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In an effort to identify novel anti-cancer agents, we employed a well-established High Throughput Screening (HTS) assay to assess the cytotoxic effect of compounds within the ChemBridge DIVERSet Library on a lymphoma cell line. This screen revealed a novel thiophene, F8 (methyl 5-[(dimethylamino)carbonyl]-4-methyl-2-[(3-phenyl-2-propynoyl) amino]-3-thiophenecarboxylate), that displays anti-cancer activity on lymphoma, leukemia, and other cancer cell lines. Thiophenes and thiophene derivatives have emerged as an important class of heterocyclic compounds that have displayed favorable drug characteristics. They have been previously reported to exhibit a broad spectrum of properties and varied uses in the field of medicine. In addition, they have proven to be effective drugs in various disease scenarios. They contain anti-inflammatory, anti-anxiety, anti-psychotic, anti-microbial, anti-fungal, estrogen receptor modulating, anti-mitotic, kinase inhibiting and anti-cancer activities, rendering compounds with a thiophene a subject of significant interest in the scientific community. Compound F8 consistently induced cell death at a low micromolar range on a small panel of cancer cell lines after a 48 h period. Further investigation revealed that F8 induced phosphatidylserine externalization, reactive oxygen species generation, mitochondrial depolarization, kinase inhibition, and induces apoptosis. These findings demonstrate that F8 has promising anti-cancer activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Swain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Grafting is widely used in horticulture. Shortly after grafting, callus tissues appear at the graft interface and the vascular tissues of the scion and rootstock connect. The graft interface contains a complex mix of tissues, we hypothesised that each tissue has its own metabolic response to wounding/grafting and accumulates different metabolites at different rates. We made intact and wounded cuttings and grafts of grapevine, and then measured changes in bulk flavonoid, phenolic acid and stilbenoid concentration and used metabolite imaging to study tissue-specific responses. We show that some metabolites rapidly accumulate in specific tissues after grafting, for example, stilbene monomers accumulate in necrotic tissues surrounding mature xylem vessels. Whereas other metabolites, such as complex stilbenes, accumulate in the same tissues at later stages. We also observe that other metabolites accumulate in the newly formed callus tissue and identify genotype-specific responses. In addition, exogenous resveratrol application did not modify grafting success rate, potentially suggesting that the accumulation of resveratrol at the graft interface is not linked to graft union formation. The increasing concentration of complex stilbenes often occurs in response to plant stresses (via unknown mechanisms), and potentially increases antioxidant activity and antifungal capacities., (© 2023 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is a progressive neurological disease characterized by the loss of cognitive function, confusion, and memory deficit. Accumulation of abnormal proteins, amyloid beta (Aß), and phosphorylated Tau (p-tau) forms plaques and tangles that deteriorate synapse function, resulting in neurodegeneration and cognitive decline in AD. The human brain is composed of different types of neurons and/or synapses that are functionally defective in AD. The GABAergic synapse, the most abundant inhibitory neuron in the human brain was found to be dysfunctional in AD and contributes to disrupting neurological function. This study explored the types of GABA receptors associated with neurological dysfunction and various biological and environmental factors that cause GABAergic neuron dysfunction in AD, such as Aβ, p-tau, aging, sex, astrocytes, microglia, APOE, mental disorder, diet, physical activity, and sleep. Furthermore, we explored the role of microRNAs (miRNAs) in the regulation of GABAergic synapse function in neurological disorders and AD states. We also discuss the molecular mechanisms underlying GABAergic synapse dysfunction with a focus on miR-27b, miR-30a, miR-190a/b, miR-33, miR-51, miR-129-5p, miR-376-3p, miR-376c, miR-30b and miR-502-3p. The purpose of our article is to highlight the recent research on miRNAs affecting the regulation of GABAergic synapse function and factors that contribute to the progression of AD., Competing Interests: Declaration of Competing Interest The author would like to inform that he filed a patent on “Synaptosomal miRNAs and Synapse Functions in Alzheimer’s Disease” TTU Ref. No. 2022–016, U.S. Patent App. No. PCT/US2023/019298 on Oct 26, 2023 related to the contents of this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The objective of the study was to investigate whether the association between binge drinking and oral health-related quality of life (OHRQoL) differs by socioeconomic position (SEP) in Brazilian older adults., Background: The adverse health effects of alcohol consumption disproportionately affect socioeconomically disadvantaged and older individuals. Moreover, measures of binge drinking may capture different domains of the association between alcohol misuse and health that might be independent of the traditional markers of volume or frequency of consumption. Evidence of the association between alcohol use and oral health outcomes has failed to consider binge drinking and possible effect modification by SEP., Methods: We conducted a secondary cross-sectional analysis using the baseline data from The Brazilian Longitudinal Study of Ageing (2015-2016). Effect Measure Modification analyses using multivariable Poisson regression models tested whether the association between past-month binge drinking and higher scores of the Oral Impacts on Daily Performance (OIDP) questionnaire differed in magnitude by level of household wealth and educational attainment, assessed using Relative Excess Risk due to Interaction (RERI) and simple slope test., Results: The analytical sample comprised 8857 individuals. Participants who were from low-wealth households or with lower education and reported past-month binge drinking had 27% (95% CI: 1.16 to 1.39) and 28% (95% CI: 1.18 to 1.40) higher OIDP scores, respectively, than those not binge drinkers from higher SEP, and super-additive associations were detected (RERI for household wealth: 0.12; RERI for educational attainment: 0.14)., Conclusion: Binge drinkers from low SEP have poorer OHRQoL. Public oral health initiatives aiming to combat binge drinking are likely to disproportionately benefit vulnerable groups., (© 2023 Gerodontology Association and John Wiley & Sons Ltd.)

Metabolic-associated fatty liver disease (MAFLD) is a complex condition characterized by steatosis and metabolic disturbances. Risk factors such as diabetes, cigarette smoking, and dyslipidaemia contribute to its development and progression. Effective and safe therapies for MAFLD are urgently needed. Pereskia grandifolia has shown potential as an alternative treatment, but its effectiveness against liver disease remains unexplored. This research aims to determine the hepatoprotective properties of P. grandifolia using a model of MAFLD. The study was carried out through various phases to assess the safety and efficacy of the ethanol-soluble fraction of P. grandifolia . Initially, an in vitro assay was performed to assess cell viability. This was followed by an acute toxicity test conducted in rats to determine the safety profile of the extract. Subsequently, the anti-inflammatory properties of P. grandifolia were examined in macrophages. For the MAFLD study, diabetic Wistar rats were made diabetic and exposed to a high fat diet and cigarette smoke, for 4 weeks. During the last 2 weeks, the rats were orally given either the vehicle (negative control group; C-), P. grandifolia (30, 100, and 300 mg/kg), or insulin in addition to simvastatin. A basal group of rats not exposed to these risk factors was also assessed. Blood samples were collected to measure cholesterol, triglycerides, glucose, ALT, and AST levels. Liver was assessed for lipid and oxidative markers, and liver histopathology was examined. P. grandifolia showed no signs of toxicity. It demonstrated anti-inflammatory effects by inhibiting phagocytosis and macrophage spreading. The MAFLD model induced liver abnormalities, including increased AST, ALT, disrupted lipid profile, oxidative stress, and significant hepatic damage. However, P. grandifolia effectively reversed these changes, highlighting its potential as a therapeutic agent. These findings emphasize the significance of P. grandifolia in mitigating hepatic consequences associated with various risk factors., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Edilson Rodrigues Albuquerque et al.)

Different methods of purification and drying of sericin were evaluated to obtain a material free of contaminating residues through the development of safer and sustainable environmental technology. Samples purified using different proportions of alcohol solvents and by freezing/thawing were compared, while drying was performed by lyophilisation and atomisation in a spray. No significant statistical differences were observed in the yield of the purification process compared with the evaluated methods. Thus, the freezing/thawing method has economic and environmental advantages over other methods. Drying by spraying and lyophilisation produced particles exhibiting different properties in terms of structure: β-sheets, random sheets, and β-turns. In general, these particles are amorphous. The particles obtained by spray drying were more luminous, soluble, and spherical. Thus, purification by freezing/thawing and drying by spray can be considered appropriate methodologies for obtaining contaminant-free sericin through sustainable environmental technology.

Although primary metabolism is well conserved across species, it is useful to explore the specificity of its network to assess the extent to which some pathways may contribute to particular outcomes. Constraint-based metabolic modelling is an established framework for predicting metabolic fluxes and phenotypes and helps to explore how the plant metabolic network delivers specific outcomes from temporal series. After describing the main physiological traits during fruit development, we confirmed the correlations between fruit relative growth rate (RGR), protein content and time to maturity. Then a constraint-based method is applied to a panel of eight fruit species with a knowledge-based metabolic model of heterotrophic cells describing a generic metabolic network of primary metabolism. The metabolic fluxes are estimated by constraining the model using a large set of metabolites and compounds quantified throughout fruit development. Multivariate analyses showed a clear common pattern of flux distribution during fruit development with differences between fast- and slow-growing fruits. Only the latter fruits mobilise the tricarboxylic acid cycle in addition to glycolysis, leading to a higher rate of respiration. More surprisingly, to balance nitrogen, the model suggests, on the one hand, nitrogen uptake by nitrate reductase to support a high RGR at early stages of cucumber and, on the other hand, the accumulation of alkaloids during ripening of pepper and eggplant. Finally, building virtual fruits by combining 12 biomass compounds shows that the growth-defence trade-off is supported mainly by cell wall synthesis for fast-growing fruits and by total polyphenols accumulation for slow-growing fruits., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

The objective of this study was to compare hemolysis marker levels after in vitro infusion of red blood cells (RBCs) according to storage time, infusion rate, and peripheral intravenous catheter size. This is an experimental study with randomly administered RBCs in quintuplicate, according to storage time shorter than and longer than 14 days, as well as infusion rate (50 mL/h and 100 mL/h) using catheters with calibers of 14-, 18-, and 20-gauge. Aliquots were collected from RBCs (V1), after equipment and catheter (V2) free-flow filling and after controlled infusion through the catheter (V3). The hemolytic markers analyzed were degree of hemolysis (%), hematocrit (Ht) (%), total hemoglobin (THb) (g/dL), free hemoglobin (FHb) (g/dL), potassium (K) (mmol/L), and lactate dehydrogenase (LDH) (U/L), considering a probability of error ≤5%. Sixty experiments were performed with the analysis of 180 aliquots. When RBCs aged <14 days were used, all catheters tended to increase THb, FHb, and K; while >14 days, RBCs presented increased FHb and degree of hemolysis with catheters of 18-gauge and THb levels at 14-gauge. Among the conditions analyzed, only 20-gauge catheters (the smallest) did not influence changes in hemolysis markers, regardless of RBC storage time., Competing Interests: Conflict of interest: The authors report no conflicts of interest., (Copyright © 2023 Infusion Nurses Society.)

Objectives: To examine the impact of dental students' usage patterns within an adaptive learning platform (ALP), using ALP-related indicators, on their final exam performance., Methods: Track usage data from the ALP, combined with demographic and academic data including age, gender, pre- and post-test scores, and cumulative grade point average (GPA) were retrospectively collected from 115 second-year dental students enrolled in a blended learning review course. Learning performance was measured by post-test scores. Data were analyzed using correlation coefficients and linear regression tests., Results: The ALP-related variables (without controlling for background demographics and academic data) accounted for 29.6% of student final exam performance (R 2 =0.296, F (10,104) =4.37, p=0.000). Positive significant ALP-related predictors of post-test scores were improvement after activities (β=0.507, t (104) =2.101, p=0.038), timely completed objectives (β=0.391, t (104) =2.418, p=0.017), and number of revisions (β=0.127, t (104) =3.240, p=0.002). Number of total activities, regardless of learning improvement, negatively predicted post-test scores (β= -0.088, t (104) =-4.447, p=0.000). The significant R 2 change following the addition of gender, GPA, and pre-test score (R 2 =0.689, F (13, 101) =17.24, p=0.000), indicated that these predictors explained an additional 39% of the variance in student performance beyond that explained by ALP-related variables, which were no longer significant. Inclusion of cumulative GPA and pre-test scores showed to be the strongest and only predictors of post-test scores (β=18.708, t (101) =4.815, p=0.038) and (β=0.449, t (101) =6.513, p=0.038), respectively., Conclusions: Track ALP-related data can be valuable indicators of learning behavior. Careful and contextual analysis of ALP data can guide future studies to examine practical and scalable interventions.

Cardiac fibrosis is the excessive accumulation of extracellular matrix components in the heart, leading to reduced cardiac functionality and heart failure. This review provides an overview of the therapeutic applications of nanotechnology for the treatment of cardiac fibrosis. We first delve into the fundamental pathophysiology of cardiac fibrosis, highlighting the key molecular players, including Matrix Metalloproteinases, Transforming Growth Factor-beta, and several growth factors, cytokines, and signaling molecules. Each target presents a unique opportunity to develop targeted nano-therapies. We then focus on recent advancements in nanotechnology and how nanoparticles can be engineered to deliver drugs or therapeutic genes. These advanced delivery approaches have shown significant potential to inhibit fibrosis-promoting factors, thereby mitigating the fibrotic response and potentially reversing disease progression. In addition, we discuss the challenges associated with developing and translating nanotechnology-based drug delivery systems, including ensuring biocompatibility, safety, and regulatory compliance. This review highlights how nanotechnology can bridge the gap between lab research and clinical practice for treating cardiac fibrosis., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.)

Sorption regulates the dispersion of pesticides from cropped areas to surrounding water bodies as well as their persistence. Assessing the risk of water contamination and evaluating the efficiency of mitigation measures, requires fine-resolution sorption data and a good knowledge of its drivers. This study aimed to assess the potential of a new approach combining chemometric and soil metabolomics to estimate the adsorption and desorption coefficients of a range of pesticides. It also aims to identify and characterise key components of soil organic matter (SOM) driving the sorption of these pesticides. We constituted a dataset of 43 soils from Tunisia, France and Guadeloupe (West Indies), covering extensive ranges of texture, organic carbon and pH. We performed untargeted soil metabolomics by liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). We measured the adsorption and desorption coefficients of three pesticides namely glyphosate, 2,4-D and difenoconazole for these soils. We developed Partial Least Square Regression (PLSR) models for the prediction of the sorption coefficients from the RT-m/z matrix and conducted further ANOVA analyses to identify, annotate and characterise the most significant constituents of SOM in the PLSR models. The curated metabolomics matrix yielded 1213 metabolic markers. The prediction performance of the PLSR models was generally high for the adsorption coefficients Kd ads (0.3 < R 2  < 0.8) and for the desorption coefficients Kf des (0.6 < R 2  < 0.8) but low for n des (0.03 < R 2  < 0.3). The most significant features in the predictive models were annotated with a confidence level of 2 or 3. The molecular descriptors of these putative compounds suggest that the pool of SOM compounds driving glyphosate sorption is reduced compared to 2,4-D and difenoconazole, and these compounds are generally more polar. This approach can provide estimates of the adsorption and desorption coefficients of pesticides, including polar pesticide, for contrasted pedoclimates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To investigate whether the association between alcohol consumption and tooth loss is modified across socioeconomic positions (SEPs) in Brazilian older adults., Methods: We conducted a secondary analysis using data of The Brazilian Longitudinal Study of Ageing (ELSI-Brazil 2015-2016). Effect Measure Modification (EMM) analyses using multivariable Poisson regression models tested whether the association between heavy drinking and lack of functional dentition (FD) varies in magnitude and direction according to levels of Household Wealth index (HWI) and educational attainment, assessed by the Relative Excess Risk due to Interaction (RERI). Sensitivity analyses using lifetime exposure to alcohol were performed., Results: The analytical sample comprised 8078 participants. Heavy drinkers living in low-wealth households and with lower education presented 7% (95% CI: 1.01-1.14) and 36% (95% CI: 1.28-1.44) higher prevalence of lack of FD, respectively, than their counterparts, and super-additive associations were detected [RERI for HWI: 0.12 (95% CI: 0.02-0.21); RERI for educational attainment: 0.20 (95% CI: 0.09-0.30)]. The associations were also super-additive in the sensitivity analyses when controlling for abstainer reference group bias., Conclusion: We suggest that alcohol consumption disproportionately impacts the prevalence of tooth loss in Brazilian older adults from lower SEP groups., (© 2022 Wiley Periodicals LLC.)

The ascorbate-glutathione (ASC-GSH) cycle is at the heart of redox metabolism, linking the major redox buffers with central metabolism through the processing of reactive oxygen species (ROS) and pyridine nucleotide metabolism. Tomato fruit development is underpinned by changes in redox buffer contents and their associated enzyme capacities, but interactions between them remain unclear. Based on quantitative data obtained for the core redox metabolism, we built an enzyme-based kinetic model to calculate redox metabolite concentrations with their corresponding fluxes and control coefficients. Dynamic and associated regulations of the ASC-GSH cycle throughout the whole fruit development were analysed and pointed to a sequential metabolic control of redox fluxes by ASC synthesis, NAD(P)H and ROS availability depending on the developmental phase. Furthermore, we highlighted that monodehydroascorbate reductase and the availability of reducing power were found to be the main regulators of the redox state of ASC and GSH during fruit growth under optimal conditions. Our kinetic modelling approach indicated that tomato fruit development displayed growth phase-dependent redox metabolism linked with central metabolism via pyridine nucleotides and H 2 O 2 availability, while providing a new tool to the scientific community to investigate redox metabolism in fruits., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

The present study evaluated renal infection resulting from the implantation of C. tropicalis in the bladder of immunosuppressed mice. Yeasts were implanted in two manners: planktonic and via preformed biofilm on a small catheter fragment (SCF). Renal histopathology and cultures was performed 72 and 144 h after cystotomy was carried out in mice from three groups: group I contained non-contaminated mice implanted with a sterile SCF; group II mice received a sterile SCF plus a yeast suspension containing 1 × 10 7 yeasts/mL in a planktonic form; group III mice were implanted with a SCF containing preformed C. tropicalis biofilm. Viable yeasts were found in the kidneys of mice from both groups II and III. However, after 72 h the planktonic cells (group II) invaded more quickly than the sessile cells (group III). Over a longer period (144 h), group III exhibited a more invasive infection (50% of the animals presented renal infection and the renal fungal load was 3.2 log10 CFU/g tissue) than in group II, where yeasts were not found. C. tropicalis introduced into the bladder in two ways (in planktonic or biofilm form) were able to reach the kidney and establish a renal fungal infection, causing interstitial disorders. The data of the present study therefore support the hypothesis of an ascending pathway for renal infections by C. tropicalis. Furthermore, the biofilm resulted in a greater and progressive risk of renal infection, attributed to the slow detachment of the yeasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Reactive oxygen species are frequently associated with various cancers including pancreatic ductal adenocarcinomas (PDACs). Superoxide dismutase 2 (SOD2) is an enzyme that plays an important role in reactive oxygen species (ROS) signaling. Investigating the molecular function and biological functions of SOD2 can help us develop new therapeutic options and uncover new biomarkers for PDAC diagnosis and prognosis. Here, we show that nimbolide (NB), a triterpene limonoid, effectively blocks the growth and metastasis of PDACs by suppressing the expression and activity of SOD2. To identify the role of SOD2 in NB-induced anticancer activity, we used RNA interference to silence and plasmid transfection to overexpress it. Silencing SOD2 significantly reduced the growth and metastatic characteristics like epithelial-to-mesenchymal transition, invasion, migration, and colony-forming capabilities of PDACs, and NB treatment further reduced these characteristics. Conversely, the overexpression of SOD2 enhanced these metastatic characteristics. ROS signaling has a strong feedback mechanism with the PI3K/Akt signaling pathway, which could be mediated through SOD2. Finally, NB treatment to SOD2-overexpressing PDAC xenografts resulted in significant inhibition of tumor growth and metastasis. Overall, this work suggests that NB, a natural and safe phytochemical that silences SOD2 to induce high levels of ROS generation, results in increased apoptosis and reduced growth and progression of PDACs. The role of SOD2 in regulating NB-induced ROS generation presents itself as a therapeutic option for PDACs.

Central line-associated bloodstream infection (CLABSI) rates increased substantially in the United States following the emergence of COVID-19 and subsequent surges. The pandemic resulted in hospital capacities being exceeded and crisis standards of care being implemented for sustained periods. As COVID-19 rates in the United States began to stabilize, some facilities did not return to previous CLABSI rates, indicating a change in practices that had a longer-term impact on CLABSI prevention. The authors' large health care system observed similar increases in CLABSI following the emergence of COVID-19, prompting investigation and intervention in the form of a quality improvement project. To identify changes related to ongoing increases in CLABSI, an assessment team conducted standardized on-site assessments at 11 facilities. Site assessments were considered an intervention, as they involved rigorous preassessment investigations and interviews, case reviews, practice observations, on-site staff interviews, and postassessment support for additional interventions. Nine facilities had enough postassessment data to analyze the impact of intervention. The overall CLABSI rate (infections per 1000 line days) at the 9 facilities in the 6 months prior to intervention was 1.42, and the postassessment rate in the 6 months following intervention was 0.44. This indicates the effectiveness of facility-specific investigation followed by targeted performance improvements to reduce the rate of CLABSI., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Infusion Nurses Society.)

Objective: The aim of this study was to investigate the occurrence of the disease and research risk factors through sociodemographic data of children aged 0 to 15 years, with symptoms suggestive of COVID-19 in 3 Brazilian municipalities in an international border region., Methods: Epidemiological and RT-PCR test results were collected from the COVID-19 notification records in suspected children and adolescents from March 1 to August 31, 2020, in municipalities (Assis Chateaubriand, Tupãssi, and Formosa do Oeste) located in an international border region. The results obtained and the variables associated were subjected to statistical analysis using the Chi-Square Test (x 2 ) or Fisher's Exact Test, using the statistical program SPSS v. 21.0 (IBM Corp., Armonk, New York, USA) at the 5% significance level., Results: Among the 147 children from the 3 municipalities, 20 (13.60%) were diagnosed as positive. The predominance of cases was in male children (60.00%) and in children living in urban areas (80%). The most frequent symptoms observed in children were fever (65.00% of the cases), followed by headache (60.00%), cough (55.00%), and nasal congestion, as well as sore throat, both found in 35.00% of the cases., Conclusion: All these data highlight the importance and the need for more epidemiological studies, especially in children and adolescents, as COVID-19 becomes part of the child health panorama worldwide, with serious direct and indirect impacts for humans, animals, and the environment.

Periodontal disease is one of the main affections of the oral cavity of dogs. Its main complication is the formation of periapical abscess, which, when affecting the maxillary canine teeth, can lead to the formation of oronasal fistulae. The objective of this study was to evaluate the efficiency of self-curing glass ionomer cement, covered by photopolymerizable adhesive, as a protective element for mucoperiosteal or gingival flap sutures in oral surgery of dogs. We studied 15 dogs from the clinical routine of the dental service of a teaching veterinary hospital, which needed oral surgeries to correct oronasal fistulae, defects or oral cavity communications, regardless of the causal agent. Group one (G1) was composed of seven animals that presented oronasal fistulae after the extraction of maxillary canine teeth compromised by severe periodontal disease. These fistulae were reduced by the double-mucoperiosteal-flap technique, 15 days after the dental extraction. Group two (G2) was composed of five other dogs that presented oronasal fistulae after the extraction of maxillary canine teeth compromised by severe periodontal disease. In this group, the fistulae were reduced by the single-flap technique, immediately after the dental extraction. Group three (G3) was composed of three animals, two of which presented oronasal fistulae due to maxillary fracture and the third one after excision of oral neoplasia. In all groups, simple interrupted sutures were used with 3.0 nylon, and a thin layer of self-curing glass ionomer cement was applied immediately over the operated area. After cement's settling time, a thin layer of photopolymerizable adhesive was applied to the already polymerized cement. In G1, the protective cement was removed on average at 15 (±2) postoperative days, in G2 at 6 (±1) days and in G3 at 11 (±9) days. In the postoperative period, the animals received antibiotics and anti-inflammatory drugs, and they received their usual dry dog food diet. No Elizabethan collar or any other protective measure was used for suturing or the surgical wound. The result was healing of 100% of the oronasal fistulae, without suture dehiscence or the need for new surgical interventions. Thus, it was concluded that the use of self-curing glass ionomer cement covered by photopolymerizable adhesive was fully satisfactory, providing protection of sutures and surgical wounds and showing the potential for routine use in oral surgery in dogs.

Objective: Adolescent mental health concerns increased during COVID-19, but it is unknown whether early increases in depression and suicide risk have been sustained. We examined changes in positive screens for depression and suicide risk in a large pediatric primary care network through May 2022., Methods: Using an observational repeated cross-sectional design, we examined changes in depression and suicide risk during the pandemic using electronic health record data from adolescents. Segmented logistic regression was used to estimate risk differences (RD) for positive depression and suicide risk screens during the early pandemic (June 2020-May 2021) and late pandemic (June 2021-May 2022) relative to before the pandemic (March 2018-February 2020). Models adjusted for seasonality and standard errors accounted for clustering by practice., Results: Among 222,668 visits for 115,627 adolescents (mean age 15.7, 50% female), the risk of positive depression and suicide risk screens increased during the early pandemic period relative to the prepandemic period (RD, 3.8%; 95% CI, 2.9, 4.8; RD, 2.8%; 95% CI, 1.7, 3.8). Risk of depression returned to baseline during the late pandemic period, while suicide risk remained slightly elevated (RD, 0.7%; 95% CI, -0.4, 1.7; RD, 1.8%; 95% CI, 0.9%, 2.7%)., Conclusions: During the early months of the pandemic, there was an increase in positive depression and suicide risk screens, which later returned to prepandemic levels for depression but not suicide risk. Results suggest that pediatricians should continue to prioritize screening adolescents for depressive symptoms and suicide risk and connect them to treatment., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate associations between oral hygiene and gingival abrasion (GA) in a rural population from southern Brazil., Materials and Methods: A population-based sample representative of individuals from a rural community in southern Brazil was included. Individuals aged 15 years or older and who had five teeth or more present were selected for this analysis. GA extent was defined as the total number of abrasions per individual. An adjusted multilevel negative binomial regression analysis was used to investigate the associations between site-, tooth- and individual-level variables and GA. Mean ratios (MR) and 95% confidence intervals (95% CI) were calculated., Results: Five hundred ninety-five dentate individuals aged 15-82 years were analysed. In the adjusted models, brushing more than twice a day (MR = 1.13; 95% CI 1.02-1.26) and brushing with a hard/medium-bristle toothbrush (MR = 1.11; 95% CI 1.01-1.23) were significantly associated with more generalized GA., Conclusions: The extent of GA was independently associated with greater brushing frequency and the use of a toothbrush with harder bristles in residents of a rural area., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The steroidogenic acute regulatory (StAR) protein principally mediates steroid hormone biosynthesis by governing the transport of intramitochondrial cholesterol. Neurosteroids progressively decrease during aging, the key risk factor for Alzheimer's disease (AD), which is triggered by brain-region specific accumulation of amyloid beta (Aβ) precursor protein (APP), a key pathological factor. We demonstrate that hippocampal neuronal cells overexpressing wild-type (WtAPP) and mutant APP (mAPP) plasmids, conditions mimetic to AD, resulted in decreases in StAR mRNA, free cholesterol, and pregnenolone levels. The magnitude of suppression of the steroidogenic response was more pronounced with mAPP than that of WtAPP. While mAPP-waned assorted anomalies correlate to AD pathology, deterioration of APP/Aβ laden StAR expression and neurosteroid biosynthesis was enhanced by retinoid signaling. An abundance of mitochondrially targeted StAR expression partially restored APP/Aβ accumulated diverse neurodegenerative vulnerabilities. Immunofluorescence analyses revealed that overexpression of StAR diminishes mAPP provoked Aβ aggregation. Co-expression of StAR and mAPP in hippocampal neurons substantially reversed the declines in mAPP mediated cell survival, mitochondrial oxygen consumption rate, and ATP production. Concurrently, induction of mAPP induced Aβ loading showed an increase in cholesterol esters, but decrease in free cholesterol, concomitant with pregnenolone biosynthesis, events that were inversely regulated by StAR. Moreover, retinoid signaling was found to augment cholesterol content for facilitating neurosteroid biosynthesis in an AD mimetic condition. These findings provide novel insights into the molecular events by which StAR acts to protect mAPP-induced hippocampal neurotoxicity, mitochondrial dysfunction, and neurosteroidogenesis, and these measures are fundamental for ameliorating and/or delaying dementia in individuals with AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens. To elucidate this, we infected mouse bone marrow-derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM), secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-α than BMDMs infected with MSC. The increased ROS and TNF-α levels in MSM-infected BMDMs correlated with elevated necrotic cell death in this group. Further, RNA-seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial-delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified the down-regulation of cancer-related signaling genes in MSM-infected cells, indicating that MsrA can potentially regulate the development and progression of cancer., Competing Interests: Declaration of competing interest “The authors declare no conflict of interest.”, (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Using continuous pulse oximetry (cSpO 2 ) to monitor children with bronchiolitis who are not receiving supplemental oxygen is a form of medical overuse. In this longitudinal analysis from the Eliminating Monitor Overuse (EMO) study, we aimed to assess changes in cSpO 2 overuse before, during, and after intensive cSpO 2 -deimplementation efforts in six hospitals. Monitoring data were collected during three phases: "P1" baseline, "P2" active deimplementation (all sites engaged in education and audit and feedback strategies), and "P3" sustainment (a new baseline measured after strategies were withdrawn). Two thousand and fifty-three observations were analyzed. We found that each hospital experienced reductions during active deimplementation (P2), with overall adjusted cSpO 2 overuse decreasing from 53%, 95% confidence interval (CI): (49-57) to 22%, 95% CI: (19-25) between P1 and P2. However, following the withdrawal of deimplementation strategies, overuse rebounded in all six sites, with overall adjusted cSpO 2 overuse increasing to 37%, 95% CI: (33-41) in P3., (© 2023 Society of Hospital Medicine.)

Background: The composition of ripe fruits depends on various metabolites which content evolves greatly throughout fruit development and may be influenced by the environment. The corresponding metabolism regulations have been widely described in tomato during fruit growth and ripening. However, the regulation of other metabolites that do not show large changes in content have scarcely been studied., Results: We analysed the metabolites of tomato fruits collected on different trusses during fruit development, using complementary analytical strategies. We identified the 22 least variable metabolites, based on their coefficients of variation. We first verified that they had a limited functional link with the least variable proteins and transcripts. We then posited that metabolite contents could be stabilized through complex regulations and combined their data with the quantitative proteome or transcriptome data, using sparse partial-least-square analyses. This showed shared regulations between several metabolites, which interestingly remained linked to early fruit development. We also examined regulations in specific metabolites using correlations with individual proteins and transcripts, which revealed that a stable metabolite does not always correlate with proteins and transcripts of its known related pathways., Conclusions: The regulation of the least variable metabolites was then interpreted regarding their roles as hubs in metabolic pathways or as signalling molecules., (© 2023. The Author(s).)

Gallesia integrifolia, a notable species in the Atlantic Forest, has been traditionally employed in folk medicine for treating rheumatism, asthma, and worms. This study investigated the cellular antioxidant, antiproliferative, and anti-inflammatory activities of the essential oils (EOs) and crude extracts (CEs) from G. integrifolia flowers, fruits, and leaves. The chemical identification of EOs was performed by GC-MS and CEs by UHPLC-MS. Cellular antioxidant and anti-inflammatory activities were assessed through mouse macrophage cell culture. In addition, the antiproliferative potential was evaluated in gastric, colorectal, breast, and lung tumor cell lines and non-tumor VERO cells. EOs predominantly contained organosulfur compounds in flowers (96.29%), fruits (94.94%), and leaves (90.72%). We found the main compound is 2,2'-Disulfanediyldiethanethiol in the EOs of flowers (47.00%), leaves (41.82%), and fruits (44.39%). Phenolic compounds were identified in CEs. The EOs and CEs demonstrated potential against the tumor cell lines tested (GI 50 between 51 and 230 µg/mL). The selectivity index values were greater than 1.0 (1.01 to 3.37), suggesting a relative safety profile. Moreover, the anti-inflammatory activity IC 50 ranged from 36.00 to 268 µg/mL, and the cellular oxidation inhibition ranged from 69% to 82%. The results suggest that oils and extracts derived from G. integrifolia have potential for use in various industrial sectors.

Introduction: The ubiquitin-proteasome system (UPS) is an intracellular organelle responsible for targeted protein degradation, which represents a standard therapeutic target for many different human malignancies. Bortezomib, a reversible inhibitor of chymotrypsin-like proteasome activity, was first approved by the FDA in 2003 to treat multiple myeloma and is now used to treat a number of different cancers, including relapsed mantle cell lymphoma, diffuse large B-cell lymphoma, colorectal cancer, and thyroid carcinoma. Despite the success, bortezomib and other proteasome inhibitors are subject to severe side effects, and ultimately, drug resistance. We recently reported an oncogenic role for non-ATPase members of the 19S proteasome in chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and several different solid tumors. In the present study, we hypothesized that ATPase members of the 19S proteasome would also serve as biomarkers and putative therapeutic targets in AML and multiple other cancers., Methods: We used data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) available at UALCAN and/or GEPIA2 to assess the expression and prognostic value of proteasome 26S subunit, ATPases 1-6 (PSMC1-6) of the 19S proteasome in cancer. UALCAN was also used to associate PSMC1 -6 mRNA expression with distinct clinicopathological features. Finally, cBioPortal was employed to assess genomic alterations of PSMC genes across different cancer types., Results: The mRNA and protein expression of PSMC1 -6 of the 19S proteasome were elevated in several cancers compared with normal controls, which often correlated with worse overall survival. In contrast, AML patients demonstrated reduced expression of these proteasome subunits compared with normal mononuclear cells. However, AML patients with high expression of PSMC2 -5 had worse outcomes., Discussion: Altogether, our data suggest that components of the 19S proteasome could serve as prognostic biomarkers and novel therapeutic targets in AML and several other human malignancies., 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 © 2023 Tychhon, Allen, Gonzalez, Olivas, Solecki, Keivan, Velazquez, McCall, Tapia, Rubio, Jordan, Elliott and Eiring.)

Implementing pediatric-focused clinical decision support (CDS) into hospital electronic health records can lead to improvements in patient care and accelerate quality improvement and research initiatives. However, its design, development, and implementation can be a time-consuming and costly endeavor that may not be feasible for all hospital settings. In this cross-sectional study, we surveyed Pediatric Research in Inpatient Settings (PRĪS) Network hospitals about the availability of CDS tools to gain an understanding of the functionality available across 8 common inpatient pediatric diagnoses. Among the conditions, asthma had the most extensive CDS availability, while mood disorders had the least. Overall, freestanding children's hospitals had the greatest breadth in CDS coverage across conditions and depth in CDS types within conditions. Future initiatives should examine the relationship between CDS availability and clinical outcomes as well as its relationship with hospitals' performance executing multicenter informatics projects, quality improvement collaboratives, and implementation science strategies., (© 2023 Society of Hospital Medicine.)

Traumatic brain injury (TBI) results in the generation of tau. As hyperphosphorylated tau (p-tau) is one of the major consequences of TBI, targeting p-tau in TBI may lead to the development of new therapy. Twenty-five pigs underwent a controlled cortical impact. One hour after TBI, pigs were administered either vehicle ( n = 13) or PNT001 ( n = 12), a monoclonal antibody for the cis conformer of tau phosphorylated at threonine 231. Plasma biomarkers of neural injury were assessed for 14 days. Diffusion tensor imaging was performed at day 1 and 14 after injury, and these were compared to historical control animals ( n = 4). The fractional anisotropy data showed significant white matter injury for groups at 1 day after injury in the corona radiata. At 14 days, the vehicle-treated pigs, but not the PNT001-treated animals, exhibited significant white matter injury compared to sham pigs in the ipsilateral corona radiata. The PNT001-treated pigs had significantly lower levels of plasma glial fibrillary acidic protein (GFAP) at day 2 and day 4. These findings demonstrate a subtle reduction in the areas of white matter injury and biomarkers of neurological injury after treatment with PNT001 following TBI. These findings support additional studies for PNT001 as well as the potential use of this agent in clinical trials in the near future.

Objectives: Individuals who prefer to communicate about health care in a language other than English (LOE) experience poorer quality medical care and challenges when communicating with health care providers. The objective of this study was to elucidate how caregivers who prefer an LOE perceive communication with their physicians on an inpatient general pediatrics service., Methods: Caregivers of patients admitted to the general pediatrics service at our urban freestanding children's hospital whose preferred language for medical care was Spanish, Arabic, Brazilian Portuguese, or Mandarin were eligible for this qualitative study. Semistructured interviews using video interpreter services were conducted to explore the participants' experiences communicating with their physicians. Interview transcripts were analyzed using conventional content analysis., Results: We interviewed 15 participants representing 7 countries of origin and 4 non-English languages: Spanish, Arabic, Brazilian Portuguese, and Mandarin. Three main domains emerged, including: (1) use of interpreter services, (2) overall communication experience with physician providers, and (3) suggestions for improvement in physician communication. Salient themes included early identification of the need for an interpreter is essential and physicians' use of body language in combination with an interpreter enhances successful communication., Conclusions: This project fills a gap in existing literature by describing the perspectives of caregivers who prefer an LOE, including those speaking languages other than Spanish, as they communicate with inpatient pediatricians. In addition to ensuring appropriate use of interpreter services, physicians can focus on using plain language and gestures during encounters, helping to facilitate communication and provide culturally competent care for this population., (Copyright © 2023 by the American Academy of Pediatrics.)

Competing Interests: None

Sodium fluoroacetate (FA) is a metabolic poison that systemically inhibits the tricarboxylic acid (TCA) cycle, causing energy deficiency and ultimately multi-organ failure. It poses a significant threat to society because of its high toxicity, potential use as a chemical weapon and lack of effective antidotal therapy. In this study, we investigated cell-permeable succinate prodrugs as potential treatment for acute FA intoxication. We hypothesized that succinate prodrugs would bypass FA-induced mitochondrial dysfunction, provide metabolic support, and prevent metabolic crisis during acute FA intoxication. To test this hypothesis, rats were exposed to FA (0.75 mg/kg) and treated with the succinate prodrug candidate NV354. Treatment efficacy was evaluated based on cardiac and cerebral mitochondrial respiration, mitochondrial content, metabolic profiles and tissue pathology. In the heart, FA increased concentrations of the TCA metabolite citrate (+ 4.2-fold, p < 0.01) and lowered ATP levels (- 1.9-fold, p < 0.001), confirming the inhibition of the TCA cycle by FA. High-resolution respirometry of cardiac mitochondria further revealed an impairment of mitochondrial complex V (CV)-linked metabolism, as evident by a reduced phosphorylation system control ratio (- 41%, p < 0.05). The inhibition of CV-linked metabolism is a novel mechanism of FA cardiac toxicity, which has implications for drug development and which NV354 was unable to counteract at the given dose. In the brain, FA induced the accumulation of β-hydroxybutyrate (+ 1.4-fold, p < 0.05) and the reduction of mitochondrial complex I (CI)-linked oxidative phosphorylation (OXPHOS CI ) (- 20%, p < 0.01), the latter of which was successfully alleviated by NV354. This promising effect of NV354 warrants further investigations to determine its potential neuroprotective effects., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The author reports no other conflicts of interest in this communication.

In this study, we used diffuse optics to address the need for non-invasive, continuous monitoring of cerebral physiology following traumatic brain injury (TBI). We combined frequency-domain and broadband diffuse optical spectroscopy with diffuse correlation spectroscopy to monitor cerebral oxygen metabolism, cerebral blood volume, and cerebral water content in an established adult swine-model of impact TBI. Cerebral physiology was monitored before and after TBI (up to 14 days post injury). Overall, our results suggest that non-invasive optical monitoring can assess cerebral physiologic impairments post-TBI, including an initial reduction in oxygen metabolism, development of cerebral hemorrhage/hematoma, and brain swelling., Competing Interests: The authors disclose partial ownership of the following patents. Pending: WO2021/091961 [TSK, DJL, WBB, AGY, TJK], 63/257685 [WBB, DJL, TSK, TJK, RMF], WO2013/090658Al [AGY], PCT/US2012/069626 [AGY], PCT/US2015/017286 [AGY], PCT/US2015/017277 [AGY]. US8082015 [AGY], US10064554 [AGY], US10342488 [WBB and AGY], US10827976 [WBB, DJL, AGY]. No author currently receives royalties or payments from these patents., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

The mitochondria have an important role in modulating cell cycle progression, cell survival, and apoptosis. In the adult heart, the cardiac mitochondria have a unique spatial arrangement and occupy nearly one-third the volume of a cardiomyocyte, being highly efficient for converting the products of glucose or fatty acid metabolism into adenosine triphosphate (ATP). In cardiomyocytes, the decline of mitochondrial function reduces ATP generation and increases the production of reactive oxygen species, which generates impaired heart function. This is because mitochondria play a key role in maintaining cytosolic calcium concentration and modulation of muscle contraction, as ATP is required to dissociate actin from myosin. Beyond that, mitochondria have a significant role in cardiomyocyte apoptosis because it is evident that patients who have cardiovascular diseases (CVDs) have increased mitochondrial DNA damage to the heart and aorta. Many studies have shown that natural products have mitochondria-modulating effects in cardiac diseases, determining them as potential candidates for new medicines. This review outlines the leading plant secondary metabolites and natural compounds derived from microorganisms as modulators of mitochondrial dysfunctions associated with CVDs.

Objectives: To systematically evaluate randomized controlled trials (RCTs) on whether a chewable toothbrush (CTB) is more effective than a manual toothbrush (MTB) in terms of full-mouth dental plaque reduction in non-orthodontic children., Materials and Methods: Six databases were searched by two independent reviewers according to pre-specified eligibility criteria up to October 2022. No restrictions regarding language, date of publication and minimum follow-up period were imposed. The Cochrane Collaboration's Risk of Bias tool (RoB 2.0) was used for quality appraisal and GRADE for assessing the certainty of evidence. Random-effects pairwise meta-analysis compared the dental plaque change scores of CTB and MTB through mean differences (MDs) and associated confidence intervals (95% CI), and sensitivity analysis determined whether an individual study significantly affected the results., Results: Seven eligible RCTs were retrieved, including data of 310 children aged 8-14 years. Five RCTs present some concerns and two have high RoB. No significant difference was detected between toothbrushes in terms of Turesky modification of the Quigley-Hein plaque index reduction (MD = -0.04, 95% CI: -0.26-0.18), with overall very low certainty on evidence. The pooled estimate remains unchanged when any RCT is omitted., Conclusion: There is very low-certainty evidence of no significant difference on plaque removal between MTB and CTB in non-orthodontic children. Due to unexplained high heterogeneity and low methodological quality of RCTs, we cannot determine the extent to which our finding reflects a true effect or bias arising from limitations of primary studies., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune checkpoint inhibitors (ICIs) targeting PD-L1 immunotherapy are state-of-the-art treatments for advanced non-small cell lung cancer (NSCLC). However, the treatment response of certain patients with NSCLC is unsatisfactory because of an unfavorable tumor microenvironment (TME) and poor permeability of antibody-based ICIs. In this study, we aimed to discover small-molecule drugs that can modulate the TME to enhance ICI treatment efficacy in NSCLC in vitro and in vivo. We identified a PD-L1 protein-modulating small molecule, PIK-93, using a cell-based global protein stability (GPS) screening system. PIK-93 mediated PD-L1 ubiquitination by enhancing the PD-L1-Cullin-4A interaction. PIK-93 reduced PD-L1 levels on M1 macrophages and enhanced M1 antitumor cytotoxicity. Combined PIK-93 and anti-PD-L1 antibody treatment enhanced T cell activation, inhibited tumor growth, and increased tumor-infiltrating lymphocyte (TIL) recruitment in syngeneic and human peripheral blood mononuclear cell (PBMC) line-derived xenograft mouse models. PIK-93 facilitates a treatment-favorable TME when combined with anti-PD-L1 antibodies, thereby enhancing PD-1/PD-L1 blockade cancer immunotherapy.

MicroRNAs (miRNAs) are non-coding RNAs that play a major role in gene regulation in several diseases. MicroRNA-502-3p (MiR-502-3p) has been previously characterized in a variety of human diseases such as osteoporosis, diabetes, tuberculosis, cancers, and neurological disorders. Our studies recently explored the new role of miR-502-3p in regulating synapse function in Alzheimer's disease (AD). AD is the most common cause of dementia in elderly individuals. Synapse is the initial target that is hit during AD progression. The most common causes of synapse dysfunction in AD are amyloid beta, hyperphosphorylated tau, and microglia activation. MiR-502-3p was found to be localized and overexpressed in the AD synapses. Overexpression of miR-502-3p was correlated with AD severity in terms of Braak stages. Studies have shown that miR-502-3p modulates the glutaminergic and GABAergic synapse function in AD. The current study's emphasis is to discuss the in-depth roles of miR-502-3p in human diseases and AD and the future possibilities concerning miR-502-3p as a therapeutic for AD treatment.

Objectives: The human papillomavirus (HPV) vaccine is recommended for females and males aged 9 to 45. Nationally, the HPV vaccination rates are lower for males than females; however, this has not been studied in a US-Mexico border community. Our study aims to report the HPV vaccination completion by gender and determine which sociodemographic factors influence vaccination., Methods: This cross-sectional study was conducted among uninsured and underinsured individuals aged between 9 and 26 years served through a community-based HPV vaccine program in El Paso, TX. Data collected included demographic information, psychosocial variables, and vaccine administration data. Descriptive statistics were used to summarize demographic data. Unadjusted t test/Fisher exact test and multivariable relative risk regression were run on significant variables to determine the association with vaccine completion by gender., Results: Most participants were female (63.4%), and an overall vaccine series completion was 30.67%. We found no significant difference in HPV vaccine completion rates by gender. Males who resided in the United States for more than a decade were 31% more likely to complete the vaccine series, and females who had 9 to 13 years of education had lower odds of vaccine completion. Knowledge significantly increased after the intervention for both genders (p = .002). There was no significant change in psychosocial variables from the preintervention to the immediate postintervention survey., Conclusions: Our multicomponent, culturally tailored intervention may equally impact male and female participants and encourages all genders to complete their HPV vaccine series. Additional studies with a larger male sample are needed., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

Bovine mastitis is an inflammation of the mammary gland in response to invasion by opportunistic agents. Due to the high economic importance of dairy production and the complexity related to animal health, the objective of this work was to identify and evaluate the antibacterial resistance profile of samples of mastitis milk, milking hand and milking equipment from small rural dairy farms belonging to the northwest region of the state of Paraná, Brazil. Five small, non-technical dairy farms in the municipalities of Boa Esperança, Juranda and Tapejara, all belonging to the northwest region of the state of Paraná, Brazil, were selected. The properties had Holstein and/or crossbred herds, carried out a bucket-by-foot milking system and all had the presence of animals with subclinical mastitis confirmed by the California Mastitis Test. Samples of sterile swabs from the milking insufflators, the milking hand and milk samples were collected-and later, isolation tests and phenotypic characterization of the samples, sensitivity tests to antimicrobials and phenotypic tests for the detection of beta-producing strains were performed with extended-spectrum beta-lactamase (ESBL), molecular identification of Staphylococcus aureus isolates and mec A gene research. Of the 199 samples collected from the 15 selected properties in the municipalities of Boa Esperança, Tapejara and Juranda, 72 (36.20%) were classified as multiresistant. Isolated from milkers' hands and milking machines, which phenotypically produce extended-spectrum beta-lactamase (ESBL), the presence of the mec A gene was also observed in 11 isolates of Staphylococcus spp. of milk samples, machines and milking hands. Mastitis can be spread to the herd through the milking process by the milkers' instruments and hands, and adequate management measures can prevent its transmission and the conscious use of antibiotics decreases the prevalence of multidrug-resistant pathogens. In this work, different pathogenic bacteria were detected in mastitic milk, milking equipment and milking hand with a high percentage (36.20%) of isolates classified as multidrug resistant. In addition, the presence phenotypically (ESBL) and molecularly ( mec A gene) of isolates carrying resistance genes was also verified. These results directly reflect on the health of the animals, the health of the workers and the health of the respective environment, which can enable the continuity of the propagation of the etiological agents involved in the mastitis infection. The awareness of producers and workers on these properties about the disease, transmission, sanitary aspects and adequate management and treatment are essential for improving milk production and production efficiency.

Introduction: Sepsis is characterized by a dysregulated host immune response to infection, leading to organ dysfunction and a high risk of death. The cecal ligation and puncture (CLP) mouse model is commonly used to study sepsis, but animal mortality rates vary between different studies. Technical factors and animal characteristics may affect this model in unanticipated ways, and if unaccounted for, may lead to serious biases in study findings. We sought to evaluate whether mouse sex, age, weight, surgeon, season of experiments, and timing of antibiotic administration influenced mortality in the CLP model., Methods: We created a comprehensive dataset of C57BL/6J mice that had undergone CLP surgery within our lab during years 2015-2020 from published and unpublished studies. The primary outcome was defined as the time from sepsis induction to death or termination of study (14 days). The Log rank test and Cox regression models were used to analyze the dataset. The study included 119 mice, of which 43% were female, with an average age of 12.6 weeks, an average weight of 25.3 g. 38 (32%) of the animals died., Results: In the unadjusted analyses, experiments performed in the summer and higher weight predicted a higher risk of mortality. In the stratified Cox model by sex, summer season (adjusted hazard ratio [aHR]=5.61, p=0.004) and delayed antibiotic administration (aHR=1.46, p=0.029) were associated with mortality in males, whereas higher weight (aHR=1.52, p=0.005) significantly affected mortality in females. In addition, delayed antibiotic administration (HR=1.42, p=0.025) was associated with mortality in the non-summer seasons, but not in the summer season., Discussion: In conclusion, some factors specific to sex and season have a significant influence on sepsis mortality in the CLP model. Consideration of these factors along with appropriate group matching or adjusted analysis is critical to minimize variability beyond the experimental conditions within a study., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Garcia et al.)

Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with Mycoplasma genitalium (Mg) and Mycoplasma penumoniae (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis. HeLa cells infected with these species showed up-and-down regulation of lncRNAs expression, indicating that both species can modulate host lncRNAs. However, the number of upregulated (200 for Mg and 112 for Mp) and downregulated lncRNAs (30 for Mg and 62 for Mp) differ widely between these two species. GREAT analysis of the noncoding regions associated with differentially expressed lncRNAs showed that Mg and Mp regulate a discrete set of lncRNA plausibly related to transcription, metabolism, and inflammation. Further, signaling network analysis of the differentially regulated lncRNAs exhibited diverse pathways such as neurodegeneration, NOD-like receptor signaling, MAPK signaling, p53 signaling, and PI3K signaling, suggesting that both species primarily target signaling mechanisms. Overall, the study's results suggest that Mg and Mp modulate lncRNAs to promote their survival within the host but in distinct manners., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Objectives: This study aimed to conduct a systematic evaluation of the literature on whether individuals exposed to alcohol intake present differences in the subgingival microbial composition compared to those unexposed., Methods: Five databases (MEDLINE, EMBASE, LILACS, SCOPUS and Web of Science) and one source of grey literature (Google Scholar) were searched by two independent reviewers up to December 2022 according to pre-specified eligibility criteria. No restrictions were imposed regarding the date and language of publication and the periodontal status of the participants. The Newcastle-Ottawa Scale was used for methodological quality appraisal and a narrative synthesis was performed., Results: Eight cross-sectional studies and one cross-sectional analysis nested in a cohort were considered for qualitative analysis, including data of 4636 individuals. Overall, the studies exhibited considerable heterogeneity in terms of characteristics of the participants and microbiological methods. Four studies have high methodological quality. Exposed individuals have higher overall quantity of periodontal pathogens in shallow and moderate to deep pockets. Findings on richness, relative abundance, alpha- and beta-diversity were limited and inconclusive., Conclusion: The subgingival microbiota of individuals exposed to alcohol intake has higher overall quantity of red (i.e., P. gingivalis ) and orange-complex (i.e., F. nucleatum ) bacteria when compared to those unexposed., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Mitochondria play several vital roles in the brain cells, especially in neurons to provide synaptic energy (ATP), Ca 2+ homeostasis, Reactive Oxygen Species (ROS) production, apoptosis, mitophagy, axonal transport and neurotransmission. Mitochondrial dysfunction is a well-established phenomenon in the pathophysiology of many neurological diseases, including Alzheimer's disease (AD). Amyloid-beta (Aβ) and Phosphorylated tau (p-tau) proteins cause the severe mitochondrial defects in AD. A newly discovered cellular niche of microRNAs (miRNAs), so-called mitochondrial-miRNAs (mito-miRs), has recently been explored in mitochondrial functions, cellular processes and in a few human diseases. The mitochondria localized miRNAs regulate local mitochondrial genes expression and are significantly involved in the modulation of mitochondrial proteins, and thereby in controlling mitochondrial function. Thus, mitochondrial miRNAs are crucial to maintaining mitochondrial integrity and for normal mitochondrial homeostasis. Mitochondrial dysfunction is well established in AD pathogenesis, but unfortunately mitochondria miRNAs and their precise roles have not yet been investigated in AD. Therefore, an urgent need exists to examine and decipher the critical roles of mitochondrial miRNAs in AD and in the aging process. The current perspective sheds light on the latest insights and future research directions on investigating the contribution of mitochondrial miRNAs in AD and aging.

Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimum physicochemical characteristics regarding particle size (598.40 ± 9.68 nm), zeta potential (-19.8 ± 0.49 mV), entrapment efficiency (62.76 ± 1.75%), and Q6h (74.00 ± 1.90%). It was selected to prepare an HPMC gel (SPNP-gel). Through metabolomic profiling of the algal extract, thirteen compounds were identified. Molecular docking of the identified compounds on the active site of the HMGB-1 protein revealed that 12,13-DiHome had the highest docking score of -7.130 kcal/mol. SPNP-gel showed higher wound closure potential and enhanced histopathological alterations as compared to standard (MEBO ® ointment) and S. platensis gel in wounded Sprague-Dawley rats. Collectively, NPS promoted the wound healing process by enhancing the autophagy process (LC3B/Beclin-1) and the NRF-2/HO-1antioxidant pathway and halting the inflammatory (TNF-, NF-κB, TlR-4 and VEGF), apoptotic processes (AIF, Caspase-3), and the downregulation of HGMB-1 protein expression. The present study's findings suggest that the topical application of SPNP-gel possesses a potential therapeutic effect in excisional wound healing, chiefly by downregulating HGMB-1 protein expression.

Bacopa monnieri (L.) Wettst. could be of interest in the control of symptoms of Parkinson's disease, but clinical evidence of its efficacy is lacking. This clinical trial assessed the effects of an extract of B. monnieri on parameters that are related to Parkinson's diseases. Twenty volunteers with Parkinson's disease were recruited for a primary, interventional, controlled, parallel, double-blind clinical study. The volunteers were assigned to treatment with either a commercial B. monnieri extract (225 or 450 mg/day) or placebo. The Parkinson's Disease Quality-of-Life (PDQL) questionnaire was applied, and motor activity was assessed before treatment and 30, 60, and 90 days after treatment with the B. monnieri extract or placebo. Characteristics such as age, body weight, and height were also collected. No differences in parkinsonian and systemic symptoms, emotional function, or social function were observed between. The delta percent (Δ%) showed time-dependent improvements in emotional function with B. monnieri treatment at the daily dose of 450 mg. A strong correlation was found between quality of life and motor outcomes at baseline and 30 days of treatment with B. monnieri , and a moderate correlation for 60 and 90 days of treatment with B. monnieri when compared with baseline time. A moderate correlation was found between motor outcomes and Hoehn and Yahr stages at baseline. Our results suggest that B. monnieri extract can improve emotional function in Parkinson's disease patients, but further clinical trials are needed to confirm this possibility.

Although cancer is the leading cause of death among Mexican-Americans, few community-based programs target obesity reduction as a way to reduce the prevalence of obesity-related cancer in underserved populations. Evidence suggests that obesity correlates with 13 types of cancer. The objective is to provide an overview of evaluation and selection of evidence-based content; details of the implementation process; modifications needed to tailor education programs to specific needs of different target audiences; and demonstrate challenges of implementing a community-based prevention program intended to reduce cancer incidence and mortality in Mexican-Americans. We used the Social Cognitive Theory (SCT) to develop a 10-topic menu of educational classes using elements of multiple evidence-based curricula. Outcome measures for physical activity and nutrition were determined using the International Physical Activity Questionnaire (IPAQ) and the Dietary Screener Questionnaire (DSQ). Weight status was determined using weight, body fat, and body mass index (BMI). To date, 2845 adults received wellness education from our program. Multiple delivery models were used to reach a larger audience; they included a 4-week model, 5-week model, employer model, low-income housing, 1- and 2-h sessions, and clinic encounters. Individuals were given education at multiple community locations including senior centers (14%), churches (0.6%), employers (17.6%), low-income housing (8.2%), community centers (16.6%), clinics (11.5%), and schools (32.5%). Our study indicates that our delivery model is feasible and can disseminate evidence-based obesity education. Further investigation is necessary to assess long-term behavioral change and to assess the most effective model for delivery., (© 2021. The Author(s).)