Arthroscopic Bankart Repair vs. Latarjet Procedure for Recurrent Shoulder Instability: A Meta-Analysis of Clinical Outcomes and Complication Rates in General and Athletic Populations.

BACKGROUND: The Bankart repair and Latarjet procedure are both effective surgical methods for treating repeated recurrent anterior dislocation of the shoulder. However, there is still little consensus regarding the standard treatment for recurrent anterior instability of the shoulder. Typically, the choice of treatment has been influenced more by training and tradition rather than the existing evidence. This systematic review and meta-analysis aimed to compare patient-reported outcomes, recurrence, and complications between the two procedures, among both athletic and non-athletic cohorts. METHODS: Relevant clinical trials were identified through a systematic search of databases in April 2023 including PubMed, Scopus, Web of Science, and Cochrane. RCTs and cohort studies were included if they compared patient-reported outcomes or complication rates of open Latarjet procedure versus arthroscopic Bankart repair. Continuous data, such as patient-reported outcomes were pooled as the weighted mean difference (WMD). For dichotomous data such as recurrence and revision rates, the pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using random effects meta-analysis. RESULTS: 21 clinical studies (3 RCTs) were included in the meta-analysis involving a total of 13176 operated shoulders. Arthroscopic Bankart showed a 3.08 times higher risk of recurrence and revision due to post operation instability (RR=3.08, 95% CI: 2.03 to 4.68) compared to those who had the Latarjet approach. The ROWE score, was higher in the Latarjet group by an average of 4.55 points (95% CI: 2.41 to 6.68). This difference was more pronounced in athletes, with an increase of 5.47 points (95% CI: 0.16 to 10.78), compared to the non-athletic population: 4.03 (95% CI: 2.04 to 6.02). Return to sport time was shorter by 0.40 months (95% CI: -0.75 to -0.05) in the Latarjet group. The total complication rate was approximately 47% lower in the Bankart group (RR=0.53, 95% CI: 0.31-0.90). Additionally, the risk of hematoma was 75% lower in patients undergoing the arthroscopic Bankart compared to the Latarjet procedure. External rotation, assessed both in abduction and adduction of the arm, as well as forward elevation, show no significant differences between the two groups. CONCLUSION: Our results demonstrate that the Latarjet procedure has a lower recurrence rate, excels in patient-reported outcomes, and requires less time for return to sports. Thus, it may be a superior alternative to arthroscopic Bankart repair. However, it is still associated with a higher incidence of complications.

BRCA1/2 Mutations and Breast/Ovarian Cancer Risk: A New Insights Review.

Breast and ovarian cancers are significant global health concerns, and understanding their genetic underpinnings is essential for effective prevention and cure. This narrative review provides a comprehensive analysis of studies conducted between 1994 and June 2024, focusing on the link between specific mutations in the breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2) and the associated risks of both breast and ovarian cancers. It encompasses the findings of various works, including observational studies and molecular profiling analyses. Conducted on large international cohorts, these studies present compelling evidence of the relationship between different BRCA1 and BRCA2 mutations and the varying risks of breast and ovarian cancer. Furthermore, this review highlights the significance of nonsense-mediated decay mutations and their impact on cancer risk, particularly concerning the age of breast cancer onset. The implications of these findings are far-reaching, offering valuable information for risk assessment and decision-making in managing individuals who carry BRCA1 or BRCA2 mutations. The molecular subtyping profile BluePrint is discussed as a potential tool for enhancing clinical care by aiding the selection of appropriate treatment options, such as endocrine therapy or chemotherapy, based on the tumor's molecular characteristics. In conclusion, we establish a robust link between specific BRCA1 and BRCA2 gene mutations and increased susceptibility to breast and ovarian cancers. These mutations impact cancer onset age and severity, underscoring the need for targeted testing and screening. The current study enhances cancer detection, prevention, and cure strategies.

A Comprehensive Systematic Review of the Effects of Photobiomodulation Therapy in Different Light Wavelength Ranges (Blue, Green, Red, and Near-Infrared) on Sperm Cell Characteristics in Vitro and in Vivo.

Around 7% of the male population in the world are entangle with considerable situation which is known as male infertility. Photobiomodulation therapy (PBMT) is the application of low-level laser radiation, that recently used to increase or promote the various cell functions including, proliferation, differentiation, ATP production, gene expressions, regulation of reactive oxygen spices (ROS), and also boost the tissue healing and reduction of inflammation. This systematic review's main idea is a comprehensive appraisal of the literatures on subjects of PBMT consequences in four light ranges wavelength (blue, green, red, near-infrared (NIR)) on sperm cell characteristics, in vitro and in vivo. In this study, PubMed, Google Scholar, and Scopus databases were used for abstracts and full-text scientific papers published from 2003-2023 that reported the application of PBM on sperm cells. Criteria's for inclusion and exclusion to review were applied. Finally, the studies that matched with our goals were included, classified, and reported in detail. Also, searched studies were subdivided into the effects of four ranges of light irradiation, including the blue light range (400-500 nm), green light range (500-600 nm), red light range (600-780 nm), and NIR light range (780-3000 nm) of laser irradiation on human or animal sperm cells, in situations of in vitro or in vivo. Searches with our keywords results in 137 papers. After primary analysis, some articles were excluded because they were review articles or incomplete and unrelated studies. Finally, we use the 63 articles for this systematic review. Our category tables were based on the light range of irradiation, source of sperm cells (human or animal cells) and being in vitro or in vivo. Six% of publications reported the effects of blue, 10% green, 53% red and 31% NIR, light on sperm cell. In general, most of these studies showed that PBMT exerted a positive effect on the sperm cell motility. The various effects of PBMT in different wavelength ranges, as mentioned in this review, provide more insights for its potential applications in improving sperm characteristics. PBMT as a treatment method has significant effectiveness for treatment of different medical problems. Due to the lack of reporting data in this field, there is a need for future studies to assessment the biochemical and molecular effects of PBMT on sperm cells for the possible application of this treatment to the human sperm cells before the ART process.

The effect of using the hip exoskeleton assistive (HEXA) robot compared to conventional physiotherapy on clinical functional outcomes in stroke patients with hemiplegia: a pilot randomized controlled trial.

TRIAL DESIGN: This study is a pilot randomized clinical trial aimed to investigate the effect of using Hip Exoskeleton Assistive (HEXA) robot compared to conventional physiotherapy on the quality of walking, disability, and quality of life of stroke patients with hemiplegia. METHODS: In this study, 24 patients were randomly assigned to the intervention group (robotic physiotherapy with HEXA robot), or control group (conventional physiotherapy). In each session, both groups received 30 min of conventional physiotherapy including electrotherapy and conventional exercises, and then the intervention group did gait training for 30 min with the HEXA robot and the control group for 30 min without the HEXA robot. The treatment program was 12 sessions, 3 times a week. Before the 1st and after the 12th sessions, both groups were evaluated for walking quality, disability, and quality of life. RESULTS: The results showed that the main effect of time was significant (P < 0.05) in all outcomes and patients in both groups achieved significant improvement in all outcomes after the intervention. The main effect of the group was also significant in the outcomes of 6MWT (P < 0.05) and TUG (P < 0.05), and the intervention group patients experienced more distance and speed in these two tests. This study was approved by the ethics committee of Mashhad University of Medical Sciences (IR.MUMS.FHMPM.REC.1400.079 dated 28th Jan 2022). The trial was registered with the clinical trials site of www.IRCT.ir (IRCT20210730052024N1) on January 28th 2022. CONCLUSION: It seems that the HEXA robot can effectively improve walking capacity and speed.

Photobiomodulation and mesenchymal stem cell-conditioned medium for the repair of experimental critical-size defects.

Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups.

Long-term survival after hepatic resection for colorectal liver metastases: a single-center study in Iran.

BACKGROUND: Surgical resection of colorectal cancer liver metastasis (CRLM) has been associated with improved survival in these patients. The purpose of this study was to investigate the usefulness of liver metastasectomy, also finding independent factors related to survival after liver metastasectomy. METHODS: In a retrospective study, all patients with CRLM who underwent resection of liver metastases between 2012 and 2022 at Imam Khomeini Hospital Complex in Tehran, Iran, were enrolled. All patients were actively followed based on clinicopathologic and operative data. RESULTS: A total of 248 patients with a median follow-up time of 46 months (Range, 12 to 122) were studied. Eighty-six patients (35.0%) underwent major hepatectomy, whereas 160 (65.0%) underwent minor hepatectomy. The median overall survival was 43 months (Range, 0 to 122 months), with estimated 1-, 3- and 5-year overall survival rates of 91%, 56%, and 42%, respectively. Multivariate analysis demonstrated that a metastasis size > 6 cm, major hepatectomy, rectum as the primary tumor site, and involved margin (< 1 mm) were independent factors associated with decreased overall survival (OS). CONCLUSION: Surgical resection is an effective treatment for patients with CRLM that is associated with relatively favorable survival. A negative margin of 1 mm seems to be sufficient for oncological resection.

Correction: Impact of School-Based Interventions on Pediatric Obesity: A Systematic Review.

[This corrects the article DOI: 10.7759/cureus.43153.].

Immobilization Period for the Non-Operative Treatment of Proximal Humerus Fractures: Systematic Review and Meta-Analysis.

Objectives: Proximal humerus fractures (PHFs) are common fractures in the elderly and are typically treated conservatively with immobilization. However, there is no consensus on whether to choose early or late conventional mobilization, taking their outcomes into account. This paper reviews comparative studies on the clinical outcomes of one- and three-week immobilization periods in terms of limb function, pain intensity, and complications following the adoption of the non-surgical treatment of PHF. Methods: The current systematic review started with searching PubMed, Scopus, and Web of Science databases for randomized clinical trials (RCTs) on PHF patients to compare the clinical outcomes between patients receiving the one-week mobilization (early mobilization) and those receiving the three-week mobilization (late mobilization). We also performed a meta-analysis to compare the two groups' limb function and pain levels at three and six months of follow-up. Results: Five of the seven RCTs had adequate data to be included in the meta-analysis. The quantitative results showed that the early mobilized patients had improved limb function at three [weighted mean difference (WMD): 5.15 (CI 95%: 0.68-9.62)] and six [WMD: 3.51 (CI 95%: 0.43-6.60)] months, but not at 12 months of follow-up. At either three, six, or 12 months, there was no difference in pain intensity between the two groups. Conclusion: This review supports the adoption of early mobilization at one week for the non-operative management of PHFs. However, to compare the long-term effects, more clinical trials with longer follow-ups are needed.

A Proposal of a Design for the Bionic Hand: Describing the Integration, Motor Controlling System, Stereognosis, and Proprioception Sensory Feedback Components.

Despite recent advancements in bionic upper limb prostheses technology, the rejection rate by users remains unacceptably high. Various factors contribute to this issue, such as limited functionality, complex control mechanisms, and discomfort, with most of these concerns being documented solely through self-assessment surveys. In this article, we introduce our proposed four components for an integrated bionic hand aimed at making it closely resemble a natural hand. These components include an integrated intramedullary stem, a kineticomyographic motor control system, sensory feedback for stereognosis, and sensory feedback for proprioception.

Improving access to psychological intervention in low-middle income settings: Results from a waitlist-controlled, proof-of-concept trial of the MemFlex intervention for trauma-exposed Afghan youth.

BACKGROUND: Low-intensity interventions targeting a range of mental health issues offer a scalable approach for young trauma survivors in low-middle income countries. AIMS: Here, we present results from a proof-of-concept, randomized, waitlist-controlled trial evaluating MemFlex, an autobiographical memory-based intervention, for trauma-exposed Afghan youth residing in Iran. MemFlex seeks to reduce the negative and overgeneral memory biases which maintain and predict poor mental health. MATERIALS AND METHODS: Young people aged 12-18 years (N = 40) with parents who had experienced forced migration from Afghanistan were recruited from high schools in Karaj City in Iran. All had experienced a traumatic event in the last year. Participants were randomized to receive four weeks of a group-based delivery of MemFlex or Waitlist. Our primary cognitive outcome was autobiographical memory flexibility, that is, the ability to deliberately retrieve any memory type on demand. Primary clinical outcome was emotional distress, measured on the Farsi version of the Hopkins Symptom Checklist. RESULTS: Results indicated that MemFlex participants demonstrated large effect sizes for pre-to-post improvement in memory flexibility (d = 2.04) and emotional distress (d = 1.23). These improvements were significantly larger than Waitlist (ds < .49), and were maintained at three-month follow-up. DISCUSSION: Positive benefits were observed for completion of MemFlex, and future comparison against an active intervention appears warranted. CONCLUSION: Further evaluation of MemFlex in this context may offer a low-cost, and low-resource intervention to improve access to psychological intervention for young migrants in low-middle income countries.

Spontaneous coronary artery dissection in patients with prior psychophysical stress: a systematic review of case reports and case series.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome, particularly in younger women. Due to limited information about SCAD, case reports and case series can provide valuable insights into its features and management. This study aimed to comprehensively evaluate the features of SCAD patients who experienced psychophysical stress before the SCAD event. METHODS: We conducted an electronic search of PubMed, Scopus, and Web of Science from inception until January 7, 2023. We included case reports or series that described patients with SCAD who had experienced psychophysical stress before SCAD. Patients with pregnancy-associated SCAD were excluded from our analysis. RESULTS: In total, we included 93 case reports or series describing 105 patients with SCAD. The average patient age was 44.29 ± 13.05 years and a total of 44 (41.9%) of patients were male. Among the included SCAD patients the most prevalent comorbidities were fibromuscular dysplasia (FMD) and hypertension with the prevalence of 36.4 and 21.9%, respectively. Preceding physical stress was more frequently reported in men than in women; 38 out of 44 (86.4%) men reported physical stress, while 36 out of 61 (59.1%) females reported physical stress (p value = 0.009). On the other hand, the opposite was true for emotional stress (men: 6 (13.6%)), women: 29 (47.6%), p value < 0.001). Coronary angiography was the main diagnostic tool. The most frequently involved artery was the left anterior descending (LAD) (62.9%). In our study, recurrence of SCAD due to either the progression of a previous lesion or new SCAD in another coronary location occurred more frequently in those treated conservatively, however the observed difference was not statistically significant (p value = 0.138). CONCLUSION: While physical stress seems to precede SCAD in most cases, emotional stress is implicated in females more than males.

The development of a serious game for laser applications in dentistry and the evaluation of dental students' satisfaction.

BACKGROUND: This study aimed to design and implement a gamified application about the theoretical aspects of laser applications in dentistry and investigate students' satisfaction with their learning experience. METHODS: An engaging educational program named Essential Skills and Knowledge in Learning Laser (ESKILLD) was developed to teach laser applications in dentistry. The program comprises two primary components: a "Tutorial and Quiz" section and a "Games" section. Final-year dental students were tasked with installing and using this application. A 29-item validated questionnaire (Cronbach's alpha = 0.97, ICC = 0.94) was used to evaluate students' perceptions of the applications' design and functionality. The influence of participants' gender and Grade Point Average (GPA) on their satisfaction levels was examined via the student t-test and Pearson's correlation, with a significance level of 0.05. RESULTS: The study had 56 participants, of which 37 were female (66.07%), and 19 were male (33.92%). The students' average GPA was 15.16 out of 20. The mean rating for ESKILLD's design and functionality was 1.39 ± 0.47 and 1.37 ± 0.46, respectively, signifying a high satisfaction level. Female students rated the application's coherence and learning perception significantly higher than their male counterparts (p < 0.05). However, gender did not significantly influence scores on other perception aspects or overall scores. Students' GPAs and their perception scores did not have a significant correlation. CONCLUSIONS: The results indicate that the participants were generally satisfied with the game's features and attitudes towards it, which underscores the potential effectiveness of gamification in dental courses focused on laser applications.

Effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19: a randomized controlled trial.

Objective: Spirulina (arthrospira platensis) is a cyanobacterium proven to have anti-inflammatory, antiviral, and antioxidant effects. However, the effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19 is currently unclear. This study aimed to evaluate the efficacy and safety of high-dose Spirulina platensis for SARS-CoV-2 infection. Study Design: We conducted a randomized, controlled, open-label trial involving 189 patients with COVID-19 who were randomly assigned in a 1:1 ratio to an experimental group that received 15.2g of Spirulina supplement plus standard treatment (44 non-intensive care unit (non-ICU) and 47 ICU), or to a control group that received standard treatment alone (46 non-ICU and 52 ICU). The study was conducted over six days. Immune mediators were monitored on days 1, 3, 5, and 7. The primary outcome of this study was mortality or hospital discharge within seven days, while the overall discharge or mortality was considered the secondary outcome. Results: Within seven days, there were no deaths in the Spirulina group, while 15 deaths (15.3%) occurred in the control group. Moreover, within seven days, there was a greater number of patients discharged in the Spirulina group (97.7%) in non-ICU compared to the control group (39.1%) (HR, 6.52; 95% CI, 3.50 to 12.17). Overall mortality was higher in the control group (8.7% non-ICU, 28.8% ICU) compared to the Spirulina group (non-ICU HR, 0.13; 95% CI, 0.02 to 0.97; ICU, HR, 0.16; 95% CI, 0.05 to 0.48). In non-ICU, patients who received Spirulina showed a significant reduction in the levels of IL-6, TNF-α, IL-10, and IP-10 as intervention time increased. Furthermore, in ICU, patients who received Spirulina showed a significant decrease in the levels of MIP-1α and IL-6. IFN-γ levels were significantly higher in the intervention group in both ICU and non-ICU subgroups as intervention time increased. No side effects related to Spirulina supplements were observed during the trial. Conclusion: High-dose Spirulina supplements coupled with the standard treatment of COVID-19 may improve recovery and remarkably reduce mortality in hospitalized patients with COVID-19. Clinical Trial Registration: https://irct.ir/trial/54375, Iranian Registry of Clinical Trials number (IRCT20210216050373N1).

Sex-based association between high-density lipoprotein cholesterol and adverse outcomes after coronary artery bypass grafting.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is shown to be an independent protective factor against coronary artery diseases (CAD). Yet there are limited studies focusing on the association between HDL-C and coronary artery bypass graft (CABG) surgery outcomes. HYPOTHESIS: Low levels of HDL-C are associated with higher incidence of adverse outcomes in patients undergoing CABG. METHODS: This registry-based study included 17,772 patients who underwent elective isolated CABG between 2007 and 2017. Patients were classified into low and desirable HDL-C groups based on their serum HDL-C levels at admission and were followed for one-year post-surgery. The study population included 13,321 patients with low HDL-C and 4,451 with desirable HDL-C. proportional hazard Cox models were performed to evaluate the association between HDL-C levels and incidence of mortality as well as major adverse cardiovascular and cerebrovascular events (MACCE), while adjusting for potential confounders. Moreover, participants were stratified based on sex and the association was also investigated in each subgroup separately. RESULTS: No significant difference was found between the groups regarding incidence of both mortality and MACCE, after adjusting with Inverse Probability Weighting (IPW) [HR (95%CI): 0.84 (0.46-1.53), p-value:0.575 and HR (95% CI): 0.91 (0.56-1.50), p-value:0.733, respectively]. According to the sex-based subgroup analysis, no significant association was observed after adjustment with IPW analysis. However, as we examined the association between the interaction of HDL-C levels, sex and cardiovascular outcomes, we found a significant association (HR;1.19 (95%CI: 1.04-1.45); p = 0.030). CONCLUSION: HDL-C level was not associated with either mortality or MACCE during one year after CABG procedure. Sex-based analysis showed that in males, HDL-C is significantly more protective against these outcomes, compared to females. Further studies are necessary to elucidate the exact mechanisms mediating such association.

Extracellular vesicles derived from dendritic cells loaded with VEGF-A siRNA and doxorubicin reduce glioma angiogenesis in vitro.

BACKGROUND: Numerous attempts have been devoted to designing anti-angiogenic agents as a strategy to slow tumor growth and progression. Clinical applications of conventional anti-angiogenic agents face some challenges, e.g., off-target effects for TKIs and also low solid tumor penetration for mAbs. Furthermore, although anti-angiogenic therapy provides a normalization window for better chemo-RT response, in long-term treatments, tumor hypoxia as a result of total removal of VEGF-A by mAbs from the TME or complete blockade of TK receptors induces over-activation of compensatory angiogenic pathways, causing escape. Herein, we investigate the efficacy of si-DOX-DC-EVs to reduce glioma angiogenesis and invasiveness. METHODS: Mature DCs were generated from PBMC and EVs were isolated from the DCs culture media. siRNA and Doxorubicin were loaded into EVs by EP and incubation. Afterward, the uptake of DC-EVs was assessed by flow cytometry, and the subcellular localization of EVs was tested by confocal imaging. Tube formation assay was performed to assess the efficacy of si-DOX-DC-EVs to reduce tumor angiogenesis which was analyzed by DHM. Morphometric analysis of apoptotic cells was performed by DHM and confocal imaging and further, ELISA was performed for hypoxia-related and angiogenic cytokines. The impact of our theranostic system "si-DOX-DC-MVs" on the formation of vascular mimics, colonies, and invasion of C6 cells was checked in vitro. Afterward, orthotropic rat models of glioma were generated and the optimal administration route was selected by in vivo fluorescent analysis. Then, the microvessel density, vimentin expression, and accumulation of immune cells in tumoral tissues were assessed by IHC. Finally, necropsy and autopsy analyses were performed to check the safety of our theranostic agent. RESULTS: DC-EVs loaded with si-DOX-DC-EVs were successfully uptaken by cells with different subcellular trafficking for MVs and exosomes, reduced tumor angiogenesis in DHM analysis, and induced apoptosis in tumoral cells. Moreover, using DHM, we performed a detailed label-free analysis of tip cells which suggested that the tip cells in si-DC-MV treatments lost their geometrical migration capacity to form tube-like structures. Furthermore, the ELISAs performed highlighted that there is a mild overactivation of compensatory Tie2/Ang2 pathway after VEGF-A blockade which confers with severe hypoxia and sustains normal angiogenesis which is the optimal goal of anti-angiogenesis therapy for cancer to avoid resistance.The results of our VM analyses indicated that si-DOX-DC-MVs completely inhibited VM process. Moreover, the invasion, migration, and colony formation of the C6 cells treated with si-DOX-MVs were the least among all treatments. IN was the optimal route of administration. The MVD analyses indicated that si-DOX-DC-MVs reduced the number of tumoral microvessels and normalized vessel morphology. Intense CD8+ T cells were observed near the tumoral vessels in the si-DOX-DC-MVs group and with minimal activation of MT (low Vimentin expression). Necropsy and toxicology results proved that the theranostic system proposed is safe. CONCLUSIONS: DC-EVs loaded with VEGF-A siRNA and Doxorubicin were more potent than BV alone as a multi-disciplinary strategy that combats glioma growth by cytotoxic impacts of DOX and inhibits angiogenesis by VEGF-A siRNAs with excess immunologic benefits from DC-EVs. This next-generation anti-angiogenic agent normalizes tumor vessel density rather than extensively eliminating tumor vessels causing hypoxia and mesenchymal transition.

Sumatriptan attenuates fear-learning despair induced by social isolation stress in mice: Mediating role of hypothalamic-pituitary-adrenal axis.

OBJECTIVES: Research has demonstrated that chronic stress experienced early in life can lead to impairments in memory and learning. These deficits are attributed to an imbalance in the interaction between glucocorticoids, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoid receptors in brain regions responsible for mediating memory, such as the hippocampus. This imbalance can result in detrimental conditions like neuroinflammation. The aim of this study was to assess the impact of sumatriptan, a selective agonist for 5-HT 1B/1D receptors, on fear learning capabilities in a chronic social isolation stress model in mice, with a particular focus on the role of the HPA axis. METHODS: Mice were assigned to two opposing conditions, including social condition (SC) and isolated condition (IC) for a duration of five weeks. All mice underwent passive avoidance test, with their subsequent freezing behavior serving as an indicator of fear retrieval. Mice in the IC group were administered either a vehicle, sumatriptan, GR-127935 (a selective antagonist for 5-HT 1B/1D receptors), or a combination of sumatriptan and GR-127935 during the testing sessions. At the end, all mice were sacrificed and samples of their serum and hippocampus were collected for further analysis. RESULTS: Isolation was found to significantly reduce freezing behavior (p<0.001). An increase in the freezing response among IC mice was observed following the administration of varying doses of sumatriptan, as indicated by a one-way ANOVA analysis (p<0.001). However, the mitigating effects of sumatriptan were reversed upon the administration of GR-127935. An ELISA assay conducted before and after the passive avoidance test revealed no significant change in serum corticosterone levels among SC mice. In contrast, a significant increase was observed among IC mice, suggesting hyper-responsiveness of the HPA axis in isolated animals. This hyper-responsiveness was ameliorated following the administration of sumatriptan. Furthermore, both the sumatriptan and SC groups exhibited a similar trend, showing a significant increase in the expression of hippocampal glucocorticoid receptors following the stress of the passive avoidance test. Lastly, the elevated production of inflammatory cytokines (TNF-α, IL-1ß) observed following social isolation was attenuated in the sumatriptan group. CONCLUSION: Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation.

Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.

Contribution of Soft Tissue Passive Forces in Thumb Carpometacarpal Joint Distraction.

Thumb carpometacarpal joint space changes when the surrounding soft tissues including the capsule, ligaments, and tendons are stretched or pulled away. When at rest, joint forces originate from passive contraction of muscles and the involvement of joint capsule and ligaments. Previous biomechanical models of hand and finger joints have mostly focused on the assessment of joint properties when muscles were active. This study aims to present an experimental-numerical biomechanical model of thumb carpometacarpal joint to explore the contribution of tendons, ligaments, and other soft tissues in the passive forces during distraction. Five fresh cadaveric specimens were tested using a distractor device to measure the applied forces upon gradual distraction of the intact joint. The subsequent step involved inserting a minuscule sensor into the joint capsule through a small incision, while preserving the integrity of tendons and ligaments, in order to accurately measure the fundamental intra-articular forces. A numerical model was also used to calculate the passive forces of tendons and ligaments. Before the separation of bones, the forces exerted by tendons and ligaments were relatively small compared to the capsule force, which accounted for approximately 92% of the total applied force. Contribution of tendons and ligaments, however, increased by further distraction. The passive force contribution by tendons at 2-mm distraction was determined less than 11%, whereas it reached up to 74% for the ligaments. The present study demonstrated that the ligament-capsule complex plays significant contribution in passive forces of thumb carpometacarpal joint during distraction.