Enhanced Treatment Strategies Research Articles

Exosomes From Muscle-Derived Stem Cells Repair Peripheral Nerve Injury by Inhibiting Ferroptosis via the Keap1-Nrf2-Ho-1 Axis.

Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting the urgent need to understand the mechanisms of nerve injury to enhance treatment strategies. Muscle-derived stem cells (MDSCs) are a diverse group of multipotent cells that hold promise for peripheral nerve regeneration due to their strong antioxidant and regenerative properties. Our research has revealed that severe ferroptosis occurs in the sciatic nerve and ipsilateral dorsal root ganglion following sciatic nerve injury. Interestingly, we have observed that MDSC-derived exosomes effectively suppress cell ferroptosis and enhance cell viability in Schwann cells and dorsal root ganglion cells. Treatment with exosomes led to increased expression of BDNF and P62 in Schwann cells, decreased expression of Keap1, Nrf2, and HO-1 in Schwann cells, and upregulated dorsal root ganglion cells. Rats treated with exosomes exhibited improvements in sciatic nerve function, sensitivity to stimuli, and reduced muscle atrophy, indicating a positive impact on post-injury recovery. In conclusion, our findings demonstrate the occurrence of ferroptosis in the sciatic nerve and dorsal root ganglion post-injury, with MDSC exosomes offering a potential therapeutic strategy by inhibiting ferroptosis, activating the Keap1-Nrf2-HO-1 pathway, and optimizing the post-injury repair environment.

Comparative meta-analysis of endovascular strategies for intracranial dissecting aneurysms: Flow diverters versus stents with or without coiling.

Intracranial dissecting aneurysms present a challenging subset linked to considerable morbidity and mortality, necessitating effective therapeutic strategies to prevent complications. Traditional treatments face technical limitations, while emerging endovascular modalities like stent-assisted coiling, multiple stenting, and flow-diverting devices (FDDs) offer promise in reducing periprocedural risks and enhancing patient outcomes. The aim of this study is to compare the safety and efficacy outcomes of endovascular treatment for intracranial dissecting aneurysms using FDDs versus stents (with or without coiling). A systematic review and meta-analysis were conducted following established guidelines. The search included PubMed, Scopus, Web of Science, and Embase databases up to July 30, 2023. Eligible studies reporting outcomes of interest in both FDD and stent-treated groups were included, and the data was extracted and analyzed using STATA software. Six studies were analyzed, involving 131 patients in the FDD group and 199 patients in the stent group. The pooled rates for favorable functional outcomes (86.8% vs. 86%), mortality (3.9% vs. 6%), adequate occlusion (79.7% vs. 86.3%), aneurysm recurrence (1.3% vs. 13.3%), in-stent stenosis/thrombosis (7% vs. 6.9%), ischemic events/infarctions (6.7% vs. 7.8%), retreatment (7% vs. 8.6%), and technical success (100% vs. 98.7%) were comparable in individuals treated with FDDs and stents (p > 0.05 in all cases). Additionally, complete occlusion rates were not significantly different between FDD (62.7%) and stent-treated patients (75.2%) (p = 0.06). However, after excluding one study in a leave-one-out analysis of the random effects meta-analysis, a significant difference in the pooled rates of this outcome was observed between the FDD (59.2%) and stent (75.2%) groups (p = 0.034). FDDs present a promising approach for the treatment of intracranial dissecting aneurysms, yielding outcomes that are roughly comparable to stent-based methods. However, the absence of randomized trials and data limitations highlight the need for further research to enhance treatment strategies.

Effect of mindfulness training in adjunct to conventional physiotherapy on pain, function, and mindfulness attention awareness score in recreational long distance runners with patellofemoral pain syndrome: A randomized controlled trial protocol

Background The Patellofemoral Pain Syndrome (PFPS) poses a significant challenge in sports medicine due to its multifactorial etiology involving both physiological and psychological factors. Though widely used, conventional physiotherapy approaches often yield limited efficacy and high recurrence rates. Mindfulness-based interventions have emerged as promising adjuncts in managing various musculoskeletal conditions, offering potential benefits in pain management, coping strategies, and overall well-being. However, their efficacy in addressing PFPS remains underexplored, particularly in the context of recreational long-distance runners. This study investigates the effects of integrating mindfulness training as an adjunct to conventional physiotherapy on pain intensity, functional outcomes, and mindfulness awareness in recreational long-distance runners with PFPS. Methods Eligible individuals will be assigned randomly to either Group A (Mindfulness Training + Conventional Physiotherapy) or Group B (Conventional Physiotherapy). Outcome measures, such as the Numeric Pain Rating Scale (NPRS), Mindfulness Attention Awareness Scale (MAAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and knee joint position sense using a goniometer will be assessed at baseline and post-intervention. Mindfulness training will encompass a variety of techniques integrated with conventional physiotherapy sessions. Result This study has the potential to offer an enhanced treatment strategy that considers both the physical and psychological aspects of Patellofemoral Pain Syndrome (PFPS), potentially improving outcomes and well-being for recreational long-distance runners. CTRI Registration Number: CTRI/2024/03/064876

Real world experience of molecular landscape of uveal melanomas: Implications for personalized medicine strategies.

e21572 Background: In the realm of ocular oncology, Uveal Melanoma (UM) stands out as a rare and formidable malignancy, necessitating a deeper understanding of its molecular landscape to enhance treatment strategies. This abstract delves into the real-world experiences of unraveling the molecular intricacies of UM and explores the implications for personalized medicine strategies. Methods: In this study, we conducted a comprehensive genomic analysis of tissue samples from 7 UM cases to identify key genetic alterations and molecular features, elucidating the heterogeneity of this ocular malignancy. Results: Consistent with other studies, 57% (4/7) of our cohort harbored a driver mutation in either the GNAQ or GNA11 genes. GNAQ Q209 codon mutations (Q209L or Q209P), were the most frequent variants identified. GNAQ/GNA11 mutations are known to activate the MAPK/ERK signaling pathway, contributing to uncontrolled cell proliferation; its presence qualifies for entry into clinical trial testing DYP688 in metastatic UM. Concurrent mutations were identified in EIF1AX (n = 1), SF3B1 genes (n = 1) and BAP1 (n = 1), highlighting the molecular diversity. EIF1AX, SF3B1, and BAP1 inactivating mutations indicate varying risks for distant metastasis, categorized as low, medium, and high risk, respectively. Notably, homologous recombination repair (HRR) pathway gene mutations were identified in 28% (2/7) of cases. Additionally, SF3B1 mutations have been proposed to induce a BRCA-like phenotype, resulting in synthetic lethality to PARP inhibitors (PARPi). These findings provide opportunities to explore additional targeted therapy (off label) options with PARPi. In a case where gene expression profiling (GEP) was performed, an upregulation in PRAME gene expression (PRAME+) was observed. This finding potentially indicates an increased metastatic risk and a shorter time to metastasis, given that PRAME+ status has been established as an independent risk modifier for metastasis, regardless of the GEP-derived UM class (Class 1 or 2). TMB ranged from 2 to 21 muts/mb, with 5 out of 7 specimens showing low TMB ( < 10 mutations/Mb) and two sample with high TMB (15 and 21muts/mb). This case with TMB of 21 muts/mb showed Deficient Mismatch Repair (dMMR) status. All samples evaluated for PD-L1 expression (n = 4) in our cohort showed < 1% PD-L1 expression in tumor cells, including the dMMR tumor. Conclusions: These findings underscore the need for a comprehensive genomic approach in guiding therapeutic decisions, understanding prognostic implications and advancing personalized medicine strategies for UM patients. Our study provides an overview of the molecular landscape of UMs with delineation of key molecular features, thereby enhancing our understanding of UM biology and setting the stage for the development of targeted therapies tailored to the unique genomic profile of each patient.

Effects of suboccipital inhibition versus soft tissue manipulation on pain intensity and disability in tension-type headache among undergraduate physiotherapy students

BackgroundTension-type headache (TTH) is prevalent among collegiate students due to academic stress. Manual therapies like suboccipital inhibition and soft tissue manipulation have shown efficacy in TTH management. However, comparative studies between these interventions in collegiate populations are scarce. Understanding their relative effectiveness can enhance treatment strategies and improve outcomes, shedding light on optimal manual therapy approaches for TTH among collegiate students. This study aimed to investigate the effects of suboccipital inhibition and soft tissue manipulation on pain intensity and disability in tension-type headache (TTH) among undergraduate physiotherapy students.MethodsForty undergraduate physiotherapy students diagnosed with TTH were randomly assigned to the suboccipital inhibition group (group A, n = 20) and the soft tissue manipulation group (group B, n = 20). The suboccipital inhibition group received manual therapy targeting the suboccipital muscles, while the soft tissue manipulation group received manipulation techniques focusing on the cervical and shoulder girdle muscles. Pain intensity and disability were assessed using Visual Analogue Scale (VAS) and Headache Disability Index (HDI) Questionnaire at baseline and after 6 weeks of intervention. The data were collected and analysed using independent t test.ResultsBoth interventions demonstrated significant reductions in pain intensity and disability after 6 weeks, with the t value − 4.3150 and − 3.3106 at p < 0.05 for VAS and HDI respectively.ConclusionSuboccipital inhibition and soft tissue manipulation are effective interventions for reducing pain intensity and disability among undergraduate physiotherapy students with TTH. However, the suboccipital inhibition group showed improvement in pain intensity and disability and it has been statistically significant when compared to the soft tissue manipulation group.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer's Disease.

Alzheimer's disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases-dementia, type 2 diabetes, hypertension, Parkinson's disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes-PSEN1, PSEN2, MAPT, APP, APOE, NOTCH, and HFE-for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene-drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases.

Role of cytokines in immunomodulation during malaria clearance.

Malaria remains a significant global health challenge, demanding a deeper understanding of host immune responses for effective clearance of the parasitic infection. Cytokines, as crucial mediators of the immune system, orchestrate a complex interplay during the various stages of malaria infection. Throughout the course of the disease, an intricate balance of pro-inflammatory and anti-inflammatory cytokines dictate the immune response's outcome, influencing parasitic clearance and disease severity. During the initial stages, interleukins such as interleukin-12 (IL-12), interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α) play pivotal roles in activating innate immune cells, initiating the anti-parasitic response. Simultaneously, regulatory cytokines like interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) modulate this immune activation, preventing excessive inflammation and tissue damage. As the infection progresses, a delicate shift occurs, characterized by a transition to adaptive immunity, guided by cytokines like interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), promoting antibody production and T-cell responses. Notably, the resolution of malaria infection crucially relies on a fine-tuned balance of cytokine networks. Dysregulation or imbalances in these mediators often result in immune hyperactivation, contributing to severe manifestations and prolonged infection. Understanding the multi-faceted roles of cytokines in malaria clearance offers promising avenues for therapeutic interventions. Targeting cytokine pathways to restore immune equilibrium or bolster protective responses could potentially enhance treatment strategies and vaccine development. In conclusion, the pivotal role of cytokines in immunomodulation during malaria clearance underscores their significance as potential targets for therapeutic interventions, offering promising prospects in the global fight against this infectious disease.

Therapeutic targeting of thioredoxin reductase 1 causes ferroptosis while potentiating anti-PD-1 efficacy in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) faces low response rates to anti-PD-1 immunotherapies, highlighting the need for enhanced treatment strategies. Auranofin, which inhibits thioredoxin reductase (TrxR) through its gold-based composition, has shown potential in cancer treatment. It targets the TrxR system, essential for safeguarding cells from oxidative stress. The overproduction of TrxR in cancerous cells supports their proliferation. However, auranofin's interference with this system can upset the cellular redox equilibrium, boost levels of reactive oxygen species, and trigger the death of cancer cells. This study is the first to highlight TXNRD1 as a crucial factor contributing to resistance to anti-PD-1 treatment in HNSCC. In this study, we identified targetable regulators of resistance to immunotherapy-induced ferroptosis in HNSCC. We observed a link of thioredoxin reductase 1 (TXNRD1) with tumoral PD-L1 expression and ferroptosis suppression in HNSCC. Moreover, HNSCC tumors with aberrant TXNRD1 expression exhibited a lack of PD-1 response, NRF2 overexpression, and PD-L1 upregulation. TXNRD1 inhibition promoted ferroptosis in HNSCC cells with NRF2 activation and in organoid tumors derived from patients lacking a PD-1 response. Mechanistically, TXNRD1 regulated PD-L1 transcription and maintained the redox balance by binding to ribonucleotide reductase regulatory subunit M2 (RRM2). TXNRD1 expression disruption sensitized HNSCC cells to anti-PD-1–mediated Jurkat T-cell activation, promoting tumor killing through ferroptosis. Moreover, TXNRD1 inhibition through auranofin cotreatment synergized with anti-PD-1 therapy to potentiate immunotherapy-mediated ferroptosis by mediating CD8+ T-cell infiltration and downregulating PD-L1 expression. Our findings indicate that targeting TXNRD1 is a promising therapeutic strategy for improving immunotherapy outcomes in patients with HNSCC.

Assessment of Nocturnal Blood Pressure: Importance of Determining the Time in Bed-A Pilot Study.

Objectives: Nocturnal blood pressure (BP) monitoring is essential for evaluating cardiovascular risk and guiding treatment decisions. However, the standardized narrow-fixed nighttime period between 10 p.m. and 6 a.m. may not accurately reflect individual sleep schedules. This pilot study aimed to investigate the comparability between the standardized nighttime period and actual time in bed (TIB) regarding BP assessment. Further, our goal was to evaluate the clinical relevance of the observed BP differences. Methods: A total of 30 participants underwent 24 h ambulatory blood pressure monitoring (ABPM). Patient-specific TIB was precisely assessed through an accelerometer and a position sensor from the SOMNOtouch NIBP™ (SOMNOmedics GmbH, Randersacker, Germany). We analysed the effect of considering individual TIB as nighttime instead of the conventional narrow-fixed interval on the resulting nocturnal BP levels and dipping patterns. Results: We observed differences in both systolic and diastolic BP between the standardized nighttime period and the TIB. Furthermore, a notable percentage of patients (27%) changed their dipping pattern classification as a function of the nighttime definition adopted. We found strong correlations between the start (r = 0.75, p < 0.01), as well as the duration (r = -0.42, p = 0.02) of TIB and the changes in dipping pattern classification. Conclusions: Definition of nocturnal period based on the individual TIB leads to clinically relevant changes of nocturnal BP and dipping pattern classifications. TIB is easily detected using a body position sensor and accelerometer. This approach may thus improve the accuracy of cardiovascular risk evaluation and enhance treatment strategies.

Creation of signatures and identification of molecular subtypes of glioblastoma based on disulfidptosis-related genes for predicting patient prognosis and immunological activity

BackgroundIn recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic. MethodsThe GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value. ResultsThe differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score. ConclusionWe have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies.

A multiscale modeling study of nanoparticle-based targeting therapy against atherosclerosis

Although researches on nanoparticle-based (NP-based) drug delivery system for atherosclerosis treatment have grown rapidly in recent years, there are limited studies in quantifying the effects of targeting drugs on plaque components and microenvironment. The purpose of the present study was to quantitatively assess the targeting therapeutic effects against atherosclerosis by establishing a multiscale mathematical model.The multiscale model involved subcellular, cellular and microenvironmental scales to simulate lipid catabolism, macrophage behaviors and dynamics of microenvironmental components, respectively. In vitro and in vivo experimental data were integrated into the mathematical model according to Bayesian statistics, in order to evaluate the therapeutic effects of a proposed NP-based platform for macrophage-specific delivery to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR-L (to stimulate cholesterol efflux). Dosage variation analysis was then performed to investigate the drug efficacy under varied dosage combinations of SR-A siRNA and LXR-L.The simulation results demonstrated that the dynamics of the microenvironmental components presented different developments in Untreated and Treated groups. We also found that the balance of lipid metabolism between uptake and efflux resulted in the improvement of lipid and inflammatory microenvironment, consequently in the plaque regression. In addition, the model predicted optimized dosage combinations according to the co-effect analysis of the two drugs on the lipid microenvironment.This study suggests that multiscale modeling can be a powerful quantitative tool for estimating the therapeutic effects of targeting drugs for plaque regression and designing the enhanced treatment strategies against atherosclerosis.

Exercise therapy, education, and cognitive behavioral therapy alone, or in combination with total knee arthroplasty, in patients with knee osteoarthritis: a randomized feasibility study

BackgroundOne in five patients experience chronic pain 1 year after total knee arthroplasty (TKA), highlighting the need for enhanced treatment strategies to improve outcomes. This feasibility trial aimed to optimize the content and delivery of a complex intervention tailored to osteoarthritis (OA) patients at risk of poor outcome after TKA and assess the feasibility of initiating a full-scale multicenter randomized controlled trial (RCT).MethodsPatients scheduled for TKA were included between August 2019 and June 2020 and block-randomized into one of three groups: (a) 12-week exercise therapy and education (ExE) and 10-module internet-delivered cognitive behavioral therapy (iCBT), (b) TKA followed by ExE and iCBT and (c) TKA and standard postoperative care. Outcomes were (i) recruitment and retention rate, (ii) compliance to the intervention and follow-up, (iii) crossover, and (iv) adverse events, reported by descriptive statistics.ResultsFifteen patients were included in the study. Only 1 out of 146 patients screened for eligibility was included during the first 4 months. During the next 3 months, 117 patients were not included since they lived too far from the hospital. To increase the recruitment rate, we made three amendments to the inclusion criteria; (1) at-risk screening of poor TKA outcome was removed as an eligibility criterion, (2) patients across the country could be included in the study and (3) physiotherapists without specific certification were included, receiving thorough information and support. No patients withdrew from the study or crossed over to surgery during the first year. Nine out of 10 patients completed the ExE program and six out of 10 completed the iCBT program. Fourteen out of 15 patients completed the 1-year follow-up. One minor adverse event was registered.ConclusionsExcept for recruitment and compliance to iCBT, feasibility was demonstrated. The initial recruitment process was challenging, and necessary changes were made to increase the recruitment rate. The findings informed how a definitive RCT should be undertaken to test the effectiveness of the complex intervention.Trial registrationThe MultiKnee RCT, including the feasibility study, is pre-registered at ClinicalTrials.gov: NCT03771430 11/12/2018.

Prevalence, Severity, and Correlation with Agenesis of Permanent Successors of Infraoccluded Primary Molars at Chonnam National University Hospital’s Department of Pediatric Dentistry

This study aimed to analyze the prevalence and severity of infraoccluded primary molars (IPM) and their correlation with the agenesis of permanent successors (APS). A total of 4,011 panoramic radiographs from children aged 4 to 11 years who had all 8 primary molars were examined. The prevalence of APS was analyzed based on the severity and tooth type of IPM. The prevalence of IPM was 13.0%, and there was no difference between genders. The majority of the children had two IPMs each. In all tooth types, mild infraocclusion was the most prevalent, whereas severe infraocclusion was the least frequent. Among the types of primary molars, the lower primary first molar (62.3%) was the most affected, followed by the lower primary second molar (27.7%), the upper primary second molar (5.8%), and the upper primary first molar (4.2%). Infraocclusion was 11.2 times more prevalent in the mandible than in the maxilla, with no significant difference between the left and right sides. The correlation between IPM and APS was also investigated. Among the subjects, 177 had one or more agenesis of premolars, of whom 54 (30.5%) had IPM. Additionally, among the 521 individuals with IPM, 54 individuals exhibited APS (10.4%). This study identified a noteworthy prevalence of infraocclusion, with notable variations among molar types. The LPFM was particularly affected. The majority of cases were classified as mild in severity. Furthermore, a compelling association between IPM and APS was established. Understanding this connection may enhance treatment strategies for infraoccluded teeth and tooth agenesis.

The role of NLRP3 inflammasome in aging and age-related diseases.

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Giggle incontinence: a scoping review.

Giggle incontinence (GI) is poorly described, defined, and understood. It is considered a bladder storage disorder in which laughter causes an uncontrollable episode of urinary incontinence that cannot be stopped until the bladder is completely emptied. It has been confused with stress urinary incontinence and overactive bladder. A thorough analysis of 26 articles on the subject of "giggle incontinence" and associated terms was performed, including all articles since the phrase first appeared. To date, 351 GI cases have been reported. It occurs mainly in women (69.5%) at 5 years of age, with a prevalence ranging from 8.4 to 16.2 years (average age of 12.4 years), and some cases have a family history of the disease (13-16.7%). This review discusses the historical background, current understanding, and challenges related to GI. It primarily affects females after the age of 5 years, causing complete bladder emptying during uncontrollable laughter. The exact cause is unknown, but hypotheses suggest involvement of the central nervous system. Diagnosis relies on clinical history, physical tests, and urine frequency evaluation. Management involves urotherapy techniques, biofeedback, and methylphenidate. Understanding GI will aid in developing more effective management techniques. IMPACT: Highlights limited awareness among healthcare professionals about giggle incontinence as a distinct condition, emphasizing the need for standardized diagnostic criteria and assessment tools. Addresses insufficient understanding of the underlying mechanisms and contributing factors, providing valuable insights for better diagnosis and treatment. Emphasizes the importance of patient education and support, calling for improved resources and counseling. Urges further research and evidence-based guidelines to enhance treatment strategies.

A war on many fronts: cross disciplinary approaches for novel cancer treatment strategies.

Cancer is a disease characterized by uncontrolled cellular growth where cancer cells take advantage of surrounding cellular populations to obtain resources and promote invasion. Carcinomas are the most common type of cancer accounting for almost 90% of cancer cases. One of the major subtypes of carcinomas are adenocarcinomas, which originate from glandular cells that line certain internal organs. Cancers such as breast, prostate, lung, pancreas, colon, esophageal, kidney are often adenocarcinomas. Current treatment strategies include surgery, chemotherapy, radiation, targeted therapy, and more recently immunotherapy. However, patients with adenocarcinomas often develop resistance or recur after the first line of treatment. Understanding how networks of tumor cells interact with each other and the tumor microenvironment is crucial to avoid recurrence, resistance, and high-dose therapy toxicities. In this review, we explore how mathematical modeling tools from different disciplines can aid in the development of effective and personalized cancer treatment strategies. Here, we describe how concepts from the disciplines of ecology and evolution, economics, and control engineering have been applied to mathematically model cancer dynamics and enhance treatment strategies.

ОПЕРАТИВНОЕ ЛЕЧЕНИЕ ДЕТСКИХ ЦЕРЕБРАЛЬНЫХ ПАРАЛИЧЕЙ

Objective: To improve surgical treatment outcomes of spastic cerebral palsy (SCP) with lower extremities involvement. Methods: The results of surgical treatment of 208 children aged 3 to 14 years with SCP affecting the lower extremities were analyzed. Depending on the treatment tactics, the patients were divided into two groups. The main group included 105 (50.5%) patients who underwent surgery in addition to continuous complex conservative treatment. The control group included 103 (49.5%) children who were operated against the background of unsystematic and incomplete course of conservative therapy with unsystematic drug administration. Results: The surgical treatment tactics were optimized by considering the patient's age, types and combinations of contractures and deformities, enhanced surgical indications, muscle spasticity, and gait disturbances. Improvements have been made in identifying the need to correct particular contractures and deformities. Alongside the commonly used techniques, several enhanced approaches for surgical correction of contractures and deformities have been suggested. In creating efficient surgical strategies, the focus was initially on conducting surgeries on soft tissues. Bone surgeries were carried out only if soft tissue surgeries were unsuccessful. Considering the factors mentioned above, there have been enhancements in the guidelines for multilevel surgical procedures, which may be implemented in single or multiple stages, considering secondary deformities. The scale proposed during the study was used to evaluate long-term treatment outcomes. Implementing the above approach contributed to a statistically significant improvement in long-term outcomes in the main group compared to the control group (72.5±4.7 and 61.2±3.6 points, respectively; p &lt; 0.001). Based on objective data, it was found that the rates of positive outcomes (scoring above 70 points) were significantly higher in the main group compared to the control group (64.4% and 11.8%, respectively, p&lt;0.001). Conversely, the control group showed a predominance of satisfactory outcomes (scoring 61 to 70 points) in comparison to the main group (27.7% versus 65.6%, p&lt;0.001). The main group had a statistically significantly lower rate of unsatisfactory results than the control group (7.9% and 22.6%, respectively, p&lt;0.01).Conclusion: The study's findings demonstrated a statistically significant improvement in the long-term outcomes of treating SCP by implementing enhanced treatment strategies. Performing surgical procedures based on optimized indications leads to favorable outcomes in 92.1% of patients. Keywords: Cerebral palsy, spastic form, surgical treatment, Lorenz-Stoffel neurotomy, Sturm-Zatsepin method, long-term outcomes, long-term outcomes assessment scale.

Current treatments of alcohol use disorder.

Emerging treatments for alcohol dependence reveal an intricate interplay of neurobiological, psychological, and circumstantial factors that contribute to Alcohol Use Disorder (AUD). The approved strategies balancing these factors involve extensive manipulations of neurotransmitter systems such as GABA, Glutamate, Dopamine, Serotonin, and Acetylcholine. Innovative developments are engaging mechanisms such as GABA reuptake inhibition and allosteric modulation. Closer scrutiny is placed on the role of Glutamate in chronic alcohol consumption, with treatments like NMDA receptor antagonists and antiglutamatergic medications showing significant promise. Complementing these neurobiological approaches is the progressive shift towards Personalized Medicine. This strategy emphasizes unique genetic, epigenetic and physiological factors, employing pharmacogenomic principles to optimize treatment response. Concurrently, psychological therapies have become an integral part of the treatment landscape, tackling the cognitive-behavioral dimension of addiction. In instances of AUD comorbidity with other psychiatric disorders, Personalized Medicine becomes pivotal, ensuring treatment and prognosis are closely defined by individual characteristics, as exemplified by Lesch Typology models. Given the high global prevalence and wide distribution of AUD, a persistent necessity exists for development and improvement of treatments. Current research efforts are steadily paving paths towards more sophisticated, effective typology-based treatments: a testament to the recognized imperative for enhanced treatment strategies. The potential encapsulated within the ongoing research suggests a promising future where the clinical relevance of current strategies is not just maintained but significantly improved to effectively counter alcohol dependence.

Precision Tactics against Salmonella: Leveraging Nanoparticle Innovations to Confront Antimicrobial Resistance for Enhanced Treatment Strategies

Precision Tactics against Salmonella: Leveraging Nanoparticle Innovations to Confront Antimicrobial Resistance for Enhanced Treatment Strategies