Treatment Approaches Research Articles

Targeted Delivery of SmacN7 Peptide Induces Immunogenic Cell Death in Cervical Cancer Treatment.

Cervical cancer is a common tumor in women and one of the common causes of cancer death in women. Due to the aggressive and non-specific nature of traditional chemotherapy, there is a growing need for new treatment modalities. Currently, tumor immunotherapy is increasingly garnering attention as a disruptive treatment approach. Therefore, we constructed CCTP-SmacN7, a delivery system capable of releasing active molecules in the tumor microenvironment. CCTP-SmacN7 can not only inhibit tumor proliferation and migration, but also induce tumors to produce large amounts of reactive oxygen species. The production of reactive oxygen species can activate tumors to release or expose damage-associated molecular patterns, promote DC cell maturation, and ultimately activate T cells. Here, we present an innovative targeted treatment approach for cervical cancer. While inducing tumor immunogenic cell death, this program can also improve the tumor microenvironment and initiate the tumor immune cycle.

Interventions and measures of social inclusion for students with extensive support needs in K-12 schools: A scoping review.

This scoping review explores (a) how k-12 schools facilitate social inclusion, specifically for students with extensive support needs (ESN) and (b) how those intervention approaches are measured. Given the cross-disciplinary nature of the topic, the search entailed ten different databases that identified 540 articles. Eight articles met the inclusion criteria and were included in this review. The approaches used to facilitate social inclusion for students with ESN are summarized as those that involve (a) comprehensive multi-level interventions, (b) peer-mediated interventions, and (c) collaborative consultation and planning with teachers. The scoping review identified three primary constructs that assess social inclusion, namely, social interactions, participation (academic and social), and social validity of the interventions used. The scoping review underscores the complexity of the concept of social inclusion and poses a challenge to identify a unifying measure of social inclusion for students with ESN.

Looking Back Looking Forward: Parent-Infant Treatment in the Anni Bergman Home-Visiting Project

ABSTRACT In this paper the authors describe the Anni Bergman Parent-Infant Program (ABPIP), with a focus on the development of the Home-Visiting Project (HVP) begun in 2014 in New York City. This primary prevention project provides psychoanalytic, relationship-based clinical intervention to mothers and their infants struggling with multiple stressors caused by poverty, histories of trauma, single parenthood, lack of employment, and limited access to health care and food. The beginnings of the project are described, including the centrality of infant observation as a port of entry into the subsequent dyadic therapy approach. Three clinical vignettes of the first mother-infant pair with whom we worked illustrate the beginnings of the treatment model that we developed. Both authors visited the mother and infant pair on a weekly basis for three years. Thinking and working together helped to create a template for the outreach project, the intervention approach, and informed further plans to expand the project and to include additional therapists and referral sources.

A case report of gastric antral vascular ectasia treated by endoscopic band ligation combined with lauromacrogol injection.

Gastric antral vascular ectasia (GAVE) is a rare acquired lesion characterized by vascular dilation in the gastric antrum, frequently results in occult or overt gastrointestinal bleeding. Endoscopic intervention remains the cornerstone of therapy. Argon plasma coagulation was previously considered a first treatment option. But recently, endoscopic band ligation (EBL) has emerged as an alternative, increasingly favored for its safety and efficacy. Nonetheless, a consensus on the most effective treatment approach has yet to be established. A 74-year-old female was hospitalized for persistent chest tightness and dyspnea for 1 year. Physical examination showed an anemic appearance with normal blood pressure. Upon admission to the hospital, the blood routine examination revealed severe anemia and the fecal occult blood test was persistently positive. The endoscopic observations and histological evidence led to a diagnosis of GAVE for the patient. Considering the poor response to prior pharmacotherapy, endoscopic intervention was selected for this hospitalization. The initial EBL alone did not yield particularly satisfactory results. Combining EBL with lauromacrogol injection as a subsequent treatment resulted in encouraging outcomes. At the 6-week follow-up, the patient exhibited a negative fecal occult blood test, normalization of hemoglobin level, and endoscopic images demonstrated near complete resolution of vascular ectasias. The combination of EBL with lauromacrogol injection has shown a satisfactory short-term outcome, providing a new option for the endoscopic management of GAVE. However, its long-term efficacy still requires further observation.

Correctly performing manual subgingival scaling and root planing exercises: part Ⅱ of a series on basic training in periodontal diagnosis and treatment

Periodontitis constitutes the primary cause of tooth loss among adults in China. The disease is characterized by the high morbidity, which significantly impairs both oral and systemic health. As the key insights of initial periodontal therapy, subgingival scaling and root planing (SRP) have been considered as simple, effective, and cost-efficient treatment approaches for managing periodontal inflammation. Substantial published evidences indicated that the majority of patients diagnosed with periodontitis could achieve lifelong retention of their natural teeth through standardized initial periodontal therapy, rigorous plaque control, and long-term supportive periodontal treatment. However, the proficiency in periodontal diagnosis and treatment among general dental practitioners in China is heterogeneous, with a notable scarcity of periodontists and a suboptimal level of SRP standardization. Drawing upon over four decades of clinical expertise from Peking University School and Hospital of Stomatology as well as comprehensive literature reviews, this paper meticulously outlines the standardized procedures for SRP, aiming at guiding clinicians to perform standardized SRP step by step, and thereby enhancing clinical efficacy of periodontal treatment, promoting periodontal health, and ultimately improving patients' quality of life.

Behavioural interventions targeting the prevention and treatment of young children's mental health problems in low- and middle-income countries: a scoping review.

Globally, 10% of children and adolescents live with mental health problems and often lack high-quality care. Over 80% of people facing mental health issues reside in low- and middle-income countries (LMICs). Failing to address children's mental health may prolong these challenges into adulthood, impeding their chances for a healthy life. This scoping review aims to describe the types, implementation strategies, effectiveness, and gaps of existing interventions for preventing and treating mental health problems in early childhood (<10 years) in LMICs. The study employed a scoping review of experimental studies published 2007-2023. Major databases including PubMed, Embase, Web of Science, and PsycINFO were searched using key terms related to the population (children), intervention (mental and/or behavioural health programmes), and outcome (mental health problems). Three authors independently conducted search strategy, article screening, data extraction, and quality assessment. The findings were presented using descriptive analysis and narrative synthesis. Of 39 499 identified articles, 33 were included in the study, covering 7629 children and published between 2009-2022. Seventeen studies (51.5%) were from upper-middle-income countries, 13 (39.4%) were from lower-middle-income, and three (9.1%) were from low-income countries. Enrolment was community-based in 23 studies and health-facility based in 10 studies; the majority (79%) focused on children aged 3-8 years old. Almost two-third (63.6%) of studies were conducted in urban settings. Programmes encompassed various interventions such as parenting programmes (33.3%). A majority of studies (57.5%) employed group therapy for delivering the programme, with mental health professionals (21.2%) acting as the primary intervention providers. Interventions were primarily received by children (39.4%), followed by mothers/caregivers (33.3%). Most studies explored disruptive disorders (20 studies), social and behavioural problems (16 studies), and anxiety disorders (12 studies). Statistically significant intervention effects on child mental health outcomes were reported for 90% of published studies. Diverse behavioural programmes that improve the mental health of young children are available and effective in LMICs. Most interventions were delivered in urban settings and focus was on the use of health care professionals. Diverse intervention approaches, including parenting programmes and group therapy, were effective in addressing various mental health issues among young children.

Failure to thrive: A proposed diagnostic approach.

Failure to thrive is a general term describing infants who do not reach weight, length, or body mass index expected for their age. It can be related often to malnutrition due to inadequate caloric and protein intake, but also to excessive loss of nutrients, inadequate metabolism, inadequate absorption, or excessive caloric and energy expenditure. It may be either organic or inorganic in origin, and in most cases, does not require investigation through complementary examinations. It is associated with social and health detrimental outcomes. Most cases of failure to thrive are of non-organic etiology, thus clinical history evaluation and physical examination are of utmost importance in the management of these patients. Therapeutics includes behavioral or nutritional interventions, as well as treatment of possible underlying diseases. The treatment approach is more effective in improving clinical outcomes if applied as early as possible.

Real-world use of biologics during the first year of treatment for newly diagnosed Crohn's disease in Japan: a claims analysis from 2010 to 2021.

Crohn's disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan. In this retrospective observational study (2010-2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis. Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%-69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types. Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

Targeting ferroptosis in gastrointestinal tumors: Interplay of iron-dependent cell death and autophagy.

Ferroptosis is a regulated cell death mechanism distinct from apoptosis, autophagy, and necroptosis, marked by iron accumulation and lipid peroxidation. Since its identification in 2012, it has developed into a potential therapeutic target, especially concerning GI disorders like PC, HCC, GC, and CRC. This interest arises from the distinctive role of ferroptosis in the progression of diseases, presenting a new avenue for treatment where existing therapies fall short. Recent studies emphasize the promise of focusing on ferroptosis to fight GI cancers, showcasing its unique pathophysiological mechanisms compared to other types of cell death. By comprehending how ferroptosis aids in the onset and advancement of GI diseases, scientists aim to discover novel drug targets and treatment approaches. Investigating ferroptosis in gastrointestinal disorders reveals exciting possibilities for novel therapies, potentially revolutionizing cancer treatment and providing renewed hope for individuals affected by these tumors.

Gold Nanorods Decorated by Conjugated Microporous Polymers for Infrared Responsive Cytostatic Drug Delivery.

Near-infrared (NIR) controlled drug delivery systems have drawn a lot of attention throughout the past few decades due to the deep penetration depth and comparatively minor side effects of the stimulus. In this study, we introduce an innovative approach for gastric cancer treatment by combining photothermal infrared-sensitive gold nanorods (AuNRs) with a conjugated microporous polymer (CMP) to create a drug delivery system tailored for transporting the cytostatic drug 5-fluorouracil (5-FU). CMPs are fully conjugated networks with high internal surface areas that can be precisely tailored to the adsorption and transport of active compounds through the right choice of chemical functionalities. By incorporation of surfactant-stabilized AuNRs into the CMP synthesis in dimethylformamide (DMF) the surfactant shell is destabilized and subsequently replaced by the CMP. Particularly, low initial surfactant concentrations led to uniform distribution of the AuNRs in the polymer matrix. Importantly, the integrated AuNRs maintain their plasmonic properties, as was confirmed via electron energy loss spectroscopy. Therefore, the significant photothermal properties are translated to the hybrid material as shown in a proof-of-principle experiment. Further, in an approximated gastric environment, 5-FU release studies were conducted with and without NIR stimulus. Thereby it was observed that increased Brownian motion due to the NIR irradiation not only accelerates the release but also increases the total released amount by influencing the adsorption-desorption equilibrium. This remarkable level of control of the release process underlines the immense potential of this hybrid material for precise and targeted drug delivery.

The role of mitochondrial dysfunction in Huntington's disease: Implications for therapeutic targeting.

Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by cognitive decline, motor dysfunction, and psychiatric disturbances. A common feature of neurodegenerative disorders is mitochondrial dysfunction, which affects the brain's sensitivity to oxidative damage and its high oxygen demand. This dysfunction may plays a significant role in the pathogenesis of Huntington's disease. HD is caused by a CAG repeat expansion in the huntingtin gene, which leads to the production of a toxic mutant huntingtin (mHTT) protein. This disruption in mitochondrial function compromises energy metabolism and increases oxidative stress, resulting in mitochondrial DNA abnormalities, impaired calcium homeostasis, and altered mitochondrial dynamics. These effects ultimately may contribute to neuronal dysfunction and cell death, underscoring the importance of targeting mitochondrial function in developing therapeutic strategies for HD. This review discusses the mechanistic role of mitochondrial dysfunction in Huntington's disease. Mitochondrial dysfunction is a crucial factor in HD, making mitochondrial-targeted therapies a promising approach for treatment. We explore therapies that address bioenergy deficits, antioxidants that reduce reactive oxygen species, calcium modulators that restore calcium homeostasis, and treatments that enhance mitochondrial dynamics to rejuvenate mitochondrial function. We also highlight innovative treatment approaches such as gene editing and stem cell therapy, which offer hope for more personalized strategies. In conclusion, understanding mitochondrial dysfunction in Huntington's disease may guide potential treatment strategies. Targeting this dysfunction may help to slow disease progression and enhance the quality of life for individuals affected by Huntington's disease.

Bridging the gap: The endocannabinoid system as a functional fulcrum for benzodiazepines in a novel frontier of anxiety pharmacotherapy.

While benzodiazepines have been a mainstay of the pharmacotherapy of anxiety disorders, their short-term efficacy and risk of abuse have driven the exploration of alternative treatment approaches. The endocannabinoid (eCB) system has emerged as a key modulator of anxiety-related processes, with evidence suggesting dynamic interactions between the eCB system and the GABAergic system, the primary target of benzodiazepines. According to the existing literature, the activation of the cannabinoid receptors has been shown to exert anxiolytic effects, while their blockade or genetic deletion results in heightened anxiety-like responses. Moreover, studies have provided evidence of interactions between the eCB system and benzodiazepines in anxiety modulation. For instance, the attenuation of benzodiazepine-induced anxiolysis by cannabinoid receptor antagonism or genetic variations in the eCB system components in animal studies, have been associated with variations in benzodiazepine response and susceptibility to anxiety disorders. The combined use of cannabinoid-based medications, such as cannabinoid receptor agonists and benzodiazepine co-administration, has shown promise in augmenting anxiolytic effects and reducing benzodiazepine dosage requirements. This article aims to comprehensively review and discuss the current evidence on the involvement of the eCB system as a key modulator of benzodiazepine-related anxiolytic effects, and further, the possible mechanisms by which the region-specific eCB system-GABAergic connectivity modulates the neuro-endocrine/behavioral stress response, providing an inclusive understanding of the complex interplay between the eCB system and benzodiazepines in the context of anxiety regulation, to inform future research and clinical practice.

Efficacy and safety of gene therapy approaches for malignant gliomas: A systematic review and meta-analysis: ConNRNRNRNR22.5NRNR1011.413.511.9NRNRNR.

Malignant gliomas are the most aggressive brain tumors with no certain therapeutic methods. Nowadays, novel treatment methods are introduced for gliomas among which gene therapy is known as a promising and robust method. In this method, genes with key roles in the prevention of cell cycle or induction of cell suicide are transferred to the tumor site using vectors. Viral vectors are the most popular transfer methods, while the liposomes are also used for gene therapy. This meta-analysis and systematic review was performed based on PRISMA guidelines. We performed a comprehensive search in databases including PubMed, Embase, and clinicaltrial.gov. After processing and filtering the articles, phase 1 clinical trials were chosen for the evaluation of the efficacy and safety of gene therapy for malignant gliomas. The obtained results showed that gene therapy increases overall survival (OS) and progression-free survival (PFS) in two years of follow-up. Subgroup analysis also showed that cytokines exhibit the highest effectiveness compared to suicide genes and oncolytic genes. It was found that gene therapy is more efficient for recurrent gliomas than primary gliomas. The subgroup analysis for vectors revealed that Adenovirus is the most effective for increasing the OS in malignant glioma patients. Gene therapy is an immunotherapy method for malignant gliomas following the standard treatment approach. Considering the effectiveness of gene therapy on the survival of patients, it is hoped that solving related issues with gene therapy will help to increase the OS rate in this malignant disease.

The role of hypoxia/ischemia preconditioning in ischemic stroke.

Ischemic stroke can cause damage to neurons, resulting in neurological dysfunction. The main treatments in the acute phase include intravenous thrombolysis, endovascular stent-assisted vascular thrombectomy and antiplatelet therapy. Due to the limitations of the time window and the risk of early intracranial hemorrhage, finding active treatment plans is crucial for improving therapy. Preconditioning can enhance the tolerance to acute injuries such as ischemic stroke and mechanical brain injury. This tolerance, induced by stressors like ischemia and hypoxia, can become an effective and convenient treatment approach for ischemic stroke. The molecular mechanisms involved in preconditioning are extremely complex. This article focuses on the main preconditioning treatment methods for ischemic stroke, discusses the specific molecular mechanisms of different treatment methods, and explores their action pathways and effects on corresponding target cells, thus opening up a brand-new direction for the treatment strategies of ischemic stroke.

Changes in Recovery Assessment Scale Scores During a Treatment Episode Among Patients in a Large Behavioral Health Care System.

The authors utilized patient-reported outcomes from a large U.S. behavioral health care system to evaluate the strength of improvements in patients' self-perceived recovery during mental health treatment. This was a cohort study conducted with electronic health records from 2021-2022 Discovery Behavioral Health patients. Patients were grouped according to their 41-item Recovery Assessment Scale (RAS) scores at admission. Linear regression models accounting for patient characteristics were used to estimate RAS score changes from admission to discharge and RAS score at discharge. Of 9,441 patients, those belonging to groups with lower RAS scores at admission showed substantial score improvements, although their scores at discharge were still much lower compared with those of patients with higher admission scores. Results were consistent across secondary analyses. Substantial improvements in recovery were evident during treatment, especially for patients with lower RAS scores at admission. The findings underline the importance of research into enhanced personalized treatment approaches to optimize recovery.

Factors affecting decisions to use antibiotic-sparing treatment approaches in women with uncomplicated urinary tract infections: a scoping review protocol.

This scoping review will explore the evidence on factors influencing the decisions to use antibiotic-sparing treatments in women with uncomplicated urinary tract infection. Overuse and misuse of antibiotics are the main drivers of antimicrobial resistance. Antibiotic-sparing treatments, such as symptomatic treatment with analgesics and delayed prescriptions, have considerable potential to reduce antibiotic consumption, but the majority of patients still receive antibiotics without delay. The reasons for the poor implementation of these alternative approaches are unknown. A better understanding of the factors influencing treatment decisions is needed. This review will consider the experiences and attitudes of health care professionals and women, in outpatient settings in high-income countries, regarding the use of antibiotic-sparing treatments for the diagnosis or suspected diagnosis of uncomplicated urinary tract infections (ie, healthy women aged 18-64years who are not pregnant, immunosuppressed, and have no functional or structural urinary tract abnormalities). This review will follow the JBI methodology for scoping reviews. MEDLINE (Ovid), Embase, and the Cochrane Library will be searched to identify peer-reviewed articles: original research (quantitative or qualitative studies, experimental or observational), reviews, case reports, and case series. Gray literature will also be searched for. Sources in any language from 2000 to 2024 will be included. Three reviewers will screen the sources and extract data using a tool developed by the reviewers. The analysis will use counts and descriptive qualitative content analysis. The results will be presented in visual, tabular, and narrative formats. https://osf.io/t8y5e/.

Immune evasion in ovarian cancer: implications for immunotherapy and emerging treatments.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, characterized by multiple histological subtypes, each with distinct pathological and clinical features. Current treatment approaches include cytotoxic chemotherapies, poly(ADP-ribose) polymerase (PARP) inhibitors, bevacizumab, hormonal therapy, immunotherapy, and antibody-drug conjugates (ADCs). In this review we discuss immune evasion mechanisms in OC and the role of genetics, the tumor microenvironment, and tumor heterogeneity in influencing these processes. We also discuss the use of immunotherapies for OC treatment, either alone or in combination with other anticancer agents, with a focus on their clinical outcomes. Finally, we highlight emerging immunotherapies that have either succeeded or are on the verge of significantly impacting cancer treatment, and we discuss their potential utility in the effective treatment of OC.

The Call to Increase Adoption of Family-Based Interventions in Global Mental Health Programming.

Family-based intervention approaches hold tremendous promise for improving mental health in scalable and relevant ways that address social determinants of health, yet family-focused prevention and care interventions are underused in global mental health. This article provides a brief overview of the evidence and types of programs. It then outlines five future directions for family-focused global mental health interventions: integrating implementation science into family-focused programs, expanding research on family-focused work to other populations and different modalities, encouraging transdisciplinary learning from other fields, understanding what works for whom and where, and disseminating family interventions grounded in locally derived theoretical frameworks.

Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.

The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.

Optimizing kinase and PARP inhibitor combinations through machine learning and in silico approaches for targeted brain cancer therapy.

The drug combination is an attractive approach for cancer treatment. PARP and kinase inhibitors have recently been explored against cancer cells, but their combination has not been investigated comprehensively. In this study, we used various drug combination databases to build ML models for drug combinations against brain cancer cells. Some decision tree-based models were used for this purpose. The results were further evaluated using molecular docking and molecular dynamics (MD) simulation. The possibility of the hit drug combinations for crossing the Blood-brain barrier (BBB) was also examined. Based on the obtained results, the combination of niraparib, as the PARP inhibitor, and lapatinib, as the kinase inhibitor, exhibited more considerable outcomes with a remarkable model performance (accuracy of 0.915) and prediction confidence of 0.92. The protein tweety homolog 3 and BTB/POZ domain-containing protein 2 are the main targets of niraparib and lapatinib with -10.2 and -8.5 scores, respectively. Due to the outcomes, this drug combination can use the CAT1 transporter on the BBB surface and effectively cross the BBB. Based on the obtained results, niraparib-lapatinib can be a promising drug combination candidate for brain cancer treatment. This combination is worth to be examined by experimental investigation in vitro and in vivo.