Therapeutic Modalities Research Articles

Application of Inflammatory Vital Pulp Therapy in the Treatment of Apical Periodontitis in a deciduous Molar: A Case Report

Due to the distinct anatomical characteristics of deciduous teeth, they are particularly susceptible to apical periodontitis when afflicted by deep caries or other endodontic diseases. Conventional, root canal therapy (RCT) has served as the standard treatment protocol all the time by the most pediatric dentists. However, researchers try to find another possible alternative mothods because of its some drawbacks. Hence this report introduces a groundbreaking therapeutic modality - inflammatory vital pulp therapy (IVPT) - which has proven effective in treating apical periodontitis in a deciduous molar. The objective of this study was to assess the practicality and efficacy of IVPT in managing apical periodontitis in deciduous teeth. Through rigorous patient examination and evaluation, IVPT was adopted as the treatment plan, followed by meticulous long-term follow-up observations. The outcomes revealed remarkable clinical improvements, with the periapical lesion healing seamlessly without any complications. Notably, the development of the permanent tooth embryo remained undisturbed and progressed as expected. In summary, this study validates the efficacy of IVPT in treating apical periodontitis in deciduous teeth, opening a new avenue for the management of deciduous tooth diseases. The clinical utilization of this method is anticipated to enhance treatment experiences and prognostic outcomes for patients with deciduous tooth pathologies.

A Review on HR-HPV: An Increasing Cause of Concern for Cervical Carcinoma

Human Papilloma virus, leads to widely prevalent viral infection with worldwide distribution of variable genotypes, it is the major cause of cancer in women and a leading cause of deaths due to cancer in India. Cervical cancer is the second most common cancer in women worldwide and the most common cancer cause of death in the developing countries. Notably, four out of every five cases of cervical cancer reported in India were attributed to infections from HPV types 16 and 18. India has a population of 483.5 million women aged 15 years and older who are at risk of developing cervical cancer. Infections with high-risk HPV types impair the function of cellular proteins and interfere with the expression of biological gene products. In high-grade intraepithelial neoplasias and cancers, HPV DNA is typically integrated into the host genome. WHO has recommended Screening of cervical cancer among young sexually-active females for early detection of HPV induced cervical carcinoma. Detection of HPV at earlier stages is essential in prevention of invasive cervical carcinoma. Based on clinical stage categories upon diagnosis, standard of care for cervical cancer management includes surgery, radiation, systemic therapy, or a combination of these therapeutic modalities.

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives—A Review

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Mental Health and Healing Practices in the Ottoman Empire: A Historical and Psychological Analysis

This study conducts a comparative analysis of mental health care within the Ottoman Empire and its impact on current psychological understandings and treatments, highlighting the significant role of cultural and historical contexts in shaping mental health practices. It demonstrates the ongoing relevance of the Ottoman Empire's holistic and integrative approaches, emphasizing compassionate, comprehensive care that incorporates a wide array of therapeutic modalities, such as herbal remedies and spiritual healing. These methods illustrate the importance of addressing the complex nature of mental well-being. The research addresses the difficulties of applying historical mental health practices to contemporary settings, advocating for a method that honors cultural and societal variances. Insights from Ottoman mental health and healing practices provide essential lessons for today, endorsing a more empathetic, patient-focused, and culturally inclusive mental health care system. The enduring influence of Ottoman methods invites further investigation into historical mental health strategies, pointing to future research opportunities, including the integration of traditional healing into modern care models and the creation of fair mental health systems. This analysis underlines the importance of historical perspectives in enhancing contemporary mental health care, proposing an approach that respects the past while catering to the diverse needs of the global community today.

Whole Pancreas and Islet Cells Transplantation for Patients with Type 1 Diabetes Mellitus: A Mini-Review and Middle East-North Africa Experience.

Pancreatic and islet cell transplantation are considered surgical therapeutic modalities for type 1 diabetes mellitus with or without end-stage renal disease. The pancreatic transplant can be performed alone or with the kidney transplant simultaneously or at different times. It contributed to an improved quality of life in those patients. Pancreatic transplantation and islet cell transplantation provide different degrees of insulin independence. Although the latter needs less monitoring, yet, it is more expensive and tedious. The experiences in the Middle East and North African countries for both procedures are young but mature. They need more scheduled national and/or regional programs to provide diverse options for their citizens.

Echocardiographic Assessment of Left Ventricular Function in Three Oncologic Therapeutic Modalities in Women with Breast Cancer: The ONCO-ECHO Multicenter Study.

Background: Oncological treatment of breast cancer may be associated with adverse effects on myocardial function. Objectives: The objective of this study was to compare the influence of three oncological treatment methods of intervention on the echocardiographic (ECHO) parameters of left ventricular function. Materials and Methods: One hundred and fifty-five women with breast cancer were divided into three groups depending on the type of therapy used: group I (AC)-anthracyclines; group II (AC + TZ)-anthracyclines + trastuzumab; and group III (RTls+)-anthracyclines with or without trastuzumab + left-sided radiotherapy. Prospective ECHO examinations were performed at baseline and every 3 months, up to 12 months from the start of the therapy. Patients with a history of chemotherapy or who were diagnosed with heart disease were not included in the study. Results: Out of 155 patients, 3 died due to cancer as the primary cause, and 12 withdrew their consent for further observation. Baseline systolic and diastolic ECHO parameters did not differ between the analyzed groups. Cardiotoxicity, according to the LVEF criteria, occurred during follow-up in 20 patients (14.3%), irrespective of the treatment method used. Diastolic echocardiographic parameters did not change significantly after 12 months in each group, except for the left atrial volume index (LAVi), which was significantly higher in the AC + TZ compared to the values in the RTls+ group. Conclusions: All three oncologic therapeutic modalities in women with breast cancer showed no significant differences in relation to the incidence of echocardiographic cardiotoxicity criterion; however, transient systolic decrease in LVEF was most frequently observed in the AC + TZ therapeutic regimen. Left-sided radiotherapy was not associated with excess left ventricular systolic and diastolic dysfunction during a 12-month follow-up period. The predictors of negative changes in diastolic parameters included age and combined anthracycline and trastuzumab therapy.

Plant-Derived Vesicle-like Nanoparticles: The Next-Generation Drug Delivery Nanoplatforms

A wide variety of natural bioactive compounds derived from plants have demonstrated significant clinical relevance in the treatment of various diseases such as cancer, chronic disease, and inflammation. An increasing number of studies have surfaced that give credence to the potential of plant-derived vesicle-like nanoparticles (PDVLNs) as compelling candidates for a drug delivery system (DDS). PDVLNs are cost-effective production, non-toxicity and non-immunogenicity and fascinating bi-ocompatibility. In this review, we attempt to comprehensively review and consolidate the position of PDVLNs as next-generation drug delivery nanoplatforms. We aim to give a quick glance to readers of the current developments of PDVLNs, including their biogenesis, characteristic features, composition, administration routes, advantages, and application. Further, we discuss the advantages and limitations of PDVLNs. We expect that the role of PDVLNs in drug delivery will be significantly enhanced, thus positioning them as the next generation of therapeutic modalities in the foreseeable future.

Management of post-autologous transplant relapse in patients with T-cell lymphomas.

Autologous hematopoietic cell transplantation (AHCT) is often used as a consolidation for patients with peripheral T-cell lymphomas (PTCLs) due to the poor prognosis associated with this heterogenous group of disorders. However, a significant number of patients will experience post-AHCT disease relapse. Here, we report a retrospective study of consecutive 124 patients with PTCLs who underwent AHCT from 2008 to 2020. With a median follow-up of 6.01 years following AHCT, 49 patients (40%) experienced disease relapse. As expected, more patients who were not in first complete remission experienced post-AHCT relapse. Following relapse, majority of the patients (70%) receiving systemic therapies intended as bridging to curative allogeneic HCT. However, only 18 (53%) patients eventually underwent allogeneic HCT. The estimated 3-year OS among patients proceeding to allogeneic HCT was 72% (95% CI 46%-87%). Our report details the pattern of post-AHCT relapse and the management of relapsed disease using different therapeutic modalities.

The tuberous sclerosis complex: a review of the literature

Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, this leads to dysregulation of the mechanistic target of rapamycin (mTOR) pathway resulting in cellular hyperplasia and the formation of benign tumors in various organs, including the brain and skin. Clinical manifestations encompass a wide range of mainly neurological and dermatological symptoms, often presenting during early childhood and posing diagnostic challenges due to phenotypic variability. Recent advancements in diagnostic criteria, genetic testing, and imaging techniques have facilitated earlier diagnosis and increased disease incidence awareness. Neurologically, TSC commonly presents with cortical tubers, subependymal nodules (SENs), and epilepsy, with seizure control being paramount in preventing long-term neurodevelopmental sequelae. Dermatologically, hypomelanotic macules, facial angiofibromas, and ungual fibromas are hallmark features, often causing significant psychological distress due to disfigurement. Management of TSC requires a multidisciplinary approach, with emerging therapies such as mTOR inhibitors showing promise in addressing both neurological and dermatological manifestations. Early intervention, including epilepsy surgery and targeted treatments for skin lesions, is essential for optimizing outcomes and improving the quality of life for patients with TSC. Continued research into novel therapeutic modalities holds potential for further enhancing the management and prognosis of this complex disorder.

Great Debates: Surgery or Watch and Wait After Total Neoadjuvant Therapy for Rectal Cancer.

Locally advanced rectal cancer has traditionally been treated with multimodal therapy including neoadjuvant chemoradiotherapy followed by surgical resection. More recent data suggests that in appropriate patients, total neoadjuvant treatment (TNT) makes it possible to adopt a "watch and wait" approach. Advocates for watch and wait argue that patients with a complete or near-complete clinical response to TNT have comparable overall and disease-free survival to their counterparts who undergo surgical resection, and also have a better quality of life, fewer complications, and potentially avoid a stoma. The dogma of surgery as regional curative intent therapy has been challenged by similar recurrence rates among those treated with total mesorectal excision (TME) and those treated with watch and wait. Furthermore, those who develop local recurrence in the watch and wait groups are equally salvageable, either by surgery, brachytherapy, or chemotherapy. While watch and wait is not appropriate in all patients, this manuscript highlights the benefits and drawbacks of both therapeutic modalities.

Intense pulsed light therapy for ocular surface diseases.

Intense pulsed light (IPL) is a non-laser, high-intensity light source that has been shown to play a valuable role in dermatology and has been adopted in ophthalmology for treating meibomian gland dysfunction (MGD). In this review, we discuss the mechanism of action of IPL, including its benefits in ophthalmology. IPL therapy has been shown to improve tear film stability, meibomian gland (MG) function, and subjective symptoms of ocular dryness in MGD patients. Moreover, emerging evidence suggests that IPL therapy is beneficial for other ocular surface diseases, such as blepharitis and chalazia. Hence, it can be inferred that IPL has potential as a therapeutic modality in future applications. Large clinical and experimental trials are needed to exploit the full potential of IPL as a treatment for recurrent chalazia, Sjögren's syndrome, and other causes of dry eye disease (DED). This paper reviews the published literature related to the application of IPL for treating ocular surface diseases.

Safety and efficacy of EsoFLIP dilation in patients with esophageal dysmotility: a systematic review.

Esophageal manometry is utilized for the evaluation and classification of esophageal motility disorders. EndoFlip has been introduced as an adjunctive test to evaluate esophagogastric junction (EGJ) distensibility. Treatment options for achalasia and EGJ outflow obstruction (EGJOO) include pneumatic dilation, myotomy, and botulinum toxin. Recently, a therapeutic 30mm hydrostatic balloon dilator (EsoFLIP, Medtronic, Minneapolis, MN, USA) has been introduced, which uses impedance planimetry technology like EndoFlip. We performed a systematic review to evaluate the safety and efficacy of EsoFLIP in the management of esophageal motility disorders. A systematic literature search was performed with Medline, Embase, Web of science, and Cochrane library databases from inception to November 2022 to identify studies utilizing EsoFLIP for management of esophageal motility disorders. Our primary outcome was clinical success, and secondary outcomes were adverse events. Eight observational studies including 222 patients met inclusion criteria. Diagnoses included achalasia (158), EGJOO (48), post-reflux surgery dysphagia (8), and achalasia-like disorder (8). All studies used 30mm maximum balloon dilation except one which used 25mm. The clinical success rate was 68.7%. Follow-up duration ranged from 1week to a mean of 5.7months. Perforation or tear occurred in four patients. EsoFLIP is a new therapeutic option for the management of achalasia and EGJOO and appears to be effective and safe. Future comparative studies with other therapeutic modalities are needed to understand its role in the management of esophageal motility disorders.

Postsynaptic potentials of soleus motor neurons produced by transspinal stimulation: A human single motor unit study.

Transspinal (or transcutaneous spinal cord) stimulation is a non-invasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and non-somatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single pulse transspinal stimulation using single motor unit discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions.

Mechanical Support in High-Risk Pulmonary Embolism: Review Article.

Acute pulmonary embolism (PE) may manifest with mild nonspecific symptoms or progress to a more severe hemodynamic collapse and sudden cardiac arrest. A substantial thrombotic burden can precipitate sudden right ventricular strain and failure. Traditionally, systemic thrombolytics have been employed in such scenarios; however, patients often present with contraindications, or these interventions may prove ineffective. Outcomes for this medically complex patient population are unfavorable, necessitating a compelling argument for advanced therapeutic modalities or alternative approaches. Moreover, patients frequently experience complications beyond hemodynamic instability, such as profound hypoxia and multiorgan failure, necessitating assertive early interventions to avert catastrophic consequences. The existing data on the utilization of mechanical circulatory support (MCS) devices are not exhaustive. Various options for percutaneous MCS devices exist, each possessing distinct advantages and disadvantages. There is an imminent imperative to develop a tailored approach for this high-risk patient cohort to enhance their overall outcomes.

Exploring a repurposed candidate with dual hIDO1/hTDO2 inhibitory potential for anticancer efficacy identified through pharmacophore-based virtual screening and in vitro evaluation

Discovering effective anti-cancer agents poses a formidable challenge given the limited efficacy of current therapeutic modalities against various cancer types due to intrinsic resistance mechanisms. Cancer immunochemotherapy is an alternative strategy for breast cancer treatment and overcoming cancer resistance. Human Indoleamine 2,3-dioxygenase (hIDO1) and human Tryptophan 2,3-dioxygenase 2 (hTDO2) play pivotal roles in tryptophan metabolism, leading to the generation of kynurenine and other bioactive metabolites. This process facilitates the de novo synthesis of Nicotinamide Dinucleotide (NAD), promoting cancer resistance. This study identified a new dual hIDO1/hTDO2 inhibitor using a drug repurposing strategy of FDA-approved drugs. Herein, we delineate the development of a ligand-based pharmacophore model based on a training set of 12 compounds with reported hIDO1/hTDO2 inhibitory activity. We conducted a pharmacophore search followed by high-throughput virtual screening of 2568 FDA-approved drugs against both enzymes, resulting in ten hits, four of them with high potential of dual inhibitory activity. For further in silico and in vitro biological investigation, the anti-hypercholesterolemic drug Pitavastatin deemed the drug of choice in this study. Molecular dynamics (MD) simulations demonstrated that Pitavastatin forms stable complexes with both hIDO1 and hTDO2 receptors, providing a structural basis for its potential therapeutic efficacy. At nanomolar (nM) concentration, it exhibited remarkable in vitro enzyme inhibitory activity against both examined enzymes. Additionally, Pitavastatin demonstrated potent cytotoxic activity against BT-549, MCF-7, and HepG2 cell lines (IC50 = 16.82, 9.52, and 1.84 µM, respectively). Its anticancer activity was primarily due to the induction of G1/S phase arrest as discovered through cell cycle analysis of HepG2 cancer cells. Ultimately, treating HepG2 cancer cells with Pitavastatin affected significant activation of caspase-3 accompanied by down-regulation of cellular apoptotic biomarkers such as IDO, TDO, STAT3, P21, P27, IL-6, and AhR.

Perioral dermatitis: nuances of the clinical picture and therapy in different age periods

Relevance. Perioral dermatitis is a common dermatosis that predominantly affects women aged 25-40 but is also observed in children and adolescents. The distinct localization of this condition in the perioral, perinasal, and periocular zones contributes to apparent psycho-emotional distress, markedly impairing patients' quality of life. Perturbations in the skin biotope, local immune dysregulation, and topical glucocorticosteroid use are among the primary etiological factors. Effective management involves addressing causative factors, discontinuation of topical steroids, adopting gentle skincare practices, and employing localized treatments like metronidazole, pimcrolimus, and activated zinc pyrithione. Maintenance therapy may be warranted in select cases. The purpose of this work is to review the current literature on the problem and to present original clinical observations concerning the utilization of activated zinc pyrithione in treating patients with this condition. Materials and methods. The article presents the results of the use of topical zinc pyrithione in patients spanning various age groups and exhibiting diverse degrees of perioral dermatitis severity. Discussion. Significant clinical evidence substantiates the remarkable efficacy and safety profile of activated zinc pyrithione in managing perioral dermatitis, both as a standalone therapeutic modality and as an integral component of combination therapy. Conclusions. The use of activated zinc pyrithione in the treatment of perioral dermatitis emerges as an efficacious and secure approach for treating mild to moderate forms of the condition. Keywords: orofacial dermatitis, skin microbiome, chronic inflammation, age periods, Demodex, Malassezia spp., S.aureus, activated zinc pyrithione

When DNA damage responses meet tumor immunity: From mechanism to therapeutic opportunity.

DNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects. This review explores the mechanisms behind DNA damage-induced antitumor immune responses, the importance of DNA damage in antitumor immunity, and potential therapeutic approaches for cancer immunotherapy targeting DDR. Additionally, we discuss the challenges of combination therapy and strategies for integrating DNA damage-targeting therapies with current cancer immunotherapy. In summary, this review highlights the critical role of DNA damage in tumor immunology, underscoring the potential of DDR inhibitors as promising therapeutic modalities for cancer treatment.

Regenerative Anterior Cruciate Ligament Healing in Youth and Adolescent Athletes: The Emerging Age of Recovery Science

Anterior cruciate ligament (ACL) injuries mainly arise from non-contact mechanisms during sport performance, with most injuries occurring among youth or adolescent-age athletes, particularly females. The growing popularity of elite-level sport training has increased the total volume, intensity and frequency of exercise and competition loading to levels that may exceed natural healing capacity. Growing evidence suggests that the prevailing mechanism that leads to non-contact ACL injury from sudden mechanical fatigue failure may be accumulated microtrauma. Given the consequences of primary ACL injury on the future health and quality of life of youth and adolescent athletes, the objective of this review is to identify key “recovery science” factors that can help prevent these injuries. Recovery science is any aspect of sports training (type, volume, intensity, frequency), nutrition, and sleep/rest or other therapeutic modalities that may prevent the accumulated microtrauma that precedes non-contact ACL injury from sudden mechanical fatigue failure. This review discusses ACL injury epidemiology, current surgical efficacy, the native ACL vascular network, regional ACL histological complexities such as the entheses and crimp patterns, extracellular matrix remodeling, the concept of causal histogenesis, exercise dosage and ligament metabolism, central nervous system reorganization post-ACL rupture, homeostasis regulation, nutrition, sleep and the autonomic nervous system. Based on this information, now may be a good time to re-think primary ACL injury prevention strategies with greater use of modified sport training, improved active recovery that includes well-planned nutrition, and healthy sleep patterns. The scientific rationale behind the efficacy of regenerative orthobiologics and concomitant therapies for primary ACL injury prevention in youth and adolescent athletes are also discussed.

Surgical management of renal cell carcinoma with subhepatic inferior vena cava tumor thrombus: a case report and review of the literature

BackgroundRenal cell carcinomas are the most common form of kidney cancer in adults. In addition to metastasizing in lungs, soft tissues, bones, and the liver, it also spreads locally. In 2–10% of patients, it causes a thrombus in the renal or inferior vena cava vein; in 1% of patients thrombus reaches the right atrium. Surgery is the only curative option, particularly for locally advanced disease. Despite the advancements in laparoscopic, robotic and endovascular techniques, for this group of patients, open surgery continues to be among the best options.Case reportHere we present a case of successful tumor thrombectomy from the infrahepatic inferior vena cava combined with renal vein amputation and nephrectomy. Our patient, a 58 year old Albanian woman presented to the doctors office with flank pain, weight loss, fever, high blood pressure, night sweats, and malaise. After a comprehensive assessment, which included urine analysis, complete blood count, electrolytes, renal and hepatic function tests, as well as ultrasonography and computed tomography, she was diagnosed with left kidney renal cell carcinoma involving the left renal vein and subhepatic inferior vena cava. After obtaining informed consent from the patient we scheduled her for surgery, which went well and without complications. She was discharged one week after to continue treatment with radiotherapy, chemotherapy, and immunotherapy.ConclusionOpen surgery is a safe and efficient way to treat renal cell carcinoma involving the renal vein and inferior vena cava. It is superior to other therapeutic modalities. When properly done it provides acceptable long time survival and good quality of life to patients.

Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.