Synovial fluid NMR-based metabolomics in septic and aseptic revision total knee arthroplasty: Implications on diagnosis and treatment.

Periprosthetic joint infection (PJI) is one of the most challenging complications following total knee arthroplasty. Despite its importance, there is a paucity of reports in the literature regarding its pathogenesis. Recently, cellular metabolic reprogramming has been shown to play an important role in the progression and outcome of infectious diseases. Therefore, the aim of this study was to evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyzes were used to identify metabolites that were differentially abundant between those groups. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non-infected synovial fluids. Lactate, acetate and 3-hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI.

Neutralizing antibody responses to the Delta variant of SARS-CoV-2 following vaccination with Ad5-nCoV (CanSino) in the Mexican population.

During the COVID-19 pandemic, the Ad5-nCoV vaccine was applied to the Mexican population before the WHO approved it. In a transversal study, we compare the CanSino vaccine efficacy and a natural SARS-CoV-2 infection in eliciting neutralizing antibodies against the SARS-CoV-2 Delta variant in Guadalajara, Mexico. Participants between 30-60 years were included in the study and classified into three groups: 1) Natural immunity (unvaccinated), 2) Vaccine-induced immunity (vaccinated individuals without a COVID-19 history), and 3) Natural immunity + vaccine-induced immunity. These groups were matched by age and gender. We assessed the ability of individuals' serum to neutralize the Delta variant and compared the results of the different groups using a neutralization test followed by plaque-forming units. Results showed that 39% of individuals' serum with a history of COVID-19 (natural immunity, Group 1) could not neutralize the Delta variant, compared to 33% in vaccinated individuals without COVID-19 (vaccine immunity, Group 2). In contrast, only 7% of vaccinated individuals with a history of COVID-19 (natural + vaccine immunities) could not neutralize the Delta variant. We concluded that the effectiveness of the Ad5-nCoV vaccine to induce neutralizing antibodies against the Delta variant is comparable to that of natural infection (61% vs. 67%). However, in individuals with both forms of immunity (Group 3), it increased to 93%. Based on these results, despite the Ad5-nCoV vaccine originally being designed as a single-dose regimen, it could be recommended that even those who have recovered from COVID-19 should consider vaccination to boost their immunity against this variant.

Percepção de enfermeiros acerca dos processos de cuidado durante a pandemia da covid-19 / Nurses' perception about care processes during the covid-19 pandemic / Percepción de las enfermeras sobre los procesos de atención durante la pandemia de covid-19

Objetivo: analisar a percepção do enfermeiro acerca dos processos de cuidado durante a pandemia da COVID-19. Métodos: estudo de campo, descritivo e abordagem qualitativa, realizado entre dezembro de 2020 a abril de 2021. Participaram 45 enfermeiros atuantes há três anos ou mais na Atenção Primária de municípios paraibanos classificados em urbano, intermediário adjacente e remoto, rural adjacente e remoto. Realizou-se a coleta através de entrevistas semiestruturadas pela plataforma Google Meet, essas eram gravadas pela própria plataforma e transcritas na íntegra para análise. A análise de dados deu-se por meio da Análise de Conteúdo considerando as etapas de pré-análise, codificação do texto e a inferência e interpretação dos resultados. O estudo atendeu ao que preconiza os padrões éticos. Resultados: no contexto pandêmico, os enfermeiros identificaram déficits existentes em suas práticas, elencando desafios e limitações nas condutas, como as de biossegurança e prevenção de doenças, fazendo-os repensar sobre futuras mudanças a serem realizadas após o período de pandemia. Conclusão: infere-se que os enfermeiros atuantes da Atenção Primária obtiveram novas percepções relacionadas ao cuidado, a preocupação com a saúde física e mental no planejamento desse cuidado, não apenas do usuário, mas de si mesmo e às pessoas do convívio. (AU)

Objective: to analyze nurses' perceptions of care processes during the COVID-19 pandemic. Methods: field study, descriptive and qualitative approach, carried out between December 2020 and April 2021. Participated 45 nurses working for three years or more in Primary Care in municipalities in Paraíba classified as urban, intermediate adjacent and remote, rural adjacent and remote. The collection was carried out through semi-structured interviews through the Google Meet platform, these were recorded by the platform itself and transcribed in full for analysis. Data analysis was carried out through Content Analysis considering the pre-analysis steps, text coding and the inference and interpretation of results. The study complied with ethical standards. Results: in the pandemic context, nurses identified existing deficits in their practices, listing challenges and limitations in conduct, such as biosecurity and disease prevention, making them rethink about future changes to be made after the period of pandemic. Conclusion: it is inferred that nurses working in Primary Care obtained new perceptions related to care, the concern with physical and mental health in the planning of this care, not only of the user, but of himself and the people around him. (AU)

Objetivo: analizar las percepciones de los enfermeros sobre los procesos de atención durante la pandemia de COVID-19. Métodos: estudio de campo, de abordaje descriptivo y cualitativo, realizado entre diciembre de 2020 y abril de 2021. Participaron 45 enfermeros que actúan desde hace tres años o más en Atención Básica en municipios de Paraíba clasificados como urbano, intermedio adyacente y remoto, rural adyacente y remoto. La recolección se realizó a través de entrevistas semiestructuradas a través de la plataforma Google Meet, estas fueron grabadas por la propia plataforma y transcritas en su totalidad para su análisis. El análisis de los datos se realizó a través del Análisis de Contenido considerando las etapas del preanálisis, la codificación del texto y la inferencia e interpretación de los resultados. El estudio cumplió con las normas éticas. Resultados: en el contexto de la pandemia, los enfermeros identificaron déficits existentes en sus prácticas, enumerando desafíos y limitaciones en la conducta, como la bioseguridad y la prevención de enfermedades, lo que les hizo repensar sobre los cambios futuros que se deben realizar después del período de pandemia. Conclusión: se infiere que los enfermeros que actúan en la Atención Primaria obtuvieron nuevas percepciones relacionadas con el cuidado, la preocupación por la salud física y mental en la planificación de este cuidado, no sólo del usuario, sino de sí mismo y de las personas que lo rodean. (AU)

A covid-19 e a reorganização do processo de trabalho do enfermeiro na atenção primária à saúde / Covid-19 and the reorganization of the nurse's work process in primary health care / Covid-19 y la reorganización del proceso de trabajo de la enfermería en la atención primaria de salud

Objetivo: descrever a experiência da reorganização do processo de trabalho de enfermeiros que atuam na Atenção Primária à Saúde no enfrentamento da covid-19, no município de João Pessoa - Paraíba. Métodos: Trata-se de um estudo descritivo com abordagem qualitativa, desenvolvido com um total de 15 enfermeiras atuantes no município de João Pessoa com idade entre 41 e 67 anos (média de 56 anos) e com tempo médio de 12 anos e 8 meses de atuação na Estratégia Saúde da Família. Resultados: foram evidenciados um campo amplo de alterações na dinâmica das Unidades Básicas de Saúde devido a pandemia, dentre elas, modificações no processo de trabalho da equipe, a estagnação das atividades coletivas, como também a implementação de ações destinadas para a covid-19. Conclusão: As experiências relatadas das participantes do estudo ressaltam o grande impacto que a pandemia trouxe para o cotidiano de uma equipe de Atenção Básica, sendo fundamental o fortalecimento da atenção primária à saúde, com recursos financeiros, incentivo e qualificação profissional, garantindo uma maior adequação da nova realidade vivida, a fim de garantir continuidade do cuidado. (AU)

Objective: to describe the experience of the reorganization of the work process of nurses who work in Primary Health Care in the face of covid-19, in the city of João Pessoa - Paraíba. Methods: This is a descriptive study with a qualitative approach, developed with a total of 15 nurses working in the city of João Pessoa aged between 41 and 67 years (average of 56 years) and with an average time of 12 years and 8 months of performance in the Family Health Strategy. Results: a wide field of changes in the dynamics of Basic Health Units due to the pandemic were evidenced, among them, changes in the team's work process, the stagnation of collective activities, as well as the implementation of actions aimed at covid-19. Conclusion: The reported experiences of the study participants highlight the great impact that the pandemic has brought to the daily life of a Primary Care team, making it essential to strengthen primary health care, with financial resources, incentives and professional qualification, ensuring greater adequacy. of the new lived reality, in order to guarantee continuity of care. (AU)

Objetivo: describir la experiencia de la reorganización del proceso de trabajo de los enfermeros que actúan en la Atención Primaria de Salud frente a la covid-19, en la ciudad de João Pessoa - Paraíba. Métodos: Se trata de un estudio descriptivo con enfoque cualitativo, desarrollado con un total de 15 enfermeros que actúan en la ciudad de João Pessoa con edades entre 41 y 67 años (promedio de 56 años) y con tiempo promedio de 12 años y 8 meses de vida. desempeño en la Estrategia de Salud de la Familia. Resultados: Se evidenció un amplio campo de cambios en la dinámica de las Unidades Básicas de Salud debido a la pandemia, entre ellos, cambios en el proceso de trabajo del equipo, el estancamiento de las actividades colectivas, así como la implementación de acciones dirigidas a la covid-19. Conclusión: Las experiencias relatadas por los participantes del estudio resaltan el gran impacto que la pandemia trajo para el cotidiano de un equipo de Atención Primaria, siendo imprescindible fortalecer la atención primaria de salud, con recursos económicos, incentivos y calificación profesional, asegurando una mayor adecuación. de la nueva realidad vivida, para garantizar la continuidad de la atención. (AU)

Trabalho interdisciplinar e condições de trabalho de enfermeiros que atuam na atenção primária à saúde / Interdisciplinary work and working conditions of nurses working in primary health care / Trabajo interdisciplinario y condiciones de trabajo de los enfermeros que actúan en la atención primaria de salud

Objetivo: Discutir acerca do trabalho interdisciplinar na prática do enfermeiro na Atenção Primária à Saúde e as suas condições de trabalho. Métodos: Pesquisa descritiva, qualitativa, realizada com 45 profissionais Enfermeiros, que atuam na Atenção Primária à Saúde do estado da Paraíba, de dezembro de 2020 a abril de 2021. A coleta de dados foi guiada por um roteiro semiestruturado. Os dados foram interpretados com base na Análise de Conteúdo e discutidos a partir da literatura existente. Resultados: Evidenciou-se que, apesar de os enfermeiros conseguirem firmar parceria com os outros trabalhadores da unidade, usuários e gestão, e sentirem autonomia para realizar procedimentos, existem condições que dificultam suas práticas, como o pouco reconhecimento profissional, os problemas com a gestão, a falta de insumos e a sobrecarga de função. Conclusão: Os enfermeiros na Atenção Primária vêm buscando seu espaço e melhores condições de trabalho que facilitem suas práticas e favoreçam o cuidado ao usuário. Dessa forma, tais profissionais necessitam de visibilidade e reconhecimento social de suas competências técnicas. (AU)

Objective: Discuss about the interdisciplinary work in the practice of nurses in Primary Health Care and their working conditions. Methods: Descriptive, qualitative research, carried out with 45 professional nurses, who work in Primary Health Care in the state of Paraíba, from December 2020 to April 2021. Data collection was guided by a semi-structured script. Data were interpreted based on Content Analysis and discussed from the existing literature. Results: It was evidenced that, although the nurses manage to establish a partnership with the other workers of the unit, users and management, and feel autonomy to carry out procedures, there are conditions that hinder their practices, such as little professional recognition, problems with management, the lack of inputs and the function overload. Conclusion: Nurses in Primary Care have been seeking their space and better working conditions that facilitate their practices and favor user care. Thus, such professionals need visibility and social recognition of their technical skills. (AU)

Objetivo: Discutir sobre el trabajo interdisciplinario en la práctica de los enfermeros en la Atención Primaria de Salud y sus condiciones de trabajo. Métodos: Investigación descriptiva, cualitativa, realizada con 45 enfermeros profesionales, que actúan en la Atención Primaria de Salud en el estado de Paraíba, de diciembre de 2020 a abril de 2021. La recolección de datos fue guiada por un guión semiestructurado. Los datos fueron interpretados con base en el Análisis de Contenido y discutidos a partir de la literatura existente. Resultados: Se evidenció que, aunque los enfermeros logran establecer una sociedad con los demás trabajadores de la unidad, usuarios y gerencia, y sienten autonomía para realizar los procedimientos, existen condiciones que dificultan sus prácticas, como poco reconocimiento profesional, problemas con la gestión, la falta de insumos y la sobrecarga de funciones. Conclusión: Los enfermeros en Atención Básica vienen buscando su espacio y mejores condiciones de trabajo que faciliten sus prácticas y favorezcan la atención al usuario. Por lo tanto, estos profesionales necesitan visibilidad y reconocimiento social de sus habilidades técnicas. (AU)

Values in Context: The (Dis)connections Between Moral Foundations and Moral Conviction.

Moral foundations theory (MFT) argues that liberals and conservatives form different moral positions because liberals emphasize the values of harm and fairness, whereas conservatives emphasize the values of group loyalty, authority, and purity. In five studies (total N = 3,327), we investigated whether political orientation moderated the relationship between the perceived relevance of each moral foundation and moral conviction (i.e., the extent to which one perceives their attitude as based on morality) across four issues. Political differences in this relationship emerged but were inconsistent across issues and did not always align with the predictions of MFT or several other theoretical explanations. Our findings together with previous research indicate that MFT may do a better job predicting attitude position than it does predicting whether people perceive that their attitudes are moral convictions, and that some foundations may reflect conventional rather than moral values (e.g., authority).

Nanomedicine-mediated drug delivery for potential treatment of inflammatory bowel disease: a narrative review.

Background & aims: Inflammatory bowel disease (IBD) is a condition characterized by chronic inflammation of the gastrointestinal tract, manifesting as either Crohn's disease (CrD) or ulcerative colitis (UC). Current treatment options for CrD and UC primarily focus on symptom management. In recent years, advancements in nanotechnology have increased the clinical applicability of nanoparticles (NPs) in treating IBD. This review explores the current research on NP-mediated drug-delivery systems for IBD treatment and assesses its advantages and limitations. Results: The authors examine diverse nanomedicine applications for IBD and address the current challenges and prospects in the field to advance nanomediated therapies in the future. Conclusion: Innovative NP-based treatment strategies promise a reliable and effective approach to IBD management.

The Intergroup Value Protection Model: A Theoretically Integrative and Dynamic Approach to Intergroup Conflict Escalation in Democratic Societies.

SCIENTIFIC ABSTRACT: We review social-psychological evidence for a theoretically integrative and dynamic model of intergroup conflict escalation within democratic societies. Viewing individuals as social regulators who protect their social embeddedness (e.g., in their group or in society), the intergroup value protection model (IVPM) integrates key insights and concepts from moral and group psychology (e.g., group identification, outrage, moralization, protest) into a functional intergroup value protection process. The model assumes that social regulators are continuously looking for information diagnostic of the outgroup's intentions to terminate the relationship with the ingroup, and that their specific cognitive interpretations of an outgroup's action (i.e., as a violation of ingroup or shared values) trigger this process. The visible value-protective responses of one group can trigger the other group's value-protective responses, thus dynamically increasing chances of conflict escalation. We discuss scientific implications of integrating moral and group psychology and practical challenges for managing intergroup conflict within democratic societies. PUBLIC ABSTRACT: The 2021 Capitol Hill attack exemplifies a major "trigger event" for different groups to protect their values within a democratic society. Which specific perceptions generate such a triggering event, which value-protective responses does it trigger, and do such responses escalate intergroup conflict? We offer the intergroup value protection model to analyze the moral and group psychology of intergroup conflict escalation in democratic societies. It predicts that when group members cognitively interpret another group's actions as violating ingroup or shared values, this triggers the intergroup value protection process (e.g., increased ingroup identification, outrage, moralization, social protest). When such value-protective responses are visible to the outgroup, this can in turn constitute a trigger event for them to protect their values, thus increasing chances of intergroup conflict escalation. We discuss scientific implications and practical challenges for managing intergroup value conflict in democratic societies, including fears of societal breakdown and scope for social change.

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. QUESTIONS/PURPOSES: (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? METHODS: Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. RESULTS: Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. CONCLUSION: Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. LEVEL OF EVIDENCE: Level II, diagnostic study.

Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review.

The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.

Accuracy of Serological Markers, Synovial Fluid, Microbiological Culture, and Histopathological Examination for Diagnosing Periprosthetic Knee Infection.

Objective This study assessed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serological tests, synovial fluid markers, microbiological tissue culture, and histopathological examination of the periprosthetic membrane in diagnosing periprosthetic knee infection. Methods This study is prospective, and it includes patients undergoing total knee arthroplasty revision surgery from November 2019 to December 2021. The analysis consisted of serological tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and D-dimer), synovial fluid markers (leukocyte and polymorphonuclear cell counts), periprosthetic tissue culture, and histopathological examination of the periprosthetic membrane of all patients. Results Sixty-two patients had periprosthetic joint infection (PJI) according to the 2018 International Consensus Meeting criteria (infection group), while 22 subjects had no infection. ESR sensitivity and specificity were 83.6% and 45.4%, respectively. CRP sensitivity and specificity were 64.5% and 100%, whereas D-dimer sensitivity and specificity were 78.9% and 25%, respectively. Leukocyte count sensitivity and specificity were 75.6% and 100%, polymorphonuclear cell count sensitivity and specificity were 33% and 100%, respectively. Periprosthetic tissue culture sensitivity and specificity culture were, respectively, 77.4% and 100%. Histopathological examination sensitivity and specificity were 43.7% and 100%, respectively. Conclusions In our study, the total blood cell count in synovial fluid and microbiological cultures of periprosthetic tissues were the most accurate tests for PJI diagnosis. In contrast, polymorphonuclear cell percentage was the least accurate test for PJI diagnosis.

In vitro assessment of antibacterial and antiviral activity of three copper products after 200 rounds of simulated use.

Copper has well-documented antibacterial effects but few have evaluated it after prolonged use and against bacteria and viruses. Coupons from three copper formulations (solid, thermal coating, and decal applications) and carbon steel controls were subjected to 200 rounds simulated cleaning using a Wiperator™ and either an accelerated hydrogen peroxide, quaternary ammonium, or artificial sweat products. Antibacterial activity against S. aureus and P. aeruginosa was then evaluated using a modified Environmental Protection Agency protocol. Antiviral activity against coronavirus (229E) and norovirus (MNV-1) surrogates was assessed using the TCID50 method. Results were compared to untreated control coupons. One hour after inoculation, S. aureus exhibited a difference in log kill of 1.16 to 4.87 and P. aeruginosa a log kill difference of 3.39-5.23 (dependent upon copper product and disinfectant) compared to carbon steel. MNV-1 demonstrated an 87-99% reduction on each copper surfaces at 1 h and 99% reduction at 2 h compared to carbon steel. Similarly, coronavirus 229E exhibited a 97-99% reduction after 1 h and 90-99% after 2 h. Simulated use with artificial sweat did not hinder the antiviral nor the antibacterial activity of Cu surfaces. Self-sanitizing copper surfaces maintained antibacterial and antiviral activity after 200 rounds of simulated cleaning.

Continuous Vertical Inside-Out Versus Traditional Vertical Inside-Out Meniscal Repair: A Biomechanical Comparison.

Background: Biomechanical assessment of meniscal repairs is essential for evaluating different meniscal suturing methods and techniques. The continuous meniscal suture technique is a newer method of meniscal repair that may have biomechanical differences compared with traditional techniques. Purpose: To evaluate the displacement, stiffness after cyclical loading, and load to failure for a continuous vertical inside-out meniscal suture versus a traditional vertical inside-out meniscal suture in a porcine medial meniscus. Study Design: Controlled laboratory study. Methods: A total of 28 porcine knees were acquired and divided into 2 test groups of 14 medial meniscus each. A 2.0-cm longitudinal red-white zone cut was made in the body of the medial meniscus for each knee. The continuous suture (CS) group received 4 vertical stitches performed with a continuous vertical meniscal suture technique, and the inside-out suture (IO) group received a traditional vertical suture with 4 stitches. Two traction tapes were passed between the sutures and positioned in the biomechanical testing fixture device. Each specimen underwent load-to-failure testing at 5 mm/s, and displacement, system stiffness, and maximum load to failure were compared between the groups. Results: The displacement after the cyclic test was 0.53 ± 0.12 and 0.48 ± 0.07 mm for the CS and IO groups, respectively. There was no significant difference between the groups (P = .2792). The stiffness at the ultimate load testing was 36.3 ± 1.9 and 35.3 ± 2.4 N/mm for groups CS and IO, respectively, with no significant difference between the groups (P = .2557). In the load-to-failure test, the ultimate load was 218.2 ± 63.9 and 238.3 ± 71.3 N in the CS and IO groups, respectively, with no significant group differences (P = .3062). Conclusion: A continuous vertical meniscal suture created a configuration for treating longitudinal meniscal lesions that was beneficial and biomechanically similar to a traditional vertical suture technique. Clinical Relevance: The study findings indicate that use of the continuous vertical inside-out meniscal suture technique is a possible therapeutic option.

Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer.

Upon heterodimerizing with other nuclear receptors, retinoid X receptors (RXR) act as ligand-dependent transcription factors, regulating transcription of critical signaling pathways that impact numerous hallmarks of cancer. By controlling both inflammation and immune responses, ligands that activate RXR can modulate the tumor microenvironment. Several small molecule agonists of these essential receptors have been synthesized. Historically, RXR agonists were tested for inhibition of growth in cancer cells, but more recent drug discovery programs screen new molecules for inhibition of inflammation or activation of immune cells. Bexarotene is the first successful example of an effective therapeutic that molecularly targets RXR; this drug was approved to treat cutaneous T cell lymphoma and is still used as a standard of care treatment for this disease. No additional RXR agonists have yet achieved FDA approval, but several promising novel compounds are being developed. In this review, we provide an overview of the multiple mechanisms by which RXR signaling regulates inflammation and tumor immunity. We also discuss the potential of RXR-dependent immune cell modulation for the treatment or prevention of cancer and concomitant challenges and opportunities.

Antimicrobial Activity of Filtered Far-UVC Light (222 nm) against Different Pathogens.

Ultraviolet (UV) light is an effective disinfection technology, able to inactivate a wide range of microorganisms, including bacteria and fungi. A safer UV wavelength of 222 nm, also known as far-UVC, has been proposed to minimize these harmful effects while retaining the light's disinfection capability. This study is aimed at exploring the antimicrobial activity of filtered far-UVC (222 nm) on a panel of pathogens commonly found in nosocomial installations. A panel of Gram-positive and Gram-negative bacteria and yeast pathogens was tested. Microorganisms were deposited on a plastic surface, allowing them to dry before exposure to the far-UVC light at a distance of 50 cm. Results showed that far-UVC light successfully inhibits the growth of the tested pathogens, although at different exposure times. In conclusion, the results of this study provide fundamental information to achieve reliable disinfection performance with far-UVC lamps with potential applications in healthcare facilities like hospitals and long-term care homes.

Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin, and musculoskeletal age-related dysfunctions. In most cases, these children die of age-related cardiovascular dysfunction by their early teenage years. The absence of effective treatments for HGPS underscores the critical need to explore novel safe therapeutic strategies. In this study, we show that treatment with the hormone ghrelin increases autophagy, decreases progerin levels, and alleviates other cellular hallmarks of premature aging in human HGPS fibroblasts. Additionally, using a HGPS mouse model (LmnaG609G/G609G mice), we demonstrate that ghrelin administration effectively rescues molecular and histopathological progeroid features, prevents progressive weight loss in later stages, reverses the lipodystrophic phenotype, and extends lifespan of these short-lived mice. Therefore, our findings uncover the potential of modulating ghrelin signaling offers new treatment targets and translational approaches that may improve outcomes and enhance the quality of life for patients with HGPS and other age-related pathologies.

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

CONTEXT: The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. OBJECTIVE: We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. RESULTS: The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 µg/mL to 8-128 µg/mL, respectively. Formulation at concentrations <64 µg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. CONCLUSIONS: The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

Antimicrobial, Cytotoxic, and Anti-Inflammatory Activities of Tigridia vanhouttei Extracts.

In this work, bulb extracts of Tigridia vanhouttei were obtained by maceration with solvents of increasing polarity. The extracts were evaluated against a panel of pathogenic bacterial and fungal strains using the minimal inhibitory concentration (MIC) assay. The cytotoxicity of the extracts was tested against two cell lines (THP-1 and A549) using the MTT assay. The anti-inflammatory activity of the extracts was evaluated in THP-1 cells by measuring the secretion of pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines by ELISA. The chemical composition of the extracts was recorded by FTIR spectroscopy, and their chemical profiles were evaluated using GC-MS. The results revealed that only hexane extract inhibited the growth of the clinical isolate of Pseudomonas aeruginosa at 200 µg/mL. Against THP-1 cells, hexane and chloroform extracts were moderately cytotoxic, as they exhibited LC50 values of 90.16, and 46.42 µg/mL, respectively. Treatment with methanol extract was weakly cytotoxic at LC50 443.12 µg/mL against the same cell line. Against the A549 cell line, hexane, chloroform, and methanol extracts were weakly cytotoxic because of their LC50 values: 294.77, 1472.37, and 843.12 µg/mL. The FTIR analysis suggested the presence of natural products were confirmed by carboxylic acids, ketones, hydroxyl groups, or esters. The GC-MS profile of extracts revealed the presence of phytosterols, tetracyclic triterpenes, multiple fatty acids, and sugars. This report confirms the antimicrobial, cytotoxic, and anti-inflammatory activities of T. vanhouttei.

Biological Activities and Chemical Profiles of Kalanchoe fedtschenkoi Extracts.

In this study, the leaves of Kalanchoe fedtschenkoi were consecutively macerated with hexane, chloroform, and methanol. These extracts were used to assess the bioactivities of the plant. The antimicrobial activity was tested against a panel of Gram-positive and -negative pathogenic bacterial and fungal strains using the microdilution method. The cytotoxicity of K. fedtschenkoi extracts was investigated using human-derived macrophage THP-1 cells through the MTT assay. Finally, the anti-inflammatory activity of extracts was studied using the same cell line by measuring the secretion of IL-10 and IL-6. The phytoconstituents of hexane and chloroform extracts were evaluated using gas chromatography-mass spectrometry (GC/MS). In addition, high-performance liquid chromatography (HPLC) was used to study the phytochemical content of methanol extract. The total flavonoid content (TFC) of methanol extract is also reported. The chemical composition of K. fedtschenkoi extracts was evaluated using Fourier-transform infrared spectroscopy (FTIR). Results revealed that the chloroform extract inhibited the growth of Pseudomonas aeruginosa at 150 µg/mL. At the same concentration, methanol extract inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). Regarding their cytotoxicity, the three extracts were highly cytotoxic against the tested cell line at IC50 < 3 µg/mL. In addition, the chloroform extract significantly stimulated the secretion of IL-10 at 50 µg/mL (p < 0.01). GC/MS analyses revealed that hexane and chloroform extracts contain fatty acids, sterols, vitamin E, and triterpenes. The HPLC analysis demonstrated that methanol extract was constituted by quercetin and kaempferol derivatives. This is the first report in which the bioactivities and chemical profiles of K. fedtschenkoi are assessed for non-polar and polar extracts.