and characterizing AIV from clinical samples. This study compared four commercially available RNA extraction protocols using AIV-known-positive clinical samples. The extracted RNA was evaluated using total RNA concentration, viral copies as measured by rRT-PCR, and purity as measured by a 260/280 absorbance ratio. After NGS testing, the number of total and influenza-specific reads and quality scores of the generated sequences were assessed. The results showed that no protocol outperformed the others on all parameters measured; however, the magnetic particle-based method was the most consistent regarding C T value, purity, total yield, and AIV reads, and it was less error-prone. This study highlights how different RNA extraction protocols influence ONT sequencing performance.

Trypanosoma cruzi , the causative agent of Chagas disease ( American trypanosomiasis ), is a highly complex zoonosis that is present throughout South America, Central America, and Mexico. The transmission of this disease is influenced by various factors, including human activities like deforestation and land use changes, which may have altered the natural transmission cycles and their connection to the environment. In this study conducted in the Argentine Chaco region, we examined the transmission dynamics of T. cruzi by collecting blood samples from wild and domestic animals, as well as triatomine bugs from human dwellings, across five sites of varying anthropic intervention. Samples were analyzed for T. cruzi infection via qPCR, and we additionally examined triatomines for bloodmeal analysis via NGS amplicon sequencing. Our analysis revealed a 15.3% infection rate among 20 wild species (n = 123) and no T. cruzi presence in 9 species of domestic animals (n = 1359) or collected triatomines via qPCR. Additionally, we found chicken (34.28%), human (21.59%), and goat (19.36%) as the predominant bloodmeal sources across all sites. These findings suggest that anthropic intervention and other variables analyzed may have directly impacted the spillover dynamics of T. cruzi 's sylvatic cycle and potentially reduced its prevalence in human habitats.

This article provides a comprehensive review of the state-of-the-art technology of polymeric mixed-matrix membranes for CO 2 /CH 4 separation that can be applied in medium, small, and domestic biogas systems operating at low pressures (0.2-6 kPa). Critical data from the latest publications of CO 2 /CH 4 separation membranes were analyzed, considering the ratio of CO 2 /CH 4 permeabilities, the CO 2 selectivity, the operating pressures at which the membranes were tested, the chemistry of the polymers studied and their gas separation mechanisms. And the different nanomaterials as fillers. The intrinsic microporous polymers (PIMs) were identified as potential candidates for biomethane purification due to their high permeability and selectivity, which are compatible with operation pressures below 1 bar, and as low as 0.2 bar. This scenario contrasts with other polymers that require pressures above 1 bar for operation, with some reaching 20 bar. Furthermore, the combination of PIM with GO in MMMs was found to not influence the permeability significantly, but to contribute to the membrane stability over time, by preventing the structural collapse of the membrane caused by aging. The systematic analysis here presented is a valuable resource for defining the future technological development of CO 2 /CH 4 separation membranes for biogas biorefining., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guerrero Piña, Alpízar, Murillo, Carpio-Chaves, Pereira-Reyes, Vega-Baudrit and Villarreal.)

Trioza erytreae (Del Guercio, 1918) (Hemiptera: Triozidae) is a citrus pest which produces gall symptoms on leaves and transmits bacteria associated with the citrus disease Huanglongbing, ' Candidatus Liberibacter' spp. In the present work, the biology and behaviour of T. erytreae were studied in different rootstock-cultivar combinations. Six rootstocks were used, Flying dragon (FD), 'Cleopatra' mandarin (CL), Carrizo citrange (CC), Forner-Alcaide no.5 (FA5), Forner-Alcaide no.517 (FA517) and Citrus macrophylla (CM), and six scion cultivars: 'Star Ruby', 'Clemenules', 'Navelina', 'Valencia Late', 'Fino 49' and 'Ortanique'. Survival and oviposition were evaluated in a no-choice trial, and preference in a choice trial, all of them under greenhouse conditions. Trioza erytreae did not show a clear settle preference for any citrus combination. However, it was able to lay more eggs in 'Fino 49' grafted on CC than on FD. In terms of survival, 'Ortanique' grafted onto FA5 was more suitable than when grafted onto FA517, and in the case of 'Valencia Late', when it was grafted onto CM rather than CC. Our results showed that T. erytreae behave differently depending on the citrus combination.

Using information-theoretic quantities in practical applications with continuous data is often hindered by the fact that probability density functions need to be estimated in higher dimensions, which can become unreliable or even computationally unfeasible. To make these useful quantities more accessible, alternative approaches such as binned frequencies using histograms and k -nearest neighbors ( k -NN) have been proposed. However, a systematic comparison of the applicability of these methods has been lacking. We wish to fill this gap by comparing kernel-density-based estimation (KDE) with these two alternatives in carefully designed synthetic test cases. Specifically, we wish to estimate the information-theoretic quantities: entropy, Kullback-Leibler divergence, and mutual information, from sample data. As a reference, the results are compared to closed-form solutions or numerical integrals. We generate samples from distributions of various shapes in dimensions ranging from one to ten. We evaluate the estimators' performance as a function of sample size, distribution characteristics, and chosen hyperparameters. We further compare the required computation time and specific implementation challenges. Notably, k -NN estimation tends to outperform other methods, considering algorithmic implementation, computational efficiency, and estimation accuracy, especially with sufficient data. This study provides valuable insights into the strengths and limitations of the different estimation methods for information-theoretic quantities. It also highlights the significance of considering the characteristics of the data, as well as the targeted information-theoretic quantity when selecting an appropriate estimation technique. These findings will assist scientists and practitioners in choosing the most suitable method, considering their specific application and available data. We have collected the compared estimation methods in a ready-to-use open-source Python 3 toolbox and, thereby, hope to promote the use of information-theoretic quantities by researchers and practitioners to evaluate the information in data and models in various disciplines.

Cochlear outer hair cells (OHCs) are electromotile and are implicated in mechanisms of amplification of responses to sound that enhance sound sensitivity and frequency tuning. They send information to the brain through glutamatergic synapses onto a small subpopulation of neurons of the ascending auditory nerve, the type II spiral ganglion neurons (SGNs). The OHC synapses onto type II SGNs are sparse and weak, suggesting that type II SGNs respond primarily to loud and possibly damaging levels of sound. OHCs also receive innervation from the brain through the medial olivocochlear (MOC) efferent neurons. MOC neurons are cholinergic yet exert an inhibitory effect on auditory function as they are coupled to alpha9/alpha10 nicotinic acetylcholine receptors (nAChRs) on OHCs, which leads to calcium influx that gates SK potassium channels. The net hyperpolarization exerted by this efferent synapse reduces OHC activity-evoked electromotility and is implicated in cochlear gain control, protection against acoustic trauma, and attention. MOC neurons also label for markers of gamma-aminobutyric acid (GABA) and GABA synthesis. GABA B autoreceptor (GABA B R) activation by GABA released from MOC terminals has been demonstrated to reduce ACh release, confirming important negative feedback roles for GABA. However, the full complement of GABAergic activity in the cochlea is not currently understood, including the mechanisms that regulate GABA release from MOC axon terminals, whether GABA diffuses from MOC axon terminals to other postsynaptic cells, and the location and function of GABA A receptors (GABA A Rs). Previous electron microscopy studies suggest that MOC neurons form contacts onto several other cell types in the cochlea, but whether these contacts form functional synapses, and what neurotransmitters are employed, are unknown. Here we use immunohistochemistry, optical neurotransmitter imaging and patch-clamp electrophysiology from hair cells, afferent dendrites, and efferent axons to demonstrate that in addition to presynaptic GABA B R autoreceptor activation, MOC efferent axon terminals release GABA onto type II SGN afferent dendrites with postsynaptic activity mediated by GABA A Rs. This synapse may have multiple roles including developmental regulation of cochlear innervation, fine tuning of OHC activity, or providing feedback to the brain about MOC and OHC activity.

Introduction: The cases of dermatophytosis are increasing and they are associated with a higher number of therapeutic failures leading the doctor to prescribe combinations of antifungals as therapy. The objective was to evaluate the interaction of terbinafine and ciclopirox, the most commonly antifungals used in the clinic, in dermatophyte isolates., Methodology: The minimum inhibitory concentrations (MIC) of ciclopirox and terbinafine were determined by the broth microdilution method according CLSI and the checkerboard assay was used to evaluate the interaction between the antifungal agents., Results: For terbinafine the mic50 was 0.125 ug/mL and mic90 was 0.250 ug/mL. For ciclopirox the values were 2.0 ug/mL for mic50 and 4.0 ug/mL for mic90. No synergistic interaction was observed for the dermatophyte isolates tested., Conclusion: These results suggest that the use of terbinafine in combination with ciclopirox, which is widely used in the clinic, may not be a good choice for the treatment of onychomycosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

We report the complete genome sequences of two non-typical Avibacterium paragallinarum (AP) strains isolated from chickens in the absence of clinical signs. The availability of these genomes can aid scientists in improving current diagnostics and increase our understanding of AP epidemiology and pathogenicity in chickens., Competing Interests: The authors declare no conflict of interest.

Introduction: Human dermatophytoses are the most widespread infections caused by fungi. These are capable of invading the keratin-containing tissues of animals. Nannizzia nana (N. nana) can cause ringworm in pigs and rarely cause infections in humans., Methods: We conducted a search using PUBMED for articles published from January 1, 1990 to March 31, 2022 to identify additional cases. The search terms used were "Microsporum nanum" and "Nannizzia nana"., Results: After reviewing the literature, we identified a total of 16 cases of dermatophytosis due to N. nana since 1990. In most of the patients, the clinical diagnosis was tinea corporis and the most widely used antifungals were: terbinafine and griseofulvin., Conclusion: N. nana is a dermatophyte species isolated infrequently in humans, but it represents a potential source of dermatophytosis in people who come into direct or indirect contact with animals and soil., (Copyright © 2023. Published by Elsevier España, S.L.U.)

The conductivity and strength of carbon nanotube (CNT) wires currently rival those of existing engineering materials; fullerene-based materials have not progressed similarly, despite their exciting transport properties such as superconductivity. This communication reveals a new mechanically robust wire of mutually aligned fullerene supramolecules self-assembled between CNT bundles, where the fullerene supramolecular internal crystal structure and outer surface are aligned and dispersed with the CNT bundles. The crystallinity, crystal dimensions, and other structural features of the fullerene supramolecular network are impacted by a number of important production processes such as fullerene concentration and postprocess annealing. The crystal spacing of the CNTs and fullerenes is not altered, suggesting that they are not exerting significant internal pressure on each other. In low concentrations, the addition of networked fullerenes makes the CNT wire mechanically stronger. More importantly, novel mutually aligned and networked fullerene supramolecules are now in a bulk self-supporting architecture.

Importance: Religious leaders commonly provide assistance to people with mental illness, but little is known about clergy views regarding mental health etiology and appropriate treatment., Objective: To assess the views of religious leaders regarding the etiology and treatment of depression., Design, Setting, and Participants: This cross-sectional study used the National Survey of Religious Leaders, which is a nationally representative survey of leaders of religious congregations in the United States, with data collected from February 2019 to June 2020. Data were analyzed in September and October 2022., Main Outcomes and Measures: Views about causes of depression (chemical imbalance, genetic problem, traumatic experience, demon possession, lack of social support, lack of faith, and stressful circumstances) and appropriate treatments (seeing a mental health professional, taking prescribed medication, and addressing the situation through religious activity)., Results: The analytic sample was limited to congregations' primary leaders (N = 890), with a 70% cooperation rate. Clergy primarily endorsed situational etiologies of depression, with 93% (95% CI, 90%-96%) endorsing stressful circumstances, 82% (95% CI, 77%-87%) endorsing traumatic experiences, and 66% (95% CI, 59%-73%) endorsing lack of social support. Most clergy also endorsed a medical etiology, with 79% (95% CI, 74%-85%) endorsing chemical imbalance and 59% (95% CI, 52%-65%) endorsing genetics. A minority of clergy endorsed religious causes: lack of faith (29%; 95% CI, 22%-35%) or demon possession (16%; 95% CI, 10%-21%). Almost all of the religious leaders who responded to the survey would encourage someone with depressive symptoms to see a mental health professional (90%; 95% CI, 85%-94%), take prescribed medication (87%; 95% CI, 83%-91%), and address symptoms with religious activity (84%; 95% CI, 78%-89%). A small but nontrivial proportion endorsed a religious cause of depression without also endorsing chemical imbalance (8%; 95% CI, 5%-12%) or genetics (20%; 95% CI, 13%-27%) as a likely cause. A similar proportion would encourage someone exhibiting depressive symptoms to engage in religious treatment without also seeing a mental health professional (10%; 95% CI, 5%-14%) or taking prescribed medication (11%; 95% CI, 8%-15%)., Conclusions and Relevance: In this cross-sectional survey, the vast majority of clergy embrace a medical understanding of depression's etiology and treatment. When clergy employ a religious understanding, it most commonly supplements rather than replaces a medical view, although a nontrivial minority endorse only religious interpretations. This should encourage greater collaboration between medical professionals and clergy in addressing mental health needs.

Background: The main aim of this study was to design and validate a questionnaire in Spanish to acknowledge the perception of the sexuality of women with intellectual disabilities. We sought to cover specific spheres of sexuality, such as sexual capacity, decision-making capacity, sexual disinhibition, and sexual education and quality of life., Methods: A questionnaire was developed based on a literature review. Validation was performed using content validation through a panel of experts; construct validation was performed using exploratory and confirmatory factorial analyses; reliability tests were also performed, using Cronbach's Alpha and the two-halves test., Results: Two-hundred forty-four participants pilot tested the initial 34-item questionnaire. After content validation and exploratory factorial analysis, the resulting 10-item questionnaire showed four domains, with Cronbach's Alpha values between 0.69 and 0.82. Confirmatory factorial analysis confirmed the domains, and the model's goodness-of-fit tests were adequate., Conclusions: The final ten-item scale developed in this research proved to be a valid and reliable instrument, as it has good psychometric properties of both validity and reliability. Thus, researchers interested in investigating the social perception of the sexuality of women with intellectual disabilities can use this tool. Future research can extend the validity of this scale to other languages and settings.

Introduction: Vaccination campaigns against influenza virus achieve coverages under recommended and desired values. In current context of SARS-CoV-2 pandemic it becomes more relevant. Our objective is to evaluate the impact on vaccination coverage of a set of implementation strategies carried out., Material and Methods: Vaccine implementation strategies were introduced in our basic health zone as active caption of patients and schedule extension. Then the vaccination coverage achieved in the current campaign was evaluated and compared with previous in the 8th week and at the end of the campaign. Besides, a transversal study through a survey was carried out to measure the impact of the applied strategies., Results: In the 8th week of the campaign significant differences were detected in the increase of vaccination coverage compared with previous years. These results were confirmed at the end of the campaign, getting a significant difference (<.05) of vaccination coverage in all the studied centers, these data support the effectivity of the applied strategies., Conclusions: The vaccine implementation strategies applied have shown effectivity, achieving an increase of until 74% in the total administered doses compared to previous campaigns and even a 15% of vaccination coverage increased in the group of patients older than 64 years; even in a pandemic context and the increasing of anti-vaccine movements., (Copyright © 2022 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

In the present investigation, the conditions for in vitro submerged culture of a native strain of Ganoderma sp. were evaluated. Different culture medium ingredients, inoculum concentrations, inoculation methods, configuration, and airflows were evaluated to improve biomass production. The addition of thiamine and olive oil to the culture medium increased biomass production, as well as inoculating 6.6 g/L since there are no significant differences in biomass growth according to inoculum origin (pre-inoculum, discs or with spores). The best configuration of the 3 L stirred tank bioreactor was using three impellers and a porous air diffuser of 0.25 volume per volume per minute (vvm), the dry biomass concentration was 22.6 g/L after 12 days of cultivation at 30 °C, much higher than other investigations. This study provides relevant information for pilot-scale production of this fungus for future secondary metabolites. The culture medium was optimized, and it was defined that the concentration and origin of the inoculum did not influence the growth of Biomass, but the aeration and the configuration of the system allowed the establishment of protocols for the cultivation of Ganoderma sp.

The use of substances or conditions as elicitors can significantly increase the production of secondary metabolites. In this research, the effects of different elicitors on the production of antioxidant secondary metabolites were evaluated in a strain of Ganoderma sp. The elicitors tested were pH changes in different growth phases of the fungus (pH 3, 5.5 and 8), different concentrations of peptone as a nitrogen source (1 g/L and 10 g/L), and the addition of chemical agents to the culture medium (ethanol, growth regulators, and salts). The alkaline pH during the stationary phase and the high availability of nitrogen were effective elicitors, producing cultures with higher antioxidant activity (37.87 g/L and 43.13 g/L dry biomass) although there were no significant differences with other treatments.

Background: The proteomic profile of cryopreserved in vitro produced bovine embryos is little known but can provide insights on the successful application of cryo procedures in support of animal breeding., Objective: To identify embryonic proteins and biomarkers related to improved cryotolerance of vitrified in vitro produced bovine embryos., Materials and Methods: Proteins were isolated from embryo pools (n = 25 embryos per replicate) and analyzed using the nanoLC - MS/MS system. Further, the UniProtKB database (Uniprot -http://www.uniprot.org/) was used for protein identification. Proteins were classified based on their molecular mass, isoelectric point, and enzymatic activity. Post-translational modification predictions and functional gene ontology analysis were performed as well. Finally, a protein-protein interaction network was created to shed light on the embryo interactome., Results: Based on the MS/MS approach, 66 proteins were identified from vitrified Bos taurus embryos. The retrieved proteins were presumably annotated, which allowed a description of the qualitative and functional aspects of the embryo proteome after the vitrification process., Conclusion: These findings allowed us to conclude that in vitro-produced vitrified embryos expressed proteins that underlie biological processes related to reproduction, stress and lipid metabolic process, which are essential to maintain embryo viability. doi.org/10.54680/fr22410110512.

Chagas disease (CD) is a neglected disease, prevalent and endemic in Latin America, but also present in Europe and North America. The main treatment used for this disease is benznidazole, but its efficacy is variable in the chronic phase and presents high toxicity. So, there is a need for the development of new therapeutic agents. The five-membered heterocyclic 1,2,4-oxadiazole ring has received attention for its unique properties and a broad spectrum of biological activities and is therefore a potential candidate for the development of new drugs. Thus, the aim of this study was to evaluate the activity of the N-cyclohexyl-3-(3-methylphenyl)-1,2,4-oxadiazol-5-amine (2) on the evolutionary forms of Trypanosoma cruzi strain Y, as well as its mechanisms of action and in silico theoretical approach. The results by computational method showed an interaction of the 1,2,4-oxadiazole (2) with TcGAPDH, cruzain, and trypanothione reductase, showing good charge distribution and affinity in those three targets. Furthermore, cytotoxicity in LLC-MK 2 cells was performed by the MTT method. In the assays with different parasite forms, the tested compound showed similar time-dependent concentration effect. The evaluation of the antiamastigote effect between the two concentrations tested showed a reduction in the number of infected cells and also in the number of amastigotes per infected cell. By flow cytometry, the compound (2) displayed alterations suggestive of necrotic events. Finally, in scanning electron microscopy structural alterations were present, characteristic of necrosisin the epimastigote forms. Overall, the 1,2,4-oxadiazole derivative (2) here evaluated opens perspectives to the development of new antichagasic agents., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Teaching Point: Subcutaneous nodules sparing the dermis and without extracutaneous involvement is a rare presentation of the diffuse large B-cell lymphoma., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

The intercellular interactions between peripheral circadian clocks, located in tissues and organs other than the suprachiasmatic nuclei of the hypothalamus, are still very poorly understood. We propose a theoretical and computational study of the coupling between two or more clocks, using a calibrated, reduced model of the circadian clock to describe some synchronization properties between peripheral cellular clocks. Based on a piecewise linearization of the dynamics of the mutual CLOCK:BMAL1/PER:CRY inactivation term, we suggest a segmentation of the circadian cycle into six stages, to help analyse different types of synchronization between two clocks, including single stage duration, total period and maximal amplitudes. Finally, our model reproduces some recent experimental results on the effects of different regimes of time-restricted feeding in liver circadian clocks of mice., Competing Interests: We declare we have no competing interests., (© 2022 The Author(s).)

Background: The development and progression of periodontal diseases is a result of the dynamic interaction of microorganisms within their habitat, and changes in this habitat generate a dysbiotic state. Fusobacterium nucleatum and Prevotella intermedia are bridging microorganisms between the pioneer communities and other microorganisms responsible for periodontitis such as Porphyromonas gingivalis . Tetracycline hydrochloride (TTC-HCl) is commonly used as a coadjutant in periodontal treatment in the form of an antiseptic. However, there are no clear dilution or concentration protocols., Objective: This study aimed to evaluate the in vitro antimicrobial activity of TTC-HCl diluted in sterile water, saline solution, and 2% lidocaine with epinephrine 1:80,000 at concentration of 125, 250, and 500 mg, at three time points- 30, 60, and 120 s - on P. intermedia , F. nucleatum , and P. gingivalis using the Kelsey-Maurer technique., Materials and Methods: The antimicrobial activity of TTC-HCl was evaluated at the proposed concentrations and times, dissolved in the different vehicles at pH 1.9 and 7.0, on F. nucleatum , P. intermedia , and P. gingivalis . The Kelsey-Maurer test was used to verify the presence or absence of colony-forming units. Each test was performed in triplicates with its respective viability controls., Results: Inhibition of F. nucleatum , P. intermedia , and P. gingivalis was achieved with TTC-HCl at all concentrations, dissolved in distilled water, saline solution, and 2% lidocaine with epinephrine 1:80,000 for all times., Conclusions: The results show that TTC-HCl is a good antimicrobial alternative against F. nucleatum , P. intermedia , and P. gingivalis regardless of the vehicle in which it was dissolved, concentration, pH, or time used in this investigation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Leishmaniasis is a neglected tropical disease that causes several clinical manifestations. Parasites of the genus Leishmania cause this disease. Spread across five continents, leishmaniasis is a particular public health problem in developing countries. Leishmania infects phagocytic cells such as macrophages, where it induces adenosine triphosphate (ATP) release at the time of infection. ATP activates purinergic receptors in the cell membranes of infected cells and promotes parasite control by inducing leukotriene B4 release and NLRP3 inflammasome activation. Moreover, uridine triphosphate induces ATP release, exacerbating the immune response. However, ATP may also undergo catalysis by ectonucleotidases present in the parasite membrane, generating adenosine, which activates P1 receptors and induces the production of anti-inflammatory molecules such as prostaglandin E2 and IL-10. These mechanisms culminate in Leishmania's survival. Thus, how Leishmania handles extracellular nucleotides and the activation of purinergic receptors determines the control or the dissemination of the disease., Competing Interests: Conflicts of interest The authors declare no competing or financial interests., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)