Cigarette smoke extract exacerbates progression of osteoarthritic-like changes in cartilage explant cultures.

Established risk factors for osteoarthritis (OA) include obesity, joint injury, age, race, and genetics. However, the relationship between cigarette smoking and OA has yet to be established. In the present study, we have employed the use of cigarette smoke extract (CSE), the water-soluble vapor phase of cigarette smoke, with porcine cartilage explants to investigate the effects of cigarette smoking on cartilage catabolism at the tissue level. Articular cartilage explants were first exposed to 2.5%, 5%, and 10% CSE to assess its effects on cartilage homeostasis. Following, the effects of CSE on OA-like inflammation was observed by culturing explants with a combined treatment of IL-1ß and TNF-α and 10% CSE (CSE + OA). Cartilage explants were assessed for changes in viability, biochemical composition, extracellular matrix (ECM) integrity, and equilibrium mechanical properties (aggregate modulus and hydraulic permeability). CSE alone leads to both a time- and dose-dependent decrease in chondrocyte viability but does not significantly affect sGAG content, percent sGAG loss, or the ECM integrity of cartilage explants. When IL-1ß and TNF-α were combined with 10% CSE, this led to a synergistic effect with more significant losses in viability, significantly more sGAG loss, and significantly higher production of ROS than OA-like inflammation only. Cartilage explant equilibrium mechanical properties were unaffected. Within the timeframe of this study, CSE alone does not cause OA but when combined with OA-like inflammation leads to worsened articular cartilage degeneration as measured by chondrocyte viability, sGAG loss, proteoglycan staining, and ROS production.

Risk Factors for Infection in Neonates With Intestinal Failure.

PURPOSE: Neonates with intestinal failure (IF) are at risk for infection due to central venous access, and intestinal surgery. Infection can cause systemic inflammation and sepsis, potentially affecting growth. The purpose of this study was to identify risk factors for, and the potential impact of infection to help with preventative strategies. METHODS: A retrospective review of infants with IF, at a single centre from 2018 to 2022 was conducted. Clinical characteristics, intestinal pathology, nutritional intake, and growth were compared among infants with bloodstream infection (BSI), other infection (OI) (urinary, respiratory, or wound), or no infection (NI) within 2 months of diagnosis. Mann-Whitney and Kruskal-Wallis tests were used for comparisons with p-values <0.05 considered significant. RESULTS: Eighty-six infants were included, with gastroschisis (41%) and necrotizing enterocolitis (26%) the most common diagnoses. Fifty-nine % of infants developed infection (22% BSI and 37% OI). Those with BSI or OI had a lower gestational age and birthweight, and were more likely to have a stoma. All infants with complex gastroschisis developed infection compared to 38% of infants with simple gastroschisis. Median daily weight gain was suboptimal across all groups and did not differ over 6 weeks following infection. CONCLUSION: Most infants with IF develop infection shortly after diagnosis. Risk factors include prematurity, complex gastroschisis, and the presence of a stoma. Growth was suboptimal but did not differ among infants with or without infection. TYPE OF STUDY: Retrospective Review. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

The Impact of the COVID-19 Pandemic on Self-Harm Attempts Observed in a Hospital Emergency Department.

Suicide is a significant public health concern, with one million lives lost to it every year. Suicidal ideation and attempts are markers of high risk. The COVID-19 pandemic has had a negative psychological impact on the population. This study aims to describe and analyze the clinical and sociodemographic characteristics of patients who have received medical attention for self-harm attempts in a hospital emergency department, comparing the period before and after the COVID-19 pandemic. This is a descriptive, retrospective study that collected data from medical records of patients who received care for self-harm attempts in the emergency department. The data included cases from 1 January 2018 to 31 December 2022. In total, 529 cases of self-harm attempts were identified, of which 62.8% were female. The number of post-pandemic self-harm attempts significantly increased compared to the period before the pandemic. The most used method for self-harm was medication ingestion. This study revealed that over one-third of the participants had previously attempted suicide. Most self-harm attempts were made by women in the 10-20 or 41-50 age groups, with a history of psychiatric illness and multiple medications. The study results also highlighted an increase in self-harm attempts during the COVID-19 pandemic.

Development of the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC) using a modified Delphi technique.

One in three hospitalized children have disease-related malnutrition (DRM) upon admission to hospital, and all children are at risk for further nutritional deterioration during hospital stay; however, systematic approaches to detect DRM in Canada are lacking. To standardise and improve hospital care, the multidisciplinary pediatric working group of the Canadian Malnutrition Taskforce aimed to develop a pediatric, inpatient nutritional care pathway based on available evidence, feasibility of resources, and expert consensus. The working group (n = 13) undertook a total of four meetings: an in-person meeting to draft the pathway based on existing literature and modelled after the Integrated Nutrition Pathway for Acute Care (INPAC) in adults, followed by three online surveys and three rounds of online Delphi consensus meetings to achieve agreement on the draft pathway. In the first Delphi survey, 32 questions were asked, whereas in the second and third rounds 27 and 8 questions were asked, respectively. Consensus was defined as any question/issue in which at least 80% agreed. The modified Delphi process allowed the development of an evidence-informed, consensus-based pathway for inpatients, the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC). It includes screening <24 h of admission, assessment with use of Subjective Global Nutritional Assessment (SGNA) <48 h of admission, as well as prevention, and treatment of DRM divided into standard, advanced, and specialized nutrition care plans. Research is necessary to explore feasibility of implementation and evaluate the effectiveness by integrating P-INPAC into clinical practice.

Assessment of animal welfare in fattening pig farms certified in good livestock practices.

Commercial swine producers are responsible for implementing changes in their production systems to ensure animal welfare. The objective of this study is to evaluate the levels of animal welfare on rearing and fattening farms certified in good animal husbandry practices using the Welfare Quality® protocol. Eighty-one certified commercial farms (n = 2,150 pigs), distributed in six geographical areas of Colombia, were evaluatedby six trained veterinarians. . A multilevel analysis was performed to identify variables associated with the animal welfare/farm rating and to identify behavioral variables. Farms evaluated had an enhanced (n = 68, 83.9%), followed by excellent (n = 7, 8.7%) and acceptable (n = 6, 7.4%) level of animal welfare. Variables significantly associated with the overall protocol rating (R2 = 0.37) were temperature comfort (OR: 1.05, p = 0.008), absence of disease (OR: 1.06, p = 0.02) and absence of pain (OR: 1.06, p = 0.0001). Significant differences in behavioral measures were observed across farms (P < 0.05). The high animal welfare scores of certified farms suggest changes in producers' understanding and attitudes towards production and animal welfare.

Angiosperm flowers reached their highest morphological diversity early in their evolutionary history.

Flowers are the complex and highly diverse reproductive structures of angiosperms. Because of their role in sexual reproduction, the evolution of flowers is tightly linked to angiosperm speciation and diversification. Accordingly, the quantification of floral morphological diversity (disparity) among angiosperm subgroups and through time may give important insights into the evolutionary history of angiosperms as a whole. Based on a comprehensive dataset focusing on 30 characters describing floral structure across angiosperms, we used 1201 extant and 121 fossil flowers to measure floral disparity and explore patterns of floral evolution through time and across lineages. We found that angiosperms reached their highest floral disparity in the Early Cretaceous. However, decreasing disparity toward the present likely has not precluded the innovation of other complex traits at other morphological levels, which likely played a key role in the outstanding angiosperm species richness. Angiosperms occupy specific regions of the theoretical morphospace, indicating that only a portion of the possible floral trait combinations is observed in nature. The ANA grade, the magnoliids, and the early-eudicot grade occupy large areas of the morphospace (higher disparity), whereas nested groups occupy narrower regions (lower disparity).

Consumo de alcohol durante el COVID-19 en Latinoamérica según edad y situación de empleo / Alcohol consumption during COVID-19 in Latin America according to age and employment situation

Esta investigación evaluó el consumo de alcohol en población adulta Latinoamericana y del Caribe latino durante el confinamiento por COVID-19, atendiendo a la edad y situación laboral. Diseño no probabilístico con muestreo por conveniencia, con una muestra de 4975 participantes. Se analizó edad, situación laboral y consumo de alcohol durante el confinamiento y retrospectivamente antes de la pandemia. Los resultados muestran que independientemente del país, los jóvenes de 18-29 años disminuyeron el consumo durante el confinamiento; mientras que el mayor aumento fue en adultos de 45-54 años. Los trabajadores a tiempo completo consumieron más que las personas desempleadas. Empleados a tiempo completo y a tiempo parcial, disminuyeron su consumo durante el confinamiento. Trabajadores por cuenta propia mostraron un consumo de alcohol significativamente superior al de empleados a tiempo completo y a tiempo parcial, durante el confinamiento. Es importante impulsar políticas de prevención del consumo de alcohol en el ámbito laboral. (AU)

This research evaluated alcohol consumption in the Latin American and Latin Caribbean adult population during COVID-19 confinement, taking into account age and employment status. Non-probabilistic design with convenience sampling, with a sample of 4975 participants. Age, employment status and alcohol consumption were analyzed during confinement and retrospectively before the pandemic. The results show that regardless of the country, young people aged 18-29 decreased consumption during confinement; while the largest increase was in adults aged 45-54 years. Full-time workers consumed more than unemployed people. Full-time and part-time employees decreased their consumption during confinement. Self-employed workers showed significantly higher alcohol consumption than full-time and part-time employees during confinement. It is important to promote policies to prevent alcohol consumption in the workplace. (AU)

Percepción de una maestra-tutora sobre la Competencia Motriz y Social en escolares de Infantil. Efecto de un programa de refuerzo motriz / Perception of a teacher-tutor on Motor and Social Competence in Children’s School. Intervention of a motor reinforcement program

El presente trabajo describe la percepción de una maestra-tutora sobre la Competencia Motriz y Relaciones Sociales en escolares de Educación Infantil. Este estudio tuvo un triple objetivo, por un lado, conocer si la maestra-tutora, participante, era capaz de identificar a los escolares con dificultades motrices y sociales. Por otro lado, analizar el impacto de un Programa de Refuerzo Motriz en la Competencia Motriz y en las Relaciones Sociales en estos escolares. Por último, conocer si la maestra-tutora percibe el efecto del programa. En el estudio participó la maestra-tutora y 6 escolares con dificultades motrices, con una edad media de 5.60 años (DT ± 0.53). Se diseñó un estudio pre-experimental mixto que combinó un enfoque cuantitativo para las medidas Pre-Test y Post-Test y un enfoque cualitativo para observar el comportamiento de los participantes. Se evaluó la Competencia Motriz de manera objetiva, mediante la Batería de evaluación (Mabc-2) y se realizó un Sociograma para conocer las Relaciones Sociales. Por otro lado, se pasó un cuestionario a la profesora tutora. Los resultados mostraron que la maestra-tutora, en líneas generales, detecta entre el alumnado a aquellos escolares que presentan dificultades motrices o/y sociales de manera muy evidente. Asimismo, los resultados muestran una mejora en los escolares en ambas variables. En conclusión, los docentes de Educación Infantil como uno de los principales agentes de socialización pueden llegar a ser un elemento fundamental para ayudar a que estos superen las dificultades motrices y sociales (AU)

This paper describes a teacher-tutor's perception of Motor Competence and Social Relationships in pre-school children. The aim of this study was threefold: on the one hand, to find out whether the participating teacher-tutor was able to identify schoolchildren with motor and social difficulties. On the other hand, to analyse the impact of a Motor Reinforcement Programme on Motor Competence and Social Relationships in these schoolchildren. Finally, to find out if the teacher-mentor perceives the effect of the programme. The study involved the teacher-tutor and 6 schoolchildren with motor difficulties, with a mean age of 5.60 years (SD ± 0.53). A mixed pre-experimental study was designed combining a quantitative approach for the Pre-Test and Post-Test measures and a qualitative approach to observe the behaviour of the participants. Motor competence was assessed objectively using the Motor Competence Assessment Battery (Mabc-2) (Henderson et al., 2007) and a Sociogram was conducted to assess Social Relationships. On the other hand, a questionnaire was given to the tutor-teacher. The results showed that the tutor-teacher, in general terms, detects among the students those who present motor and/or social difficulties in a very evident way. Likewise, the results show an improvement in the pupils in both variables.In conclusion, early childhood teachers, as one of the main agents of socialisation, can become a fundamental element in helping children to overcome motor and social difficulties (AU)

The Prevalence of Depression and Anxiety Symptoms and Their Association With Respiratory Diseases.

INTRODUCTION: Patients with respiratory diseases face adverse situations such as symptom management, general condition deterioration, and a hostile perception of the hospital environment, favoring the appearance of anxiety and depression. METHODS: A total of 317 patients hospitalized for a disease of pulmonary origin were analyzed and divided into the following subgroups: infectious, oncological, acute, and chronic diseases. Patients over 18 years of age with preserved cognitive capacity were included in the study. The Hospital Anxiety and Depression Scale (HADS) was applied to them on the second or fourth day of their hospital stay and five days after the first evaluation. Multiple linear regression models were carried out to analyze the association between anxiety and depression measured over two different periods. The models present the statistically significant variables with a 95% confidence level. RESULTS: The patients presented with anxiety in 74.4% of cases, mainly those with acute respiratory diseases (42.4%) and neoplastic diseases (27.5%). A total of 69.5% presented with depression, with symptoms more significant in those with chronic and oncological pulmonary diseases and those with no job. Patients with at least one comorbidity presented with anxiety in 53.9% of cases and depression in 52.1% of cases. Linear regression models were carried out and showed that anxiety was 1.75 and 1.84 times more frequent in patients with chronic diseases compared to those with infectious pathologies in the first and second reviews, respectively. The linear regression model also showed a higher frequency of depressive symptoms in patients with chronic conditions (1.62 times) compared to the group with infectious and contagious pathologies, and prolonged hospital stays were associated with depressive symptoms 1.37 times more than short stays. CONCLUSIONS: Anxiety and depression are frequent disorders in patients with respiratory diseases, negatively affecting the prognosis. Routine mental health screening and multidisciplinary management are essential in this population.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Inclusion of optic neuritis in dissemination in space improves the performance of McDonald 2017 criteria in Hispanic people with suspected multiple sclerosis.

BACKGROUND: Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria. OBJECTIVE: To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON. METHODS: Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria (p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70)). CONCLUSION: This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people.

Quantifying the Accuracy of Density Functionals on Transition Metal Bulk and Surface Properties.

Density functional theory would be exact when the exact exchange-correlation (xc) functional would be known, but since it is regretfully not known, dozens of xc functionals have been developed in the past decades, with some of them better suited for describing certain systems and/or properties. For transition metals (TMs), recent systematic studies assessing bulk properties─shortest interatomic bond distance, δ, cohesive energy, Ecoh, and bulk modulus, B0─and surface features─surface energy, γ, work function, ϕ, and interlayer distances, δij─of 27 TM bulks and 81 TM surfaces, highlighted that generalized gradient approximation (GGA) based xc functionals are, overall, better suited than other types of xc functionals for the TMs bulk and surfaces description, such as Perdew-Burke-Ernzerhof (PBE) or Vega-Viñes (VV). Still, some basic local density approximation xc functionals were not assessed, such as the Hedin-Lundqvist (HL) and Perdew-Zunger (PZ), or GGAs such as the revised Perdew-Burke-Ernzerhof (revPBE) or the Armiento-Mattsson (AM05). Here, we expand the analysis by not only including them but also the recent meta-GGA strongly constrained appropriately normed (SCAN) xc functional, characterized by fulfilling all 17 mathematical conditions an xc must comply, plus the Bayesian error estimation functional (BEEF) xc, a functional parametrized over a large and diverse set of experimental results using machine learning. The present results reveal that none of the xc studied excel neither PBE nor VV, yet AM05 and SCAN performance is quite acceptable, while BEEF xc probably needs more shells of parametrization to reach competitive accuracy levels.

Establishing the Relationship Between Flavonoid Content, Mycorrhization, and Soil Nutritional Content in Different Species of the Genus Passiflora in Colombia.

The genus Passiflora comprises more than 500 species distributed in tropical and semitropical regions. With a great diversity of species, it is estimated that one-third is found in Colombian territory. Besides the food importance, Passiflora species are important sources of biologically active compounds, such as flavonoids. The most important symbiosis between soil fungi and vascular plants related to plant nutrition and tolerance to stress conditions is mycorrhizae. Passiflora species form arbuscular mycorrhizae, with several species of Glomeromycota. This association has been reported to alter the production of secondary metabolites. Thus, the objective of this study was to determine the relation between flavonoid content, mycorrhization, and soil nutritional content of Passiflora alata, Passiflora quadrangularis, Passiflora maliformis, and Passiflora ligularis in Colombian crops. The extracts were prepared and analyzed using UPLC/PDA-MS, and total flavonoids were quantified with the method of AlCl3. Soil characteristics, including nutritional content and percentage of colonization by arbuscular mycorrhizal fungi, were also determined. All variables were analyzed using Spearman's correlation and principal component analysis. Chromatographic analysis of the extracts allowed us to visualize the different flavonoid compositions of each extract, identifying several C-glycosylflavonoids. In this paper, we report for the first time the presence of luteolin-8-C-rhamnosyl-4'-O-glucoside, apigenin-6-C-arabinosyl-7-O-glucoside, and orientin for P. maliformis. Statistical analysis showed a negative correlation between available phosphorus (ρ = -0.90, p = <0.05) and magnesium (Mg) saturation (ρ = -0.70, p = <0.05) on flavonoid content, whereas the calcium magnesium (Ca/Mg) ratio was positively correlated (ρ = 0.70, p = <0.01). There was a nonsignificant correlation between mycorrhization and flavonoid content (ρ = -0.70, p = >0.1). These results contribute to understanding the relationship between flavonoid-mycorrhization-soil nutritional content on Passiflora spp.

Cholinergic neurodegeneration and cholesterol metabolism dysregulation by constitutive p75NTR signaling in the p75exonIII-KO mice.

Degeneration of basal forebrain cholinergic neurons (BFCNs) is a hallmark of Alzheimer's disease (AD). However, few mouse models of AD recapitulate the neurodegeneration of the cholinergic system. The p75 neurotrophin receptor, p75NTR, has been associated with the degeneration of BFCNs in AD. The senescence-accelerated mouse prone number 8 (SAMP8) is a well-accepted model of accelerated and pathological aging. To gain a better understanding of the role of p75NTR in the basal forebrain during aging, we generated a new mouse line, the SAMP8-p75exonIII-/-. Deletion of p75NTR in the SAMP8 background induces an increase in the number of BFCNs at birth, followed by a rapid decline during aging compared to the C57/BL6 background. This decrease in the number of BFCNs correlates with a worsening in the Y-maze memory test at 6 months in the SAMP8-p75exonIII-/-. We found that SAMP8-p75exonIII-/- and C57/BL6-p75exonIII-/- mice expressed constitutively a short isoform of p75NTR that correlates with an upregulation of the protein levels of SREBP2 and its targets, HMGCR and LDLR, in the BF of both SAMP8-p75exonIII-/- and C57/BL6-p75exonIII-/- mice. As the neurodegeneration of the cholinergic system and the dysregulation of cholesterol metabolism are implicated in AD, we postulate that the generated SAMP8-p75exonIII-/- mouse strain might constitute a good model to study long-term cholinergic neurodegeneration in the CNS. In addition, our results support the role of p75NTR signaling in cholesterol biosynthesis regulation.

Inhibition of vascular endothelial growth factor-A downregulates angiogenesis in psoriasis: A pilot study.

Background: Vascular Endothelial Growth Factor (VEGF)-A-mediated angiogenesis participates in the pathogenesis of psoriasis, thus inviting the hypothesis that anti-VEGF-A therapy could be beneficial in psoriasis. While anti-angiogenic agents are used in oncology and ophthalmology, these therapeutic strategies remain unexplored for the management of psoriasis. Objective: Our objective was to investigate ex vivo how VEGF-A blockade impacts blood vessels, epidermis and immune cells in organ-cultured plaque and non-lesional skin from patients with psoriasis. Methods: Skin biopsies from patients with psoriasis (n = 6; plaque and non-lesional skin) and healthy controls (n = 6) were incubated with anti-VEGF-A monoclonal antibody (bevacizumab, Avastin®) or a human IgG1 isotype control for 72-h in serum-free organ culture. CD31/LYVE-1, Ki-67, and mast cell tryptase expression were assessed by quantitative immunohistomorphometry. VEGF-A levels in plasma, PBMCs and skin culture supernatants were measured. Results: Inhibition of VEGF-A blocked all free VEGF-A ex vivo, reduced blood vessel area and the number of blood vessel endothelial cells in plaques of psoriasis (*p < 0.05). The treatment effect correlated significantly with levels of VEGF-A in organ culture supernatants (r = 0.94; *p < 0.05) from plaque skin and with plasma levels of VEGF-A from patients with psoriasis (r = 0.943; *p = 0.017). Conclusions: These ex vivo data are the first studies to objectively investigate the potential of VEGF-A inhibition as a novel adjuvant treatment strategy for psoriasis. Taken together, our data encourage further investigation by clinical trial to explore whether downregulating pathological angiogenesis has clinical utility, especially in patients with severe psoriasis or those with elevated levels of VEGF-A in plasma and/or skin.

Beta-Blockers and Their Current Role in Maternal and Neonatal Health: A Narrative Review of the Literature.

Beta-blockers are a class of medications that act on beta-adrenergic receptors and are categorized as cardio-selective and non-selective. They are principally used to treat cardiovascular conditions such as hypertension and arrhythmias. Beta-blockers have also been used to treat non-cardiogenic indications in non-pregnant individuals and the pediatric population. In pregnancy, labetalol is the mainstay treatment for hypertension and other cardiovascular indications. However, contraindications to certain sub-types of beta-blockers include bradycardia, heart failure, obstructive lung diseases, and hemodynamic instability. There is conflicting evidence of the adverse effects on fetal and neonatal health due to a scarce safety and efficacy profile, and further studies are necessary to understand the pharmacokinetics of the different classes of beta-blockers in pregnancy and fetal health. Understanding the hemodynamic changes during the stages of pregnancy is important to target a more beneficial therapy for both mother and fetus as well as better neonatal outcomes. Beta-blocker use in the pediatric population is less documented in studies but does have the potential to treat various cardiogenic and non-cardiogenic conditions. Future comprehensive studies would further benefit the direction of beta-blocker treatment during pregnancy in neonates and pediatrics.

Combining the Peptide RWQWRWQWR and an Ethanolic Extract of Bidens pilosa Enhances the Activity against Sensitive and Resistant Candida albicans and C. auris Strains.

The antifungal activity of palindromic peptide RWQWRWQWR and its derivatives was evaluated against clinical isolates of Candida albicans and C. auris. Also, Bidens pilosa ethanolic extracts of leaves and stem were evaluated. Furthermore, combinations of peptide, extract, and/or fluconazole (FLC) were evaluated. The cytotoxicity of peptides and extracts in erythrocytes and fibroblasts was determined. The original palindromic peptide, some derivative peptides, and the ethanolic extract of leaves of B. pilosa exhibited the highest activity in some of the strains evaluated. Synergy was obtained between the peptide and the FLC against C. auris 435. The combination of the extract and the original palindromic peptide against C. albicans SC5314, C. auris 435, and C. auris 537 decreased the minimal inhibitory concentrations (MICs) by a factor of between 4 and 16. These mixtures induced changes in cell morphology, such as deformations on the cell surface. The results suggest that the combination of RWQWRWQWR and B. pilosa extract is an alternative for enhancing antifungal activity and decreasing cytotoxicity and costs and should be considered to be a promising strategy for treating diseases caused by Candida spp.

Evaluation of Immune Infiltrates in Ovarian Endometriosis and Endometriosis-Associated Ovarian Cancer: Relationship with Histological and Clinical Features.

BACKGROUND: the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups. METHODS: TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from n = 43 OE and n = 54 EAOC patients. RESULTS: we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC (p < 0.001). TILs were more abundant in OE (p < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC (p < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 (p < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated (p = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC (p < 0.05). CONCLUSIONS: the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC.