Late Treatment Group Research Articles

Macrophages overexpressing interleukin-10 target and prevent atherosclerosis: regression of plaque formation and reduction in necrotic core

Abstract Background Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte-derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)-10 is widely acknowledged for its anti-inflammatory effects, systemic administration of IL-10 has limitations due to its short half-life and significant systemic side effects. Purpose We aimed to investigate the effectiveness of an approach designed to overexpress IL-10 in macrophages and subsequently introduce these genetically modified cells into ApoE-/- mice to promote atherosclerosis regression. Methods We engineered RAW264.7 cells to overexpress IL-10 (referred to as IL-10M) using lentivirusvectors. The ApoE-/- mice were divided into two groups based on the timing of the intervention. The early intervention group (n = 45) received intravenous tail injections from the beginning of Western diet (WD) at six weeks old. The late intervention group (n = 45) started receiving injections at 16 weeks old, 2 months after being fed the WD. Both the early and late intervention group stopped receiving injections after 5 months of being fed the WD. Results The IL-10M exhibited robust IL-10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL-10M can selectively target plaques in ApoE-/- mice, and oil red staining of the entire aorta unequivocally demonstrated that intervention with IL-10M elicited a substantial reduction in plaque area. H&E staining revealed that mice treated with IL-10M in the early intervention group showed a significant reduction in the ratio of plaque area to lumen area. However, the late intervention group did not exhibit statistically significant differences. Notably, mice treated with IL-10M exhibited significantly smaller necrotic cores and reduction in matrix metalloproteinase 9 within the aortic plaques in both the early and late intervention groups. Additionally, the administration of IL-10M showed no obvious side effects. Conclusion We developed an anti-inflammatory protein delivery system based on engineered macrophages that can target atherosclerotic plaques and reduce the plaque area and necrotic core. This approach has a promising safety profile and has the potential to be a therapeutic strategy for the intervention of atherosclerosis.

Defining the Treatment Window: Early Versus Late Pulsed Dye Laser Therapy for Posttraumatic and Surgical Scars in Asian Patients

ABSTRACTObjectivesThis retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes.MethodsThe medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re‐visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow‐up visits where photographs of their current skin condition were captured. The pretreatment and latest follow‐up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale.ResultsAmong the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week‐to‐treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04).ConclusionsEarly intervention using a PDL within 10 weeks post‐injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions.

Macrophages overexpressing interleukin‐10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core

AbstractAtherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.

Investigating the Effectiveness of a Workplace Musculoskeletal Disorders Management Program.

Musculoskeletal disorders (MSDs) present a major occupational health challenge, especially among office workers. Objective: To evaluate the effectiveness of a workplace intervention program for managing MSDs and measure its impact on presenteeism/absenteeism and health status. Methods: This semi-experimental study was conducted between May 2019 and October 2022 in Greece and involved 247 office workers randomly assigned to early and late intervention groups. The intervention included a seminar on ergonomics and proper workstation practices with a demonstration of exercises. Data were collected by the SF-36, the Standardised Nordic, and the Work Productivity and Activity Impairment Questionnaires. Results: In the early intervention group (n = 143), presenteeism significantly decreased (p = 0.045), from a mean value of 0.11 to 0.07, but not absenteeism. Significant improvements were observed in physical (p = 0.007) and mental health (p = 0.012). Reductions in pain were recorded for the neck (p = 0.032), shoulders (p = 0.015), wrists (p = 0.014), upper back, lower back, hips, and knees (p = 0.044 for each). In the late intervention group (n=104), there were no significant changes in absenteeism or presenteeism. Mental health improved significantly (p = 0.008), and reductions in pain were noted for the neck (p = 0.001), wrist (p = 0.0005), and upper back (p = 0.001). Conclusions: This workplace intervention program proved effective both in reducing pain in various body areas and reducing presenteeism, and improved physical and mental health were observed in the intervention groups while absenteeism remained unchanged.

THE IMPACT OF EARLY SURGICAL INTERVENTION ON ANISEIKONIA IN PATIENTS WITH EPIRETINAL MEMBRANE: A Prospective Cohort Study.

To investigate the efficacy of early surgical intervention in ameliorating aniseikonia among patients with epiretinal membrane. This prospective cohort study enrolled patients who underwent surgery for epiretinal membrane. Patients were divided into early (symptom onset within 1 year) and late (symptom onset ≥1 year) treatment groups. Changes in aniseikonia, best-corrected visual acuity, and tangential retinal displacement were assessed and compared at 6 and 12 months postoperatively. Of the 56 patients, 30 (53.6%) belonged to the early treatment group and 26 (46.4%) to the late treatment group. The early treatment group demonstrated a significant reduction in aniseikonia score at 6- and 12-month follow-up visits (-1.10 ± 1.50 [P = 0.002] and -1.18 ± 1.79 [P = 0.003], respectively); however, no improvement was observed in the late treatment group (0.98 ± 4.62 [P = 0.310] and 1.52 ± 4.35 [P = 0.124], respectively). The early treatment group showed larger tangential retinal displacement at the 12-month postoperative follow-up visit. In addition, the amount of tangential retinal displacement was associated with postoperative changes in aniseikonia. Early surgical intervention is helpful in improving aniseikonia in patients with epiretinal membrane. The degree of recovery in inner retinal displacement was associated with the improvement of aniseikonia.

The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study.

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65-56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.

Assessing the Efficacy of Early versus Late Orthodontic Intervention in the Management of Class II Malocclusion: A Comparative Analysis

ABSTRACT Background: Class II malocclusion is a common orthodontic issue characterized by the excessive protrusion of the upper teeth relative to the lower teeth. Early intervention during mixed dentition has been advocated to guide skeletal growth and potentially reduce the severity of malocclusion. Materials and Methods: A comparative analysis was conducted to evaluate the efficacy of early (before the pubertal growth spurt) versus late (after the pubertal growth spurt) orthodontic intervention in managing Class II malocclusion. A cohort of 100 patients diagnosed with Class II malocclusion was divided into two groups: early intervention group (n = 50) and late intervention group (n = 50). Treatment outcomes including changes in overjet, molar relationship, and cephalometric measurements were assessed before and after orthodontic treatment. Results: In the early intervention group, the mean reduction in overjet was 5.2 mm (SD = 1.3), while in the late intervention group, it was 3.8 mm (SD = 1.6). The improvement in molar relationship was greater in the early intervention group (mean change = 4.5 mm, SD = 1.1) compared to the late intervention group (mean change = 3.1 mm, SD = 1.4). Cephalometric analysis revealed significant differences in skeletal and dental parameters between the two groups, with greater improvements observed in the early intervention group. Conclusion: Early orthodontic intervention shows superior efficacy in managing Class II malocclusion compared to late intervention. Early treatment leads to greater reductions in overjet, improvements in molar relationship, and favorable changes in skeletal and dental parameters. These findings underscore the importance of timely orthodontic intervention, particularly during the mixed dentition stage, for optimal management of Class II malocclusion.

Effects of early nutritional intervention on oral mucositis and basic conditions in patients receiving radiotherapy for head and neck cancer: Randomized controlled trial (ChiCTR2000031418)

Background & AimsThis study aims to observe the effects of early nutritional intervention on radiation-induced oral mucositis (OM) and the nutritional status of patients with head and neck cancer (HNC) receiving radiotherapy. MethodsEligible patients receiving radiotherapy for HNC were randomly divided into an early nutritional intervention group (enteral nutritional intervention was administered at the beginning of radiotherapy) and a late nutritional intervention group (enteral nutritional intervention was administered at the beginning of eating restriction) in a 1:1 ratio. The primary endpoint was radiation-induced OM. Secondary endpoints included nutrition-related indicators, immune function, overall survival (OS), progression-free survival (PFS), quality of life, and other radiotherapy-induced adverse effects. ResultsA total of 100 patients were enrolled between 2020 and 2021, including 50 each in the early nutritional intervention group and in the late group. The incidence of Grade-III/IV OM was lower in the early treatment group than in the late treatment group (2% vs 14%, P = 0.059). By week 7 weight loss was significantly lower in the early group than in the late group (1.08 kg, 95% CI: 0.08-2.09, P = 0.035). Regarding the PG-SGA scores after receiving radiotherapy, the early group comprised more well-nourished and fewer malnourished patients than those in the late group (P = 0.002). The scores of the immune function indices of T cell CD3+, CD4+/CD8+, and B cell CD19+ were slightly higher in the early group than in the late group; however, the difference was not statistically significant (all P > 0.05). PFS and OS were better in the early group than in the late group; however, the differences were not statistically significant (P > 0.05). ConclusionsEarly nutritional intervention can effectively improve the nutritional status and reduce the incidence of high-grade OM in patients with HNC receiving radiotherapy. Trial registrationChinese Clinical Trials Registry (http://www.chictr.org.cn) ChiCTR-IDChiCTR2000031418.

Effect of Timing of Rehabilitation Nursing Intervention on Children with Acute Viral Encephalitis

Background: Viral encephalitis (VE) refers to an acute intracranial inflammation mainly caused by various viral infections. Objectives: Viral encephalitis (VE) refers to an acute inflammation of the brain primarily caused by various viral infections. Methods: Data from 60 children with acute viral encephalitis (VE) who received 4 weeks of rehabilitation nursing from July 2019 to July 2020 were collected for retrospective analysis. These children were divided into two groups: An early intervention group (n = 30), where rehabilitation nursing started in the second week after admission, and a late intervention group (n = 30), where rehabilitation nursing began in the fourth week after admission. Motor function, daily living abilities, and limb spasticity were compared before and four weeks after nursing. Additionally, the outcomes of rehabilitation nursing—including recovery times from convulsions, cranial nerve disorders, and consciousness disorders—were also compared. Results: The scores for motor function and daily living ability were significantly higher, while the score for limb spasticity was lower in the early intervention group compared to the late intervention group (P < 0.05). Additionally, the early intervention group experienced a significantly shorter recovery time from convulsions, cranial nerve disorders, and consciousness disorders than the late intervention group (P < 0.05). Conclusions: Early rehabilitation nursing is effective in enhancing motor function, relieving limb spasticity, and improving the nursing outcomes for children with acute viral encephalitis (VE).

Effects of Metreleptin in Patients with Generalized Lipodystrophy Before vs After the Onset of Severe Metabolic Disease.

Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD). Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health. Retrospective analysis of patients ≥ 6 months old with congenital (n=47) or acquired (n=16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means (LSM) for HbA1c, insulin area under the curve (AUC) from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24, 108) months follow-up. Compared to late groups, early groups based on metabolic status had higher mean±SEM insulin AUC (20831±1 vs 11948±1), lower HbA1c (5.3±0.3 vs 6.8±0.3%), triglycerides (101±1 vs 193±1 mg/dL), urine protein excretion (85±1.5 vs 404±1.4 mg/24 hr), ALT (30±1 vs 53±1 U/L), AST (23±1 vs 40±1 U/L), and APRI (0.22±1.3 vs 0.78±1.3), and higher platelets (257±24 vs 152±28 K/µL) during follow-up (P<0.05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5±0.5 vs 6.4±0.2%) and higher AST (40±1vs 23±1 U/L) during follow (P<0.05). Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.

Lengthening in congenital posteromedial bowing of tibia: a follow-up series at skeletal maturity.

Congenital posteromedial bowing (CPMB) of tibia is a rare, usually self-resolving condition that is present at birth. The data on the long-term outcome of lengthening, choice of fixator, outcome in early and late age groups, and complications is sparse, hence the need for this study. This retrospective study included 93 patients with 94 affected legs from 1991 to 2023. The patients were categorized into early (under 10years) and late (10years or above) intervention groups. Eighteen patients with nineteen lengthening episodes who attained skeletal maturity made the basis of this study and will be discussed in detail. The outcome for the lengthening group at maturity was satisfactory, with 5.53cm of average length gained per lengthening episode, a mean LLD of 0.31cm at final follow-up, a mean age of 23.63years (range 14-38years), and an average follow-up of 12.51years (range 3-28years) post-lengthening, but the procedure was associated with difficulties like ankle stiffness, tibial valgus, pin tract infections, and fractures through regenerate. This study represents a large single-centre series on CPMB. We recommend that surgery for lengthening should be done at an older age, close to skeletal maturity, wherever possible to reduce the risk of repeat lengthening procedures. Based on our experience, we recommend the use of a circular fixator. Uniplanar distractors should have an adequate number and spread of Schanz screws in each segment to reduce the risk of valgus malalignment of distracting segments of bone.

Effects of Blood-Derived Products on Cellular Senescence and Inflammatory Response: A Study on Skin Rejuvenation.

Blood-derived products, such as citrate platelet-rich plasma (CPRP) and hyperacute serum (HAS), are recognized for their rich growth factor content. When human dermal fibroblast (HDF) cells are exposed to combined mitogenic and DNA-damaging stimuli, it can lead to an increased burden of senescent cells and a modified senescence-associated secretory phenotype. In this study, the senescent state was comprehensively assessed through various methods, including phosphorylated histone H2AX (γH2AX) staining, p21 and p16 q-PCR, p21-western blot, growth curves, and senescence-associated ß-galactosidase staining. Two primary treatments with blood products were administered, one early (immediately after etoposide) and the other late (11 days after etoposide treatment). The effects of the blood product treatment were evaluated by measuring interleukin 6 and 8 (IL-6 and IL-8) levels, as well as collagen 1 (COL1) and p21 mRNA expression. Additionally, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays, cell size measurements, viability assays, and cell number calculations were conducted. The results revealed that cells treated with hyperacute serum in the early treatment phase exhibited the lowest observed IL-6 and IL-8 levels. In contrast, a clear inflammatory response for IL-8 was observed in cells treated with hyperacute serum and citrate platelet-rich plasma during the late treatment. Furthermore, an upregulation of COL1 expression was observed in the early treatment, while cells in the late treatment group remained unaffected. Notably, citrate platelet-rich plasma-treated cells showed a decrease in COL1 expression. Overall, the treatment with blood products appears to have slightly positive effects on skin rejuvenation.

Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. This is a retrospective study using a nationwide data set. The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).

Influence of preoperative symptom duration on effectiveness of cervical disc arthroplasty in cervical spondylotic radiculopathy patients

To investigate the influence of preoperative symptom duration on effectiveness of cervical disc arthroplasty (CDA) in cervical spondylotic radiculopathy (CSR) patients. The clinical data of 90 CSR patients who underwent single-segment CDA between January 2008 and March 2020 and met the selection criteria were retrospectively analyzed. Based on preoperative symptom duration, patients were divided into an early intervention group (preoperative symptom duration <24 months) and a late intervention group (preoperative symptom duration ≥24 months). There was no significant difference in baseline data between the two groups ( P>0.05), including age, gender, body mass index, smoking status, surgical segment, preoperative neck disability index (NDI), visual analogue scale (VAS) score, cervical lordosis (CL), C 2-C 7 range of motion (ROM), disc angle (DA), disc ROM (DROM), and disc intervertebral height (DIH). The early intervention group had a slightly higher preoperative Japan Orthopedic Association (JOA) score than the late intervention group ( P<0.05). Perioperative indicators such as operation time, intraoperative blood loss, and postoperative hospital stay were recorded. The changes of JOA score, NDI, and VAS score at last follow-up compared with those before operation were used to evaluate the clinical efficacy, and the imaging evaluation of CL, C 2-C 7 ROM, DA, DROM, and DIH was performed before operation, immediately after operation, and at last follow-up. The incidence of prosthesis-related complications, including heterotopic ossification (HO), anterior bone loss (ABL), and prosthesis subsidence, was also assessed at last follow-up. Patients in both groups were followed up 24-120 months, with an average of 53.4 months. There was no significant difference in operation time, intraoperative blood loss, or follow-up duration between the groups ( P>0.05). However, the late intervention group had significantly longer postoperative hospital stay compared to the early intervention group ( P<0.05). At last follow-up, there was no significant difference in the changes of JOA score, NDI, and VAS score between the two groups before and after operation ( P>0.05). During the follow-up, there was no surgical revision in the two groups, and there was no significant difference in the incidence of HO, ABL, and prosthesis subsidence between the two groups at last follow-up ( P>0.05). Imaging evaluation showed that there was no significant difference in CL, C 2-C 7 ROM, DA, DROM, and DIH between the two groups at each time point before and after operation ( P>0.05). The intra-group comparison showed that the early intervention group could maintain the immediate postoperative CL at last follow-up, while the late intervention group had recovered to the preoperative level. Additionally, the C 2-C 7 ROM, DROM, and DA had all recovered to preoperative levels at last follow-up in both groups; meanwhile, the DIH significantly increased immediately after operation and sustained until the last follow-up. Preoperative symptom duration significantly affects the effectiveness of CDA in CSR patients. Patients with preoperative symptom duration ≥24 months have longer postoperative hospital stays and potentially poorer ability to maintain CL compared with patients with preoperative symptom duration <24 months.

Effectiveness of Early Intervention with Palatal Expansion Versus Late Orthodontic Treatment for Correcting Maxillary Crowding

ABSTRACT Background: Maxillary crowding is a common orthodontic issue that can impact a patient’s oral health and overall well-being. The timing of orthodontic treatment plays a crucial role in achieving optimal results. Materials and Methods: Thirty patients who received early intervention with palatal expansion (Group A) and 30 patients who underwent late orthodontic treatment (Group B) were included in this study. The age range for Group A was 8–10 years, while Group B had an age range of 16–18 years. Pretreatment and posttreatment records, including dental models and cephalometric radiographs, were analyzed to assess the effectiveness of the respective treatments. Results: In Group A, the mean duration of treatment was 12 months, and the maxillary crowding was corrected by an average of 4.5 mm. In Group B, the mean treatment duration was 24 months, and maxillary crowding was corrected by an average of 3.2 mm. The early intervention group (Group A) exhibited a statistically significant reduction in treatment duration and greater correction of maxillary crowding compared to the late orthodontic treatment group (Group B) (P &lt; 0.05). Conclusion: Early intervention with palatal expansion is an effective approach for correcting maxillary crowding, leading to shorter treatment duration and greater improvement compared to late orthodontic treatment.

Long-term skeletodental changes with early and late treatment using modified C-palatal plates in hyperdivergent Class II adolescents.

To compare skeletodental changes between early and late treatment groups using modified C-palatal plates (MCPP) and long-term retention outcomes in hyperdivergent Class II adolescents. Seventy-one hyperdivergent Class II patients were divided into four groups according to treatment modality and treatment timing: group 1, early treatment with MCPP (n = 16; 9.9 ± 0.9 years); group 2, late treatment with MCPP (n = 19; 12.3 ± 0.8 years); group 3, early treatment with headgear (HG; n = 18; 9.6 ± 0.8 years); and group 4, late treatment with HG (n = 18; 12.1 ± 1.2 years). Lateral cephalograms were taken and skeletal and dental variables were measured. For statistical analysis, paired t-tests, independent t-tests, and multiple regression were performed. The early MCPP group showed a more significant decrease in mandibular plane angle than the late MCPP group did, and vertical control was more efficient in the early group than in the late group. In the MCPP groups, both FMA and SN-GoGn were increased with late treatment but decreased with early treatment, and the difference was statistically significant (P < .01). The early-treatment MCPP group had a significant decrease in SN-GoGn of 0.6° compared with an increase of 1.7° in the early treatment HG group (P < .01). Posttreatment stability of both the early and late MCPP groups was maintained in long-term retention. Early MCPP showed more significant vertical control than late MCPP. However, there was no difference in long-term stability between early and late groups.

Wharton's Jelly Mesenchymal Stem Cell Conditioned Medium Ameliorates Diabetes-Induced Testicular Damage and Sperm Abnormalities by Mitigating Oxidative Stress, Apoptosis, and Inflammation.

Diabetes leads to testicular damage and infertility. Mesenchymal stem cells and their secretory trophic factors have shown potential as regenerative therapies for diabetes and its associated complications. This study examined the effects of conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJMSCs-CM) on sperm parameters, reproductive hormones, biochemical parameters, and histological changes in the testes of diabetic rats. Fifty-six male Sprague-Dawley rats (250-300 g) were assigned to eight groups: control, diabetes, and six diabetic groups receiving early or late treatments with WJMSCs-CM (D-CME, D-CML), insulin (D-INSE, D-INSL), or DMEM (D-DME, D-DML). In the early treatment groups, insulin (3 U/day, subcutaneously) and WJMSCs-CM (10 mg/week, intraperitoneally) were administered immediately after diabetes induction; in the late treatment groups, these interventions began 30 days postinduction. Blood glucose and insulin levels, along with sperm parameters, were assessed. Sex hormones, testicular antioxidant enzyme activity, malondialdehyde (MDA), and glutathione (GSH) concentrations were measured using colorimetric methods. Real-time PCR detected Bax, Bcl-2, and tumor necrosis factor-alpha (TNF-α) gene expression. Our results showed that diabetes increased blood glucose levels, decreased insulin and sex hormone levels, induced testicular oxidative stress and apoptosis, and reduced sperm parameters compared to the control. WJMSCs-CM significantly ameliorated hyperglycemia, increased insulin and sex hormone levels, and improved sperm quality. In WJMSCs-CM-treated diabetic rats, MDA levels were reduced, while GSH and antioxidant enzyme activity increased. Furthermore, WJMSCs-CM decreased the testicular Bax/Bcl-2 ratio and TNF-α expression, as well as enhanced spermatogenic, Sertoli, and Leydig cells. In conclusion, WJMSC-CM administration effectively mitigated diabetes-induced testicular damage by reducing oxidative stress, inflammation, and apoptosis. Early treatment with WJMSCs-CM was more effective than late treatment for diabetes-induced reproductive dysfunction.

Corticosteroid Therapy Duration and Dosage According to the Timing of Treatment Initiation for Post-COVID-19 Organizing Pneumonia.

COVID-19 can lead to pulmonary complications, including organizing pneumonia. Steroids are essential in treating post-COVID-19 organizing pneumonia. However, research on the clinical benefits of initiating steroid treatment early for this condition is limited. To investigate the steroid initiation time in its association with treatment duration and corticosteroid dose for treating post-COVID-19 organizing pneumonia, we analyzed the data of 91 patients with post-COVID-19 organizing pneumonia at Chonnam National University Hospital between October 2020 and December 2022. Patients were categorized into early and late groups based on time from COVID-19 diagnosis to steroid initiation time for organizing pneumonia. The mean time interval between COVID-19 infection and steroid initiation time for treating organizing pneumonia, was 18.4±8.6 days. Within the early treatment group (treatment initiated <18.4 days after COVID-19), which included 55 patients, the mean duration of steroid treatment was 43.1±18.3days. In contrast, the late treatment group (initiated ≥18.4 days after COVID-19), which consisted of 36 patients, had a longer mean duration of steroid treatment 59.1±22.6 days) (p<0.01). Regarding corticosteroid dosing, the early treatment group had an average dosage of 0.5±0.3 mg/kg/day, in contrast to the late group, which averaged 0.8±0.3 mg/kg/day (p<0.01). Regression analysis showed steroid initiation time significantly influenced treatment duration (β=0.80 , p<0.01) and dosage (β=0.03, p<0.01). The clinical benefits of early steroid treatment for post-COVID-19 organizing pneumonia may lie in its association with reduced steroid treatment duration and dosage.

Auranofin attenuates Schistosoma mansoni egg-induced liver granuloma and fibrosis in mice.

Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by Schistosoma (S.) mansoni eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1β (IL-1β), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total S. mansoni worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1β and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of S. mansoni egg-induced hepatic granuloma and consequent fibrosis.

Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock

BackgroundExtracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-β-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model.MethodsThis randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65–75 mmHg. The experiment was blinded and lasted maximum 24 h.ResultsDuring the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70–90] mmHg for early treatment, 57 [70–90] mmHg for late treatment, and 55 [49–60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived.ConclusionsNeutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.